Home   Chapter Home   Jobs   Conferences   Fellowships   Books



Advertisement

Mediastinum

Superpage


Revised: 20 March 2013
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.


General


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Mediastinum is thoracic cavity between pleural cavities, from sternum to spine, thoracic inlet to diaphragm
● Symptomatic tumors are usually 2-3 cm or more; most masses are detected incidentally, and undergo needle biopsy
Superior mediastinum: thymomas, thymic cyst, lymphoma, thyroid lesions, parathyroid adenoma
Anterior mediastinum: ventral to anterior cardiac border and aortic root - thymic epithelial tumors and cysts, germ cell neoplasms, lymphoproliferative lesions, retrosternal thyroid glandular proliferations, parathyroid lesions, aorticopulmonary-type paragangliomas, lymphangioma, hemangioma, lipoma
Middle mediastinum: between (a) anterior cardiac silhouette and aortic root and (b) posterior tracheal carinii - pericardial cyst, bronchogenic cyst, lymphoma
Posterior mediastinum: dorsal to large conducting airways - neurogenic tumors: schwannoma, neurofibroma, ganglioneuroma, ganglioneuroblastoma, MPNST, neuroblastoma, paraganglioma, gastroenteric cysts
Acquired hypogammaglobulinemia or pure anerythrogenesis: thymoma, leukemia, lymphoma
Myasthenia gravis: thymic hyperplasia, thymoma
Superior vena cava syndrome: usually indicates malignancy, most commonly metastatic lung carcinoma and lymphoma in adults and lymphoma and acute leukemia in children; also fibrous mediastinitis
Systemic symptoms (weight loss, fever, night sweats): lymphoma, Castleman’s disease, microcystic anemia

Diagrams
=========================================================================


Transverse section

Lateral divisions



Inflammatory disorders

Acute mediastinitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually in posterior mediastinum, due to traumatic perforation of esophagus or descending infection along prevertebral fascia
● Initial lesion may be a neck abscess
● Often causes mediastinal abscess which requires surgical drainage
● Other causes: chest wall infection or post-cardiac surgery, often due to CMV

Case reports
=========================================================================

● Sternum osteolysis following staphylococcus mediastinitis (Cardiovasc Pathol 2006;15:297)
● Descending necrotizing mediastinitis: rare spreading of cervical infection to mediastinum (Clin Imaging 2005;29:138)

Micro images
=========================================================================


Extensive acute inflammation

Fibrinoinflammatory exudate


Inflammatory disorders

Chronic mediastinitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● May compress superior vena cava and simulate malignancy
● Usually anterior to tracheal bifurcation
● Some cases may represent fibrosing mediastinitis

Micro description
=========================================================================

● Granulomas, fibrosis; may be fungus, Histoplasma (with thick fibrous capsule), mycobacteria (thin fibrous capsule)



Inflammatory disorders

Sclerosing mediastinitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called idiopathic mediastinal fibrosis, fibrosing mediastinitis
● Fibroinflammatory lesion, usually anterosuperior mediastinum, often presenting with superior vena cava syndrome or cardiorespiratory compromise
● All ages

Etiology
=========================================================================



Table of causes

Clinical features
=========================================================================

● Associated with other idiopathic fibrosing conditions such as inflammatory pseudotumor of orbit, retroperitoneal fibrosis, Riedel’s struma, sclerosing cholangitis
● Also associated with pulmonary or mediastinal nodal infection due to fungi (Histoplasma), methysergide treatment, phlebitis, syphilis, trauma


Table of clinical features

Radiology
=========================================================================

● Asymmetric mediastinal widening with projection of mass into upper lung field
● Radiologically divided into 2 types: focal (common) and diffuse
Focal: Localized and calcified mass in paratracheal or subcarinal compartments of mediastinum or in pulmonary hilum
Diffuse: diffusely infiltrating, non-calcified mass affecting multiple mediastinal compartments
● Additional pulmonary findings includes infiltrates, consolidation and pleural effusion

Prognostic factors
=========================================================================

● Prognosis depends mainly on location of fibrosis and structures involved

Case reports
=========================================================================

● 30 year old man with idiopathic mediastinal fibrosis presenting as mediastinal compression syndrome (Indian J Med Sci 2005;59:268)
● 46 year old woman with tracheobronchial narrowing, severe hyperemia and mucosal edema (Rev Pneumol Clin 2009;65:159)
● 70 year old woman with multifocal fibrosclerosis with intracardiac solid masses (Hum Pathol 2006;37:493)
● Involving ascending aorta in setting of a multifocal fibrosclerotic disorder (Pathol Res Pract 2011;207:60)

Treatment
=========================================================================

● Steroids, surgical excision

Gross description
=========================================================================

● Tan-yellow, gelatinous masses to gray-white, hard fibrotic masses that compress or infiltrate mediastinal structures
● Often well demarcated from surrounding tissue

Gross images
=========================================================================



(a) Fibrosis encases the mediastinal vessels, thus causing stenosis

Micro description
=========================================================================

Different patterns:
● Cellular fibrous reaction with polymorphic inflammatory infiltrate with plasma cells and eosinophils
● Dense, fibrohyaline tissue with focal spindle cells and inflammatory cells or scattered lymphoid follicles with occasional dystrophic calcification
● Paucicellular areas with keloid like fibrosis may occur
● Necrosis and metaplastic bone can occasionally be present (Arch Pathol Lab Med 2010;134:417)

Micro images
=========================================================================



Various images


(b) Dense fibrosis with denser inflammation at the periphery
(c) Lamellar bands of fibrosis similar to a keloid scar


Differential diagnosis
=========================================================================

Hodgkin lymphoma-nodular sclerosis
Mesothelioma
Metastatic carcinoma



Thyroid / parathyroid lesions

Thyroid nodular hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Presents as either a large mass causing compression or multiple independent nodules



Thyroid / parathyroid lesions

Parathyroid adenoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 7% are found in superior mediastinum, grow larger than counterparts in neck



Thymus

Normal


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

Embryology:
  Primordial thymus appears at week 6 from third branchial (pharyngeal) pouch
  Descends from high in neck with inferior parathyroid glands; lymphocytes invade at 10 weeks
  Differentiation into cortex and medulla is completed by 14–16 weeks
  Thymus attains its greatest weight in relation to body weight before birth (15g)
● Has critical role in development of cell mediated immunity and T cell differentiation
● Grows until puberty, then involutes and undergoes fatty replacement, although still present in adult prepericardial or retrocarinal fat
● Early thymus programming, sexual dimorphism, efficiency of specific T-cell progenitors and thymic microenvironment may determine immune activity (Aging Dis 2012;3:280)
● At age>60 years, thymocytes have higher levels of Ki-67 and p53 (Bull Exp Biol Med 2011;151:460)

Diagrams
=========================================================================


Fetal thymus

12 year old boy normal thymus

Gross description
=========================================================================

● Lobulated organ covered by a capsule, with cortical (outer and deep) and medullary compartments
● May resemble lymph nodes (if no epithelial cells) or tumors (if no lymphocytes)

Micro description
=========================================================================

● Composed of epithelial cells (endoderm, important for T lymphocyte differentiation), Hassall’s corpuscles (regressed epithelial cells), T cells of varying phenotypes; B cells in thymic medulla and thymic perivascular space (increase with age, Hum Pathol 2001;32:926); also interdigitating reticulum cells, Langerhans cells, mast cells, eosinophils, stromal cells
● Dendritic cells modulate autoimmune regulation through tissue restricted antigens (TSA) and promote central tolerance in thymus (Am J Pathol 2010;176:1104)
● Wnt4 regulates thymic cellularity through expansion of thymic epithelial cells and early thymic progenitors (Blood 2011;118:5163)

Micro images
=========================================================================


Low power

High power

Virtual slides
=========================================================================



Normal thymus gland (bottom slide)

Positive stains
=========================================================================

● Epithelial cells: keratin, HLA-DR



Thymus

Acute thymic involution


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Due to stress (chronic debilitating disease), HIV or other infections, prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction
● Seen in newborn infants with chorioamnionitis and sepsis
● Thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis (Hum Pathol 2000;31:1121)

Micro description
=========================================================================

● Preservation of lobular architecture and Hassall’s corpuscles, but marked lymphocyte depletion (particularly with HIV)
● Vessels are large compared to size of lobules
● Frequent plasma cells, fibrohyaline changes of basement membrane of vessels and thymic epithelium
● HIV patients also have effacement of corticomedullary junction and inconspicuous Hassall’s corpuscles

Micro images
=========================================================================


Due to sepsis

Differential diagnosis
=========================================================================

Thymic hyperplasia
Thymic dysplasia



Thymus

Diffuse thymic fibrosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Uncommon disorder with no/Limited symptoms; may have dyspnea, cough or hemoptysis
● Area of diffuse fibrosis varies from 3.5 to 17 cm, confined to anterior mediastinum
● Unknown etiology; altered immunity or infection may play a role
● Males and females, mean age 48 years

Micro description
=========================================================================

● Diffuse fibrosis with variable collagen deposition, lymphoplasmacytic infiltrates and involution/atrophy of thymus
● May show IgG4+ plasma cells and focal obliterative phlebitis (Am J Surg Pathol 2010;34:211)



Thymus

Ectopic thymus


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Remnants, implants or accessory nodules that may appear from angle of mandible to thyroid gland, most commonly at level of thyroid gland
● Rarely becomes hyperplastic or neoplastic

Epidemiology
=========================================================================

● Usually an incidental finding during thyroid surgery in preteens, very rare in adults due to thymic involution

Case reports
=========================================================================

● 12 month old boy with neck mass (Arch Pathol Lab Med 2001;125:278)
● 22 year old woman with anterior neck mass (Arch Pathol Lab Med 2001;125:842)
● With micronodular epithelial hyperplasia (Int J Surg Pathol 2006;14:73)

Xray images
=========================================================================



Homogeneous mass in submandibular space, extending toward parapharyngeal space

Micro description
=========================================================================

● Normal appearing thymic tissue

Micro images
=========================================================================


Various images

Central cervical epithelial rest

CK5/6, p63, CD10

Differential diagnosis
=========================================================================

● Other heterotopic epithelial elements, including misplaced cutaneous structures and salivary gland tissue (Am J Clin Pathol 2009;132:707)
Ectopic cervical thymoma: "the great mimic"; considered in differential diagnosis of neck masses in elderly (Indian J Pathol Microbiol 2007;50:553)



Thymus

Ectopic tissue in thymus


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually parathyroid tissue or sebaceous glands, rarely thyroid tissue

Case reports
=========================================================================

● Woman with heterotopic intrathymic thyroid tissue (Pathol Int 2006;56:629)



Thymus

Myasthenia gravis (MG)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Defect in nicotinic acetylcholine receptor (AChR) present in subsynaptic membrane of neuromuscular junction (at motor end plate), due to circulating autoantibodies to receptor
● Acetylcholine receptor also present in normal thymus, in myoid type cells
● Thymus may contain ectopic germinal centers with B cells producing pathogenic anti-acetylcholine receptor antibodies (Ann N Y Acad Sci 2008;1132:135)

Pathophysiology
=========================================================================

● May be due to T cells attacking myoid cells, then T cells induce B cells to produce autoantibodies; physiological connection with thymomas is unclear
● Two step hypothesis: hyperplastic medullary thymic epithelial cells are involved in provoking infiltration and thymic myoid cells (with intact AChR) are involved in germinal center formation (Am J Pathol 2007;171:893)
● MG patients have high number / ratio and abnormal distribution of thymic dendritic cells, which may be actively involved in pathogenesis (Zhonghua Yi Xue Za Zhi 2008;88:3349)
● Autoimmunity may be related to increased toll-like receptor 4 expression in thymus of some myasthenic patients (Am J Pathol 2005;167:129)

Clinical features
=========================================================================

● 12% of MG patients have other autoimmune diseases, including Graves’ disease, rheumatoid arthritis
● MG patients with thymomas may have autoantibodies to titin or other striated muscle antigens
● 65% of patients have thymic hyperplasia, 25% normal thymus, 10% thymomas; risk factors for thymoma are males with initial MG symptoms age 50+ years
● Present or develops in 30-45% of patients with thymomas, usually months/years after excision of thymoma
● Lymphoid follicles in thymoma or adjacent thymus indicates higher risk for MG
● MG associated thymomas are morphologically similar to non-MG associated thymomas

Prognostic factors
=========================================================================

● Mildest clinical outcome associated with normal thymus, most severe associated with thymoma (Clin Neurol Neurosurg 2012 Jul 5 [Epub ahead of print])

Treatment
=========================================================================

● Thymectomy (regardless of presence of thymoma)

Micro images
=========================================================================

Thymic follicular hyperplasia

Differential diagnosis
=========================================================================

Lambert-Eaton syndrome: muscle weakness due to antibodies to neuronal calcium channel



Thymus

Thymic dysplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Congenital thymic alteration due to developmental arrest
● Lack of differentiation of thymic epithelium, responsible for absence of Hassal's corpuscles, is main feature (Histopathology 1992;21:499)

Clinical features
=========================================================================

● Associated with severe combined immunodeficiency syndrome, ataxia-telangiectasia, chromosomal instability syndromes, Nezelof syndrome (Arch Pathol Lab Med 1987;111:1118)
● Incomplete form of DiGeorge syndrome is congenital anomaly with a constellation of findings that includes thymic hypoplasia (J Cutan Pathol 2008;35:380); complete form has absent thymus

Gross description
=========================================================================

● Small thymus (< 5g)

Micro description
=========================================================================

● Tubules and rosettes of primitive appearing epithelium without segregation into cortical and medullary regions
● No Hassall’s corpuscles, no/rare lymphocytes

Differential diagnosis
=========================================================================

Acute thymic involution



Thymus

Thymic follicular hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Defined as substantial numbers of lymphoid follicles in thymus of adults
● Thymus usually has normal size / weight

Clinical features
=========================================================================

● Present in 65% with myasthenia gravis
● Also associated with hyperthyroidism, Addison’s disease, SLE, early HIV, multilocular cysts, other immune-related diseases
● Often differerent clinical history than true thymic hyperplasia (Pathologica 2009;101:175)

Micro description
=========================================================================

● Follicles with germinal centers, medullary epithelial cells may be disordered or hypertrophied

Micro images
=========================================================================

Lymphoid follicles in the thymus in a patient with myasthenia gravis

Differential diagnosis
=========================================================================

● Normal lymphoid follicles of infants / children (few present)



Thymus

True thymic hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Thymus larger than normal limits for age, based on tables
● Otherwise histologically unremarkable

Epidemiology
=========================================================================

● Often in infants or children, or in adults after cancer chemotherapy

Case reports
=========================================================================

● 5 week old boy with severe thymic cyst bleeding (Ann Diagn Pathol 2007;11:358)
● 22 year old man with thymic hemorrhage (Pathol Res Pract 2010;206:331)
● 24 year old woman who was treated for T-cell lymphoma (J Clin Oncol 2004;22:953)
● 26 year old woman with thymolipoma, suggesting an origin from thymic true hyperplasia (Int J Surg Pathol 2010;18:526)
● 53 year old woman with unilocular thymic cyst (Ann Diagn Pathol 2006;10:32)

Micro images
=========================================================================


Low power view

Histologically normal thymus

Normal thymus-Hassall’s corpuscle

p63, XIAP

Immunostains
=========================================================================

● p63+, XIAP- (Am J Clin Pathol 2009;131:689)



Cystic lesions

Cystic lesions-general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Comprise 10-15% of radiologically detected mediastinal masses, which may also be bronchogenic, enteric, parathyroid or pericardial
● May have developmental origin
● Imaging of cystic mediastinal masses is useful (Radiographics 2002;22:S79)

Clinical images
=========================================================================



Translucent round thymic cyst protruding from thorax



Cystic lesions

Bronchogenic cyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Due to developmental defect from fusion of tracheoesophageal septum
● Along tracheobronchial tree, usually posterior to carina
● Usually asymptomatic

Epidemiology
=========================================================================

● Childhood or middle life

Clinical features
=========================================================================

● Usually symptomatic at diagnosis, complete excision is curative (Lung 2008;186:55)

Case reports
=========================================================================

● 30 year old man with bronchogenic cyst presenting as a thyroid mass (Head Neck Pathol 2011;5:416)
● 41 year old woman with carcinoid tumor arising in a thymic bronchogenic cyst associated with thymic follicular hyperplasia (Pathol Int 2012;62:49)

Xray description
=========================================================================

● Round/oval mass that molds to adjacent structures
● Wall may contain linear calcifications
● May have independent vascular supply

Clinical images
=========================================================================



Translucent round cyst behind descending aorta

Gross description
=========================================================================

● Unilocular or multilocular with internal septation; contain viscous or turbid fluid

Micro description
=========================================================================

● Resemble normal bronchi
● Lined by respiratory-type epithelium (pseudostratified columnar, often ciliated) with underlying fascicles of smooth muscle and mature cartilage
● No cholesterol granulomas
● May have extensive squamous metaplasia

Micro images
=========================================================================


Cyst wall with respiratory epithelium

Cyst lining has pseudostratified ciliated columnar epithelium

Bronchial-type seromucinous glands beneath epithelium

Differential diagnosis
=========================================================================

Mature teratoma: see Am J Clin Pathol 2008;130:265



Cystic lesions

Enteric cyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Children or teens, with cysts usually in posterior mediastinum, due to developmental defect from fusion of tracheoesophageal septum
● Gastric cysts may produce acid and rupture or hemorrhage

Clinical features
=========================================================================

● Associated with vertebral anomalies (hemivertebrae, spina bifida)
● Leaky cysts are associated with pleural effusion or pulmonary consolidation
● Paraesophageal cysts are associated with dysphagia or subnormal weight gain
● Gastroesophageal cysts are associated with cough, vomiting, fever, pneumonia, empyema

Case reports
=========================================================================

● 39 year old man with adenocarcinoma arising from a mediastinal enteric cyst (Intern Med 2007;46:781)
● Neonate with posterior mediastinal gastoenteric cyst (Saudi Med J 2004;25:955)

Gross description
=========================================================================

● 2-10 cm, rounded or irregular, with fibromuscular wall of variable thickness
● Usually unilocular but may be multiloculated
● Smooth inner lining, often mucoid contents

Micro description
=========================================================================

● Squamous, simple columnar, pseudostratified columnar or mixed epithelial lining, usually with some gastric glandular mucosa, overlying a double layer of smooth muscle
● No cholesterol granulomas, no cartilage



Cystic lesions

Lymphangioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called cystic hygroma
● Benign proliferation of lymphatic channels
● Common; in anterior, middle or posterior mediastinum or soft tissue of neck
● Large lesions may compress lungs, heart, nerves, but most lesions are asymptomatic and found on Xray

Epidemiology
=========================================================================

● Usually in children, often with cervical component, rarely in adults (Ann Thorac Cardiovasc Surg 2001;7:103)

Case reports
=========================================================================

● 52 year old woman with mediastinal cystic lymphangioma (Jpn J Thorac Cardiovasc Surg 2004;52:567)

Xray description
=========================================================================

● Variegated appearance, appears to infiltrate mediastinal soft tissue

Gross description
=========================================================================

● Gray-white masses, edematous appearing, variable sized cystic cavities, serous type fluid, smooth inner lining

Micro description
=========================================================================

● Large, irregular vascular spaces lined by flattened, bland epithelial cells with fibroblastic or collagenous stroma
● Variable lymphocytic infiltrates; no specialized epithelium, no cholesterol granulomas

Micro images
=========================================================================



Lymphatic channels lined by attenuated endothelial cells



Cystic lesions

Meningocele - cystic


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Posterior mediastinum cysts in infants or children which communicate with meninges, usually through a defect in vertebral bodies
● Contain clear/amber cerebrospinal fluid
● Usually incidental finding identified prior to surgery

Micro description
=========================================================================

● Thick fibrous wall, lined by flattened arachnoid cells
● Variable neural tissue, calcification



Cystic lesions

Mullerian cyst (Hattori’s Cyst)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● First described in 2005 (Virchows Arch 2005;446:82)
● Typically women, in posterior mediastinum, showing müllerian differentiation (Ann Diagn Pathol 2007;11:417)
● Initially classified as bronchogenic or unspecified benign serous cysts

Case reports
=========================================================================

● 53 year old woman with previous mediastinal teratoma (Ann Thorac Cardiovasc Surg 2012;18:39)

Gross description
=========================================================================

● 1.3 to 5 cm with thin wall containing smooth muscle

Micro description
=========================================================================

● Lined by simple cylindrical or cuboidal, nonmucinous, and often ciliated epithelium resembling uterine tubal epithelium

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CK7, EMA, ER, PR



Cystic lesions

Pancreatic pseudocyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rarely is present in mediastinum
● Encapsulated collection of pancreatic secretion, blood, and necrotic material
● Almost always occurs in the lower part of the posterior mediastinum
● Gains access to the chest via esophageal or aortic hiatus

Clinical features
=========================================================================

● Cystic posterior mediastinal mass that develops over a short time in a patient with pancreatitis (pseudocyst)
● CT/MRI shows fluid-containing mediastinal cystic mass (Radiographics 2002;22:S79)



Cystic lesions

Parathyroid cyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare causes of neck swelling accounting for 0.6% of thyroid and parathyroid lesions (Br J Hosp Med (Lond) 2012;73:108)
● Derived from third and fourth branchial pouch, as does thymus
● Cysts may be present in low cervical or anterosuperior mediastinum

Clinical features
=========================================================================

● Pure cysts are present at any age; contain high levels of parathyroid hormone; can diagnose by FNA via PTH in fluid (Am J Clin Pathol 1986;86:776)
● Patients usually are normocalcemic and present with an asymptomatic mass on Xray

Case reports
=========================================================================

● 46 year old woman with thyroid nodule (Indian J Pathol Microbiol 1996;39:297)
● 50 year old woman with neck mass (Med Ultrason 2011;13:157)
● 66 year old man with a palpable neck mass and hypercalcemia (West J Med 1999;170:118)

Gross description
=========================================================================

● 1-10 cm, unilocular, thin walled, clear fluid, no nodules

Micro description
=========================================================================

● Lined by flattened parathyroid chief cells, oxyphils, clear cells
● Cyst wall has uniform thickness
● May contain granular material resembling colloid
● No cholesterol granulomas, no cartilage, no smooth muscle

Micro images
=========================================================================



Giant cystic parathyroid adenoma

Positive stains
=========================================================================

● Chromogranin A, glycogen, parathyroid hormone

Negative stains
=========================================================================

● Thyroglobulin

Differential diagnosis
=========================================================================

Parathyroid adenoma with secondary cystic change (J Clin Endocrinol Metab 2006;91:1635)
● Heterotopic salivary gland like tissue: see Am J Surg Pathol 2000;24:837



Cystic lesions

Pericardial cyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually at right cardiophrenic angle, adherent to pericardium and diaphragm; may communicate with pericardial cavity
● Due to failure of one of multiple disconnected lacunae to merge with the others

Clinical features
=========================================================================

● Usually asymptomatic patients of all ages anywhere in mediastinum; rarely associated with dyspnea or chest pain

Case reports
=========================================================================

● 30 year old man with large cyst and pericarditis (Ann Thorac Surg 2009;88:e11)

Xray description
=========================================================================

● Irregular, adjacent to cardiac contour

Gross description
=========================================================================

● Thin fibrous wall, unilocular, collapses when opened, smooth cyst lining, serous fluid contents

Micro description
=========================================================================

● Fibrous tissue lined by bland mesothelium, rarely with papillary hyperplasia, no cholesterol granulomas, no smooth muscle, no cartilage, no specialized epithelium

Micro images
=========================================================================



Cyst wall composed of thin layer of fibrous tissue lined with single layer of mesothelial cells

Positive stains
=========================================================================

● Keratin



Cystic lesions

Seminoma - cystic


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Cysts are due to degenerative changes, may be prominent (Am J Surg Pathol 1995;19:1047)
● Usually in anterosuperior mediastinum

Clinical features
=========================================================================

● Associated with Klinefelter’s syndrome (XXY), hematologic abnormalities

Case reports
=========================================================================

● Prominent cystic change and high CA19-9 level of cystic fluid (Ann Thorac Surg 2009;88:1693)

Gross description
=========================================================================

● Variable cystic contents, unilocular or multilocular

Micro description
=========================================================================

● Seminoma cells present in cyst wall, but may not be numerous
● Have glycogen rich cytoplasm with marked retraction, coarse chromatin with prominent nucleoli, variable mitotic figures
● Subdivided by fine fibrous trabeculae
● Associated with germinal centers, giant cells
● No cholesterol granulomas (may have other granulomas), no cartilage, no smooth muscle

Positive stains
=========================================================================

● PAS, PLAP



Cystic lesions

Teratoma - cystic


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Subtypes: immature, malignant transformation

General
=========================================================================

● Common - 10-20% of mediastinal lesions
● In anterosuperior mediastinum
● Neoplastic, not a developmental malformation
● Usually contain tissue derived from at least 2 of 3 germ cell layers - endoderm, mesoderm, ectoderm
● 50% have cough, dyspnea or chest pain
● Tumors adhering to lung, pericardium or blood vessels are either malignant or ruptured mature teratomas with inflammatory reaction

Epidemiology
=========================================================================

● Usually children or young adults (mean age 20 years)

Clinical features
=========================================================================

● May be associated with Klinefelter’s syndrome (XXY)
● Rarely associated with acute myelogenous leukemia

Gross description
=========================================================================

● Cystic with variable solid component
● Malignant tumors are often adherent to adjacent structures or have necrosis
● Benign tumors often have keratinous debris, cartilage or mucus

Case reports
=========================================================================

● 19 year old man with extrathyroidal multi-septate, predominantly cystic neck mass (J Med Case Rep 2008;2:23)
● 22 year old man with obliteration of right cardiophrenic sinus by mass (J Med Case Rep 2011;5:193)
● 28 year old woman with concomitant mature cystic teratoma in mediastinum and ovary (J Thorac Dis 2012;4:434)

Micro description
=========================================================================

● Mature squamous epithelium with cutaneous appendages (commonly), GI columnar epithelium, neuroglia, bone, cartilage, fat, striated muscle
● Also choroid plexus, hepatocytes, pancreas, retinal-type tissue
● May contain immature neuroepithelial tissue (see below)
● No cholesterol granulomas

Micro images
=========================================================================


Mature cystic teratoma

Mature teratoma


Immature teratoma

General
=========================================================================

● Contains immature neuroepithelial tissue such as embryonic tubules
● Benign behavior in patents under age 15


Mature teratoma with malignant transformation

General
=========================================================================

● Very rare
● Contain overtly malignant tissue
● Tumors with germ cell components are classified as malignant mixed germ cell tumors

Case reports
=========================================================================

● 44 year old man with adenocarcinoma with sarcomatous dedifferentiation (Pathol Res Pract 2012;208:741)
● 66 year old man with mature cystic teratoma with focal well-differentiated adenocarcinoma (Am J Clin Pathol 1994;101:531)



Cystic lesions

Thymic cyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also proliferating multilocular thymic cyst below

General
=========================================================================

● Thymus derived from third and fourth branchial pouch, as is parathyroid gland
● Usually presents as incidental mass in anterosuperior mediastinum
● Congenital (unilocular) or acquired (multilocular)
● Rarely occur post-operatively
● Mixed multilocular thymic cyst: has parathyroid or salivary gland tissue

Epidemiology
=========================================================================

● Usually ages 20-50 years

Clinical features
=========================================================================

● May be associated with thymic carcinoma (Am J Surg Pathol 2011;35:1074), mediastinal Hodgkin lymphoma, but not non-Hodgkin lymphoma

Case reports
=========================================================================

● 6 year old boy with huge cervico-thoracic thymic cyst (Interact Cardiovasc Thorac Surg 2003;2:339)
● 23 year old man with epithelioid granulomas within cyst (Ann Diagn Pathol 2012;16:38)

Xray description
=========================================================================

● Rounded, circumscribed masses in anterior mediastinum, may have peripheral rim of calcification

Gross description
=========================================================================

● Up to 18 cm
● Unilocular with thin wall and serous fluid or multilocular with turbid, cheesy or hemorrhagic material, thick wall and fibrous adhesions
● Either centered in thymus or connected to it by a small pedicle

Gross images
=========================================================================


Huge thymic cyst

Thin walled cyst with thyroid

Micro description
=========================================================================

Unilocular cysts:
● Have thin wall with a few layers of bland squamoid cells and thymic tissue in wall, no inflammation, no cholesterol granulomas, no hemorrhage

Multilocular cysts:
● May have more layers of squamoid, cuboidal, columnar, micropapillary or mixed glandular epithelium
● May have pseudoepitheliomatous hyperplasia
● Usually cholesterol granulomas
● Commonly lymphocytes, granulation tissue, hemorrhage
● Cysts separated by thick fibrous septae
● 50% have Hassall’s corpuscles or other thymic tissue, but not in cyst wall
● No cartilage or smooth muscle is present

Micro images
=========================================================================


Thymic cyst

Flat epithelial lining #1

#2

Proliferative epithelium lining cyst wall

Bland squamoid epithelium

Papillary outpouchings

Cholesterol clefts

Thymic tissue in cyst wall

Squamous epithelial lining

Differential diagnosis
=========================================================================

Cystic degeneration in Hodgkin lymphoma
Seminoma
Thymoma
Cystic lymphangioma


Proliferating multilocular thymic cyst

General
=========================================================================

● Resembles cutaneous proliferating epidermoid cyst and proliferating trichilemmal cyst

Micro description
=========================================================================

● Pseudoepitheliomatous hyperplasia of cyst lining cells (narrow tongues of squamoid epithelium extending deeply into fibrous cyst wall) with reactive changes but no dysplasia
● Typical mitotic figures present

Differential diagnosis
=========================================================================

Squamous cell carcinoma: extremely rare in thymic cysts



Cystic lesions

Thymomas - cystic


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Cystic degeneration of thymoma in anterosuperior mediastinum

Clinical features
=========================================================================

● Associated with paraneoplastic syndromes

Gross description
=========================================================================

● Encapsulated, uniloculated or multiloculated
● Variable cystic contents

Micro description
=========================================================================

● Bland proliferation of thymic epithelium (spindle or polygonal cells) present in cyst wall
● Usually no cholesterol granulomas, no cartilage, no smooth muscle

Micro images
=========================================================================



Spindle cell thymoma (type A) has cysts of various sizes

Differential diagnosis
=========================================================================

Thymic cyst: no/minimal thymic epithelial cells in cyst wall; no evidence of thymoma



Tumors

Tumors - general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Macroscopic invasion into lung, pericardium or vessels is usually associated with the potential for invasive growth, although not necessarily malignancy (thymomas, fibromatosis, fibrosing mediastinitis)
● Hemorrhage and necrosis are usually associated with malignancy
● Encapsulation is associated with indolent processes (benign cysts, thymomas)
● Stromal bands are associated with thymomas (bands intersect at right angles) or lymphoma (bands intersect obliquely)
Sternberg’s approach to mediastinal tumors: cystic or not, atypical cells or not, if malignant-either small cells, large polygonal cells, mixed small and large polygonal cells, spindle/pleomorphic cells, myxoid-adipose



Cystic lesions

Thymic cyst


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also proliferating multilocular thymic cyst below

General
=========================================================================

● Thymus derived from third and fourth branchial pouch, as is parathyroid gland
● Usually presents as incidental mass in anterosuperior mediastinum
● Congenital (unilocular) or acquired (multilocular)
● Rarely occur post-operatively
● Mixed multilocular thymic cyst: has parathyroid or salivary gland tissue

Epidemiology
=========================================================================

● Usually ages 20-50 years

Clinical features
=========================================================================

● May be associated with thymic carcinoma (Am J Surg Pathol 2011;35:1074), mediastinal Hodgkin lymphoma, but not non-Hodgkin lymphoma

Case reports
=========================================================================

● 6 year old boy with huge cervico-thoracic thymic cyst (Interact Cardiovasc Thorac Surg 2003;2:339)
● 23 year old man with epithelioid granulomas within cyst (Ann Diagn Pathol 2012;16:38)

Xray description
=========================================================================

● Rounded, circumscribed masses in anterior mediastinum, may have peripheral rim of calcification

Gross description
=========================================================================

● Up to 18 cm
● Unilocular with thin wall and serous fluid or multilocular with turbid, cheesy or hemorrhagic material, thick wall and fibrous adhesions
● Either centered in thymus or connected to it by a small pedicle

Gross images
=========================================================================


Huge thymic cyst

Thin walled cyst with thyroid

Micro description
=========================================================================

Unilocular cysts:
● Have thin wall with a few layers of bland squamoid cells and thymic tissue in wall, no inflammation, no cholesterol granulomas, no hemorrhage

Multilocular cysts:
● May have more layers of squamoid, cuboidal, columnar, micropapillary or mixed glandular epithelium
● May have pseudoepitheliomatous hyperplasia
● Usually cholesterol granulomas
● Commonly lymphocytes, granulation tissue, hemorrhage
● Cysts separated by thick fibrous septae
● 50% have Hassall’s corpuscles or other thymic tissue, but not in cyst wall
● No cartilage or smooth muscle is present

Micro images
=========================================================================


Thymic cyst

Flat epithelial lining #1

#2

Proliferative epithelium lining cyst wall

Bland squamoid epithelium

Papillary outpouchings

Cholesterol clefts

Thymic tissue in cyst wall

Squamous epithelial lining

Differential diagnosis
=========================================================================

Cystic degeneration in Hodgkin lymphoma
Seminoma
Thymoma
Cystic lymphangioma


Proliferating multilocular thymic cyst

General
=========================================================================

● Resembles cutaneous proliferating epidermoid cyst and proliferating trichilemmal cyst

Micro description
=========================================================================

● Pseudoepitheliomatous hyperplasia of cyst lining cells (narrow tongues of squamoid epithelium extending deeply into fibrous cyst wall) with reactive changes but no dysplasia
● Typical mitotic figures present

Differential diagnosis
=========================================================================

Squamous cell carcinoma: extremely rare in thymic cysts



Thymoma and related entities

Thymoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Most common primary anterior mediastinal neoplasm

Epidemiology
=========================================================================

● Commonly ages 49-62 years
● Childhood thymomas are rare (usually are lymphoblastic lymphomas), usually near puberty, similar behavior and morphology as adult tumors, but only occasionally associated with myasthenia gravis

Sites
=========================================================================

● Usually anterosuperior mediastinum
● Rarely posterior mediastinum, lung hilum or parenchyma, neck, pleura, thyroid

Clinical features
=========================================================================

● Associated with myasthenia gravis [MG] (10% with MG have thymoma, 30-45% with thymoma develop MG, higher risk for MG if lymphoid follicles are present in thymoma or adjacent thymus)
● Associated with other immune-mediated disorders: acquired hypogammaglobulinemia (12%), aplastic anemia, pure anerythrogenesis, dermatomyositis, leukemia, lymphoma, lymphopenia, motor neuropathy, mucocutaneous candidiasis, myeloma, myocarditis, myositis, relapsing polychondritis, rheumatoid arthritis, scleroderma, Sjogren’s disease, syndrome of inappropriate antidiuretic hormone secretion, systemic lupus erythematosus
● Patients with thymomas have increased risk of developing additional malignancies, especially thymomas with predominantly cortical component (Histopathology 2012;60:437)
● All thymic tumors, regardless of histology, are associated with invasion and metastases (Mod Pathol 2012;25:370)

Prognostic factors
=========================================================================

Poor prognostic factors: high stage, B3 or C classification, positive margin, invasion of capsule (Am J Surg Pathol 2002;26:1605)
● Prognostic factors for OS were age, WHO histology, Masaoka stage and recurrence, while pleural involvement, WHO histology and Masaoka stage had significant impacts on DFS (Oncol Rep 2008;19:1525)
● Weakly prognostic: podoplanin overexpression may predict lymph node metastasis and poor clinical outcome (Hum Pathol 2011;42:533)
● Not prognostic: hemorrhage and necrosis in well encapsulated noninvasive thymomas (Am J Surg Pathol 2001;25:1086)
● Controversial: transcapsular invasion (Arch Pathol Lab Med 2008;132:926, Arch Pathol Lab Med 2008;132:1859)

Case reports
=========================================================================

● 60 year old man with invasive thymoma and paraneoplastic retinopathy (Hum Pathol 2003;34:717)
● 61 year old man with metaplastic thymoma (Int J Surg Pathol 2009;17:51)
● 62 year old man with composite thymoma and CLL/SLL (Arch Pathol Lab Med 2003;127:E76)
● 70 year old man with a calcified mediastinal mass (Case of the Week #99)
● Two cases of thymoma arising within cardiac myxoma (Am J Surg Pathol 2005;29:1208)

Treatment
=========================================================================

● Surgical excision
● Possibly chemotherapy or radiation

Gross description
=========================================================================

● 80% encapsulated, 20% infiltrative into surrounding structures
● Usually large unless incidental with coronary bypass surgery
● Multinodular, yellow-gray
● Sharp lobulations due to fibrous bands with some nodules having pointed ends
● Cystic degeneration common

Micro description
=========================================================================

● Spindle cell histologic patterns have indolent behavior, may be associated with hematologic malignancies
● Non-spindle cell thymomas are also called cortical thymomas
● Cytologically bland epithelial cells and non-neoplastic lymphocytes
● Capsule may be thick and calcified
● May have prominent vasculature, microcystic and pseudopapillary patterns, extensive sclerosis
● Rarely has marked plasma cell infiltrate, amyloid, rosettes without central lumina
● Usually no well formed Hassall’s corpuscles
Thymoma with pseudosarcomatous stroma: highly cellular spindle cell proliferation without nuclear atypia (Am J Surg Pathol 1997;21:1316)

Micro images
=========================================================================


AB: medullary and spindle cells and lymphocytes

B1: cellular lobules of lymphocytes with scattered medullary cells

B3: epithelial cells with nuclear atypia

Various stains

Virtual slides
=========================================================================



Thymoma

Positive stains
=========================================================================

● CEA, CD3 (lymphocytes outside lymphoid follicles are T cells), EMA (some tumors), keratin (epithelial cells), Ki-67, S100 (interdigitating reticulum cells),
● CD205, Foxn1 (Am J Surg Pathol 2007;31:1038)
● PAX8 (Am J Surg Pathol 2011;35:1305)
● XIAP (Am J Clin Pathol 2009;131:689)

Negative stains
=========================================================================

● CD70, vimentin (Am J Surg Pathol 2000;24:742)

Electron microscopy description
=========================================================================

● Branching tonofilaments, complex desmosomes, elongated cell processes, basal lamina

Molecular / cytogenetics description
=========================================================================

● Rarely alterations of #6 (Arch Pathol Lab Med 2000;124:1714)

Differential diagnosis
=========================================================================

Thymic cyst
Thymic carcinoid: well formed rosettes
● Lymphoma
Seminoma
Solitary fibrous tumor



Thymoma and related entities

Staging


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Staging (Masaoka)
=========================================================================

I: Totally encapsulated grossly and microscopically (includes microscopic invasion into but not through the capsule)
IIA: Microscopic invasion through capsule but totally excised
IIB: Transcapsular infiltration into thymus, mediastinal soft tissue or pleura
III: Invades pericardium, great vessels, lungs
IVA: Seeds pericardial or pleural surfaces multifocally
IV: Distant metastases

Substaging (Haniuda)
=========================================================================

II-p0: No adhesion to pleura
II-p1: Fibrous adhesions between tumor and pleura without true invasion of pleura
II-p2: Actual pleural invasion

Additional references
=========================================================================

Am J Clin Pathol 2012;137:451, J Cardiovasc Surg (Torino) 2006;47:89



Thymoma and related entities

Thymoma classification


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also these types below: A, AB, B1, B2, B3, microthymoma, nodular hyperplasia

WHO Classification
=========================================================================

A: also called epithelial, spindle cell, medullary; atrophic, mimics adult thymus; homogenous population of neoplastic epithelial cells with spindle/oval shape, no nuclear atypia, and accompanied by few or no non-neoplastic lymphocytes
AB: mixed thymoma; tumor in which foci having the features of type A thymoma are mixed with foci rich in lymphocytes; the segregation of the two patterns can be sharp or indistinct (Am J Surg Pathol 1999;23:955)
B: bioreactive, resembles thymus in fetus and infant
B1: lymphocyte rich; resembles normal functional thymus by combining large expanses having normal thymic cortical areas with those resembling thymic medulla
B2: cortical; neoplastic epithelial component appears as scattered plump cells with vesicular nuclei, distinct nucleoli; heavy population of lymphocytes, perivascular spaces are common
B3: epithelial cells with round/polygonal shape and mild atypia, mixed with minor component of lymphocytes; foci of squamous metaplasia and perivascular spaces common
C: thymic carcinoma


Table

● World Health Organization histologic classification has some prognostic value (Int J Surg Pathol 2009;17:255, Hematol Oncol Clin North Am 2008;22:543, J Cardiovasc Surg (Torino) 2006;47:89), although interobserver variation is common (Histopathology 2008;53:483) and other problems exist ((Semin Diagn Pathol 2005;22:188)

Suster and Moran classification
=========================================================================

● References: Am J Clin Pathol 2006;125:542

Favorable prognostic categories: Groups I-III
Group I
  Encapsulated or minimally invasive thymoma
  Completely excised
  Equivalent to WHO histologic types A, AB, B1, B2

Group II
  Encapsulated or minimally invasive thymoma
  Completely excised
  Equivalent to WHO histologic type B3

Group III
  Widely invasive thymoma or thymoma with implants
  Completely excised
  All histologic types

Unfavorable prognostic categories: Groups IV-VI
Group IV
  Widely invasive thymoma or thymoma with implants
  Incompletely excised
  All histologic types

Group V
  Widely invasive thymoma with or without intrathoracic metastases
  Unresectable/biopsy only
  All histologic types

Group VI
  Widely invasive thymoma with distant metastases
  Unresectable/biopsy only
  All histologic types

Clinical features
=========================================================================

● All thymomas have the potential to become invasive tumors (Am J Clin Pathol 2012;137:444)
● The histopathological spectrum and clinical profile of thymic neoplasms (Indian J Pathol Microbiol 2006;49:1)
● Although much emphasis in recent years has been placed on the histological classification of thymoma, the bulk of the evidence continues to point to clinical staging as the most important parameter for prognostication (J Clin Pathol 2006;59:1238)
● Thymus cancer symptoms, diagnoses, and clinical staging (Biol 345 - Immunology)

Prognostic factors
=========================================================================

● Must distinguish types with benign behavior (A, AB, B, B1, B2) from those with atypical behavior (B3, Ann Thorac Cardiovasc Surg 2005;11:367) and those that are cytologically malignant (type C, also called thymic carcinoma Am J Surg Pathol 2002;26:1605)

Positive stains
=========================================================================

● p63 (also normal thymus, Am J Clin Pathol 2007;127:415)


WHO type A

General
=========================================================================

● Also called spindle cell thymoma
● Rosai believes composed of nonfunctional, postmature thymic epithelial cells that match epithelial cells of involuted thymus in adult life, not cortical or medullary cells

Clinical features
=========================================================================

● May have papillary and pseudopapillary features (Am J Surg Pathol 2011;35:372), adenomatoid like appearance with signet ring cell morphology (Am J Surg Pathol 2010;34:1544)
● May be associated with hematologic malignancies

Prognostic factors
=========================================================================

● Excellent prognosis

Gross description
=========================================================================

● Usually encapsulated or minimal capsular invasion

Gross images
=========================================================================



Well circumscribed with lobulated cut surface

Micro description
=========================================================================

● Epithelial predominant with fusiform epithelial tumor cells
● Gland like spaces, storiform patterns are common
● No / rare lymphocytes
● May have atypical features (Am J Surg Pathol 2012;36:889)
● Either short-spindled (57%), long-spindled (31%) or micronodular (12%) (Am J Surg Pathol 2001;25:111)

Short-spindled:
● 57%, often in hemangiopericytic or microcystic pattern
● Epithelial cells often CD20+

Long-spindled:
● 31%, fibroblast-like epithelial cells resembling fibrohistiocytic neoplasms
● Epithelial cells often CD20+

Micronodular:
● 12%, small nests of short spindle cells without atypia in lymphoid stroma with frequent germinal centers
● No mitotic activity; epithelial cells are CAM5.2+, keratin+, CD20-
● Often incidental findings on chest Xray or at coronary artery bypass surgery
● Not associated with autoimmune disorders

Micro images
=========================================================================


Various images

Thymic epithelial cells without atypia

A: bland spindled epithelial cells with occasional small T cells

A: spindle epithelial cells (arrows) with lymphocytes (arrowheads)

Rosette-like structures mimicking a neuroendocrine neoplasm

Negative stains
=========================================================================

● CD5 (in epithelial cells)


WHO type AB

Micro images
=========================================================================


Various images

AB: immature T cells and scattered large, round thymic epithelial cells

AB: A (asterisk) and B (star) type lobules


WHO type B1

General
=========================================================================

● Also called lymphocyte predominant

Micro description
=========================================================================

● 2/3 or more small lymphocytes
● Lymphocytes efface thymic architecture
● Thick fibrous capsule present, also fibrous septae that intersect at acute angles
● Lymphocytes have folded nuclei (T cells) and mitotic figures
● Lymphocytes mixed with bland thymic epithelial cells, may have perivascular serum “lakes”, mast cells and focal medullary differentiation with loose aggregates of lymphocytes resembling thymic medulla

Micro images
=========================================================================



Case of Week #99


CD3

CD20

Keratin

CD68

Various images

B1: immature T cells (arrows), epithelial tumor cells with large nuclei (arrowheads)

Positive stains
=========================================================================

● Keratin demonstrates finely arborizing network of interconnecting epithelial cell processes
● T cells: CD1, CD2, CD3, CD99, BCL2, TdT

Electron microscopy description
=========================================================================

● Well-formed intercellular junctions between epithelial cell processes, numerous tonofilaments

Differential diagnosis
=========================================================================

Burkitt lymphoma: HIV+, different nuclear histology
Castleman disease: not centered in thymus, “onion-skinning” by lymphocytes, either fibrohyaline or plasma cell subtypes
Lymphoblastic lymphoma: usually teens/young adults, similar staining except negative for keratin, but beware of positive staining of trapped epithelial cells
● Thymic lymphoid hyperplasia: normal cortical and medullary glandular distinction is maintained, well-formed germinal centers present, does not produce a mass


WHO type B2

Micro images
=========================================================================


Various images

B2: abundant epithelial cells with irregular nuclei (arrowheads) and fewer lymphocytes (arrows) than B1


WHO type B3

Micro images
=========================================================================


Various images

B3: perivascular spaces, sheets of large polygonal epithelial cells with nuclear atypia, few lymphocytes

B3: polygonal epithelial cells (arrows) with irregular nuclei

Microthymoma

General
=========================================================================

● Incidental small thymomas, not grossly evident, morphologically identical to conventional B1/B2 thymoma (Am J Surg Pathol 2005;29:415)
● May represent early phase of thymoma development

Micro description
=========================================================================

● Ovoid epithelial cells with pale nuclei and distinct nucleoli, in background of small lymphocytes
● Foci of medullary differentiation and perivascular spaces present


Nodular hyperplasia of thymic epithelium

General
=========================================================================

● Nodular epithelial proliferations in normal sized or enlarged glands removed from adults for myasthenia gravis or as incidental findings during coronary bypass surgery (Indian J Pathol Microbiol 2011;54:539)
● Also called microthymoma, but epithelium have reactive, not thymoma-like appearance

Case reports
=========================================================================

● Two cases (Pathology 2006;38:586)

Micro description
=========================================================================

● Nodular aggregates of bland cells subdivided by fibrous bands



Thymoma and related entities

Ectopic hamartomatous thymoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, supraclavicular-sternal soft tissue mass

Epidemiology
=========================================================================

● Usually adult men

Clinical features
=========================================================================

● May arise from ectopic tissue of third branchial pouch
● Benign behavior

Case reports
=========================================================================

● 19 year old man with supraclavicular subcutaneous mass (J Cutan Pathol 2006;33:369)
● 59 year old man whose tumor had CD99+ lymphocytes and a low proliferation index (Arch Pathol Lab Med 2003;127:e378)

Gross description
=========================================================================

● Well circumscribed, firm, yellow-white, variable microcysts

Gross images
=========================================================================



Yellow-white solid tumor

Micro description
=========================================================================

● Sheets of spindled epithelial cells resembling neurogenic or fibroblastic tumors
● Also epithelial nests, thin anastomosing cords and epithelial lined cysts
● May have focal adipose tissue, small lymphocytes
● No atypia, no necrosis, no mitotic figures

Micro images
=========================================================================


Various images

CD99, CD3, CD20

Positive stains
=========================================================================

● Keratin
Lymphocytes: CD3, CD20, CD99

Electron microscopy description
=========================================================================

● Tonofilaments, well developed cell junctions

Electron microscopy images
=========================================================================



Tonofilaments and cell junctions

Differential diagnosis
=========================================================================

Angiomyolipoma: HMB45+
Biphasic synovial sarcoma: more cellular, more atypia, more mitotic figures
Glandular MPNST: resembles fibrosarcoma, S100+, cytokeratin-
Mixed tumor: chondromyxoid, S100+
Myoepithelioma of soft tissue: chondromyxoid, S100+
Thymolipoma: mediastinum, not neck, no spindle cells



Thymoma and related entities

Ectopic thymoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Resembles thymoma, but in neck ( Histopathology 2005;46:583)
● All reported cases had benign behavior

Epidemiology
=========================================================================

● Usually women

Case reports
=========================================================================

● 69 year old woman with ectopic mid mediastinum thymoma of unusual histological type (Ann Thorac Cardiovasc Surg 2006;12:200)
● 75 year old man with primary pleural thymoma (Arch Pathol Lab Med 2006;130:e62)

Micro images
=========================================================================


Pleural thymoma: right-keratin+, CK5/6+, p63+, Tdt+


Thymoma and related entities

Thymolipoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Increased thymic volume, due to lobules of mature adipose tissue mixed with unremarkable thymic tissue
● Benign
● May be neoplasm of thymic fat (Ann Diagn Pathol 2009;13:185)

Epidemiology
=========================================================================

● Usually young to middle-aged adults, found incidentally

Clinical features
=========================================================================

● 10% associated with thymoma-like paraneoplastic symptoms

Case reports
=========================================================================

● 26 year old woman with possible origin from thymic true hyperplasia (Int J Surg Pathol 2010;18:526)
● 36 year old woman with thymoma and thymic carcinoma arising in thymolipoma (Int J Surg Pathol 2009;17:55)
● 69 year old man with 570g mediastinal mass (Arch Pathol Lab Med 2004;128:e159)

Gross description
=========================================================================

● Encapsulated, up to 20 cm
● Resembles lipoma

Micro description
=========================================================================

● Thin fibrous capsule surrounding lobules of mature adipose tissue intimately associated with unremarkable thymic tissue containing cortex, medulla and Hassall’s corpuscles
● May have thymic epithelial proliferation, myoid cells, zones of dense fibrosis

Micro images
=========================================================================



Various images, CK903



Other benign / low grade tumors

Angiomyolipoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign tumor, common in kidney, rare in mediastinum

Clinical features
=========================================================================

● May arise in setting of tuberous sclerosis complex

Case reports
=========================================================================

● Angiomyolipomas in mediastinum and lung, possibly associated with lymphangioleiomyomatosis and tuberous sclerosis complex (J Thorac Imaging 2012;27:W21)
● Incidentally discovered angiomyolipoma in the anterior mediastinum (Ann Diagn Pathol 2008;12:293)

Gross images
=========================================================================



Large fatty anterior mediastinal mass

Micro description
=========================================================================

● Composed of varying proportions of smooth muscle cells, blood vessels, and adipose tissue

Micro images
=========================================================================



Confluencing vessel lumina partly filled with blood (right) and interstitial stroma containing mostly smooth muscle cells and focal fat cells

Positive stains
=========================================================================

● IHC: positive for smooth muscle actin and HMB-45.



Other benign / low grade tumors

Elastolipoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 57 year old woman with mature fat, sclerotic connective tissue, extensive eosinophilic deposits resembling elastic fibers (Am J Surg Pathol 1995;19:364)

Micro description
=========================================================================

● Lipoma with abnormal elastic fibers or dense zones of fibrosis

Micro images
=========================================================================



Collagenous material and roundly shaped elastic fibers

Positive stains
=========================================================================

● Elastin



Other benign / low grade tumors

Ependymoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● CNS tumor, very rarely occurs as mediastinal primary

Epidemiology
=========================================================================

● Most patients are female

Clinical features
=========================================================================

● Usually do not invade surrounding tissues but lymph node metastases have been reported
● May derive from paravertebral ependymal rests due to location, sympathetic ganglia, lack of teratomatous elements (Ann Diagn Pathol 1998;2:293)

Case reports
=========================================================================

● 39 year old woman with myxopapillary ependymoma of mediastinum (Ann Diagn Pathol 2006;10:283)
● 46 year old woman with primary ependymoma in the posterior mediastinum (Ann Thorac Cardiovasc Surg 2011;17:494)
● 50 year old woman with back pain and cystic tumor (Ann Thorac Cardiovasc Surg 2009;15:332)
● Tumor adherent to the lung with metastasis to adjacent mediastinal lymph nodes (Arch Pathol Lab Med 1988;112:194)

Gross description
=========================================================================

● Tumor shows both cystic and solid elements

Micro images
=========================================================================



Various images (scroll down)



Other benign / low grade tumors

Fibromatosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Anterior or posterior mediastinum

Epidemiology
=========================================================================

● Children and young adults

Clinical features
=========================================================================

● Associated with superior vena cava syndrome, nerve entrapment or dysphagia

Case reports
=========================================================================

● 48 year old man with intra-thoracic desmoid tumor and with a previous aortocoronary bypass (World J Surg Oncol 2006;4:43)
● 61 year old man with de novo fibromatosis and no history of thoracotomy or trauma (Rev Mal Respir 2008;25:82)

Gross description
=========================================================================

● Poorly demarcated (often receive in multiple fragments), gritty, tan-white, centered in soft tissue

Micro description
=========================================================================

● Fibromyxoid matrix with paucicellular, bland tumor cells in parallel or fascicular patterns
● Cells have dispersed chromatin, minimal nucleoli, eosinophilic or amphophilic cytoplasm
● Thick walled venule-sized vessels with open lumina
● No staghorn vessels
● No storiform growth, no nuclear pleomorphism, no / rare mitotic activity, no inflammatory infiltrate

Micro images
=========================================================================



A: fusiform cells; B: myxoid degeneration

Positive stains
=========================================================================

● Actin, desmin, vimentin

Electron microscopy description
=========================================================================

● Myofibroblastic features of intrareticular collagen fibers, thin filament bundles, cytoplasmic dense bodies

Differential diagnosis
=========================================================================

Inflammatory myofibroblastic tumor
Sclerosing mediastinitis



Other benign / low grade tumors

Ganglioneuroma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign neural tumor; more common than neuroblastoma or ganglioneuroblastoma

Epidemiology
=========================================================================

● Usually children; also age 20-39 years

Clinical features
=========================================================================

● No symptoms in most cases
● Rarely watery diarrhea from vasoactive intestinal peptide (VIP) synthesis or symptoms of spinal nerve root compression
● Clinical diagnosis is aided by integrating age, clinical findings, location, imaging (AJR Am J Roentgenol 2011;197:W643)

Case reports
=========================================================================

● 8 year old boy with ganglioneuroblastoma (J Med Case Rep 2011;5:322)
● 34 year old man whose tumor had perineural cell differentiation (Cesk Patol 2012;48:94)
● 45 year old woman with 21 cm tumor (Interact Cardiovasc Thorac Surg 2011;13:344)

Treatment
=========================================================================

● Excision is curative

Gross description
=========================================================================

● Encapsulated, glistening tumor
● May have intradural growth and dumbbell shape
● Soft, yellow-gray cut surface, may have cystic and fatty areas, usually no necrosis

Gross images
=========================================================================


21 cm ganglioneuroma

Well-circumscribed tumor with whorled appearance

Micro description
=========================================================================

● Spindle cell (schwannian) proliferation similar to neurofibroma, but with well-formed ganglion cells, often in clusters and multinucleated
● Focal lymphocytes present

Micro images
=========================================================================



Proliferation of spindled Schwann cells and scattered ganglion cells

Positive stains
=========================================================================

● Synaptophysin (ganglion cells)



Other benign / low grade tumors

Hemangioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 1 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign proliferation of blood vessels, most commonly in anterior compartment
● In adults, usually cavernous hemangioma

Case reports
=========================================================================

● 55 year old woman with venous hemangioma (Ann Thorac Cardiovasc Surg 2012;18:247)
● 60 year old man with lymphangiohemangioma (Gen Thorac Cardiovasc Surg 2011;59:575)
● Sclerosing hemangioma (Clin Radiol 2011;66:792)

Treatment
=========================================================================

● Excision is curative

Micro description
=========================================================================

● Dilated vessels with flattened endothelium, separated by fine septa
● May have focal thrombosis, calcification, cholesterol granulomas

Micro images
=========================================================================



Various images



Other benign / low grade tumors

Inflammatory myofibroblastic tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also Soft tissue chapter

General
=========================================================================

● May present with superior vena cava syndrome or cardiorespiratory compromise
● Any age

Terminology
=========================================================================

● Also called inflammatory pseudotumor

Case reports
=========================================================================

● 22 year old woman with calcifying fibrous pseudotumours and multiple pleural and mediastinal lesions (Interact Cardiovasc Thorac Surg 2010;10:652)
● 58 year old woman with mediastinal mass invading sternum, pericardium and pleura (Ann Thorac Surg 2008;86:1362)
● 59 year old man with ALK abnormalities (Virchows Arch 2005;446:451)
● 72 year old man with spontaneous regression of IMT in cardiophrenic angle (Diagn Interv Radiol 2008;14:197)
● Treatment with salvage irradiation and monitoring with FDG-PET/CT (Tumori 2010;96:322)

Xray description
=========================================================================

● Asymmetric mediastinal widening with projection of mass into upper lung field

Gross description
=========================================================================

● Dense white fibrosis, well demarcated from surrounding tissue

Micro description
=========================================================================

● Bland fusiform cells, haphazard or fascicular, with lymphocytes and other inflammatory cells

Micro images
=========================================================================



Recurrent tumor

Positive stains
=========================================================================

● Alpha smooth muscle actin, vimentin

Differential diagnosis
=========================================================================

Sclerosing mediastinitis: see Ann Thorac Surg 2009;88:293



Other benign / low grade tumors

Lipoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Common, occur throughout mediastinum
● Often very large and located just above diaphragm
● Anterosuperior lipomas clinically resemble thymolipoma

Case reports
=========================================================================

● 41 year old man with fat necrosis (Arch Bronconeumol 2008;44:641)
● 71 year old woman with 27 cm tumor (Kyobu Geka 2010;63:426)
● Case of spindle cell lipoma (J Thorac Imaging 2007;22:355)

Micro images
=========================================================================



Necrotic adipocytes (circle) and peripheral histiocytic reaction (arrow)

Differential diagnosis
=========================================================================

Lipomatosis
Thymolipoma: thymic tissue present



Other benign / low grade tumors

Lipomatosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Diffuse accumulation of mature adipose tissue

Clinical features
=========================================================================

● Associated with obesity, Cushing’s disease, steroid therapy and alcohol abuse (J Assoc Physicians India 2001;49:1026)

Case reports
=========================================================================

● 9 month old boy with unusually complex chromosomal aberrations (Pediatr Dev Pathol 2009;12:469)
● 46 year old woman with mixed connective tissue disease treated with corticosteroids (Ann Dermatol Venereol 2006;133:257)
● 68 year old woman with morbid obesity and incidental finding (Cases J 2008;1:171)

Radiological images
=========================================================================



58 year old man with asymptomatic lipomatosis and obesity



Other benign / low grade tumors

Meningioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● CNS tumor, very rarely occurs as mediastinal primary
● May originate in stellate ganglion

Case reports
=========================================================================

● 41 year old man with primary mediastinal malignant meningioma (Eur J Cardiothorac Surg 2009;36:217)
● 64 year old man (World J Surg Oncol 2012;10:17)
● Angioblastic meningioma of posterior mediastinum causing spontaneous hemothorax (Ann Thorac Surg 2006;81:1903)

Gross images
=========================================================================


Solid, yellow-white

Micro images
=========================================================================


Various images

Uniform spindle cell proliferation separated by collagen bundles


Other benign / low grade tumors

Neurofibroma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually in posterior mediastinum, asymptomatic
● May be multiple
● Plexiform tumors are specific for neurofibromatosis
● Benign

Epidemiology
=========================================================================

● Young adults

Treatment
=========================================================================

● Excision is usually curative (Chirurgia (Bucur) 2011;106:199)

Gross description
=========================================================================

● Often encapsulated in mediastinum (not at other sites)
● Usually centered on or grow within a large spinal nerve root
● May have intradural and extradural components and protrude through neural foramina of vertebral column
● Plexiform tumors resemble a neural plexus
● Degenerative changes are common (fat, hemorrhage, cysts)

Gross images
=========================================================================



Well circumscribed myxomatous tumor surrounded by thin pseudocapsule

Micro description
=========================================================================

● Uniform growth pattern of bland spindle cells in fascicles, storiform arrays or tactoids (“elongated particles that appears as spindle-shaped bodies under polarizing microscope”)
● Myxoid stroma, frequent mast cells, no distinct biphasic pattern
● No thick walled blood vessels

Micro images
=========================================================================



Fascicular proliferation of spindle tumor cells

Electron microscopy description
=========================================================================

● Fibroblast-like tumor cells with abundant rough endoplasmic reticulum, rudimentary cytoplasmic processes, sparse pericellular basal lamina
● May lack evidence of schwannian differentiation



Other benign / low grade tumors

Paraganglioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, 0.3% of mediastinal tumors

Epidemiology
=========================================================================

● Usually young women

Sites
=========================================================================

● Aorticopulmonary vascular root (anterosuperior mediastinum) or paravertebral (posterior mediastinum)

Aorticopulmonary:
● Mean 49 years old, no gender preference, 3% synthesize catecholamines
● May be fatal if extensive local invasion

Paravertebral:
● Mean 29 years old, usually men, 50% synthesize catecholamines
● Only rarely cause death

Clinical features
=========================================================================

● Associated with MEN II syndrome
● Also associated with Carney triad of pulmonary hamartomas, malignant gastrointestinal stromal tumors, extraadrenal paragangliomas

Diagnosis
=========================================================================

Catecholamine secreting tumors:
● Present with symptoms of pheochromocytoma, usually hypertension (abrupt; with tachycardia, palpitations, headaches, tremor, sense of apprehension, unresponsive to treatment; isolated paroxysmal episodes of hypertension in < 50%)
● Triad of sweating attacks, tachycardia and headaches is relatively specific

Catecholamine cardiomyopathy:
● Myocardial instability, ventricular arrhythmias
● Due to ischemic damage from vasoconstriction of coronaries or direct toxicity
● Myocytolysis, interstitial fibrosis, mononuclear inflammation

Diagnosis for catecholamine secreting tumors:
● Increased urinary excretion of catecholamines or metabolites (vanillylmandelic acid [VMA] or metanephrines)
● Elevated chromogranin A serum levels

Prognostic factors
=========================================================================

Poor prognostic features:
● Invasion into contiguous soft tissue
● Also combination of confluent tumor necrosis, coarse tumor nodularity and lack of globular cytoplasmic inclusions

Case reports
=========================================================================

● 43 year old man with cystic changes (Ann Diagn Pathol 2010;14:341)
● 49 year old woman with non-functional paraganglioma (Interact Cardiovasc Thorac Surg 2009;9:540)
● 50 year old man with paraganglioma that was embolized preoperatively, and was resected without the need for cardiopulmonary bypass (World J Surg Oncol 2012;10:134)
● 54 year old woman with incidental finding (J Cardiothorac Surg 2010;5:19)

Gross description
=========================================================================

● Firm, red-pink-brown
● Hemorrhage and necrosis common
● Partial or no capsule

Gross images
=========================================================================



Various tumors

Micro description
=========================================================================

● Tumor cells grow in tight nests of similar size (Zellballen), surrounded by fibrovascular stroma
● Cytoplasm is granular, eosinophilic or amphophilic; hyaline globules may be present
● Nuclei are round, fusiform or pleomorphic
● Chromatin may be dense or vesicular
● Usually no / scant mitotic figures
● Occasionally contain melanin

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Neurofilament, reticulin (highlights stromal tissue), S100 (sustentacular cells), vimentin

Negative stains
=========================================================================

● EMA, keratin

Electron microscopy description
=========================================================================

● Pleomorphic secretory granules if secrete norepinephrine
● Nondescript endocrine granules in nonsecretors
● No intermediate filament whorls, no tonofibrils, no microvilli

Molecular description
=========================================================================

● Ret proto-oncogene mutations in exons 10, 11, 13, 15, 16 in 15%



Other benign / low grade tumors

Schwannoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually in posterior mediastinum, asymptomatic
● Most common mediastinal neurogenic tumor
● May present with symptoms of esophageal or nerve root compression
● Benign

Terminology
=========================================================================

● Also called neurilemoma

Epidemiology
=========================================================================

● Usually in young adults

Case reports
=========================================================================

● 33 year old man with asymptomatic tumor (G Chir 2004;25:35)
● 65 year old man diagnosed by endoscopic ultrasonography-guided fine needle aspiration cytology (Case Rep Gastroenterol 2011;5:411)

Treatment
=========================================================================

● Excision is almost always curative

Gross description
=========================================================================

● Encapsulated and sharply demarcated from adjacent soft tissue
● May appear to “hang” from large nerves
● Usually yellow cut surface, rarely dark red/black due to hemorrhage
● Degenerative changes common (fat, hemorrhage, cysts)

Gross images
=========================================================================


51 year old man

Micro description
=========================================================================

● Biphasic pattern of fusiform cells
● Cellular areas with nuclear pallisading (Antoni A) and Verocay bodies and myxoid areas with only occasional cells (Antoni B)
● Prominent thick walled blood vessels
● No / rare mitotic figures

Micro images
=========================================================================


Antoni A

Antoni B


Ancient change / ancient schwannoma

Micro description
=========================================================================

● Cystic changes, marked nuclear atypia, but no mitotic figures

Electron microscopy description
=========================================================================

● Neural differentiation with elongated overlapping cell processes
● Primitive junctions may resemble mesaxons
● Abundant pericellular basal lamina


Cellular schwannoma

Micro description
=========================================================================

● Densely cellular with herringbone, storiform or fascicular growth patterns, mild nuclear atypia, brisk mitotic activity, but no necrosis, no atypical mitotic figures

Differential diagnosis
=========================================================================

MPNST or other sarcoma: atypical mitotic figures, necrosis, not encapsulated


Glandular schwannoma

General
=========================================================================

● Epithelial differentiation is focally present


Melanotic schwannoma

General
=========================================================================

● Pigment present


Psammomatous-melanotic schwannoma

General
=========================================================================

● Psammomatous calcification and pigment are present



Other benign / low grade tumors

Solitary fibrous tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 2 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually pleural, but also elsewhere and in mediastinum
● No association with asbestos
● Either no symptoms or symptoms of mass effect

Case reports
=========================================================================

● 18 year old man with 6 cm tumor (Gen Thorac Cardiovasc Surg 2010;58:205)
● 62 year old woman with stridor and a mass (Tumori 2007;93:508)
● En-bloc resection of malignant tumor (J Thorac Oncol 2008;3:1068)

Gross description
=========================================================================

● Firm, gray-white cut surface, well demarcated from adjacent tissue
● May resemble uterine leiomyoma
● Often polypoid protrusions from pleural reflections or derived from soft tissue between the lungs

Micro description
=========================================================================

● Bland spindle cells arranged haphazardly in fibrohyaline stroma resembling keloid
● Abundant thick walled blood vessels, often with staghorn appearance
● May have mesothelial lining
● Usually few mitotic figures but may have up to 10 per 10 HPF
● Occasional myxohyaline degeneration, storiform growth, nuclear pleomorphism, marked cellularity; no necrosis

Positive stains
=========================================================================

● CD34, vimentin

Negative stains
=========================================================================

● Actin, desmin, EMA, keratin, S100

Electron microscopy description
=========================================================================

● Nondescript spindle cells with prominent rough endoplasmic reticulum, focal intrareticular collagen fibers
● No features of myofibroblasts, smooth or skeletal muscle, epithelial differentiation



Thymic carcinoma - general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 27 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● By definition, has overt cellular anaplasia

Epidemiology
=========================================================================

● Ages 50+, occasionally children

Clinical features
=========================================================================

● Associated with hypercalcemia, elevated parathyroid hormone levels, pulmonary sarcoidosis
● Not associated with paraneoplastic syndromes such as myasthenia gravis or pure red cell aplasia
● Patients usually present with mass related symptoms
● Aggressive clinical course
● Must exclude other primaries, which are much more common (lung, trachea, bronchi, esophagus)
● Usually squamous cell carcinoma and variants (lymphoepithelioma-like, basaloid)
● Proposed staging system (Am J Clin Pathol 2012;138:115)

Prognostic factors
=========================================================================

● May be less aggressive than commonly believed; important prognostic factors are lymph node status and tumor size (Am J Clin Pathol 2012;138:103)

Diagrams
=========================================================================


Proposed stage T1, tumor limited to thymic gland

Proposed stage T2, tumor invades nearby structures

Proposed stage T3, direct (continuous) extrathoracic tumor extension beyond thoracic inlet or below diaphragm

Gross description
=========================================================================

● Unencapsulated, no internal fibrous septation, firm / hard / gritty with gray-white cut surface, necrosis and hemorrhage

Micro description
=========================================================================

● Usually cohesive cellular growth, regularly round/oval nuclear outlines, eosinophilic nucleoli, geographic necrosis
● Usually foci of medullary differentiation, abortive Hassall’s corpuscles, rosettes, gland-like spaces, T lymphocytes; no perivascular spaces,
● Subtypes discussed as separate topics

Micro images
=========================================================================


Histological features (b & d)

CK18, GLUT1, CA-IX, c-kit, CD5, MUC1, CEA

Various subtypes

Positive stains
=========================================================================

● Keratin, CD5, CD70, often EMA, variable CEA (if overt glandular differentiation), c-kit, GLUT1 (Am J Surg Pathol 2000;24:742, Am J Surg Pathol 2011;35:1296, Virchows Arch 2011;458:615)

Negative stains
=========================================================================

● Vimentin, proteasome beta subunit (Am J Surg Pathol 2011;35:1296)

Electron microscopy description
=========================================================================

● Well-formed desmosome-like intercellular junctions, cytoplasmic tonofilaments that may insert into junctional complexes

Differential diagnosis
=========================================================================

Metastatic carcinoma
Thymoma type B3: GLUT1 usually negative (Mod Pathol 2009;22:1341)



Thymic carcinoma

Adenocarcinoma of thymus, NOS


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, <10 cases reported
● Most common type is papillary, mucinous subtype also reported

Epidemiology
=========================================================================

● Mean age 50 years, but wide range

Clinical features
=========================================================================

● Must rule out metastatic tumor
● More likely to be thymic primary if CD5+ and transition from thymoma or thymic cyst to adenocarcinoma is present
● Outcome is highly variable

Case reports
=========================================================================

● 15 year old with mucinous adenocarcinoma and 39 year old with papillary adenocarcinoma (Am J Surg Pathol 2003;27:124)
● 41 year old man with primary mucinous adenocarcinoma (Arch Pathol Lab Med 2006;130:201)
● 59 year old man with tumor demonstrating papillary, acinar and cribriform structure, and which produced abundant extracellular mucin (Hum Pathol 2005;36:219)
● 61 year old woman with tumor with numerous psammoma bodies and 82 year old woman with case arising from thymic cyst with areas of transition from benign to dysplastic epithelium (Am J Surg Pathol 2007;31:1330)
● Tubular adenocarcinoma (Int J Surg Pathol 2006;14:243)

Micro images
=========================================================================



Mucinous adenocarcinoma of the thymus



Thymic carcinoma

Adenosquamous thymic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also Lung tumor chapter

General
=========================================================================

● Almost always fatal

Micro description
=========================================================================

● Resembles nonkeratinizing squamous cell carcinoma but with well-formed glandular lumina

Positive stains
=========================================================================

● Mucicarmine, PAS



Thymic carcinoma

Anaplastic thymic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Undifferentiated thymic carcinoma
● Symptoms related to anterior mediastinal masses: shortness of breath, chest pain, and cough

Epidemiology
=========================================================================

● More common in women
● Age range 42-72 years

Clinical features
=========================================================================

● Aggressive clinical course

Micro description
=========================================================================

● Infiltrative with marked cytologic atypia, bizarre tumor giant cells, and atypical mitoses; no areas of other well-defined types of thymic carcinoma (Hum Pathol 2012;43:874)

Micro images
=========================================================================



No appreciable differentiation toward any specific type

Positive stains
=========================================================================

● Pancytokeratin, PAX8 (40%)

Negative stains
=========================================================================

● TTF1



Thymic carcinoma

Basaloid squamous cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Primary thymic tumor or metastatic tumor to mediastinum from oropharynx, hypopharynx, larynx, esophagus, lung, anorectum

Clinical features
=========================================================================

● Present with intrathoracic mass
● Primary tumors are associated with multilocular thymic cysts
● Capable of aggressive behavior and significant mortality (Am J Surg Pathol 2009;33:1113)

Prognostic factors
=========================================================================

● Good prognosis with few fatalities if well differentiated

Micro description
=========================================================================

● Nests, cords and sheets of small polygonal cells with minimal cytoplasm, hyperchromatic round nuclei, abundant mitotic figures
● No nuclear molding
● Separated by myxoid or eosinophilic stroma
● May have peripheral pallisading of nuclei
● May have areas of squamous differentiation with keratin pearls, or stromal mucin containing gland-like profiles
● May have cystic structures

Micro images
=========================================================================



Prominent peripheral palisading

Positive stains
=========================================================================

● CD117, EMA, keratin

Negative stains
=========================================================================

● Neuroendocrine markers

Electron microscopy description
=========================================================================

● Poorly differentiated squamous proliferation with limited cytoplasmic tonofilaments, well-formed desmosomes, redundant basal lamina
● No neurosecretory granules



Thymic carcinoma

Clear cell thymic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare; clear cytoplasm due to either glycogen or degenerative changes
● Almost always fatal

Case reports
=========================================================================

● 42 year old man (Gen Thorac Cardiovasc Surg 2010;58:98)

Micro description
=========================================================================

● Lobular or occasionally sheet-like growth pattern of polygonal cells with clear cytoplasm, rather bland nuclear features, round vesicular nuclei, prominent nucleoli; delicate fibrovascular stroma (Am J Surg Pathol 1995;19:835)
● No blood lakes, no mucin

Micro images
=========================================================================



Large amount of glycogen-rich cytoplasm creates superficial resemblance to renal cell carcinoma


Large cells with abundant optically clear cytoplasm

Positive stains
=========================================================================

● PAS

Differential diagnosis
=========================================================================

Metastatic renal cell carcinoma



Thymic carcinoma

Lymphoepithelioma-like thymic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Type of poorly differentiated squamous cell carcinoma
● Almost always fatal

Case reports
=========================================================================

● 16 year old boy with secondary nephrotic syndrome (Pediatr Nephrol 2008;23:1001)
● Rare association of paraneoplastic syndrome of polymyositis (Clin Nucl Med 2009;34:686)

Micro description
=========================================================================

● Syncytial groups of large, anaplastic, polyhedral cells with indistinct cell boundaries, amphophilic cytoplasm, round / oval vesicular nuclei, prominent eosinophilic nucleoli, mixed with mature lymphocytes
● Micronodular growth pattern in stroma showing florid lymphoid hyperplasia; epithelial cell component shows unequivocal signs of malignancy characterized by cytological atypia and increased mitotic activity (Mod Pathol 2012;25:993)
● Brisk mitotic activity, narrow fibrovascular septae, variable necrosis

Micro images
=========================================================================


Syncytial epithelial cells and T cells

Large, round, vesicular nuclei with prominent nucleoli

Positive stains
=========================================================================

Large tumor cells:
● EMA, keratin

Negative stains
=========================================================================

Large tumor cells:
● CD3, CD15, CD20, CD30, CD43, CD45, CD45RO



Thymic carcinoma

Mucoepidermoid thymic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Clinical features
=========================================================================

● Usually low grade, may be associated with multilocular thymic cysts (Am J Surg Pathol 2004;28:1526)
● Poor behavior if poorly differentiated with marked cytologic atypia or high stage (Am J Surg Pathol 1995;19:826)
● Good prognosis with few fatalities if well differentiated

Case reports
=========================================================================

● 31 year old man with thymic mucoepidermoid carcinoma with massive calcification (Kyobu Geka 2010;63:919)
● 53 year old man with asymptomatic hilar mass (Ann Thorac Cardiovasc Surg 2006;12:273)
● 53 year old man with chest discomfort, dyspnea and weakness (Pathol Res Pract 2004;200:567)

Micro description
=========================================================================

● Sheets, lobules and nests of squamous, mucinous and intermediate cells in densely fibrotic stroma

Micro images
=========================================================================



Well differentiated mucoepidermoid carcinoma of the thymus


Poorly differentiated mucoepidermoid carcinoma of the thymus



Other mediastinal carcinoma
NUT midline carcinomas (NMCs)

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Sites
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Head & neck
Cytology images
=========================================================================
Head & neck


Thymic carcinoma

Parathyroid carcinoma of thymus


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● May arise within thymus or adjacent soft tissue of anterosuperior mediastinum

Clinical features
=========================================================================

● Usually extreme hypercalcemia (> 14 mg/dl), markedly elevated parathyroid hormone (PTH) levels

Poor prognostic factors
=========================================================================

● > 5 MF/HPF, thick fibrous capsule or infiltrative growth pattern

Case reports
=========================================================================

● 33 year old man with postoperative hungry bone syndrome (Endocr Pract 2003;9:152)
● Hemodialysis patient with unusual thymic involvement (J Laryngol Otol 2004;118:162)

Gross description
=========================================================================

● Resembles primary thymic carcinoma
● May invade adjacent lung, pericardium, thoracic great vessels
● Unencapsulated

Micro description
=========================================================================

● Modest to marked atypia
● Sheets, nests or cords of polyhedral cells with round/oval hyperchromatic nuclei, occasional nucleoli, clear/granular cytoplasm
● Focal mitotic activity, necrosis
● May have internal collagenous bands

Micro images
=========================================================================



Parathyroid carcinoma: site unknown

Positive stains
=========================================================================

● Diastase sensitive, PAS+, PTH (mosaic staining), variable chromogranin A or synaptophysin

Electron microscopy description
=========================================================================

● Primitive intercellular junctional complexes, prominent cytoplasmic glycogen, primitive blunt microvilli, sparse neurosecretory granules
● No tonofilaments



Thymic carcinoma

Sarcomatoid thymic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare; usually presents as rapidly growing, anterior mediastinal mass
● Must exclude metastases before making this diagnosis
● May arise from malignant transformation of preexisting spindle cell thymoma (Am J Surg Pathol 1999;23:691)
● Aggressive - recurrence, metastasis and death are common

Terminology
=========================================================================

● Also called spindle cell thymic carcinoma

Case reports
=========================================================================

● 43 year old man with tumor arising in metaplastic thymoma (Histopathology 2008;52:409)
● 63 year old woman with tumor arising in metaplastic thymoma (Int J Surg Pathol 2011;19:677)

Gross description
=========================================================================

● Large (mean 15 cm), well circumscribed, locally infiltrative
● Firm cut surface, focal hemorrhage, necrosis, cystic changes

Micro description
=========================================================================

● Irregular fascicles of fusiform and pleomorphic cells with amphophilic or eosinophilic cytoplasm, hyperchromatic nuclei, prominent nucleoli (at least focally), brisk mitotic activity, often atypical mitotic figures
● May have epithelioid foci
● Usually transitional areas with spindle cell thymoma
● May also have lymphoepithelioma-like or anaplastic areas
● Rarely rhabdomyogenic foci with cross striations

Micro images
=========================================================================



Atypical population of spindle cells with frequent mitotic figures

Positive stains
=========================================================================

● EMA (may be focal), keratin (including CAM5.2), vimentin, muscle markers in areas of myogenic differentiation

Negative stains
=========================================================================

● CEA, S100, HMB45, CD5, CD34, CD99

Electron microscopy description
=========================================================================

● Focal junctional complexes between spindle cells, tonofibrils

Differential diagnosis
=========================================================================

Germ cell tumor
Malignant schwannoma: triton tumor



Thymic carcinoma
Small cell carcinoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 9 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Terminology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Small cell carcinoma
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Thymic carcinoma
Squamous cell thymic carcinoma, keratinizing

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Prognostic factors
=========================================================================
Clinical features
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Left: well-differentiated squamous cell carcinoma of the thymus showing focus of keratinization
Differential diagnosis
=========================================================================


Thymic carcinoma
Squamous cell thymic carcinoma, nonkeratinizing

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 3 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Prognostic factors
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Clear-cut features of malignancy; usually lack immature T lymphocytes
Differential diagnosis
=========================================================================


Thymic carcinoma
Undifferentiated thymic carcinoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================


Other mediastinal carcinoma
Metastatic carcinoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 9 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Clinical features
=========================================================================
Stains
=========================================================================
Electron microscopy description
=========================================================================


Other mediastinal carcinoma
Neuroendocrine carcinoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 9 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Terminology
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Nests of cells with uniform nuclei and finely granular chromatin
Nests, ribbons and festoons
Various stains
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================


Hematological neoplasms / lesions
Burkitt lymphoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Terminology
=========================================================================
Epidemiology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Starry sky pattern: sheets of monomorphic lymphoid cells mixed with large, clear macrophages containing apoptopic debris
Monomorphic blast cells with glandular nuclear chromatin; cytoplasm is well-defined, amphophilic and contains small lipid vacuoles
Positive stains
=========================================================================


Hematological neoplasms / lesions
Castleman disease

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Terminology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Prognostic features
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Mediastinal mass
Micro description
=========================================================================
Micro images
=========================================================================
Onion-like appearance


Hematological neoplasms / lesions
Diffuse large B cell lymphoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Epidemiology
=========================================================================
Sites
=========================================================================
Pathophysiology
=========================================================================
Clinical features
=========================================================================
Prognostic factors
=========================================================================
Treatment
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Figure (b)
Figures (a)-(d)
Primary mediastinal (thymic) large B-cell lymphoma
Figures a/b: MAL protein
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular description
=========================================================================
Differential diagnosis
=========================================================================


Hematological neoplasms / lesions
Extramedullary hematopoiesis

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Clinical features
=========================================================================
Differential diagnosis
=========================================================================


Hematological neoplasms / lesions
Granulocytic sarcoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Terminology
=========================================================================
Epidemiology
=========================================================================
Clinical features
=========================================================================
Diagnosis
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Positive stains
=========================================================================
Electron microscopy description
=========================================================================


Hematological neoplasms / lesions
Hodgkin lymphoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See Lymphoma and plasma cell neoplasms chapter

See subtypes mixed cellularity, nodular sclerosis below

General
=========================================================================
Epidemiology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images and immunostains
Molecular description
=========================================================================


Classic Hodgkin lymphoma: mixed cellularity
Micro description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================


Nodular sclerosis
General
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Fig A: effacement of normal lymph node structure
Positive stains
=========================================================================
Negative stains
=========================================================================


Hematological neoplasms / lesions
Langerhans cell histiocytosis

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Terminology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Gross images
=========================================================================
Mediastinal mass
Micro description
=========================================================================
Micro images
=========================================================================
Neoplastic Langerhans cells
Nodular infiltrates of Langerhans cells
Positive stains
=========================================================================
Electron microscopy description
=========================================================================


Hematological neoplasms / lesions
Lymphoblastic lymphoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Epidemiology
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Diffuse infiltrate of blasts replaces lymph node structure
Blasts have ill defined pale cytoplasm, fine nuclear chromatin
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Hematological neoplasms / lesions
MALT lymphoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Thymic tumor
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================


Hematological neoplasms / lesions
NK lymphoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Sites
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Atypical lymphocytes with angioinvasive lesions
CD3, granzyme, TIA1
Positive stains
=========================================================================
Electron microscopy description
=========================================================================
Electron microscopy images
=========================================================================
Cytoplasmic dense core granules


Hematological neoplasms / lesions
Nodal inclusions

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================


Hematological neoplasms / lesions
Plasmacytoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Epidemiology
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
CD138+ plasma cells
Plasma cells show excess lambda chain expression
Positive stains
=========================================================================
Negative stains
=========================================================================
Elecron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Other malignancies
Carcinoid tumor

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See spindle cell carcinoid of thymus below

General
=========================================================================
Terminology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Figures a-d
Thymic carcinoid
Atypical carcinoid
Various stains
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Spindle cell carcinoid of thymus
Clinical features
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Spindle cell pattern
Positive stains
=========================================================================
Electron microscopy description
=========================================================================


Other malignancies
Chordoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Abundant, bubbly vacuolated cytoplasm is CK+ (inset)
Positive stains
=========================================================================
Electron microscopy description
=========================================================================


Other malignancies
Follicular dendritic cell tumor

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Terminology
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Diagnosis
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
CD21/CD35 stain highlights ovoid spindle cells
Haphazard, bland spindle cells
CD21 staining
Head and neck:
Vague whorls of spindle cells in storiform pattern with lymphocytes and plasma cells
Indistinct cell borders and occasional multinucleated giant cells
Strong CD21 (left) and CD35 (right) staining
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Other malignancies
Ganglioneuroblastoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Epidemiology
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Immature neuroblastic tissue
Mature ganglion tissue and Schwannian stroma
Homer Wright rosettes


Other malignancies
Germ cell tumors

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See choriocarcinoma, embryonal carcinoma, mixed, seminoma, teratoma-immature, teratoma-mature, yolk sac tumor

General
=========================================================================
Epidemiology
=========================================================================
Clinical features
=========================================================================
Prognostic factors
=========================================================================
Gross description
=========================================================================
Cytology description
=========================================================================
Differential diagnosis
=========================================================================


Choriocarcinoma
Epidemiology
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Resemble Reed-Sternberg cells
CAM5.2+
Diffuse cytotrophoblasts, syncytiotrophoblasts are β-hCG+
Cytology images
=========================================================================
Transbronchial aspirate: syncytiotrophoblast
Positive stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Embryonal carcinoma
Epidemiology
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Primitive polygonal cells
Immunostains
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular description
=========================================================================


Germ cell tumor - mixed
General
=========================================================================
Case reports
=========================================================================
Cytology images
=========================================================================
Metastatic tumor



Seminoma
Epidemiology
=========================================================================
Sites
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Thymic seminoma
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Teratoma - immature
General
=========================================================================
Clinical features
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================
Excised tumor with rib
Micro images
=========================================================================
Primitive glomeruli
Cartilage and ossification


Teratoma - mature
General
=========================================================================
Sites
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross images
=========================================================================
Solid and cystic mass
Micro description
=========================================================================
Micro images
=========================================================================
Post chemotherapy
Various mature tissues
Various stains


Yolk sac tumor
General
=========================================================================
Terminology
=========================================================================
Epidemiology
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Figures 4-6
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================


Other malignancies
Hemangioendothelioma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also kaposiform below

Epithelioid
Gross description
=========================================================================
Poor prognostic factors
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various stains
Histologic sections of a tumor
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Kaposiform
General
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Spindled cells surround residual thymic structures
Glomeruloid nests with intracytoplasmic lumina
Tumor cells are keratin-, residual thymus is keratin+
Positive stains
=========================================================================
Negative stains
=========================================================================


Other malignancies
Leiomyosarcoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Epidemiology
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Cigar-shaped spindle cells are smooth muscle actin+
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================


Other malignancies
Liposarcoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Clinical features
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================

Thinly encapsulated mass with smooth surface consisting of adipose tissue with a fibrous core
Micro images
=========================================================================
Various patterns


Other malignancies
Malignant peripheral nerve sheath tumor (MPNST)

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Clinical features
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Low-grade tumor has increased cellularity, nuclear atypia, scattered mitotic figures
Fascicular proliferation of atypical spindle cells


Other malignancies
Melanoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================
Internal fibrous bands and necrosis
Micro description
=========================================================================
Micro images
=========================================================================
Melanoma and adjacent thymus
HMB45+
Invasive melanoma in teratoma
Epithelioid and spindle cells
(D) Melanocytes with pleomorphic nuclei
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Electron microscopy images
=========================================================================
Melanosomes
Differential diagnosis
=========================================================================


Other malignancies
Mesothelioma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also sarcomatoid mesothelioma below

Epidemiology
=========================================================================
Sites
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Sarcomatoid mesothelioma
General
=========================================================================
Differential diagnosis
=========================================================================


Other malignancies
Neuroblastoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Clinical features
=========================================================================
Laboratory
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================


Other malignancies
Primitive neuroectodermal tumor (PNET)

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Site unspecified
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular description
=========================================================================
Differential diagnosis
=========================================================================


Other malignancies
Reticulum cell tumors

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 26 February 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Reticulum cell tumors: see also follicular dendritic cell tumor, interdigitating dendritic cell tumor

Interstitial reticulum cell tumors
General
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Interdigitating dendritic cell tumor
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================


Other malignancies
Rhabdomyosarcoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Positive stains
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Other malignancies
Synovial sarcoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Other malignancies
Thymoliposarcoma

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Clinical features
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================


Miscellaneous
Features to report for thymic epithelial neoplasms

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================


Miscellaneous
Grossing

Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

End of Mediastinum > Superpage


This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).