Mediastinum
Last revised 15 June 2009
Copyright (c) 2003-2007, PathologyOutlines.com, Inc.
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Inflammatory disorders: acute mediastinitis, chronic mediastinitis, sclerosing mediastinitis
Thyroid/parathyroid: thyroid nodular hyperplasia, parathyroid adenoma
Thymus: normal, acute thymic involution, ectopic thymus, ectopic tissue in thymus, myasthenia gravis, thymic dysplasia, thymic follicular hyperplasia, true thymic hyperplasia
Cystic lesions: general, bronchogenic, enteric, lymphangioma, meningocele, pancreatic pseudocyst, parathyroid, pericardial, seminoma, teratoma, thymic, thymoma-cystic
Tumors: general
Thymoma and related entities: thymoma, staging, classification, ectopic hamartomatous thymoma, ectopic thymoma, thymolipoma
Other benign/low grade tumors: elastolipoma, ependymoma, fibromatosis, ganglioneuroma, hemangioma, inflammatory myofibroblastic tumor, lipoma, lipomatosis, meningioma, neurofibroma, paraganglioma, schwannoma, solitary fibrous tumor
Thymic carcinoma: general, adenocarcinoma, adenosquamous, basaloid squamous cell, clear cell, lymphoepithelioma-like, mucoepidermoid, parathyroid, sarcomatoid, squamous cell-keratinizing, nonkeratinizing
Other mediastinal carcinoma: metastatic, neuroendocrine, small cell
Hematological neoplasms/lesions: Burkitt’s lymphoma, Castleman’s, diffuse large B cell lymphoma, extramedullary hematopoiesis, granulocytic sarcoma, Hodgkin’s lymphoma, Langerhans cell histiocytosis, lymphoblastic lymphoma, MALT lymphoma, NK lymphoma, nodal inclusions, plasmacytoma
Other mediastinal malignancies: carcinoid, chordoma, follicular dendritic cell tumor, ganglioneuroblastoma, germ cell, hemangioendothelioma, leiomyosarcoma, liposarcoma, malignant peripheral nerve sheath tumor, melanoma, mesothelioma, metastases, neuroblastoma, PNET, reticulum cell, rhabdomyosarcoma, thymoliposarcoma
Miscellaneous: features to report, grossing
American Journal of Surgical Pathology (AJSP), Jan 1999 to Nov 2003
Archives of Pathology and Laboratory Medicine (Archives), July 1998 to Nov 2003
Human Pathology (Hum Path), Jan 1999 to Oct 2003
Modern Pathology (Mod Path), Jan 1999 to Nov 2003
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
Please refer to these primary references for more detailed discussions
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
Images: middle and posterior mediastinum
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
Inflammatory disorders
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
Micro images: fibrinoinflammatory infiltrate #1, #2
May compress superior vena cava and simulate malignancy
Usually anterior to tracheal bifurcation
Some cases may represent fibrosing mediastinitis
Micro: granulomas, fibrosis; may be fungus, Histoplasma (with thick fibrous capsule), mycobacteria (thin fibrous capsule)
Also called idiopathic mediastinal fibrosis
A fibroinflammatory lesion of mediastinum associated with other idiopathic fibrosing conditions such as retroperitoneal fibrosis, sclerosing cholangitis, Riedel’s struma, inflammatory pseudotumor of orbit
Also associated with pulmonary or mediastinal nodal infection due to Histoplasma or other fungi; trauma, syphilis, methysergide treatment, phlebitis
Usually anterosuperior mediastinum, presenting at any age, often with superior vena cava syndrome or cardiorespiratory compromise
Xray: asymmetric mediastinal widening with projection of mass into upper lung field
Treatment: steroids, surgical excision
Gross: dense white fibrosis, well demarcated from surrounding tissue
Micro: 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
DD: fibrotic component of Hodgkin’s lymphoma, mesothelioma, metastatic carcinoma
References: Mod Path 1999;12:257
Thyroid/parathyroid lesions
Thyroid nodular hyperplasia
Presents as either a large mass causing compression or multiple independent nodules
7% are found in superior mediastinum, grow larger than counterparts in neck
Thymus
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
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
Gross: 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)
Gross drawing: fetal thymus
Micro: 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 (increasing with age, Hum Path 2001;32:926); also interdigitating reticulum cells, Langerhans cells, mast cells, eosinophils, stromal cells
Micro images: islands of lymphoid tissue and fat
Positive stains: epithelial cells - keratin, HLA-DR
Virtual slides: normal thymus gland (bottom slide)
Due to stress (chronic debilitating disease), HIV or other infections
Seen in newborn infants with chorioamnionitis and sepsis
Micro: preservation of lobular architecture and Hassall’s corpuscles, but marked lymphocyte depletion (particularly with HIV); vessels are large compared to size of lobules
HIV patients also have effacement of corticomedullary junction and inconspicuous Hassall’s corpuscles
DD: thymic hyperplasia, thymic dysplasia
References: Hum Path 2000;31:1121
Remnants, implants or accessory nodules may appear from angle of mandible to thyroid gland, most commonly at level of thyroid gland
Usually an incidental finding during thyroid surgery in preteens, very rare in adults due to thymic involution
Rarely becomes hyperplastic or neoplastic
Case reports: anterior neck mass in 22 year old woman (Archives 2001;125:842), infant with neck mass (Archives 2001;125:278)
Xray images: MRI of neck mass
Micro: normal appearing thymic tissue
Micro images: ectopic thymus adjacent to thyroid and parathyroid tissue, FNA of neck mass, keratin
Usually parathyroid tissue or sebaceous glands
Defect in nicotinic acetylcholine receptor 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
MG may be due to T cells attacking myoid cells, then T cells induce B cells to produce autoantibodies; physiological connection with thymomas is unclear
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 cases have thymic hyperplasia, 25% normal thymus, 10% thymomas
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
Risk factors for thymomas: male, initial MG symptoms after age 50 years
MG associated thymomas are morphologically similar to non-MG associated thymomas
Treatment: thymectomy (regardless of presence of thymoma)
DD: Lambert-Eaton syndrome (muscle weakness due to antibodies to neuronal calcium channel)
Congenital thymic alteration due to developmental arrest
Associated with severe combined immunodeficiency syndrome, ataxia-telangiectasia, chromosomal instability syndromes, Nezelof syndrome, incomplete form of DiGeorge syndrome (complete form of DiGeorge syndrome has absent thymus)
Gross: small thymus size (< 5g)
Micro: tubules and rosettes of primitive appearing epithelium without segregation into cortical and medullary regions; no Hassall’s corpuscles, no/rare lymphocytes
DD: acute thymic involution
Defined as substantial numbers of lymphoid follicles in thymus of adults
Thymus usually has normal size / weight
Present in 65% with myasthenia gravis; also associated with hyperthyroidism, Addison’s disease, SLE, early HIV, multilocular cysts, other immune-related diseases
Micro: follicles with germinal centers, medullary epithelial cells may be disordered or hypertrophied
DD: normal lymphoid follicles of infants/children (few present)
Thymus larger than normal limits for age, based on tables
Otherwise histologically unremarkable
Often in infants or children, or in adults after cancer chemotherapy
Cystic lesions
10-15% of radiologically detected mediastinal masses
Often developmental
Thymic, pericardial, bronchogenic, enteric, parathyroid cysts or mixtures
Due to developmental defect from fusion of tracheoesophageal septum
Along tracheobronchial tree, usually posterior to carina
Childhood or middle life
Usually asymptomatic
Xray: round/oval mass that molds to adjacent structures; wall may contain linear calcifications; may have independent vascular supply
Gross: unilocular or multilocular with internal septation; contain viscous or turbid fluid
Micro: 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
DD: mature teratomas
Posterior mediastinum of children or teens
Due to developmental defect from fusion of tracheoesophageal septum
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
Gastric cysts may produce acid and rupture or hemorrhage
Gross: 2-10 cm, rounded or irregular, fibromuscular wall of variable thickness, usually unilocular but may be multiloculated; smooth inner lining; often mucoid contents
Micro: 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
Also called cystic hygroma
Benign proliferation of lymphatic channels
Common; in anterior, middle or posterior mediastinum or soft tissue of neck
Usually in children, often with cervical component
Large lesions may compress lungs, heart, nerves, but most lesions are asymptomatic and found on Xray
Xray: appear to infiltrate mediastinal soft tissue, variegated appearance
Gross: gray-white masses, edematous appearing, variable sized cystic cavities, serous type fluid, smooth inner lining
Micro: large, irregular vascular spaces lined by flattened, bland epithelial cells with fibroblastic or collagenous stroma; variable lymphocytic infiltrates; no specialized epithelium, no cholesterol granulomas
Cystic lesions occur in infants or children in posterior mediastinum
Communicate with meninges, usually through a defect in vertebral bodies
Contain clear/amber cerebrospinal fluid
Usually incidental findings identified prior to surgery
Micro: thick fibrous wall, lined by flattened arachnoid cells; variable neural tissue, calcification
Rarely is present in mediastinum
Derived from third and fourth branchial pouch, as is thymus
Cysts may be present in low cervical or anterosuperior mediastinum
Pure cysts are present at any age; contain high levels of parathyroid hormone; can diagnose by FNA via PTH in fluid, AJCP 1986;86:776
Patients usually are normocalcemic and present with an asymptomatic mass on Xray
Gross: 1-10 cm, unilocular, thin walled, clear fluid, no nodules
Micro: 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
Positive stains: glycogen, parathyroid hormone, chromogranin A
Negative stains: thyroglobulin
DD: parathyroid adenomas with secondary cystic change or heterotopic salivary gland like tissue, AJSP 2000;24:837
Usually at right cardiophrenic angle, adherent to pericardium and diaphragm; may communicate with pericardial cavity
Usually asymptomatic patients of all ages anywhere in mediastinum; rarely associated with dyspnea or chest pain
Due to failure of one of multiple disconnected lacunae to merge with the others
Xray: irregular, adjacent to cardiac contour
Gross: thin fibrous wall, unilocular, collapses when opened, smooth cyst lining, serous fluid contents
Micro: fibrous tissue lined by bland mesothelium, rarely with papillary hyperplasia, no cholesterol granulomas, no smooth muscle, no cartilage, no specialized epithelium
Positive stains: keratin
Cysts are due to degenerative changes
Usually in anterosuperior mediastinum
Associated with Klinefelter’s syndrome (XXY), hematologic abnormalities
Gross: variable cystic contents, unilocular or multilocular
Micro: 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
Common - 10-20% of mediastinal lesions
In anterosuperior mediastinum, usually children or young adults (mean age 20 years)
Neoplastic, not a developmental malformation
Usually contain tissue derived from at least 2 of 3 germ cell layers - endoderm, mesoderm, ectoderm
50% have symptoms of cough, dyspnea, chest pain
May be associated with Klinefelter’s syndrome (XXY)
Tumors adhering to lung, pericardium or blood vessels are either malignant or ruptured mature teratomas with inflammatory reaction
Rarely associated with acute myelogenous leukemia
Gross: 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
Micro: 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
Immature teratoma
Contains immature neuroepithelial tissue such as embryonic tubules
Benign behavior in patents under age 15
Mature teratoma with malignant transformation
Very rare
Contain overtly malignant tissue
Tumors with germ cell components are classified as malignant mixed germ cell tumors
Derived from third and fourth branchial pouch, as is parathyroid gland
Usually ages 20-50 years, present as incidental masses in anterosuperior mediastinum
Congenital (unilocular) or acquired (multilocular)
Xray: rounded, circumscribed masses in anterior mediastinum, may have peripheral rim of calcification
May be associated with mediastinal Hodgkin’s lymphoma, but not non-Hodgkin’s lymphomas
Rarely occur post-operatively
Gross: 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
Micro:
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
DD: cystic degeneration in Hodgkin’s lymphoma, seminoma, thymomas; cystic lymphangioma
Mixed multilocular thymic cyst
Parathyroid or salivary gland tissue present
Proliferating multilocular thymic cyst
Resembles cutaneous proliferating epidermoid cyst and proliferating trichilemmal cyst
Micro: 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
DD: squamous cell carcinoma (extremely rare in thymic cysts)
Cystic degeneration of thymomas in anterosuperior mediastinum
Associated with paraneoplastic syndromes
Gross: encapsulated, uniloculated or multiloculated; variable cystic contents
Micro: bland proliferation of thymic epithelium (spindle or polygonal cells) present in cyst wall; usually no cholesterol granulomas, no cartilage, no smooth muscle
DD: thymic cyst (no thymic epithelial cells in cyst wall)
Tumors
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
Thymoma and related entities
Most common primary anterior mediastinal neoplasm
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
Commonly ages 49-62 years in adults
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
Spindle cell histologic patterns have indolent behavior, may be associated with hematologic malignancies
Non-spindle cell thymomas are also called cortical thymomas
Site: usually anterosuperior mediastinum; rarely posterior mediastinum, neck, thyroid, pulmonary hilum, lung parenchyma, pleura
Poor prognostic factors: high stage, B3 or C classification (see below), positive margin, invasion of capsule (AJSP 2002;26:1605)
Hemorrhage and necrosis in well encapsulated, noninvasive thymomas don’t affect prognosis (AJSP 2001;25:1086)
Case reports: Case of the Week #99 (B1 type), with SLL/CLL (Archives 2003;127:E76), invasive thymoma with cancer associated retinopathy (Hum Path 2003;34:717)
Treatment: surgical excision; possibly chemotherapy or radiation
Gross: 80% encapsulated, 20% are infiltrative into surrounding structures; usually large unless incidental with coronary bypass surgery; cystic degeneration common; multinodular, yellow-gray; sharp lobulations due to fibrous bands with some nodules having pointed ends
Gross images: thymoma
Micro: 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
Micro images: thymoma and SLL/CLL; see also subtypes below
Virtual slides: thymoma
Positive stains: keratin (epithelial cells), CEA, CD3 (lymphocytes outside lymphoid follicles are T cells), S100 (interdigitating reticulum cells), Ki-67, EMA (some tumors)
Negative stains: vimentin, CD70 (AJSP 2000;24:742)
Cytogenetics: rarely alterations of #6 (Archives 2000;124:1714)
EM: branching tonofilaments, complex desmosomes, elongated cell processes, basal lamina
DD: thymic cyst, thymic carcinoid (well formed rosettes), lymphoma, seminoma, solitary fibrous tumor (see also below)
Recently discussed by Suster and Moran (Am J Clin Pathol 2006;125:542)
For prognostic purposes, must distinguish types with benign behavior (types A, AB, B, B1 and B2), from those with atypical behavior (type B3, Ann Thorac Cardiovasc Surg 2005;11:367) and those that are cytologically malignant (type C, also called thymic carcinoma, AJSP 2002;26:1605)
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
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 - carcinoma
Thymoma subtypes (some)
Lymphocyte predominant
WHO type B1
Micro: 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
B1 type - #1; #2; #3; #4; #5; CD3; CD20; keratin; CD68
Positive stains: keratin demonstrates finely arborizing network of interconnecting epithelial cell processes; CD1, CD2, CD3, CD99, bcl2, TdT
EM: well-formed intercellular junctions between epithelial cell processes, numerous tonofilaments
DD: thymic lymphoid hyperplasia (normal cortical and medullary glandular distinction is maintained, well-formed germinal centers present, does not produce a mass), Castleman’s 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), Burkitt’s lymphoma (HIV+, different nuclear histology)
Spindle cell
WHO type A
Excellent prognosis
May be associated with hematologic malignancies
Rosai believes composed of nonfunctional, postmature thymic epithelial cells that match epithelial cells of involuted thymus in adult life, not cortical or medullary cells
Gross: usually encapsulated or minimal capsular invasion
Gross images: well circumscribed with lobulated cut surface
Micro: epithelial predominant with fusiform epithelial tumor cells; gland like spaces, storiform patterns are common; no/rare lymphocytes
Micro images: spindle cell thymoma
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 CAM5.2+, keratin+, CD20-; in one study, all were incidental on chest Xray or during coronary artery bypass surgery; not associated with autoimmune disorders
Negative stains: CD5 (in epithelial cells)
References: AJSP 2001;25:111, AJSP 1999;23:955
Microscopic thymoma
Normal sized or enlarged glands removed from adults for myasthenia gravis or as incidental findings during coronary bypass surgery
Micro: nodular aggregates of bland cells subdivided by fibrous bands
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
Rare, supraclavicular-sternal soft tissue mass
Usually adult men; may arise from ectopic tissue of third branchial pouch
Case report in 59 year old man, Archives 2003;127:e378
Benign behavior
Gross: well circumscribed, firm, yellow-white, variable microcysts
Gross images: yellow-white solid tumor
Micro: 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: H & E, CD99, CD3, CD20
Positive stains: keratin; lymphocytes - CD3, CD20, CD99
EM: tonofilaments, well developed cell junctions
EM images: tonofilaments and cell junctions
DD: mixed tumor (chondromyxoid, S100+), myoepithelioma of soft tissue (chondromyxoid, S100+), angiomyolipoma (HMB45+), thymolipoma (mediastinum, not neck, no spindle cells), biphasic synovial sarcoma (more cellular, more atypia, more mitotic figures), glandular MPNST (resembles fibrosarcoma, S100+, cytokeratin-)
Resembles thymoma, but in the neck
Usually women
All reported cases had benign behavior
Usually young to middle-aged adults, found incidentally
10% associated with thymoma-like paraneoplastic symptoms
Absolute mass of thymic tissue is increased far beyond that in normal thymus glands
Benign
Gross: encapsulated, up to 20 cm; resembles lipoma
Micro: 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
Other benign/low grade tumors
Micro: lipoma with abnormal elastic fibers or dense zones of fibrosis
Positive stains: elastin
CNS tumor, very rarely occurs as mediastinal primary
Anterior or posterior mediastinum
Children and young adults
Associated with superior vena cava syndrome, nerve entrapment or dysphagia
Gross: poorly demarcated (often receive in multiple fragments), gritty, tan-white, centered in soft tissue
Micro: 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
Positive stains: vimentin, actin, desmin
EM: myofibroblastic features of intrareticular collagen fibers, thin filament bundles, cytoplasmic dense bodies
DD: sclerosing mediastinitis, inflammatory myofibroblastic tumor
Usually children; also age 20-39 years
More common than neuroblastoma or ganglioneuroblastoma
Benign; no symptoms in most cases; rarely watery diarrhea from vasoactive intestinal peptide (VIP) synthesis or symptoms of spinal nerve root compression
Treatment: excision is curative
Gross: encapsulated, glistening tumor of paraspinal soft tissue in posterior mediastinum; may have intradural growth and dumbbell shape; soft, yellow-gray cut surface, may have cystic and fatty areas, usually no necrosis
Micro: spindle cell (schwannian) proliferation similar to neurofibroma, but with well-formed ganglion cells, often in clusters and multinucleated; focal lymphocytes present
Positive stains: synaptophysin (ganglion cells)
In adults, usually cavernous hemangioma
Benign proliferation of blood vessels, most commonly in anterior compartment; excision is curative
Micro: dilated vessels with flattened endothelium, separated by fine septa; may have focal thrombosis, calcification, cholesterol granulomas
Inflammatory myofibroblastic tumor
Also called inflammatory pseudotumor
May present with superior vena cava syndrome or cardiorespiratory compromise
Any age
Xray: asymmetric mediastinal widening with projection of mass into upper lung field
Gross: dense white fibrosis, well demarcated from surrounding tissue
Micro: bland fusiform cells, haphazard or fascicular, with lymphocytes and other inflammatory cells
Positive stains: vimentin, alpha smooth muscle actin
Common, occur throughout mediastinum
Often very large and located just above diaphragm
Anterosuperior lipomas clinically resemble thymolipoma
DD: thymolipoma (thymic tissue present), lipomatosis
Diffuse accumulation of mature adipose tissue associated with obesity, Cushing’s disease, steroid therapy
CNS tumor, very rarely occurs as mediastinal primary
May originate in stellate ganglion
Usually in posterior mediastinum, asymptomatic, young adults
May be multiple
Plexiform tumors are specific for neurofibromatosis
Benign, excision is almost always curative
Gross: 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)
Micro: 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
EM: fibroblast-like tumor cells with abundant rough endoplasmic reticulum, rudimentary cytoplasmic processes, sparse pericellular basal lamina; may lack evidence of schwannian differentiation
Rare, 0.3% of mediastinal tumors
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
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
Associated with MEN II syndrome
Also associated with Carney triad of pulmonary hamartomas, malignant gastrointestinal stromal tumors, extraadrenal paragangliomas; usually in young women
Poor prognostic features: invasion into contiguous soft tissue; also combination of confluent tumor necrosis, coarse tumor nodularity and lack of globular cytoplasmic inclusions
Gross: firm, red-pink-brown; hemorrhage and necrosis common; partial or no capsule
Micro: tumor cells grow in tight nests of similar size (Zellballen), surrounded by fibrovascular stroma; nuclei are round, fusiform or pleomorphic; chromatin may be dense or vesicular; cytoplasm is granular, eosinophilic or amphophilic; hyaline globules may be present; usually no/scant mitotic figures; occasionally contain melanin
Positive stains: neurofilament, vimentin, S100 (sustentacular cells), reticulin (highlights stromal tissue)
Negative stains: keratin, EMA
Molecular: ret proto-oncogene mutations in exons 10, 11, 13, 15, 16 in 15%
EM: pleomorphic secretory granules if secrete norepinephrine; nondescript endocrine granules in nonsecretors; no intermediate filament whorls, no tonofibrils, no microvilli
Also called neurilemoma
Usually in posterior mediastinum, asymptomatic, young adults
Most common mediastinal neurogenic tumor
May present with symptoms of esophageal or nerve root compression
Benign, excision is almost always curative
Gross: 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)
Micro: 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
Ancient change / ancient schwannoma
Cystic changes, marked nuclear atypia, but no mitotic figures
EM: neural differentiation with elongated overlapping cell processes; primitive junctions may resemble mesaxons; abundant pericellular basal lamina
Cellular schwannoma
Densely cellular with herringbone, storiform or fascicular growth patterns, mild nuclear atypia, brisk mitotic activity, but no necrosis, no atypical mitotic figures
DD: MPNST or other sarcoma (atypical mitotic figures, necrosis, not encapsulated)
Glandular schwannoma
Epithelial differentiation is focally present
Melanotic schwannoma
Pigment present
Psammomatous-melanotic schwannoma
Psammomatous calcification and pigment are present
Usually pleural, but also elsewhere and in mediastinum
No association with asbestos
Either no symptoms or symptoms of mass effect
Gross: 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: 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: keratin, EMA, S100, desmin, actin
EM: nondescript spindle cells with prominent rough endoplasmic reticulum, focal intrareticular collagen fibers; no features of myofibroblasts, smooth or skeletal muscle, epithelial differentiation
Thymic carcinoma
By definition, has overt cellular anaplasia
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
Ages 50+, occasionally children
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)
Gross: unencapsulated, no internal fibrous septation, firm / hard / gritty with gray-white cut surface, necrosis and hemorrhage
Micro: usually cohesive cellular growth, regularly round/oval nuclear outlines, eosinophilic nucleoli, geographic necrosis; subtypes are discussed below; usually no perivascular spaces, foci of medullary differentiation, abortive Hassall’s corpuscles, rosettes, gland-like spaces, T lymphocytes
Positive stains: keratin, CD5, CD70 (AJSP 2000;24:742), often EMA, variable CEA (if overt glandular differentiation)
Negative stains: vimentin
EM: well-formed desmosome-like intercellular junctions, cytoplasmic tonofilaments that may insert into junctional complexes
DD: metastatic carcinoma
Rare, <10 cases reported, with mean 50 years old but wide age range
Must rule out metastatic tumor
More likely to be thymic primary if CD5+ and transition from thymoma or thymic cyst to adenocarcinoma is present
Most common type is papillary adenocarcinoma
Outcome is highly variable
References: AJSP 2003;27:124
Adenosquamous thymic carcinoma
Almost always fatal
Micro: resembles nonkeratinizing squamous cell carcinoma but with well-formed glandular lumina
Positive stains: mucicarmine, PAS
Basaloid squamous cell carcinoma
Primary thymic tumor or metastatic tumor to mediastinum from oropharynx, hypopharynx, larynx, esophagus, lung, anorectum
Present with intrathoracic mass
Primary tumors associated with multilocular thymic cysts
Good prognosis with few fatalities if well differentiated
Micro: 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
Positive stains: keratin, EMA
Negative stains: neuroendocrine markers
EM: poorly differentiated squamous proliferation with limited cytoplasmic tonofilaments, well-formed desmosomes, redundant basal lamina; no neurosecretory granules
Rare; clear cytoplasm due to either glycogen or degenerative changes
Almost always fatal
Micro: vaguely organoid pattern of polygonal cells with round, vesicular nuclei, prominent nucleoli, clear cytoplasm, delicate fibrovascular stroma; no blood lakes
Positive stains: PAS
DD: metastatic renal cell carcinoma
Lymphoepithelioma-like thymic carcinoma
Type of poorly differentiated squamous cell carcinoma
Almost always fatal
Micro: syncytial groups of large, anaplastic, polyhedral cells with indistinct cell boundaries, amphophilic cytoplasm, round/oval vesicular nuclei, prominent eosinophilic nucleoli, mixed with mature lymphocytes; brisk mitotic activity, narrow fibrovascular septae, variable necrosis
Positive stains (large tumor cells): keratin, EMA
Negative stains (large tumor cells): CD3, CD15, CD20, CD30, CD43, CD45, CD45RO
Mucoepidermoid thymic carcinoma
Good prognosis with few fatalities if well differentiated
Micro: foci of well differentiated keratinized squamous cell carcinoma mixed with goblet-like cells arranged around microcysts with mucinous contents
Parathyroid carcinoma of thymus
May arise within thymus or adjacent soft tissue of anterosuperior mediastinum
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
Gross: resemble primary thymic carcinoma; may invade adjacent lung, pericardium, thoracic great vessels; unencapsulated
Micro: 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
Positive stains: PAS+, diastase sensitive, PTH (mosaic staining), variable chromogranin A or synaptophysin
EM: primitive intercellular junctional complexes, prominent cytoplasmic glycogen, primitive blunt microvilli, sparse neurosecretory granules; no tonofilaments
Also called spindle cell thymic carcinoma
Very rare; usually present as rapidly growing, anterior mediastinal mass
Must exclude metastases before making this diagnosis
Aggressive; recurrence, metastasis and death are common
Gross: large (mean 15 cm), well circumscribed, locally infiltrative; firm cut surface, focal hemorrhage, necrosis, cystic changes
Micro: irregular fascicles of fusiform and pleomorphic cells with hyperchromatic nuclei, prominent nucleoli (at least focally), amphophilic or eosinophilic cytoplasm, 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
Positive stains: keratin (including CAM5.2) and EMA (may be focal), vimentin, muscle markers in areas of myogenic differentiation
Negative stains: CEA, S100, HMB45, CD5, CD34, CD99
EM: focal junctional complexes between spindle cells, tonofibrils
DD: germ cell tumor, malignant schwannoma (triton tumor)
References: AJSP 1999;23:691
Squamous cell thymic carcinoma, keratinizing
Good prognosis with few fatalities if well differentiated
Associated with hypercalcemia, elevated PTH levels
Micro: similar to tumor in skin, lung, other sites; lobular growth with fibrous bands; nests and cords of large polyhedral cells with intercellular bridges; vesicular or hyperchromatic nuclei, prominent nucleoli, eosinophilic or glassy cytoplasm, keratin pearls; also angiolymphatic invasion, necrosis; rarely coexist with thymomas
DD: metastatic carcinoma
Squamous cell thymic carcinoma, nonkeratinizing
Almost always fatal
Micro: angular nests of malignant squamous cells in desmoplastic stroma; no intercellular bridges, no eosinophilic cytoplasm, no keratin pearls; no internal fibrous septae
DD: thymoma (fibrous septae)
Other mediastinal carcinoma
Most mediastinal epithelial neoplasms are metastases, usually from trachea, bronchi, lung, esophagus
Primary lung tumors may present as huge mediastinal mass with occult bronchial primary
Usually fatal in short period of time due to metastases to other locations
Stains may be helpful: thyroglobulin (thyroid), PSA (prostate), PLAP (germ cell), S100 (melanoma, others), CD5 (suggestive of thymic)
EM may be helpful: premelanosomes (melanoma, others)
Atypical carcinoids are considered moderately differentiated neuroendocrine carcinomas
Undifferentiated or poorly differentiated neuroendocrine carcinomas are called small cell carcinoma (below)
May have aggressive behavior
Case reports: mediastinal atypical carcinoid in 63 year old woman with neurofibromatosis type 1 (Archives 2000;124:319), paravertebral mass in 47 year old man (Archives 1999;123:933)
Micro: larger cells with more cytoplasm than small cell carcinoma, organoid growth pattern, spindle cell foci; may have prominent angiomatoid features, Hum Path 1999;30:635
Micro images: round/oval cells with mild atypia, solid tumor with necrosis, Flexner-Wintersteiner rosette-like glands, CEA,
Positive stains: chromogranin A, cytokeratin, CEA, EMA, NSE, synaptophysin
Negative stains: CD99
EM: desmosomes, neurosecretory granules
EM images: desmosomes, neurosecretory granules
Also called oat cell carcinoma, undifferentiated neuroendocrine carcinoma
Rare, less than 100 well-documented primary cases in mediastinum
Occurs anywhere in mediastinum, usually metastatic from lung or esophagus
Symptoms due to primary intrabronchial tumor (cough, hemoptysis, dyspnea) or esophageal tumor (dysphagia)
May have paraneoplastic syndrome (Cushing’s syndrome, syndrome of inappropriate antidiuretic hormone)
Almost always fatal, although median survival is 36 months
Gross: fleshy, gray-white (similar to lymphoma), hemorrhagic, necrotic
Micro: centered in thymus (suggests primary) or nodal; clusters of small blue cells with minimal cytoplasm, hyperchromatic nuclei, no/minimal nucleoli, nuclear molding, frequent mitotic figures, frequent necrosis, crush artifact common, encrustation of basophilic nuclear material around intratumoral blood vessels (Azzopardi phenomenon); may be mixed with squamous cell carcinoma or adenocarcinoma
Positive stains: keratin (perinuclear globules), chromogranin A, synaptophysin, CD57/Leu7
Negative stains: CD45
EM: uniformly sized (80 to 250 nm) neurosecretory granules with a peripheral halo, usually in clusters, primitive junctional complexes
DD: lymphoma (keratin-, CD45+), basaloid carcinoma (eosinophilic basement membrane material, associated with thymic cysts)
Hematological neoplasms/lesions
Also called small non-cleaved cell lymphoma
Usually children/teens
May arise in mediastinum without disease elsewhere; often occurs in HIV+ patients
5 year survival of 50% with multiagent chemotherapy
Micro: coarsely clumped chromatin, prominent nucleoli, numerous mitotic figures; starry sky appearance due to tingible body macrophages
Positive stains: CD10, CD20
Also called angiofollicular lymphoid hyperplasia, giant lymph node hyperplasia
Associated with fever, weight loss, anemia
Primarily affects mediastinal lymph nodes, occasionally affects thymus
Excision is curative if localized; poor prognosis if multifocal disease
Gross: enlarged, distorted lymph nodes
Micro: follicular aggregates of small, mature lymphocytes with compression of sinuses; increased number of small-caliber vessels, surrounded by fibrohyaline eosinophilic material or mature plasma cells; follicles also surrounded by “onion-skin” arrays of lymphocytes
Most common primary malignancy of mediastinum, except for Hodgkin’s lymphoma
Usually anterior mediastinum of young women (65%) in 20’s and 30’s or men (35%) in 40’s and 50’s
Usually confined to chest at diagnosis, often presents with superior vena cava syndrome
<25% have extrathoracic involvement after staging
May spread to brain, liver, ovaries, kidneys, adrenals, intestines
Aggressive, but responds to chemotherapy with 5 year survival of 60%
May arise from germinal center B cells normally present in thymic medulla, AJSP 2001;25:1277
Poor prognostic factors: high stage, size > 10 cm, extrathoracic involvement at diagnosis, poor response to chemotherapy, pericardial or pleural effusion at diagnosis
Gross: bulky anterior intrathoracic mass, often centered in thymus; fleshy, multilobated, poorly delineated, unencapsulated with hemorrhage and necrosis; may directly extend to thoracic structures
Micro: sheets or irregular clusters of large cells with vesicular or hyperchromatic nuclei with irregular contours / nuclear blebs, prominent nucleoli; may appear immunoblastic or resemble Reed-Sternberg cells; amphophilic or clear cytoplasm; may trap benign thymocytes; may have mixture of small mature lymphocytes in tight perivascular cuffs; usually frequent mitotic figures, apoptosis, but no broad zones of necrosis; usually stromal sclerosis; residual thymus may be cystic
Micro images: MAL protein staining
Positive stains: CD19, CD20, CD22, CD79a, bcl6, CD10 (32%), CD30 (some), MAL (70%, Mod Path 2002;15:1172), LCA/CD45 (variable), rarely beta-hCG (AJSP 1999;23:717)
Negative stains: CD3, CD15, CD21, keratin, CD23 (variable), TdT, PAS, PLAP, CEA, S100 (variable), EMA (variable), muscle specific actin, surface immunoglobulin
Molecular: IgH and IgL rearrangements, 9p amplification involving REL gene (% unknown); no bcl-6 gene rearrangement or mutations
EM: no intercellular junctional complexes, pericellular basal lamina, complex nucleoli, premelanosomes, tonofibrils or branching surface microvilli, although filiform projections of cellular membranes may resemble microvilli
DD: Anaplastic lymphoma (CD30+, CD45-), Hodgkin’s lymphoma, lymphoblastic lymphoma, germ cell tumors
May present as large solitary mass along paravertebral column, associated with thalassemia or hereditary spherocytosis
DD: myelolipoma (no associated hematologic disorder)
Also called extramedullary myelogenous leukemia, chloroma
May be associated with myeloproliferative disease, acute myelogenous leukemia
Either 35 years old or less or 65 years old or more
Touch preps are helpful for diagnosis; show Auer rods with Romanowsky stain
Poor prognosis, since usually evolves to acute myelogenous leukemia
Gross: bulky anterior intrathoracic mass, green on cut section (derivation of chloroma), often centered in thymus; fleshy, multilobated, poorly delineated, unencapsulated with hemorrhage and necrosis; may directly extend to thoracic structures
Micro: sheets of large, monomorphic, polyhedral cells with irregular nuclear contours, vesicular chromatin, variable nucleoli; mature and immature eosinophils
Positive stains: myeloperoxidase, chloroacetate esterase, CD13, CD15, CD33, CD68
EM: primary granules often present
Most common mediastinal malignant tumor
Usually young women in 20’s and 30’s
Often involves thymus, mediastinal nodes or both; involves adjacent structures by direct extension
Systemic symptoms (fever, weight loss, night sweats, fatigue) are common
90% curable at stages I-II
Gross: may produce multilocular thymic cysts
Micro: prominent cysts at low power; extensive fibrosis
Molecular: t(2;5) of anaplastic large cell lymphoma is NOT present
Mixed cellularity
Micro: classic Reed-Sternberg cells with multilobulated nuclei, vesicular chromatin, multiple eosinophilic nucleoli; also mononuclear Reed-Sternberg cells, mature small lymphocytes, eosinophils, plasma cells, immunoblasts
Positive stains: CD15, CD30 (membranous and perinuclear globular staining)
Negative stains: keratin, CD45, CD3, CD43
Nodular sclerosis
Most common subtype in mediastinum
Gross: pseudoencapsulated with internal fibrous bands; thick capsule if thymus involved; nodular (solitary or multiple); residual thymic tissue usually present; may form thymic cysts
Micro: refractile collagen bands intersect at oblique angles, surround highly atypical mononuclear cells with vesicular nuclei and eosinophilic nucleoli; also small mature lymphocytes, eosinophils, lacunar cells; residual thymic elements also present
Positive stains: CD15, CD30 (membranous and perinuclear globular staining)
Negative stains: keratin (thymic epithelial cells are positive), CD45, CD3, CD43
Syncytial variant
Micro: resembles nodular sclerosis but with confluent sheets of Reed-Sternberg and variant cells
Also called Langerhans cell granulomatosis, histiocytosis X, eosinophilic granuloma, Letterer-Siwe disease, Hand-Schuller-Christian disease
Rare; neoplastic proliferation of Langerhans cells
Usually affects bone, less commonly lymph node, skin; typically thymus is unaffected
Rarely presents as thymic mass in children with myasthenia gravis, even less often in adults with myasthenia gravis
Langerhans cells are interdigitating dendritic cells, which process and present antigens
Excellent prognosis in children
Case reports: 49 year old woman with leiomyosarcoma but without myasthenia gravis (Archives 2003;127:e294); 11 month infant with small nodules discovered incidentally at surgery for tetralogy of Fallot (Archives 2003;127:218); associated with multilocular thymic cyst in middle-aged man (Hum Path 2000;31:1532)
Gross: large, often encapsulated, tan-gray, firm cut surface with bands of gray-white fibrous tissue
Gross images: mediastinal mass
Micro: sheets of oval cells with slightly eosinophilic cytoplasm and grooved, convoluted nuclei with fine chromatin, thin nuclear membranes, up to 5 mitoses/10 HPF; mixed with sheets and microabscesses of eosinophils; bands of fibrous tissue, islands of residual thymus tissue
Micro images: neoplastic Langerhans cells, nodular infiltrates of Langerhans cells
Positive stains: CD1a, S100, fascin; usually CD68
EM: intracytoplasmic Birbeck granules
Usually teens/young adults, males more common than females; also ages 60-79 years
5 year survival is 50% with multiagent chemotherapy
Usually T cell
Typically presents with acute respiratory distress in teenager; systemic dissemination common
Gross: solid, soft, nonencapsulated, often extensive necrosis
Micro: diffuse growth or pseudonodular pattern; lymphocytes have even chromatin, inconspicuous nucleoli, increased nuclear / cytoplasmic ratios, but with nuclear grooves, frequent mitotic figures, extension into adipose tissue, vascular invasion; residual Hassall’s corpuscles may be present
Positive stains: CD1, CD2, CD3, CD43, CD99, bcl2, TdT
Negative stains: keratin
DD: lymphocyte rich thymomas (unusual in children)
Very rare in thymus, < 10 cases reported
Case reports: coexisting thymic MALT and gastric MALT in 36 year old woman with Sjogren’s syndrome (Archives 2000;124:770); 63 year old woman with possible connective tissue disease (Hum Path 2000;31:255)
Gross: centered in thymus
Micro: clusters of centrocyte-like lymphoid cells in lymphoepithelial lesions mixed with mature lymphocytes and lymphoid follicles with reactive germinal centers; also plasma cells; variable microcysts
Micro images: thymic tumor (figure 1)
Positive stains: CD20, CD45, CD79a, monotypic immunoglobulin light chain, variable CD10
Negative stains: CD5, CD43, CD99, bcl2, TdT
EM: nuclei with irregular protrusions or blebs; no intercellular junctions, no cytoplasmic filament bundles, neurosecretory granules, synaptic vesicles, microtubules, basal lamina, cytoplasmic processes or primitive sarcomeres
Rare in non-nasal location
Case report in black American man with AIDS with death 5 weeks after onset, Archives 2000;124:304
Gross images: anterior mediastinal mass
Micro: diffuse dense infiltrate of atypical intermediate to large lymphoid cells and occasional immunoblasts, with angiocentric and angiodestructive growth and extensive necrosis; azurophilic granules with Giemsa stain
Micro images: atypical lymphocytes with angioinvasive lesions, CD3, granzyme, TIA1
Positive stains: EBV, CD3, CD16, CD56, granzyme, TIA1
EM: dense cytoplasmic granules
EM images: cytoplasmic dense core granules
Rarely benign mesothelial cells are present in nodal sinuses as single cells or small clusters, identifiable with CAM5.2
References: AJSP 1999;23:1264
Elderly, often with multiple myeloma or paraproteinemia
Micro: sheets of polygonal cells with round, eccentric nuclei, coarsely stippled chromatin (clockface nuclei), homogenous amphophilic cytoplasm; also binucleated forms, perinuclear clearing (perinuclear hofs), discohesive cells at periphery
Positive stains: CD38, light chain restriction, variable EMA
Negative stains: keratin, chromogranin A, synaptophysin
EM: abundant rough endoplasmic reticulum, no intercellular junctional complexes, no neurosecretory granules
DD: large B cell lymphoma, neuroendocrine tumors
Other malignancies
Also called well differentiated neuroendocrine carcinoma
Usually of thymic origin in anterior mediastinum, occasionally in middle or posterior mediastinum
Mean 48 years old, 80% men
One-third have paraneoplastic Cushing’s syndrome, syndrome of inappropriate antidiuretic hormone, Eaton-Lambert syndrome, or rarely PTH production; 20% occur in MEN I or II patients
Carcinoid syndrome is very unusual
Act like atypical carcinoid at other sites; must be considered to have metastatic potential with metastasis to mediastinal lymph nodes, bone, liver, skin; may recur after 10 years
Radiation therapy and chemotherapy have not been effective
Adverse prognostic factors: ectopic ACTH production or association with MEN syndromes
5 year survival: 70% without endocrinopathy vs. 35% with endocrinopathy
Gross: well circumscribed but unencapsulated, firm, gray-pink, fleshy, gritty on cut section, hemorrhage, necrosis, no internal fibrous septa
Micro: organoid pattern with islands, ribbons, festoons, trabeculae, rosettes of small round cells with salt and pepper chromatin, minimal cytoplasm, mitotic activity; cellular nests may become detached from septa during processing and contain foci of central geographic necrosis with dystrophic calcification; marked vascularization, frequent angiolymphatic invasion, may have amyloid-type stroma, sclerotic (desmoplastic-type) stroma, melanin pigment, mucin, mixture of sarcomatoid carcinoma, thymomas, thymic cyst; no lymphocytes, no perivascular spaces
Micro images: irregular nests in cellular stroma, salt and pepper chromatin #1, #2, #3 with areas of spindling
Positive stains: keratin, EMA, NSE, synaptophysin, CD57/Leu7, chromogranin A, variable peptides, variable CEA
Negative stains: CD45/LCA, PLAP, S100, muscle specific actin
EM: numerous dense core neurosecretory granules, perinuclear whorls of intermediate filaments, intercellular junctions; no complex nucleoli, no premelanosomes, no branching surface microvilli, no complex desmosomes, no tonofilaments
DD: parathyroid carcinoma (PAS+, diastase sensitive, PTH+), paraganglioma (tight nests, S100+, keratin-)
Spindle cell carcinoid of thymus
Very rare (< 10 cases reported)
May cause death
Associated with MEN-1, syndrome of inappropriate antidiuretic hormone secretion
Gross: tan-brown, well circumscribed, encapsulated, 2-15 cm
Micro: fascicles of plump spindle cells separated by thin fibrovascular septa; with finely dispersed chromatin; amphophilic and granular cytoplasm; frequent mitotic figures, frequent focal necrosis; no/vague organoid pattern, no prominent nucleoli
Positive stains: chromogranin, synaptophysin, keratin
EM: neurosecretory granules
References: Mod Path 1999;12:587
May present as paramedian posterior mediastinal mass in adults or children
More common location is base of skull or sacrococcygeal region
Gross: circumscribed, unencapsulated, with mucoid gray-white cut surface
Micro: nests and cords of physaliphorous cells (polygonal with multiple small cytoplasmic vacuoles) with hyperchromatic nuclei, prominent nucleoli), frequent mitotic activity, in myxochondroid matrix
Positive stains: keratin, EMA, S100, CD57/Leu7
EM: intercellular junctions, intermediate filaments, rough endoplasmic reticulum complexed to mitochondria
Follicular dendritic cell tumor
Also called follicular dendritic reticulum cell tumor, follicular dendritic cell sarcoma
Affect lymph nodes and extranodal sites, including liver, oral cavity, bowel, spleen
Reticulum cells (reticulum means netlike formation or structure) are nonlymphoid, nonphagocytic cells that capture and present antigens and immune complexes
Follicular dendritic reticulum cells are found in B cell zones, particularly in germinal centers (interdigitating reticulum cells are found in T cell zones, and are related to Langerhans cells; fibroblastic reticulum cells are found in the parafollicular and deep cortex areas)
Usually low grade malignant behavior, with local recurrence common and occasional distant metastases to liver or lung
Poor prognostic factors: intraabdominal location, size > 6 cm, 6 or more mitotic figures/10 HPF, atypia and coagulative necrosis
Often misdiagnosed
Immunostains necessary for diagnosis
Case reports: Case of the Week #1
Gross: well circumscribed, light tan and solid; variable hemorrhage and necrosis
Micro: fascicles, sheets, storiform or whorled patterns of a syncytium of oval and spindled cells, with pale to eosinophilic cytoplasm, oval nuclei with finely dispersed chromatin and small nucleoli; variable lymphocytes and plasma cells, often with perivascular cuffing; multinucleated tumor giant cells are often present
Micro images: CD21/CD35 stain highlights ovoid spindle cells #1a; #1b; #1c;
head and neck - vague whorls of spindle cells in a storiform growth pattern, with lymphocytes and plasma cells present; tumor cells have indistinct cell borders, and occasional multinucleated giant cells are present (arrows); strong immunostaining for CD21 (left) and CD35 (right)
Positive stains: CD21 and CD35; variable S100, CD68 and EBV
Negative stains: CD1a
EM: numerous interwoven long cytoplasmic processes joined focally by desmosomes
DD: melanoma, thymoma, other sarcomas, some carcinomas and possibly inflammatory myofibroblastic tumors
Fibroblastic reticulum cell tumors: positive for vimentin, smooth muscle actin, desmin, focal CD68; negative for CD21, CD35, S100 and EBV
Histiocytic tumors: positive for CD68 and lysozyme
Interdigitating dendritic cell tumors: positive for S100, vimentin, fascin, focal CD68; negative for CD1a, CD21, CD35, B and T cell markers, actin, desmin, keratin
Langerhans cell tumors: positive for S100, CD1a, CD68, vimentin
References: inflammatory pseudotumor-like variant-AJSP 2001;25:721, Mod Path 2002;15:50, AJSP 1994;18:148, AJSP 1996;20:944, Mod Path 2001;14:354
Usually < 1 year old
Most patients can be cured
Gross: well circumscribed, often encapsulated
Micro: intermediate degree of differentiation between neuroblastoma and ganglioneuroma, comparable to a differentiating neuroblastoma or immature ganglioneuroma
Germ cell tumors
Account for 20% of mediastinal tumors and cysts
Usually males ages 20-49 years
Mediastinal tumor in male in this age group should be presumed to be a germ cell tumor until proven otherwise
Often elevated serum AFP, hCG, HPL, LDH, PLAP
Associated with i(12p)+ acute leukemia, Klinefelter’s syndrome (30x risk)
Nonteratomas are often very large at diagnosis
Prognosis: worse than gonadal germ cell tumors, with 5 year disease free survival of 50-65% for seminomas, 20% for other subtypes
Favorable prognostic factors for non-seminomatous tumors: rapid decline in serum AFP or hCG after surgery and chemotherapy, no vascular invasion, no yolk sac or choriocarcinoma components
Gross: unencapsulated, homogenous fleshy mass with indistinct boundaries and invasion of adjacent structures, hemorrhage or necrosis
DD: metastatic germ cell tumor (although unlikely if single tumor with no retroperitoneal involvement)
Germ cell tumors - choriocarcinoma
Usually males in 20’s with elevated hCG and gynecomastia, impotence
Poor prognosis
Positive stains: keratin, EMA, hCG
EM: cytoplasmic tonofibrils and plasmalemmal microvilli
DD: metastasis from occult testicular primary (although treatment and prognosis are similar)
Germ cell tumors - embryonal carcinoma
Usually males
Gross: invasive, highly necrotic
Micro: poorly differentiated, pleomorphic cells with prominent nucleoli, often with eosinophilic intracellular globules or primitive lumina; variable geographic necrosis; no nuclear blebs
Positive stains: PLAP, keratin, PAS, CD57/Leu7, variable AFP
Negative stains: EMA, CD45, CEA, S100, muscle specific actin
Molecular: i(12p)
EM: well developed junctional complexes, complex nucleoli, primitive microvillous structures or intracellular lumina
Germ cell tumors - mixed
Common, should describe individual components present and percentage of each
Germ cell tumors - seminoma
Almost always males, within thymus
5 year disease free survival is 50-65%; 10 year actuarial survival is 69%
Favorable prognostic factors: age 35 years or less at diagnosis, no superior vena caval syndrome, no mediastinal lymphadenopathy, no fever
Treatment: excision, radiation therapy
Gross: solid, homogenous, tan-white bulging cut surface, residual thymic tissue may be present
Micro: nests of large tumor cells with clear cytoplasm, distinct cell membranes, prominent nucleoli, separated by fibrous stroma with abundant lymphocytes; often epithelioid granulomas, numerous germinal centers, cytoplasmic glycogen, variable geographic necrosis, no nuclear blebs; may entrap normal thymus cells
Positive stains: PLAP (membranous), PAS, CD57/Leu7
Negative stains: keratin (may be focal, thymic epithelial cells are keratin+), EMA, LCA, CEA, S100, muscle specific actin
EM: primitive appositional intercellular junctions, prominent and complex nucleoli (nucleolonemata), abundant cytoplasmic glycogen, no premelanosomes, no complex branching microvilli
DD: thymomas, diffuse large cell lymphoma
Germ cell tumors - mature teratomas
Most common mediastinal germ cell neoplasm
Benign; peripheral eggshell calcifications in anterior mediastinal mass are relative specific
Often adheres to surrounding structures
Xanthogranulomatous reaction if sebaceous material escapes
May perforate trachea/bronchi, causing patient to cough up hair and oily/sebaceous material
Micro: cysts lined by stratified squamous material with sebaceous glands and hair follicles; also neural tissue, GI, cartilage, respiratory structures, pancreatic tissue
Germ cell tumors - immature teratomas
Teratoma with immature epithelial, mesenchymal or neural elements
Good prognosis if 14 years old or less
Germ cell tumors - yolk sac tumors
Also called endodermal sinus tumors
Usually males
Often mixed with other germ cell elements
Poor prognosis
Micro: intracellular eosinophilic globules (PAS+, AFP+)
Sarcomatoid variant has spindle cells, storiform pattern, myxoid stroma, but is otherwise similar
Positive stains: PLAP, keratin, variable AFP
Negative stains: EMA
EM: redundant basal lamina, globular secretions of AFP+ dense material within rough endoplasmic reticulum
Epithelioid
Gross: circumscribed but unencapsulated mass, associated with adventitia of large blood vessels; has glistening and hemorrhagic cut surface
Micro: cords or disorganized sheets of markedly vacuolated polygonal cells in myxohyaline stroma; variable nuclear atypia; variable mitotic activity
Positive stains: CD31, CD34, von Willebrand factor
Negative stains: keratin, EMA, S100
EM: Weibel-Palade bodies
DD: metastatic carcinoma, liposarcoma
Kaposiform
Rare pediatric neoplasm, usually in soft tissue of retroperitoneum and extremities
May be locally invasive, but distant metastases are rare
Associated with Kasabach-Merritt syndrome, a consumptive coagulopathy associated with vascular lesions
Not associated with Kaposi’s sarcoma or human herpesvirus 8
Case report in 1 month old infant with stridor and infiltrative thymic tumor extending into pericardium and carotid sheaths, Archives 2000;124:1542
Treatment: aggressive chemotherapy may be helpful
Micro: diffusely infiltrative, vascular, spindled tumor infiltrating lobules of thymus, which may be depleted of lymphocytes; resembles capillary hemangioma and Kaposi’s sarcoma; may have glomeruloid proliferations of epithelioid endothelial cells; cells may have intracytoplasmic lumina with hyaline globules, hemosiderin deposition; spindled cells have slitlike vascular spaces resembling Kaposi’s sarcoma; frequent mitotic activity
Micro images: spindled cells, glomeruloid nests, intracytoplasmic lumina, pigment, tumor cells are keratin-, residual thymus is keratin+
Positive stains: CD31, CD34
Negative stains: cytokeratin, Factor VIII
Ages 25-70
Gross: circumscribed, tan-white, firm, with cystic or myxoid degeneration
Micro: smooth muscle in fascicles with moderate to marked atypia and frequent mitotic activity; often epithelioid cells
Positive stains: desmin, muscle-specific actin, variable vimentin
Negative stains: keratin, EMA, S100, HMB45
EM: epithelioid tumors have plasmalemmal dense patches, pinocytotic activity, basal lamina, thin cytoplasmic filaments, dense bodies
Associated with liposarcoma of thigh or retroperitoneum as a multicentric tumor
Report of mediastinal well differentiated liposarcoma with leiomyosarcomatous differentiation (lipoleiomyosaroma), AJSP 2002;26:742
Malignant peripheral nerve sheath tumor (MPNST)
Often associated with neurofibromatosis
Often spreads to pleura or lungs
Extremely poor prognosis if glandular or rhabdomyosarcomatous features
Gross: unencapsulated, degenerative changes common (fat, hemorrhage, cysts)
Micro: bizarre cells and tumor giant cells; also atypical mitotic figures and necrosis; may have areas of uniform bland spindle cells; rarely has rhabdomyosarcomatous features (“triton tumor”) or glandular differentiation
Rarely occurs as mediastinal tumor with no known primary lesion
Very poor prognosis
Case reports: primary thymic tumor apparently derived from a nevus in 26 year old woman (AJSP 2000;24:1305), mediastinal tumor in 11 year old boy (AJSP 2000;24:747), 69 year old man with intrathymic tumor, no prior melanoma history (Archives 2000;124:130)
Gross images: internal fibrous bands and necrosis
Micro: pleomorphic polygonal cells, often with delicate intracellular pigment and intranuclear pseudoinclusions of cytoplasm, prominent eosinophilic nucleoli, brisk mitotic activity; variable geographic necrosis, no nuclear blebs
Micro images: melanoma and adjacent thymus, HMB45
Positive stains: S100, HMB45, MelanA/Mart1, vimentin, p53, variable PAS
Negative stains: keratin, EMA, PLAP, CD15, CD30, LCA/CD45, CEA, muscle specific actin
EM: premelanosomes, no branching surface microvilli
EM images: melanosomes
DD (other primary pigmented mediastinal tumors): pigmented paraganglioma, pigmented thymic carcinoid, melanotic neuroectodermal neoplasm, melanotic schwannoma
May originate in hilar reflections of pleura, although clear-cut connection to serosal surface may not be present
Usually men age 50+ years
50% have history of high levels of aerosolized asbestos exposure
Often with pleural or pericardial effusion
Very poor prognosis
Micro: biphasic or papillotubular pattern; also sheets or nests of malignant polygonal cells with pleomorphism, prominent nucleoli and mitotic activity; variable geographic necrosis, no nuclear blebs
Positive stains: keratin, vimentin, EMA (if epithelioid),
Negative stains: CEA, CD15, PAS (variable), CD45/LCA, PLAP, CEA, S100, muscle specific actin
EM: long, branching, cellular microvilli with length/diameter ratio of 10-15:1; cytoplasmic tonofibrils, elongated intercellular junctional complexes, no premelanosomes
DD: metastatic carcinoma
Sarcomatoid mesothelioma
Similar to classic mesothelioma except for presence of spindled and pleomorphic tumor cells
DD: sarcomatoid carcinoma
Osteosarcoma, Ewing’s sarcoma of bone, melanoma
Young children, usually < 1 year
Usually primary tumors of posterior mediastinum associated with paraspinal nerve roots; rarely represents metastases to mediastinum
Symptoms due to compression of nerve roots or esophagus
May have opsoclonus-myoclonus (dancing feet and eyes) due to paraneoplastic syndrome
Tumors of thymus and anterior mediastinum are associated with syndrome of inappropriate antidiuretic hormone
May relapse in central nervous system
Lab: elevated HMA and VMA; hyponatremia
Gross: partially encapsulated, infiltrative, pink-gray fleshy cut surface, hemorrhage, necrosis, calcification
Micro: small round blue cell tumor with sheets of monomorphic cells with uniform chromatin, minimal nucleoli, scant eosinophilic cytoplasm; often brisk mitotic activity; necrosis, dystrophic calcification, arborizing vasculature; variable fibrillary eosinophilic intercellular matrix; variable ganglion cells
Positive stains: CD57/Leu7, synaptophysin, variable vimentin and neurofilament
Negative stains: EMA, keratin, CD45, desmin, actin
EM: complex, long, interdigitating cytoplasmic processes with microtubules; may have synaptic vesicles and scant neurosecretory granules; no/minimal basal lamina, no/minimal intermediate filaments
Primitive neuroectodermal tumor (PNET)
Usually children
Rapidly growing mass in anterior or posterior mediastinum
Gross: bulky, poorly circumscribed, gray-white, fleshy, may adhere to spinal nerve root if in posterior mediastinum
Micro: primitive round cell sarcoma that may have vaguely organoid pattern or primitive rosettes; prominent network of intratumoral blood vessels; no cytoplasmic neurofibrillary maturation; may have rhabdomyosarcomatous areas or primitive glandular areas
Positive stains: vimentin, CD99, beta2-microglobulin, synaptophysin, CD57/Leu7; rarely keratin, desmin, actin
Negative stains: neurofilament
Molecular: t(11;22)(q24;q12)
EM: blunt and rudimentary cytoplasmic processes; no intracellular microtubules, no/sparse synaptic vesicles or neurosecretory granules; primitive intercellular junctions
Cytokeratin-positive interstitial reticulum cells
Present in normal lymph nodes, subset of fibroblastic reticulum cells
May have bizarre giant cell and multinucleated features in HIV associated lymphadenopathy
Tumors are rare; case report of 2 malignant mediastinal tumors, AJSP 2000;24:107
Micro: non-cohesive, ill-defined fascicles of spindle cells with long, slender cytoplasmic processes, in a background of lymphocytes and plasma cells; mild nuclear atypia; variable mitotic activity; usually no tumor necrosis
Positive stains: CK8/18, vimentin (normal and tumor); variable smooth muscle actin and desmin
Negative stains: EBV, CD5
EM: long interdigitating microvillous-like cell processes, some desmosomes between cells
DD: metastatic sarcomatoid carcinoma, inflammatory myofibroblastic tumor (composed of myofibroblasts)
Follicular dendritic cells
Positive stains: CD21, CD35
Negative stains: cytokeratin
EM: numerous interwoven long cytoplasmic processes joined focally by desmosomes
Interdigitating dendritic cells
Positive stains: S100, variable CD1a, CD68
Negative stains: cytokeratin
EM: interdigitating cytoplasmic processes
Children and teens
Mass related symptoms, but no paraneoplastic syndromes
Gross: poorly demarcated, bulky tumor of soft tissue, gray-white fleshy cut surface, hemorrhage and necrosis common
Micro: small round blue cell tumor; largely monomorphic but also with nuclear and cellular pleomorphism, scattered large multinuclear cells, eccentric nuclei, deeply eosinophilic cytoplasm, myxoid stromal change, alveolar growth, clear cell change
Positive stains: desmin, muscle-specific actin, vimentin, CD99, variable myoglobin
Negative stains: synaptophysin, CD57/Leu7 (usually)
EM: tight aggregates of cytoplasmic intermediate filaments, sometimes associated with thick filaments and organized as sarcomeres with Z bands; glycogen, short segments of pericellular basal lamina; no intercellular junctions, no cytoplasmic processes, no microtubules, no synaptic vesicles, no dense-core granules
DD: triton tumor (may have partial rhabdomyosarcomatous differentiation, but occurs in adults), PNET, neuroblastoma
Adults
More indolent than liposarcomas elsewhere - may respond to radiation therapy or chemotherapy
One case recurred 32 years after diagnosis
Gross: resembles thymolipoma
Micro: malignant spindle cells resembling well-differentiated, pleomorphic or poorly differentiated liposarcoma mixed with thymic tissue
Miscellaneous
Features to report for thymic epithelial neoplasms
Tumor location
Tumor size
Histologic type
Extent of capsular invasion
Extent of invasion of adjacent tissue
Angiolymphatic invasion
Perineural invasion
Margin involvement (distance from closest approach of tumor)
Lymph node involvement (total number examined, number involved by tumor, size of largest metastasis, presence of extranodal extension of tumor)
Additional findings (additional tumors, nonneoplastic tissue)
References: Archives 2003;127:1298
At least 1 section of tumor per cm of tumor diameter
Tumor and adjacent tissue
Tumor invading adjacent tissue
Numerous sections of tumor capsule, particularly in areas of apparent disruption
Margins
Areas with other pathologic findings
Other organs or tissues
End of Mediastinum chapter / outline