Mediastinum-Printer Friendly Version
Last revised 20 December 2006
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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, thymoma staging, 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
Other: 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
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
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)
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
Positive stains: epithelial cells - keratin, HLA-DR
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)
Micro: normal appearing thymic tissue
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
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, neck, thyroid, pulmonary hilum, lung parenchyma, pleura
Poor prognostic factors: high stage, tumor related signs/symptoms at diagnosis, tumor diameter > 15 cm, age 29 years or less, microscopic predominance of epithelial cells, nuclear atypia
Invasion of capsule (micro- or macroscopically) is a poor prognostic factor, as 7% show idiosyncratic metastatic spread, although 15% of encapsulated thymomas recur
Presence of myasthenia gravis has mild or no favorable prognostic value
Hemorrhage and necrosis in well encapsulated, noninvasive thymomas don’t affect prognosis, AJSP 2001;25:1086
Treatment: surgical excision; chemotherapy or radiation recommended for stage II-p1
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 thymomas; 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
Outcome similar for A, B, AB, worse for C
Highest recurrence rate for B2/B3, then B1, then AB, none/rare in A, AJSP 2001;25:103
Case reports: with SLL/CLL (Archives 2003;127:E76), invasive thymoma expressing photoreceptor protein recoverin, with cancer associated retinopathy and autoantibodies to recoverin (Hum Path 2003;34:717)
Gross: 80% encapsulated, 20% 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
Micro: cytologically bland epithelial neoplasm; subtypes (except for carcinoma) have no/minimal prognostic value but help with diagnostic problems; rarely has rosettes without central lumina; also varying amounts of non-neoplastic lymphocytes; well formed Hassall’s corpuscles are usually lacking; capsule may be thick and calcified; may have prominent vasculature, microcystic and pseudopapillary patterns, extensive sclerosis; rarely has marked plasma cell infiltrate or amyloid
Positive stains: keratin (epithelial cells), CEA, CD3 and Ki-67 (lymphocytes outside lymphoid follicles are T cells), S100 (interdigitating reticulum cells), 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
References: AJSP 2002;26:1605 (WHO classification)
Epithelial predominant
2/3 or more epithelial cells
Micro: internal fibrous septa, intralesional microcysts, perivascular serum lakes present; rarely staghorn type vessels or storiform growth pattern
Positive stains: CD5 in 40% with cytologic atypia
DD: fibrous histiocytoma (rare in mediastinum, vimentin+, keratin-), hemangiopericytoma (rare in mediastinum, reticulin stain shows intercellular matrix deposition around individual tumor cells, vimentin+, keratin-)
Lymphocyte predominant
Associated with myasthenia gravis
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 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
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), 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)
Mixed lymphoepithelial
1/3-2/3 plump epithelial cells, remainder small lymphocytes
Excellent prognosis if stage I or II
Negative stains: CD5 (in epithelial cells)
Spindle cell
Also called medullary, 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
Micro: epithelial predominant with fusiform epithelial tumor cells; gland like spaces, storiform patterns are common; no/rare lymphocytes
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
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
Positive stains: keratin; lymphocytes - CD3, CD20, CD99
EM: tonofilaments, well developed 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