Pleura
Last revised 8 February 2011
Copyright (c) 2003-2010, PathologyOutlines.com, Inc.
See also Lung
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Primary references, normal anatomy, normal histology
Asbestos related disorders: general, pleural plaques
Non-neoplastic conditions: black spots, endometriosis, pleural effusion, pleuritis, pneumothorax, tuberculosis
Mesothelial tumors: atypical mesothelial hyperplasia, benign epithelial mesothelioma, benign mesothelial proliferations, benign multicystic mesothelioma, mesothelioma, mesothelioma vs. adenocarcinoma
Other pleural mesothelioma: staging, features to report, grossing
Other tumors: angiosarcoma, fibromatosis, liposarcoma, metastases, nodular histiocytic hyperplasia, pleuropulmonary blastoma, post-transplant lymphoproliferative disorder, sinus histiocytosis with massive lymphadenopathy, smooth muscle tumor, solitary fibrous tumor, synovial sarcoma, thymoma
AJCC Cancer Staging Manual (7th ed)
American Journal of Surgical Pathology (AJSP), Jan 1998 to Jan 2004
Archives of Pathology and Laboratory Medicine (Archives), Jan 1998 to Feb 2004
Human Pathology (Hum Path), Jan 1998 to Jan 2004
Modern Pathology (Mod Path), Jan 1998 to Feb 2004
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 and photographs
Lungs are surrounded by visceral pleural, a delicate serous membrane arranged as a closed invaginated sac
Inner chest cavity is lined by parietal pleural membrane
Visceral and parietal pleura define the pleural space/cavity, which normally has minimal volume, unless lungs collapse or air / fluid collects between the two layers
Only minimal contact between right and left pleural sacs
Regional lymph nodes are internal mammary, intrathoracic, scalene and supraclavicular
Drawings: pleura and chest wall #1, #2
Lined by mesothelial cells overlying vascularized connective tissue
Mesothelium provides smooth, low friction surface to facilitate the gliding motion of lungs in pleural cavity, heart in pericardial cavity, viscera in abdominal cavity
Gliding facilitated by numerous surface microvilli, thick glycocalyx, secretion of hyaluronic acid and other glycosaminoglycans
Mesothelial cells
Micro: monolayer of flat or low cuboidal cells with bland and uniform nuclei, fine delicate chromatin, inconspicuous nucleoli; in fine needle aspirates have well defined cytoplasm and distinct cell borders
Positive stains: keratin
EM: apical tight junctions, desmosomes, surface microvilli, cytoplasmic tonofilaments in bundles
Connective tissue cells
Micro: resemble fibroblasts
Positive stains: vimentin; keratin in reactive conditions
EM: resemble fibroblasts
Asbestos related disorders
Asbestos causes localized fibrous plaques, pleural effusions, parenchymal interstitial fibrosis (asbestosis), bronchogenic carcinoma, mesothelioma, laryngeal carcinoma, possibly colon carcinoma
Exists in serpentine/chrysotile (curly, flexible) and amphibole (straight, stiff, brittle) forms; most asbestos in industry is serpentine, but amphiboles are more pathogenic; link with mesothelioma is almost always with amphibole form
Chrysotiles usually are caught in upper respiratory passages, removed by mucociliary elevator; they are soluble and leached from tissue if they reach alveoli
Amphiboles go deeper into lungs; fibers > 8 mm and thinner than 0.5 mm are more injurious
Both types are fibrogenic; act as tumor initiator and promoter; toxic chemicals such as tobacco smoke may be adsorbed to asbestos fibers; asbestos fibers may also generate reactive free radicals
However, asbestos bodies are common in normals; present in 40% at autopsy in US in lung smears
Asbestos may act by countering antioxidant effect of Vitamin C (ascorbic acid), Hum Path 2003;34:737
In pleura, asbestos causes pleural plaques and mesothelioma
Relative risk (RR) compared to normal population: for bronchogenic carcinoma, RR is 5x, increasing to 55x for asbestos exposure plus tobacco use; for mesothelioma (pleural, pericardial, peritoneal), RR is 1000x, with no change for asbestos plus tobacco use
Due to chronic injury of pleural surface
Do not contain asbestos bodies, but rare if no asbestos history (may be from other pneumoconiosis)
May induce pleural effusions, but usually no symptoms
Gross: on parietal pleura near vertebral column, lower lung, dome of diaphragm
Gross images: fibrotic plaque on diaphragm
Micro: well circumscribed plaques of dense, hyalinized, acellular collagen, may have with basket-weave morphology, often calcified
Micro images: dense layers of collagen
Non-neoplastic conditions
Carbonaceous/anthracotic pigments in parietal pleura
Present in >90% of urban dwellers in Belgium at autopsy
Not related to hyaline pleural plaques, AJSP 2002;26:1198
Associated with lymphatic drainage
Micro: deposits of opaque particles (intra- or extracellular) of various sizes under an intact mesothelial layer, associated with chronic inflammatory cells
Associated with diffuse abdominal disease
Involve pleura or lung
In one study, 9 women were median 36 years old, range 27-74 years, Hum Path 1998;29:1495
Micro: well circumscribed or infiltrative, cystic, nodular or both, with cycling endometrium exhibiting metaplastic changes
Positive stains: glandular epithelium - CK7, BER-EP4, ER, PR; stroma - vimentin, actin and smooth muscle actin, desmin, ER, PR
Negative stains: mucin
15 cc or more of fluid within pleural cavities
Most common causes are congestive heart failure and metastatic disease
Due to increased hydrostatic pressure (congestive heart failure), increased vascular permeability (pneumonia), decreased oncotic pressure (nephrotic syndrome), increased intrapleural negative pressure (atalectasis), decreased lymphatic drainage (carcinomatosis)
May or may not be inflammatory
Malignant effusions are usually greater than 500 ml; are often first evidence of malignancy
For lung, breast and ovarian metastases, 92% of pleural effusions are ipsilateral to primary lesion
Inflammatory pleural effusion
Either serous, serofibrinous or fibrinous
Due to inflammation in lung (tuberculosis, pneumonia, infarct, abscess, bronchiectasis), collagen vascular disease (rheumatoid arthritis, systemic lupus erythematosis, uremia) or radiation therapy
Empyema: pus in pleural cavity; due to bacteria or fungal seeding of pleural space; often from lung infection; usually organizes into dense adhesions, but does not disappear
Noninflammatory pleural effusion
Hydrothorax: clear/straw colored fluid; usually due to congestive heart failure
Isolated right sided hydrothorax seen in Meig syndrome (hydrothorax, ascites, ovarian fibroma)
Usually is NOT loculated, collects basally
Hemothorax: usually due to rupture of aneurysm or vascular trauma; associated with large clots
Chylothorax: accumulation of milky white fluid, usually lymph, contains fat (DD: turbid serous fluid); usually left sided, caused by thoracic duct trauma/obstruction due to malignancy
May be secondary to lung disease, hematoma
Fibrosis may cause pleural symphysis (fusion of visceral and parietal layers)
Thickened pleura may prevent lung expansion; treat with decortication
Hemorrhagic pleuritis: rare, associated with hemorrhage, Rickettsiae infection, tumor
Micro: thickened pleura is composed of fibrous tissue without elastic fibers
Negative stains: telomerase reverse transcriptase, AJSP 2002;26:365
All types may cause compression, collapse, atelectasis of lung and associated respiratory distress
Either spontaneous, traumatic or therapeutic
Spontaneous: due to abscess, tuberculosis, emphysema, asthma
Traumatic: due to puncture of chest wall or lung
Therapeutic: formerly used to treat tuberculosis
Spontaneous idiopathic: young people, rupture of small, peripheral, apical subpleural blebs, usually subsides spontaneously, but may recur and be disabling
Tension pneumothorax: acts as one-way valve to trap air during inhalation; may compress contralateral lung, mediastinal structures
Due to direct spread from lung or hematogenous spread
See extensive discussion in Lung chapter
Mesothelial tumors
Atypical mesothelial hyperplasia
Associated with benign and malignant processes; clinical correlation may be helpful to differentiate
Micro: single layer of hyperchromatic, discrete mesothelial cells, often forming a picket fence arrangement
Benign epithelial mesothelioma
Common in peritoneal cavity, very rare in pleura
Called adenomatoid tumors in peritoneum but have epithelioid features
Occasionally may be a low grade malignant mesothelioma with a protracted clinical course
Gross: soft friable mass, pink-gray-yellow
Micro: well circumscribed fibrous lesion of bland fibroblast-like, spindle cells; bland cytology
DD: benign papillary hyperplasia of mesothelium, well differentiated papillary mesothelioma, malignant mesothelioma (marked atypia and infiltrative)
Benign mesothelial proliferations
Due to various injuries (chemical, mechanical), adjacent inflammatory or neoplastic process or asbestos exposure
Initially is loss of surface monolayer, then surface deposition of fibrin, neutrophils, macrophages; then proliferation of fibroblast-like cells that restore mesothelial surface layer
Fibroblast-like cells are apparently derived from perivascular cells in submesothelial mesenchyme
Micro: may be flat, papillary or have three dimensional groupings; reactive mesothelial cells are more pleomorphic, have dense center with lighter peripheral skirt representing long, slender microvilli; may see superficial entrapment of mesothelial glands and cells by organizing effusions or fat (differentiate from true stromal invasion)
Reactive cells may be parallel to pleural surface and uniformly distributed, as highlighted by keratin stains
Linear arrays of atypical mesothelial cells on free surface of pleura is not malignancy by itself; often associated with fibrin deposition; more common in inflamed areas
Atypia and densely packed mesothelial cells within the pleural space are common
May see zonation with high cellularity and cytologic atypia toward the pleural space and fibrosis and less atypia toward the chest wall
See elongated capillaries perpendicular to the pleural surface
Necrosis and storiform patterns are rare in benign lesions but mitosis may be plentiful
Note: keratin staining may indicate distribution of mesothelial cells in stroma, but both benign and malignant are keratin positive
Stains: similar to mesothelioma (including p53, keratin, EMA), Archives 1996;120:959
References: AJSP 2000;24:1183
Benign multicystic mesothelioma
Common in peritoneal cavity, rare in pleura
Arises from serosal membranes lining pleural, pericardial, peritoneal and scrotal cavities
Usually ages 40-60 years, 75% men, rarely children (not related to asbestos exposure)
Strong association with asbestos, including duration and intensity of exposure; 2/3 of cases involve asbestos exposure; lifetime risk is 7-10% if heavy asbestos exposure, usually occurs after 25-45 year delay; relative risk is 1000x compared to non-asbestos exposure
Initial studies were on South African asbestos miners by Wagner et al.
Not associated with smoking
Grows relatively slowly, but usually diagnosed at advanced stage
50% die within 1 year; few live > 2 years; longer survival with epithelioid histology and perhaps low Ki-67, Hum Path 1998;29:246
Resistance to treatment may be mediated by glutathione associated pathways, Hum Path 2002;33:748
Case reports: CD30+ tumor (Archives 2000;124:1077), tumor cells containing lipid vacuoles (Hum Path 2000;31:876)
Treatment: no effective treatment
Metastases: regional lymph nodes, rarely to hilar/cervical nodes (primary lung carcinoma more likely); late distant metastases to peritoneum, contralateral pleura, lung; often to uncommon sites such as retroperitoneal lymph nodes, brain, spine, thyroid, prostate; rarely presents initially with nodal metastases (DD: benign mesothelial cells, AJSP 1999;23:1264, Hum Path 1998;29:339)
Cytology: useful for diagnosis of epithelial or mixed variants, cells must be neoplastic and have features of mesothelial cells; knobby outline of cell clusters / morules; highly cellular, usually minimal desmoplasia; epithelial; dense cytoplasm with small, regular, centrally located vacuoles, atypical nuclei or binucleation, high nuclear/cytoplasmic ratio; brush border-like image over most of free cell surface; cannot diagnose sarcomatoid variant by cytology; often high levels of hyaluronic acid
Sites: pleura, peritoneum, pericardium, tunica vaginalis testis, hernia and hydrocoele sacs; in pleura, often involves lower half of a hemithorax, but may spread to entire pleural space
Signs/symptoms: recurrent pleural effusions, chest pain, shortness of breath
Xray: irregular pleural thickening, particularly after evacuation of pleural fluid; irregular thickening of interlobar fissures
Gross: confluent gray-white nodular patches in a thickened pleura obliterating pleural space and encasing lung, particularly lower lung and at diaphragm; often invades thoracic structures; associated with pleural effusion; rarely presents as a localized pleural mass; associated with pleural plaques (due to asbestos exposure)
Gross images: tumor encasing lung, gray-white tumor, large tumor mass, diffuse tumor
Micro: classified as epithelial (papillary/tubular, 60-76%), sarcomatoid (resembles spindle cell sarcoma, 2-16%), mixed (22-24%) or desmoplastic (variant of sarcomatoid)
Epithelioid: fibrovascular papillae, tubules, pseudoacini or solid nests lined by atypical mesothelial cells, large three dimensional groupings with irregular arranged cuboidal cells; abundant eosinophilic cytoplasm with a bulging, domelike, apical portion; necrosis, atypical mitotic figures, psammoma bodies; usually not pleomorphic; may have sharply defined vacuoles with metachromatic hyaloruronic acid, representing intracytoplasmic lumina; cell surface may have brush border-like staining particularly with HBME-1 immunostain
Sarcomatoid: grossly are more nodular and less plaque-like with more hemorrhage, necrosis and cystic change; microscopically composed of poorly defined storiform pattern of densely packed spindled cells with high cellularity, nuclear atypia and frequent mitotic figures; heterologous elements are rare; may resemble synovial sarcoma; spindle cells are strongly keratin positive
Desmoplastic: paucicellular storiform or "patternless" pattern and either stromal invasion, bland necrosis (pale staining area with either no nuclei or nuclear fragmentation and no inflammatory response), overtly sarcomatous foci or distant metastases; spindle cells are intensely keratin positive
Mixed: easiest pattern to diagnosis
Note: may see asbestos bodies, but they are more common in lung and hilar nodes than in mesothelioma
Criteria for malignancy: (a) true stromal invasion, with deep penetration of thickened or fibrotic pleura or penetration into fat/muscle of chest wall or into an organ; (b) no zonation (zonation more common with organizing effusions); (c) marked cytologic atypia (although may be bland); (d) necrosis or extensive storiform pattern usually indicates malignancy; (e) branching glands, papillae or large cell groupings usually indicates malignancy, AJSP 2000;24:1183
Micro images: epithelial mesothelioma, mixed mesothelioma #1, #2 with focal bone and cartilage
Virtual slides: epithelioid mesothelioma #1, #2
Positive stains: telomerase reverse transcriptase (AJSP 2002;26:365), CK7
Negative stains: c-kit (Mod Path 2003;16:818), CK20, p63, MUC4 (Mod Path 2004;17:150), rarely mucin positive (Archives 1992;116:874)
Other stains (see below)
Molecular: often diploid
EM: long, slender microvilli (length > 15x diameter), abundant tonofilaments, no lamellar bodies (adenocarcinoma has short stubby microvilli)
DD: reactive processes/fibrous pleuritis (may have atypical mesothelial proliferation or fibrinous exudate; often zonation and perpendicular capillaries; no stromal invasion, no atypia, no necrosis, no atypical mitotic figures, preliminary study indicates negative for telomerase reverse transcriptase)
DD: metastatic papillary serous carcinoma of ovary
DD of sarcomatoid/desmoplastic mesothelioma: solitary fibrous tumor (CD34+, keratin-, if benign, has no atypia, no necrosis, no infiltration), chronic pleuritis (benign on chest Xray, no atypia, no necrosis, no infiltration, keratin stains demonstrate lack of invasion), metastatic sarcoma (primary tumor is usually evident, keratin-), sarcomatoid renal cell carcinoma (may have occult primary), synovial sarcoma (extensive BerEp4+, focal keratin+ only, CD141-, WT1-, AJSP 2001;25:610)
DD: adenocarcinoma (use stains and EM to differentiate; mesotheliomas have windows, denser cytoplasm, more uniform cells, no mucin), thymoma and thymic carcinoma (variable calretinin+ but p63+, thrombomodulin-, WT1- vs. mesothelioma: p63-, thrombomodulin+, WT1+, Hum Path 2003;34:1155)
Clear cell variant
Very rare
Case report of 52 year old man with recurrent pleural effusions, no asbestos exposure, Archives 2001;125:1588
Micro: sheets of large round to polygonal cells with abundant clear cytoplasm, distinct cell membranes, eccentric small round nuclei; brisk lymphoplasmacytic infiltrate, occasional papillary structures, psammoma bodies, necrosis; no glycogen or mucin, rare mitotic figures
Micro images: H&E, calretinin
Positive stains: keratin, EMA, calretinin, HBME-1
Negative stains: CEA, Ber-EP4, S100
EM: long slender microvilli, large desmosomes
EM images: long slender microvilli
DD: metastatic clear cell carcinoma
Deciduoid variant
Rare; < 20 cases reported; highly aggressive
Case reports: 30 year old woman with Hodgkin’s lymphoma treated with radiotherapy and anterior mediastinal mass 12 years later (AJSP 2001;25:547), 41 year old man with Hodgkin’s lymphoma treated with radiotherapy and chemotherapy and pleural-based mass with effusion 14 years later (AJSP 2000;24:1440)
Micro: sheet-like proliferation of large, rounded, ovoid or polygonal cells with pale to bright, eosinophilic cytoplasm resembling decidua with marked vacuolation, imparting a focal clear cell appearance; large, round/oval nuclei, vesicular chromatin, central prominent nucleoli; occasional binucleated tumor cells; fibrotic stroma with extensive coagulative tumor cell necrosis; frequent mitotic figures; no squamous or glandular differentiation; atypical mesothelial cells present on pleura of adherent lung; may have focal rhabdoid areas
Positive stains: AE1/AE3, CAM5.2, calretinin, vimentin, p53
Negative stains: mucicarmine, LeuM1, B72.3, CEA, BerEP4
References: AJSP 2000;24:285 (1 pleural, 5 peritoneal tumors), AJSP 2000;24:816
The cells have abundant cytoplasm and well-defined cell borders that are the result of the presence of numerous microvilli covering the cell membranes
Well differentiated papillary mesothelioma
Unusual variant of epithelial mesothelioma
Either pleura or peritoneum of young women with no history of asbestos exposure, or older population (mean age 58 years) of usually men, may be related to asbestos exposure, AJSP 2001;25:1304
Usually indolent, may be aggressive and cause death
Micro: well-differentiated papillary neoplasm, with fibrovascular papillary core with variable hyalinization covered by single layer of relatively uniform cuboidal mesothelial cells; cells have no/minimal atypia, moderately abundant eosinophilic cytoplasm, central vesicular nuclei, no/rare mitotic figures; occasional single nucleoli, hyalinized fibrovascular cores, psammoma bodies; may invade stroma
Positive stains: AE1/AE3, Cam5.2, calretinin, HBME-1, variable EMA
Negative stains: CEA, B72.3, CD15
EM: long, slender, microvilli, length > 10x diameter, abundant mitochondria and rough endoplasmic reticulum, desmosomes, papillary cores composed of fibroblast-like cells
DD: mesothelial hyperplasia (only focal papillary structures, more reactive changes)
Mesothelioma versus Adenocarcinoma
Difficult to differentiate histologically if adenocarcinoma does not produce mucin
Adenocarcinomas tend to have columnar morphology with more pleomorphism, nuclear molding and cellular crowding
Stains recommended to differentiate these 2 tumors: calretinin, cytokeratin 5/6 or WT1 and CEA, MOC31 (or B72.3, Ber-EP4 or BG8), AJSP 2003;27:1031; another study recommends Ber-EP4, CK 5/6 and either calretinin or CEA, AJSP 2001;25:43
Stains that are specific for mesothelioma vs. adenocarcinoma: calretinin (100% vs. 8%, cytoplasmic granular staining), cytokeratin 5/6 (100% vs. 2%), WT1 (93% vs. 0%, nuclear staining), thrombomodulin (77% vs. 14%, membranous staining, also stains endothelium), N-cadherin (73% vs. 30%)
Stains that are specific for adenocarcinoma vs. mesothelioma: MOC31 (100% vs. 8%), Ber-EP4 (100% vs. 18%, basolateral surface staining), BG8 (96% vs. 7%, diffuse and intense staining), CEA (88% vs. 0%, granular cytoplasmic staining), B72.3 (84% vs. 0%, membranous and cytoplasmic staining), TTF1 (74% vs. 0%), CD15/LeuM1 (72% vs. 0%, cytoplasmic staining)
Stains frequently positive in both tumors: keratin cocktails, EMA, E-cadherin, HBME, CD44S, mesothelin, vimentin
Not recommended since findings not reproducible or not good discriminants: PAS, glycogen, hyaluronic acid staining, mesothelin
Pleural fluid measurements: high levels of hyaluronic acid levels are suggestive of mesothelioma; high levels of CEA are associated with adenocarcinoma
Intracytoplasmic neutral mucins (mucicarmine positive after hyaluronidase predigestion) is relatively specific but not sensitive for adenocarcinoma
Micro images of mesotheliomas: calretinin, CK5/6, thrombomodulin, WT-1 (figures 1, 3)
EM: helpful in distinguishing mesothelioma from adenocarcinoma in well differentiated tumors; not helpful in distinguishing benign, reactive or malignant mesothelial proliferations
References: Mod Path 2000;13:107, AJSP 2000;24:598, AJSP 2003;27:150
Other pleural mesothelioma
Same staging system for clinical and pathologic staging
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or without diaphragmatic pleural involvement
T1a: No involvement of the visceral pleura
T1b: Tumor also involving the visceral pleura
T2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic and visceral pleura) with at least one of the following: involvement of diaphragmatic muscle, extension of tumor from visceral pleura into the underlying pulmonary parenchyma
T3: Locally advanced but potentially resectable tumor
Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic and visceral pleura) with at least one of the following: involvement of the endothoracic fascia extension into the mediastinal fat, solitary completely resectable focus of tumor extending into the soft tissues of the chest wall, nontransmural involvement of the pericardium
T4: Locally advanced technically unresectable tumor
Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic and visceral pleura) with at least one of the following: diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction; direct transdiaphragmatic extension of tumor to the peritoneum; direct extension of tumor to the contralateral pleura; direct extension of tumor to mediastinal organs; direct extension of tumor into the spine; tumor extending through to the internal surface of the pericardium with or without a pericardial effusion or tumor involving the myocardium
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastases
N1: Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes
N2: Metastases in the subcarinal or the ipsilateral mediastinal lymph nodes including the ipsilateral internal mammary and peridiaphragmatic nodes
N3: Metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes
Distant metastasis (M)
M0: No distant metastasis
M1: Distant metastasis present
Anatomic stage / prognostic groups
Stage I: T1 N0 M0
Stage IA: T1a N0 M0
Stage IB: T1b N0 M0
Stage II: T2 N0 M0
Stage III: T1-2 N1-2 M0 or T3 N0-2 M0
Stage IV: T4 Any N M0 or Any T N3 M0 or Any T Any N M1
Tumor size and location
Histologic type
Extent of invasion
Surgical resection margins
Involvement of pleura, pulmonary vessels, bronchus, mediastinal structures, diaphragm, chest wall, other
Lymph nodes: total examined, number involved by tumor, extracapsular extension
Presence of pleural plaques, ferruginous bodies, pulmonary interstitial fibrosis, other significant findings
Tumor (1 section per cm of tumor)
Tumor and pleura
Tumor and adjacent lung
Tumor and extrapleural tissue
Other structures (including lung)
Margins (bronchus, pulmonary vessels, parietal pleura, other)
Lymph nodes
Other tumors
Rare, < 50 cases reported
90% men, mean age 57 years, range 22-79 years
Almost all patients with pleural vascular tumors with epithelioid features die of disease shortly after diagnosis, even with low grade features, Hum Path 2000;31:29
Micro: often epithelioid; high grade to low grade features of epithelioid hemangioendothelioma
Positive stains: CD31, CD34, Factor IV, vimentin, spotty keratin
DD: epithelioid hemangioendothelioma
Also called desmoid tumor
Associated with local trauma
May recur locally, particularly if incompletely resected
Gross: mean 12 cm, bosselated, firm, white cut surface
Micro: resembles fibromatosis at other sites, infiltrates adjacent fat and skeletal muscle
Positive stains: vimentin, desmin, smooth muscle actin, muscle specific actin
Negative stains: S100
DD: solitary fibrous tumor, benign neurogenic tumor
References: Mod Path 1999;12:9
Very rare, < 20 cases reported
Ages 19-80 years, mean 49 years, usually men
Usually myxoid subtype
Gross: 16-20 cm; yellow-gray, rubbery, nodular, lobulated, gelatinous or mucoid
Micro:
Myxoid/round cell: elongated, interconnected spindle cells with hyperchromatic nuclei and fibrillary, pale staining myxoid stroma; more cellular areas had atypical cells with hyperchromatic nuclei; occasional lipoblasts found (vacuolated cytoplasm, scalloping of nuclei); round cells have hyperchromatic, somewhat indented nuclei, extensive capillaries, multiple mitotic figures, occasional cytoplasmic vacuoles
Well differentiated/sclerosing liposarcoma: mature adipose tissue with fibrous tissue dissecting adipose, occasional lipoblasts
Micro images: round cell/myxoid liposarcoma #1, #2, #3, well differentiated liposarcoma #1, #2
Positive stains: vimentin
Negative stains: keratin, EMA, desmin, actin, HMB45
DD: chest wall or mediastinal sarcoma, metastases
References: Archives 2000;124:699
Metastases to pleura are more common than primary tumors of pleura
Usually from breast (direct spread), lung, stomach, ovary (widespread implants)
For lung, breast and ovarian metastases, 92% of pleural effusions are ipsilateral to primary lesion
Note: 21% of prostate carcinomas have pleural metastases at autopsy, Hum Path 2000;31:578
Cytology helpful since associated pleural effusion contains tumor cells
Note: desmoplastic stroma of metastases may be calretinin+ (don’t confuse with mesothelioma), Hum Path 2003;34:994, metastatic adenocarcinoma
Micro images: metastatic breast carcinoma
Virtual slides: small cell carcinoma
Nodular histiocytic hyperplasia
Case reports of 23 year old and 78 year old women, AJSP 1998;22:285
Micro: proliferation of signet ring-like cells; may have atypia or mitotic activity
Positive stains: CD68
Negative stains: keratin
DD: mesothelial hyperplasia, malignancy
Rare, children less than age 10 years
Associated with cystic lung lesions
May arise in lung, mediastinum or pleura
Case report of tumor diagnosed by fine needle aspiration in girl at 21 months and 5 years, Archives 2000;124:416
Dismal prognosis
Gross: solid or multiloculated cysts in continuity with pleural surface
Micro: biphasic neoplastic population of sheets of primitive, small round cells with scanty cytoplasm, round/oval nuclei with finely granular chromatin, 1-2 nucleoli, occasional binucleation; also larger spindle cells with similar nuclei; may have features of chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, undifferentiated sarcoma; no malignant epithelial component although mesothelium or epithelium may become entrapped; cysts lined by hypertrophied type II pneumocytes
Micro images: cystlike blebs, fine needle aspirate, biphasic tumor with malignant cartilage
Cytology: moderately cellular, small ovoid blastemal elements and scattered spindled tumor cells
Molecular: associated with trisomy 8
DD: PNET (rosettes with fibrillar background material), lymphoblastic lymphoma (highly cellular aspirates, numerous dispersed lymphoblasts with irregular nuclear membranes and fine powdery chromatin, lymphoglandular bodies), metastatic neuroblastoma (neuroblasts, ganglion cells, rosettes, filamentous background material), metastatic embryonal rhabdomyosarcoma, mesenchymal chondrosarcoma (chondroid matrix), desmoplastic small round cell tumor (larger cells, rounded not spindled)
Post-transplant lymphoproliferative disorder
Rare to involve pleura
Case report of monomorphic disease in 57 year old man 2 years post liver transplant, Archives 2001;125:419
Cytology often not helpful for diagnosis
Micro: large immunoblasts with plasmacytoid differentiation
Micro images: H&E, stains
Positive stains: CD20, CD79a, light chain restriction (if lymphoma), EBV
Negative stains: CD3, CD5, HHV8
Sinus histiocytosis with massive lymphadenopathy
Also called Rosai-Dorfman disease; primarily a lymph node disease
Very rare; case report in 81 year old man with pleural effusion and pleural thickening but no lung involvement, Hum Path 2003;34:1210
Micro: infiltrating plump, pale eosinophilic histiocytes with emperipolesis (ingesting other cells); may be accompanied by fibrosis
Positive stains: S100, CD68
Negative stains: CD1a, CEA, CK7, CK20, TTF-1, HMB45, MelanA
Extremely rare, < 10 cases reported
Case report in 32 year old white man of tumor with malignant behavior, Archives 2000;124:1688
Low but definite malignant potential
Gross: well circumscribed, encapsulated, pink and shiny cut surface with fibrous streaks and yellow calcifications
Micro: proliferation of bland spindle cells with elongated nuclei, eosinophilic cytoplasm; rare mitotic figures, focal areas of increased cellularity and atypia; scattered calcifications
Positive stains: alpha smooth muscle actin, HHF-35, desmin, vimentin, CD34 (weak)
Negative stains: keratin, S100, bcl2, CD99
EM: discohesive spindle cells with elongated nuclei; parallel arrays of intracytoplasmic actin microfilaments; no microvilli, tonofilaments or desmosomes
DD: sarcomatoid mesothelioma (keratin+), thymoma, spindle cell carcinoma, solitary fibrous tumor
Also called localized fibrous tumor
Formerly called benign or solitary fibrous mesothelioma
Confined to surface of lung, usually does not produce a pleural effusion
Associated with pulmonary osteoarthropathy, digital clubbing and hypoglycemia, which regress after tumor resection
Most likely fibroblastic and not mesothelial in origin, arising from submesothelial mesenchyme
Not associated with asbestos
May recur locally
May cause death due to extensive intrathoracic growth or if malignant (see below)
Treatment: surgical excision
Gross: arises from pleural surface by a pedicle; solitary, well circumscribed, may be encapsulated; composed of dense, gray-white fibrous tissue with firm, whorled cut surface (like uterine leiomyoma), large tumors may be cystic and hemorrhagic
Gross images: massive tumor, smooth rounded mass
Micro: fibroblast-like cells with variable cellularity in collagenous, keloid-like stroma, reticulin fibers, hemangiopericytoma-like vessels; no/rare mitotic activity, no atypia; may entrap mesothelium or epithelium at periphery; may have focal or marked myxoid change with bland spindle cells in myxoid, vascularized stroma, Mod Path 1999;12:463
Positive stains: CD34 (strong), CD99, vimentin
Negative stains: cytokeratin, EMA, S100, smooth muscle actin, desmin
DD: sarcomatoid/desmoplastic mesothelioma (diffuse on Xray, infiltrative, often atypia or mitotic figures); fibrosarcoma, MPNST, spindle cell carcinomas
Malignant solitary fibrous tumors
Very rare
Case report of 66 year old man with pleural tumor exhibiting liposarcomatous differentiation, Archives 2001;125:406
Micro: fascicles or patternless pattern of spindled or plump cells in dense collagenous stroma; increased cellularity, marked nuclear atypia, prominent necrosis, high mitotic activity
Micro images: storiform pattern of spindle cells with mitotic figures, mitotic activity, haphazard growth pattern, CD34, cytology of pleural effusion, cell block of pleural effusion
Positive stains: CD34, vimentin
Negative stains: cytokeratin, desmin, smooth muscle actin, S100
Very rare, <20 cases reported
Case report in 15 year old boy, Archives 2003;127:85
Usually represents metastatic disease from extremity
Mean age 47 years
Chest pain, pleural masses, pleural effusions
Gross: soft, friable, gray cut surface with solid and cystic areas, focal hemorrhage, myxoid change
Micro: biphasic or monophasic; dense, spindle cells in fascicles with mild pleomorphic oval nuclei, focally less cellular areas; may have hemangiopericytoma-like vessels, myxoid areas; mild atypia, frequent mitotic activity; monophasic cases lack epithelial differentiation
Micro images: H&E, stains, FISH
Cytology: spindle cells with uniform oval nuclei, fine chromatin, inconspicuous nucleoli, scant cytoplasm with cytoplasmic processes; branching blood vessels
Positive stains: CK7, vimentin, bcl2, CD99 (focal), variable EMA
Negative stains: CD34, desmin, smooth muscle actin
Molecular: SYT-SSX1 or SYT-SSX2 fusion transcript due to t(X;18)(p11.2;q11.2)
DD: solitary fibrous tumor, sarcomatous mesothelioma
Case report of ectopic thymoma of pleura resembling mesothelioma, Hum Path 1998;29:409
Gross: tumor may encase lung
Micro: lymphocytes and epithelial cells; involuted thymus present
End of Pleura chapter / outline