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Pathology of Mesothelioma-

Microscopic features :

Dr Sampurna Roy MD





Histological Patterns of Diffuse Malignant Mesothelioma (DMM):


 Epithelial Connective Tissue 
Tubulopapillary  Desmoplastic
Adenomatoid (Microglandular pattern)  Muscle-like
Solid (Well and poorly differentiated Pattern)  Fibroblastic
Acinar (Glandular) Pattern  Angiomatoid
Small cell  Cartilaginous and Osseous
Other rare types: Clear cell ; Adenoid cystic ; Signet ring (Lipid rich) and Deciduoid patterns




The histological appearance ranges from pure epithelial to the pure mesenchymal forms.

A combination of above patterns may be present. It is important for the pathologist to be aware of these patterns to make a histologic differentiation between DMM and other neoplasms.

The three broad histological types:

(i) Epithelial ; (ii) Sarcomatous/Fibrous ; and (iii) Biphasic or mixed.

50% - Pleural  and  75% - Peritoneal mesothelioma.

30% are biphasic. 

15% - 20%- Pure sarcomatous subtype.

Recognition of histopathologic patterns of diffuse malignant mesothelioma in differential diagnosis of pleural biopsies.

Epithelial Mesothelioma:

In diffuse mesothelioma epithelial DMM are the most commonly diagnosed histologic type.

1. Tubulopapillary Pattern:

Mixture of small tubules and papillary structures with fibrovascular cores, often with clefts and trabeculae.

In well differentiated tumours the fibrohyaline papillae are lined by neoplastic mesothelial cells - (uniformly cuboidal cells with large vesicular nuclei and prominent nucleoli).

Psammoma bodies may be present.    

Differential diagnosis:  Adenocarcinoma metastatic to the pleura.

2. Acinar Pattern:

Characterized by acinar or glandlike structures.

Differential diagnosis: Metastatic adenocarcinoma.

3. Adenomatoid Pattern (also termed microglandular): 

Small gland-like structures lined by bland flat to cuboidal cells.

Differential diagnosis : Metastatic adenocarcinoma.

4. Small cell pattern :

Sheets of monotonous small hyperchromatic uniform cells with a high nucleocytoplasmic ratio.

Differential diagnosis :  This variant may mimic small cell carcinoma or lymphoma.

Nuclear karyorrhexis and haematoxyphilic vessels are not a feature in mesothelioma .

Lymphoma is distinguished from small cell variant of mesothelioma by immunohistochemical examination.

5. Deciduoid Pattern:  

Identified in the pleura of elderly patients.

Histologically the tumour is characterized by proliferation of large, round to polygonal cells with sharp cell borders, abundant glassy eosinophilic cytoplasm, and round vesicular nuclei with prominent nucleoli.

Differential diagnosis :  Squamous Cell Carcinoma,  trophoblastic neoplasia , gastrointestinal autonomic nerve tumour , anaplastic large cell lymphoma, oxyphilic variant of ovarian clear cell carcinoma .

6. Signet Ring (Lipid-Rich) Pattern:

Tumour cells exhibiting secretory change with cytoplasmic vacuolation.

Differential diagnosis : Metastatic Signet ring cell adenocarcinoma.

7. Clear Cell Pattern:

There are tumor cells with clear cytoplasm. Other patterns may be present in the tumour.

Differential diagnosis : Clear cell tumours that are metastatic to the pleura.

Example:  Renal cell carcinoma, clear cell carcinomas of the lung, clear cell melanoma.

8. Adenoid Cystic:

Cribriform and tubular growth patterns set in a fibrous stroma.

Differential diagnosis : Metastatic adenoid cystic carcinoma and adenocarcinoma.

9. Solid Pattern: Well differentiated and Poorly differentiated:

Well differentiated- Nests and sheets of round cells with abundant cytoplasm and round, vesicular nuclei with prominent nucleoli. Mitoses are usually not prominent.

Differential diagnosis : Benign reactive mesothelial hyperplasia.

Poorly differentiated-  Monotonous sheets of cytologically malignant polygonal cells with abundant glassy eosinophilic cytoplasm with uniform nuclei.

Differential Diagnosis: Lymphoma and large cell carcinoma.

Sarcomatous Mesothelioma: 

Sarcomatoid mesothelioma is composed of a fascicular proliferation of spindle cells with oval nuclei, scanty cytoplasm and occasionally prominent nucleoli.   

Tumour cells display a fibrosarcoma-like appearance with elongated fascicles showing herringbone formations and abundant intercellular collagen deposition.

Tumour may show a prominent storiform appearance indistinguishable from that of malignant fibrous histiocytoma.

Sarcomatoid mesothelioma show i) more atypia  ii) display mitotic activity iii) foci of necrosis.

Lymphohistiocytoid Mesothelioma: 

Histologically, the tumour is characterized by a diffuse discohesive proliferation of atypical histiocytoid cells intermixed with a marked lymphocytic and moderate plasmacytic infiltrate.

In lymphohistiocytoid mesothelioma, the demonstration of cytokeratin expression by the neoplastic cells is the most useful diagnostic finding that allows exclusion of other neoplasms with which this entity may be confused.

Desmoplastic Mesothelioma: 

This is a rare variant of malignant mesothelioma with a storiform collagen pattern, collagen necrosis, bland acellular collagen and focal cytological features of malignancy.

Though rare, it is important to recognise this variant and distinguish it from a pleural plaque, nonspecific reactive pleural fibrosis, pleurisy, rheumatoid disease, or, rarely, spindle cell sarcomas.

Biphasic (Mixed) Mesothelioma: 

Characterized by a combination of epithelial and sarcomatoid patterns.

Differential diagnosis: Carcinosarcomas, biphasic pulmonary blastoma, and biphasic synovial sarcoma.

Miscellaneous Pattern: 

Pleomorphic : Both epithelial and sarcomatous pattern are present ; There are tumour giant cells and anaplastic cells .

Transitional :  Tumor cells with a “transitional” appearance, displaying both epithelial and sarcomatous features in the same cell.



Further reading:

Epithelioid and sarcomatoid malignant pleural mesothelioma in endoscopic gastric biopsies: A diagnostic pitfall.

Macroscopic, histologic, histochemical, immunohistochemical, and ultrastructural features of mesothelioma.

Expression of renal cell carcinoma-associated markers erythropoietin, CD10, and renal cell carcinoma marker in diffuse malignant mesothelioma and metastatic renal cell carcinoma.

Recognition of histopathologic patterns of diffuse malignant mesothelioma in differential diagnosis of pleural biopsies.

Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies.

Malignant peritoneal mesothelioma in women: a study of 75 cases with emphasis on their morphologic spectrum and differential diagnosis.

Malignant mesothelioma with a pronounced myxoid stroma: a clinical and pathological evaluation of 19 cases.

Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review.

Pathology of mesothelioma.

Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals.

Unusual intraparenchymal growth patterns of malignant pleural mesothelioma.

Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study.

Unusual clear cell variant of epithelioid mesothelioma.

Deciduoid mesothelioma: a rare, distinct entity with unusual features.

Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females.

'Mucin-positive' epithelial mesothelioma of the peritoneum: an unusual diagnostic pitfall.

Lymphohistiocytoid mesothelioma. An often misdiagnosed variant of sarcomatoid malignant mesothelioma.

An autopsy case of malignant mesothelioma with osseous and cartilaginous differentiation: bone morphogenetic protein-2 in mesothelial cells and its tumor.

Pseudomesotheliomatous carcinoma involving pleura and peritoneum: A clinicopathologic and immunohistochemical study of three cases.

Pathology of diffuse malignant pleural mesothelioma.

Aspects of histopathologic subtype as a prognostic factor in 85 pleural mesotheliomas.

Pleural mesothelioma: an approach to diagnostic problems.  

Localized malignant mesothelioma. A clinicopathologic and flow cytometric study.

Desmoplastic malignant mesothelioma: a review of 17 cases.



Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)






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