Malignant Mesothelioma



Malignant Mesothelioma


Cyril Fisher, MD, DSc, FRCPath





Key Facts


Terminology



  • Malignant tumor of mesothelial cells arising in pleura, peritoneum, or pericardium


Etiology/Pathogenesis



  • Asbestos exposure



    • Amphibole: Crocidolite, amosite


    • Thin long fibers most oncogenic


Clinical Issues



  • 5-10x more common in males


  • Invades underlying organs and adjacent structures


  • Metastasizes


Microscopic Pathology



  • Sheet-like, tubular, papillary, microglandular, or mixed patterns


  • Fibrosarcoma-like fascicles


Top Differential Diagnoses



  • Reactive mesothelial proliferation



    • No atypia, necrosis, invasion


    • Desmin(+), EMA(-)


  • Adenocarcinoma of lung



    • BER-EP4, MOC-31, CEA, CD15, TTF-1 (some) typically positive


    • Calretinin, thrombomodulin, CK5/6, WT1 typically negative


  • Synovial sarcoma


  • Solitary fibrous tumor



    • No pattern


    • CD34(+)


    • Cytokeratin, EMA typically negative


  • Angiosarcoma



    • CD34, CD31, FLI-1 positive






Low magnification of a section of the lung shows pleural thickening image by malignant mesothelioma. The tumor also extends along fissures and septa.






Hematoxylin & eosin shows microglandular, tubular, and papillary patterns of malignant mesothelioma with papillae growing within cystic spaces.


TERMINOLOGY


Abbreviations



  • Malignant mesothelioma (MM)


Synonyms



  • Diffuse mesothelioma


Definitions



  • Malignant tumor of mesothelial cells arising in pleura, peritoneum, or pericardium


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • Asbestos



    • Occupational exposure



      • Mining, construction, vehicle maintenance, shipbuilding


      • Risk relates to intensity and duration of exposure


    • Amphibole fiber types most carcinogenic



      • Persist in lung with or without tissue reaction


      • Crocidolite and amosite have highest risk


      • Longer, thinner fibers more oncogenic


    • Latent period: 15-40 years


  • Occasionally other fiber types implicated, e.g., erionite


Infectious Agents



  • SV40 DNA oncogenic virus



    • Viral sequences found in some mesotheliomas


    • Contaminated polio vaccine unproven association


Radiation



  • Therapeutic


  • Contrast media, e.g., thorium dioxide


Chronic Inflammation



  • Rarely after prolonged fibrosing inflammation, e.g., empyema


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Geographic variation



      • In USA, ˜ 20 cases per million of population in males, now peaked and declining


      • In UK, Australia, incidence higher and increasing


      • In Europe, incidence beginning to plateau


  • Age



    • Most > 60 years


    • Occasional cases at any age


  • Gender



    • 5-10x more common in males


    • Only 20% of cases in females are asbestos-related


Presentation



  • Dyspnea, chest pain, cough, weight loss


  • Abdominal pain, distension, vague mass


Natural History



  • Multiple small lesions fuse to form diffuse sheet


  • Invades underlying organs and adjacent structures



    • Lung, mediastinum, through diaphragm, chest wall


    • Viscera, abdominal wall


  • Metastasizes



    • To lung, lymph nodes


    • Rarely to liver, bone, brain, kidney, adrenal


Treatment



  • Options, risks, complications



    • Multimodal therapy more effective than single


  • Surgical approaches



    • Extrapleural pneumonectomy


    • Decortication


  • Adjuvant therapy



    • Chemotherapy and radiotherapy can prolong survival


    • More often palliative



Prognosis



  • Poor



    • Median survival: 7 months; mortality: 100%


  • Desmoplastic sarcomatoid variant is most aggressive


IMAGE FINDINGS


General Features



  • Pleural effusion


  • Diffuse pleural thickening extending into fissures


  • Peritoneal thickening


  • Mass


MACROSCOPIC FEATURES


General Features



  • Multiple small nodules grow and coalesce


  • Firm diffuse white tumor o Encases lung



    • Locules contain fluid


    • Invades adjacent structures



      • Lung, mediastinum, diaphragm


      • Chest wall, abdominal wall


MICROSCOPIC PATHOLOGY


Histologic Features



  • Epithelioid malignant mesothelioma



    • Polygonal, cuboidal, or flattened discohesive cells


    • Cytoplasm eosinophilic, rarely clear


    • Mild nuclear pleomorphism, variable mitoses


    • Sheet-like, tubular, papillary, microglandular, or mixed patterns


    • Psammoma bodies


    • Variable stromal collagen, inflammation, rare myxoid change


    • Asbestos bodies in adjacent tissues


  • Sarcomatoid malignant mesothelioma



    • Fibrosarcoma-like fascicles


    • Variably pleomorphic spindle cells


    • Giant cells


    • Fibrosis, hyalinization (desmoplastic variant)


    • Necrosis


    • Heterologous osteosarcoma, chondrosarcoma, rhabdomyosarcoma


  • Biphasic malignant mesothelioma



    • Mixed epithelioid and sarcomatoid morphology


  • Other histological variants of malignant mesothelioma



    • Small cell


    • Clear cell


    • Deciduoid


    • Lymphohistiocytoid


    • Pleomorphic


Predominant Pattern/Injury Type



  • Diffuse

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Malignant Mesothelioma

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