# Malignant Mesothelioma > Malignant mesothelioma for NEET-PG Medicine: asbestos latency, pleural thickening rind, immunohistochemistry with BAP1 loss and p16 deletion. - Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/malignant-mesothelioma - Exam / course: NEET-PG · Subject: Medicine - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Malignant Mesothelioma", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/malignant-mesothelioma ## Direct answer A primary tumour of the pleural (or peritoneal) mesothelium, strongly linked to asbestos exposure with a latency of 20 to 40 years or more — amphibole fibres such as crocidolite carrying the highest risk — malignant mesothelioma presents with progressive breathlessness from effusion, chest wall pain and weight loss, and is confirmed by image-guided biopsy with immunohistochemistry. Epithelioid histology carries the best prognosis and sarcomatoid the worst; treatment combines chemotherapy, immunotherapy and pleurodesis. ## What you must remember - Exposure sources: shipbuilding and ship repairs, asbestos cement and insulation, textile and brake-lining manufacture, and domestic or neighbourhood exposure from workers' clothing; the mineral erionite and prior radiation are recognised secondary associations, and a familial (BAP1 germline) predisposition exists. - Clinical picture: insidious dyspnoea and non-pleuritic chest pain with a blood-stained exudative effusion; later, a fixed contracted hemithorax, chest wall masses, weight loss and ascites in peritoneal disease. - Imaging: computed tomography shows nodular and circumferential pleural thickening — a rind encasing the lung with fissure involvement, volume loss and mediastinal pleural disease; magnetic resonance imaging or positron-emission tomography assists staging of chest wall and nodal involvement. - Diagnosis: pleural fluid cytology alone is often insufficient; image-guided cutting-needle core biopsy of parietal pleura is standard, with thoracoscopy when needed — tract seeding is recognised and prophylactic port-site radiotherapy is largely abandoned. - Immunohistochemistry separates the mimics: mesothelioma expresses calretinin, WT1, cytokeratin 5/6 and D2-40, while lacking the carcinoma markers Ber-EP4 and claudin-4; loss of BAP1 by immunohistochemistry and homozygous deletion of CDKN2A (p16) by fluorescence in situ hybridisation distinguish malignant from benign mesothelial proliferation — invaluable when cytology is ambiguous. - Histological subtypes drive prognosis: epithelioid (commonest, best survival), sarcomatoid (worst) and biphasic (intermediate, needing adequate sampling). - Treatment: first-line platinum-pemetrexed chemotherapy with or without bevacizumab; nivolumab plus ipilimumab immunotherapy is an established first-line option from the CHECKMATE-743 trial; talc pleurodesis or an indwelling catheter controls effusion; surgery (pleurectomy-decortication in selected early epithelioid disease) remains debated, and extrapleural pneumonectomy has fallen from favour; the disease remains incurable in most, with median survival around a year in historical series. ## From a dockyard history of decades ago to a diagnosis A 67-year-old who worked in ship repairs forty years ago presents with breathlessness and chest wall pain; the CT shows nodular, circumferential pleural thickening — a rind encasing the lung, with fissure involvement, volume loss and mediastinal pleural disease — alongside a blood-stained exudative effusion. The exposure history is the foundation: shipbuilding and repairs, asbestos cement and insulation, textile and brake-lining manufacture, or domestic exposure from a worker's clothing. The first immunohistochemistry question is mesothelioma versus metastatic adenocarcinoma, which far outnumbers it: mesothelioma expresses calretinin, WT1, cytokeratin 5/6 and D2-40 while lacking Ber-EP4 and claudin-4. The second is malignant versus benign mesothelial proliferation — what BAP1 loss and homozygous CDKN2A (p16) deletion were developed to resolve. Histology then sets the prognosis: epithelioid commonest and best, sarcomatoid worst, biphasic intermediate. Treatment is palliative in intent — platinum-pemetrexed with or without bevacizumab, or nivolumab plus ipilimumab as an established first-line option — with talc pleurodesis or an indwelling catheter for the effusion; the disease remains incurable in most, with median survival around a year in historical series. ## Where students slip The chief confusion is metastatic adenocarcinoma involving the pleura, and the settled answer is the immunohistochemistry panel, not the radiograph — calretinin and WT1 positive, Ber-EP4 and claudin-4 negative. The second error is over-calling benign reactive mesothelial proliferation, which is precisely what BAP1-p16 testing exists to adjudicate. The asbestos relationship is the third: pleural plaques indicate exposure, but the tumour arises from retained fibres, not from the plaques, and asbestosis is not a prerequisite — a question implying "plaques become mesothelioma" is testing exactly that distinction. The tested one-liners: latency 20 to 40 years, the rind-like thickening, the histology-prognosis hierarchy, nivolumab-ipilimumab as current first-line systemic therapy, and peritoneal disease as the non-pleural presentation. ## Frequently asked questions ### What exposure causes malignant mesothelioma? Asbestos, especially amphibole crocidolite fibres, with a latency of 20 to 40 or more years from first exposure. ### How is the diagnosis established? Image-guided cutting-needle core biopsy with immunohistochemistry, since pleural fluid cytology is often inconclusive. ### Which markers favour mesothelioma over metastatic adenocarcinoma? Positivity for calretinin, WT1, cytokeratin 5/6 and D2-40 with negativity for Ber-EP4 and claudin-4. ### Which tests separate benign from malignant mesothelial proliferation? Loss of BAP1 expression and homozygous CDKN2A (p16) deletion, which indicate malignancy. ### Which histological subtype has the worst prognosis? Sarcomatoid mesothelioma, with epithelioid the best and biphasic intermediate. ### What systemic therapy is used first-line? Platinum-pemetrexed chemotherapy or nivolumab-ipilimumab immunotherapy, alongside pleurodesis for effusion control.