Malignant Mesothelioma (MM) is a rare form of cancer, which affects the mesothelium, the membrane covering and protecting the vital organs. The most common form of MM is pleural mesothelioma, affecting the lining of the lung cavity. Peritoneal and pericardial forms of mesothelioma, affecting the abdominal and the cardiac mesothelium, respectively, are rare. Symptoms of the disease vary, according to the mesothelium affected. Chest pain and shortness of breath (pleural MM), abdominal swelling and pain, weight loss, bowel obstruction, anemia and fever (peritoneal MM), and cough and irregular breathing patterns upon the slightest of exertion (pericardial MM) are some of the most common signs and symptoms of MM.
MM is seen to occur more often in men than in women. The single most important risk factor for developing this disease is exposure to asbestos. About 70-80% of cases of MM have a history of prolonged asbestos exposure. Unfortunately, the disease manifests its symptoms as long as 40-50 years after the exposure, in its advanced stage. Since none of the symptoms are specific to MM, diagnosis, purely on the basis of clinical features is very difficult. Complete physical examination needs to be followed up by CT and MRI or PET scans. Confirmation of MM can only be done after biopsy. Of late, the presence of Soluble Mesothelin Related Protein (SMR) in the blood is being used as a marker for the disease condition. As in most cancers, treatment involves surgical removal of the affected part of the mesothelium, followed by radiation and chemotherapy. Intracavitary chemotherapy, where the drugs are injected straight into the pleural or abdominal cavity, is also being looked into.
In patients with malignant mesothelioma, somatic mutations have been detected in the CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A) gene, NF2 (Neurofibromin 2) gene, WT1 (WT1 Transcription Factor) gene, BCL10 (BCL10 Immune Signaling Adaptor) gene, and BAP1 (BRCA1 Associated Protein 1) gene. In addition to this, certain chromosomal aberrations have also been noted in MM. The most frequently observed of these is loss of material from the long arm of chromosome 14, especially involving 14q11.2-13.2, 14q22.3-24.3, and 14q32.12.
Gaafar and Eldin NH (2005) collected epidemiological data for 635 malignant mesothelioma (MM) patients over 4 years. A clinicopathological study was done for 100 malignant pleural mesothelioma (MPM) patients and showed that asbestos exposure and SV40 positivity were evident in 67% and 60% of cases, respectively. The median survival was 14.3 months and the 1 and 2 year survival rates were 60% and 27%, respectively. Evaluation of p53 and pRb immunohistochemically showed that pRb alteration was related to poor survival. Other biological prognostic factors such as EGFR, HER-2, glutathione S transferase (GST) and MDR were evaluated in 50 cases. Over-expression of EGFR was correlated with lack of clinical benefit and poor survival. GST potentiated the effect of EGFR on survival. Gaafar and Eldin NH (2005) indicated that asbestos in Cairo is a silent killer and measures toward eliminating it entirely or at least strictly controlling human contact with this dangerous carcinogen have to be taken in order to combat the coming epidemic of mesothelioma in Egypt.
Pinto et al. (1993) reported a case of malignant peritoneal mesothelioma without the exposure to asbestos in a 60 year old Omani female. The patient presented with a one-month history of abdominal discomfort, weakness, low grade fever, loss of appetite and weight loss (four kg), without any history of vomiting or diarrhea. Clinically, she was underweight, had palpable, firm, non-tender supraclavicular and inguinal lymph nodes, and a 10 x10 cm firm, non-tender, abdominal mass extending from the left hypochondrium to the left iliac fossa was detected but there was no ascites. Investigations revealed microcytic hypochromic anemia (Hb of 8.3 g/dl), ESR of 85 mm/hr, and radiological investigations (chest x-ray, barium examination of the upper gastrointestinal tract, intestine and colon) were normal. Cervical lymph node biopsy showed non-specific lymphadenitis. Abdominal ultrasound revealed a sheet-like solid tumor with areas of low and bright echogenity (representing entrapped mesenteric and omental fat) with the pancreas and pelvic organs unable to be differentiated from the mass and minimal ascites. The kidney and spleen were normal and the liver had no nodular lesions or metastasis. The CT scan of the abdomen confirmed this soft tissue mass which had a mantle-like appearance extending from the intestine (compressed and stretched at various places) up to the peritoneal wall with thickened and rigid mesentery and peritoneum with an increase in the distance between the abdominal wall and bowel with minimal ascites. No nodular lesions or scalloping of the liver or other abdominal organs was present. As the above findings suggested primary peritoneal tumor, three percutaneous trucut biopsies of the tumor were taken under ultrasound guidance, which histologically was formed of polygonal cells arranged in solid cords, tuboalveolar (predominant picture) and papillary patterns with most nuclei displaced to the luminal part of the pseudoglandular spaces giving a hobnail appearance. The cells had a sharp nuclear membrane with vesicular chromatin, prominent nucleoli and deep eosinophilic cytoplasm with low mitotic rate. Upon special staining, a negative reaction for periodic acid Schiff-diastase (PAS-D) and positive for Alcian blue (this was negative after treatment with hyaluronidase) was noticed. Immunohistochemical reactions with cytokeratin showed a strong cytoplasmic positivity with perinuclear accentuation and focal positivity was detected with epithelial membrane antigen, while it was negative with carcinoembryonic antigen (CEA), S100 and vimentin. Electron microscopy revealed cells with many slender, long and bushy microvilli intercellularly and in the intracellular lumina with well formed desmosome-like intracellular junctions. The above findings confirmed the diagnosis of malignant mesothelioma.
[Pinto MR, Mohammed SH, Rajan KG. Malignant peritoneal mesothelioma, a case report. Oman Med J. 1993; 10(1):24-8.]