Peritoneal Mesothelioma—An Update

Abstract

A remarkable amount of new information has been generated on peritoneal mesothelioma (PeM), ranging from nomenclature changes, including the removal of “malignant” when referring to this neoplasm and the use of the term “tumor” rather than “mesothelioma” to designate the neoplasm formerly known as “well-differentiated papillary mesothelioma”, to the acknowledgment that PeMs can be associated with tumor predisposition syndromes or germline mutations. Although the disease is still more frequently seen in caucasian males, PeM is not uncommon in women. In addition, it can represent a diagnostic challenge when it has an uncommon presentation (ie, paraneoplastic syndrome or incidental finding) or when it has confounding histologic features. Ancillary testing, including immunohistochemical stains, in situ hybridization for CDKN2A or NF2, and molecular studies, in selected cases, allows its correct diagnosis. The molecular landscape of PeM is still a work in progress; however, some findings, such as ALK gene rearrangements and EWSR1/FUS-ATF1 fusions, are specifically seen in PeM of young patients. The biological behavior of PeM is variable; however, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have markedly improved the survival of patients affected by this disease.

Risk factors and prognosis of malignant peritoneal mesothelioma with paraneoplastic syndrome

“…In addition, the risk of PS in MPM patients with increased preoperative CA 125 is 2.921 times higher than that in patients with normal preoperative CA 125. The level of CA 125 is parallel to the growth and decline of the tumor [ 5 ]. Therefore, the above studies suggest that MPM with PS often indicates that the primary tumor is at the advanced stage and predicts a large tumor burden and poor prognosis.…”

“…The clinical symptoms of MPM are nonspecific and usually include abdominal pain, bloating, weight loss, and abdominal mass, and a few may manifest as intestinal obstruction and microcirculatory hypercoagulable state [ 4 ]. In addition, some patients may also develop a variety of paraneoplastic syndrome (PS), which has various manifestations and present particular difficulties in clinical practice, resulting in missed diagnosis and misdiagnosis [ 5 ].…”

Malignant Peritoneal Mesothelioma: An In-Depth and Up-to-Date Review of Pathogenesis, Diagnosis, Management and Future Directions

“…In comparison to MPM, the development of pleural mesothelioma has a well-established association with asbestos, with more than 80 percent of cases in the literature having a link to prior exposure [2,24]. The link between MPM and asbestos exposure is not as strong, with only 30-50 percent of cases having an association [1,18,24,25]. The reported latency periods between exposure to asbestos and the development of different types of mesotheliomas also vary, with MPM averaging around 20 years, whilst the period for pleural mesothelioma is significantly longer, averaging around 30-40 years.…”

“…These include several germline mutations, such as the Breast Cancer (BRCA) gene, and genetic syndromes, such as BAP-1 tumour predisposition syndrome, Lynch syndrome, and Li-Fraumeni-like syndrome. Other risk factors include therapeutic irradiation; peritoneal irritation from previous surgeries; chronic peritonitis; autoimmune inflammatory processes affecting the abdomino-pelvic cavity such as Crohn's disease; Hodgkin's disease; endometriosis; exposure to erionite and thorotrast; talcum; some viruses including papovavirus and simian vacuolating virus; Mediterranean familial fever; and the presence of long-standing intra-abdominal catheters [2,19,[24][25][26][27].…”

“…Current guidelines recommend the use of at least two mesothelioma and two carcinoma markers [39]. Positive stains for MPM include calretinin, Wilm's tumour (WT-1) and cytokeratin 5/6, which are the most sensitive, as well as mesothelin, osteopontin, podoplanin (D2-40), fibulin-3, vimetin, human mesothelial cell (HBME-1) and epithelial membrane antigen [21,25,49,50]. Negative stains include carcinoembryonic antigen (CEA), Ber-Ep4, LeuM1, Bg8, Pax-2, B72.3, and thyroid transcription factor-1, which all aid in differentiating MPM from other malignancies, such as adenocarcinoma [15,25,49,50].…”