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We report a case of cystic mesothelioma of the peritoneum in a young male with local recurrences and whose diagnosis was confirmed by standard histological studies and immunohistochemistry. This rare tumor appears generally in young females through abdominal pain and mass. Local recurrences without distant metastases are a feature of this pathology. The adequate treatment requires complete resection.
Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining of the pelvis and abdomen. Although it is histologically indistinguishable from serous ovarian carcinoma, PSCP exhibits minimal or absent ovarian involvement and may even develop in a woman years after prophylactic oophorectomy. We have shown previously that patients with germ-line BRCA1 mutations who develop PSCP are more likely to have disease originating from multiple peritoneal sites compared with patients with wild-type BRCA1. In this study, we tested the hypothesis that BRCA1-related PSCP has a unique molecular pathogenesis. DNA was extracted from normal tissue and multiple tumor sites in patients with PSCP. BRCA1 and p53 gene mutations were screened for using single-strand conformation polymorphism. Loss of heterozygosity was determined at the BRCA1 and p53 loci. Immunohistochemical analyses of p53, epidermal growth factor receptor, erbB-2, erbB-3, erbB-4, and Bcl-2 expression were performed. We detected germ-line BRCA1 mutations in 11 (26%) of 43 PSCP patients. BRCA1 mutation carriers had a higher overall incidence of p53 mutations (89% versus 47%; P = 0.052), were more likely to exhibit multifocal or null p53 mutations (63% versus 7%; P = 0.014), and were less likely to exhibit erbB-2 overexpression (P = 0.013) than wild-type BRCA1 case subjects. We propose that the unique molecular pathogenesis of BRCA1-related PSCP may affect the ability of current methods to reliably prevent or detect this disease prior to metastasis.
Scirrhous gastric cancer is often accompanied by metastasis to the peritoneum and/or lymph nodes, resulting in the highest mortality rate among gastric cancers. Mechanisms involved in gastric cancer metastasis are not fully clarified because metastasis involves multiple steps and requires the accumulation of altered expression of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer metastasis. In this study, we performed global analysis on differential gene expression of a scirrhous gastric cancer cell line (OCUM-2M) and its derivative sublines with high potential for metastasis to the peritoneal cavity (OCUM-2MD3) and lymph nodes (OCUM-2MLN) in a nude mice model. By applying a high-density oligonucleotide array method, expression of approximately 6800 genes was analyzed, and selected genes were confirmed by the Northern blot method. In our observations in OCUM-2MD3 cells, 12 genes were up-regulated, and 20 genes were down-regulated. In OCUM-2MLN cells, five genes were up-regulated, and five genes were down-regulated. The analysis revealed two functional gene clusters with altered expression: (a) down-regulation of a cluster of squamous cell differentiation marker genes such as small proline-rich proteins [SPRRs (SPRR1A, SPRR1B, and SPRR2A], annexin A1, epithelial membrane protein 1, cellular retinoic acid-binding protein 2, and mesothelin in OCUM-2MD3 cells; and (b) up-regulation of a cluster of antigen-presenting genes such as MHC class II (DP, DR, and DM) and invariant chain (II) in OCUM-2MLN cells through up-regulation of CIITA (MHC class II transactivator). We then analyzed six gastric cancer cell lines by Northern blot and observed preferential up-regulation of trefoil factor 1, alpha-1-antitrypsin, and galectin 4 and down-regulation of cytidine deaminase in cells prone to peritoneal dissemination. Genes highly correlated with invasion or peritoneal dissemination of gastric cancer, such as E-cadherin or integrin beta4, were down-regulated in both of the derivative cell lines analyzed in this study. This is the first demonstration of global gene expression analysis of gastric cancer cells with different metastatic potentials, and these results provide a new insight in the study of human gastric cancer metastasis.
Malignant mesothelioma of the peritoneum is a rare tumor that must be distinguished from the more common primary peritoneal serous epithelial neoplasms. We report a case of a 66-year-old female presenting with weight loss, anemia, and a large pelvic mass on ultrasound. At laparotomy a large (9 x 6.5 x 3.5 cm) mass in the anatomical position of the uterus was found in the minor pelvis. The uterus, tubes and ovaries could not be identified. Palpable paraaortic lymph nodes and liver nodules were found. Immunohistochemically the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin-CEA, but S-100 protein and Leu-M1 were negative. Remnants of the uterine corpus, fallopian tubes and ovaries could not be identified. The overall features were best regarded as malignant peritoneal mesothelioma. There have been reports of mesotheliomas involving the uterus. However, this is the first reported case of mesothelioma causing total replacement of the uterus.
Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.
When operating as an emergency for a perforation of the colon should one carry out a by-pass operation, colostomy or restore intestinal continuity? 36 colonic perforations are reported here, as a complication of cancer in 50 p. 100 of cases, or sigmoiditis in 38 p. 100 of cases. The perforation was situated on the sigmoid in 77 p. 100 of cases. 13 by-pass operations were carried out with a 23 p. 100 mortality, 12 colectomies without anastomosis with a 50 p. 100 mortality, and 2 colectomies with restoration of continuity, 9 p. 100 mortality. The overall mortality was 27.7 p. 100 much less than reported by other authors but, nevertheless partly due to the severity of peritonitis due to the presence of feces and, partly due to the operation adopted. The present attitude of the authors depends on the merits of each case. A large incision is made and the peritoneum thoroughly cleaned. If the surgeon is experienced, colonic resection is advisable for perforated cnacer and certain cases of sigmoiditis. Restoration of continuity depends, above all, on the anatomical condition of the colon above the lesion. Hartmann's resections or by-pass operations thus still have indications.
Treatment for dissemination of hepatocellular carcinoma to the peritoneum has not yet been established. A case of a 62-year-old man who underwent curative resection for hepatocellular carcinoma 1 month after ultrasonically guided needle biopsy is presented. At 23 months after surgery, computed tomography revealed a mass in the abdominal cavity. At laparotomy 3 months later, a peritoneal tumor deposit directly invading the colon was resected in continuity with a portion of large intestine. The tumor was confirmed histopathologically to represent dissemination of hepatocellular carcinoma. No other lesions were detected 20 months after the second operation. Surgical treatment can locally control peritoneally disseminated hepatocellular carcinoma provided that lesions have limited extent.
A report is presented on a rapidly evolving, fatal case of localized malignant mesothelioma of the peritoneum revealed by an abdominal wall mass. Although the tumor was at an advanced stage, a large excision of the primary mass and its metastases was attempted. On the basis of this observation the authors point out the main features of these rare tumors, the diagnostic difficulties they involve, and their possible relationship to asbestos dust exposure.
In the present report we describe a rare papillary serous tumor of the peritoneum occurring in a woman without evidence of ovarian neoplasia. Histochemical, immunohistochemical and ultrastructural findings are reported, with particular emphasis on electron microscopic results and on their importance in the differential diagnosis with malignant mesotheliomas.
The authors described three cases of intraabdominal desmoplastic small round cell tumour of the peritoneum (IDSRT). In one case the patient was a woman, and in the other two men. The age ranged from 20-29 years. Common of all the cases was a rapid onset of clinical symptoms during the period of twelve to eighteen months. In one case, a 22-year-old woman presented with a symptomless course of disease documented by medical examination one month ago. Intensive chemotherapy was applied but two patients died of generalisation. The 22-year-old woman is alive but with clinical evidence of generalisation in the abdominal cavity. The "classical" type of IDSRT was found in all the cases. Sharply demarcated groups of tumour cells of different size were surrounded by dense fibrous stroma. In some regions desmoplastic areas prevailed. In one case the tumour consisted of round and oval cells resembling a lymphoma. In the other two cases, the slightly elongated cells were present. Immunohistologically, the small round cells were positive for cytokeratins with antibody AE1-AE3. Membrane and dot-like paranuclear positivity were found. In 2 cases the reaction to desmin was seen in a dot-like paranuclear distribution, whereas the reaction to smooth muscle actin (MSA) was negative. In all the cases positivity to vimentin and neuron specific enolase (NSE) were apparent. Negative reactions were found for WT-1 antibody in all three cases. In one of the cases the RT PCR reaction for chimeric gene EWS/WT1 was performed, and found to be negative. Many different tumour types, such as lymphoma, Ewing sarcoma/PNET, neuroblastoma, alveolar rhabdomyosarcoma, malignant mesothelioma must be excluded. Cytogenetic examination should be performed on tumours with a "non-typical" histological pattern and uncommon immunohistological examinations.
We have examined the immunosuppressive effects of ascitic fluids from patients with advanced cancer metastatic to the peritoneum and compared them with noncancerous abdominal or pleural effusions, serum from cancer patients, or the proteins human serum albumin and bovine gamma-globulin. The ascitic fluids from cancer patients produce a nontoxic, dose-dependent suppression of DNA and protein synthesis of phytohemagglutinin-stimulated human peripheral blood lymphocytes. This suppression reached 100% with an ascitic protein concentration of 4 to 6 mg/ml, whereas control effusions, serum from cancer patients, or added extraneous proteins were not suppressive. Ascitic proteins also suppress the mixed lymphocyte reaction and the response of human peripheral blood lymphocytes to the antigen keyhold limpet hemocyanin, in vivo, the primary plaque-forming response to sheep red blood cells in mice could be suppressed, and this suppression was not due to antigenic competition.
Well differentiated papillary mesothelioma (WDPM) is a very uncommon neoplasm of peritoneum. Most frequently it appears like little numerous nodules on peritoneal surface, omentum or mesentery. WDPM is characterized by indolent course and is diagnosed in most cases incidentally during operations for other reasons. Sometimes differentiation between WDPM and other mesothelial lesions may be difficult. In the described case a 22 year old female, cystic peritoneal lesions were first recognized histological as WDPM. In verification after two months, they were proved to be cystic mesotheliosis. WDPM may cause adhesions followed by torsion or strangulation. In the second reported case a 24 year old male, WDPM provokes torsion of the omentum. Twelve months after operation and diagnosis this patient is symptom free.
The aim of our study was to review and show the long-term results of the cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinomas of the peritoneum. We wanted to find clinical factors and in this way to select patients who can benefit from this kind of treatment. The clinical data of 32 patients searched retrospectively are presented in our research work. In 29 patients was possible radical cytoreductive surgery. Neoadjuvant and early postoperative chemotherapy were applied in most of the patients. The median follow up after cytoreductive surgery was 50 months. The overall median survival after cytoreduction was 38.5 months. We consider the cytoreductive surgery to be effective only when combined with neoadjuvant or with early postoperative chemotherapy. The surgical approach without chemotherapy leads to bad results.
Malignant mesothelioma (MM) is a rare neoplasm that is commonly fatal within 12-17 months after diagnosis. There are no widely accepted curative approaches. It recurs even after the most aggressive surgical resection. MM is resistant to chemotherapy and radiation. Most of the chemotherapeutics have been evaluated in MM, however, no drugs have a response rate greater than 20%. The combination of drugs has no increased efficacy compared with single agents. Vinorelbine has useful clinical activity against MM with a response rate of 24%. Vascular endothelial growth factor (VEGF) is expressed in MM and pleural effusion of MM. There is a significant inverse correlation between serum VEGF levels and MM patient survival. Cyclooxygenase-2 (COX-2) is expressed in MM. COX-2 plays an important role in tumor growth, invasion, and angiogenesis. VEGF and COX-2 are potential targets in MM. The downregulation of bFGF, VEGF, and maybe some other angiogenesis stimulators, is one of the antiangiogenic mechanisms of thalidomide. Celecoxib is a potent selective COX-2 inhibitor. Here we report a case of disseminated malignant mesothelioma of peritoneum responding remarkably to thalidomide, celecoxib, vinorelbine and CDDP.
A 49-year-old woman developed ascites 31 years after radiation therapy for ovarian cancer and was admitted to hospital 1 year later. Diffuse infiltration of both sheets of the peritoneum was found by CT, which on histological investigation turned out to be an advanced malignant peritoneal carcinoma. When there is a history of radiation exposure, malignant peritoneal mesothelioma should be considered as the cause of ascites.
Although differential WT-1 expression between ovarian and uterine serous carcinoma has been discussed in the literature, there have been no studies of WT-1 expression in serous carcinomas in the peritoneum with or without concurrent serous carcinoma in an endometrial polyp. This study addresses this issue and includes a small series of uterine and ovarian serous carcinomas for comparison. Nine peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp, 10 peritoneal serous carcinomas without serous carcinoma in an endometrial polyp, 9 uterine serous carcinomas, and 12 ovarian serous carcinomas were stained with antibody to WT-1. Ninety-two percent of ovarian serous carcinomas and 80% of peritoneal serous carcinomas without serous carcinoma involving an endometrial polyp expressed WT-1. In contrast, 12% of peritoneal serous carcinomas with serous carcinoma in an endometrial polyp expressed WT-1 with the serous carcinoma in the endometrial polyp staining concordantly. For uterine serous carcinoma without an endometrial polyp, only 11% expressed WT-1. Peritoneal serous carcinomas without coexistent serous carcinoma in an endometrial polyp have a WT-1 expression pattern similar to ovarian serous carcinoma while peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp have a staining pattern similar to uterine serous carcinoma. The difference in WT-1 expression among serous carcinomas suggests a difference in biology based on the site of origin. Additionally, the difference in WT-1 expression between peritoneal serous carcinomas with and without coexistent serous carcinoma in endometrial polyps suggests that peritoneal serous carcinoma may have different pathogenetic pathways.
We report the case of a 28-year-old woman, who presented with acute abdominal and pelvic pain, the appearance of appendicitis. Because of her symptoms urgent operation was performed. Appendicetomy was performed, during the operation multiple cystic lesions were discovered on the right ovary and the peritoneal surface of the mesentery. Laparatomy was performed with removal of the visible cystic lesions, which contained mucous fluid. Final histology revealed benign cystic mesothelioma, which is a rare lesion of the peritoneum, occurring mainly in women in reproductive age. The etiology of cystic mesothelioma is still unclear. The short-term prognosis is favourable, but high recurrence rate. Some authors reported effective intraperitoneal chemotherapy, but no clinical study is available about long term outcome. We hope that surgical eradication was effective to prevent recurrence. One year after the operation the patient is complaint and symptom free.
The role of immunohistochemical markers in distinguishing peritoneal mesothelioma from primary or metastatic serous papillary carcinoma of the peritoneum was evaluated. We immunostained 20 peritoneal mesotheliomas (from 14 men and 6 women), 14 primary peritoneal carcinomas, and 14 metastatic serous ovarian carcinomas with a panel of 16 antibodies. Positive staining for calretinin was identified in 17 (85%) of 20 mesotheliomas, but all carcinomas were negative. Positive staining for Ber-EP4 was identified in 27 (96%) of 28 carcinomas and in 2 (10%) of 20 mesotheliomas. Estrogen receptors were positive in 26 (93%) of 28 carcinomas, and progesterone receptors were positive in 8 (29%) of 28 carcinomas. All mesotheliomas were negative for estrogen and progesterone receptors. The other antibodies evaluated were insufficiently sensitive and/or specific to be diagnostically useful. In conjunction with calretinin and Ber-EP4, estrogen and progesterone receptors are useful discriminatory markers for distinguishing peritoneal mesothelioma from primary or metastatic serous carcinoma.