Novel EWSR1::TEAD3 Fusion in an Adolescent With a Highly Aggressive Peritoneal Mesothelioma.

Rationale:Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor.Patient's concerns:A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month.Diagnosis:The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected.Interventions:The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times.Outcomes:Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction.Lessons:Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.

Background: Malignant peritoneal mesothelioma (PeM) is a rare form of malignant mesothelioma that accounts for 10-15% of all cases of mesothelioma. Of these rare tumors, the rhabdoid subtype is exceptionally infrequent with only three cases reported in the current literature. PeM most commonly presents with non-specific symptoms such as abdominal distention, anorexia and weight loss that are difficult to diagnose until the disease is advanced. In this case report, we present a case of malignant peritoneal rhabdoid mesothelioma and review the literature. Case presentation: The patient is a 76-year-old woman who originally presented with necrotizing pancreatitis one year prior to diagnosis. The patient continued to complain of abdominal pain, nausea, vomiting, and weight loss. She experienced recurrent deep vein thrombosis (DVT), recurrent chylous, and mucinous ascites. Diagnostic work-up including MRI, repeat CT, EUS, and MRCP were inconclusive. Additionally, cytology from multiple paracenteses were negative for malignancy. Diagnostic laparoscopy revealed diffuse carcinomatosis, abdominal wall and peritoneal implants and a large epigastric mass. Biopsies of lesions taken during the procedure were identified as peritoneal mesothelioma. Conclusions: To our knowledge, we have presented the first case of PeM with rhabdoid features present in the peritoneum and in gastric polyps. The large amount of histopathogical variation of these tumors requires surgical biopsy, as cytology alone is non-diagnostic.

69-year-old male presented with a three-month history of new-onset ascites and lower extremity edema. The patient reported marked weight loss, decreased appetite and night sweats. The patient had no known history of asbestos exposure. Physical examination was remarkable for distended abdomen and tense ascites. There were no organomegaly or physical findings suggestive of chronic liver disease. Laboratory tests were within normal limits. CT scan of chest and abdomen revealed massive ascites. The mesentery showed anterior omental caking suspicious for disseminated occult malignancy. Endoscopic ultrasound (EUS) showed extensive mesenteric inflammation and moderate amount of ascites. No intra-abdominal lymphadenoapthy was present. EUS guided fine needle aspiration of ascitic fluid was perfomed. Cyotology revealed atypical mesothelial cells with malignant morphology. Immunostains for keratin 7, keratin 5/6, and P53 were positive confirming the diagnosis of mesothelioma. Fiberoptic bronchoscopy with transbrochial biopsy and bronchoalveolar lavage showed no evidence of pleural mesothelioma. Primary peritoneal mesothelioma diagnosis was established. To our knowledge this is the first case of primary peritoneal mesothelioma to be diagnosed with EUS Guided Fine Needle Aspiration. Discussion: Malignant peritoneal mesothelioma is a rare, locally aggressive neoplasm arising from the abdominal serosal lining. Exposure to asbestos fibers has been recognized as a risk factor for pleural mesothelioma. However, the implication of asbestos in the causation of peritoneal mesothelioma is less evident. The definite diagnosis of peritoneal mesothelioma can only be established by histological examination. CT-guided percutaneous core-needle biopsy of the omentum is a safe, and highly accurate procedure for the diagnosis. In our patient, EUS guided fine needle aspiration was an easy and safe technique for diagnosis. There are no uniformly accepted approaches for treatment. Cytoreductive surgery followed by intraperitoneal chemotherapy with cisplatin and paclitaxel has been effective in a number of cases. Favorable prognostic factors for long-term survival include epithelioid tumor subtype, comparatively young age, and female gender.

Malignant mesotheliomas develop commonly in the pleural cavity and rarely arise in the peritoneal cavity. It is well established that asbestos exposure is related to malignant pleural mesothelioma, but the asbestos burden in the abdominal cavity in patients with malignant peritoneal mesothelioma has not been well studied. The purpose of the present study was therefore to report on an autopsy case of malignant peritoneal mesothelioma with quantitative analysis of the asbestos burden in tissues from the pleura and organs in the abdominal cavity. The patient was a 67-year-old man with a history of asbestos exposure. The peritoneum was thickened with diffuse tumor proliferation. This patient was diagnosed as having malignant peritoneal epithelioid mesothelioma. The number of asbestos fibers was >10,000/g dry tissue in all samples examined except in the small intestine. The number of asbestos fibers in the stomach was 53,000/g, which was higher than that in a control asbestosis subject. The existence of numerous asbestos fibers found in the abdominal cavity suggests that asbestos stimuli are related to the tumorigenesis of malignant peritoneal mesothelioma.

Introduction/BackgroundPrimary peritoneal mesothelioma is a rare and aggressive neoplastic disease with a poor prognosis. The rarity of this entity and the challenging differential diagnosis with other ovarian and peritoneal neoplasms...

Introduction: Malignant Mesothelioma (MM) is a great masquerader, presenting as infection, metastasis, other cancers or as a paraneoplastic syndrome. Malignant peritoneal mesothelioma (PeM) accounts for about 10-15% of all cases of mesothelioma. MM presenting with malignant gastrointestinal (GI) polyps is also rare, with only 16 reported cases of mesothelioma presenting as metastatic disease in the GI tract. Here, we present the clinicopathologic findings of a case of a malignant peritoneal rhabdoid mesothelioma presenting as a necrotizing pancreatic mass, recurrent deep vein thrombosis (DVT), chylous ascites, and late onset weight loss. Case Description/Methods: A 76-year-old female initially presenting with idiopathic necrotizing pancreatitis. She continued to report persistent vague lower and mid abdominal pain. Six months after her initial admission the patient developed a DVT and pulmonary embolism (PE) requiring thrombectomy and anticoagulation with a recurrent DVT requiring IVC filter placement. She continued to have recurrent ascites and an enlarging peripancreatic fluid collection. Multiple paracenteses were performed with studies negative for infection and cytology negative for malignancy; however, most samples could not be analyzed due to fluid viscosity. An endoscopic retrograde cholangiopancreatography was performed with pancreatic and biliary stents placed. Almost one year after the patient's initial admission, cross-sectional abdominal imaging showed omental caking with enlargement of the proximal pancreas. An endoscopic ultrasound with fine needle aspiration was performed was non-diagnostic. Lymphangiogram performed chylous nature of ascites. MRI showed a large fluid volume surrounding the pancreas and extended into the pararenal spaces. There was a mass effect leading to displacement of the surrounding structures. Diagnostic laparoscopy showed abdominal wall and peritoneal implants in addition to a large, firm, and highly vascularized epigastric mass. Pathology showed peritoneal mesothelioma. Discussion: We have presented a case of PeM with rhabdoid features present in the peritoneum and in gastric polyps. PeMs are rare tumors with a non-specific clinical presentation. These lesions are also difficult to diagnose and definitive diagnosis of MPM requires surgically obtained tissue. To our knowledge, this is the first case with these features.

Malignant peritoneal mesothelioma with invasion of the liver is an invariably fatal disease. We aimed to clarify the characteristics of malignant peritoneal mesothelioma cases with liver involvement. The clinical presentation, computed tomography images, and immunohistochemical and histopathological features of 5 patients with malignant peritoneal mesothelioma and liver involvement were evaluated. The diagnosis was established by imaging and immune profiles of the tumours. A review of 8 cases with primary or invading malignant mesothelioma in liver is presented. All 5 mesothelioma cases were asbestos-related. CT images of malignant peritoneal mesothelioma with the liver involvement typically showed that the lesion grew inside the liver along the capsule and was possibly accompanied by capsule breakthrough and extrahepatic infiltration. The tumours exhibited a common epithelioid appearance in all 5 patients and most cases revealed positive Cal, CK, and MC with negative CEA and HeP. Different from our findings, the review of literature revealed that most malignant mesothelioma of liver was due to primary intrahepatic malignant mesothelioma. Finally, we concluded that the diagnosis of malignant peritoneal mesothelioma cases with liver invasion is reliably achieved by the history of asbestos exposure, the characteristic CT imaging, and immune profiles of the tumours.

Objective To evaluate the values of combined detection of soluble mesothelin related proteins(SMRP) and carbohydrate antigen 125(CA125) in the diagnosis of malignant peritoneal mesothelioma. Methods 20 patients with malignant peritoneal mesothelioma were selected as the malignant group, 50 patients with benign ovarian tumor were selected as the benign group, 60 healthy women were selected as the control group.Enzyme-linked immunosorbent assay(ELISA) was adopted to detect serum SMRP levels and electrochemiluminescence immunifaction(ECLI) was adopted to detect serum CA125 levels.The SMRP, CA125 levels were compared among all groups, the sensitivity, specificity of SMRP and CA125 in the diagnosis of peritoneal malignant mesothelioma were analyzed. Results Serum levels of SMRP, CA125 in malignant group were (14.8±1.6)μg/L, (189.1±15.3)μg/L respectively, which were significantly higher than those in the benign group[(3.9±0.9)μg/L, (28.6±4.2)μg/L](t=27.40, 49.610, all P<0.01) and the control group[(2.8±0.7)μg/L, (16.9±3.8)μg/L](t=29.877, 53.334, all P<0.01).The sensitivities of SMRP, CA125 detection alone for malignant peritoneal mesothelioma diagnosis were 65.0%, 50%, respectively, while their specificities were 83.6%, 79.1%.The sensitivity and specificity of combined detection of SMRP and CA125 for malignant peritoneal mesothelioma were 95.0% and 93.6%. Conclusion SMRP has some value in the diagnosis of peritoneal malignant mesothelioma.SMRP combined with CA125 detection can markedly improve the diagnostic sensitivity and specificity for malignant peritoneal mesothelioma. Key words: Mesothelioma; Peritoneal neoplasms; Diagnosis

Novelty: Malignant peritoneal mesothelioma (MPM) is a rare disease confined to peritoneal cavities in most cases, seldom seen in intraand extra-abdominal invasion. In addition, MPM is easy of misdiagnosis and has a poor prognosis. Here, we report a case of colonic invasion induced by MPM in order to help prevent from misdiagnosis and prolong survival time. A 53-year-old male who presented with constipation, weight loss, and occasional abdominal discomfort for 2 months was admitted to the Department of Surgical Oncology, Harbin Medical University Cancer Hospital, November 2013. He was a heavy smoker of 15 packs/month with a history of asbestos exposure in childhood and diabetes mellitus. On physical examination, he had a fixed mass in the right lower quadrant. Routine blood tests and evaluation for tumor markers CEA, CA724, CA19-9, and CA-125 were all in normal range except for a thrombocytosis of 397×10/L. A 3D-enhanced CT of the abdomen showed an irregular thickening wall of hepatic flexure of colon, and the thickener area can be reached 16.8 mm, closely adjacent to intestine. At the same time, an infiltrating mass of 67.7 mm in size, multiple small peritoneal nodules, and abdominal swelling lymph nodes can also be seen in abdominal CT. There were no remarkable findings on the endoscopic examination, and the colonoscopy suggested an infiltrating lesion located in the hepatic flexure of colon, ruptured in the surface, and easily bled when touched. Laparotomy was performed, peritoneal nodules were intraoperatively found throughout the peritoneum, and the infiltrating mass had penetrated the range of serosal and right side of the peritoneum, widely planting in the peritoneum, omentum, and surface of peritoneal cavities. Necrotic tissue sample was delivered for examination, and quick pathology revealed malignancy. In addition, 2.0 cm×1.5 cm×1.0 cm omental tissue was cut for detection during surgery. Histology revealed a well-differentiated epithelioid malignant mesothelioma. It was positive for HBME-1, CK5/6, CK7, and calretinin, supporting the diagnosis of MPM. After surgery, the patient was referred to the Department of Medical Oncology. Our patient recovered well after the operation, and he had successfully accepted 2 cycles of chemotherapy of pemetrexed combined with carboplatin; unfortunately, he did not tolerate the therapy, and the disease progressed with the appearance of ascites and rectum occupation revealed by abdominal and pelvic CT. However, there are no significant abnormalities found in colonoscopy. We deemed that rectum occupation was caused by the compression of swelling lymph nodes. Oxaliplatin and capecitabine were adjusted to the following treatment, and he felt symptoms released at present. MPM is an uncommon, fatal disease arising from the peritoneum with an increasing incidence of 7–40/million and a negative prognosis of within 12 months [1]. The main risk factor for MPM is asbestos exposure, and the onset of about 60 % of MPM patients was correlated with direct or indirect asbestos contact. In addition, exposure to radiation, talc, mica, erionite, Thorotrast, SV40, and Hodgkin’s disease has also been reported to be related to MPM [2]. The most common presentations of MPM are abdominal pain and distension which resulted from the accumulation of tumors and ascites, while constipation is exceptional. MPM is usually diagnosed at advanced stage due to its nonspecific clinical and S. B. Cao and S. Jin contributed equally to this work. S. B. Cao : S. Jin : J. Y. Cao : J. Shen : J. W. Zhang :Y. Yu (*) Department of Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Hapin Road, 150081 Harbin, China e-mail: yuyan_hrb@126.com

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X

Objective: To reduce the misdiagnosis rate of ascites and improve the diagnosis rate of malignant peritoneal mesothelioma. Methods: From May 2008 to May 2018, in Xiangya Hospital of Central South University,the clinical data of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis were retrospectively analyzed. Results: (1) Among the 6 patients, they were male; the age of onset was 42-70 (52±9.57) years old, and there was no history of asbestos exposure. (2) All cases with abdominal pain or abdominal distension were there and the course of disease was more than 1 month to more than 2 years. (3) In all patients,the nature of ascites was exudate; ADA was higher than normal value and below 45 U/L; LDH value in ascites was higher than 200 U/L (83.3%); mesothelioma was considered in ascites cytology in 1 case. (4) Laparoscopic biopsy was performed in 2 cases and B-ultrasound guided biopsy in 4 cases; Among them, malignant peritoneal mesothelioma diagnosed by pathology. (5) In Immunohistochemical positive markers, MC was the most sensitive (100%), followed by CR (67%), CK-Pan (67%), Ki-67 (67%) and EMA (67%). (6) Two patients received treatment with operation, abdominal hyperthermic perfusion and postoperative systemic chemotherapy. Conclusions: (1) Malignant peritoneal mesothelioma should be considered in middle-aged and aged male patients with unexplained ascites and early laparoscopy or laparotomy for diagnosis. (2) ADA and LDH level in ascites are significant in differentiating tuberculous peritonitis from malignant peritoneal mesothelioma. (3) Immunohistochemical positive marker MC may be a potential specific marker for malignant mesothelioma. (4) The survival time of patients is improved by comprehensive treatment such as operation and chemotherapy.

In the United States, mesothelioma, a rare cancer, is estimated to occur in approximately 2,500 people annually [1]. Sporadic cases have been reported in Korea. Although, malignant pleural mesothelioma is the most common type of mesothelioma, mesothelioma has also observed in the peritoneum and pericardium. Malignant pleural mesothelioma is observed mainly in older men (median age, 72 years) who have been exposed to asbestos, although it occurs decades after exposure (20 to 40 years later) [2]. Most cases of mesothelioma have been linked to asbestos exposure, however, some reports have suggested that radiotherapy may also be a cause of mesothelioma [3,4]. Reports of malignant peritoneal mesotheliomas in women are rare. The significant variation in incidence may reflect erroneous diagnosis of peritoneal serous carcinomas or well-differentiated papillary mesotheliomas as malignant peritoneal mesothelioma. Frequency of exposure of asbestos in patients with malignant peritoneal mesothelioma ranges from 0 to 50% [5]. Malignant peritoneal mesotheliomas are most commonly diagnosed during the fifth to seventh decades of life [6]. We report on a case of malignant peritoneal mesothelioma in a 53-year-old woman with no history of exposure to asbestos or previous radiotherapy, along with a brief review of the literature.

Peritoneal mesothelioma is a rare cause of a peritoneal mass in adults and can occur in malignant or benign forms. Compared to the pleural variant of mesothelioma, the peritoneal form is understudied due to the small number of reported cases. We present a case of an 84-year-old male with a history of asbestos exposure who initially presented for an aggravated hernia, was found to have an incidental mass on imaging, and ultimately was diagnosed with malignant peritoneal mesothelioma (MPM)1 likely related to prior asbestos exposure. This case study will provide a review of literature and discuss the role of imaging for MPM.

Peritoneal mesotheliomas in children are of rare occurrance. We herein report the clinical, radiological, and pathological findings of a rare case of malignant peritoneal mesothelioma occurring in nine-year-old female child. The child presented with abdominal distension and awareness of a painless mass in the abdomen which on radiology appeared as a large heterogeneous pelvic mass with peritoneal deposits at multiple sites. To the best of our knowledge, this is the first case of a peritoneal malignant mesothelioma on which fine needle aspiration (FNA) was performed as first line investigation of the primary tumor. The cytological features, major differential diagnoses, and the pitfalls therein are discussed. Histopathology revealed biphasic pattern of mesothelioma which is again a rare pattern. Immunochemistry was carried out on the cell block made from the FNA as well as the biopsy specimen essentially showed the same features. There was positivity for vimentin, EMA, and cytokeratin 5/6 while WT1, calretinin, and CEA were negative; however, D2-40 showed diffuse membranous positivity in the epithelial areas and cytoplasmic positivity in the spindle areas confirming a mesothelioma. We emphasize the use of immunochemistry on cell block material for a confident diagnosis of mesothelioma in such cases.

e20535 Background: Malignant peritoneal mesothelioma (MPM) is a rare disease with about 600 new cases per million people diagnosed annually in the U.S. High incidence of germline mutations has been reported in MPM patients (pts) without asbestos exposure. However, the incidence rate of developing multiple primary cancers in this population is unknown. The aim of this study is to investigate the frequency of additional malignancies in MPM pts. Methods: Using the Mayo Clinic Cancer Registry, we identified 64 pts who were treated for MPM from January 2002-December 2022 with updated follow-up data until 01/15/2023. Electronic medical records were reviewed. Results: Among the patient cohort, 25 pts were male, and 39 pts were female. 14/64 (22%) pts were found to have at least one additional malignancy, including breast cancer (4/14, 29%), colon cancer (3/14, 21%), lymphoma (3/14, 21%), ovarian cancer (2/14, 14%), melanoma (2/14, 14%), anal squamous cell carcinoma (1/14, 7%), papillary thyroid cancer (1/14, 7%), Chronic lymphocytic leukemia (1/14, 7%), renal cell carcinoma (1/14, 7%), squamous cell carcinoma of tongue (1/14, 7%), hepatocellular carcinoma (1/14, 7%) and pituitary macroadenoma (1/14, 7%). 4/14 (29%) pts had more than one (2-4) non-MPM malignancies. The median age at diagnosis of MPM was 65 years (44-82). The median age at diagnosis of non-MPM malignancies was 66 years (18-81). Most of the patients (11/14) were diagnosed with non-MPM malignancy within 12 months of diagnosis of MPM. Most pts (11/14, 78%) were diagnosed with non-MPM malignancy first, among which 5 pts (45%) were found to have MPM on surveillance scans. Germline mutation information was not available except for 2 pts with known family history (FH) of Lynch syndrome and Li-Fraumeni syndrome. FH was available in 29 pts, out of which 28 pts had FH of cancer identified in first-degree relatives. Among the 14 pts with additional malignancies, 9 pts had FH of cancer in first-degree relatives. Among all pts, 15 (18%) pts had a history of asbestos exposure. Among pts who also had non-MPM malignancies, 3/14 (21%) pts had a history of asbestos exposure. Among the 21 non-MPM cancers, 1/21 (5%), 11/21(52%), 1/21(5%), 3/21(14%), and 5/21(24%) non-MPM malignancies were stage 0, stage I, II, and III, or unknown at the diagnosis respectively. All except 1 pt underwent curative treatment for their non-MPM malignancies, and 12 pts had no evidence of disease at death or the time of last follow-up. Conclusions: The rate of multiple primary malignancies in pts with MPM is high, indicating possible genetic predisposition associated with this disease. Early genetic consultation and evaluation for germline mutations may need to be considered for these pts to improve long-term outcomes.