Reactive Mesothelial Hyperplasia Research Articles

Comparative study of BAP1 and CD147 expression in the diagnosis of malignant mesothelioma

Background: Malignant mesothelioma (MM) is a lethal tumor of serosal surfaces. Its differentiation from reactive mesothelial hyperplasia is mandatory, and may be problematic in many situations. Thus, the application of a targeted panel of specific markers permits proper diagnosis in the majority of cases. Aim: This study aimed to determine the potential use of BRCA associated protein-1 (BAP1) and CD147 antibodies to differentiate between MM and reactive mesothelial hyperplasia. Materials and Methods: The current work was carried out on 120 cases (56 reactive mesothelial hyperplasia and 64 malignant mesothelioma cases), retrieved as 70 cell blocks and 50 tissue samples. Immunohistochemical staining, using calretinin (to confirm the mesothelial lineage), BAP1, and CD147 antibodies, was performed for each case. Results: Lost nuclear BAP1 expression was detected in 45.3% of the mesotheliomas versus 19.6% of reactive mesothelial hyperplasia cases. Positive membranous CD147 expression was found in 84.4% of mesothelioma cases versus 8.9% of reactive mesothelial hyperplasia cases. BAP1 showed 44.6% sensitivity and 80% specificity, while CD147 showed 84.3% sensitivity and 91% specificity in the diagnosis of malignant mesothelioma. Conclusions: The loss of BAP1 expression and positive CD147 expression could be of diagnostic value for malignant mesothelioma and can exclude the diagnosis of reactive mesothelial proliferations in both biopsy and cytology specimens. CD147 exhibits higher sensitivity and specificity than BAP1.

MALIGNANT MESOTHELIOMA AND GERMLINE HETEROZYGOUS BAP1 MUTATION IN A YOUNG WOMAN PRESENTING WITH RECURRENT PLEURAL EFFUSIONS AND WORSENING PNEUMOTHORAX AFTER TALC PLEURODESIS

SESSION TITLE: Fellows Lung Cancer Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Germline BAP1 mutations are associated with a pattern of hereditary malignancies, namely uveal and cutaneous melanoma, malignant mesothelioma (MM), and renal cell carcinoma. We present a rare case of a young woman who was diagnosed with malignant pleural and peritoneal mesothelioma. CASE PRESENTATION: A 23 year-old woman with no known medical conditions or exposure to asbestos was referred to medical oncology after completing a video-assisted thoracoscopic surgery (VATS) followed by talc pleurodesis for recurrent pleural effusions of unknown etiology. Initial pleural fluid studies showed total protein 4.5 g/dL and LDH 150 U/L. Pleural fluid contained clusters of atypical mesothelial cells surrounded by inflammation suggestive of reactive mesothelial hyperplasia. VATS found abnormal reticulated surfaces and a white plaque-like tissue at the apex. Pleural biopsies showed atypical mesothelial proliferation suspicious for MM in a background of reactive changes, but ultimately results were considered non-diagnostic. Due to inconclusive pathology we recommended further evaluation with diagnostic laparoscopy because her CT scans also showed small volume ascites and pelvic fluid. Studding was noted on peritoneum, bowel, pelvic tissues, and omentum, and biopsies showed markedly atypical proliferation of epithelioid cells forming glandular and tubulopapillary structures with disorganized growth and focal invasion into adjacent adipose tissue. Immunostains of tumor cells were consistent with mesothelial differentiation. BAP-1 immunohistochemistry showed loss of expression only in tumor cells. Collectively these features supported a diagnosis of MM of epithelioid type. Peripheral blood testing for BAP1 tumor predisposition syndrome (BAP1-TPDS) was positive for a heterozygous germline BAP1 mutation, c.2050 C>T, p.Gln684* (Pilarski et al. 2013, Haugh et al. 2017). Staging scans prior to chemotherapy showed interval development of a pneumothorax in the right lung months after her talc pleurodesis. She was treated with cisplatin, pemetrexed, and bevacizumab with subsequent improvement of her pneumothorax. DISCUSSION: Our case report showed the clinical features of a patient with MM from BAP1-TPDS. Loss of BAP1 expression can help distinguish MM from reactive mesothelial cells (Cigognetti et al. 2015). Progression of her disease after having a talc pleurodesis manifested radiographically as a worsening pneumothorax, and chemotherapy was able to reverse this process. CONCLUSIONS: Unexplained pleural effusions or pleural or peritoneal biopsies showing atypical mesothelial cells should have immunohistochemistry testing for loss of BAP1 expression to evaluate for MM. MM due to BAP1-TPDS is responsive chemotherapy. Young MM patients without risk factors for MM should have germline testing for BAP1-TPDS. Reference #1: Pilarski, Robert, et al. “Expanding the Clinical Phenotype of hereditaryBAP1cancer Predisposition Syndrome, Reporting Three New Cases.” Genes, Chromosomes and Cancer, vol. 53, no. 2, 15 Nov. 2013, pp. 177–182., doi:10.1002/gcc.22129. Reference #2: Haugh, Alexandra M., et al. “Genotypic and Phenotypic Features of BAP1 Cancer Syndrome.” JAMA Dermatology, vol. 153, no. 10, 9 Aug. 2017, p. 999-1006., doi:10.1001/jamadermatol.2017.2330. Reference #3: Cigognetti, Marta, et al. “BAP1 (BRCA1-Associated Protein 1) Is a Highly Specific Marker for Differentiating Mesothelioma from Reactive Mesothelial Proliferations.” Modern Pathology, vol. 28, no. 8, 29 May 2015, pp. 1043–1057., doi:10.1038/modpathol.2015.65. DISCLOSURES: Speaker/Speaker's Bureau relationship with Daiichi Sankyo/AstraZeneca Please note: $1-$1000 Added 03/18/2020 by Blakely Kute, source=Web Response, value=Honoraria No relevant relationships by Eric Luk, source=Web Response

Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops).

A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.

Mesothelial proliferation of the tunica vaginalis testis

Proliferative changes seen in reactive mesothelial hyperplasia of ahydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both ahigh specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.

Differential Diagnosis of Malignant Pleural Mesothelioma on Cytology: A Gene Expression Panel versus BRCA1-Associated Protein 1 and p16 Tests

Pleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% to 75%). Particularly, it can be hard to discriminate epithelioid MPM, the most common histotype, from reactive mesothelial hyperplasia (MH). Currently, BRCA1-associated protein 1 (BAP1) and CDKN2A (p16), evaluated by immunohistochemistry and fluorescent in situ hybridization, respectively, are the most valuable markers to discriminate MPM and MH. Both markers have a high specificity, but their sensitivity is not always satisfying, even when used together. We have recently developed a 117-gene expression panel, based on Nanostring technology, able to differentiate epithelioid MPM from MH pleural tissues better than BAP1 and p16. Herein, we evaluated the efficacy of the same panel on an independent retrospective cohort of 23 MPM and 11 MH pleural effusions (cell blocks and smears). The overall sensitivity and specificity of the panel were equal to 0.9565 and 1, respectively. Moreover, the panel performance was compared with BAP1 and p16 on 25 cell blocks. Sensitivity levels of gene panel, BAP1 alone, p16 alone, and BAP1 plus p16 were 1, 0.5882, 0.4706, and 0.7647, respectively. Specificity was always 1. Although further validation is needed, this gene panel could really facilitate patients' management, allowing a definitive MPM diagnosis directly on pleural effusions.

1101 Multimodality imaging in the assessment of pericardial malign disease

Abstract Metastases to the heart and pericardium are discovered at autopsy in 10%–12% of all patients with malignancies. The most common primary tumor involving the pericardium is lung cancer, followed by breast, melanoma, and lymphoma. Pericardial effusion may be the result of the tumor spreading to the visceral pericardium which increases production of fluid, or accumulation of the fluid due to the obstruction of venous and lymphatic outflow. A malignant pericardial effusion is associated with decreased survival rate. We present a 72 year-old woman, former smoker with dyslipidemia and psoriatic arthritis as well as previous bladder carcinoma that was healed in 1986. On august 2017 after an acute intestinal obstruction she was diagnosed with stage IV ileum adenocarcinoma treated initially with palliative chemotherapy (Capecitabine and oxaliplatin) that was suspended for poor tolerance and according to patient desire. Few months later the patient complained of rapidly progressive dyspnoea that prevented her normal life activity, arterial pressure and blood oxygen saturation was normal, but she was tachycardic. Echocardiogram was performed (see figure) which showed marked pericardial nodular thickening and severe pericardial effusion with echocardiographic signs of cardiac tamponade. Curiously, pericardial effusion was dense and markedly hyperechogenic. A computed tomography (CT) was performed to rule out pericardial carcinomatosis and find out the pericardial fluid composition and demostrated several pericardial nodular thickenings that suggested metastases. The pericardial fluid was dense (40 hounsfield units) and consistent with blood. After multidispiplinar consultation and in accordance with patients wishes a palliative pericardial window was performed and hematic pericardial fluid was obtained. Pericardial liquid citology demonstrates atipical cells compatible with carcinoma and pericardial biospy showed fibrinous pericarditis and reactive mesothelial hyperplasia. Pericardial carcinomatosis consists of macroscopic or microscopic affection of pericardial layers. Metastasis from colorectal cancer to the pericardium is uncommon, and usually indicates terminal stage with multiple metastases, only a few cases have been reported. Malignant Pericardial effusions in patients with cancer may also be triggered by other mechanism than cancer itself, including chemotherapy, radiation therapy, and, less commonly, an infectious disease. Whereas echocardiography is most frequently used to examine the heart and pericardium, multimodaliy imaging with magnetic resonance (MR) or/and CT offer advantages when dealing with metastatic disease. Abstract 1101 Figure. Echocardiogram and CT images

Cytopathological diagnosis of filariasis by fine-needle aspiration cytology in different body locations: A retrospective study of 5 years in central India

Background: Filariasis is one of the common health problems in tropical countries. The parasite causing the disease primarily resides in lymphatic channels or lymph nodes. It can remain viable in these places for decades. The clinical presentation may vary from superficial palpable swelling to pain and erythema. The cytopathological diagnosis of microfilaria on fine-needle aspiration cytology (FNAC) helps in prompt recognition of the disease. Aim: The aim of the study was to analyze the presence of microfilariae (MF) diagnosed on FNAC from different body locations based on clinicopathological data and cytopatholgical features. Methods: It was a retrospective observational study in which cases of MF over last 5 years which were diagnosed on FNAC were analyzed. Results: Of 34069 cases of FNAC and 45623 cases of fluid cytology, 27 cases (0.033%) of filariasis were diagnosed on cytopathology smears. The various sites included the skin and soft tissue (8 cases), lymph node (6 cases), breast (5 cases), pleural fluid (4 cases), scrotal swelling (3 cases), and thyroid gland (1 case). Eosinophilia was found in 18 cases (66.67%). The background showed inflammatory infiltrate in 17 cases (62.96%), while florid reactive mesothelial hyperplasia was seen in 2 cases (7.4%). We found 4 cases (14.81%) of incidental malignancies along with MF (3 breast and 1 pleural fluid). Conclusion: Although rare, filariasis should always be suspected as a differential diagnosis of FNAC in different body location swellings. A careful attitude while screening cytopathological smears helps to diagnose MF even in asymptomatic cases.

Immunohistochemical Differentiation between Reactive and Malignant Mesothelial Proliferations in Pleural Effusion

AbstractBackground: The differentiation between benign and malignant mesothelial cells in pleural effusion in some cases can be a challenge. In the current study, we investigated the value of immunohistochemistry (IHC) in making that differ-entiation.Aim of Study: This study aims to examine the value of IHC expression of desmin, EMA, GLUT-1, p53, Ki67, and BAP1 in discrimination between benign and malignant mes-othelial proliferation in pleural effusions and compare their results regarding sensitivity and specificity.Material and Methods: Pleural fluids from 30 cases diagnosed as malignant meothelioma (MM) epitheloid type and 20 cases diagnosed as reactive mesothelial hyperplasia (RMH) were selected, and stained with immunohistochemical stains included BAP-1, desmin, epithelial membrane antigen (EMA), glucose-transport protein 1 (GLUTA]1), Ki67, and p53.Results: BAP-1 was negative in 5% (1 of 20) cases of reactive MH and in 63.3% (19 of 30) of MM cases (p 40% of mesothelial cells in 10% (2 of 20) of benign and 16.7% (5 of 30) of malignant cases (p=0.40). EMA negativity and desmin positivity were found in 75% (15 of 20) of reactive MH cases and 3.3% (one of 30) of MM cases. EMA positivity and desmin negativity were found in 5% (1 of 20) of reactive MH cases and 90% (27 of 30) of MM cases (p<.001). Positivity for both of Desmin and BAP-1 was detected in 80% (16 of 20) of RMH cases. The combination of Desmin and BAP-1 negativity was detected in 60% (16 of 30) of MM cases (p-value p<.001).Conclusions: Cases showed positivity for EMA and neg-ativity for desmin strongly favors malignant mesothelioma. On the contrary, cases showed negative EMA and positive desmin strongly favors Reactive mesothelial hyperplasia. also the combination of Desmin and Bap-1 postivity favors diagnosis of RMH, and the combination of Desmin and BAP-1 negativity favors the diagnosis of MM. Similarly, cases showed strong membranous expression of GLUT-1 and/or strong nuclear expression of p53 strongly favors diagnosis of malignant mesothelioma. Proliferative index showed detected by Ki67 showed no significant difference between reactive and malignant cases.

Can novel adipokines, asprosin and meteorin-like, be biomarkers for malignant mesothelioma?

ABSTRACTMalignant mesothelioma (MM) is a rare tumor of serous surfaces that has a poor prognosis. Cancer is a multistage process by which cells undergo metabolic and behavioral changes that cause excessive and untimely proliferation. Asprosin (ASP) and meteorin-like (METRNL) are two peptides associated with glucose and energy metabolism. We used immunohistochemistry to investigate whether these peptides could be biomarkers for diagnosis and treatment of MM. We reviewed 30 cases of MM and 30 cases of reactive mesothelial hyperplasia (RMH); we used the cases with RMH as control group. The specimens were examined using immunohistochemical staining for ASP and METRNL. ASP and METRNL immunoreactivity was more prominent in the MM specimens than the RMH specimens. Therefore, ASP and METRNL potentially could be used as markers for differentiating MM from benign diseases.

Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma.

Neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene located on chromosome 22q12.2, is frequently abnormal in mesothelioma. Recent studies have revealed the effectiveness of diagnostic assays for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. These include detection of homozygous deletion of the 9p21 locus by fluorescence in situ hybridization (FISH) (9p21 FISH), loss of expression of BAP1 as detected by immunohistochemistry, and loss of expression of methylthioadenosine phosphorylase (MTAP) as detected by immunohistochemistry. However, the application of FISH detection of NF2 gene deletion (NF2 FISH) in differentiation of malignant pleural mesothelioma from reactive mesothelial hyperplasia has not been fully evaluated. In this study, we investigated whether NF2 FISH, either alone or in a combination with other diagnostic assays (9p21 FISH, MTAP immunohistochemistry, and BAP1 immunohistochemistry), is effective for distinguishing malignant pleural mesothelioma from reactive mesothelial hyperplasia. This study cohort included malignant pleural mesothelioma (n = 47) and reactive mesothelial hyperplasia cases (n = 27) from a period between 2001 and 2017. We used FISH to examine deletion status of NF2 and 9p21 and immunohistochemistry to examine expression of MTAP and BAP1 in malignant pleural mesothelioma and in reactive mesothelial hyperplasia. Hemizygous NF2 loss (chromosome 22 monosomy or hemizygous deletion) was detected in 25 of 47 (53.2%) mesothelioma cases. None of the mesothelioma cases showed homozygous NF2 deletion. Hemizygous NF2 loss showed 53.2% sensitivity and 100% specificity in differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. A combination of NF2 FISH, 9p21 FISH, and BAP1 immunohistochemistry yielded greater sensitivity (100%) than that detected for either diagnostic assay alone (53.2% for NF2 FISH, 78.7% for 9p21 FISH, 70.2% for MTAP immunohistochemistry, or 57.4% for BAP1 immunohistochemistry). Thus, NF2 FISH in combination with other diagnostic assays is effective for distinguishing malignant pleural mesothelioma from reactive mesothelial hyperplasia.

The importance of FISH signal cut-off values for 9p21 deletion in malignant pleural mesothelioma: Is it underestimated?

Malignant mesothelioma (MM) is an aggressive cancer with a poor prognosis. The most common genetic alteration in MM is the deletion of the INK4a/ARF locus, which encodes the p16 protein and is located on the short arm of chromosome 9 (9p21). Recently, it has been shown that homozygous deletion of 9p21 has both diagnostic and prognostic significance in MM. It is a known fact that, to interpret fluorescence in situ hybridization (FISH) signals, a cut-off value for each probe should be determined for a correct diagnosis. To our knowledge, there is no consensus or confirmed protocol for cut-off values to evaluate FISH signals in MMs. Therefore, the aim of our research was to address 9p21 deletion status and p16 expression profiles of MM by determining our own cut-off values and the effectiveness of using p16 negativity and 9p21 deletion as markers for differentiating MMs from benign mesothelial proliferations in 114 cases. We established a cut-off value for the detection of 9p21 deletion by using 13 benign reactive cases (6 reactive mesothelial hyperplasias and 7 chronic fibrinous pleuritis cases) and found between 0–7%. According to our calculations, homozygous deletion was defined by loss of both p16 gene signals in at least 13.3% of the nuclei that showed at least 1 signal for the CEP 9 probe. Our FISH results showed homozygous 9p21 deletion in 82 of the 114 cases of MM (71.9%), and p16 expression was negative in 75 of the 114 cases (65.8%). The correlation between loss of p16 protein expression and 9p21 deletion was statistically significant. Among the p16-negative cases, 86.7% also had the 9p21 deletion.The combined examination of the 9p21 deletion and loss of p16 expression is helpful for diagnostic purposes, but because the FISH method is an expensive technique and loss of p16 expression is not specific for mesotheliomas, p16 negativity can guide practitioners to eliminate cases that require further investigation by FISH. The variability in the significance of 9p21 homozygous deletion results from inconsistencies among different institutes, suggesting that each institute should establish its own cut-off value using reactive mesothelial proliferations. Alternatively, global studies are needed to assess cut-off values.

Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia

ObjectiveMalignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor prognosis. Loss of BRCA-associated protein 1 (BAP1) protein expression as detected by immunohistochemistry (IHC) and homozygous deletion (HD) of the 9p21 locus as detected by fluorescence in situ hybridization (FISH) permits differentiation of MPM from reactive mesothelial hyperplasia (RMH). We have previously reported that detecting the loss of methylthioadenosine phosphorylase (MTAP) using IHC is a surrogate assay for 9p21 FISH. Furthermore, enhancer of zeste homolog 2 (EZH2), which encodes a component of polycomb repressor complex 2 (PRC-2), has been overexpressed in various tumors as well as MPM. In the current study, we investigated whether EZH2 IHC assay, alone or in combination with BAP1 and MTAP IHC, is useful for distinguishing MPM from RMH. Materials and methodsWe examined IHC expression of EZH2, BAP1, and MTAP, and 9p21 FISH in MPM (n = 38) and RMH (n = 29) and analyzed the sensitivity and specificity of each detection assay for distinguishing MPM from RMH. Results and conclusionEZH2, BAP1, and MTAP IHC, and 9p21 FISH were characterized by a 100% specificity each and 44.7%, 52.6%, 47.4%, and 65.8% sensitivities, respectively. A combination of EZH2 and BAP1 IHC, and 9p21 FISH showed the greatest sensitivity (89.5%). Using IHC alone (EZH2, BAP1, and MTAP IHC) also yielded a good sensitivity of 86.9%; this level is high enough for routine diagnostics. There were no statistically significant associations between expression of EZH2 and that of other markers (BAP1 and MTAP IHC) or 9p21 HD. However, a high expression level of EZH2 was significantly associated with short survival (P = 0.025). In conclusion, adding a high expression level of EZH2 to a combination of BAP1 and MTAP loss, all detected by IHC, demonstrated useful for discriminating MPM from RMH.

Chronic diarrhea due to lymphosarcoma in an adult cow: a sporadic clinical report

The present clinical report describes a rare sporadic clinical case of chronic diarrhea due to lymphosarcoma in a 7-yearold crossbred Holstein?Friesian cattle. Diarrhea occurred due to intestinal lymphoid tissue involvement. The clinical diagnosis of lymphosarcoma was derived from peritoneal fluid aspirate, lymph node enlargement, and absence of serological and fecal evidence of any parasitic or bacterial infection. Reactive proliferative mesothelial hyperplasia in peritoneal fluid examination confirmed lymphosarcoma. The cells form numerous 3-dimensional clusters in mesothelial lymphosarcoma. Postmortem examinations confirmed visceral lymph node enlargements. A hematological examination revealed leukocytosis and a marked decrease in hemoglobin level, which reflected a severe degree of anemia. A clinical diagnosis of bovine lymphosarcoma was made, with visceral lymph node enlargement resulting in consistent chronic diarrhea in the adult cow.

Mesotelioma

Mesothelioma is a tumor of mesothelial cell origin and in 80% of cases pleura is concerned. Asbestos exposure is the major cause of this tumor. In order to identify both pleural abnormalities and the extent disease, CT with intravenous contrast is necessary in patient suspected of malignant pleural mesothelioma. In case of pleural effusion diagnostic thoracocentesis and closed pleural biopsy have to be performed. Stromal invasion is the major criteria to identify reactive mesothelial hyperplasia or organizing pleuritis. The most important prognostic factors are TNM stage, histological type (the greater variety of epithelial cells the greater survival), age and general condition of the patient. Treatment has to be addressed by a multidisciplinary mesothelial committee. Approximately 20% of patients are candidates for surgical resection.

Role of p16 deletion and BAP1 loss in the diagnosis of malignant mesothelioma.

Malignant mesothelioma (MM) is a rare but highly aggressive neoplasm. It has a poor prognosis and a median survival time of 20 months after diagnosis (1). Tumor development is associated with exposure to several known carcinogens such as asbestos fiber, rhesus virus 40, and radiation, of which asbestos exposure is the most important risk factor (2). The early clinical symptoms of MM lack specificity and are often characterized by large amounts of pleural effusion, which make clinical and imaging diagnoses difficult. Mesothelioma often goes undiagnosed until the late stages of the disease, at which time no marked effects can be achieved, regardless of whether the patient and medical team select surgery or radiotherapy and chemotherapy. Differential diagnosis of MM from reactive mesothelial hyperplasia (RMH) or metastatic carcinoma is crucial to patient care and prognosis, but distinguishing these specific conditions from each other can be very difficult. RMH is a benign condition, but it often mimics the features of neoplasm including high cellularity, the presence of numerous mitotic figures and cytologic atypia, the formation of papillary groups, the presence of necrosis, and entrapment of mesothelial cells within fibrosis, mimicking invasion (3). This makes MM and RMH appear very similar in histological appearance. Immunohistochemistry (IHC) for calretinin, podoplanin, cytokeratin 5/6, and Wilms’ tumor-1 proteins are commonly used to diagnosis MM, with a sensitivity of greater than 90%, 90–100%, 75–100%, and 70–95%, respectively (3). Although these immunohistochemical markers have high sensitivity for MM, they are also positively expressed in some RMH cases (4). Similarly, histopathologic differentiation between MM and lung adenocarcinoma is often challenging. Epithelial MM is a tumor with a small tube, acinar, flaky atypical growth pattern formed by epithelial mesothelial cells, similar to the histological structure of lung adenocarcinoma. Distinguishing MM from lung adenocarcinomas can be difficult, even when multiple immunohistochemical stains are deployed. Sometimes MM expresses “carcinoma” markers such as epithelial membrane antigen (5), and lung adenocarcinomas do not always express thyroid transcription factor 1 or Napsin A, so their sensitivity is not more than 80% (6). For this reason, it is important to identify more specific markers that facilitate the early and accurate diagnosis of MM. Recently two new markers that appeared to be useful for distinguishing benign from MM were discovered, namely p16 [cyclin-dependent kinase inhibitor 2A (CDKN2A)], a tumor suppressor gene, and BRCA1-associated protein 1 (BAP1). Deletion of p16 has proven to be a reliable way of differentiating benign from MM proliferation, which is one of the most common cytogenetic abnormalities in MM and can be detected by fluorescence in situ hybridization (FISH). P16 deletion has been found in 47.4–81.3% of MM cases, but no cases of RMH have been reported to harbor p16 deletion (4,5,7,8). However, even at a specificity of 100%, some MM cases do not show p16 deletion. Thus, another useful marker, BAP1 was identified. Previous studies have shown that BAP1 loss can occur as a result of gene deletion, point mutations, or other indirect mechanisms and BAP1 loss can be assessed by IHC (9,10). Loss of BAP1 staining has been observed in many tumors such as epithelioid atypical Spitz tumors, melanoma, renal cell carcinoma, and MM (11). The relationship between BAP1 loss and MM is significant. BAP1 loss has been reported in 15–67.5% of MM cases, with a specificity of 100% for differentiating between MM and RMH (4,7,12-15). Thus together, p16 and BAP1 are reliable markers for differentiating MM from RMH. BAP1 has also been used to identify MM and lung adenocarcinoma. Although the correlation between BAP1 loss and lung cancer is not completely understood, it is known that loss of BAP1 expression is rare in lung adenocarcinoma (16,17). Thus, it is reasonable to assume that loss of BAP1 in a thoracic malignancy would provide strong support for the diagnosis of MM. The goal of this study was to establish the value of p16 deletion detected by FISH and BAP1 loss detected by IHC for MM diagnosis, and to determine the value of p16 deletion and BAP1 loss in distinguishing MM from RMH and lung adenocarcinoma.

Is the pathology related to the amount of pleural thickening measured by thorax CT?

Background: Pathologies associated with pleural thickening are presented along with similar clinical and radiological findings. The present study highlights the importance of the differential diagnosis verification of patients with pleural thickening. Video-assisted thoracoscopic surgery (VATS) is one of the most common diagnostic and therapeutic method used for this purpose. In this study, we aim to deliver our clinical investigation results on patients diagnosed with pleural pathology in the light of recent literature. Methods: During the period of May 2012-June 2014, single port VATS pleural biopsy were successfully performed on 40 patients (25 male and 15 female) in our hospital. Thoracic CT and pathology results were compared. Clinical diagnosis, radiologic findings, and biopsy results were evaluated retrospectively. Results: The average age of the patients is 59.15 ±12.13 (age range 23, 82). There was an environmental exposure to asbestos in 14 patients (35%). 25 patients (62.5 %) was followed with clinical pre-diagnosis of mesothelioma, 8 patients (20%) of tuberculosis, 4 patients (10%) of pleural metastasis and 3 patients (7.5 %) of pleuritis. Histopathologically 8 patients (20%) were diagnosed with malignant mesothelioma, 1 patient (2.5 %) was localized fibrous tumor, 2 patients were (5%) diagnosed with reactive mesothelial hyperplasia, 6 patients (15%) were malignant epithelial tumor metastasis, 16 patients (40%) were fibrinous pleuritis, 6 patients (15%) were chronic granulomatous inflammation, and 1 patient (2.5%) was chronic lymphocytic inflammation. Conclusions: The present study demonstrates insufficency of thoracic CT for diagnosis and differential diagnosis due to similar clinical and radiological findings associated with pathological pleural thickening. Histopathologic examination is required for diagnosis. However, thoracic CT is still a method of radiographic imaging that is actively used in determination of pleural biopsy position, evaluation, and clinical monitoring of response to treatment.

Utility of Survivin, BAP1, and Ki-67 immunohistochemistry in distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia.

Histological distinction between epithelioid mesothelioma (EM) and reactive mesothelial hyperplasia (RMH) can be challenging. The aim of this study was to assess the diagnostic utility of Survivin, Ki-67, and loss of BRCA1-associated protein 1 (BAP1) expressions in distinguishing EM from RMH using immunohistochemistry. Formalin-fixed, paraffin-embedded specimens from 78 cases of EM and 80 cases of RMH were immunohistochemically examined for Survivin, BAP1, and Ki-67. In addition, receiver operating characteristic curve analyses were performed to establish the cut-off values for Survivin and Ki-67 labelling indices. Survivin (cut-off value: 5%) had 67.7% sensitivity and 100% specificity, while Ki-67 (cut-off value: 10%) had 85.1% sensitivity and 87.5% specificity, and BAP1 had 66.2% sensitivity and 100% specificity for the differentiation of EM from RMH. Among the combinations of two markers, the combination of Survivin and BAP1 (Survivin-positive and/or BAP1-loss finding) had the highest diagnostic accuracy (sensitivity: 89.8%; specificity: 100%; accuracy: 95.3%). We recommend using the combination of Survivin and BAP1 to distinguish EM from RMH.

Tunica Vaginalis Thickening, Hemorrhagic Infiltration and Inflammatory Changes in 8 Children with Primary Hydrocele; Reactive Mesothelial Hyperplasia? A Prospective Clinical Study.

The aim of this study is to describe an entity of primary hydrocele accompanied with fibrosis, thickening and hemorrhagic infiltration of parietal layer of tunica vaginalis (PLTV). During a 4-year period (2011-2014), 94 boys (2.5-14 years old) underwent primary hydrocele repair. Hydrocele was right sided in 55 (58.5 %), left sided in 26 (28.7%) and bilateral in 12 patients (13.8%). Eighty three out of 94 patients (88.30%) had communicating hydrocele and the rest eleven patients (11.7%) had non-communicating. Our case group consists of 8 patients (8.51%) based on operative findings consistent with PLTV induration, thickening and hemorrhagic infiltration. Preoperative ultrasonography did not reveal any pathology of the intrascrotal structures besides hydrocele. There weren't hyperechoic reflections or septa within the fluid. Evaluation of thickness of the PLTV was not feasible. Presence of lymph or exudate was excluded after fluid biochemical analysis. Tunica vaginalis histological examination confirmed thickening, hemorrhagic infiltration and inflammation, while there was absence of mesothelial cells. Immunochemistry for desmin was positive, excluding malignant mesothelioma. One patient underwent high ligation of the patent processus vaginalis and PLTV sheath fenestration, but one year later, he faced a recurrence. An elective second surgery was conducted via scrotal incision and Jaboulay operation was performed. The latter methodology was our treatment choice in other 7 out of 8 patients. During a 2-year postoperative follow-up, no other patient had any recurrence. We conclude that in primary hydrocele with macroscopic features indicative of tunica vaginalis inflammation, reversion of the tunica should be a part of operative strategy instead of sheath fenestration, in order to minimize the recurrence.

Challenging and uncommon diagnosis of long-evolution ascites

This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No history of liver disease or asbestos exposure. He complained of ascites during the last 3 years...

A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions. The authors examined IHC expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45 cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC expression of MTAP was compared with the deletion status of 9p21 FISH. MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks. A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54-63. © 2017 American Cancer Society.