Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology

Andrici, Juliana; Sheen, Amy; Sioson, Loretta; Wardell, Kathryn L.; Clarkson, Adele; Watson, Nicole; Ahadi, Mahsa; Farzin, Mahtab; Toon, Christopher W.; Gill, Anthony J.

doi:10.1038/modpathol.2015.87

Cited by 99 publications

(99 citation statements)

References 33 publications

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“…The clinical and pathological characteristics of the patient cohort are presented in table 1 and table 2 We also compared the serous adenocarcinomas to the thoracic mesothelioma cases diagnosed at our institution during the study period including those cases which have been previously reported. [19,21] 131 of 277 (47%) of thoracic mesotheliomas showed loss of BAP1 expression, and when combined with the abdominal mesothelioma cases, it was again clear that BAP1 loss occurred with much greater frequency in thoracic mesotheliomas than in gynaecological serous adenocarcinomas (p<0.001).…”

Section: Resultsmentioning

confidence: 92%

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Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma

et al. 2016

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Section: Resultsmentioning

confidence: 92%

“…[19][20][21][22] Abdominal mesotheliomas also frequently harbour BAP1 mutations which result in loss of BAP1 expression. [20,23] However the incidence of loss of BAP1 expression in gynaecological and peritoneal serous carcinoma is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma

et al. 2016

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“…8,23 However, other studies reported lower specificity. For instance, Andrici et al 9 reported 95% specificity (interpreted by them as more likely due to artefactual negative staining), and Walts et al (Table 1), specificity would be 88.6% in our case series (by excluding from the formulae cases with an initial diagnosis uncertain between MM and MH).…”

Section: Discussionmentioning

confidence: 93%

“…8,9,[21][22][23][24][25] The aim of this study was to evaluate the utility of BAP1 IHC in the diagnosis of MM in effusions. To do this, we investigated the BAP1 protein expression on a large series of cell blocks from pleural/peritoneal effusions, with a definite diagnosis of MM or an uncertain diagnosis between MM and MH, and benign effusions.…”

mentioning

confidence: 99%

Loss of BRCA1‐associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions

Cozzi

Oprescu

Rullo

et al. 2017

Diagnostic Cytopathology

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Background: The important diagnostic challenge facing the cytopathologist is whether a mesothelial proliferation on effusions represents a malignant mesothelioma (MM) or a benign mesothelial hyperplasia (MH). Here, we evaluated the diagnostic utility of BAP1 immunohistochemistry (IHC) in distinguishing between reactive and neoplastic mesothelial cells. Methods:In pleural and peritoneal effusions from 147 patients with diagnosed MM or with a differential diagnosis of MM and MH, the expression of BAP1 was examined by IHC on paraffinembedded cell blocks (n 5 121) and biopsies (n 5 44). Included were also synchronous and methacronous cytology/biopsy pair samples. BAP1 IHC was evaluated for nuclear staining as positive or negative on target mesothelial cells, with appropriate internal control.Results: In MM cases, loss of BAP1 nuclear staining was observed in 76.5% of the cell blocks and 47.5% of the biopsies. All BAP1-negative cases with a differential diagnosis of benign and malignant mesothelial proliferations were MM at follow-up. All MH cases, the 29% of epithelial MM and the 90% of nonepithelial MM, retained BAP1 expression. Synchronous and methacronous biopsy/cytology pairs showed matching BAP1 results. Conclusion:In effusions with mesotheliomatous cells or atypical mesothelial cells of uncertain significance, negative BAP1 IHC strongly supports a diagnosis of MM. With prudence in interpreting immunostaining, BAP1 may be included in IHC panels for MM cytodiagnosis, given its high specificity and sensitivity. 1 An effusion is the only available sample in specific settings, as in the elderly or in patients with co-morbidities. Based on cytomorphology alone, the differential diagnosis between MM, mesothelial hyperplasia (MH), and metastatic carcinoma may be difficult. It is necessary to use ancillary techniques, primarily immunohistochemistry (IHC). 1 IHC markers to distinguish epithelioid MM from metastatic carcinoma are well-defined, 2,3 whereas those to distinguish epithelioid MM from MH are less definite, except for GLUT-1, IMP-3, Desmin, and EMA. Regarding the practical utility of the latter two markers, Desmin shows low sensitivity 4 and EMA shows low specificity. 5-7Recently, a new marker has been proposed to aid in distinguishing MM from MH, namely BRCA1-associated protein 1 (BAP1 The aim of this study was to evaluate the utility of BAP1 IHC in the diagnosis of MM in effusions. To do this, we investigated the BAP1 protein expression on a large series of cell blocks from pleural/peritoneal effusions, with a definite diagnosis of MM or an uncertain diagnosis between MM and MH, and benign effusions. BAP1 immunostaining was also performed on biopsy samples with the same diagnoses to evaluate the differences between effusion and tissue samples. | M A TE RI A L S A ND M E TH ODSThis study was designated as exempt by the ethics committee due to its retrospective nature; moreover, no protected health information The following formulae of BAP1 testing for the outcome MM were calculated: sensitivity, defined as ...

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“…However, the loss of expression of BAP1 , as determined in cell-block preparations from pleural effusion specimens, has been proposed as a useful adjunct to support the diagnosis of mesothelioma. Loss of BAP1 expression is not definitive but can be used to aid the diagnosis of mesothelioma in effusion cytology [14]. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor (CDKN2A/p16) gene, also frequently occurs in mesothelioma, but was not identified in our case.…”

Section: Discussionmentioning

confidence: 81%

Diffuse Malignant Peritoneal Mesothelioma Presenting with Psammomatous Calcification on a Cervical Smear

Tan¹,

Cohen²,

Raoofi³

et al. 2015

Acta Cytologica

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Background: Psammoma bodies in cervical smears are rare but may be associated with benign and malignant diseases of the female genital tract. Case: A 52-year-old nulliparous woman presented with a 2-month history of intermittent vaginal spotting and post-coital bleeding. A cervical smear showed an inconclusive high-grade glandular lesion with psammomatous calcification. Previous cervical smears had been normal. This smear contained papillary tissue fragments, occasional spheres of gland-like cells and frequent psammoma bodies. The patient underwent a laparoscopic hysterectomy, bilateral salpingo-oophorectomy and omentectomy. The surface of the omentum and both ovaries contained psammoma bodies with groups of cells identical to those in the cervical smear. Within the omentum, there were invasive malignant epithelioid cells positive for CK7, CK5/6, calretinin, D2-40, WT-1, CK5/6, p16 and EMA. Desmin and PAX-8 immunostains were negative. There was also evidence of BRCA1-associated protein 1 (BAP1) dysfunction compatible with diffuse malignant peritoneal mesothelioma (DMPM). Conclusion: We describe the first reported case of DMPM presenting with an abnormal cervical smear, a rare but important differential diagnosis to consider in abnormal cervical smears showing psammomatous calcification.

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Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology

Cited by 99 publications

References 33 publications

Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma

Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma

Loss of BRCA1‐associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions

Diffuse Malignant Peritoneal Mesothelioma Presenting with Psammomatous Calcification on a Cervical Smear

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