Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study

Lucas, David R.; Pass, Harvey I.; Madan, Shashi; Adsay, Volkan; Wali, Anil; Tabaczka, Pamela; Lonardo, Fulvio

doi:10.1046/j.1365-2559.2003.01583.x

Cited by 127 publications

(94 citation statements)

References 23 publications

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“…It is known that epithelioid and sarcomatoid mesotheliomas show different antigen expression, with many mesothelial markers being frequently negative in sarcomatoid subtype. [67][68][69][70][71][72][73] A recent gene expression profile analysis applied to a large series of pleural mesothelioma cell lines and tissue samples identified two mesothelioma subgroups. Although sarcomatoid and desmoplastic mesotheliomas belonged to a single group associated with poorer prognosis, epithelioid mesotheliomas were either included in the sarcomatoid/desmoplastic group or fell in a distinct subgroup with a better prognosis.…”

Section: Discussionmentioning

confidence: 99%

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

et al. 2015

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The distinction between malignant mesothelioma and reactive mesothelial proliferation can be challenging both on histology and cytology. Recently, variants of the BRCA1-associated protein 1 (BAP1) gene resulting in nuclear protein loss were reported in hereditary and sporadic mesothelioma. Using immunohistochemistry, we evaluated the utility of BAP1 expression in the differential diagnosis between mesothelioma and other mesothelial proliferations on a large series of biopsies that included 212 mesotheliomas, 12 benign mesothelial tumors, and 42 reactive mesothelial proliferations. BAP1 stain was also performed in 70 cytological samples (45 mesotheliomas and 25 reactive mesothelial proliferations). BAP1 was expressed in all benign mesothelial tumors, whereas 139/212 (66%) mesotheliomas were BAP1 negative, especially in epithelioid/biphasic compared with sarcomatoid/desmoplastic subtypes (69% vs 15%). BAP1 loss was homogeneous in neoplastic cells except for two epithelioid mesotheliomas showing tumor heterogeneity. By fluorescence in situ hybridization, BAP1 protein loss was paralleled by homozygous deletion of the BAP1 locus in the vast majority of BAP1-negative tumors (31/41, 76%), whereas 9/10 BAP1-positive mesotheliomas were normal. In biopsies interpreted as reactive mesothelial proliferation BAP1 loss was 100% predictive of malignancy, as all 6 cases subsequently developed BAP1-negative mesothelioma, whereas only 3/36 (8%) BAP1-positive cases progressed to mesothelioma. On cytology/cell blocks, benign mesothelial cells were invariably positive for BAP1, whereas 64% of mesotheliomas showed loss of protein; all 6 cases showing BAP1 negativity were associated with histological diagnosis of BAP1-negative mesothelioma. BAP1 stain also showed utility in the differential of mesothelioma from most common pleural and peritoneal mimickers, such as lung and ovary carcinomas, with specificity and sensitivity of 99/70% and 100/70%, respectively. Our results show that BAP1 protein is frequently lost in mesothelioma, especially of epithelioid/biphasic subtype and is commonly associated with homozygous BAP1 deletion. BAP1 immunostain represents an excellent biomarker with an unprecedented specificity (100%) in the distinction between benign and malignant mesothelial proliferations. Finding BAP1 loss in mesothelial cells should prompt to immediately reevaluate the patient; moreover, it might be useful in mapping tumor extent and planning surgical resection.

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Section: Discussionmentioning

confidence: 99%

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

et al. 2015

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“…As with other currently used immunohistochemical markers of malignant mesothelioma, 21,22 D2-40 is limited by its performance in areas of sarcomatoid differentiation. In addition to the reduced frequency of positively staining tumor cells, the interpretation of D2-40 staining in areas of sarcomatoid growth is complicated by the loss of the characteristic membranous staining pattern seen in epithelioid mesotheliomas and the high level of background staining present in both benign reactive pleural tissue and desmoplastic tissue surrounding infiltrating tumor cells.…”

Section: D2-40 In Malignant Mesotheliomamentioning

confidence: 99%

Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma

et al. 2005

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Although immunohistochemistry has proven to be valuable in the differentiation of epithelioid mesothelioma from pulmonary or metastatic adenocarcinoma, no single antibody has demonstrated absolute sensitivity or specificity in making this distinction. Using immunohistochemical analysis with D2-40, a recently available monoclonal antibody that has been used as a lymphatic endothelial marker, we examined 53 cases of mesothelioma, 28 cases of reactive pleura, 30 cases of pulmonary adenocarcinoma, 35 cases of renal cell carcinoma, 26 cases of ovarian serous carcinoma, 16 cases of invasive breast carcinoma, 11 cases of prostatic adenocarcinoma, and seven cases of urothelial carcinoma. In addition, immunohistochemistry using calretinin, cytokeratin 5/6, and WT1 was performed on all cases of mesothelioma, pulmonary adenocarcinoma, ovarian serous carcinoma, and renal cell carcinoma. Predominantly, membranous D2-40 immunoreactivity was present in 51 of 53 (96%) mesotheliomas, 27 of 28 (96%) cases of reactive pleura, and 17 of 26 (65%) ovarian serous carcinomas; membranous staining was not seen in any other tumors examined. Compared to other immunohistochemical markers of mesothelioma, D2-40 was as sensitive as calretinin and more sensitive than cytokeratin 5/6 and WT1. We conclude that D2-40 immunoreactivity is sensitive for cells of mesothelial origin, and may be useful in the differential diagnosis of epithelioid malignant mesothelioma vs adenocarcinoma.

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“…Calretinin is expressed in both the cytoplasm and nucleus. According to the literature, its expression in malignant mesothelioma varies, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] but most authors report frequent expression in epithelioid malignant mesothelioma, with only few studies reporting expression below 90%. Interestingly, calretinin expression has been described in a wide variety of cells, including steroid-producing cells of the testis and ovary, adipocytes, eccrine-glands, keratinizing thymic epithelial cells and numerous tumors, for example Merkel cell carcinoma, Leydig cell tumors of the testis, esthesioneuroblastoma, adenomas of the adrenal gland, small cell carcinoma of the lung and adenomatoid tumor.…”

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confidence: 99%

“…The few publications that have evaluated calretinin expression in the three most frequent types of malignant mesothelioma separately present data that diverge from 18 to 100% positivity in sarcomatoid malignant mesothelioma, and 8 to 100% in biphasic malignant mesothelioma. 5,7,15,[18][19][20]33 The D2-40 staining frequency is also controversial in sarcomatoid and biphasic malignant mesothelioma. Whereas Chu et al 23 reported staining in all types of malignant mesothelioma, Ordóñ ez 24 did not detect any D2-40 staining in either sarcomatoid malignant mesothelioma or sarcomatoid areas of biphasic malignant mesothelioma.…”

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confidence: 99%

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

et al. 2007

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Anti-calretinin antibodies are useful to differentiate adenocarcinomas from malignant mesotheliomas of the lung. Therefore, calretinin expression is rarely reported for sarcomatoid mesotheliomas. Anti-podoplanin antibodies (eg D2-40) react with lymphatic endothelia, Kaposi's sarcoma, lymphangioma and mesotheliomas. For the interpretation of spindle cell lesions of the pleura, knowledge of calretinin and D2-40 expression frequencies in sarcomatoid mesothelioma is desirable. To systematically investigate the sensitivity of calretinin and D2-40 antibodies in epithelioid and sarcomatoid areas of malignant mesotheliomas, a tissue microarray with 341 malignant mesotheliomas, including 112 epithelioid, 46 sarcomatoid and 183 biphasic tumors was constructed. Epithelioid and sarcomatoid differentiated tumor areas were clearly separated within the tissue microarray. Expression of calretinin and D2-40 was separately studied in epithelioid and sarcomatoid areas by immunohistochemistry. Calretinin expression was found in 91% of epithelioid and 57% of sarcomatoid tumor areas. D2-40 immunostaining was present in 66% of the epithelioid and 30% of the sarcomatoid tumor areas. A combination of calretinin and D2-40 increased the sensitivity in epithelioid tumor areas to 0.96 and in sarcomatoid tumor areas to 0.66. These data indicate that a combination of calretinin and D2-40 will improve diagnostic accuracy for spindle cell lesions of the pleura, whereas almost all epithelioid mesotheliomas are identified by calretinin alone. Modern Pathology (2007) 20, 248-255.

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Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study

Cited by 127 publications

References 23 publications

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

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