Claudin‐4 immunohistochemistry is a useful pan‐carcinoma marker for serous effusion specimens

Vojtek, Melissa; Walsh, Michael D.; Papadimos, David; Shield, Paul

doi:10.1111/cyt.12765

Cited by 24 publications

(44 citation statements)

References 11 publications

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“…Similar results were observed in a recent study by Vojtek et al 15 in 284 effusion cell blocks, including 172 metastatic tumors with various origins and cell differentiation, 49 benign reactive lesions, and 63 MMs. Claudin-4 expression outperformed BerEP4, with 95.6% sensitivity, 99.1% specificity, a 95% NPV, and a 99.2% PPV.…”

Section: Cancer Cytopathology April 2021supporting

confidence: 86%

“…BAP1 expression also was very helpful in the differential diagnosis of MM from carcinomas with complete specificity and high sensitivity (70%) 11 . The results of these pathologists were promptly replicated and confirmed by other researchers in several publications 14‐22 …”

Section: Introductionmentioning

confidence: 78%

“…11 The results of these pathologists were promptly replicated and confirmed by other researchers in several publications. [14][15][16][17][18][19][20][21][22] In the current study, we investigated the role of the 2-hit, highly specific and limited panel of Claudin-4 and BAP1 (called the Brescia panel) in the differential diagnosis between MM with epithelioid features (epithelioid and biphasic) and metastatic carcinoma, collecting a consecutive series of 49 cases each of MM and pleural metastatic carcinoma from different primary sites on cell blocks and concurrent available biopsies.…”

Section: Cancer Cytopathology April 2021mentioning

confidence: 99%

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The “Brescia panel” (Claudin‐4 and BRCA‐associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas

Bernardi¹,

Bizzarro²,

Pironi

et al. 2020

Cancer Cytopathology

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Background The distinction between mesothelioma with epithelioid features and metastatic carcinoma may be challenging, particularly on cytology. A novel 2‐hit Claudin‐4 and BRCA‐associated protein 1 (BAP1) panel was investigated. Methods The objective of this study was to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the panel on cytology from pleural effusions and matched biopsies, including 49 malignant mesotheliomas on cytology with 43 matched biopsies, 49 normal/reactive mesothelial proliferations, and 49 pleural metastatic carcinomas from different primaries with 21 matched pleural biopsies. The diagnostic role of the 4 categories obtained by crossing the immunostaining results was analyzed. Results Claudin‐4 strongly stained all metastatic carcinomas and tested completely negative in normal mesothelium, benign reactive mesothelial hyperplasia, and malignant mesothelioma. All normal and benign mesothelial proliferations and all carcinomas except 1 were immunoreactive for BAP1, whereas BAP1 loss was observed in 88% of malignant mesotheliomas. The expression of Claudin‐4 alone excluded all benign and malignant mesothelial growth, consistently characterizing all metastatic carcinomas. Double negativity was evident in all malignant mesotheliomas, and double positivity was observed in all metastatic carcinomas. BAP1‐positive/Claudin‐4–negative status was observed only in malignant mesotheliomas and benign mesothelial proliferations. A single metastatic anal squamous cell carcinoma had BAP1‐negative/Claudin‐4–positive staining. Conclusions Claudin‐4 expression was completely specific and sensitive for metastatic carcinoma, excluding mesothelial proliferations. BAP1 staining characterized 98% of metastatic carcinomas and 100% of benign mesothelial proliferations, whereas negativity was observed almost exclusively in mesotheliomas. This 2‐hit panel is probably the best compromise for differentiating malignant mesothelioma and metastatic carcinoma on either cytology or biopsy specimens.

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Section: Cancer Cytopathology April 2021supporting

confidence: 86%

Section: Introductionmentioning

confidence: 78%

Section: Cancer Cytopathology April 2021mentioning

confidence: 99%

See 1 more Smart Citation

The “Brescia panel” (Claudin‐4 and BRCA‐associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas

Bernardi¹,

Bizzarro²,

Pironi

et al. 2020

Cancer Cytopathology

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“…Positive staining for these markers is cytoplasmic with membranous accentuation, although strong staining may simply appear cytoplasmic. Both MOC-31 and Ber-EP4 are generally reported to be 85-100% sensitive for adenocarcinoma and squamous cell carcinoma of the lung, adenocarcinoma of the breast, and serous ovarian carcinoma (7,8,14,(19)(20)(21)23,24,26,40,(52)(53)(54)(55). Conversely, they mark only half of renal cell carcinomas, limiting their usefulness in this differential diagnosis (11).…”

Section: Markers Of Epithelial Lineagementioning

confidence: 99%

Application of immunohistochemistry in diagnosis and management of malignant mesothelioma

Chapel¹,

Schulte²,

Husain³

et al. 2020

Transl Lung Cancer Res

103

111

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Immunohistochemistry plays an indispensable role in accurate diagnosis of malignant mesothelioma, particularly in morphologically challenging cases and in biopsy and cytology specimens, where tumor architecture is difficult or impossible to evaluate. Application of a targeted panel of mesothelialand epithelial-specific markers permits correct identification of tumor lineage in the vast majority of cases.An immunopanel including two mesothelial markers (calretinin, CK5/6, WT-1, or D2-40) and two epithelial markers (MOC-31 and claudin-4) offers good sensitivity and specificity, with adjustments as appropriate for the differential diagnosis. Once mesothelial lineage is established, malignancy-specific studies can help verify a diagnosis of malignant mesothelioma. BAP1 loss, CDKN2A homozygous deletion, and MTAP loss are highly specific markers of malignancy in a mesothelial lesion, and they attain acceptable diagnostic sensitivity when applied as a diagnostic panel. Novel markers of malignancy, such as 5-hmC loss and increased EZH2 expression, are promising, but have not yet achieved widespread clinical adoption. Some diagnostic markers also have prognostic significance, and PD-L1 immunohistochemistry may predict tumor response to immunotherapy. Application and interpretation of these immnuomarkers should always be guided by clinical history, radiographic findings, and above all histomorphology.

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“…When the cytomorphology of the atypical cells is equivocal as to the nature of the cells (mesothelial vs epithelial), the recommendation is to use at least two mesothelial and two carcinoma markers; these markers are not entirely specific and may show expression in both entities 153–157 (Table 8). Among the carcinoma markers, claudin 4 has been found to be superior to others for distinguishing carcinoma from MM 158–160 . Lineage specific markers can be used to identify the origin of a metastasis; the selection of the ICC panel should be guided by the clinical history, including the age and gender of the patient, imaging features, and location of the effusion 154–157,161–163 (Table 9).…”

Section: Immunocytochemistry For Effusion Cytologymentioning

confidence: 99%

Immunocytochemistry for diagnostic cytopathology—A practical guide

2021

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Cytological specimens, which are obtained by minimally invasive methods, are an excellent source of diagnostic material. Sometimes they are the only material available for diagnosis as well as for prognostic/predictive markers. When cytomorphology is not straightforward, ancillary tests may be required for a definitive diagnosis to guide clinical management. Immunocytochemistry (ICC) is the most common and practical ancillary tool used to reach a diagnosis when cytomorphology is equivocal, to differentiate entities with overlapping morphological features, and to determine the cell lineage and the site of origin of a metastatic neoplasm. Numerous immunomarkers are available, and some are expressed in multiple neoplasms. To rule out entities within a differential diagnosis, the use of more than one marker, sometimes panels, is necessary. ICC panels for diagnostic purposes should be customised based on the clinical context and cytomorphology, and the markers should be used judiciously to preserve material for additional tests for targeted therapies in the appropriate setting. This review offers a practical guide for the use of ICC for diagnostic cytopathology, covering the most commonly encountered non‐hematolymphoid diagnostic scenarios in various body sites.

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Claudin‐4 immunohistochemistry is a useful pan‐carcinoma marker for serous effusion specimens

Cited by 24 publications

References 11 publications

The “Brescia panel” (Claudin‐4 and BRCA‐associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas

The “Brescia panel” (Claudin‐4 and BRCA‐associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas

Application of immunohistochemistry in diagnosis and management of malignant mesothelioma

Immunocytochemistry for diagnostic cytopathology—A practical guide

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