Immunohistochemistry for the detection of renal cell carcinoma in effusion cytology

Abstract

Renal cell carcinoma (RCC) is known for its unpredictable behavior. RCC rarely involves serosal surfaces and, when present, can be difficult to distinguish from mesothelial cells in cytologic preparations. Immunohistochemical stains are frequently used with effusion cytology; however, RCCs express traditional glandular antigens less frequently than other adenocarcinomas. We investigated the utility of typical immunohistochemical stains for identifying effusion involvement by RCC, along with more specific RCC markers. The cytology databases from two academic institutions were searched for all effusions involved by RCC with retrievable cell-block material. A four-marker immunohistochemical panel we generally use for distinguishing adenocarcinoma from mesothelial proliferations was then applied (calretinin, WT1, MOC31, and B72.3). In addition, each case was stained for RCC antigen, CD10, and PAX2. Eleven cases of RCC involving serous effusions were identified: six conventional clear-cell RCCs, three papillary RCCs, and two RCCs, not otherwise specified. Neoplastic cells were positive for MOC-31 in 3 of 11 cases, RCC antigen in 5 of 11 cases, and CD10 in 10 of 11 cases. RCC cells were negative for B-72.3, WT1, and calretinin in all cases. Background mesothelial cells showed high-background cytoplasmic staining for PAX-2; all RCC tumor cells were negative or equivocal. A conventional panel used for the diagnosis of adenocarcinoma in fluids will fail to detect most cases of metastatic RCC, particularly clear-cell RCC. Additional antibodies, such as those to CD10 and RCC, may be helpful to identify these tumors. PAX2 shows high background in mesothelial cells, which makes interpretation of nuclear staining difficult.

The importance of EZH2 and MOC‐31 expression in the differential diagnosis of benign and malignant effusions

“…In a previous study of 11 cases comprising 6 clear cell, 3 papillary, and 2 unclassified RCC, Chute et al 8 reported that MOC-31 applied in cell blocks was negative for all clearcell and unclassified RCC, and positive for 3 papillary RCC. In a previous study of 11 cases comprising 6 clear cell, 3 papillary, and 2 unclassified RCC, Chute et al 8 reported that MOC-31 applied in cell blocks was negative for all clearcell and unclassified RCC, and positive for 3 papillary RCC.…”

“…The nuclear/cytoplasmic ratio varies. 8 While approximately 67% of malignant effusions can be diagnosed with smear preparations, this rate can be increased to 83-85% by applying various immunohistochemical (IHC) markers to the cell blocks. [1][2][3][4] If the malignant effusion is biphasic, neoplastic cells would show contrast with existing benign mesothelial cells.…”

Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update

“…WT1, however, has no utility in discriminating between peritoneal mesotheliomas and serous carcinomas of the ovary and peritoneum because the latter tumors have been reported to be positive for this marker in most cases (83%-100%) [57,[59][60][61][62]. Only a few studies have investigated the expression of WT1 in renal cell carcinomas, and they have shown that this marker is rarely expressed in these tumors [27,57,63]. In an investigation by this author, only 1 (4%) of 24 clear cell renal cell carcinomas and none of the papillary, chromophobe, or sarcomatoid renal cell carcinomas included in that study were WT1 positive [27].…”

Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma

“…Only a few studies with a relatively small number of cases have been published on WT1 expression in renal cell carcinomas. 10,102,104,105 In the largest of these studies, which was by this author, WT1 positivity was demonstrated in only 1 (4%) of 24 clear cell, but in none of 8 papillary or 12 chromophobe, renal cell carcinomas included in that investigation. 10 Mesothelin is a marker that has been reported to be commonly expressed in epithelioid mesotheliomas (B90-100%).…”