Low-grade Spindle Cell Proliferation in Clear Cell Renal Cell Carcinoma is Unlikely to be an Initial Step in Sarcomatoid Differentiation

Abstract

Spindle cell proliferation within clear cell renal cell carcinoma (ccRCC) is usually considered as sarcomatoid differentiation. Low-grade spindle cell proliferation (LG-SCP) in ccRCC was first described in 2001. This phenomenon is not common and can pose diagnostic challenges particularly in core biopsies. The aim of this study was to describe morphologic, immunohistochemical and molecular characteristics of ccRCCs with LG-SCP.

11 cases of ccRCC with LG-SCP were retrieved from approximately 21,000 renal tumors in our registry. 10 cases of conventional ccRCC and 10 cases of typical sarcomatoid ccRCC were included as control groups. Morphologic and immunohistochemical characteristics of epithelial mesenchymal transition (EMT) were analyzed. VHL gene abnormalities were also analyzed using molecular genetics.

Among ccRCC with LG-SCP cases, there were 5 males and 5 females (clinical information was not available in one case) with median age of 67 years (mean 68.5, range 60-81 years). Average tumor size was 7.1 cm (median 7.5, range 1.7-12 cm). Follow up data were available in 9 cases (mean 44.78 months), with no aggressive behavior seen. On average, LG-SCP areas constituted 5-80% of tumor volume (mean 32.3%). Necrotic/regressed areas were seen in all cases ranging 5-30%. LG-SCP was clearly epithelial with no mitoses or any evidence of mesenchymal differentiation.

Immunohistochemical profile of LG-SCP was consistent with "conventional" ccRCC. Compared with sarcomatoid ccRCC, some EMT markers showed alteration in LG-SCP, including lower expression of N-Cadherin and Zeb1 as well as higher expression of E-cadherin. However, there were no significant differences in EMT markers between LG-SCP and conventional ccRCC. Abnormalities in VHL gene (mutations, LOH3p) were found in 6/11 cases.

Conclusions

Our findings showed that LG-SCP in ccRCC have comparable immunohistochemical and molecular characteristics to those seen in "conventional" ccRCC. Further, immunohistochemical analysis of EMT markers showed that LG-SCP did not differ from "conventional" ccRCC. We believe that LG-SCP is a part of morphologic heterogeneity in ccRCCs and that they may not represent an initial stage of sarcomatoid differentiation. This is further supported by the fact that ccRCC with LG-SCP did not display more aggressive behavior than "conventional" ccRCC.

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