Figure 3
From: Molecular subtyping of metastatic renal cell carcinoma: implications for targeted therapy
Metastatic renal cell carcinomas not previously classified. A metastatic tumor nodule involving a lymph node (A) exhibited a nested to sheet-like architecture (B). Although morphologic features supported a diagnosis of metastatic renal cell carcinoma, the precise tumor subtype was not initially apparent. The tumor cells did not label for CK7 (C), but demonstrated moderately strong granular cytoplasmic reactivity for AMACR (D). Dual-color fluorescence in situ hybridization revealed intact chromosome 3p (E) as indicated by two green signals (3p25) and two red chromosome 3 centromeric signals (CEP3). FISH demonstrated trisomy of chromosomes 7 and 17, as indicated by three green signals (CEP7) and three red signals (CEP17) per nucleus (F), supporting reclassification of this tumor as papillary renal cell carcinoma. Another metastatic renal cell carcinoma involving the lung showed architectural and cytologic features not initially recognizable as those of a particular renal cell carcinoma subtype (G). The tumor exhibited a mixture of solid, trabecular, and tubulopapillary growth, lined by cells with eosinophilic cytoplasm (H). Dual-color fluorescence in situ hybridization demonstrated a characteristic 3p25 deletion as indicated by one green signal (3p25) and two chromosome 3 centromere red signals (CEP3) per cell (I), supporting subtyping as high-grade manifestation of clear cell renal cell carcinoma. A third metastatic lesion involving bone (J) contained cells with clear cytoplasm and prominent nucleoli, dispersed in a hemorrhagic and fibrinous (K) background. These morphologic findings raised the possibility of metastatic clear cell renal cell carcinoma. However, FISH revealed trisomy of chromosomes 7 and 17 (L), as demonstrated by three green signals (CEP7) and three red signals (CEP17) per nucleus. These findings were in line with the patient’s history of papillary renal cell carcinoma resected via radical nephrectomy many years prior, despite the morphologic appearance raising the possibility of clear cell renal cell carcinoma.