Thirty-one cases of low-grade renal cell carcinoma (RCC) with clear cells and tubulopapillary/papillary
architecture were analyzed retrospectively with immunohistochemical and genetic markers
to gain more experience with the differential diagnosis of such cases. All samples
coexpressed CK7 and CA9; the TFE3 or TFEB reactions were negative; the CD10 and the
AMACR stainings were negative in 27 cases and 30 cases, respectively. The FISH assays
for papillary RCC, available in 27 cases, and deletion of chromosome 3p, available
in 29 cases, gave negative results. The results for 3p deletion, VHL gene mutation
or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity
in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no
3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no
3p loss, VHL abnormality mutation/hypermethylation present). In CCPRCCs, the representative
growth pattern was branching tubulo-acinar, commonly accompanied by cyst formation.
The linear nuclear arrangement or cup-shaped staining of CA9 did not necessarily indicate
CCPRCC, and the absence of these did not exclude the diagnosis of CCPPRC. One tumor
infiltrated the renal sinus; the others exhibited pT1 stage; and metastatic outcome
was not recorded. The CCRCC cases were in pT1 stage; 6 exhibited cup-shaped staining
of CA9, and 1 displayed lymph node metastasis at the time of surgery. Distant metastatic
disease was not observed. In summary, the VHL abnormalities distinguished the subset
of CCRCC with diffuse CK7-positivity and no 3p loss from cases of CCPRCC.
