Chromosomal alterations in 7, 17, and Y demonstrate comparable sensitivity and superior specificity to diffuse strong...

The diagnostic criteria for papillary renal cell carcinoma (PRCC) include diffuse strong AMACR and retained FH expression. Although chromosomal alterations in 7/17/Y are frequent molecular findings in PRCC, they are not included in its diagnostic criteria. This study analyzed 154 PRCC cases and 120 PRCC mimics using AMACR immunostaining and chromosomal analyses. Positive AMACR expression demonstrated the highest sensitivity (98.1 %), while a combination of diffuse strong AMACR expression and ≥2 chromosomal alterations achieved optimal specificity (93.3 %). Detection of ≥1 chromosomal alteration provided comparable sensitivity (86.4 % vs. 83.8 %) to diffuse strong AMACR expression alone but with significantly enhanced specificity (73.3 % vs. 48.3 %). Non-PRCC tumors demonstrating both diffuse strong AMACR expression and ≥2 chromosomal alterations predominantly included TFE3-rearranged RCC (3/29) and FH-deficient RCC (3/13) cases, with rare cases in clear cell RCC (1/10) and SMARCB1-deficient RCC (1/2). Collecting duct carcinoma occasionally showed multiple chromosomal alterations but usually showed negative or focal AMACR expression. These findings indicated that chromosomal alterations demonstrated comparable sensitivity and superior specificity compared to diffuse strong AMACR immunostaining for PRCC diagnosis. We propose incorporating chromosomal alterations in 7/17/Y as a desirable diagnostic criterion for PRCC. In addition, unclassified metastatic RCCs with papillary architecture should not be definitively diagnosed as PRCC based solely on chromosomal alterations. A definite diagnosis of metastatic PRCC requires exclusion of these histological and molecular mimics.