PNL 2: an adjunctive biomarker for renal angiomyolipomas and perivascular epithelioid cell tumours

Aims Renal angiomyolipoma ( AML ) and perivascular epithelioid cell tumour ( PEC oma) are members of the microphthalmia‐associated transcription factor (Mi TF ) family of tumours. Traditionally, HMB 45 and melan‐A have been used to diagnose these lesions; however, low sensitivity can make interpretation difficult. PNL 2 is a sensitive and specific biomarker for epithelioid melanoma, and immunoreactivity has also been shown in small series of PEC omas. This study was aimed at determining the utility of PNL 2 in Mi TF and non‐Mi TF renal tumours. Methods and results PNL 2 immunostaining was performed on 196 tumours, including 40 Mi TF renal tumours [ AML s, epithelioid AML s, sclerosing PEC omas, malignant PEC omas, and Xp11.2 renal cell carcinomas ( RCC s)] and 156 non‐Mi TF renal tumours. HMB 45, melan‐A and cathepsin K were also evaluated in a subset of Mi TF tumours. Overall, 85% of AML s and PEC omas were positive for PNL 2, as compared with 81%, 76% and 95% that were positive for HMB 45, melan‐A, and cathepsin K, respectively. In 55% of cases, PNL 2 stained more extensively than HMB 45. PNL 2 staining was more frequent than HMB 45 (78%) and melan‐A (38%) staining in sclerosing and malignant PEC omas (89%). All remaining renal tumours, except one melanocytic Xp11.2 RCC , were negative for PNL 2. Conclusions PNL 2 has high sensitivity and specificity for AML and PEC omas as compared with non‐Mi TF renal tumours, and PNL 2 appears to be a more useful biomarker for sclerosing and malignant PEC omas. For cases that are limited in tissue quantity (i.e. core biopsies) and/or are morphologically suspicious for AML / PEC oma, but negative or focally positive for HMB 45 and melan‐A, PNL 2 may be a useful adjunctive biomarker.