PNL2: an adjunctive biomarker for renal angiomyolipomas and perivascular epithelioid cell tumours

Renal angiomyolipoma (AML) and perivascular epithelioid cell tumour (PEComa) are members of the microphthalmia-associated transcription factor (MiTF) family of tumours. Traditionally, HMB45 and melan-A have been used to diagnose these lesions; however, low sensitivity can make interpretation difficult. PNL2 is a sensitive and specific biomarker for epithelioid melanoma, and immunoreactivity has also been shown in small series of PEComas. This study was aimed at determining the utility of PNL2 in MiTF and non-MiTF renal tumours.

PNL2 immunostaining was performed on 196 tumours, including 40 MiTF renal tumours [AMLs, epithelioid AMLs, sclerosing PEComas, malignant PEComas, and Xp11.2 renal cell carcinomas (RCCs)] and 156 non-MiTF renal tumours. HMB45, melan-A and cathepsin K were also evaluated in a subset of MiTF tumours. Overall, 85% of AMLs and PEComas were positive for PNL2, as compared with 81%, 76% and 95% that were positive for HMB45, melan-A, and cathepsin K, respectively. In 55% of cases, PNL2 stained more extensively than HMB45. PNL2 staining was more frequent than HMB45 (78%) and melan-A (38%) staining in sclerosing and malignant PEComas (89%). All remaining renal tumours, except one melanocytic Xp11.2 RCC, were negative for PNL2.

PNL2 has high sensitivity and specificity for AML and PEComas as compared with non-MiTF renal tumours, and PNL2 appears to be a more useful biomarker for sclerosing and malignant PEComas. For cases that are limited in tissue quantity (i.e. core biopsies) and/or are morphologically suspicious for AML/PEComa, but negative or focally positive for HMB45 and melan-A, PNL2 may be a useful adjunctive biomarker.