Ancillary Diagnostic Utility of Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) in Diagnostically Challenging Hepatic Angiomyolipoma.

Hepatic angiomyolipoma (HAML) is a rare mesenchymal neoplasm within the perivascular epithelioid cell tumor (PEComa) family that may pose significant diagnostic challenges because of its variable radiologic, histologic, and immunophenotypic features. HAML demonstrates a broad morphologic spectrum, including component-predominant and other uncommon histologic variants, which may obscure the classic triphasic morphology, particularly in limited biopsy specimens. Recently, glycoprotein nonmetastatic melanoma protein B (GPNMB) has emerged as a sensitive immunohistochemical marker for PEComa-family tumors. A 39-year-old man with a history of Hodgkin lymphoma presented with intermittent abdominal pain and an enlarging abdominal mass. Imaging demonstrated a hypervascular fat-containing lesion arising from the left hepatic lobe. Core biopsy revealed a mesenchymal neoplasm composed of mature adipose tissue, epithelioid cells, and thick-walled blood vessels without significant atypia or mitotic activity. Immunohistochemical studies demonstrated focal, patchy positivity for HMB45 and Melan-A; diffuse positivity for GPNMB and smooth muscle actin (SMA); and negativity for HepPar-1, glypican-3, CAM5.2, CK7, S100, and desmin. The morphologic and immunophenotypic findings supported the diagnosis of HAML. The patient subsequently underwent left lateral segmentectomy, and surgical pathology confirmed hepatic angiomyolipoma with negative margins. The postoperative course was uncomplicated. HAML remains a diagnostically challenging hepatic neoplasm because of its broad morphologic spectrum and variable radiologic and immunophenotypic features. Component-predominant and other uncommon variants may complicate recognition of the classic triphasic morphology, particularly in limited biopsy specimens. This case highlights the potential diagnostic utility of GPNMB as an ancillary immunohistochemical marker in challenging HAMLs that demonstrate limited or focal expression of conventional melanocytic markers, such as HMB45 and Melan-A.