Immunohistochemical Expression of PAX8 in Central Nervous System Hemangioblastomas: A Potential Diagnostic Pitfall for Neuropathologists

Abstract

The histologic differential diagnosis between intracranial hemangioblastoma (HB) and metastatic clear cell renal cell carcinoma may be challenging, especially considering that both tumors exhibit clear cell morphology and can be associated with vHL mutation and/or Von Hippel-Lindau syndrome. As the execution of immunohistochemical analyses is often mandatory, the expression of PAX8 has been traditionally considered a reliable marker of metastatic clear cell renal cell carcinoma, being consistently negative in intracranial HB. However, as in recent years, some cases of PAX8-positive HBs have been reported in the literature; we studied the expression of this antibody on a series of 23 intracranial HB, showing that about 40% of these tumors may express PAX8 and that this immunoreactivity is often focal and weak. We would like to emphasize that the possibility of a PAX8-positive intracranial HB does exist and must be taken into account by neuropathologists to avoid misdiagnoses; in this regard, a broader immunohistochemical panel also including CD10, Inhibin-α, PAX2, S100, and anti-Renal cell carcinoma (RCC) antibody is highly recommended.

Keywords: PAX8; diagnostic pitfall; differential diagnosis; hemangioblastoma; immunohistochemistry.

FIGURE 1

Histologic and immunohistochemical features of the reticular (A) and cellular (B) HB samples on H&E (A and B), and immunoperoxidase staining (C and D). A, Reticular subtype is predominantly composed of variable-sized capillary vessels, while neoplastic stromal cells are poorly recognizable. B, Cellular HB exhibits a striking prevalence of large stromal cells with clear/foamy cytoplasm; note the focal degenerative nuclear atypia. C and D, Neoplastic cells are weakly to moderately and focally to heterogeneously stained with PAX8 at medium (C) and high (D) magnification. Scale bars: 100 μm (A–C), 50 μm (D). HB indicates hemangioblastoma; H&E, hematoxylin and eosin.