D2-40, a novel monoclonal antibody against the M2A antigen as a marker to distinguish hemangioblastomas from renal cell carcinomas

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Abstract
Hemangioblastomas (HB) are characterized by the presence of vacuolated tumor cells resembling the tumor cells seen in clear cell renal cell carcinomas (CRCC). The distinction between HB and metastatic CRCC in the brain is critical as they have different therapeutic and prognostic ramifications. The issue is further complicated by the possibility of both HB and metastatic CRCC in brains of patients with Von Hippel Lindau (VHL) disease. We studied the expression of a novel monoclonal antibody D2-40, which recognizes an oncofetal antigen (M2A) in HB and CRCC, by immunohistochemistry. The vacuolated tumor cells in all HB were stained positively with D2-40. Nineteen of 23 (83%) HB showed strong, membranous staining in the vacuolated tumor cells, and 4 of 23 (17%) showed weaker staining. No expression was seen in CRCC, either primary in the kidney (0/20), or metastatic CRCC in the brain (0/8). Three of the patients with HB also had VHL disease, and no difference was seen in D2-40 staining of HB in patients with or without VHL disease. Two of these three VHL disease patients had both primary CRCC and HB resected at our institution. In these two patients, strong D2-40 expression was seen in the HB, but no expression was seen in the CRCC, underlying the utility of this marker in distinguishing HB from CRCC in patients with VHL disease in addition to sporadic cases. In summary, the monoclonal antibody D2-40 is a useful marker to distinguish HB from CRCC.