B-cell lymphoma unclassifiable, intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, with translocations involving MYC and BCL2 (double hit). (A) A high-grade lymphoma involves the gastric mucosa of a patient with a history of low-grade follicular lymphoma (H&E). (B) At higher magnification, the cells are medium-sized and monomorphic with a high mitotic rate (H&E). (C) The cells are strongly positive for Bcl2 (Bcl2 immunoperoxidase stain). (D) FISH on interphase nuclei using a dual-color dual fusion probe for the BCL2 and IGH loci (top) shows one abnormal (yellow) signal in most cells, indicating a translocation involving the BCL2 and IGH genes. FISH on interphase nuclei with the use of a dual-color break-apart probe for the MYC locus (bottom) shows 1-2 yellow signals (normal) and 2-3 red signals, indicating a break at the MYC locus, with loss of the 3′ end of MYC, consistent with an unbalanced or complex MYC rearrangement. Panels A, B, and C were provided by Dr Aliyah Sohani, Department of Pathology, Massachusetts General Hospital. Panel D is reprinted from Snuderl et al.¹⁰⁶