EBV-Negative Cutaneous Lymphomatoid Granulomatosis With Concomitant EBV-Positive Pulmonary Involvement: A Potential Diagnostic and Prognostic Pitfall.

Lymphomatoid granulomatosis (LYG) is a rare, T-cell-rich Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorder. Although LYG presents most often with lung involvement, up to half of affected individuals have concomitant cutaneous LYG. EBV-encoded RNA (EBER) is detected in the majority of pulmonary lesions but is often negative in skin lesions. Herein, we describe a case of concomitant EBV-positive pulmonary and EBV-negative cutaneous LYG in a 70-year-old woman. Histologically, both skin and lung biopsies demonstrated angiocentric necrosis with vascular wall compromise and a brisk inflammatory infiltrate comprised of plasma cells, histiocytes, and lymphocytes. Immunohistochemical studies on the skin biopsy demonstrated predominance of T cells and scattered B cells within the inflammatory infiltrate. Chromogenic in situ hybridization (CISH) for EBER was negative in the cutaneous infiltrate. The lung biopsy showed similar immunohistochemical findings but CISH for EBER demonstrated numerous EBV-positive B cells. Overall, this case demonstrates the variability of EBER positivity by CISH in multisystem LYG and underscores that its absence in cutaneous lesions does not exclude LYG from the differential diagnosis. Additionally, this case highlights the fact that cutaneous specimens should not be used in grading LYG by the World Health Organization criteria.