Challenges in the Diagnosis of Gray Zone Lymphomas

The diagnosis of B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, also called gray zone lymphoma (GZL), is frequently challenging. Incorrect diagnosis as either classic Hodgkin lymphoma or diffuse large B-cell lymphoma has significant implications for choice of upfront therapy based on recent large multi-institutional series from the United States and Europe. These studies have clarified some diagnostic challenges and provided guidance on the spectrum of morphologic features in this entity. This article clarifies some of the diagnostic conundrum surrounding GZL and provides an evidence-based approach to GZL diagnosis using morphology and immunohistochemistry.