Fine needle sampling is a fast, safe, and potentially cost-effective method of obtaining tissue for cytomorphologic assessment aimed at both initial triage and, in some cases, complete diagnosis of patients that present clinically with lymphadenopathy. The cytologic diagnosis of B-cell non-Hodgkin lymphomas composed of small-/intermediate-sized cells, however, has been seen as an area of great difficulty even for experienced observers due to the morphologic overlap between lymphoma and reactive lymphadenopathies as well as between the lymphoma entities themselves. Although ancillary testing has improved diagnostic accuracy, the results from these tests must be interpreted within the morphological and clinical context to avoid misinterpretation. Importantly, the recognition of specific cytologic features is crucial in guiding the appropriate selection of ancillary tests which will either confirm or refute a tentative diagnosis. For these reasons, we here review the cytologic characteristics particular to five common B-cell non-Hodgkin lymphomas which typically cause the most diagnostic confusion based on cytological assessment alone: marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and lymphoplasmacytic lymphoma. We summarize the most pertinent cytomorphologic features for each entity as well as for reactive lymphoid hyperplasia, contrast them with each other to facilitate their recognition, and highlight common diagnostic pitfalls. 1. Introduction Over the past 25 years, a large number of articles have been published and significant academic discourse has occurred, and continues to occur, around the usefulness and role of cytopathology in the diagnosis of lymphoma [1–3]. Sophisticated ancillary techniques have changed the landscape considerably and now play a major role in the diagnosis of lymphoproliferative disorders. We decided therefore to revisit the cytologic diagnosis of the five most common B-cell non-Hodgkin lymphomas (NHL) with small-/intermediate-sized cells with a renewed focus on morphology itself. In the following article, we will focus on cytologic samples obtained from lymph nodes by the use of small caliber needles, that is, fine-needle sampling/aspiration. We will not discuss the specifics of other specimen types such as samples of body cavity effusions or cerebrospinal fluid. The primary and most significant role of fine-needle sampling in undiagnosed lymphadenopathy is to triage the patient appropriately for further management which may include subsequent
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