Pitfalls in Lymph Node Fine Needle Aspiration Cytology

<b><i>Background:</i></b> Fine needle aspiration cytology (FNAC) is an accurate, minimally invasive, and cost-effective biopsy method for enlarged lymph nodes. While the role of lymph node FNAC in the diagnosis of infectious or reactive conditions and metastatic malignancy is unquestioned, differing views still exist on its role in the diagnosis of lymphoma. Nevertheless, regardless of the practice setting, pitfalls and potential for error exist, and it is incumbent upon the pathologist to be aware of these pitfalls, as this is the first line of defence against errors. <b><i>Summary:</i></b> This discussion will focus on potential interpretational errors, specifically highlighting scenarios leading to false-negative and false-positive diagnosis and errors in tumour classification, with an emphasis on cytomorphology. Potential entities that may fly below the radar of the pathologist – so-called off-radar entities – are also discussed, as a reminder to consider broad differentials in cases with unusual morphologic features. Some reasons for false-negative diagnoses include low-grade lymphomas that mimic a mixed, polymorphous reactive lymphoid population or aspirates with a paucity of lesional cells, through either sampling error or the intrinsic nature of the entity, e.g., nodular lymphocyte predominant Hodgkin lymphoma. Some of the potential causes of false-positive diagnoses that are discussed include viral-associated lymphadenopathy, Kikuchi-Fujimoto lymphadenitis, or benign adnexal lesions mimicking metastatic malignancy. Errors in tumour classification covered include metastatic carcinoma, sarcoma, melanoma, and lymphoma mimicking each other, and Hodgkin lymphoma and its mimics. Finally, less common entities such as follicular dendritic cell sarcoma and others are briefly mentioned, to remind us of conditions that may slip under our diagnostic radar. <b><i>Key Messages:</i></b> A systematic review of diagnostic pitfalls and traps is elucidated here, with some tips to avoid these traps. The triple approach to the diagnostic workup is emphasised, which includes rigorous clinicopathologic correlation, attention to cytomorphology, and judicious application of ancillary tests.