How do I interpret cytology from skin, lymph node, and effusion samples in practice?

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Skin mass cytology begins with categorizing the tumor as epithelial, mesenchymal, or round cell, which determines malignancy potential and guides subsequent diagnostic and treatment decisions. Fine-needle aspiration and cytologic examination should be a standard component of the diagnostic workup for every skin mass. 6 Lymph node interpretation hinges on cell population uniformity and nuclear size relative to red blood cells. Normal, hyperplastic, and early neoplastic lymph nodes all show a mixed population — predominantly small lymphocytes with variable numbers of medium and large lymphoid cells and some plasma cells. A uniform population indicates neoplasia. Neoplastic lymphoid cells have nuclei at least 1.5 times the diameter of red blood cells, whereas normal mature lymphocytes have nuclei the same size as red blood cells. 1 The threshold for diagnosing lymphoma on cytology is greater than 50% immature cells in the population, though some cytologists require a higher percentage, particularly when only one lymph node is enlarged. Lymphomatous nodes may still contain a significant number of normal lymphoid cells, so the proportion of smaller mature lymphocytes must be compared directly against the larger immature cells to distinguish hyperplasia from neoplasia. When the diagnosis is in doubt, biopsy is indicated — histopathologic confirmation is always required before initiating lymphoma therapy and is necessary for full grading. 1 Large granular lymphocyte (LGL) morphology is a recognized cytologic pattern in lymphoid neoplasia. In confirmed cases, the characteristic finding is multiple large, irregular, magenta cytoplasmic granules clustered in one area of the cytoplasm, present in approximately 80–90% of lymphocytes. Affected small and intermediate lymphocytes may also display cytoplasmic projections described as a hand-mirror appearance. LGLs can be identified not only in lymph node aspirates but also in concurrent effusion fluid and bone marrow aspirates when