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A 48-year-old man presented for a second opinion after being diagnosed with a cancer of unknown primary with fluorodeoxyglucose positron emission tomography−negative lesions in his right thyroid lobe, liver, and sacrum. Prior biopsies of the thyroid and sacrum, as well as laboratory analyses, including alpha fetoprotein, had failed to yield a definitive diagnosis. A fine-needle aspiration of the thyroid lesion had produced a morphological description consistent with plasma cells, but was not followed up with appropriate immunohistochemistry or flow cytometry. Treatment with bevacizumab/atezolizumab for an assumed hepatocellular carcinoma was unsuccessful. A repeat fine-needle aspiration of the thyroid lesion (panel A, magnetic resonance imaging, enhanced T1) confirmed the presence of small, occasionally granulated cells with an eccentric nucleus and light blue cytoplasm consistent with plasma cells (panels B-C: aspirate smear, Pappenheim stain, magnification ×1000). Flow cytometry detected 61.5% plasma cells that expressed CD45, CD38, and CD138 and showed lambda light chain restriction, while being negative for CD19 (panel D). A bone marrow biopsy revealed no involvement. Paraproteinemia was absent on electrophoresis and immunofixation.

Thyroid involvement in multiple myeloma is extremely rare, especially at the time of primary diagnosis. This case highlights the necessity of cytomorphology-guided diagnostics and the usefulness of flow cytometry on fine-needle aspirates.

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