The spindle cell variant is a rare presentation of medullary thyroid carcinoma (MTC) that can represent a diagnostic challenge due to the many benign and malignant lesions with similar cytomorphological characteristics. The use of immunocytochemistry (ICC) proved vital for an accurate diagnosis in a case report recently published in Diagnostic Cytopathology.

The case involved a 27-year-old woman with a 3-year history of progressive, painless thyroid swelling with a normal thyroid profile and parathyroid hormone levels. The patients denied diarrhea, flushing, dyspnea, and dysphagia, as well as any relevant family history. 

A thyroid ultrasound revealed a TIRADS 4 heterogeneous nodule in the right lobe. Fine needle aspiration (FNA) of the nodule was performed, and the samples were stained with May-Grünwald Giemsa (MGG) and hematoxylin and eosin (H&E) stains, revealing spindle-shaped tumor cells. The spindle cells had granular chromatin and oval nuclei.

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Currently, there are 14 histological variants of MTC described by the World Health Organization (WHO), with the epithelioid/plasmacytoid presentation being the most frequent. 

Read more about MTC diagnosis

“The cytological interpretation is difficult in rare spindle cell variant of MTC and those cases with the usual MTC where cytological smears show exclusive/prominent spindle cell morphology like the index case,” the authors wrote.

MTC and spindle epithelial tumor with thymus-like differentiation (SETTLE) were regarded as the 2 more likely differential diagnoses. In this context, spindle cell variants of ATC and PTC, Reidel thyroiditis, and nerve sheath tumor were among other diagnostic differentials. 

ICC was performed to reach a definitive diagnosis. Calcitonin, cytokeratin 7, pancytokeratin, and chromogranin were found in the tumor cells. Although pancytokeratin can also be found in SETTLE, the presence of calcitonin and chromatin confirmed the MTC diagnosis. The histopathologic report following total thyroidectomy further confirmed it. 

“The presence of spindle cells in smears from the thyroid FNA is a potential diagnostic pitfall that can be overcome by careful observation of smears and ancillary techniques like immunocytochemistry,” the authors concluded. 


Saini T, Kundu R, Bhujade H. Extensive spindling in medullary thyroid carcinoma posing a diagnostic challenge: a case report. Diagn Cytopathol. Published online July 25, 2022. doi:10.1002/dc.25020