Diagnostic dilemmas of hyalinizing trabecular tumours on fine needle aspiration cytology: a study of seven cases with BRAF mutation analysis

Objective: Hyalinizing trabecular tumours (HTTs) are rare follicular-derived neoplasms that behave in an almost benign manner. HTT is frequently misdiagnosed as papillary carcinoma by fine needle aspiration (FNA) cytology or as papillary or medullary carcinoma on surgical resection. Methods: The authors examined FNA material from seven cases of histologically verified HTT. Cytological findings were reviewed and correlated with ultrasonographic and histological features. In addition, MIB-1 and calcitonin immunostaining was performed on surgical specimens, and BRAF mutation analysis on three pre-operative FNA specimens and seven histology specimens. Results: The original cytological diagnosis was either suspicious or positive for papillary carcinoma in all patients. The FNA-based differential diagnoses included HTT, papillary carcinoma or, less likely, medullary carcinoma in two patients. Aspirates showed oval to spindle-shaped cells with frequent intranuclear inclusions, isolated in loosely cohesive groups with a trabecular or syncytial pattern in a bloody background. Radiating arrangements of tumour cells surrounding hyaline stroma with serrated calcifications and a lack of papillary or sheet-like fragments may suggest HTT on FNA. Spherical calcified bodies and possible psammoma bodies were frequently found in three cases. Retrospectively, six of the seven cases showed membranous immunoreactivity for MIB-1, but none of the seven possessed the BRAF (V600E) mutation or showed calcitonin reactivity. Conclusions: Although the recognition of HTT on FNA cytology is difficult, because of its morphological similarities to papillary and medullary carcinoma, its characteristic cytological features along with ultrasonographic findings may suggest the diagnosis preoperatively and avoid surgical over-treatment.