When Suspicious Thyroid Cytology Isn't Thyroid Cancer: Multinodular Goiter With Granulomatous Lymphadenopathy

Suspicious thyroid lesions are often evaluated using fine-needle aspiration (FNA) with the Bethesda System for Reporting Thyroid Cytopathology (TBSRCT) to estimate malignancy risk and guide management. Indeterminate findings create a diagnostic gray zone where neither molecular testing nor imaging alone can provide certainty. We report the case of a 57-year-old female with a progressively enlarging right-sided thyroid nodule, classified as Bethesda IV on FNA cytology, with a positive neuroblastoma rat sarcoma viral oncogene homolog (NRAS) mutation on ThyroSeq v3, suggestive of high-risk malignancy. Preoperative imaging also revealed suspicious cervical lymphadenopathy concerning for metastatic disease. Given these findings, the patient underwent a total thyroidectomy. Final pathology demonstrated benign nodular hyperplasia with no evidence of carcinoma, revealing a false-positive molecular result. Notably, excised cervical lymph nodes revealed non-necrotizing granulomas, raising suspicion for sarcoidosis or other granulomatous diseases. Infectious and malignant etiologies were excluded. Subsequent evaluation with chest computed tomography (CT) confirmed pulmonary sarcoidosis, despite a normal serum angiotensin-converting enzyme (ACE) level. This case highlights the diagnostic challenges of evaluating indeterminate thyroid nodules where radiographic, cytologic, and molecular findings may obscure the distinction between granulomatous inflammation and malignancy. This patient's presentation illustrates the importance of maintaining a broad differential diagnosis and using a multimodal approach to optimize clinical management and navigate diagnostic uncertainty.