Primary secretory carcinoma of thyroid with unusual features mimicking metastasis?

Secretory Carcinoma (SC) of the thyroid is a relatively new and often misdiagnosed cancer. Like SC of the breast and salivary gland, it is characteristically diffusely positive for S100 and Mammaglobin by immunohistochemical (IHC) staining. Case report. A 63-year-old female presented with neck swelling and difficulty breathing. CT scan showed a large thyroid mass. Tracheal compression and deviation required stent placement and urgent radiation. Microscopic analysis showed neoplastic cells with frequent intracytoplasmic globules, including signet-ring cells. IHC stains were inconclusive to tumor type and metastasis from an occult primary was considered. However, PET-CT scan, mammography, and upper endoscopy were negative. Next-generation sequencing was performed revealing an ETV6-NTRK3 fusion favoring SC of the thyroid. SC of the thyroid with unusual histomorphology and IHC staining may be overlooked and can mimic a metastasis. Given that a correct diagnosis critically affects prognosis and treatment, pitfalls can be avoided by utilizing molecular testing in complicated cases.