Diagnostic Utility of T-PIT, PIT-1, and SF-1 in Differentiating Pituitary Neuroendocrine Tumors From Sinonasal and Skull Base Tumors

Pituitary adenoma (pituitary neuroendocrine tumor) can present a diagnostic pitfall when it involves the sinonasal tract ectopically or by direct extension due to morphologic and immunohistochemical overlap with sinonasal small round blue cell tumors. T-box transcription factor (T-PIT), pituitary-specific transcription factor (PIT-1), and steroidogenic factor 1 (SF-1) have emerged as lineage-specific markers for corticotroph, somatotroph, and gonadotroph-type adenomas, respectively, but have not been extensively tested in sinonasal tumors. We examined T-PIT, PIT-1, and SF-1 expression across sinonasal and skull base tumors to assess their specificity in this differential diagnosis. Staining for T-PIT, PIT-1, and SF-1 was performed on tissue microarrays including 199 sinonasal tumors and 12 nonsinonasal head and neck neuroendocrine carcinomas. Whole tissue sections from 20 adenomas, 2 olfactory carcinomas, and 1 Merkel cell carcinoma of nasal skin also underwent staining for all 3 markers, while 9 other sinonasal or skull base tumors underwent staining for T-PIT and PIT-1 only. All 223 sinonasal tumors and neuroendocrine carcinomas of the head and neck were negative for T-PIT and PIT-1. Only 7 of 214 nonpituitary tumors (3.3%) showed SF-1 expression, including 2 of 43 HPV-positive squamous cell carcinomas, 1 of 75 HPV-negative squamous cell carcinomas, 2 of 8 SMARCB1-deficient sinonasal carcinomas, 1 of 4 salivary neuroendocrine carcinomas, and 1 of 5 NUT carcinomas. All pituitary tumors stained as expected. These findings demonstrate that T-PIT and PIT-1 are highly specific for pituitary origin, while SF-1 shows limited off-target expression in certain high-grade sinonasal tumors with chromatin remodeling (e.g., NUT carcinoma and SMARCB1-deficient carcinoma).