Expression of FOXI1 and POU2F3 varies among different salivary gland neoplasms and is higher in Warthin tumor.

PURPOSE: Salivary gland tumors are histologically diverse. Ionocytes and tuft cells, rare epithelial cells found in normal salivary glands, might be associated with salivary tumors. Here, we explored the expression of FOXI1 and POU2F3, master regulators of ionocytes and tuft cells, respectively, for common salivary neoplasms using immunohistochemistry. METHODS: We analyzed normal salivary tissues and nine salivary gland tumors; Warthin tumors (WT), pleomorphic adenomas (PA), basal cell adenomas, and oncocytomas were benign, whereas mucoepidermoid, adenoid cystic, acinic cell, salivary duct carcinomas, and polymorphous adenocarcinomas were malignant. RESULTS: Normal salivary glands contained a few FOXI1- and POU2F3-positive cells in the ducts instead of the acini, consistent with ionocytes and tuft cells, respectively. Among the benign tumors, only WTs and PAs consistently expressed FOXI1 (10/10 and 9/10, respectively). The median H-score of WTs was significantly higher than that of PAs (17.5 vs. 4, P = 0.01). While WTs and PAs harbored POU2F3-positive cells (10/10 and 9/10, respectively), the median H-score was higher in WTs than in PAs (10.5 vs 4, respectively). Furthermore, WTs exhibited a unique staining pattern of FOXI1- and POU2F3-positive cells, which were present in luminal and abluminal locations, respectively. Whereas none of the malignant tumors expressed FOXI1, only adenoid cystic carcinoma consistently expressed POU2F3 (5/5), with a median H-score of 4. CONCLUSION: The expression patterns of the characteristic transcription factors found in ionocytes and tuft cells vary among salivary gland tumor types and are higher in WT, which might be relevant for understanding and diagnosing salivary gland neoplasms.

The association of ectopic craniopharyngioma in the fourth ventricle with familial adenomatous polyposis: illustrative case.

BACKGROUND: Craniopharyngioma (CP) often arises in the sellar and suprasellar areas; ectopic CP in the posterior fossa is rare. Familial adenomatous polyposis (FAP) is a genetic disorder involving the formation of numerous adenomatous polyps in the gastrointestinal tract, and it is associated with other extraintestinal manifestations. OBSERVATIONS: The authors reported the case of a 63-year-old woman with FAP who presented with headache and harbored a growing mass in the fourth ventricle. Magnetic resonance imaging (MRI) findings revealed a well-circumscribed mass with high intensity on T1-weighted images and low intensity on T2-weighted images and exhibited no contrast enhancement. Gross total resection was performed and histopathology revealed an adamantinomatous CP (aCP). The authors also reviewed the previous reports of ectopic CP in the posterior fossa and found a high percentage of FAP cases among the ectopic CP group, thus suggesting a possible association between the two diseases. LESSONS: An ectopic CP may be reasonably included in the differential diagnosis in patients with FAP who present with well-circumscribed tumors in the posterior fossa.

POU2F3 beyond thymic carcinomas: expression across the spectrum of thymomas hints to medullary differentiation in type A thymoma.

The thymic medulla comprises various cell types, including tuft cells that are involved in innate immunity. We recently reported that in Western cohorts of patients, most thymic squamous cell carcinomas (TSQCCs), in contrast to thymomas, exhibit strong and extensive expression of tuft cell markers, including the tuft cell master regulator, POU2F3. On closer inspection of 94 thymomas that cover the full spectrum of thymoma histotypes, we now find by immunohistochemistry that approximately half of types A, AB, and B1 thymomas contain small numbers (< 10%) of cells expressing POU2F3, while most types B2 and B3 thymomas do not (p < 0.05). Further, in rarer types A and AB thymomas with adenoid growth pattern, POU2F3( +) cells formed aggregates and co-expressed KIT, as did the tumor cells in 100% (9/9) of TSQCCs expressing POU2F3. However, the expression of another tuft cell marker, L1CAM, still distinguished TSQCC from the spectrum of thymomas that were all L1CAM-negative. This study is the first to demonstrate the high frequency of POU2F3 expression in an Asian cohort of TSQCCs. The common occurrence of scattered POU2F3( +) cells in types A and AB thymomas hints at their variable degree of medullary differentiation and supports the historical hypothesis of the medullary nature of type A thymomas. Immunohistochemistry of L1CAM may be a valuable tool to differentiate TSQCCs from thymomas.