A unique presentation of multiple synchronous tumors in a patient with POT1 tumor predisposition syndrome

POT1 (Protection of Telomeres 1) is a gene on chromosome 7 that is essential for telomere stability. Germline mutations in POT1 are well recognized for conferring a lifelong risk of various malignancies. We present a 63-year-old female who developed a sudden cough and was found to have a large adrenal mass abutting adjacent organs, along with an incidental pancreatic lesion. Her medical history was significant for renal cancer, uterine carcinosarcoma, pituitary adenoma, and chronic lymphocytic leukemia (CLL). Next-generation sequencing identified a pathogenic germline mutation in POT1 (c.854_855del (p.Val285Glyfs*27)). Microscopically, the adrenal mass showed tumor cells arranged in sheets and nests with high-grade nuclei and abundant cytoplasm. Immunohistochemistry (IHC) study showed diffuse AE1/AE3 positivity but was negative for markers of other metastatic carcinomas or melanoma. Given the unusual immunoprofile and clinical history, SF-1 was performed and was diffusely positive, confirming the diagnosis of adrenal cortical carcinoma. The pancreatic lesion was composed of well-formed nests of tumor cells with speckled chromatin in a background of lymphocyte aggregates. Synaptophysin was positive in the tumor nests, and the lymphoid component was positive for CD5, CD23, and CD20, while negative for CD3. The findings supported a diagnosis of a well-differentiated neuroendocrine tumor involved by small cell lymphoma. Retrospectively, similar lymphoma cells were also identified in the adrenal mass. Overall, this is the first case report describing a unique malignancy profile in patient with POT1 tumor predisposition syndrome, highlighting the diagnostic challenge posed by diffuse cytokeratin positivity in adrenal cortical carcinoma.