MON-029 Poorly Differentiated Neuroendocrine Carcinoma of Unknown Primary Origin

Abstract Disclosure: M. Nassiri: None. A. Telesford: None. V. Geslani: None. Introduction: Neuroendocrine neoplasms (NEN) are abnormal growths of cells originating from the endocrine and nervous systems. Most arise sporadically and there is no established genetic link to their formation, though rare inherited conditions can increase the risk of developing NENs. Identifying the primary site of a NEN and assessing its stage and differentiation assists in determining treatment options and prognostication. However, this is not always possible as 10-14% of all NENs arise from unknown primary sites, posing challenges in diagnosis and treatment. In this report, we discuss a unique case of NEN of unknown primary origin.Case Presentation: A female in her 30s with a medical history of type 2 diabetes mellitus, hypertension, obesity, hypothyroidism, and amenorrhea presented with lower abdominal pain and was noted to have a non-mobile, firm, and severely tender cervix. Pap smear was normal 1 year prior. An endocervical curettage with biopsies showed atypical cells and necrotic tissue. CT imaging revealed a 2.8x2.1 cm uterine mass with bilateral adnexal masses up to 3.6 cm. Gyn Oncology diagnosed the patient with an advanced metastatic disease process with local spread into the anterior vaginal wall. Based on rapid spread, working diagnosis was an atypical Neuroendocrine or Gastrointestinal type tumor. Further imaging showed bulky pelvic and retroperitoneal adenopathy and scattered pulmonary nodules. A retroperitoneal lymph node biopsy showed a poorly differentiated carcinoma with neuroendocrine features. Immunohistology stains were positive for AE1/AE3, CK7, synaptophysin, partial chromogranin, focal p16 and CDX2, with increased nuclear Ki-67 staining. The origin of the primary tumor could not be determined. The patient was started on platinum-based chemotherapy but unfortunately succumbed to her illness and passed away.Discussion: NENs of unknown primary origin (NEN-UPO) comprise approximately 10-14% of all NEN, most presenting with metastatic disease. Our patient had poorly differentiated carcinoma with neuroendocrine features, however, the immunohistochemical and special stains were inconclusive regarding the origin of the tumor. Since there are no standard treatment guidelines for NEN-UPO, therapies are largely determined on tumor characteristics and disease burden. Poorly differentiated neuroendocrine tumors share fundamental features with small cell carcinoma due to their aggressive, rapidly dividing cells, that present at an advanced stage. Since small-cell carcinomas respond well to platinum-based chemotherapies, similar therapies can be initiated from some NEN-UPO patients. Unfortunately, many of these tumors are biologically aggressive and prognosis can be poor. Presentation: Monday, July 14, 2025