Jejunal Mixed Adenoneuroendocrine Carcinoma (MANEC) With a Novel PTPRK-RSPO3 Fusion Initially Presenting as a Large Ovarian Mass: Diagnostic Challenges and Poor Prognosis.

BACKGROUND/AIM: Jejunal mixed adenoneuroendocrine carcinomas (MANECs) are rare but aggressive tumors. We report such a case initially present as a large ovarian mass with a novel gene fusion. CASE REPORT: A 51-year-old female presented with multiple episodes of abdominal pain. Computed tomography (CT) scan showed a 16.1 cm right ovarian mass. Surgery was performed and intraoperative frozen sections of the ovarian mass showed adenocarcinoma. Further histopathologic evaluation of the ovarian tumor demonstrated intestinal type of adenocarcinoma with CDX2 and SATB2 immunoreactivities, suggestive of metastatic colorectal adenocarcinoma. Colonoscopy and upper gastrointestinal (GI) endoscopy failed to identify the GI primary lesion. The patient subsequently received chemotherapy and later developed small bowel obstruction and perforation. Pathology assessment of the small bowel revealed a perforation associated jejunal MANEC with 45% of large cell type of neuroendocrine carcinoma with diffuse immunoreactivity of synaptophysin and chromogranin, and 55% of intestinal type of adenocarcinoma with mucin-producing features and negative for neuroendocrine markers. The Jejunal tumor showed similar histology and immunoprofile of the prior ovarian tumor. The next generation sequencing (NGS) of the jejunal tumor identified a novel mutation involving protein tyrosine phosphatase receptor type K and R-spondin 3 (PTPRK-RSPO3) fusion. The patient underwent palliative chemotherapy and expired in seven months. CONCLUSION: This is the first documented case of jejunal MANEC with novel PTPRK-RSPO3 fusion initially presenting as ovarian metastasis with diagnostic and therapeutic challenges. The aggressive high-grade MANEC likely contributed to disease progression despite therapy.