Unusual Keratin Immunoprofile in a Rare Primary Pancreatic Ewing Sarcoma

Abstract

Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor is part of the small round blue cell tumors primarily occurring in bone and soft tissue, although rare cases in solid organs do exist. Diagnosis remains a challenge often requiring confirmation of a genetic translocation, as histopathology may be positive for a wide array of tumor markers sometimes causing misdiagnosis. We present an 11 year old female with primary pancreatic EWS/PNET, and an unusually broad cytokeratin profile. Our patient with no past medical or family history presented with abdominal pain, fatigue, and jaundice for 2 weeks. Physical exam noted jaundice, icterus, and a palpable non-tender RUQ mass. Labs showed normocytic anemia with elevated reticulocyte count, and LFTs indicative of an obstructive pattern. MRI confirmed a 7.4 x 6.2 x 4.8 cm mass centered within the pancreatic head/ampullary region, and invasion with tumor thrombus in the main portal vein. Endoscopy revealed a large antral impression from the tumor, with friable mucosa and active oozing in the duodenum. EUS displayed a pancreatic head mass abutting the common hepatic artery with invasion into the portal vein and a 22mm common bile duct. Biopsies were obtained from the friable duodenal tissue, with biliary stent placed for decompression. Duodenal biopsy showed a small round blue cell tumor with very scant cytoplasm, round hyperchromatic nuclei, finely dispersed chromatin and inconspicuous nucleoli embedded in a markedly desmoplastic fibrous stroma. Similar cells were seen from a pancreatic head mass FNA. Tumor cells were CD99 (MIC2) positive in a diffuse cytoplasmic pattern only. Immunohistochemistry had broad keratin positivity including cytokeratin CAM 5.2, cytokeratin AE1/AE3, cytokeratin 5/6, and cytokeratin 34BE12. P63, E-cadherin and CD117 (c-Kit) were also positive. FISH study and RT-PCR were positive for EWSR1-FLI1 fusion transcript and confirmed a EWS/ PNET, with a broad cytokeratin profile, primary to the pancreas. This is the first case of pancreatic PNET with immunohistochemistry showing such diffuse positivity in cytokeratin markers, and the 28th case of primary pancreatic PNET reported in the literature. CD99 is usually positive in membranous staining, however this case showed diffuse cytoplasmic positivity only, making the diagnosis challenging. This new pattern could reflect potential markers for prognostic studies or new targets for therapy.Figure: Keratin Cam 5.2 (20X): Positive in small round tumor cells.Figure. CD117: (20X): Positive in small round tumor cells.