Serotonin Elevation in a Patient With Metastatic Pancreatic Adenocarcinoma

Abstract

We report a rare case of pancreatic ductal adenocarcinoma (PDAC) presenting as chronic diarrhea with serotonin elevation. PDAC is often diagnosed at an advanced stage and commonly presents with weight loss, abdominal pain, and jaundice. While PDAC can disrupt exocrine function and cause diarrhea and steatorrhea, diarrhea associated with hormone production is more typical of pancreatic neuroendocrine tumors. A 79-year-old woman with breast and endometrial cancer status post right mastectomy and total hysterectomy presented with persistent diarrhea. Prior to admission, the patient was in New Zealand and Australia when she noticed more fatigue and coughing. She took clindamycin and afterwards had up to 10 watery, non-bloody bowel movements per day. The patient was treated with loperamide and then metronidazole, for presumed Clostridium difficile infection. After no improvement, the patient presented to our institution without fever, abdominal pain, nausea, or vomiting. Gastrointestinal pathogen PCR, C. difficile, ova and parasites were sent and returned negative. Abdominal computed tomography (CT) revealed a pancreatic body/tail lesion with pancreatic ductal dilatation and hepatic lesions. Additional labs were sent for secretory tumor, pancreatic insufficiency, and pancreatic cancer. These revealed elevated CA-19-9 (44 U/mL), chromogranin A (49380 ng/mL), serum serotonin (1560 ng/mL), 24-hour urine 5-hydroxyindoleacetic acid (122 mg/day), carcinoembryonic antigen (10.3 ng/mL), alpha-fetoprotein (13.6 ng/mL), calcitonin (1492 pg/mL); normal vasoactive intestinal peptide (< 13 pg/mL); and decreased fecal pancreatic elastase (21 ug/g). The patient underwent EUS with fine needle biopsy of the pancreas and liver lesions with pathology showing high-grade PDAC. Patient was started on octreotide for diarrhea, but transitioned to pancrelipase for pancreatic insufficiency with mild improvement. Patient deferred systemic chemotherapy treatment. While impaired exocrine activity is well documented with PDAC, direct endocrine activity is very rare and poorly understood. PDAC can be associated with disseminated neuroendocrine cells, which may be missed on biopsy but identified by immunohistochemistry. The persistent diarrhea in our patient may have been due to loss of ability to secrete fat-digesting enzymes, but the highly elevated serotonin and chromogranin A suggest neuroendocrine involvement. Future studies are needed to identify the role of neuroendocrine cells in PDAC.Figure. 3: 6 x 3.0 cm lesion in the pancreatic body/tail with numerous hepatic lesions.Figure: Typical morphology of pancreatic adenocarcinoma with focal gland formation and desmoplastic stroma.Figure: Area of solid tumor growth with necrosis.