Not All That Is at the Terminal Ileum is Crohn’s Disease: Case of Hereditary Paraganglioma-Pheochromocytoma Syndrome With Metastatic Ileal Neuroendocrine Tumor

Background: Crohn’s disease (CD) is a systemic inflammatory disorder with predisposition for involving the terminal ileum (TI) and cecum. The differential diagnosis for TI and cecal inflammation is broad. The following case describes a female with diarrhea who was found to have TI inflammation on cross-sectional imaging and referred to the inflammatory bowel disease (IBD) center for CD. Further evaluation revealed a diagnosis of metastatic ileal neuroendocrine tumor in the setting of hereditary paraganglioma-pheochromocytoma syndrome. Case: A 65-year-old female with a medical history significant for fibromyalgia, hyperthyroidism, and recurrent small bowel obstruction presented to the IBD center for evaluation of CD treatment following recent hospitalization for abdominal pain and worsening diarrhea. At the time of hospitalization, a non-contrast enhanced computed tomography (CT) had revealed TI and cecal inflammation with an associated hepatic abscess. As such, a tentative diagnosis of CD had been made. Outside colonoscopy 6 months prior had been unremarkable, however the TI had not been intubated. During her IBD clinic appointment, the patient noted 1 year of intermittent abdominal pain, diarrhea, and urgency, with 3-6 non-bloody bowel movements daily. She also endorsed a 30lb unintentional weight loss over the same period. CT enterography noted cecal and ascending colonic wall thickening, with a 2.0 × 1.8cm enhancing lesion at the TI concerning for neoplasm. Additionally, two hepatic lesions measuring 7.4 × 5.8cm and 1.6 × 1.1cm were noted in the left and right hepatic lobes respectively. Repeat colonoscopy at our institution demonstrated edematous and inflamed cecal mucosa with deformity of the ileocecal valve, precluding TI intubation. Given the high concern for neoplasm, the patient underwent PET/CT imaging, noting (a) 2.3cm mass at the TI associated with adjacent lymph node enlargement, (b) two previously described hepatic masses, (c) a 4.0 × 2.7cm right carotid body mass, (d) numerous sub-centimeter thyroid nodules, (e) 1.5cm pancreatic mass with additional punctate lesions, and (f) a sub-centimeter vertebral lesion. Subsequent liver biopsy noted metastatic well-differentiated neuroendocrine tumor (Ki-67: 1.4%), with thyroid biopsy noting medullary thyroid cancer. Given findings, a referral was made to medical genetics and oncology. Testing indicated a pathologic germline mutation in the SDHB gene (c.146del), with her presentation consistent with hereditary paraganglioma-pheochromocytoma syndrome manifesting as (a) right carotid body paraganglioma, (b) medullary thyroid cancer, and (c) grade 1 ileal neuroendocrine tumor with metastasis to the liver, pancreas, and bone. Following exclusion of pheochromocytoma, the patient underwent left hepatectomy and right colectomy with future thyroid resection planned. Close monitoring of tumors ensues, with annual urinary metanephrine testing and biennial cross-sectional imaging to detect recurrence or new tumors. Conclusions: CD often presents in adults with diarrheal illness, however the differential for TI and cecal inflammation must remain broad. Herein our patient presented to the IBD center for treatment of CD, later to be diagnosed with metastatic ileal neuroendocrine tumor in the setting of hereditary paraganglioma-pheochromocytoma syndrome. With an estimated prevalence of approximately 1 in 1,000,000, the current case represents an exceedingly rare condition and interesting educational opportunity.