A 61-year-old man with a known history of hypertension and gastroesophageal reflux disease presented to the emergency room with worsening abdominal pain, intractable nausea, and 3 days of vomiting. He was experiencing episodes of nonspecific abdominal pain that would last for 4-5 days every month for the previous year. Over-the-counter medications such as ranitidine and magnesium oxide provided minimum relief. Prior to admission, the patient took 4 tablets of 81-mg aspirin and 9 tablets of 250-mg acetaminophen over 3 days. Review of systems was positive for intermittent constipation, heartburn, and anorexia. He denied use of alcohol and herbal medications or supplements. Vital signs at the time of triage were stable.
Physical examination was significant for scleral icterus, jaundice, and tenderness in the epigastrium and right lower quadrant of the abdomen. Laboratory data revealed a normal white blood cell count and platelet count, with hemoglobin 16.1 g/dL. The liver enzymes were remarkable for total bilirubin 10.6 mg/dL, conjugated bilirubin 7 mg/dL, alanine aminotransferase (ALT) 371 IU/L, aspartate aminotransferase (AST) 252 IU/L, gamma-glutamyl transpeptidase 301 IU/L, and alkaline phosphatase 199 IU/L. Serological tests for viral hepatitis A, hepatitis B, hepatitis C, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, and herpes virus were negative. Acetaminophen, salicylate, and ethanol levels were undetectable. Autoimmune disease was also ruled out by negative immunological assays.
During the course of his admission, his aminotransferases rose gradually, peaking at 512 IU/L AST and 593 IU/L ALT at hospital day 11. Total bilirubin trended down slightly to 7.2 mg/dL. Computed tomography (CT) of the abdomen with contrast performed in the emergency room revealed a 2 cm x 3 cm calcified speculated mass located in the ileocecal valve with associated right lower quadrant mesenteric lymphadenopathy and an unremarkable liver, spleen, and pancreas (Figure 1). Repeat CT of the chest/abdomen/pelvis performed as part of the metastatic work-up at our institute revealed findings similar to the prior CT imaging. Tumor markers carcinoembryonic antigen and alpha-fetoprotein were negative. The patient refused magnetic resonance imaging due to severe claustrophobia. An upper endoscopy revealed a segment of Barrett's esophagus Prague Classification C8M9, with gastroesophageal junction 38 cm from the incisors; biopsies confirmed goblet cell metaplasia consistent with Barrett's esophagus. A colonoscopy revealed evidence of a submucosal mass in the ileocolonic region/terminal ileum, which was obstructing the terminal ileum (Figure 2). The biopsies of the mass were consistent with carcinoid tumor (Figure 3). An octreotide scan revealed focal radiotracer uptake within the partially calcified soft tissue mass that abutted and involved the medial wall of the cecum. There was an additional focus of radiotracer uptake in a soft tissue mass within the mesentery adjacent to the cecal mass, which represented a lymph node. There was a physiologic distribution of radiotracer uptake in the liver but no evidence of metastasis (Figure 4).
The ileocecal mass was surgically resected, along with lymph node dissection. Final surgical pathology revealed a low-grade neuroendocrine tumor (carcinoid), 1.5 cm in the largest dimension, infiltrating through the muscularis propria to the subserosal adipose. Seven of the 12 lymph nodes resected were positive for metastatic carcinoma. The margins of the resection were negative. The appendix was negative for neuroendocrine tumor. Tumor cells were positive for chromogranin, synaptophysin, and pan-cytokeratin (AE1/AE3), and negative for CD56 and TTF-1. Ki-67 labeling index was <=2%. The liver abnormalities without a discernable cause called for a liver biopsy, which showed benign liver parenchyma.
After the surgical resection of the tumor, the liver enzymes trended down and normalized within 2 weeks. The absence of any definite cause of cholestasis in conjunction with immediate downward trending of liver enzymes after resection of the carcinoid suggests a paraneoplastic phenomenon.