Case report
We present a 42 years old man referred to the gastroenterology clinic for more than six months of persistent diarrhea. He reported about 8 to 10 loose bowel movements a day but no reported weight loss with diarrhea. He reported no constitutional symptoms and took no prescription medications. He had tried loperamide over the counter without any benefit. Initial workup negative for fecal leukocyte, ova/parasites, clostridium difficile, Escherichia coli, Shiga toxin, campylobacter, giardia, cryptosporidium, and stool culture. Stool pancreatic elastase and fecal calprotectin were in the reference range.
Additional blood analysis noted no abnormality in complete blood count but had an increase in creatinine to 1.37 and GFR greater than 60 mL/min/1.73 sq meter. Endoscopic gastroduodenoscopy showed prepyloric erosions and grade B erosive esophagitis. A stomach biopsy was negative for helicobacter pylori, and a small bowel biopsy was negative for celiac sprue. Colonoscopy revealed no abnormal findings and random biopsies revealed no evidence of microscopic colitis. Three months later, he noticed a small swelling in his left neck, and computerized tomography (CT) of his neck confirmed bilateral cervical adenopathy extending through the thoracic inlet into the upper mediastinum. A core needle biopsy of the neck lymph node revealed infiltrating nests of malignant cells. The individual tumor cells have enlarged nuclei with a surrounding moderate cytoplasm. Individual cell necrosis was present, along with mitotic figures. The tumor cells were positive for synaptophysin, chromogranin, and TTF1, positive for Ki-67 in 5% of nuclei, and negative for p40 and p16 (Figure 1). The final pathology was determined as an atypical carcinoid tumor. Positron emission tomography (PET) showed bilateral uptake in supraclavicular lymph nodes with a standard value unit (SUV) uptake of 2.9. Additional findings included bilateral upper neck lymph nodes (SUV of 2.2), bilateral lower-level neck lymph nodes (SUV of 3) bilateral upper mediastinal adenopathy (4.2 SUV) and pre-tracheal adenopathy (3.4 SUV). Focal area of increased uptake in left ischium/acetabulum (SUV 2.9) (Figure 2).
Further workup included a serotonin level of 83 (56-244 ng/mL), chromogranin A 392 (less than 311 NG/mL), and a 24-hour urinary 5-HIAA of 3.6 (less than 6.0 mg/24h). Serum cortisol, gastrin, plasma metanephrines, and vasoactive intestinal peptide levels were within the reference range. He started subcutaneous octreotide injection but noted no change in his diarrhea rather started noticing frequent night sweats and weight loss. Follow up Gallium 68 Dotatate PET scan showed persistent multiple dotatate avid bilateral cervical nodes, upper mediastinal conglomerate nodes at bilateral paratracheal/thoracic inlet regions, and several osseous lesions consistent with the metastatic neuroendocrine disease. Since his clinical presentation was atypical for carcinoid syndrome, we further investigated with a CEA level and calcitonin. Both CEA and calcitonin were elevated to 236 (<2.5 ng/mL) and 6400 (<10 pg/mL), respectively, raising the concern for medullary thyroid cancer, although no evidence of thyroid nodule was noted in the PET scans. Ultrasound thyroid revealed a suspicious small left thyroid nodule and bilateral cervical lymph nodes. A repeat biopsy of the left lymph node and immunohistochemical analysis confirmed patchy positivity of calcitonin in the tumor cells, thereby confirming metastatic medullary thyroid carcinoma. He was seen at a tertiary care cancer clinic and eventually was enrolled in a clinical trial to receive a RET-directed targeted therapy. His diarrhea and diaphoresis significantly improved in one week after starting therapy.