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.