Neuroendocrine tumors (NETs) are epithelial tumors with neuroendocrine differentiation that synthetize or secrete bioactive hormones and monoamines.1 They are an infrequent cause of chronic diarrhea and their diagnosis in young patients is rare.

NETs account for 0.4% of all tumors and 2.5% of gastrointestinal tumors. Sixty-five percent of NETS arise in the gastrointestinal tract and pancreas. A total of 12.9% are found in the colon, of which 70% affect the right-sided colon. Even though they are responsible for less than 1% of cases of chronic diarrhea, it is essential to consider them in the differential diagnosis, after ruling out other more frequent causes.

A 28-year-old man had a past medical history of obsessive-compulsive disorder treated with lamotrigine, vilazodone, and clonazepam, which he decided to suspend 4 months before his initial consultation. He sought medical attention due to 12 months of presenting with Bristol 6–7 stools, abundant and explosive, with a frequency of 4–5 bowel movements per day, many of which were nocturnal, that did not decrease with fasting. He stated having steatorrhea, and no creatorrhea or lientery. He reported the presence of occasional mucus and blood in his stools, tenesmus, and colicky, nonradiating abdominal pain in the mesogastrium of 4/10 intensity, associated with food intake, with relief after bowel movements. Physical examination revealed pain upon superficial and deep palpation of the flank and right iliac fossa and a body mass index of 18. He had previously been seen for those symptoms, undergoing upper gastrointestinal endoscopy, resulting in a diagnosis of irritable bowel syndrome and treatment with antispasmodics, with no improvement.

The patient was now studied for chronic diarrhea, ordering blood and stool tests (Table 1). Esophagogastroduodenoscopy was within normal parameters. The histopathologic study reported non-atrophic congestive gastropathy, with no villous atrophy in the duodenum. Colonoscopy revealed a 30 mm exophytic lesion in the cecum, with an ulcerated surface and friable to manipulation (Fig. 1A). Contrast-enhanced abdominopelvic tomography identified a lesion on the medial and inferior edge of the cecum, with focal thickening measuring 18 mm, necrosis, and paracecal lymph nodes (Fig. 1B and C).

Figure 1.

(A) Colonoscopy showing a 3 cm lesion in the cecum. (B and C) Coronal and axial views of contrast-enhanced CAT scans, showing a lesion at the medial and inferior edge of the cecum, characterized by an 18 mm focal thickening of the wall, with endoluminal extension. (D) Histopathologic section of a grade 2, well differentiated neuroendocrine tumor, showing an epithelial tumor with nest-shaped growth, cells with moderately pleomorphic nuclei, and lax or dense chromatin, as well as mitosis and scant cytoplasm. The tumor is developed in a vascularized stroma and shows infiltration through all the layers of the colon, extending beyond the serosa.

Source: Clinical history of the patient.

The patient then underwent right hemicolectomy with lymph node resection. His preoperative chromogranin A level was 117 ng/mL (NV < 85 ng/mL), and his somatostatin level was 6 ng/mL (NV < 10 ng/mL), which were within normal parameter ranges. The histopathologic study reported a well-differentiated grade 2 neuroendocrine tumor (NET) (pT2, pN1, pM0) with invasion in all layers, extending beyond the serosa, and exhibiting lymphovascular permeation. The tumor was positive for chromogranin +++, synaptophysin +++, and Ki-67 (3–20%), and metastasized to 2/28 lymph nodes (Fig. 1D).

Postoperative controls at 2, 4, and 6 months showed improved bowel movement pattern and mild abdominal pain. Serologic studies 12 months later: chromogranin A 58 ng/mL (NV 85 ng/mL), 5-hydroxyindoleacetic acid (5-HIAA) in urine at 24 h of 2 mg (NV < 2−9 mg/24 h), and Tc-99 m octreotide scintigraphy negative for somatostatin receptors, indicative of remission. Colonoscopy and biopsies of the anastomosis showed no tumor activity. Chronic diarrhea, defined as three or more bowel movements per day with soft stools (Bristol 6–7) for more than 4 weeks, is a frequent cause of gastroenterology consultation and is more common in adults >65 years of age. Its approach requires a detailed anamnesis and the identification of alarm symptoms, to differentiate organic disease and functional disease, and select the patients who warrant an early invasive study. It includes a wide spectrum of conditions, such as tumors, inflammation of the colon or small bowel, malabsorption, and motility disorders, which leads to performing an excessive number of studies. Of the clinical forms, secretory diarrhea is produced by an imbalance between the intestinal absorption and secretion processes, characterized by an increase in fluid and electrolyte secretion from the plasma into the intestinal lumen. It is clinically manifested as abundant liquid stools (>1 liter per day) that persist even during fasting and are predominantly nocturnal.2

In our patient, the presence of alarm symptoms of large volume, continuous, nocturnal stools associated with weight loss, together with elevated fecal calprotectin, guided the approach toward an underlying organic cause.3

NETs of the colon are differentiated from neuroendocrine carcinomas by their degree of aggressiveness. They have an estimated prevalence of 5.2/100,000 persons/year,4 and a mean patient age at diagnosis of 63 years.5 Diagnosis can be delayed 5–7 years, underlining the importance of timely evaluation.6 NETs account for 25% of all gastroenteropancreatic neuroendocrine carcinomas. They are aggressive in the colon, unlike those located in the appendix and rectum, which are more indolent. Their detection is mainly incidental but they are also associated with abdominal pain, rectal bleeding, chronic secretory diarrhea, weight loss and/or anorexia.7 Gastroenteropancreatic NETs have a high metastatic capacity, affecting the liver, lymph nodes, peritoneum, bone, and lung.8 Diagnosis is based on the combination of morphology through endoscopic, imaging, and immunohistochemical studies, due to the presence of serotonin-producing enterochromaffin cells. They are positive for synaptophysin, chromogranin A, and CD56 and should be classified as well-differentiated G1/G2/G3 tumors; when they share non-neuroendocrine histology, they should be classified as poorly differentiated.9 Surgical resection is the treatment of choice whenever feasible.10 Unfortunately, clinical and pathologic characteristics do not always enable patients at a high risk for recurrence or metastasis to be selected. Most of these tumors are detected at advanced stages and have a 5-year survival rate of 71% in stage 1 and 10% in stage IV.11