Abstract

To the Editor:

Chronic diarrhea is a common gastrointestinal (GI) complaint with an overall prevalence of 3–5% in the United States. Common causes include irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, malabsorption syndromes, chronic infections, and medications. The laboratory tools available for evaluation are often expensive and invasive. As such, the diagnostic evaluation must be rationally directed by a careful history and physical examination.¹

A 66-year-old male presented to our hospital with recurrent episodes of profuse, nonbloody, watery stools of 6 months' duration. The patient denied any consumption of unpasteurized dairy products/undercooked meat or seafood. He denied any travel history, antibiotics/NSAID use, or exposure to sick contacts. There was a history of significant weight loss of 30 pounds during this time period. His other medical problems included coronary artery disease, hypertension, chronic obstructive pulmonary disease (COPD), and gastroesophageal reflux disease (GERD). There was no change in his medication antecedent to the onset of diarrhea. Physical examination was unremarkable with no evidence of dehydration, lymphadenopathy, cardiac murmurs, wheeze, abdominal tenderness, or organomegaly.

His labs showed normal basal metabolic profile and cell counts. Serum thyroid stimulating hormone and tissue transglutaminase antibody were within normal limits. Stool studies were negative for infectious etiology, including Clostridium difficile and the stool osmolar gap was within normal limits. Colonoscopy revealed normal colonic mucosa and random colonic biopsies were obtained to rule out microscopic colitis. Colonic biopsy revealed atypical lymphoid infiltrate comprised mostly of expanded mantle zones and a few areas of identifiable residual germinal centers consistent with mantle cell lymphoma. A majority of the lymphoid infiltrate was positive for CD20, bcl-2, CD5, and cyclin D1. Flow cytometry showed clonal proliferation of B-cells consistent with the diagnosis of mantle cell lymphoma. Thus, the patient was diagnosed with mantle cell lymphoma involving the colon. Imaging study of the thorax, abdomen, and pelvis did not show any lymphadenopathy or organomegaly. A positron emission tomography scan revealed multiple metabolically active lymph nodes in the axillary, external iliac, and inguinal regions. The patient was initiated on chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab with resolution of his diarrhea and steady weight gain over the next few months.

Primary gastrointestinal lymphomas are rare conditions. Mantle cell lymphoma (MCL) comprises about 7 percent of adult non-Hodgkin lymphomas, and the GI tract is involved in about 20% of cases. It is characterized by a monotonous proliferation of small- to medium-sized lymphocytes with co- expression of CD5, CD20, and Cyclin D1. Median age at diagnosis is 68 years. Colon and rectum were affected in about 90% of GI lymphomas, followed by the small bowel (69%), stomach (57%), and duodenum, (52%).²

Mantle cell lymphomas (MCLs) behave as aggressive neoplasms. The most frequent endoscopic finding is multiple lymphomatous polyposes. It is characterized by multiple polypoid lesions involving long segments of the gastrointestinal tract. Abdominal pain, diarrhea, hematochezia, and palpable mass are the most common presenting manifestations of MCL. The prognosis is poor, with a mean survival time of less than three years. Response to chemotherapy is seen in up to half of the patients.³ Cyclophosphamide, doxorubicin, and prednisolone and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) are used as conventional chemotherapies for MCL.⁴ Infiltrating lymphoma cells express CD20 molecules on their surfaces. Using this as the cellular target, rituximab (a chimeric monoclonal antibody to CD20) is now used in chemotherapy regimens. Single agent rituximab has produced response rates of about 30%, and, when combined with CHOP, response rates increase to above 90%.⁵

Of interest, our patient presented with chronic diarrhea and weight loss, and colonoscopy did not reveal any polypoid lesions. The underlying malignancy was diagnosed by histopathological analysis of random biopsies of normal-appearing colon. A combination chemotherapy with CHOP-rituximab resulted in complete resolution of his diarrhea, along with steady weight gain over the next four months.