Nadeen Hussain, MD1, Saad Saffo, MD1, Katherine Gielissen, MD, MHS-Med Ed1, Kenneth H. Hung, MD, MS2; 1Yale University, School of Medicine, New Haven, CT; 2Yale School of Medicine, New Haven, CT
Introduction: Paraneoplastic syndromes are an exceedingly rare cause of chronic diarrhea. Thymomas have been associated with two known paraneoplastic diarrheal syndromes, namely in the context of hypogammaglobulinemia (Good’s syndrome) or a graft-versus-host disease (GVHD)-like condition. However, exocrine pancreatic insufficiency has yet to be reported as a cause of diarrhea in patients with thymoma.
Methods: A 36-year-old woman with no known medical morbidities presented with postprandial watery diarrhea, emesis, and 100-lb unintentional weight loss over two years. Labs were notable for lymphocytosis up to 8,100/mL with normal flow cytometry and no abnormalities on blood smear. Celiac disease serologies and stool infectious studies were negative. Immunoglobulin G levels were elevated at 3,010 mg/dL, and stool pancreatic elastase levels were low (< 15 mg/g). Additional labs were consistent with fat soluble vitamin deficiency: vitamin A < 5 mcg/dL, 25-hydroxyvitamin D < 4 ng/dL, vitamin E 7 mg/L, vitamin K 69 pg/mL. Computed tomography (CT) of the chest revealed an 11-cm anterior mediastinal mass with pleural and nodal metastases, and biopsy was suggestive of malignant thymoma (Figure 1). CT of the abdomen revealed a normal-appearing pancreas. Subsequent endoscopy and colonoscopy showed healthy-appearing mucosa with no abnormalities (Figure 2). However, colonic biopsies were notable for mild diffuse inflammatory changes including scattered intraepithelial lymphocytes and neutrophils, increased apoptotic bodies, and crypt architectural distortion. Her diarrhea ultimately improved after four cycles of induction chemotherapy. Discussion: GVHD-like colitis in patients with malignant thymoma has been reported in several instances. This has been attributed to alterations in the thymic microenvironment, which lead to dysregulation and loss of anergy. Autoreactive T-cells can mount an immune response that impacts a number of organs, especially in the gastrointestinal tract. Although our patient had histopathological changes reflective of colitis secondary to GVHD, the severity of her diarrhea was out-of-proportion to these findings. The postprandial nature of her symptoms and markedly low stool pancreatic elastase were suggestive of possible pancreatic insufficiency, likely secondary to an autoimmune phenomenon impacting the exocrine glands of the pancreas. This case proposes a possible novel paraneoplastic mechanism for diarrhea in patients with thymoma.
Cross-section image of anterior mediastinal mass
Normal-appearing duodenal mucosa
Disclosures: Nadeen Hussain indicated no relevant financial relationships. Saad Saffo indicated no relevant financial relationships. Katherine Gielissen indicated no relevant financial relationships. Kenneth Hung indicated no relevant financial relationships.