A 50-year-old gentleman presented with 4 months of chronic watery, non-bloody diarrhea up to 10 times a day, and weight loss. He had a history of a thymoma first diagnosed 7 years earlier, which was resected with positive histological margins. There was no macroscopic residual disease or vascular invasion. He did not receive any adjuvant treatment and developed recurrent Masaoka-Koga stage IVa thymoma with pleural, pericardial, and lung invasion requiring further treatment with resection, chemotherapy (3 cycles of cisplatin, doxorubicin, and cyclophosphamide), and radiotherapy (54 Gy in 30 fractions). There was no mediastinal lymph node involvement or evidence of distant hematogenous metastasis. Histopathology demonstrated multiple nodules of mixed WHO type B1 and B2, but predominantly type B1 thymoma. His diarrhea commenced after his thymoma recurrence. He did not have any features suggesting other autoimmune diseases associated with thymoma including myasthenia gravis. Physical examination and initial laboratory investigations were unremarkable. Stool cultures were negative for bacterial, viral, and parasitic infections. A computed tomography (CT) scan of the abdomen revealed wall thickening and fat stranding affecting the small intestine and colon (Fig. 1a). Correspondingly, mild patchy erythematous colitis in the rectum and sigmoid colon was seen on colonoscopy (Fig. 1b). Histologically, colonic biopsies showed active colitis with prominent regenerative changes. Goblet cells were noticeably absent, and there was prominent apoptosis, features typical of autoimmune enteropathy (Fig. 1c). Patient serum was incubated with frozen sections of normal small intestinal mucosa, showing strong staining by immunofluorescence for human IgA and IgG with a goblet cell distribution (Fig. 2). A diagnosis of thymoma-associated autoimmune enteropathy was made, and the patient was commenced on a weaning dose of prednisone starting at 25 mg daily leading to resolution of his symptoms. Thymomas are associated with concomitant autoimmune diseases in up to 30% of patients, possibly due to defective immune regulation. Differentials for thymoma-associated autoimmune conditions causing diarrhea include autoimmune enteropathy and Good's syndrome (thymoma-associated hypogammaglobulinemia). Thymoma-associated autoimmune enteropathy is rare with only five reported cases in the literature. Proposed diagnostic criteria include chronic diarrhea lasting over 6 weeks, malabsorption, and abnormal histology of the small bowel (villous blunting, deep crypt lymphocytosis, minimal intraepithelial lymphocytosis, and increased crypt apoptotic bodies). A spectrum of changes can be seen in the colon including increased mononuclear inflammatory infiltrate, active inflammation including neutrophilic cryptitis and microabscesses, intraepithelial lymphocytosis, and increased crypt epithelial apoptosis. Changes of chronicity including crypt architectural distortion and Paneth cell metaplasia have also been described. The presence of anti-enterocyte or anti-goblet antibodies is supportive, but the sensitivity and specificity of these markers are unknown. Steroids are the first-line management for autoimmune enteropathy; however, further immunosuppression (azathioprine, cyclosporin, tacrolimus, or infliximab) may be required in up to 90% of cases. For patients with thymoma-associated autoimmune enteropathy, resection of the thymoma may also improve symptoms.
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May 1, 2024
Kenneth A Kesler + 2
Open Access
