Duodenal Villous Blunting: Hint for Underlying Malignancy

Abstract

Introduction: The characteristic changes found during small intestinal remodeling in celiac disease include inflammatory villous blunting or atrophy. Villous blunting with sero-negativity for celiac disease is a diagnostic and therapeutic challenge. Case Description: 66 years old woman was referred to our clinic for the evaluation of chronic diarrhea, unintentional weight loss and malabsorption. She had a history of vitamin B12 deficiency, peripheral neuropathy and frequent falls leading to subdural hematomas. She had tried gluten free diet for a few months without improvement. Laboratory investigations including CBC, CMP, lipase, albumin, Iron, Folate, prothrombin time, vitamin B1, B6, B12 and D were within normal limits. Work up of celiac disease including IgA and IgG Tissue transglutaminase and gliadin peptide were negative. Her intrinsic factor blocking antibody was negative. Biopsies of the duodenal mucosa revealed focal chronic inflammation with villous blunting (Figure 1) which was not pathognomonic for Celiac disease. She was found to be HQ2/HQ8 negative. Magnetic Resonance Enterography (MRE) showed a right ovarian cystic carcinoma with metastatic lymphadenopathy without any bowel inflammation.She was treated by bilateral salphingo- oophorectomy and total hysterectomy, followed by chemotherapy. Discussion: Villous atrophy of the small intestine mucosa occurs most commonly in Celiac disease.The histological changes in celiac disease are best defined by the Modified Marsh classification (Table-1). Villous atrophy (VA) associated with malignancy is infrequently seen and reported. Creamer et al have reported 6 cases of extra intestinal solid malignancies causing villous atrophy. Local tumor infiltration with CD4+ cells and increased production of Th1 cytokines and interferon gamma leads to oligoclonal expansion of CD4+ helper T cells as an antitumor response. Tumor specific T cells can be found to circulate in 50 % of patients with ovarian carcinoma. The small intestine can be affected by this activation of CD4+ T helper 1 cells leading to intraepithelial lymphocytosis (lymphocytic duodenosis) and features of villous atrophy and crypt hyperplasia without gluten hypersensitivity. Conclusion: Villous atrophy without celiac disease can occur in underlying extra intestinal malignancies like ovarian cancer leading to diarrhea, malabsorption and weight loss. Sero- negative celiac disease with villous atrophy should be evaluated for underlying malignancy.Figure 1Table 1: Modified Marsh Classification of Small intestinal changes