Primary Small Intestinal CD4+ T-Cell Lymphoma: An Indolent Lymphoma with Distinct Features
Elizabeth McMillen, Vaidehi Jobanputra, Suzanne Lewis, Peter Green, Bachir Alobeid, Govind Bhagat. New York Hospital-Columbia University Medical Center, New York, NY
Background: Primary small intestinal (SI) T-cell lymphomas are rare and generally aggressive, with median overall survival of 10 and 7 months reported for Enteropathy-associated T-cell lymphoma (EATL) types 1 and 2, respectively. Rare cases of primary SI CD4+ T-cell lymphomas have been described, but are not well characterized. Hence, we evaluated the pathologic, genetic, and clinical features of such cases.
Design: We searched for all primary SI T-cell lymphomas diagnosed at our institution between 1996 and 2012 to identify cases expressing CD4. Morphologic features and immunophenotype were assessed. T-cell receptor gene rearrangement and SNP array (Affymetrix) analyses were performed. Clinical outcomes were obtained from treating physicians.
Results: We identified 3 cases of primary SI CD4+ lymphomas (2M/1F, ages 37-53). SI biopsies showed crypt hyperplasia, villous atrophy and a dense infiltrate of small-medium sized CD4+ T-cells in the lamina propria. Intraepithelial lymphocytosis was absent. However, lymphoepithelial lesions were seen in crypt epithelium in all cases. All cases showed CD7 downregulation or loss. Gastric (n=2) and colonic (n=2) involvement was detected. Clonal TCR gene rearrangements were identified at multiple locations in the GI tract in all cases, which persisted in subsequent biopsies. SNP array analysis showed relative genomic stability: loss of 19q and X (n=1 each) and no abnormalities (n=1) at diagnosis, but complex changes were seen at disease transformation (n=1). Novel candidate oncogenes were identified. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease at outside institutions, but failed to respond to gluten-free diets. Two patients are alive with persistent disease (3 and 17 years post diagnosis), despite immunomodulatory therapy. One developed large cell transformation 11 years post diagnosis and died due to small bowel perforation.
Conclusions: Primary SI CD4+ lymphomas represent a unique entity with distinct morphologic and phenotypic features and have a relatively indolent clinical course. In contrast to EATL types 1 and 2, these lymphomas display relative genetic stability at diagnosis. A multi-modality approach, including immunophenotypic and molecular analyses aids in diagnosis. Currently, optimal management of these patients remains unclear and greater awareness of this entity may clarify additional biologic features of these lymphomas.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 222, Monday Morning