Atypical NK-cell Proliferation of the Gastrointestinal Tract in a Patient With Antigliadin Antibodies but not Celiac Disease

Abstract

We describe a unique case of atypical natural killer (NK)-cell proliferation likely related to gluten sensitivity, mimicking NK-cell lymphoma. The patient, a 32-year-old man, has had persistent multiple erythematous bull-eye lesions in the stomach, small bowel, and large bowel for 3 years. Histologically, the lesions were well circumscribed and relatively superficial, composed of atypical medium-sized to large-sized lymphocytes with slightly irregular nuclear contours, a dispersed chromatin pattern, and clear cytoplasm. Immunohistochemistry and flow cytometry showed that the cells were NK cells expressing CD56 (aberrantly bright), T-cell intracellular antigen (TIA)-1, cytoplasmic CD3, and CD94, but not surface CD3, with bright aberrant expression of CD7 and a lack of other NK cell-associated markers. Polymerase chain reaction for rearrangement of the T-cell receptor-gamma chain gene showed no evidence of a clonal T-cell population, and in situ hybridization for Epstein-Barr virus encoded RNA was negative. There was no evidence of the involvement of peripheral blood or bone marrow. Although a diagnosis of extranodal NK/T-cell lymphoma was considered because of the atypical morphology and immunophenotypic aberrancy, no chemotherapy was given because of the relatively superficial nature of the infiltrates, lack of significant symptoms, and negativity for Epstein-Barr virus. Two years after initial presentation, the patient was found to have high titers of antigliadin antibodies with no other evidence of celiac disease. After instituting a gluten-free diet, many of the lesions regressed, suggesting that this atypical NK-cell proliferation may be driven by an anomalous immune response. Awareness of this case may prevent pathologists from misdiagnosing similar lesions as NK/T-cell lymphomas. It is as yet unknown whether this process occurs more commonly in patients with gluten sensitivity, or in other settings, and the pathogenesis is as yet undetermined.

Early lymphoid lesions: conceptual, diagnostic and clinical challenges

“…[101][102][103] Patients are either asymptomatic or have non-specific GI symptoms and no history of celiac disease, inflammatory bowel disease or malabsorption. 102 A subset of patients in one study had a prior history of gastric carcinoma and frequent H.pylori infection.…”

Lymphoproliferative Disorders of the Gastrointestinal Tract: A Review and Pragmatic Guide to Diagnosis

“…96 At endoscopy, multiple superficial, discrete, flat or hemorrhagic lesions may be observed or small (less than 1 cm), patchy, superficial ulcers are discovered. [94][95][96] Biopsy specimens demonstrate a diffuse, well-circumscribed, mucosal infiltrate of atypical intermediate to large lymphoid cells with clear to eosinophilic cytoplasm and with invasion or destruction of mucosal glands (Figure 5, E). [94][95][96] Acute inflammation may accompany the infiltrate.…”

“…[94][95][96] Biopsy specimens demonstrate a diffuse, well-circumscribed, mucosal infiltrate of atypical intermediate to large lymphoid cells with clear to eosinophilic cytoplasm and with invasion or destruction of mucosal glands (Figure 5, E). [94][95][96] Acute inflammation may accompany the infiltrate. The atypical lymphocytes express cytoplasmic, but not surface, CD3, as well as CD56 and TIA-1.…”

“…Similar to true NK-cell lymphomas of extranodal nasal type, the T-cell receptor in the enteropathy cases is germline; but, in contrast to NK nasal-type lymphomas, studies for Epstein-Barr virus using Epstein-Barr virus-encoded RNA yield negative results. [94][95][96] Of most significance, and as opposed to both extranodal NK/T-cell lymphomas and EATL, patients with NK-cell enteropathy pursue an uneventful clinical course. 94,95 The etiology of this syndrome is unknown.…”

NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series

“…5 We previously reported a case in which an atypical NK-cell proliferation with multiple ulcerative lesions in the gastrointestinal tract mimicked NK-cell lymphoma. 18 That patient had antigliadin antibodies but lacked other evidence of celiac disease. Since then, we have encountered in our consultation practice 7 additional patients with similar clinicopathologic findings.…”