Natural killer cell enteropathy mimicking lymphoma

Montenegro Almeida, Andrea Isabel; Vidal Aguirre, Steffi Verónica; Piris Pinilla, Miguel Ángel; Saperas, Esteban

doi:10.1016/j.gastre.2023.04.003

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The patient was a 47-year-old man with no past history of interest with abdominal pain and diarrhoea of three months’ duration, IgA deamidated gliadin peptide antibodies (anti-DGP) of 51.5AU/ml (<15AU/ml), undetectable anti-transglutaminase antibodies.Oral panendoscopy with duodenal biopsies was normal. Colonoscopy with ileoscopy showed micronodular lesions in the terminal ileum consistent with nodular hyperplasia.Pathology examination of the endoscopic biopsies identified expansion of the lamina propria by a well-demarcated superficial infiltrate of medium to large cells with irregular nuclei with fine chromatin, inconspicuous nucleoli and moderate amounts of pale cytoplasm with eosinophilic granules. Mucous glands without destruction. No villous atrophy, necrosis, angioinvasion or angiodestruction. Neoplastic cells expressed T-markers (CD3 and CD7), CD56 and cytotoxic markers (TIA1), but not CD5, CD4, CD8, CD21, CD30, cyclinD1, S-100 or SOX11. Ki-67 proliferation index of 20%. No EBV- or CMV-positive cells were detected. Molecular study of TCR alpha/beta and gamma/delta rearrangement was not possible due to lack of histological material. These IHC study results led to a diagnosis of NKCE (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The study was completed with nuclear magnetic resonance imaging, which was normal, and capsule endoscopy, which showed two clean millimetric vascular lesions in the jejunum and isolated millimetric polyps in the terminal ileum. Due to the initial suspicion of lymphoma, chest CT, PET–CT and bone marrow aspiration were also performed, which were normal. We considered that the patient also had potential coeliac disease, as he had suggestive symptoms, positive serology and was a heterozygous carrier of the HLA-DQ 2.2 gene, but no compatible histological lesions were associated.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Removal of gluten from the diet was indicated and symptoms improved. A follow-up ileoscopy was performed at one year of follow-up, which continued to show micronodular lesions consistent with nodular hyperplasia, but histology only reported lymphoid aggregates with a reactive appearance.NKCE, described by Mansoor in 2011, is rare, with fewer than 45 cases reported, with a mean age of 58years.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The series involve one or more organs of the digestive tract, including the oesophagus, stomach, small intestine, colon and biliary tract.<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> Patients are asymptomatic or present with non-specific symptoms such as abdominal pain, diarrhoea, constipation or weight loss.<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a>Endoscopic findings include erythematous lesions, erosions/ulcers, raised lesions and polyps. There is no adenopathic involvement or organomegaly. The clinical course is indolent, with spontaneous resolution or prolonged persistence of symptoms and lesions. No dissemination or death from this condition has been reported.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>NKCE is recognised as a pseudomalignant process because it remits spontaneously without any treatment.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> It is not known whether this process occurs more frequently in patients with gluten sensitivity. Vega et al.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> described a case of NKCE in which the patient was found to have high titres of anti-gliadin antibodies. The lesions subsided with a gluten-free diet, although there was no clinical or histological evidence of concomitant coeliac disease.NKCE usually consists of a diffuse infiltrate limited to the lamina propria that displaces but does not destroy mucosal glands, consisting of medium to large cells with irregular nuclei, fine chromatin, inconspicuous nucleolus and a pale cytoplasm accompanied by characteristic eosinophilic granules. A key point is the negativity of EBV-encoded RNA in situ hybridisation, as well as the lack of clonality in the clonal rearrangement of TR genes, a consistent finding in lymphomas.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>On histological examination, this entity may mimic a primary intestinal NK/T-cell lymphoma and lead to misdiagnosis. Due to prognostic and therapeutic differences, this condition must be distinguished from extranodal NK/T-cell lymphoma, nasal type and monomorphic intestinal epitheliotropic T-cell lymphoma.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>In conclusion, we present a patient with NKCE in whom endoscopic biopsy of the terminal ileum showed a diffuse infiltrate consisting of cells with cytological atypia, and irregular nuclei with eosinophilic granular cytoplasm that initially simulated NK-cell lymphoma. A deeper understanding of this rare lymphoproliferative disorder and review by an expert pathologist is the key to avoiding misdiagnosis and inappropriate intensive treatment.FundingNo funding was received for this study.Conflicts of interestThe authors declare that they have no conflicts of interest." 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Gastroenterología y Hepatología

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