Benign Indolent CD56-Positive NK-Cell Lymphoproliferative Lesion Involving Gastrointestinal Tract in an Adolescent
A fourteen-year-old boy was admitted to our hospital due to chronic recurrent vomiting and abdominal discomfort, which began several months previously and intensified to occurrence of vomiting once a day. He also had intermittent diarrhea without severe abdominal pain or fever. His height and weight were both estimated to place him in the lowest 3% of the growth curve for his age. There was no remarkable family history except for hyperthyroidism in his farther. Initially, under the impression of eosinophilic gastroenteritis, prednisolone therapy was administered. However after short-term improvement of symptoms, vomiting recurred. After colonoscopic biopsy, he was presumptively diagnosed with EATL. He was readmitted to our hospital for further workup and nutritional therapy. Endoscopic examinations including capsule endoscopy revealed multiple small lesions with mucosal nodularity and hyperemic change in esophagus, stomach, duodenum, small intestine, and colon with several erosions of the intestine (). Computed tomography scan revealed diffuse thickening of the distal esophageal wall, stomach, duodenum and small intestine, slightly enlarged mesenteric lymph nodes and borderline-sized (10 cm) splenomegaly. On positron emission tomography scan, the only notable finding was mild fluorodeoxyglucose uptake in GI tract, suggestive of physiologic change. Laboratory tests showed mild leukocytosis (white blood cell count, 12,540/µL) with a differential count within normal range, anemia (hemoglobin, 7.4 g/dL), hypoferritinemia (3.88 ng/mL), hypocalcemia (5.5 mg/dL), hypoproteinemia (total protein 3.3 g/dL), and hypoalbuminemia (1.7 g/dL). Lactate dehydrogenase (LDH) was elevated up to 372 IU/L. The presumptive diagnosis of EATL led physicians to perform serologic tests to rule out celiac disease. Anti-tissue transglutaminase antibody was negative, and the patient was positive for HLA-DQ5 and DQ6, which made the possibility of underlying celiac disease less likely. A test for food allergies was also unremarkable.\nMultiple endoscopic biopsies were taken from the esophagus to the colon, which all exhibited similar histological features. The lamina propria was expanded by infiltration of atypical monomorphic lymphoid cells. The infiltrate was vaguely demarcated from the adjacent relatively unaffected mucosa in the colon. The atypical lymphoid cells were medium-sized with slightly irregular nuclei, inconspicuous nucleoli and finely clumped chromatin. They had a moderate amount of pale to eosinophilic cytoplasm (). Mitotic figures were occasionally observed. Necrosis, apoptosis, and angiocentricity were absent. Some scattered eosinophils were noted in the lamina propria. Enteropathy features including villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis were not observed. On immunohistochemistry, the lymphoid cells were positive for cytoplasmic CD3, CD56, CD8, and T-cell-restricted intracellular antigen-1, and negative for CD4, CD20, and TCRβF1 (clone 8A3, Thermo Scientific, Rockford, IL, USA) (). This immunophenotype suggested an NK-cell or γδ T-cell origin. The proliferation rate as determined by Ki-67 was low, up to 19.8%. EBV was not detected by in situ hybridization using an EBV-encoded RNA 1/2 probe. Molecular analysis for TCRγ gene rearrangement using BIOMED-2 multiplex PCR for TCRG: V-J; TCRG: V-J (InVivo-Scribe Technologies, San Diego, CA, USA) on formalin-fixed paraffin-embedded tissue showed no evidence of T-cell monoclonality. Later immunohistochemistry for TCRG (1:20, γ3.20, Endogen, Rockford, IL, USA) was carried out, which was negative.\nDespite a presumptive pathologic diagnosis of intestinal γδT-cell or NK-cell lymphoma, no chemotherapy was administered due to low clinical suspicion of malignancy and the poor nutritional status of the patient. He instead has been closely followed with regular clinical evaluation. Gastroduodenoscopy six months later demonstrated persistent mucosal nodularity in the duodenum, but biopsy revealed mild lymphoplasma cell infiltration with only a few scattered CD3(+) cells and no CD56(+) cells. The patient's symptoms and LDH level waxed and waned, while anemia and hypoalbuminemia have been persistent. However, 40 months later, GI symptoms were aggravated and multifocal ulcerations were observed in colon and stomach. The result of endoscopic biopsy proved recurrence of disease.