Indolent CD8-positive T-Cell Lymphoma of the Gastrointestinal Tract: A Novel Entity Analogous to the Cutaneous CD4-positive Small/medium T-Cell Lymphoma?

Background/Aim: Primary T- or NK (T/NK)-cell lymphomas of the gastrointestinal (GI) tract are uncommon diseases, comprising mainly some aggressive subtypes such as enteropathy-associated T-cell lymphoma and extranodal NK/T-cell lymphoma, nasal type. Rare cases of some T/NK-cell lymphoproliferative disorders with an indolent clinical course, however, have been recently described. We report herein five cases of a unique and rare subtype of GI indolent T-cell lymphoma that has not been recognized in the current WHO classification. Methods: Hematoxylin and eosin-stained sections of the five cases were reviewed. Immunohistochemical studies as well as in situ hybridization for Epstein-Barr virus-encoded small RNAs (EBER) were performed on formalin-fixed, paraffin-embedded tissue sections using a BechMark XT automated immunostainer. In four cases with available tissue, PCR-based analysis for the rearrangement of the T-cell receptor (TCR) genes was also performed. Results: There were one female and four male patients, with a median age of 52 years (range, 29 to 66 years). The most common presenting symptoms included abdominal pain or distention, diahhrea, dyspepsia, and weight loss. Gastric body was the most commonly involved site, followed by colorectum and small intestine. Three patients had involvement of only one site, whereas an extensive whole-bowel involvement or disseminated disease was noted in the other two patients. Endoscopically, the lesions presented with multiple or solitary polyps or nodules, diffuse finely nodular lesions throughout the bowels, and alternatively, giant ulcerating masses. Staging work-up revealed the lesions were restricted to the GI tract in most cases at diagnosis. Histologically, the lesions were characterized by either non-destructive infiltration of the lamina propria, or sometimes, transmural massive infiltration of the entire wall, by small to medium-sized atypical T-cells with a similar phenotype of CD3+, CD4-, CD5+, CD8–, CD30–, CD56–, TIA1+, EBER–. All lesions featured an extremely low proliferation activity reflected by the Ki-67 index. The molecular studies for the TCR gene rearrangement confirmed a clonal lymphoproliferative disorder in all four cases examined. Except for one patient was managed by a ‘watch and wait’ approach, four of the five patients were treated with CHOP-based chemotherapy due to an initial diagnosis of peripheral T-cell lymphoma, among whom two patients with giant ulcerating lesions also received a prior total or subtotal gastrectomy to reduce the risk that might caused potentially by chemotherapy. The two patients treated merely with chemotherapy showed little response and were both alive with persistent disease at last follow-up, whereas the other two patients received combined surgery and chemotherapy kept well without disease during follow-up. Conclusions: We suppose the currently reported lesions might represent a novel subtype of peripheral T-cell lymphomas featuring a peculiar indolent clinical course. These lesions display clinicopathological features similar to but not identical to those described recently by Jaffe and Chan. Awareness of these indolent T-cell lymphoproliferative disorders of the GI tract is important for the correct diagnosis and optimal management.