Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract: a tricky diagnosis of a gastric case

Abstract

Background Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a rare low-grade clonal lymphoid proliferation, included as a provisional entity in the current World Health Organization classification. The disease is generally localized to the gastrointestinal tract, mainly small bowel and colon. Involvement of other organs is infrequently reported. The majority of patients show a protracted clinical course with persistent disease. A prolonged survival, even without treatment, is common. Case presentation A 28-year-old woman had a 2-year history of dyspepsia and lactose intolerance. Autoimmune diseases and celiac disease were excluded. No gross lesions were identified by endoscopy. Multiple gastric biopsies showed a small-sized lymphoid infiltrate, expanding the lamina propria, with a non-destructive appearance. The lymphoid cells were positive for CD3, CD4, CD5, CD7 and negative for CD20, CD8, CD56, CD103, PD1, CD30, ALK1, CD10, BCL6, perforin, TIA-1, Granzyme B and Epstein-Barr virus-encoded RNA. KI-67 index was low (5%). Molecular analysis revealed a clonal T-cell receptor γ rearrangement. Bone marrow was microscopically free of disease, but molecular testing identified the same T-cell receptor γ rearrangement present in the gastric biopsies. After the diagnosis of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, the patient received steroid therapy, only for 2 months. She is alive, with a stable disease restricted to the stomach, at 12 months from diagnosis. Conclusions Indolent T-cell lymphoproliferative disorder is usually a disease of adulthood (median age: 51 yrs). The small bowel and colon are the sites most commonly involved. Our case occurred in a young woman and affected the stomach, sparing small intestine and colon. Clonality testing identified involvement of bone marrow, a site infrequently affected in this disease. Our aim is focusing on the main diagnostic issues. If appropriate immunostainings and molecular analysis are not performed, the subtle infiltrate may be easily overlooked. The risk of misdiagnosis as more aggressive lymphomas, causing patient overtreatment, needs also to be considered.

Indolent T-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract (iTLPD-GI): A Review

“…TIA-1 is expressed in most CD4− cases, both CD8− and CD8+ (75% and 83%, respectively), and in three out of four tested cases with subsequent transformation to high-grade lymphoma (the three of them being CD4−/CD8+). Positivity for granzyme B is far lower in both groups, and negativity for both cytotoxic markers has been reported in all CD4+ cases [ 12 , 13 , 17 , 26 , 28 , 36 ]. These findings highlight the striking similarities between CD8+ iTLPD-GIs and indolent CD8+ lymphoid proliferations of the ear/primary cutaneous acral CD8+ T-cell lymphomas, which affect mostly males [ 37 , 38 , 39 ].…”

“…There is a characteristic variably dense, monomorphous, lymphoid infiltrate without destruction, which is usually confined to the lamina propria, where it usually segregates and deforms glands or crypts [ 1 , 2 , 7 , 12 , 14 , 16 , 28 ], and occasionally spreads into the muscularis mucosae and submucosa [ 1 , 2 , 7 , 12 , 16 ] in the absence of well-defined masses and full thickness wall involvement [ 12 ]. The infiltrate consists of small to occasionally medium-sized lymphocytes exhibiting a mature phenotype, with round or slightly atypical nuclei, normal-appearing chromatin, very small nucleoli, and a low amount of cytoplasm [ 1 , 2 , 7 , 12 , 14 , 16 ] ( Figure 1 a,b); the Ki-67 proliferation index is very low, being <10% in all cases and mostly <5% [ 1 , 2 , 12 , 16 ].…”

“…The lymphoid infiltrate expresses CD3, and may be CD4+CD8− and, less commonly, CD4−CD8+ [ 1 , 2 , 7 , 12 , 16 , 17 ]. CD4 expression alone has been documented in almost two-thirds of the reported cases so far, while both CD4−CD8− (double negative) and CD4+CD8+ (double positive) cases have been rarely described [ 12 , 17 , 21 , 23 , 28 , 29 ]; some authors questioned whether these constitute bona fide examples of iTLPD-GI.…”

“…Due to their morphologic, immunophenotypic, and clinical features, iTLPD-GIs have been postulated to be part of the spectrum of primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphomas, which are thought to be of TFH cell origin [ 15 , 16 , 33 ]. Most cases were negative for TFH markers [ 11 , 15 , 16 , 28 ]; however, it cannot be ruled out that CD4+ iTLPD-GIs may arise from a particular TFH subtype, or another functional subset or lineage of CD4+ T-cells [ 16 , 35 ].…”

“…The integrin protein CD103 is expressed on intraepithelial lymphocytes T-cells and on some peripheral regulatory and lamina propria T-cells [ 41 , 42 ]. Lack of CD103 expression has been reported in most iTLPD-GIs [ 7 , 9 , 11 , 15 , 28 ], with exceptions belonging to the CD4−/CD8+ group (three out of five cases, 60%) [ 6 , 14 , 21 , 36 ]; due to its presence in at least a subset of CD8+ cases, Matnani et al [ 36 ] suggested an origin of these iTLPD-GIs from a mucosal CD8+ T-cell precursor. Moreover, it has been hypothesized that CD103+ iTLPD-GIs could arise either from specific integrin expressing lamina propria T-cells [ 43 ] or through activation induced upregulation of CD103 [ 44 , 45 ].…”