Clinicopathologic Analysis of Primary Gastrointestinal T-Cell Lymphoma with a Special Reference to Intestinal and Gastric Type in Japan.
Authors: Yamamoto Hideko , Matsuo Keitaro , Goto Hidemi , Nakamura Shigeo 
Published: April 2020

Abstract
Primary gastrointestinal T-cell lymphomas (PGITL) are very rare and heterogeneous diseases with poor prognosis. Their incidence and pathogenesis may vary with geographical locations. In this study, we aimed to define clinicopathologic and prognostic features of PGITL in Japan, non endemic area for celiac disease, with compared to those in Western countries. 79 patients with PGITL (41 gastric and 38 intestinal lymphoma cases) were enrolled. Epstein-Barr virus associated NK-/T-cell lymphoma and human T-cell leukemia virus type 1 associated adult T-cell leukemia/lymphoma cases were excluded from this study. Our intestinal cases (63%) were histopathologically characterized by monomorphic small-to medium-sized tumor cells, which appeared to be contrasted with higher incidence of pleomorphic appearance among Western patients, and by frequent expression of CD8, CD56, and cytotoxic molecules (CM) of those cells, which is consistent with immunohistochemical features of Western cases. Our gastric cases were unique in showing a wide range of histologic and immunophenotypical characteristics with a significantly higher inclusion of non-cytotoxic lymphoma than intestinal cases (33% vs. 9%, P=.0299). Approximately 62% of patients also showed pleomorphic appearance most frequently with CD4+CD8− and CD4–CD8-phenotype. In comparison with gastric patients, intestinal ones were significantly associated with several clinical factors to indicate poor prognosis such as poorer performance status (P=.0232), lower total protein level (P=.0018), and lower serum albumin level (P=.0303). Overall survival of intestinal cases were significantly inferior to that of gastric patients (P = 0.026), while no statistically significant differences were found in survival between CM-positive PGITL cases and –negative ones (P = 0.6). In univariate analysis, the factors that turned out to correlate significantly with survival were total protein level (&lt;6.0g/dL) (HR, 3.696; 95% CI, 1.671 to 8.171; P=.0012), platelet level (&lt;10.0 /μl) (HR, 10.706; 95% CI, 2.713 to 42.244; P=.0007), a higher than normal serum lactate dehydrogenase (LDH) level (HR, 2.574; 95% CI, 1.266 to5.231; P=.009), direct invasion or gastrointestinal perforation (HR, 2.079; 95% CI, 1.013 to 4.267; P=.046), bone marrow involvement of the disease (HR, 3.134; 95% CI, 1.136 to 8.651; P=.0274), performance status equal to or more than 2 (HR, 3.988; 95% CI, 1.763 to 8.882; P=.0007), the International Prognostic Index (IPI) more than low-intermediate (HR, 3.317; 95% CI, 1.304 to 8.441; P=.0119), Prognostic Index for T-cell lymphoma (PIT) scores more than 2 (HR, 8.166; 95% CI, 2.574 to25.904; P=.004), CD8 positivity (HR, 2.041; 95% CI, 1.032 to 4.037; P=.0404), and intestinal case (HR, 2.955; 95% CI, 1.493 to 5.849; P=.0019). Multivariate analysis with individual factors confirmed that PIT scores was a significant (HR, 6.622; 95% CI, 1.108 to 39.566; P=.0382) and platelet level (&lt;10.0 /μl) was a marginally significant (HR, 5.343; 95% CI, .837 to 34.116; P=.0765) prognostic factors independent from other clinical factors. In conclusion, Japanese intestinal lymphoma patients were in keeping with characteristics of Enteropathy type T-cell lymphoma other than an association with celiac disease and monomorphic histology. However, gastric T-cell lymphomas were distinct from intestinal ones, and were separately considered.