Primary Gastric T-cell Lymphoma Research Articles

The epidemiology and prognosis of patients with primary gastric T-cell lymphoma in the SEER program.

Primary gastric T-cell lymphoma (PG-TCL) is a rare hematological malignancy with few data reported. The objective of this study is to investigate the epidemiology, clinical characteristics, and survivals of PG-TCL. Totally, 164 patients with PG-TCL from 1975 to 2016 extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database were analyzed. Kaplan-Meier method was applied to plot overall survival (OS) and cancer-specific survival (CSS). The prognostic factors of OS and CSS were explored by Cox proportional hazard regression. Nomograms were constructed to predict survival possibilities. The age-adjusted incidence rate of PG-TCL was 0.0091 per 100,000 person-years and increased with age. The median age at onset was 65 years old with male predominance. The major histological type was peripheral T-cell lymphoma, NOS (63.4%). The 1-, 2-, and 5-year OS were 45.5%, 34.7%, and 23.5%, respectively while the 1-, 2-, and 5-year CSS were 47.4%, 37.3%, and 29.6%, respectively. Multivariate Cox analysis demonstrated that age at diagnosis, use of chemotherapy, and radiotherapy were the independent prognostic factors for OS. Chemotherapy combined with radiotherapy could significantly improve patients' OS compared with chemotherapy alone. Moreover, age at diagnosis and use of chemotherapy were also the independent prognostic factors for CSS. Nomograms for PG-TCL were developed to predict 1-, 2-, and 5-year OS possibilities. The predictability of nomograms was verified by high concordance index and good agreement with the predicted value in calibration plots. PG-TCL is a rare neoplasm with low incidence. Patients with PG-TCL generally exhibited poor prognosis. Use of chemotherapy plus radiotherapy was associated with favorable OS.

Novel gammaherpesvirus associated with primary gastric T-cell lymphoma in a free-ranging giant armadillo in Brazil.

The number of viral-associated neoplasms reported in wildlife has increased over the last decades, likely because of growing research efforts and a potentially greater burden of carcinogenic pathogens. Herein, we describe a primary gastric T-cell lymphoma in one free-ranging giant armadillo (Priodontes maximus) from Brazilian Pantanal infected by a novel gammaherpesvirus, proposed as Cingulatid gammaherpesvirus 1 (CiHV-1). By chromogenic in situ hybridisation against Epstein-Barr virus some neoplastic cells were labeled. Subsequently, a molecular screening was carried out to detect the occurrence of this pathogen in other giant armadillos in the same region. Overall, this novel virus was detected in 14.3% (3/21) of the tested giant armadillos. We suggest this herpesvirus, the first in Xenarthra, as a plausible aetiology of the neoplasm. The implications of CiHV-1 for this species are uncertain; while no outbreaks of disease have been recorded, the present study raises concerns. Further research is warranted to assess the real significance of CiHV-1 and its potential oncogenic role in this species.

CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review

There have been rare reported cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) that co-expressed CD20. A 44-year-old Japanese male was initially misdiagnosed as CD20-positive diffuse large B-cell lymphoma with a background of reactive CD3-positive T-cells in the stomach. After four cycles of R-CHOP [rituximab plus cyclophosphamide (CY), doxorubicin, vincristine, and prednisolone (PSL)], total gastrectomy with regional lymph node dissection was performed due to the poor response to R-CHOP. A final diagnosis of CD20-positive primary gastric PTCL-NOS was made based on the immunohistochemical, flow cytometric, and molecular genetic findings. In the present case, CD20 immunostaining for T-cell lymphoma cells in tumor tissue varied; in a large part, these were strong to weak-positive, and in some parts, absent. We additionally reviewed the literature focusing on CD20-positive PTCL-NOS treated with rituximab. The administration of rituximab has been performed as an initial treatment in 11 cases, including the case reported here. The response was good in cases with high expression of CD20, while it was poor in cases with variable intensity in CD20 staining, which is consistent with our experience in the present case. The efficacy of rituximab may be associated with intensity of CD20 expression in T cells and its homogeneity in the tumor tissue.

Clinicopathological characteristics of primary gastric T‐cell lymphoma

To investigate the clinicopathological characteristics of 20 primary gastric T-cell lymphoma (GTCL) cases without human T-lymphotropic virus type I infection in Japan, a non-endemic area for coeliac disease. Fifteen cases had no history of persistent diarrhoea or severe hypoproteinaemia. Histologically, 13 cases (65%) consisted of large cell lymphoma and seven (35%) were of medium-sized cells. Intraepithelial lymphoma cell invasion was found in three cases (15%). Two of 10 surgical cases (20%) showed intramucosal tumour cell spreading with enteropathy-like features. Helicobacter pylori CagA gene was detected in three of 10 cases (30%). The lymphoma cells of all 20 cases were positive for CD3 and/or TCRbetaF1 and negative for CD56. CD4- and CD8- lymphoma was found in 11 cases (55%), CD4+ lymphoma in seven (35%) and CD8+ lymphoma in two (10%). CD30+, CD5+ and CD25+ lymphomas were detected in nine (45%), 10 (50%) and 11 (55%) cases, respectively. Five-year survival of the 16 available cases was 54%. Early clinical stage and medium-sized cell lymphoma were significantly (P < 0.05) better prognostic factors. Patients with GTCL exhibit distinct clinicopathological findings and prognoses from those with enteropathy-associated T-cell lymphomas. GTCL may be mainly derived from lamina propria and parafollicular T cells.

Long-term Remission of Primary Gastric T Cell Lymphoma Associated with Human T Lymphotropic Virus Type 1: A Report of Two Cases and Review of the Literature

Two cases of primary gastric T-cell lymphoma associated with human T lymphotropic virus type 1 (HTLV-1) are presented. Case 1 was a 54-year-old man who had multiple ulcerating tumors in the lower corpus and gastric antrum. Case 2, a 60-year-old man, showed a large ulcerating tumor in the upper corpus. Both patients were positive for serum anti-HTLV-1 antibody and for the monoclonal integration of HTLV-1 proviral DNA in the tumor cells by Southern blot analysis. The patients were thus diagnosed as having primary gastric T-cell lymphoma associated with HTLV-1 of stage II(1). Case 1 underwent total gastrectomy followed by chemotherapy, while Case 2 was treated by chemotherapy and radiotherapy. Both patients have been in complete remission for more than 4 years (96 months in Case 1 and 50 months in Case 2) after the treatments. Although primary gastric T-cell lymphomas associated with HTLV-1 is characterized by an extremely poor prognosis, the present cases suggest that in the early stage, long-term survival can possibly be achieved with appropriate treatments.

Primary Gastric T-cell Lymphoma without Human T-lymphotropic Virus type 1

Most primary gastric lymphomas are of B-cell origin and those of T-cell origin are very rare. We report a case of T-cell lymphoma without human T-lymphotropic virus type 1 (HTLV-1). A 73-year-old Japanese woman was admitted with epigastralgia and lumbago. Endoscopic examination visualized a submucosal tumor on the greater curvature of the cardia. Biopsy yielded a diagnosis of gastric malignant lymphoma. Lymph node swelling was recognized from the lesser curvature of the stomach to the lesion surrounding the aorta on computed tomography and ultrasonography, but no swelling of lymph nodes in the chest or superficial lymph nodes was seen. Total gastrectomy and local lymph node dissection was performed. HTLV-1 pro-viral DNA was negative in the resected specimen. Immunological findings in the resected specimen were positive in CD3, CD4, and negative in CD20, CD79α, and CD8. Gastric T-cell lymphoma without HTLV-1 was diagnosed. After the operation, chemotherapy was performed for lymph node swelling at the posterior of the pancreas head and surrounding the aorta. Two courses of chemotherapy (CHOP) yielded a complete response. The patient was well and disease free for 6 months, but she died 18 months after the operation with recurrence of lymph node swelling surrounding the aorta. Gastric T-cell lymphoma without HTLV-1 is associated with a poor prognosis in the literature.

Primary Gastric T-Cell Lymphoma: Clinicopathologic Features and Treatment Outcome.

Primary gastric lymphoma is the most frequent type of extranodal malignant lymphoma. The large majority of cases are of B-cell lineage, while primary gastric T-cell lymphomas are exceedingly rare and least well characterized malignancy and the clinical features have been described only in a few case reports. In this study, we conducted a retrospective analysis to investigate the natural history and the clinical outcome after treatment. Between 1990 and 2004, 444 patients with primary gastric lymphoma had been diagnosed at four institutes. Among these 444 patients, 17 patients (3.8%) were identified as primary gastric lymphoma with T-cell immunophenotype. The pathologic review was performed by two experienced hematopathologist to confirm T-cell lymphoma with typical immunohistochemical features including CD3. All of the patients were staged according to the Mushoff system. Among these 17 gastirc T-cell lymphoma patients, 14 patients were treated with combination chemotherapy including CHOP with or without radiotherapy. The two patients were treated with high-dose chemotherapy with autologous peripheral hematopoietic stem cell transplantation. The median age of the 13 male and 4 female patients was 49 years (range 22–76 years). The pathologic subtypes of these patients with T-cell immunophenotype were as follows; precursor T-lymphoblastic lymphoma in 2 patients, peripheral T-cell lymphoma, unspecified in 6 patients, NK/T cell lymphoma in 3 patients, and T-cell others in 5 patients. The many of the patients showed poor performance status (PS), and high LDH level (65%). 12 patients (71%) showed stage III or IV diseases, and 9 patients (53%) showed high or high-risk according to the International Prognostic Index (IPI). A response to treatment was observed in 8 patients (47%), with 6 Complete Response (CR) and 2 Partial Response (PR). The median Progression-Free Survival (PFS) and Overall Survival (OS) were only 5 months (95% C.I.; 4–6 months), and 14 months (95% C.I.; 0–189 months). 5 patients of these 17 patients (29%) presented only in stomach and regional lymph nodes. The patients with localized gastric T-cell lymphoma showed good therapeutic outcome (median PFS; 53 months, median OS; 123 months, p =0.024 by log-rank test). Other clinical factors including PS, age, and LDH did not show clinical significance in this series. Although our series had limitation to interpret due to small population, this study showed that the incidence of this subtype of T-cell gastric lymphoma was very rare, and poor prognosis, like as other T-cell lymphoma. However, about 30% of the patients had localized diseases limited to gastric area and regional lymph nodes with relative good prognosis. New therapeutic strategies need to improve the outcome of patients with gastric T-cell lymphoma.

Non-HTLV-1-associated primary gastric T-cell lymphomas show cytotoxic activity: clinicopathological, immunohistochemical characteristics and TIA-1 expression in 31 cases.

Most primary gastrointestinal lymphomas are of B-cell origin and T-cell origin is very rare. Recent studies have suggested that human T-cell lymphotrophic virus type 1 (HTLV-1) may be involved in the development of primary gastric T-cell lymphoma. We analysed 31 patients with primary gastric T-cell lymphoma in south-west Japan, an area endemic for HTLV-1, and determined their phenotypes, genotypes, and HTLV-1 status. Here we present 31 cases of primary gastric T-cell lymphoma in a HTLV-1-endemic area in Japan and analyse the clinical status, histology, phenotype and virus status. The median age at onset of primary gastric T-cell lymphoma was 57 years with a gender ratio of M:F = 1.58:1. Six of the 31 primary gastric T-cell lymphoma cases had HTLV-1 proviral DNA (five males, one female), nine of the 31 cases were positive for anti-adult T cell leukaemia antibody, without examination of HTLV-1 proviral DNA (five males, four females), eight were non-HTLV-1-associated primary gastric T-cell lymphoma (four males, four females) and the other eight cases were unknown. Primary gastric T-cell lymphoma usually presented as a large ulcerated tumour at the corpus to the antrum and histologically consisted of anaplastic large cell type (n = 2), pleomorphic large cell type (n = 3), pleomorphic medium and large cell type (n = 14), pleomorphic medium cell type (n = 11), and angioimmunoblastic T-cell lymphoma type (n = 1). There were no clear macroscopic and microscopic differences between HTLV-1-associated and non-HTLV-1-associated primary gastric T-cell lymphoma. Most patients died within 2 years of diagnosis, and both types of primary gastric T-cell lymphoma (with and without HTLV-1) were associated with poor prognosis. Cytotoxic marker analysis showed that HTLV-1-associated lymphomas were negative for TIA-1, while non-HTLV-1-associated lymphomas were positive for TIA-1. Our results suggest that in HTLV-1-endemic areas, patients with HTLV-1-associated primary gastric T-cell lymphoma should be managed carefully and that TIA-1 seems to be useful for identifying the aetiology of this lesion.

Primary Gastric T-cell Lymphoma Associated with Human T-cell Leukemia Virus Type I shows 'Lymphoepithelial Lesions': Case report.

We describe an unusual case of adult T-cell leukemia/lymphoma (ATL) appearing in a 44-year-old female without leukemic change and systemic lymphadenopathy, which originated from the gastric wall and partially involved the paragastric lymph nodes. No other intraabdominal or intrathoracic organs, such as the liver, spleen, kidneys, adrenals, lungs, or bone marrow, were involved at the time of surgery. The clinical stage of this case was evaluated as IIE according to the Ann Arbor classification. Lymphoma cells were CD3+, CD4+, CD8-, and CD79a-. Southern blot analysis revealed monoclonal integration of proviral DNA from human T-cell leukemia virus type I. Interestingly, the lymphoma cells formed ‘lymphoepithelial lesions’ which are usually observed in gastric mucosa-associated lymphoid tissue (MALT) B-cell lymphomas. A rare pattern involving ATL cells and the presence of lymphoepithelial lesions in this case indicated a diagnostic pitfall of gastric MALT lymphoma.

Genotype Configuration in a Case of Primary Gastric Lymphoma with T-cell Phenotype

T-cell malignant lymphoma of the gastrointestinal tract is rare. The genotype of gastric T-cell lymphoma remains unclear. The aim of this study was to elucidate the pathogenesis of a case of primary gastric T-cell lymphoma by using cytogenetics and molecular biology. Gastric biopsy specimens and lymphoma cells in the ascites were examined by immunocytology, cytogenetic analysis, and Southern blot analysis. The histological diagnosis of the gastric lymphoma was diffuse large cell type. T-cell markers were positive in immunocytochemistry of the gastric lymphoma cells and in FACS analysis of lymphoma cells in the ascites. All lymphoma cells in the ascites had complex abnormal karyotypes containing t(8;14)(q24;q32). Southern blot analysis revealed rearrangement of the IgH and C-MYC genes of the lymphoma cells in both the stomach and the ascites, but no comigration of the C-MYC with the JH locus could be detected. The TCR-β and -γ genes were in their germ-line configurations. In this patient, although the phenotype was T-cell lymphoma, the karyotype t(8;14)(q24;q32) and genotype had the characteristics of B-cell lymphoma. The unique B-cell genotype configuration and the C-MYC activation suggested that the cellular origin of this rare case of malignant lymphoma with a T-cell phenotype was quite immature lymphocytes.

Primary gastric T-cell lymphoma with and without human T-lymphotropic virus type 1.

Gastric T-cell lymphomas are rare, and their incidence and viral status have not yet been fully clarified. Sixty-seven cases of surgically resected gastric lymphomas from city hospitals in Tokyo were evaluated. The surface phenotype was determined by immunohistochemistry, gene rearrangement by Southern blot hybridization, association with Epstein-Barr virus (EBV) by EBV-encoded small RNAs in situ hybridization, and the presence of human T-cell lymphotropic virus type 1 (HTLV-1) by serology, Southern blot hybridization, and polymerase chain reaction analysis. Five of the 67 cases were T-cell lymphoma (7%): 3 cases were HTLV-1 negative (-) and 2 were HTLV-1 positive (+). Systemic eosinophilia was observed in the three HTLV-1(-) gastric lymphomas. Neoplastic cells were morphologically similar in both groups, but a granulomatous reaction with marked eosinophilia was observed only in the two cases of HTLV-1(-) lymphoma. They also had characteristics of natural killer (NK) cell-like T-cell lymphoma, expressing NK markers and TCRgamma gene rearrangement. Positivity with HML-1 (specific for intestinal epithelial T-cells lymphoma was observed in one HTLV-1(+) lymphoma. The EBV gene was detected in only one case of B-cell lymphoma but not in any case of T-cell lymphoma. Gastric T-cell lymphoma occurs in 7% of gastric lymphomas in Japan and is comprised of HTLV-1-related lymphomas and lymphomas unrelated to HTLV-1, including NK cell-like lymphomas with eosinophilia.

Primary gastric T-cell lymphoma of suppressor-cytotoxic (CD8+) phenotype: Discordant expression of T-cell receptor subunit βF1, CD7, and CD3 antigens

Primary gastric T-cell lymphomas are rare neoplasms, and all but one of the previously phenotyped cases have shown a helper-inducer phenotype. The present case is the second reported case of a primary gastric T-cell lymphoma of suppressor-cytotoxic phenotype. The tumor histology was similar to that described in some forms of node-based peripheral T-cell lymphomas. Phenotypic analysis revealed low expression of pan-T marker CD7, reduced expression of CD3, but higher density and frequency of expression of CD8 antigens that could be predicted on the basis of the pan-T markers. Natural killer cell (NK) related markers CD16, HNK-1 and NKH-1 were not expressed by the neoplastic cells. T-cell receptor (TCR) β subunit expression was detected on fewer cells than would have been predicted on the basis of CD3 and CD8 expression, and TCR δ chain expression was undetectable.