Gastrointestinal T-cell Research Articles

Acute Peritonitis Revealing a Gastrointestinal T-Cell Lymphoma Associated with Celiac Disease

This case report describes a 52-year-old man who had undiagnosed and poorly managed celiac disease, and presented with acute peritonitis. Further examination revealed a rare complication of celiac disease, which was a T-cell lymphoma of the gastrointestinal tract. Imaging is important in confirming the diagnosis and chemotherapy is the main treatment option.

Clinical, endoscopic and pathological characteristics of primary gastrointestinal T-cell and NK/T-cell lymphomas

Background and aims Gastrointestinal T-cell and NK/T-cell lymphomas are relatively rare and may be difficult to diagnose. Therefore, we performed a retrospective study of the clinical, endoscopic and pathological characteristics of these lymphomas, to provide additional data on this issue. Methods From April 2013 to April 2021, consecutive patients diagnosed with primary gastrointestinal T-cell and NK/T-cell lymphomas were retrospectively reviewed. Their medical histories, laboratory, imaging, endoscopic, and pathology results were analyzed. Results Forty-two patients were finally chosen, among whom, 24 patients had ENKTCL, 9 patients had MEITL, 2 patients had ALCL, ALK–, 1 patient had ALCL, ALK+, and 6 patients had PTCL, NOS. The median age of all the patients was 48 years old, and 73.81% (31 patients) were male. The patients’ symptoms were abdominal pain, diarrhea, gastrointestinal bleeding, weight loss, fever, and others. The endoscopic results of 26 patients could be traced, and 69.23% of the patients showed multiple lesions. Ulcerative and ulceroinfiltrative lesions were common. Among the pathologic findings, necrosis, ulceration, and crypt atrophy were commonly found while epitheliotropism was relatively less common. Twelve patients (28.57%) had a history of misdiagnosis. After a median follow-up time of 26.9 months, 26 patients (66.70%) died of the disease. The median overall survival time was 8 months. Conclusions These lymphomas had nonspecific clinical manifestations, various endoscopic features, and were likely to be misdiagnosed as other diseases. The prognosis is still poor, and more in-depth research is needed to develop more precise treatments.

Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches.

Simple SummaryIt is challenging for pathologists to diagnose primary gastrointestinal T-cell neoplasms. Besides the rarity of the diseases, the small biopsy material makes it more difficult to differentiate between non-neoplastic inflammation and secondary involvement of extra gastrointestinal lymphoma. Since this group of diseases ranges from aggressive ones with a very poor prognosis to indolent ones that require caution to avoid overtreatment, the impact of the diagnosis on the patient is enormous. Although early treatment of aggressive lymphoma is essential, the treatment strategy is not well established, which is a problem for clinicians. This review provides a cross-sectional comparison of histological findings. Unlike previous reviews, we summarized up-to-date clinically relevant information including the treatment strategies as well as practical differential diagnosis based on thorough literature review.Primary gastrointestinal (GI) T-cell neoplasms are extremely rare heterogeneous disease entities with distinct clinicopathologic features. Given the different prognoses of various disease subtypes, clinicians and pathologists must be aware of the key characteristics of these neoplasms, despite their rarity. The two most common aggressive primary GI T-cell lymphomas are enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. In addition, extranodal natural killer (NK)/T-cell lymphoma of the nasal type and anaplastic large cell lymphoma may also occur in the GI tract or involve it secondarily. In the revised 4th World Health Organization classification, indolent T-cell lymphoproliferative disorder of the GI tract has been incorporated as a provisional entity. In this review, we summarize up-to-date clinicopathological features of these disease entities, including the molecular characteristics of primary GI T-cell lymphomas and indolent lymphoproliferative disorders. We focus on the latest treatment approaches, which have not been summarized in existing reviews. Further, we provide a comprehensive review of available literature to address the following questions: How can pathologists discriminate subtypes with different clinical prognoses? How can primary GI neoplasms be distinguished from secondary involvement? How can these neoplasms be distinguished from non-specific inflammatory changes at an early stage?

Updates and Diagnostic Challenges in Surgical Pathology and Cytopathology.

Updates and Diagnostic Challenges in Surgical Pathology and Cytopathology.

S3015 Primary Gastrointestinal T-cell Lymphoma Presenting as Spontaneous Perforation Peritonitis: A Case Report

S3015 Primary Gastrointestinal T-cell Lymphoma Presenting as Spontaneous Perforation Peritonitis: A Case Report

Update on the Classification of and Diagnostic Approaches to Mature T-Cell Lymphomas.

In the 2017 revised World Health Organization classification of tumors of hematopoietic and lymphoid tissues, some mature T-cell lymphomas were reclassified and a few new provisional entities were established based on new data from clinical and laboratory studies. T follicular helper cell lymphoma is identified by T follicular helper cell markers. Anaplastic large cell lymphoma, ALK negative, is a better-defined entity based on genetic abnormalities, and breast implant-associated anaplastic large cell lymphoma is recognized as a provisional entity. The gastrointestinal T-cell lymphomas are reclassified, with addition of a new provisional entity, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, characterized by an indolent clinical course. To review the diagnostic approaches to reclassified and newly established entities of mature T-cell lymphomas, focusing on significant immunophenotypic features and molecular genetic abnormalities. Relevant new discoveries after the publication of the 2017 World Health Organization classification are included. Information from the literature most relevant to the 2017 World Health Organization revised classification and publications after 2016. Incorporating clinical, morphologic, and immunophenotypic features usually provides sufficient evidence to reach a preliminary diagnosis of mature T-cell lymphoma. Molecular genetic studies can be very helpful for the final diagnosis and classification, especially in challenging cases. Some molecular genetic features have been found in breast implant-associated anaplastic large cell lymphoma, distinct from anaplastic large cell lymphoma, ALK negative. Immunohistochemical staining of 4 markers may enable further subtyping of peripheral T-cell lymphomas.

NKp46 Is a Useful Diagnostic Biomarker in Gastrointestinal T-Cell Lymphoproliferative Diseases and Constitutes a Therapeutic Target. a Celac Network Study

Introduction:Primary gastrointestinal (GI) T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which diagnoses and therapeutic options remain to be standardized. Beside aggressive lymphoma, such as enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), the indolent T-cell lymphoproliferative disease (indolent T-LPD) has been recently described. A differential diagnosis to consider is type II refractory coeliac disease (RCDII) that may complicate CD. Intraepithelial lymphocytes (IEL) from RCDII are dependent for survival on IL-15, which reprograms T-lymphocytes towards a cytotoxic NK phenotype. We previously showed that NKp46 is a new biomarker for both diagnosis and prognosis in GI T-LPD (ICML-2017 Lugano, unpublished).Patients and Methods:The expression of NK receptors was assessed on CD/RCD by flow-cytometry. The number of NKp46 positive IEL per 100 epithelial cells (NKp46+ IEL/100 EC) was studied by immunohistochemistry (IHC) on 195 biopsies from 84 CD/RCD, 44 GI T-cell lymphoma, and on a blinded confirmatory cohort of 48 CD/RCD.8B6A-PBD is an anti-NKp46 monoclonal antibody conjugated (ADC) to a potent cytotoxic drug, pyrrolobenzodiazepine (PBD). For in vivo assessment, tumor-bearing NOD-SCID mice were randomly assigned to PBS, isotype-matched irrelevant Ig-PBD controls, or 8B6A-PBD treatment groups. For ex vivo cytotoxicity assays, isolated cells from fresh small bowel biopsies of RCDII patients were incubated with 8B6A-PBD, Ig-PBD, anti-NKp46 deglycosylated or PBD alone.Results:NKp46 was the only NK receptor that differs between RCDII and CD or RCDI. By doing ROC analysis, a number of NKp46+ IEL/100 EC above 25 clearly discriminated RCDII from CD and RCDI, with excellent positive and negative predictive values of 100 and 95% respectively. Among CD and RCD patients, the survival was shorter if this count is above 25 (OS-5years 72.8% vs. 96.4%, P=0.0004). NKp46 was expressed in EATL (n=20/25) and MEITL (n=4/4) but was never expressed in indolent T-LPD (n=0/15). Positive NKp46 GI T-cell lymphoma had a shorter survival compared to negative NKp46 cases (OS-5years 5.4% vs. 50.5%, P=0.0011).In vivo the anti-NKp46-PBD promoted tumor regression (Fig. B) and prolonged survival (Fig. A) of NOD-SCID mice injected by human NKp46-transfected Raji tumors embedded in matrigel. Ex vivo and as a proof of concept, the anti-NKp46-PBD was highly potent (Fig. D) and selective (Fig. C) against NKp46 positive primary sorted IEL (n=5).Conclusion:NKp46 provides a new biomarker for both diagnosis and prognosis in GI T-LPD. We propose a diagnostic algorithm for GI T-LPD based on the NKp46 expression, which is adapted to immediate, individual patient management. Overall, our results demonstrate for the first time that anti-NKp46 ADC may serve as an effective therapy for RCDII, EATL and MEITL and provide strong preclinical rationale for evaluation of 8B6A-PBD in clinical studies. [Display omitted] DisclosuresCheminant:Innate Pharma: Research Funding. Bruneau:Innate Pharma: Research Funding. Malamut:Cellimmune: Research Funding. Pouyet:MI-mAbs: Employment. Lhospice:Innate Pharma: Employment. Molina:Merck Serono: Honoraria; Takeda: Other: travel support to the ASH meeting; Novartis: Honoraria. Cellier:Cellimmune: Research Funding. Cerf-Bensussan:Cellimmune: Research Funding. Hermine:Novartis: Research Funding; Celgene: Research Funding; AB Science: Equity Ownership, Honoraria, Patents & Royalties, Research Funding; Hybrigenics: Research Funding; INatherys: Equity Ownership, Research Funding.

NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: a CELAC study.

Primary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs). NKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies. NKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo. NKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL.

消化管原発末梢性T細胞性リンパ腫と胃放線菌症が合併した1例

消化管原発末梢性T細胞性リンパ腫と胃放線菌症が合併した1例

Clinicopathologic Spectrum of Gastrointestinal T-cell Lymphoma: Reappraisal Based on T-cell Receptor Immunophenotypes.

The differential diagnosis of primary gastrointestinal EBV T-cell lymphoma (GITCL) includes enteropathy-associated T-cell lymphoma (EATL), peripheral T-cell lymphoma, not otherwise specified, adult T-cell leukemia/lymphoma, and anaplastic large cell lymphoma. Type II EATL is considered to be a tumor of intraepithelial lymphocytes. However, the evaluation of intraepithelial lymphocytosis by biopsy specimens is challenging, which poses a diagnostic problem between the EATL and peripheral T-cell lymphoma, not otherwise specified. This situation requested us to establish a pragmatic diagnostic approach for the classification of GITCL. We identified 42 cases of GITCL and analyzed clinicopathologic features, especially addressing their T-cell receptor (TCR) phenotype. Nine (21%) of 42 GITCL cases were positive for TCRγ protein expression. Among these TCRγ cases, TCRβ expression or not was detected in 5 and 4, respectively, but resulted in no further clinicopathologic differences. TCRβ positivity without TCRγ expression (βγ) was seen in 9 GITCL patients (21%). Twenty-four patients (57%) were negative for TCRβ and γ expression (βγ). Compared with TCRβγ or βγ type, TCRγ cases were characterized by exclusive involvement of intestinal sites (100% vs. 11%, P<0.001; 100% vs. 58%, P=0.032, respectively), but not of stomach (0% vs. 78%, P=0.002; 0% vs. 38%, P=0.039, respectively). Notably, TCRγ positivity was an independent unfavorable prognostic factor among our GITCL patients (P<0.001). Considering our results, TCRγ GITCL, that is, intestinal γδ T-cell lymphoma, appears to constitute a distinct disease entity.

Epitheliotropic Gastrointestinal T-Cell Lymphoma With Concurrent Insulinoma and Adrenocortical Carcinoma in a Domestic Ferret (Mustela putorius furo)

A 5-year-old male castrated ferret was presented for evaluation of chronic diarrhea, unresponsive to medical therapy. Initial examination and minimum database findings failed to determine an underlying etiology for the ferret’s gastrointestinal disorder. Biopsies obtained by exploratory surgery confirmed a diagnosis of epitheliotropic gastrointestinal T-cell lymphoma. Several treatment strategies were discussed, and ultimately palliative care with prednisolone was elected. Over the course of treatment, the ferret developed concurrent pancreatic beta-cell adenomas (insulinoma) and a left adrenocortical carcinoma. At the time of necropsy, nearly 15 months after the exploratory surgery, the lymphoma appeared to be in regression despite the use of only palliative therapy.

Endoscopic and clinical analysis of primary T‐cell lymphoma of the gastrointestinal tract according to pathological subtype

Little is known about the clinicopathological characteristics of primary gastrointestinal T-cell lymphomas (PGITL). This study evaluated the clinical and endoscopic features of the pathological subtypes of PGITL. Forty-two lesions in 36 patients with PGITL were assessed, including 15 enteropathy-associated T-cell lymphomas (EATL), 13 peripheral T-cell lymphomas (PTCL), 10 NK/T-cell lymphomas (NK/TL), and four anaplastic large cell lymphomas (ALCL). PTCL occurred more frequently in the stomach and duodenum and NK/TL more frequently in the small and large intestines (P = 0.009). The endoscopic features of the four subtypes were similar (P = 0.124). Fifteen of 41 lesions (36.6%) were Epstein-Barr virus (EBV) positive, with NK/TL more likely to be EBV positive than the other types (P < 0.001). First endoscopy and first computed tomography (CT) scan indicated that 65.4% and 51.4% of the lesions, respectively, were malignant, and that 43.2% and 42.3%, respectively, were GI lymphomas. The two modalities together correctly diagnosed about half of the lesions before biopsy. Intestinal perforation was associated with small bowel location (P < 0.001) and infiltrative type (P = 0.009), and was more common in NK/TL than in the other subtypes (P = 0.015). Multivariate analysis showed that higher international prognosis index (P = 0.008) and the presence of complications (P = 0.006) were associated with poor prognosis. Survival was poorer in patients with small bowel lesions than with lesions at other locations (P = 0.048). The four main pathological types of PGITL differed in clinical characteristics. As PGITL was often not diagnosed by initial endoscopic or radiological examination, a high index of suspicion is necessary to ensure its early diagnosis.

Indolent T-cell lymphoproliferative disease of the gastrointestinal tract

AbstractPrimary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4−/CD8+, 1 was CD4+/CD8−, and another was CD4−/CD8−. T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name “indolent T-LPD of the GI tract” for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy.

The many faces of gastrointestinal T-cell lymphoma manifest simultaneously in the same patient

The many faces of gastrointestinal T-cell lymphoma manifest simultaneously in the same patient

Type II enteropathy‐associated T‐cell lymphoma: A multicenter analysis from the Asia Lymphoma Study Group

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary gastrointestinal T-cell lymphoma. A multicenter study from the Asia Lymphoma Study Group identified 38 EATL patients within a 19-year period. All cases were type II EATL. Men were affected twice as common as women, at a median age of 59 (23-89) years. None had a history of celiac disease. The sites of involvement were small bowel and stomach (5%), small bowel (63%), small and large bowel (16%), and large bowel (18%). Common presenting features were bowel perforation (34%), pain (32%), and obstruction (21%). Lymphomas showed monomorphic neoplastic lymphoid infiltrates that were CD3⁺ (100%), CD56⁺ (91%), TIA-1⁺ (96%), CD4⁻CD8⁺ (63%), CD4⁺CD8⁺ (19%), CD4⁻CD8⁻ (16%), and CD4⁺CD8⁻ (3%). Epstein Barr virus was demonstrable in three cases. Despite chemotherapy and/or surgical resection, the overall response and complete response rates were poor at 46% and 38%. The median overall survival (OS) was 7 months and progression-free-survival (PFS) 1 month. Five patients underwent hematopoietic stem cell transplantation all were alive. Age and the prognostic index for peripheral T-cell lymphoma were not prognostically significant. Good performance status was associated with better OS (P = 0.03), and response to initial treatment led to better OS and PFS (P < 0.001).

The Early Diagnostic Accuracy for Gastrointestinal T-cell Lymphoma from a Perspective of Gastroenterologists

most common initial presenting symptoms of primary gastrointestinal T-cell lymphomas was abdominal pain (n=11, 73%). The anatomic location of the primary lesion the small bowel (n=8, 53%), colon (n=5, 33%), and stomach (n=3, 20%). There were no cases of T-cell lymphomas diagnosed based on clinical symptoms, radiologic findings, or endoscopic findings without biopsy alone. Pathologic confirmation of T-cell lymphomas by endoscopic examination was achieved in 7 cases (64%) and the remaining cases (n=8, 53%) were diagnosed with T-cell lymphomas based on pathologic examination after surgery. Conclusions: All of the patients with primary T-cell lymphomas of the gastrointestinal tract were diagnosed exclusively by endoscopic or surgical pathologic examainations, suggesting that gastroenterologists should scrutinize and suspect this disease with caution due to atypical gastrointestinal ulcers. (Intest

Clinicopathologic Analysis of Primary Gastrointestinal T-Cell Lymphoma with a Special Reference to Intestinal and Gastric Type in Japan.

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 (<6.0g/dL) (HR, 3.696; 95% CI, 1.671 to 8.171; P=.0012), platelet level (<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 (<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.

S2021 Clinical and Endoscopic Analysis of Primary T Cell Lymphoma of the Gastrointestinal Tract According to Pathology and EBV Status

Background:Primary gastrointestinal(GI) T-cell lymphomas are rare tumors and mostly reported from the East. The aims of this study were to determine the clinical and endoscopic features of primaryGI T cell lymphoma, with special emphasis on the pathologic classification, and to elucidate the correlation between Estein-Barr virus (EBV)/ T-cell receptor gene rearrangement (TCR) status and prognosis of this disease. Patients and Methods:35 cases of primary GI T cell lymphomas that satisfied Dawson's criteria were enrolled. The mean age at the time of diagnosis was 47.3 years (range 27 70), and the male:female ratio was 24:11. The 38 lesions from 35 patients were analyzed and classified into enteropathy-type (ETCL), NK/T cell (NK/T), peripheral T cell (PTCL), and anaplastic large cell (ALCL). Clinical characteristics, and endoscopic features were analyzed according to these types, and the survival analysis was done according to clinical factors and EBV/TCR status. EBV/TCR was determined by in situ hybridization and PCR. Results:The initial presenting symptoms were abdominal pain (n=18, 35.0%), fever (n=8, 21.0%), gastrointestinal bleeding (n=6, 15.8%), diarrhea (n=4, 10.5%), and soreness (n=2, 5.3%). As for the location, PTCL more commonly involved stomach (7/12, 58.3%) and duodenum (4/12, 33.3%) while ETCL occurred most frequently in small intestine (8/13, 61.5%), NK/T involved small (4/11, 36.4%) and large intestine (5/11, 45.6%) (p<0.05). The stage of disease at diagnosis was less advanced in NK/T than in ETCL and PTCL (p<0.05). Perforation developed more frequently in NK/T (46.2%) and ETCL (46.2%) than in PTCL (0%) (p<0.05). On endoscopy the lesions were ulcerative in 9 (33.4%), ulcerofungative in 7 (25.9%), ulceroinfiltrative in 5 (18.5%), infiltrative in 3 (11.1%), superficial/erosive in 2 (7.4%), and fungating in 1 (3.7%). The distribution was not different according to the pathologic types. The EBV positivity was higher in NK/T than other types (p<0.05). Initial treatment was surgical resection (n=22, 57.9%), chemotherapy (n=15,39.5%), or supportive care (n=1,2.6%). The median survival was 12.1 months. The poor prognosis is associated with more advanced stage, small bowel location, and perforation (p<0.05). Perforation was found to be the only independent predictor for the prognosis by multivariate analysis (p<0.05). Conclusion:Primary GI T cell lymphoma showed characteristic clinical features according to the 4 major pathologic types. The poor prognosis in this disease is associated with more advanced stage, small bowel location, and perforation. EBV is the most prevalent in NK/T cell type and is not affecting the prognosis.

Chromosomal Gains at 9q Characterize Enteropathy-Type T-Cell Lymphoma

Genetic alterations in enteropathy-type T-cell lymphoma (ETL) are unknown so far. In this series, 38 cases of ETL were analyzed by comparative genomic hybridization (CGH). CGH revealed chromosomal imbalances in 87% of cases analyzed, with recurrent gains of genetic material involving chromosomes 9q (in 58% of cases), 7q (24%), 5q (18%), and 1q (16%). Recurrent losses of genetic material occurred on chromosomes 8p and 13q (24% each), and 9p (18%). In this first systematic genetic study on ETL, chromosomal gains on 9q (minimal overlapping region 9q33-q34) were found to be highly characteristic of ETL. Fluorescence in situ hybridization analysis on four cases of ETL, using a probe for 9q34, indicated frequent and multiple gains of chromosomal material at 9q34 (up to nine signals per case). Among 16 patients with ETL who survived initial disease presentation, patients with more than three chromosomal gains or losses (n = 11) followed a worse clinical course than those with three or less imbalances (n = 5). The observation of similar genetic alterations in ETL and in primary gastric (n = 4) and colonic (n = 1) T-cell lymphoma, not otherwise specified, is suggestive of a genetic relationship of gastrointestinal T-cell lymphomas at either localization.

Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis

An extremely rare case of primary gastrointestinal T-cell lymphoma involving the stomach and intestine is reported. Radiographic and endoscopic examinations showed multiple polypoid lesions covered by a normal-appearing mucosa in the stomach, duodenal bulb, and terminal ileum and numerous small aphthoid lesions throughout the entire colorectum. Histopathologic, immunohistochemical, and polymerase chain reaction studies were performed using paraffin-embedded or fresh-frozen specimens from endoscopic biopsies and endoscopic mucosal resections. All lesions were composed of small, atypical lymphoid cells, which were classified as low-grade pleomorphic lymphoma. The tumor cells expressed CD3, CD4, and the T-cell receptor gamma gene phenotype as well as human mucosal lymphocyte 1 antigen, suggesting that the lymphoma cells were derived from intraepithelial T lymphocytes. This is the first description of primary gastrointestinal T-cell lymphoma with expression of human mucosal lymphocyte 1 antigen and a novel morphology resembling multiple lymphomatous polyposis. (Gastroenterology 1996 Sep;111(3):778-82)