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Objective:To investigate the histopathological morphology, immunophenotype, molecular pathological features, clinical prognosis and treatment of monomorphic epithelial intestinal T-cell lymphoma (MEITL).Methods:The clinicopathological data of 5 patients with MEITL in Sichuan Jinyu Medical Laboratory Center Co., Ltd from March 2019 to February 2021 were retrospectively analyzed, and literatures were reviewed. All cases were tested by using histopathology, immunohistochemistry, in situ hybridization of Epstein-Barr virus (EBV) and T-cell clonability assessment, and 1 case had second-generation sequencing (NGS) test. Clinical follow-up was performed in 2 patients.Results:All 5 MEITL cases were middle-aged and old men. The histopathology showed that intestinal wall was diffuse with tumor cells infiltrating, and the cells were obviously epitheliophilic. All the tumor cells CD3, CD8, CD56, GrB were positively expressed, and expressions of other T-cell markers were different, among which 1 case had CD30 positive and 1 case had CD20 positive. All 5 cases were negative for EBV by in situ hybridization. Monoclonal rearrangement of T-cell receptor gene was detected in all 5 cases. Mutations of BCOR, JAK3, STAT5B and ATM were detected in 1 case by using NGS. Among 2 cases followed-up, 1 patient relapsed 7 months after he had the initial onset and underwent the first operation, and then he had another operation. This patient finally died of extensive metastasis in the lung, liver and abdominal cavity as well as ascites 13 months later; another patient died 1 month after emergency surgery for perforation.Conclusions:MEITL is a rare primary T-cell lymphoma of the digestive tract. The oncogenic event in the pathogenesis of MEITL mainly involves mutations in the tumor suppressor gene SETD2 and mutations in one or more genes of the JAK/STAT pathway. Currently, there is no standard treatment for MEITL. Most treatment options include surgical resection and anthracycline-based chemotherapy.
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Objective To summarize the clinicopathological features of monomorphic epitheliotropic intestinal T cell lymphoma (MEITL),and provide the experiences and lessons for diagnosis and treatment.Methods The clinical manifestations,histopathological and immunohistochemical characteristics,diagnosis,treatment and prognosis of 3 cases of MEITL were analyzed retrospectively.Meanwhile,the other cases published in the literatures were reviewed and summarized.Results Two cases of middle aged and aged men and one young woman were reported in present paper.These lesions of all the 3 patients were at the small intestine,of which the female patients had skin and mammary gland involvement.The clinical manifestations were abdominal distention,mulligrubs and intestinal perforation,and the main pathological feature was the diffuse infiltration of the homogeneous tumor cells in the whole layer intestinal wall.Immunohistochemical examination showed that tumor cells expressed all T cell markers CD3,CD8,CD56,T cell cytoplasmic antigen (TIA-1),CD4 and CD5,and Ki-67 proliferation index was 50％-70％.As to the treatment,case 1 received CHOP and GDP regimens successively,and died 2 years after final diagnosis.Case 2 received CHOP regimen for 1 course of chemotherapy and died of giving up treatment.Case 3 gave up treatment,voluntary discharged and then lost.It is clear according to the previous literatures and our experiences that the MEITL possesses high invasiveness and low incidence,and makes the diagnosis difficult;the patient's response to the current treatment is poor.Conclusions MEITL is prone to be in the small intestine.The diagnosis of MEITL should be based on clinical manifestations,pathological features and immunohistochemical detection results.MEITL is rare,the course of disease progresses rapidly,and the patients have the tendency to have intestinal perforation and poor prognosis.Early diagnosis and positive chemotherapy may lead to a better prognosis.
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Objective To clarify the clinical features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with minor endoscopic abnormalities. Methods The clinical data of 6 patients with MEITL characterized by minor endoscopic abnormalities in Peking Union Medical College Hospital from 2012 to 2016 were retrospectively analyzed, including clinical manifestations, endoscopic, pathological features, medications and prognosis. Results Five out of 6 patients were male, with an average age of 61.2 years old. The median disease duration was 4.5 months. All patients initially presented with diarrhea without specific findings for serologic testing. CT enterography showed continuous intestinal lesions, including symmetric thickening of the bowel wall, abnormal hyperenhancement of mucosal surface and lymphadenopathy. Endoscopic appearances were only mildly abnormal, including mucosal swelling, atrophy of villus, mosaic sign and shallow ulcers. Histopathologic findings revealed massive small to medium sized T lymphocytes infiltration with positive expression of CD3 and CD8. Chemotherapy and palliative treatment were administrated after diagnosis. Conclusions Clinical presentations of MEITL are non-specific with minor endoscopic abnormalities. Therefore, biopsy is indispensable for patients with a relatively normal endoscopic result.
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Objective To analyze clinical features and prognosis of primary intestinal T cell lymphoma (ITCL)which was misdiagnosed as Crohn′s disease (CD),and summarized the key points of differentiation between ITCL and CD.Methods From January 2003 to January 2014,clinical data of patients with ITCL once misdiagnosed as CD were retrospectively analyzed,which included demographic,clinical,pathological and prognostic data.The data of 177 patients diagnosed as CD from January 2012 to January 2014 were collected. The demographic,clinical,pathological and prognostic data of these two groups were analyzed and compared. The continuous variables were compared with t test or Mann-WhitneyU test,and the differences of classification variables between two groups were analyzed by Chi-square test or Fisher exact probability method.Results A total of 18 patients (17 males and one female)with ITCL misdiagnosed as CD were enrolled in the study,and the median age at diagnosis was 38.5 (28.8 to 42.5)years and the median duration of diagnosis was 6.00 (3.75 to 13.25)months.The common primary symptoms were abdominal pain (12/18),diarrhea (13/18)and anemia (13/18).Intestinal perforation was primary symptom in two cases (2/18).However,B symptoms of lymphoma was observed in 16 patients,which included fever in 13 patients,weight loss in 16 patients and night sweat in one patient.One or more serious complications appeared in 12 patients,which included intestinal perforation in nine patients,severe gastrointestinal bleeding in seven patients and intestinal obstruction in two patients.In 177 patients with CD,104 patients were male (58.8%),and the median age at diagnosis was 22.0 (18.0 to 29.0) years.The primary symptoms were abdominal pain (88.7%,157/177),diarrhea (55.9%,99/177),anemia (63.8%,113/177),fever (33.3%,59/177)and weight loss (59.9%,106/177).During the disease course,30 patients (16.9%)had intestinal perforation (mainly chronic),12 patients (6.8%)had intestinal obstruction and seven patients (4.0%)had severe gastrointestinal bleeding.Compared to CD patients,male patients were more common in ITCL (χ2 =8.837,P <0.01),age at diagnosis was older (χ2 =314.5,P <0.01),the disease course was shorter (U=385.0,P <0.01),weight loss (χ2 =5.867,P <0.05)and fever (χ2 =10.609,P <0.01)were more common in clinical symptoms and intestinal perforation and severe gastrointestinal bleeding were more common in complications (χ2 =9.185,24.908,both P <0.01).The lesions of ITCL were multiple lesions, small bowel involved in eight cases,colon involved in 14 cases and one case with esophagus involved.Under endoscopy examination,most lesions appeared as ulcerations and were segmentally distributed.Compared to CD, lymphocyte proliferation was more common in the intestinal histopathological findings of ITCL (17/18 vs 19.7%(35/177);χ2 =42.844,P <0.01)and granuloma was rare (0 vs 42.8%(76/177),χ2 =12.665,P <0.01). Among 18 patients with ITCL,nine received chemotherapy and the median survival time was two months. Conclusions Primary ITCL had non-specific symptoms and was easily misdiagnosed as CD.More attention should be paid to the differential diagnosis of the two disease.
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Objective To investigate the status of Epstein Barr virus (EBV) latent infection, the subtypes of EBV, and the expression of EBV genome in intestinal T cell lymphoma (ITCL). Methods In situ hybridization for EBER1/2 and polymerase chain reaction for EBV nuclear antigen gene (EBNA 3C) of two EBV subtypes were performed in forty two cases of ITCL. Some cases which were positive in both in situ hybridization and immunohistochemistry were detected by double staining. Amplified product of EBNA 3C gene was analyzed by DNA sequencing. For immunohistochemical staining, EBNA 2 and LMP 1 monoclonal were applied. Results EBV infection was detected in 41 of the 42 cases ( 97.6% ). Thirty eight cases ( 90.5% ) exhibited specific bands by polymerase chain reaction, in which 32 (84.2%) were EBV type A, 2 (5.3%) were type B and 4 ( 10.5% ) were mixtures of type A and B. There were seldom base insertion and base deletion in EBNA 3C gene. In 36 ( 85.7% ) cases, the tumor cells showed positive in EBER1/2 ISH, and they were demonstrated to express CD 45 RO, CD 4, CD 8, CD 56 , or TIA 1 by in situ hybridization immunohistochemistry double staining. The expression frequency of LMP 1 was 38.1% (16/42). None case presented EBNA 2 positive reaction. There were two patterns of EBV latent infection in ITCL, the more common one was type Ⅰ and the other was type Ⅱ. Conclusions A high level EBV latent infection is present in ITCL in China, and EBV type A frequently occurs. The patterns of EBV latent infection in ITCL are either type Ⅰ or type Ⅱ. ITCL and nasal NK/T cell lymphoma might belong to the same spectrum.