Hemorragia digestiva y enfermedad celíaca complicada en paciente anticoagulado / Gastrointestinal bleeding and complicated celiac disease in anticoagulated patient

Resumen La enfermedad celíaca tiene una considerable frecuencia en nuestro medio. La mayoría de los pacientes presenta mejoría clínica, serológica y endoscópica al poco tiempo de iniciada la dieta libre de gluten. Un muy bajo porcentaje puede presentar o desarrollar una "enfermedad celíaca complicada", entidad que comprende el esprue refractario, la yeyunitis ulcerativa y el linfoma intestinal, que conllevan pronósticos desfavorables, con requerimiento de tratamientos más radicales. Presentamos aquí el caso de un paciente de 77 años evaluado en nuestro centro, que ingresó para estudio de hemorragia digestiva aguda y se realizó finalmente diagnóstico de enfermedad celiaca complicada, requiriendo inicio de tratamiento con corticoides sistémicos y seguimiento estrecho ambulatorio.

Abstract Celiac disease is considerably frequent in our media. Gluten-free diet shows clinical, serological and endoscopic improvement in most patients shortly after its start. A few patients may present or develop a "complicated celiac disease", an entity that includes refractory sprue, ulcerative jejunitis and intestinal lymphoma, which carry unfavorable prognoses, requiring more radical treatments. We present here the case of a 77-year-old male patient evaluated in our center, who was admitted for study of acute gastrointestinal bleeding. Complicated celiac disease was diagnosed, systemic corticosteroids were started and a close follow-up was carried out.

Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological analysis of twelve cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features, diagnosis and differential diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).@*Methods@#A total of 12 specimens were collected, which were surgically resected and verified as MEITL by postoperative pathology, immumohistochemical staining and gene rearrangement at the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018, and all of these had complete clinical and pathological data. The MEITL cases were reviewed to compare the clinicopathological characteristics, including morphologic and immunophenotypic features and followed up by telephone and clinic visit.@*Results@#All the cases were diagnosed with MEITL. There were 8 males and 4 females. Male to female ratio was 2∶1, at a median age of 54 years. The sites of involvement included jejunum (4 cases), ileum (5 cases), duodenum (1 case), ileocecal junction (1 case) and rectum (1 case). The neoplastic cells were monotonous of small to intermediate cells in size with round to slightly irregular nuclei in 11 cases. The immunophenotyping showed that CD3 (12/12), CD8 (11/12), CD43 (11/12), CD56 (11/12), TIA-1 (12/12) were positive; CD5 (12/12), Gran B (9/12), and perforin (7/12) were negative. Two cases aberrantly expressed the B-cell marker CD20. A high proliferation index was demonstrated by Ki-67 immunostaining. In situ hybridization for EBER was all negative(12/12). The whole exome sequencing(WES) mutational landscape of MEITL was remarkably homogeneous, showing significantly enriched clusters among histone modifier genes, JAK-STAT and MAPK-signal pathways. Histonelysine N-methytransferase SETD2 gene was mutated in 2/4 tumors. All the patients analyzed harbored at least one mutation in the JAK-STAT signal pathway, including STAT5B (2/4), JAK3 (3/4) and STAT5A (2/4). Furthermore, frequent alterations (TP53) were observed in the MAPK pathway in 3/4 of MEITL cases. The CNV analysis derived from WES data identified multiple regions of frequent gains and losses. In particular, gains in 1q, 7q and 9q, and recurrent losses involving 7p and 8p were observed.@*Conclusions@#MEITL is a rare and aggressive type of extranodal T-cell lymphoma. The differential diagnosis of MEITL includes EATL, extranodal NT/T-cell lymphoma and other types of PTCL. Diagnosis should be correlated to clinical symptoms while the final diagnosis is mainly based on the pathological features, immunophenotypes and genetic testing.

Clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract: a report of five cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract.@*Methods@#Five cases of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract from the Affiliated Hospital of Qingdao University from 2016 to 2019 were retrospectively reviewed. The clinical and pathological parameters were analyzed by combining clinical data and reviewing the available literature of 35 cases (34 cases abroad and 1 case in China).@*Results@#There were 4 males and 1 female with a median age of 47 years (18-66 years). All patients had abdominal pain and constitutional symptoms including diarrhea, emaciation, intermittent mucous stool or oral and epiglottic ulcers. Endoscopic manifestations included multiple punctate congestion, erosion and ulcer at the terminal ileum and colorectum. Two cases had congestion and erosion of antrum and angle of stomach, and the lesions did not fuse and form tumors. Histologically, the lamina propria was expanded by a dense, medium to small lymphocyte infiltration, which was monomorphic, with slightly irregular nuclei without prominent nucleolus or lymphoepithelial lesions. There were admixed small amount of plasma cells and eosinophils. In 4 cases, immunohistochemistry showed the lesional cells were positive for CD3, CD8, TIA1, and negative for CD4, CD56, granzyme B and Ki-67 index was ≤10%. In situ hybridization showed that EBER was negative and clonal TCR gene rearrangement was detected. One consultation case was CD3+, CD5- and Ki-67 index of 10%, although other indicators were not done. All five patients were treated with symptomatic support. In follow-up observation for 2 to 25 months, all patients were alive with the disease.@*Conclusions@#Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a newly classified monoclonal T-cell proliferative disease, with low incidence, clinical inertia and long-term survival. It has unique clinicopathological features but pathologically it is easily misdiagnosed as inflammatory bowel disease or T-cell lymphoma. Correct diagnosis is of great important clinical significance.

Enteropathy-associated T-cell lymphoma: An extremely rare cause of chronic diarrhoea

Chronic diarrhoea in tropical countries may be due to a myriad of causes from infective to non-infective. This case report illustrates the challenges faced in the investigation of a middle-age Chinese gentleman who presented with chronic diarrhoea and weight loss. The diagnosis of type II enteropathy-associated T-cell lymphoma (EATL) was finally made. The diagnosis of EATL was least suspected as the condition is almost unheard of in this part of the world. The epidemiology, presentation, diagnosis, management and prognosis of this rare condition are discussed.

Endoscopic Findings of Enteropathy-Associated T-Cell Lymphoma Type II: A Case Series

Enteropathy-associated T-cell lymphoma (EATL) is a rare extranodal T-cell lymphoma arising from the intestine. Two types of EATL have been reported. In contrast to the classic EATL type I, EATL type II occurs sporadically, is unrelated to celiac disease, and comprises 10% to 20% of all EATL cases. A total of five cases of EATL type II were diagnosed at our clinic from January 2009 to September 2012. Four of the five patients were diagnosed with the help of endoscopy. Among the four patients, two of the cases involved both the small and large intestines, whereas in the other two patients, EATL was limited to the small intestine. Common endoscopic findings included innumerable fine granularities (also called mosaic mucosal patterns) and diffuse thickening of the mucosa with a semicircular shallow ulceration in the lesions of the small bowel. In contrast, the endoscopic findings of the colon were nonspecific and could not distinguish EATL type II from other diseases. There are only few published reports regarding the representative endoscopic findings of EATL. Here, we present the clinical and endoscopic findings of four cases of EATL type II diagnosed by endoscopy.

Analysis of clinicopathological features of 21 patients with enteropathy-associated T-cell lymphoma / 肿瘤研究与临床

Objective To investigate the clinicopathological and prognosis features of enteropathy-associated T-cell lymphoma (EATL).Methods 21 cases of EATL,6 cases of peripheral T-cell lymphoma (PTCL) and 11 cases of natural-killer/T-cell lymphoma (NKTCL) were collected from January 2008 to May 2015.The immunophenotype of the tumor cell was tested by EnVision and as well as EBV-EBER for EB virus.Some patients were performed with follow-up data.Results 21 EATL patients included 14 males,7 females and the middle age was 55 years old (40-79 years old).15 patients affected the small bowel,4 cases affected colon,2 cases affected more than one site.18 cases were mono-morpholohic EATL while 3 cases were classical EATL.The expression rates of neoplastic cells for CD3ε,CD4,CD8,CD56,Granzyme B,TIA-1 were 95.24 ％ (20/21),20.00 ％ (3/15),73.68 ％ (14/19),85.71％ (18/21),64.71％ (11/17),88.89 ％ (16/18) respectively.The expression of EBER in EATL patients (0,0/21) was obviously lower than that in NKTCL patients (100 ％,11/11).17 EATL patients had follow-up data,and the middle survival time was 15 months.No different prognosis was found in the three kinds of T-NHL (P =0.697).Conclusions EATL usually occurs in elder male and jejunum.The diagnosis of EATL needs a lot of information,including clinical history,endoscopy,histomorphology,immunophenotype and EBV-EBER result.EATL has low mobidity and high malignancy,it still lacks impactful therapeutic regimen.

Linfoma T intestinal monomórfico CD56+. Primer caso informado en Colombia y revisión de la literatura / Monomorphic Intestinal T-Cell Lymphoma. First reported case in Colombia and review of the literature

Se informa el caso de una mujer de 80 años con hallazgo incidental de masa abdominal en mesogastrio. Se le realiza resección de intestino delgado por sospecha de absceso con síndrome adherencial. El estudio patológico de la pieza quirúrgica demostró compromiso por linfoma no Hodgkin T monomórfico CD56+. Los linfomas T del tubo digestivo son inusuales; corresponden al 5% de las neoplasias linfoides de esta localización. El linfoma intestinal T monomórfico CD56+ corresponde a 10-20% de los linfomas T intestinales. Se presenta en regiones donde la enfermedad celiaca es infrecuente y no se asocia a enteropatía. Su curso es agresivo y habitualmente se manifiesta como una emergencia quirúrgica por obstrucción o perforación intestinal.

80 year old woman with incidental finding of abdominal mass in midgut, in which small bowel resection is performed for suspected abscess associated to surgical adhesions. Pathological examination of the surgical specimen showed a monomorphic CD56+ T cell lymphoma. T-cell lymphomas of the digestive tract are rare, accounting for 5% of all lymphoid neoplasms in this location. Monomorphic CD56+ intestinal T cell lymphoma corresponds to 10 - 20% of T cell intestinal lymphomas. This tumor occurs in regions where celiac disease is rare and it is not associated with enteropathy. Its course is aggressive and usually manifests as a surgical emergency by intestinal obstruction or perforation.

Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre.

Purpose: Retrospective analysis of 81 routinely diagnosed gastrointestinal (GI) lymphoma to illustrate clinicopathological and immunohistochemical characteristics with predisposing condition. Materials and Methods: Age, sex, site, tumour stage, associated pathological features like lympho-epithelial lesion (LEL), atrophic gastritis (AG), intestinal metaplasia (IM) and enteropathy changes were analysed. Requisite immunohistochemical panel was applied wherever needed. Results: There were 55 male and 26 female patients with median age of 54.5 years. Site wise distributions were stomach 40, small intestine 22, colon 4, cecum 2, ileocecum 3, esophagus 1 and multiple sites 9. Histological subtypes were mucosa associated lymphoid tissue lymphoma (MALTOMA) 48, diffuse large B cell lymphoma (DLBL) 21, T cell lymphoma 9 [5 anaplastic large cell lymphoma (ALCL) and 4 enteropathy associated T cell lymphoma (EATL)], immunoproliferative small intestinal disease (IPSID) 2 and follicular lymphoma 1. LEL was present in 31 cases. Of the 19 AG, 8 had associated IM, and 1 case each had associated H Pylori infection and neuroendocrine tumor. Enteropathy was observed in 4 EATL, and one case each of DLBL and high grade MALTOMA. Giardia infection was present in 1 low grade duodenal MALTOMA. Of the 24 resected specimens, 16 were stage IE, 7 stage IIE and 1 stage IV (Mushoff's staging). Conclusion: Primary GI lymphoma was frequently observed in 6 th decade of life with male preponderance. Stomach was the commonest site and high grade MALTOMA being the commonest histological variant. Isolated colonic involvement and intestinal perforations were not infrequent. Rare variants like ALCL and follicular lymphomas were also observed.

Enteropathy associated T cell lymphoma-monomorphic variant, presenting as bilateral ovarian masses.

Enteropathy associated T cell lymphoma (EATL) is a rare type of T-cell lymphoma, often associated with a history of celiac disease. It usually arises in the jejunum, but can involve other gastrointestinal tract sites such as stomach and colon. Monomorphic variant of EATL often occurs without a history of celiac disease, has variable histologic evidence of enteropathy, and is usually CD56+. We report a case of EATL in a 49-year-old female presenting as bilateral ovarian masses. The morphology and immunophenotypic features were compatible with monomorphic variant of EATL.

Enfermedad Celiaca y Obstrucción Intestinal por Linfoma de Células T / Celiac disease and intestinal obstruction by T cell lymphoma

Paciente varón de 55 años, raza blanca (ascendencia española), natural y procedente de Ayacucho, que ingresó por una enfermedad de seis meses de evolución, caracterizada por dolor abdominal tipo cólico y baja ponderal de 10 Kg. Había estado hospitalizado seis meses antes y dado de alta con el diagnóstico de síndrome de intestino irritable. Entre sus antecedentes refería intolerancia a la lactosa y artritis reumatoidea. Los exámenes mostraron: Hb:12 g/dl, leucocitos: 5260 cel/mm, abastonados: 11%, albúmina: 2,7 mg/ml y VSG: 33mm/h. El resto de exámenes -incluyendo los marcadores tumorales- fueron normales. El tránsito gastrointestinal mostraba las asas delgadas con fragmentación del bario y dilatación focal moderada de un asa yeyunal distal. La tomografía de tórax, abdomen y pelvis sin alteraciones; Rx tórax normal. La colonoscopia fue normal; el íleon tenía pocos pliegues y pequeñas nodulaciones, las biopsias indicaron "ileitis inespecífica". La endoscopia mostró gastritis y una cicatriz de úlcera duodenal; la mucosa duodenal mostraba áreas con aspecto de mosaico rosado-blanquecino. La biopsia duodenal evidenció acortamiento de vellosidades, infiltrado inflamatorio crónico e incremento de linfocitos intraepiteliales, hallazgos compatibles con los criterios de celiaquía Marsh-tipo 3. Los anticuerpos IgA antiendomisio y antitransglutaminasa tisular estaban incrementados. Durante su hospitalización aumentó el dolor y aparecieron signos de obstrucción. En la laparotomía se encontraron una tumoración yeyunal estenosante y una perforación adyacente. El espécimen mostró un linfoma intestinal de células T. Se ha demostrado que existen más celiacos subclínicos que celiacos con esprue clásico; el conocimiento de esta situación nos debe llevar a tenerla presente por sus complicaciones o asociaciones, una de las cuales es el linfoma primario intestinal.

A male patient, 55 years old, born in Ayacucho, with Spanish ancestors, was hospitalized through emergency referring abdominal pain, and 10 kilograms weight loss. Six months before he was diagnosed as having irritable bowel syndrome. His previous diseases were rheumatoid arthritis and intolerance to lactose. Laboratory results were: Hb 12 gr./dL, white cells 5200 per mm3, albumin 2.7 gr./dL, erythrocyte sedimentation rate 32 mm/hr., and tumor markers were negative. Radiographic study of the small bowel showed barium fragmentation, and a focal dilation in distal jejunum. Chest X-ray and CT scan of thorax, abdomen and pelvis were normal. Colonoscopy was normal for colonic mucosa, but in ileum it showed an irregular mucosa, little nodules and fewer folds than usual. Biopsy from ileum demonstrated unspecific inflammation. Upper endoscopy showed gastritis, a duodenum scar ulcer and an irregular mosaic pattern pink and white. Duodenum biopsy demonstrated short villi, chronic inflammation and an increase in the number of intraepithelial lymphocytes, all these was consistent with celiac disease Marsh 3. Antibodies anti-endomisium and anti-transglutaminase were positive. After some days he developed signs of bowel obstruction and was operated. A tumor was found in jejunum with a bowel perforation. Pathological study showed a small bowel T-cell lymphoma. Fortunately this patient did well, and was sent home to continue treatment on ambulatory basis. Celiac disease is more common than what is thought, and it has been demonstrated that there are more persons with subclinical celiac disease, than those with the typical clinical pattern. It is necessary to be aware of this disease to improve diagnosis in order to avoid late complications as small bowel lymphoma.

A Case of Enteropathy-Associated T-cell Lymphoma (EATL) Presenting Perforation after Chemotherapy for Primary Intestinal Lymphoma / 대한소화기내시경학회지

Intestinal T-cell lymphomas are fairly uncommon, and can sometimes be associated with enteropathy. Enteropathy-associated T-cell lymphoma (EATL) is commonly accompanied by a nonspecific mucosal ulceration, similar to that observed as a complication of celiac disease. The clinical course of EATL is quite unfavorable, and tends to have a generally poor prognosis. When a tumor invades the bowel wall and is treated with corticosteroids and chemotherapy, cell lysis with perforation often occurs, particularly in case of lymphoma. Recent data indicate that extensive resection may improve local control, and eliminate the risk of early mortality due to visceral perforation or hemorrhaging in unresected lesions during chemotherapy. Here, we report the case of a 51-year-old male who was diagnosed with primary gastrointestinal lymphoma after colonoscopy, and presented with EATL after emergent exploratory laparatomy. We also include a review of the literature regarding this uncommon entity.