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The Asian small-clawed otter ( Aonyx cinereus) is an endangered species that is common in zoologic collections. A 17-y-old female Asian small-clawed otter under human care, with a clinical history of chronic renal disease, was euthanized because of deteriorating health. Histologically, the jejunal wall was infiltrated by a monomorphic population of small neoplastic lymphocytes that expanded the lamina propria of the villi and crypts, and on rare occasions invaded the submucosa. The tumor was composed of T cells (CD3+) with a proliferation index of 16%. Based on the World Health Organization (WHO) Classification of Hematopoietic Neoplasms in Domestic Animals, this lymphoma was classified as an enteropathy-associated T-cell lymphoma (EATL) type 2. We also present here a review of the literature on intestinal lymphoma in the subfamily Lutrinae (otters).

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.

Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.

Monomorphic epitheliotropic intestinal T-cell lymphoma, formerly known as enteropathy-associated T-cell lymphoma, is an extremely rare, aggressive peripheral extranodal T-cell lymphoma, that is infrequent in native European and Caucasian populations. The current study presents the clinicopathological features, diagnostic approach, and clinical outcomes of this rare entity of lymphoma and highlights the importance of the early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Main symptoms and/or important clinical findings: We present the case of a 69-year-old male patient presenting with an abdominal mass, intestinal transit disorder, and weight loss. The abdominal computed tomography (CT) revealed features suggestive of a malignancy. Following clinical and imaging investigations, surgical resection of the small intestine with other areas of involvement has been performed and further to the histopathological examination and immunohistochemical testing are mandatory.Histopathological evaluation of the tumor revealed a proliferation of medium- to large-sized monomorphic lymphocytes, with vesicular nuclei, prominent nucleoli, and a moderate amount of clear to pale eosinophilic cytoplasm, with an association of infrequent Reed-Sternberg-like cells. Immunohistochemical assessment of the aforementioned tumor using CD3, CD8, CD5, CD20, and CD30 confirmed the T cell proliferation line and the monomorphic epitheliotropic intestinal T-cell lymphoma diagnosis.The current report highlights the importance of early diagnosis of MEITL owing to its poor prognosis and presents histopathological features that help distinguish MEITL from inflammatory bowel diseases and less aggressive T-cell lymphomas.

Celiac disease (CD) is a chronic immune-mediated intestinal disease with genetic susceptibility. It is characterized by inflammatory damage to the small intestine after ingestion of cereals and products containing gluten protein. In recent years, the global prevalence rate of CD has been approximately 1%, and is gradually increasing. CD patients adhere to a gluten-free diet (GFD) throughout their entire life. However, it is difficult to adhere strictly to a GFD. Untreated CD may be accompanied by gastrointestinal symptoms, such as diarrhea, abdominal pain, and extraintestinal symptoms caused by secondary malnutrition. Many studies have suggested that CD is associated with intestinal tumors such as enteropathy-associated T-cell lymphoma (EATL), small bowel cancer (SBC), and colorectal cancer. In this study, we reviewed related studies published in the literature to provide a reference for the prevention and treatment of intestinal tumors in patients with CD. Compared with the general population, CD patients had a high total risk of SBC and EATL, but not colorectal cancer. The protective effect of GFD on CD-related malignancies is controversial. Further studies are needed to confirm whether GFD treatment can reduce the risk of intestinal neoplasms in CD.

Enteropathy-associated T cell lymphoma (EATL) is a rare subtype of mature T cell lymphoma. The available literature about this rare type T cell lymphoma is relatively limited. This article provides a summary and review of the available literature addressing this entity in terms of risk factors, pathogenesis, diagnostic, and therapeutic options. EATL has two distinct subtypes. Type I EATL, now known as EATL, is closely, but not exclusively linked to celiac disease (CD), and it is primarily a disease of Northern European origin. It accounts for < 5% of peripheral T cell lymphoma (PTCL). Risk factors for EATL include advanced age, male sex, and most importantly, genetic susceptibility in the form of HLA-DQ2 homozygosity. The pathogenesis of EATL is closely related to celiac disease as it shares common pathogenic features with refractory celiac disease. The gold standard of diagnosis is histological diagnosis. EATL carries an aggressive course and a poor prognosis. Treatment of EATL includes surgery, induction chemotherapy, and consolidation in first complete remission and autologous stem cell transplant. The role of targeted and biologic therapies in newly diagnosed EATL patients along with relapsed, refractory cases is evolving and discussed in this review. EATL is an aggressive peripheral T cell lymphoma with poor overall treatment outcome using currently available therapy options. Clinical trials are considered the best approach for treatment of EATL. Early diagnosis and early referral to specialized centers would be the best way to deal with such patients. Development of new prognostic models and early surgical intervention are warranted. Prevention is where all the efforts should be spent, by counseling patients with CD regarding the importance of adherence to gluten-free diet and development of periodic surveillance programs in celiac disease patients for early detection of pre-lymphoma lesions.

The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. It will review evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, potential therapeutic options, and surveillance for complications of this condition.This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: In patients believed to have celiac disease who have persistent or recurrent symptoms or signs, the initial diagnosis of celiac disease should be confirmed by review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. BEST PRACTICE ADVICE 2: In patients with confirmed celiac disease with persistent or recurrent symptoms or signs (nonresponsive celiac disease), ongoing gluten ingestion should be excluded as a cause of these symptoms with serologic testing, dietitian review, and detection of immunogenic peptides in stool or urine. Esophagogastroduodenoscopy with small bowel biopsies should be performed to look for villous atrophy. If villous atrophy persists or the initial diagnosis of celiac disease was not confirmed, consider other causes of villous atrophy, including common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy. BEST PRACTICE ADVICE 3: For patients with nonresponsive celiac disease, after exclusion of gluten ingestion, perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, lactose or fructose intolerance, and small intestinal bacterial overgrowth. BEST PRACTICE ADVICE 4: Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish between subtypes of refractory celiac disease and to exclude enteropathy-associated T-cell lymphoma. Type 1 refractory celiac disease is characterized by a normal intraepithelial lymphocyte population and type 2 is defined by the presence of an aberrant, clonal intraepithelial lymphocyte population. Consultation with an expert hematopathologist is necessary to interpret these studies. BEST PRACTICE ADVICE 5: Perform small bowel imaging with capsule endoscopy and computed tomography or magnetic resonance enterography to exclude enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis at initial diagnosis of type 2 refractory celiac disease. BEST PRACTICE ADVICE 6: Complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies in patients diagnosed with refractory celiac disease. Check albumin as an independent prognostic factor. BEST PRACTICE ADVICE 7: Correct deficiencies in macro- and micronutrients using oral supplements and/or enteral support. Consider parenteral nutrition for patients with severe malnutrition due to malabsorption. BEST PRACTICE ADVICE 8: Corticosteroids, most commonly open-capsule budesonide or, if unavailable, prednisone, are the medication of choice and should be used as first-line therapy in either type 1 or type 2 refractory celiac disease. BEST PRACTICE ADVICE 9: Patients with refractory celiac disease require regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy. Identify local experts with expertise in celiac disease to assist with management. BEST PRACTICE ADVICE 10: Patients with refractory celiac disease without response to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials.

Background Enteropathy-associated T cell lymphoma (EATL) is an aggressive intestinal T cell lymphoma derived from intraepithelial lymphocytes, which occurs in individuals with celiac disease (CD). Cerebral involvement is an extremely rare condition and as described so far, lymphoma lesions may present as parenchymal predo-minantly supratentorial or leptomeningeal involvement. We describe a case of EATL with multifocal supra- and infratentorial brain involvement in a patient with refractory celiac disease (RCD). Case summary A 58-years old man with known CD developed ulcerative jejunitis and was diagnosed with RCD type II. Six months later he presented with subacute cerebellar symptoms (gait ataxia, double vision, dizziness). Cranial magnetic resonance imaging (MRI) revealed multifocal T2 hyperintense supra- and infratentorial lesions. Laboratory studies of blood and cerebrospinal fluid were inconspicuous for infectious, inflammatory or autoimmune diseases. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) scan showed a suspect hypermetabolic lesion in the left upper abdomen and consequent surgical jejunal resection revealed the diagnosis of EATL. During the diagnostic work-up, neurological symptoms aggravated and evolved refractory to high-dosage cortisone. Recurrent MRI scans showed progressive cerebral lesions, highly suspicious for lymphoma and methotrexate chemotherapy was initiated. Unfortunately, clinically the patient responded only transiently. Finally, cerebral biopsy confirmed the diagnosis of cerebral involvement of EATL. Considering the poor prognosis and deterioration of the performance status, best supportive care was started. The patient passed away three weeks after diagnosis. Conclusion EATL with cerebral involvement must be considered as a possible differential diagnosis in patients with known RCD presenting with neurological symptoms.

BACKGROUND Enteropathy-associated T-cell lymphoma (EATL) is a rare invasive lymphoma derived from gastrointestinal epithelial T lymphocytes. EATL involving the whole gastrointestinal tract accompanied with early colon cancer is extremely rare. CASE SUMMARY We present the case of a 67-year-old man with diarrhea for more than 5 mo whose colonoscopy in another hospital showed multiple colonic polyps, which indicated moderate to severe dysplasia and focal early cancer. Therefore, he was referred to our hospital for further endoscopic treatment. Colonoscopy after admission showed that the mucosa of the terminal ileum and the entire colon were slightly swollen and finely granular. Endoscopic mucosal resection was performed for colonic polyps located in the liver flexure of the colon and descending colon, respectively. Histopathological findings revealed diffuse infiltration of medium-sized lymphoid cells in the colonic mucosa and visible lymphoepithelial lesions. The histopathology of the polyp in the descending colon indicated moderately differentiated adenocarcinoma limited to the mucosa with negative resection margins. Additionally, immunohistochemical analysis showed positive staining for CD7 and CD8. Therefore, we arrived at a diagnosis of EATL with early colon cancer. Subsequently, the patient was transferred to the hematology department for chemotherapy. The patient’s diarrhea was not significantly relieved after receiving chemotherapy, and he ultimately died of severe myelosuppression. CONCLUSION EATL should be considered in unexplained chronic diarrhea. EATL progresses rapidly with a poor prognosis, especially when accompanied with early colon cancer.

The intestinal T-cell lymphomas are a rare group of lymphatic malignancies arising from the gastrointestinal tract. They frequently manifest with non-specific clinical and radiographic findings that may mimic several other disease processes. The most common subtype is linked with refractory coeliac disease and commonly affects the small intestine. We report a case where the diagnosis was uncovered endoscopically in a patient presenting with colonic perforation on a background of long-standing ulcerative colitis. Surgical source control was required prior to considering chemotherapy, which is the usual treatment option in lymphatic malignancies. The case highlights the importance endoscopic evaluation in inflammatory conditions of the colon.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a primary intestinal T-cell lymphoma and other organ involvement is very rare. A rare case of MEITL involving the lung and brain is herein reported. The patient developed panperitonitis with a small intestinal perforation, and emergency surgery was performed. The pathological findings from the surgical specimens demonstrated atypical lymphoid cells which were positive for CD3, CD8, and CD56. Moreover, the pathological findings of lung specimens taken by bronchoscopy were consistent with those of the small intestine. It is therefore important to include the possibility of MEITL in the differential diagnosis of cancer patients.

Background In order to study the CXCR4 expression with [68Ga]pentixafor PET in different types of non-Hodgkin lymphoma, we performed a retrospective study to describe the [68Ga]pentixafor PET/CT imaging in a spectrum of lymphomas and to compare it with [18F]FDG PET/CT. Results Twenty-seven patients with newly diagnosed non-Hodgkin lymphoma were recruited retrospectively. [68Ga]pentixafor PET showed increased radioactivity in lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), diffuse large B cell lymphoma (n = 3), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), unclassified indolent B cell lymphoma (n = 3), and enteropathy associated T cell lymphoma (n = 3). However, peripheral T cell lymphoma, not otherwise specified (n = 1), and NK/T cell lymphoma (n = 2) were not avid for [68Ga]pentixafor. In comparison to [18F]FDG PET, [68Ga]pentixafor PET demonstrated more extensive disease and higher radioactivity in lymphoplasmacytic lymphoma and marginal zone lymphoma. Conclusion CXCR4 expression varies in different types of non-Hodgkin lymphoma. Overexpression of CXCR4 was detected with [68Ga]pentixafor PET/CT in lymphoplasmacytic lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, unclassified indolent B cell lymphoma, and enteropathy associated T cell lymphoma. The uptake of [68Ga]pentixafor was higher than [18F]FDG in lymphoplasmacytic lymphoma and marginal zone lymphoma.

Background The incidence of intestinal NK/T cell lymphoma (NKTCL) is extremely low, and the clinical symptoms are atypical, which makes it difficult to distinguish this disorder from Crohn's disease (CD), T lymphocyte proliferative disease, and other immune disorders. The misdiagnosis rate is high, and the patient's prognosis is poor. Case summary In this case, the patient had repeated high fever, colonoscopy revealed multiple ulcers, and the initial diagnosis was CD. The patient's condition did not improve after treatment with hormones and infliximab, and she eventually died. Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged. Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive. Colonoscopy, tissue biopsy, and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype. On the basis of the patient's medical history, auxiliary examination, and pathological findings, digestive physicians and pathologists gave the diagnosis of NKTCL. Conclusion Clinicians need to improve their comprehensive knowledge of NKTCL, and combination of clinical symptoms, histological characteristics, as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.

Background Differentiation of lymphocytic-plasmacytic enteropathy (LPE) from small cell lymphoma (SCL) in cats can be challenging. Hypothesis/objective Histology-guided mass spectrometry (HGMS) is a suitable method for the differentiation of LPE from SCL in cats. Animals Forty-one cats with LPE and 52 cats with SCL. Methods This is a retrospective clinicopathologic study. Duodenal tissue samples of 17 cats with LPE and 22 cats with SCL were subjected to HGMS, and the acquired data were used to develop a linear discriminate analysis (LDA) machine learning algorithm. The algorithm was subsequently validated using a separate set of 24 cats with LPE and 30 cats with SCL. Cases were classified as LPE or SCL based on a consensus by an expert panel consisting of 5-7 board-certified veterinary specialists. Histopathology, immunohistochemistry, and clonality testing were available for all cats. The panel consensus classification served as a reference for the calculation of test performance parameters. Results Relative sensitivity, specificity, and accuracy of HGMS were 86.7% (95% confidence interval [CI]: 74.5%-98.8%), 91.7% (95% CI: 80.6%-100%), and 88.9% (95% CI: 80.5%-97.3%), respectively. Comparatively, the clonality testing had a sensitivity, specificity, and accuracy of 85.7% (95% CI: 72.8%-98.7%), 33.3% (95% CI: 14.5%-52.2%), and 61.5% (95% CI: 48.3%-74.8%) relative to the panel decision. Conclusions and clinical importance Histology-guided mass spectrometry was a reliable technique for the differentiation of LPE from SCL in duodenal formalin-fixed paraffin-embedded samples of cats and might have advantages over tests currently considered state of the art.

T- and NK-cell lymphoproliferative disorders of the gastrointestinal (GI) tract are uncommon, but are important to recognise as there may be morphological and immunophenotypic overlap between lymphoid lesions with vastly different clinical outcomes. Recent data have led to the reclassification of some lymphomas and inclusion of new entities in the 2016 revision of World Health Organization (WHO) classification of lymphoid neoplasms. It has become clear that enteropathy associated T-cell lymphoma (EATL), formerly thought to be composed of two subtypes known as type I and type II, are distinct entities. Type I EATL is now simply classified as EATL; it is strongly associated with coeliac disease and occurs mainly in Western populations. Type II EATL has been renamed monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL); it shows no definite association with coeliac disease and occurs worldwide with a predominance in Asian populations. There is also a group of aggressive intestinal T-cell lymphomas which do not meet criteria for EATL, MEITL, extranodal NK/T-cell lymphoma of nasal type or anaplastic large cell lymphoma. These neoplasms are now designated intestinal T-cell lymphoma, not otherwise specified. Indolent T-cell lymphoproliferative disorder of the GI tract has been included as a provisional entity in the most recent WHO classification. It is a clonal T-cell lymphoproliferative disorder (CD4+ or CD8+) with an indolent clinical course. Finally, benign NK-cell proliferations of the GI tract, variably designated 'NK-cell enteropathy' and 'lymphomatoid gastropathy' have also been recognised in the last two decades but have not been included in the WHO classification as their neoplastic nature is not established. This review covers the aforementioned lymphoid proliferations, emphasising their salient clinicopathological features and genetic abnormalities. It also provides practical insights into resolving difficult differential diagnoses in daily surgical pathology practice.

DUSP22 gene rearrangements are recurrent in systemic and cutaneous ALK-negative anaplastic large cell lymphomas, rarely encountered in other cutaneous CD30+ lymphoproliferations, and typically absent in other peripheral T-cell lymphomas. We report the case of a 51-year-old woman, with longstanding celiac disease and a rapidly enlarging leg ulcer, due to a DUSP22-rearranged CD30+ T-cell lymphoproliferation. Subsequent history revealed an intestinal enteropathy-associated T-cell lymphoma (EATL). Identical monoclonal TR gene rearrangements and mutations in STAT3 and JAK1 typical of EATL were present in the cutaneous and intestinal lesions. No DUSP22 rearrangement was detected in the patient's intestinal tumour, nor in 15 additional EATLs tested. These findings indicate that DUSP22 rearrangements are not entirely specific of ALCLs, may rarely occur as a secondary aberration in EATL, and expand the differential diagnosis of DUSP22-rearranged cutaneous CD30+ lymphoproliferative disorders.

A 48-year-old female patient presented with longstanding unrecognized celiac disease (CD), a family history of CD, and a short duration of alarming symptoms. The diagnostic evaluation revealed the concomitant presence of small and large bowel ulcers raised a dilemma about differential diagnosis in her case. Pathologic examination of tissue specimens from the jejunal ulcer led to the diagnosis of enteropathy- associated T-cell lymphoma. In recent years, the availability of modern cross- sectional imaging and endoscopy modalities has dramatically improved the detection and characterization of small bowel lesions. Characterization of small bowel ulcers by endoscopy and radiology imaging in a patient with suspected complicated CD (CCD) needs to be made in conjunction with all clinical factors, as there is a wide overlap of the possible etiologic factors. Enteropathy-associated T-cell lymphoma is a highly aggressive T-cell lymphoma with a poor prognosis, since early diagnosis and appropriate treatment may be delayed due to nonspecific clinical and endoscopic presentation. Therefore, it is crucial to timely recognize patients with suspected CCD and properly navigate diagnostic imaging tools, acquire adequate biopsy, and perform immunophenotyping to set early diagnosis in patients with diffuse intestinal ulcers and CD.

We read the article by Chuan YY et al (1) with interest when we searched the literature to guide our care for a patient with Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis. Chuan YY et al (1) reported a patient with EATL developed intracranial involvement and died nine months after the initial diagnosis. They also summarized previous studies and found the survival after initial diagnosis was no longer than sixteen months.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as enteropathy-associated T-cell lymphoma (EATL) type II, is a rare disease with a poor prognosis that is often diagnosed when patients present with intestinal perforation or obstruction. Our patient, a man in his 60 s, had a 5-month history of persistent watery diarrhea. Upper and lower gastrointestinal endoscopy, abdominal computed tomography (CT), and stool culture results were unremarkable. He was admitted to our hospital 8 months later with a weight loss of 20 kg, general fatigue, and hypokalemia. Contrast-enhanced CT of the abdomen revealed mild thickening and contrast enhancement of the small intestinal wall. Video capsule endoscopy and double-balloon enteroscopy were performed to reveal a broad ulcer in the jejunum and multiple erosions throughout the small intestine. Examination of the biopsy specimens showed infiltration of atypical lymphocytes with pale cytoplasm in the glandular epithelium. The atypical lymphocytes were positive for CD3, CD8, CD56, granzyme B, and T-cell intracellular antigen-1 by immunostaining. Early diagnosis of MEITL was made, and the patient survived for 21 months with continuous chemotherapy. Aggressive examination of the small intestine is effective for the early diagnosis of serious diseases, such as MEITL, in patients with chronic diarrhea of unknown origin.

Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called “intraepithelial lymphocytosis”) in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IEL+CE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8+ in CD3+ IELs was significantly lower in IEL+CE than in CE without intraepithelial lymphocytosis (IEL−CE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8− IEL among IEL+CE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3+ cells, Ki67 immunopositivity was highest in ITCL, intermediate in IEL+CE, and lower in IEL−CE. A clonal TCR gene rearrangement was detected in 1/19 IEL−CE cases (5%), 15/54 IEL+CE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8−GRB+) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IEL+CE suggest that canine ITCL originates from these IELs, similar to human EATL.

Simple Summary: It 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. Abstract: 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?

Background Primary intestinal T-cell lymphomas are uncommon malignancies that pose a diagnostic dilemma, because the clinical features and imaging findings commonly overlap with those encountered in inflammatory bowel diseases. Case presentation The current clinical case report describes the clinical history, laboratory findings and histopathological analysis from a patient with non-specific gastrointestinal symptoms with a presumptive clinical diagnosis of inflammatory bowel disease, and two intestinal biopsy specimens with non-specific findings. Due to the persistent symptoms a third biopsy was consistent with primary intestinal T-cell lymphoma, a diagnosis that was elusive for months after the initial presentation. Clinical correlation with laboratory and histopathological findings is required to establish a definitive diagnosis and to further stratify the patients. In addition, the neoplastic cells featured partial expression of CD30, which had relevant therapeutic implications. Conclusions Suspicion for an intestinal T-cell lymphoproliferative disorder should always exist in patients with persistent abdominal symptoms with no clear etiology. The current discussion provides a summary and review of the key diagnostic histological features for the classification of primary intestinal T-cell lymphomas. In addition, the discussion describes how specific the histological findings are relevant for the clinical management decisions.

Enteropathy-associated T-cell lymphoma (EATL) is a tumor of intraepithelial T-lymphocytes arising in the small intestine. Based on the genetic profile, immunohistochemistry, and histology, EATL is divided into two subtypes. EATL type I occurs in individuals with celiac disease (CD) while EATL type II is a sporadic form that occurs in individuals without CD. Intensive chemotherapy and surgery are the mainstay treatment. However, despite the currently available treatment options, the five-year survival rate is only 9%. EATL presents as abdominal pain, nausea, or slow gastrointestinal bleeding. Severe bleeding leading to hemodynamic instability is rarely known in EATL. Therefore, we present a unique case of EATL who presented with acute and severe gastrointestinal bleeding with no prior history of CD.