Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.

BACKGROUND: Small intestinal monomorphic-epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. METHODS: The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein-Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. RESULTS: Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. CONCLUSIONS: Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

Acute abdominal perforation as a clinical presentation of coeliac disease.

Intestinal perforation is described in coeliac disease in the setting of refractoriness or Enteropathy-Associated T-cell Lymphoma (EATL). We report the case of a man with untreated coeliac disease who presented intestinal perforation and was diagnosed with EATL over one year later.

Advanced enteropathy-associated T cell lymphoma (EATL) presenting with severe malabsorption and concomitantly diagnosed coeliac disease (CD).

Enteropathy-associated T cell lymphoma (EATL) is an aggressive subtype of non-Hodgkin's lymphoma often associated with coeliac disease (CD). We describe a previously healthy man in his 50 s who presented with a history of abdominal pain, failure to thrive and significant weight loss over a 3-month period. Investigations revealed a positive coeliac serology, diffuse duodenal atrophy with multiple duodenal and jejunal ulcers on endoscopy and mesenteric lymphadenopathy on CT imaging. Duodenal tissue biopsy confirmed a diagnosis of EATL Stage IVB. Chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone regimen was initiated. This case highlights the need for greater awareness and consideration of EATL in individuals with worsening malabsorption and abdominal pain, irrespective of coeliac history.

Patients with enteropathy-associated T-cell lymphoma in the United States from 2000 to 2018: SEER data-base analysis.

BACKGROUND: Enteropathy-Associated T-Cell Lymphoma (EATL) is a rare lymphoma of T-cell origin associated with celiac disease. There is limited evidence in the literature about the incidence and causes of death in patients with EATL. METHODS: We performed a retrospective study through analyzing the Surveillance, Epidemiology, and End Results (SEER) data base to determine the incidence, trends and causes of death of patients with EATL in the U.S from 2000 to 2018. Baseline characteristics with treatment options (surgery, radiotherapy, and chemotherapy), status of patients either alive, dead due to cancer itself or other non-cancerous causes with listing of those non-cancerous causes was retrieved. Sub-group analysis based on sex was also done. Multiple latency periods (<2 year, 2-5, 6-10, 11-15, and more than 15 years) were analyzed following EATL diagnosis. RESULTS: There were 259 EATL patients, majority were aged 70-74 years old (n = 36, 13.9%), predominantly males 155 (59.8%), most common in whites, (76.4%, n = 198), EATL was the only primary tumor in 177 (68.3%) cases, most common site was small bowel at different sites 84 (32.4%) followed by jejunum specifically 57 (22%), majority went for surgical resection (69.9%, n = 181) followed by chemotherapy (47.5%, n = 123), 217 (83.7%) died during follow-up in this study, CONCLUSION: EATL is a rare entity, mostly seen in males, between 70 and 74 years, and mostly originated in the small bowel. With over 80% death in five-year follow up period, EATL patients showed better survival if they underwent chemotherapy. More studies are needed for further understanding of this rare entity.

[Difficulties in diagnosing intestinal T-cell lymphoma. Case report].

The article describes a rare diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), due to its veiled by a number of so-called "masks" of enteropathies. A detailed analysis of all clinical, morphological and immunohistochemical data made it possible to establish the correct diagnosis. The revealed pathology is extremely rare in practice, even among specialists in hematology. The article demonstrates the main stages of both a complex diagnosis and an attempt at therapy for this aggressive form of intestinal lymphoma.

PEG-Asparaginase Single-Agent Rescue in an Advanced Case of Monomorphic Epitheliotropic Intestinal T Cell Lymphoma.

PURPOSE: MEITL is a very rare and highly aggressive peripheral T cell lymphoma with poor prognosis and for which there is no standard treatment. Treatment options for patients patients with relapsed/refractory disease are scarce and the choice of an appropriate rescue still represents an unmet need. METHODS: Here, we report the case of a 65-year-old woman affected by MEITL, progressing after initial treatment with an anthracycline-based chemotherapy and surgery, who received single-agent PEG-asparaginase salvage therapy at our institution. RESULTS: PEG-asparaginase single-agent rescue proved to be rapidly effective in controlling the disease and its associated paraneoplastic features. Nevertheless, toxicity was high and the patient died due to a treatment-related complication. CONCLUSION: The case we described brings new evidences on the effectiveness of PEG-asparaginase therapy in MEITL patients. Whether PEG-asparaginase should be included in the treatment course of MEITL patients could be the subject of future studies.

Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome.

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.

Intestinal T-cell lymphoma in an Asian small-clawed otter: case report and literature review of lymphoma in the subfamily Lutrinae.

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 involving the central nervous system: a rare case report with comprehensive autopsy neuropathological examinations.

Monomorphic epitheliotropic T-cell lymphoma (MEITL) of gastrointestinal tract is an aggressive T-cell lymphoma that can rarely involve the brain. We present detailed descriptions of clinical and autopsy neuropathological findings of a rare case of an elderly woman who had surgery and chemotherapy for MEITL of the small intestine. Following her surgery, she progressively exhibited neurologic decline towards the end of her treatment. The patient eventually succumbed to her illness and was found to have MEITL with intracranial involvement on autopsy. Brain autopsy was performed and examination of tissues with hematoxylin-eosin staining under optical microscopy with 100 X magnification. Immunostaining for CD3, CD4, CD5, CD7, CD8, CD56, CD20, beta-amyloid, c-Myc, TCR-beta, TCR-delta, and EBER-ish was conducted on the formalin-fixed paraffin-embedded (FFPE) brain tissues. A neuropathological exam revealed multifocal friable necrotic and hemorrhagic areas in the supratentorial region. Histologically, monotonous small to medium-sized atypical lymphocytes infiltrated the brain parenchyma, prominently around the vessels. The immunophenotype of the atypical lymphocytes was positive for CD-3, CD-7, and CD-56 and negative for CD-5, CD-4, CD-8, CD-20, and c-Myc. EBER-ish was negative. The histology and immunophenotype confirmed the MEITL brain involvement. Neurologic decline and cognitive changes in patients with known MEITL can be the first clue of brain involvement upon which prompt evaluation is warranted.

[A Case of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Causing Perforation of the Small Intestine].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is very rare and aggressive subtype of lymphoma with poor prognosis. A 60-year-old man complaining of abdominal pain was underwent partial resection of the jejunum for panperitonitis with a small intestinal perforation. The histopathological and immunohistochemical findings led to the diagnosis of MEITL. Postoperative course was uneventful. One month after the operation, the patient was scheduled for 6 courses of CHOP regimens. He presented with bowel obstruction twice during the 3 courses of CHOP. As the recurrence of MEITL could not be ruled out, diagnostic laparoscopy was performed. Laparoscopic findings revealed no recurrence and adhesive small bowel obstruction. The patient was followed closely without treatment after 6 courses of CHOP. The patient has been alive without recurrence 18 months after the resection. We reported a case of monomorphic epithelial intestinal T- cell lymphoma causing jejunal perforation.

Proteomics and genomics of a monomorphic epitheliotropic intestinal T-cell lymphoma: An extremely rare case report and short review of literature.

RATIONALE: 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). PATIENT CONCERNS: 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. DIAGNOSES AND INTERVENTIONS: 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. LESSONS: 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.

Pegylated liposomal doxorubicin (PLD)-containing regimen as a novel treatment of monomorphic epithelial intestinal T-cell lymphoma (MEITL): A case report and review of literature.

INTRODUCTION: Monomorphic intestinal T-cell lymphoma (MEITL) is a rare, aggressive peripheral T-cell lymphoma that arises from intestinal epithelial lymphocytes. Currently, MEITL lacks standard treatment options. Under the current treatment regimen, the median survival time for patients is only 7 months. Chemotherapy followed by hematopoietic stem cell transplantation may improve patient outcomes. New anti-lymphoma drugs, including chidamide and PEG-asparaginase, are being tested against MEITL. To our knowledge, there are currently no data on the pegylated liposomal doxorubicin (PLD) regimen for MEITL therapy.Patient concerns, diagnosis and interventions: We report the case of a 54-year-old patient diagnosed with MEITL who presented with abdominal pain and was treated with a cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide regimen containing PLD. OUTCOMES: After 15 months of follow-up, the patient is currently alive and disease free. The application of doxorubicin liposomes in chemotherapy regimens may be a new way to treat MEITL. REVIEW: We searched the literature on MEITL and selected 52 case reports. We summarized the clinical characteristics and treatment of 53 patients (including the current patient). CONCLUSION: It highlights 2 important clinical findings. First, for patients with MEITL treated with the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide regimen, PLD has fewer adverse reactions and better long-term survival than doxorubicin. Second, an early diagnosis is necessary for prompt treatment. We believe that this manuscript will be valuable to all the researchers who are interested in.

Long term survival of Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis: letter to the Editor.

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.

AGA Clinical Practice Update on Management of Refractory Celiac Disease: Expert Review.

DESCRIPTION: 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. METHODS: 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.

Surface CD3-negative monomorphic epitheliotropic intestinal T-cell lymphoma.

Intestinal T/NK-cell lymphomas include enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), indolent T-cell lymphoproliferative disorders of the GI tract (ITCLPD), extranodal NK/T-cell lymphoma, nasal type (ENKTL), and intestinal T-cell lymphoma NOS (ITCL-NOS). Here we describe a case of surface CD3-negative MEITL. A 63-year-old Japanese female had a tumor located in the conglomerated ileum, which formed multiple mass lesions. The resected tissue showed a diffuse infiltration of monomorphic medium-sized lymphocytes with epitheliotropism. Flowcytometry using a fresh specimen of the tumor revealed positivity for CD7, CD8, CD38, and CD56, but not surface CD3. On immunohistochemistry, the tumor showed positivity for cytoplasmic CD3, CD8, CD56, TIA-1, Granzyme B, and perforin. EBER with in situ hybridization was negative. Moreover, H3K36me3, which is negative in MEITL with SETD2-mutation, was positive. This is an important case of MEITL due to its oncogenesis.

Successful early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma manifesting as chronic diarrhea and hypokalemia using video capsule endoscopy and double-balloon enteroscopy.

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.

CD30 + Primary intestinal T-cell lymphoma (unclassified) masquerading as chronic inflammation: a case report.

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.

Targeted Next-generation Sequencing Reveals a Wide Morphologic and Immunophenotypic Spectrum of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma.

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.

Cutaneous presentation of enteropathy-associated T-cell lymphoma masquerading as a DUSP22-rearranged CD30+ lymphoproliferation.

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.