• cat
• clonality testing
• gastrointestinal tract
• immunohistochemistry
• lymphoma
• lymphoproliferative disorders
• natural killer cells

• Cats
• Cat Diseases/pathology
• Animals
• Male
• Female
• Lymphoma, T-Cell/veterinary
• Lymphoma, T-Cell/pathology
• Immunohistochemistry/veterinary
• Sclerosis/veterinary
• Sclerosis/pathology

• Humans
• Lymphoma, Extranodal NK-T-Cell/diagnosis
• Lymphoma, Extranodal NK-T-Cell/pathology
• Lymphoma, T-Cell, Peripheral/pathology
• Phenotype
• Receptors, Antigen, T-Cell/genetics

• Epstein-Barr virus
• Extranodal natural killer/T-cell lymphoma
• Hepatosplenic involvement

• Humans
• Adult
• Retrospective Studies
• Epstein-Barr Virus Infections/complications
• Lymphoma, Extranodal NK-T-Cell/pathology
• Asparaginase
• Herpesvirus 4, Human
• Killer Cells, Natural/pathology

• 81272626 National Natural Science Foundation of China
• 81900197 National Natural Science Foundation of China

• T cell lymphoma
• asparaginase/therapeutic use
• efficacy
• physiopathology
• retrospective analysis

• extranodal NK/T-cell lymphoma
• gastrointestinal
• nomogram
• prognosis
• survival

• CD8αα+ T-cells
• EATL
• ENKTL
• ITCL
• Indolent T-cell LPD
• MEITL
• NK cells
• NK-cell enteropathy
• NOS
• iCD3+ ILC
• iCD8α ILC
• lymphomatoid gastropathy

• OF-LCG18May-0028 National Medical Research Council
• CSSSP20nov-0019 National Medical Research Council

• Epstein–Barr virus
• chronic active EBV infection
• extranodal NK/T-cell lymphoma
• nasal type
• post-transplant lymphoproliferative disorders

• 21198 AIRC

Extranodal NK/T-cell lymphoma of the breast (ENKTL-Breast) is rarely detected in clinical practice, and its clinicopathological features remain unclear.

A consecutive 11-year (2010–2020) ENKTL-Breast case series was retrospectively analyzed. Eight cases of ENKTL-Breast were selected, with three primary and five secondary lesions, accounting for 3.5% (8/228) of all breast lymphomas. All patients were female with a median age of 46 years. Lesions presented as solid breast masses (8/8, 100%) and were usually located in the upper outer quadrant of the breast (7/8, 87.5%). B-symptoms were observed in seven (7/8, 87.5%) cases. Two primary ENKTL-Breast cases showed concomitant diseases (IgA nephropathy and chronic active hepatitis B). Histological and immunohistochemical features of ENKTL-Breast were similar to those of ENKTL at other sites. T-cell receptor rearrangement revealed clonality in all examined primary cases (2/2, 100%), but only in one secondary case (1/5, 20%). The disease progressed rapidly in two primary cases and both patients died within 3 and 9 months. For secondary cases, the disease manifested as a disseminated disease, with a median survival time of 6 months.

Our data suggested that ENKTL-Breast clinically mimics breast cancer to some extent, though B-symptoms might serve as a distinguishing factor. ENKTL-Breast is highly aggressive and patients with this disease exhibit a short survival time. Primary ENKTL-Breast tends to originate from activated cytotoxic T-cells, and immune-related diseases may be involved in its pathogenesis and development.

The online version contains supplementary material available at 10.1186/s13023-021-02110-x.

• Breast lymphoma
• Epstein–Barr virus
• Extranodal natural killer/T-cell lymphoma
• T-cell lymphoma

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.

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?

• EATL
• ITLPD-GI
• MEITL
• NK-cell enteropathy
• enteropathy-associated T-cell lymphoma
• indolent T-cell lymphoproliferative disorder
• monomorphic epitheliotropic intestinal T-cell lymphoma
• primary gastrointestinal T-cell lymphoma

• B-cell lymphoma
• Hodgkin lymphoma
• T-cell lymphoma
• gastrointestinal lymphoma
• lymphoma

• T-cell lymphomas
• epstein-Barr virus
• extranodal natural killer lymphomas
• gastrointestinal perforation
• lymphoma

Background: Extranodal NK/T cell lymphoma is a rare non-Hodgkin lymphoma mainly involving the upper aerodigestive tract, even rarer is primary extranasal disease involving the intestine. We present a case of primary intestinal NK/T cell lymphoma with diagnostic challenge, which eventually developed into multiple intestinal perforations.

Case Presentation: A 35-year-old man presented with diarrhea and recurrent fever. Abdominal CT revealed multi-segmental intestinal wall thickening. Colonoscopy showed multiple irregular ulcers in colon. During the hospitalization, the patient developed intestinal perforation and an emergency surgery was performed. The resected specimen showed multiple perforations of the colon. The surgical samples underwent pathological analysis, and a diagnosis of extranodal NK/T cell lymphoma nasal type was confirmed. After recovering from surgery, the patient started receiving chemotherapy and PD-1 monoclonal antibody. Fortunately, he was discharged after significant improvement in his general condition. Eleven months follow-up was uneventful.

Conclusion: Early diagnosis of primary intestinal NK/T cell lymphoma is frequently difficult. Most patients were definitely diagnosed only after surgical resection following complications, resulting in a poor prognosis. Therefore, doctors should maintain high suspicion of this malignancy for early diagnosis at an early stage clinically.

• Intestinal neoplasm
• Nk/t cell lymphoma
• extranodal
• non-Hodgkin lymphoma
• perforation

• childhood
• extranodal natural killer/t-cell lymphoma
• gi tract

• Child
• Colon/pathology
• Colonic Neoplasms/diagnostic imaging
• Colonic Neoplasms/pathology
• Humans
• Lymphoma, Extranodal NK-T-Cell/diagnostic imaging
• Lymphoma, Extranodal NK-T-Cell/pathology
• Male
• Tomography, X-Ray Computed

Anaplastic large cell lymphoma (ALCL) with uniform CD56 expression is a rare condition, that has been described in limited literature, and its clinicopathological features have not yet been well illustrated. The aim of our study was to fully investigate the clinical, histological, immunohistochemical and molecular features of CD56+ ALCL.

The clinical and histological characteristics of CD56+ ALCL cases were retrospectively evaluated. The immunohistochemical phenotype, status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. Overall survival was also analyzed.

Eighteen (5.8%) cases with diffuse CD56 expression were identified out of 313 archived ALCL cases with CD56 test. CD56 expression was significantly higher in ALK+ systemic ALCLs (sALCLs) (13/64, 20.3%) than in ALK- sALCLs (3/101, 3.0%) (p < 0.001) as well as primary cutaneous ALCLs (2/148, 1.4%) (p < 0.001). Regarding the CD56+ ALK+ sALCLs, the median age was 20 years (range, 8–60 years) with a male-to-female ratio of 2.3:1, and these cases more frequently affected extranodal sites (11/38, 28.9%) rather than lymph nodes (2/26, 7.7%) (p = 0.038). Eleven (84.6%) cases presented with stage I-II diseases, which was significantly more than their CD56- ALK+ counterparts (45.5%) (p = 0.015). Histologically, 2 ALK+ cases were of small cell variant and all the others displayed characteristic morphology of classic ALCL. Regarding the immunophenotype, both CD30 and CD56 were diffusely positive in all cases. CD3, CD43, anaplastic lymphoma kinase-1 (ALK1), TIA-1, EMA expression was observed in 30.8% (4/13), 90.9% (10/11), 100% (13/13), 100% (9/9), and 80.0% (8/10) cases, respectively. EBV infection was consistently absent. Monoclonal TCR gene rearrangement was found in 100% (5/5) of investigated ALK+ cases. Chemotherapy with a CHOP regimen was most frequently employed. The 3-year overall survival (OS) rate for CD56+ ALK+ patients was 92.0%, compared with 73.0% for their CD56- counterparts, but there was no significant difference in OS between the two groups (p = 0.264).

Uniform CD56 expression is an unexpected condition in ALCL. Of ALK+ ALCLs, CD56 expression correlated with a high frequency of early stage and an extranodal predominance. It is of great importance to raise awareness of this condition and familiarity with its characteristic features to avoid diagnostic and therapeutic pitfalls. Further investigations are warranted for a better understanding of this unusual phenotype and the significance of CD56 expression in ALCL.

• ALK
• Anaplastic large cell lymphoma
• CD56 expression
• Differential diagnosis
• Overall survival

• ATLL
• Colorectum
• Lymphocytic proctocolitis
• MEITL
• T/NK-cell lymphoma

• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms/pathology
• Endoscopy, Digestive System
• Enteropathy-Associated T-Cell Lymphoma/pathology
• Female
• Humans
• Lymphoma, Extranodal NK-T-Cell/pathology
• Male
• Middle Aged

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.

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.

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.

• NK/T cell lymphoma
• Indolent T lymphocyte proliferative disease
• Crohn's disease
• Endoscopy
• Misdiagnosis
• Case report

• Adult
• Crohn Disease/diagnosis
• Diagnosis, Differential
• Enteropathy-Associated T-Cell Lymphoma
• Epstein-Barr Virus Infections/diagnosis
• Female
• Herpesvirus 4, Human
• Humans
• Intestines

• Abdominal Pain/etiology
• Adult
• Diagnosis, Differential
• Diagnostic Errors
• Diarrhea/etiology
• Endoscopy, Gastrointestinal
• Epstein-Barr Virus Infections/complications
• Female
• Fever/etiology
• Gastrointestinal Hemorrhage/etiology
• Granzymes/metabolism
• Herpesvirus 4, Human/genetics
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Lymphoproliferative Disorders/complications
• Lymphoproliferative Disorders/diagnosis
• Lymphoproliferative Disorders/pathology
• Lymphoproliferative Disorders/virology
• Male
• Middle Aged
• Natural Killer T-Cells/metabolism
• Rectum
• T-Cell Intracellular Antigen-1/metabolism
• Tuberculosis/diagnosis
• Young Adult

• Clinicopathologic
• Intestinal neoplasm
• NK/T lymphoma
• Primary

The paradoxical reports about the prognostic value of the CD30 expression in extranodal NK/T-cell lymphoma (ENKTL) have restricted its further applications in clinical practice. To identify the common effects and the variation, we conducted this systematic review and meta-analysis.

PubMed, MEDLINE, Embase, and Web of Science were searched between January 1975 and 31 January 2017. The pooled hazard ratio was used to estimate the effect of the CD30 expression on overall survival. Bias was assessed by prespecified criteria referring to Reporting Recommendations for Tumor Marker Prognostic Studies and Newcastle-Ottawa Scale.

Ten retrospective cohort studies with 310 patients are included. CD30 is associated with better overall survival significantly (HR 0.71, 95% CI 0.51 to 0.99, I² = 0%). A greater effect is observed among studies including participants predominant in regional involvement (HR 0.31, 95%CI 0.13 to 0.76, I² = 0%) compared with those in systemic involvement.

This study indicates that the CD30 expression is significantly associated with better prognosis in ENKTL, especially for patients with regional lymphoma involvement.

• CD30
• extranodal natural killer/T-cell lymphoma
• meta-analysis
• prognostic value