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Stuver R, Epstein-Peterson ZD, Horwitz SM. Few and far between: clinical management of rare extranodal subtypes of mature T-cell and NK-cell lymphomas. Haematologica 2023; 108:3244-3260. [PMID: 38037801 PMCID: PMC10690914 DOI: 10.3324/haematol.2023.282717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 07/03/2023] [Indexed: 12/02/2023] Open
Abstract
While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated clinical trials in these rare subtypes, and data are generally limited to case reports and retrospective case series. Therefore, clinical management is often based on this limited literature and extrapolation of data from the more common, nodal T-cell lymphomas in conjunction with personal experience. Nevertheless, thanks to tremendous pre-clinical efforts to understand these rare diseases, an increasing appreciation of the biological changes that underlie these entities is forming. In this review, we attempt to summarize the relevant literature regarding the initial management of certain rare subtypes, specifically subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, intestinal T-cell lymphomas, and extranodal NK/T-cell lymphoma. While unequivocally established approaches in these diseases do not exist, we make cautious efforts to provide our approaches to clinical management when possible.
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Affiliation(s)
- Robert Stuver
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center.
| | - Zachary D Epstein-Peterson
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; Department of Medicine, Weill Cornell Medical College
| | - Steven M Horwitz
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; Department of Medicine, Weill Cornell Medical College; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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2
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Indolent T-cell lymphoproliferative disorder of gastrointestinal tract with unusual clinical courses: report of 6 cases and literature review. Virchows Arch 2022; 482:729-743. [PMID: 36472661 DOI: 10.1007/s00428-022-03467-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 11/20/2022] [Accepted: 11/22/2022] [Indexed: 12/12/2022]
Abstract
Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (iTLPD-GI) is a rare neoplasm usually having an indolent clinical course and easily misdiagnosed as inflammatory bowel disease or other T-cell lymphomas. A subset of the disorders that progressed to overt peripheral T-cell lymphoma have been reported, and the etiology and pathogenesis are poorly understood. The current study retrospectively examined the pathological, molecular, and clinical features of 6 cases of iTLPD-GI. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, T-cell receptor gene rearrangement, and next-generation sequencing (NGS) were performed with the diseased tissues. All the 6 patients were immunocompetent Chinese men, who presented with recurrent abdominal pain and diarrhea for 4 to 13 years. Histologically, the intestinal tissue was expanded by lymphoid infiltration, composed of small-to-medium-sized lymphocytes with gland intact. The neoplastic cells were CD4 - /CD8 + with expression of TIA1 and variable granzyme B in five cases, and the other one was CD4 + /CD8 - . Two of the 5 patients progressed to more aggressive T-cell lymphoma and died of disease with complications. NGS identified TET2 and DDX3X mutations in patient 1, and BIRC6 and REV3L mutations in patient 2. Literature review indicated that iTLPD-GI with CD4 - /CD8 + immunophenotype was more commonly reported in Chinese cases. Our limited data indicated CD4-/CD8 + iTLPD-GI have similar potential to progress to more aggressive T-cell lymphoma as that of CD4 + /CD8 - , and gradually increased expression of granzyme B and Ki-67 may be early signs of the disease progression. Gain of novel gene mutations may be indicators of the pathogenesis.
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3
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Weng CY, Ye C, Fan YH, Lv B, Zhang CL, Li M. CD8-positive indolent T-Cell lymphoproliferative disorder of the gastrointestinal tract: A case report and review of literature. World J Clin Cases 2022; 10:4971-4984. [PMID: 35801019 PMCID: PMC9198890 DOI: 10.12998/wjcc.v10.i15.4971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/13/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPD-GI), a primary tumor forming in the gastrointestinal (GI) tract, represents a rarely diagnosed clonal T-cell disease with a protracted clinical course.
CASE SUMMARY This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation. Postsurgical histopathological analysis, combined with hematoxylin-eosin staining, immunohistochemistry and TCRβ/γ clonal gene rearrangement test, confirmed the diagnosis of CD8+ ITLPD-GI.
CONCLUSION Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize. So far, indolent CD8+ ITLPD-GI has not been comprehensively examined. The current mini-review focused on evaluating indolent CD8+ ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis, detection of genetic and epigenetic alterations, and therapeutic target identification.
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Affiliation(s)
- Chun-Yan Weng
- Department of Gastroenterology, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Cheng Ye
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Hong Fan
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Bin Lv
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Chun-Li Zhang
- Department of Pathology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou 310006, Zhejiang Province, China
| | - Meng Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
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Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches. Cancers (Basel) 2021; 13:cancers13225774. [PMID: 34830926 PMCID: PMC8616126 DOI: 10.3390/cancers13225774] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 12/12/2022] Open
Abstract
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?
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Sanguedolce F, Zanelli M, Zizzo M, Luminari S, Martino G, Soriano A, Ricci L, Caprera C, Ascani S. Indolent T-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract (iTLPD-GI): A Review. Cancers (Basel) 2021; 13:cancers13112790. [PMID: 34205136 PMCID: PMC8199971 DOI: 10.3390/cancers13112790] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/26/2021] [Accepted: 06/01/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary This review aims to better define the clinical, pathological, and molecular features of the novel lymphoproliferative disease termed “indolent T-cell lymphoproliferative disorder of the gastro-intestinal tract (iTLPD-GI)”, to discuss potential pitfalls in differentiating this entity from other neoplastic and non-neoplastic disorders arising at the same site, and to point out a biomarker-based approach to the diagnosis. Abstract iTLPD-GI is a low-grade clonal T-cell lymphoproliferative disease arising in GI organs. It is an uncommon disease, and only recently has it been enlisted as a distinct provisional entity in the current WHO Classification. Data from the literature disclose high heterogeneity in terms of pathological and molecular features; on the other hand, establishing an accurate diagnosis of iTLPD-GI is of pivotal importance, since treatment options are different from that of other, more frequent lymphomas that arise in the gastrointestinal tract. In this review, we aimed to better define this novel entity, and to identify useful diagnostic biomarkers; moreover, we provide a biomarker-based approach to the diagnosis and describe the most common issues in differentiating iTLPD-GI from other neoplastic and non-neoplastic disorders.
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Affiliation(s)
- Francesca Sanguedolce
- Pathology Unit, Policlinico Riuniti, University of Foggia, 71121 Foggia, Italy
- Correspondence: ; Tel.: +39-881-736-315
| | - Magda Zanelli
- Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
| | - Maurizio Zizzo
- Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Stefano Luminari
- Hematology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
| | - Giovanni Martino
- Hematology Unit, University of Perugia, CREO Perugia, 06124 Perugia, Italy;
| | - Alessandra Soriano
- Gastroenterology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
| | - Linda Ricci
- Pathology Unit, Azienda Ospedaliera S. Maria di Terni, University of Perugia, 05100 Terni, Italy; (L.R.); (C.C.); (S.A.)
| | - Cecilia Caprera
- Pathology Unit, Azienda Ospedaliera S. Maria di Terni, University of Perugia, 05100 Terni, Italy; (L.R.); (C.C.); (S.A.)
| | - Stefano Ascani
- Pathology Unit, Azienda Ospedaliera S. Maria di Terni, University of Perugia, 05100 Terni, Italy; (L.R.); (C.C.); (S.A.)
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Susan SSH, Ng SB, Wang S, Tan SY. Diagnostic approach to T- and NK-cell lymphoproliferative disorders in the gastrointestinal tract. Semin Diagn Pathol 2021; 38:21-30. [PMID: 34016481 DOI: 10.1053/j.semdp.2021.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/11/2021] [Accepted: 03/22/2021] [Indexed: 12/13/2022]
Abstract
Most gastrointestinal NK and T cell lymphomas are aggressive in behavior, although in recent years a subset of indolent lymphoproliferative disorders have been described, which must be distinguished from their more malignant mimics. Intestinal T-cell lymphomas may arise from intra-epithelial lymphocytes and display epitheliotropism, such as enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. They are both aggressive in behavior but differ in their clinic-pathological features. On the other hand, intra-epithelial lymphocytes are not prominent in intestinal T-cell lymphoma, NOS, which is a diagnosis of exclusion and probably represents a heterogeneous group of entities. Indolent lymphoproliferative disorders of NK- and T-cells of both CD8 and CD4 subsets share a chronic, recurring clinical course but display differences from each other. CD8+ T-cell lymphoproliferative disorder of GI tract has a low proliferative fraction and does not progress nor undergo large cell transformation. Whilst NK-cell enteropathy runs an indolent clinical course, it may display a high proliferation fraction. On the other hand, CD4+ indolent T-cell lymphoproliferative disorder displays variable proliferation rates and may progress or transform after a number of years. In Asia and South America, it is not uncommon to see involvement of the gastrointestinal tract by EBV-associated extranodal NK/T cell lymphoma, nasal type, which must be distinguished from NK cell enteropathy and EBV-associated mucocutaneous ulcers.
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Affiliation(s)
- Swee-Shan Hue Susan
- Department of Pathology, National University Hospital Health Service, Singapore, Singapore; Department of Pathology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
| | - Siok-Bian Ng
- Department of Pathology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
| | - Shi Wang
- Department of Pathology, National University Hospital Health Service, Singapore, Singapore
| | - Soo-Yong Tan
- Department of Pathology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore.
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7
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Jaffe ES. T-cell and NK-cell neoplasms of the gastrointestinal tract - recurrent themes, but clinical and biological distinctions exist. Haematologica 2021; 105:1760-1762. [PMID: 32611576 DOI: 10.3324/haematol.2020.252924] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Elaine S Jaffe
- Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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8
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New developments in non-Hodgkin lymphoid malignancies. Pathology 2021; 53:349-366. [PMID: 33685720 DOI: 10.1016/j.pathol.2021.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 12/23/2022]
Abstract
The revised fourth edition of the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues (2017) reflects significant advances in understanding the biology, genetic basis and behaviour of haematopoietic neoplasms. This review focuses on some of the major changes in B-cell and T-cell non-Hodgkin lymphomas in the 2017 WHO and includes more recent updates. The 2017 WHO saw a shift towards conservatism in the classification of precursor lesions of small B-cell lymphomas such as monoclonal B-cell lymphocytosis, in situ follicular and in situ mantle cell neoplasms. With more widespread use of next generation sequencing (NGS), special entities within follicular lymphoma and mantle cell lymphoma were recognised with recurrent genetic aberrations and unique clinicopathological features. The diagnostic workup of lymphoplasmacytic lymphoma and hairy cell leukaemia has been refined with the discovery of MYD88 L265P and BRAF V600E mutations, respectively, in these entities. Recommendations in the immunohistochemical evaluation of diffuse large B-cell lymphoma include determining cell of origin and expression of MYC and BCL2, so called 'double-expressor' phenotype. EBV-positive large B-cell lymphoma of the elderly has been renamed to recognise its occurrence amongst a wider age group. EBV-positive mucocutaneous ulcer is a newly recognised entity with indolent clinical behaviour that occurs in the setting of immunosuppression. Two lymphomas with recurrent genetic aberrations are newly included provisional entities: Burkitt-like lymphoma with 11q aberration and large B-cell lymphoma with IRF4 rearrangement. Aggressive B-cell lymphomas with MYC, BCL2 and/or BCL6 rearrangements, so called 'double-hit/triple-hit' lymphomas are now a distinct entity. Much progress has been made in understanding intestinal T-cell lymphomas. Enteropathy-associated T-cell lymphoma, type II, is now known to not be associated with coeliac disease and is hence renamed monomorphic epitheliotropic T-cell lymphoma. An indolent clonal T-cell lymphoproliferative disorder of the GI tract is a newly included provisional entity. Angioimmunoblastic T-cell lymphoma and nodal T-cell lymphomas with T-follicular helper phenotype are included in a single broad category, emphasising their shared genetic and phenotypic features. Anaplastic large cell lymphoma, ALK- is upgraded to a definitive entity with subsets carrying recurrent rearrangements in DUSP22 or TP63. Breast implant-associated anaplastic large cell lymphoma is a new provisional entity with indolent behaviour. Finally, cutaneous T-cell proliferations include a new provisional entity, primary cutaneous acral CD8-positive T-cell lymphoma, and reclassification of primary small/medium CD4-positive T-cell lymphoma as lymphoproliferative disorder.
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9
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van Wanrooij RLJ, Bontkes HJ, Neefjes-Borst EA, Mulder CJ, Bouma G. Immune-mediated enteropathies: From bench to bedside. J Autoimmun 2021; 118:102609. [PMID: 33607573 DOI: 10.1016/j.jaut.2021.102609] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 01/22/2021] [Accepted: 01/23/2021] [Indexed: 12/13/2022]
Abstract
Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to malabsorption-related symptoms and include (severe) chronic diarrhea, weight loss and vitamin deficiencies. Parenteral feeding and immunosuppressive therapy are needed in severe cases. Celiac disease has long been recognized as the most common immune-mediated enteropathy in adults, but the spectrum of immune-mediated enteropathies has been expanding. Histological and clinical features are sometimes shared among these enteropathies, and therefore it may be challenging to differentiate between them. Here, we provide an overview of immune-mediated enteropathies focused on clinical presentation, establishing diagnosis, immunopathogenesis, and treatment options.
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Affiliation(s)
- Roy L J van Wanrooij
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam, the Netherlands.
| | - Hetty J Bontkes
- Amsterdam UMC, Laboratory Medical Immunology, Department of Clinical Chemistry, AI & I Institute, AGEM Research Institute, Amsterdam, the Netherlands
| | | | - Chris J Mulder
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam, the Netherlands
| | - Gerd Bouma
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam, the Netherlands
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10
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Foukas PG, Bisig B, de Leval L. Recent advances upper gastrointestinal lymphomas: molecular updates and diagnostic implications. Histopathology 2020; 78:187-214. [PMID: 33382495 DOI: 10.1111/his.14289] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 10/21/2020] [Accepted: 10/22/2020] [Indexed: 12/14/2022]
Abstract
Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases.
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Affiliation(s)
- Periklis G Foukas
- Second Department of Pathology, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Bettina Bisig
- Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland
| | - Laurence de Leval
- Second Department of Pathology, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
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11
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van Vliet C, Spagnolo DV. T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: review and update. Pathology 2019; 52:128-141. [PMID: 31727264 DOI: 10.1016/j.pathol.2019.10.001] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 10/08/2019] [Accepted: 10/08/2019] [Indexed: 12/13/2022]
Abstract
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.
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Affiliation(s)
- Chris van Vliet
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia.
| | - Dominic V Spagnolo
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia; University of Western Australia, School of Pathology and Laboratory Medicine, Nedlands, WA, Australia
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12
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Abstract
Herein we review the following selection of gastrointestinal lymphomas: monomorphic epitheliotropic intestinal T-cell lymphoma; indolent T-cell lymphoproliferative disorder of the gastrointestinal tract; intestinal T-cell lymphoma, not otherwise specified; duodenal-type follicular lymphoma; and Epstein-Barr virus-positive mucocutaneous ulcer. Definitions reflect the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Clinical, morphologic, and immunophenotypic characteristics of each entity are emphasized.
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Affiliation(s)
| | | | - Scott R Owens
- From the Department of Pathology, University of Michigan, Ann Arbor
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13
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Jassim SH, Smith LB. New/Revised Entities in Gastrointestinal Lymphoproliferative Disorders. Surg Pathol Clin 2019; 12:733-743. [PMID: 31352985 DOI: 10.1016/j.path.2019.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The gastrointestinal tract is a common extranodal site of involvement by lymphomas. These may be diagnostically challenging because they can mimic a variety of benign conditions and may be difficult to subclassify when malignant. The classification of gastrointestinal lymphomas is an evolving area with some recent changes. Although some of these entities are rare, they are important to recognize because of the variable clinical presentations, comorbidities, and treatment implications. This article explores new and revised entities in gastrointestinal lymphoproliferative disorders.
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Affiliation(s)
- Sarmad H Jassim
- Pathology Department, University of Michigan, 2800 Plymouth Road, North Campus Research Complex, Building 36, Ann Arbor, MI, USA
| | - Lauren B Smith
- Pathology Department, University of Michigan, 2800 Plymouth Road, North Campus Research Complex, Building 36, Ann Arbor, MI, USA.
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14
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Perry AM, Bailey NG, Bonnett M, Jaffe ES, Chan WC. Disease Progression in a Patient With Indolent T-Cell Lymphoproliferative Disease of the Gastrointestinal Tract. Int J Surg Pathol 2018; 27:102-107. [PMID: 29986618 DOI: 10.1177/1066896918785985] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract is a new provisional entity in the 2016 revision of the World Health Organization classification. The disease has an indolent course and progression to aggressive T-cell lymphoma has rarely been reported. We describe a case of a 37-year-old male with indolent T-LPD of the GI tract who 3 years later developed aggressive T-cell lymphoma and died of progressive disease. An infiltrate of indolent T-LPD in the GI tract and aggressive lymphoma diagnosed from the liver biopsy had similar immunophenotype, but cellular infiltrate in the liver showed more atypia compared with the GI biopsies of indolent T-LPD. Moreover, T-cell gene rearrangement studies showed an identical clonal rearrangement in indolent T-LPD and aggressive lymphoma. Patients with indolent T-LPD of the GI tract need a long-term follow-up, as some of them may develop more aggressive lymphoma.
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Affiliation(s)
| | | | | | - Elaine S Jaffe
- 4 National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Wing C Chan
- 5 City of Hope National Medical Center, Duarte, CA, USA
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15
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Vetro C, Bonanno G, Giulietti G, Romano A, Conticello C, Chiarenza A, Spina P, Coppolino F, Cunsolo R, Raimondo FD. Rare gastrointestinal lymphomas: The endoscopic investigation. World J Gastrointest Endosc 2015; 7:928-949. [PMID: 26265987 PMCID: PMC4530327 DOI: 10.4253/wjge.v7.i10.928] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/01/2015] [Accepted: 07/09/2015] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal lymphomas represent up to 10% of gastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. However, the gastrointestinal tract can be the site of rarer lymphoma subtypes as a primary or secondary localization. Due to their rarity and the multifaceted histology, an endoscopic classification has not been validated yet. This review aims to analyze the endoscopic presentation of rare gastrointestinal lymphomas from disease diagnosis to follow-up, according to the involved site and lymphoma subtype. Existing, new and emerging endoscopic technologies have been examined. In particular, we investigated the diagnostic, prognostic and follow-up endoscopic features of T-cell and natural killer lymphomas, lymphomatous polyposis and mantle cell lymphoma, follicular lymphoma, plasma cell related disease, gastrointestinal lymphomas in immunodeficiency and Hodgkin’s lymphoma of the gastrointestinal tract. Contrarily to more frequent gastrointestinal lymphomas, data about rare lymphomas are mostly extracted from case series and case reports. Due to the data paucity, a synergism between gastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinical and prognostic features are different from nodal and extranodal or the bone marrow (in case of plasma cell disease) counterpart. Therefore, the approach should be based on the knowledge of the peculiar behavior and natural history of disease.
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Abstract
Primary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4(-)/CD8(+), 1 was CD4(+)/CD8(-), and another was CD4(-)/CD8(-). T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name "indolent T-LPD of the GI tract" for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy.
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Hirata N, Tominaga K, Ohta K, Kadouchi K, Okazaki H, Tanigawa T, Shiba M, Watanabe T, Fujiwara Y, Nakamura S, Oshitani N, Higuchi K, Arakawa T. A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small intestine. World J Gastroenterol 2007; 13:1453-7. [PMID: 17457982 PMCID: PMC4146935 DOI: 10.3748/wjg.v13.i9.1453] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophagogastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano’s classification, its staging was clinically diagnosed as stage II. Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone) regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow-up EGD and histological examinations detected no recurrence of the disease.
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MESH Headings
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Biopsy
- Cyclophosphamide/administration & dosage
- Doxorubicin/administration & dosage
- Endoscopy, Digestive System
- Female
- Humans
- Intestinal Polyposis/diagnosis
- Intestinal Polyposis/etiology
- Intestine, Small/pathology
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/diagnosis
- Lymphoma, B-Cell, Marginal Zone/drug therapy
- Middle Aged
- Prednisolone/administration & dosage
- Rituximab
- Vincristine/administration & dosage
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Affiliation(s)
- Naoto Hirata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
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