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Current Oncology (Toronto, Ont.) Dec 2021Angioimmunoblastic T cell lymphoma (AITL) is a common subtype of mature peripheral T cell lymphoma (PTCL). As per the 2016 World Health Organization classification, AITL... (Review)
Review
Angioimmunoblastic T cell lymphoma (AITL) is a common subtype of mature peripheral T cell lymphoma (PTCL). As per the 2016 World Health Organization classification, AITL is now considered as a subtype of nodal T cell lymphoma with follicular helper T cells. The diagnosis is challenging and requires a constellation of clinical, laboratory and histopathological findings. Significant progress in the molecular pathophysiology of AITL has been achieved in the past two decades. Characteristic genomic features have been recognized that could provide a potential platform for better diagnosis and future prognostic models. Frontline therapy for AITL was mainly depending on chemotherapy and the management of relapsed or refractory AITL is still unsatisfactory with a very poor prognosis. Upfront transplantation offers better survival. Novel agents have been introduced recently with promising outcomes. Several clinical trials of combinations using novel agents are underway. Herein, we briefly review recent advances in AITL diagnosis and the evolving treatment landscape.
Topics: Humans; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Prognosis
PubMed: 34940095
DOI: 10.3390/curroncol28060456 -
Cancer Cell Mar 2020Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To...
Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Gene Dosage; Gene Expression Regulation, Neoplastic; Genomics; Herpesvirus 4, Human; Humans; Lymphoma, T-Cell; Molecular Targeted Therapy; Mutation; Natural Killer T-Cells; Phylogeny; Transcriptome; Whole Genome Sequencing; Xenograft Model Antitumor Assays; Zebrafish
PubMed: 32183952
DOI: 10.1016/j.ccell.2020.02.005 -
Blood Mar 2017Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the... (Review)
Review
Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the literature would suggest given the many names that have preceded it. Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. Induction strategies continue to focus on increasing complete remission rates that allow more transplant-eligible patients to proceed toward consolidative high-dose therapy and autologous stem cell rescue with improving long-term survival. There are several clinical trials in which recently approved drugs with known activity in AITL are paired with induction regimens with the hope of demonstrating long-term progression-free survival over cyclophosphamide, doxorubicin, vincristine, and prednisone. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell
PubMed: 28115369
DOI: 10.1182/blood-2016-09-692541 -
Blood Oct 2020Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell neoplasm that most commonly arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. HSTCL is... (Review)
Review
Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell neoplasm that most commonly arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. HSTCL is more common in adolescent and young adults and has a rapidly progressive clinical course and poor outcome due to its refractoriness to conventional chemotherapy regimens. Approximately 20% of the cases arise in the background of chronic immunosuppression or immune dysregulation. Patients commonly present with constitutional symptoms, hepatic and liver enlargement, and cytopenias; hematophagocytic syndrome can also occur. The most frequent chromosomal aberrations associated with HSTCL are isochromosome 7q and trisomy 8, and most cases harbor mutations in genes involved in chromatin modification or the JAK/STAT pathway. The rarity of this disease, along with lack of nodal involvement and presenting symptoms that mimic different entities including infectious etiologies, makes this lymphoma a significant diagnostic challenge. In this review, we highlight the clinical and pathologic features of HSTCL. Moreover, we summarize the results of recent molecular studies suggesting potential targets for novel therapeutics strategies.
Topics: Animals; Humans; Liver Neoplasms; Lymphoma, T-Cell; Splenic Neoplasms
PubMed: 32756940
DOI: 10.1182/blood.2019004118 -
Leukemia Oct 2020It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970's. Our understanding of the disease has... (Review)
Review
It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970's. Our understanding of the disease has dramatically changed due to multiple discoveries and insights. One of the key features of AITL is aberrant immune activity. Although AITL is now understood to be a neoplastic disease, pathologists appreciated that it was an inflammatory condition. The more we understand AITL at cellular and genetic levels, the more we view it as both a neoplastic and an inflammatory disease. Here, we review recent progress in our understanding of AITL, focusing on as yet unsolved questions.
Topics: Animals; Humans; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell; Mutation; Prognosis; Tumor Microenvironment
PubMed: 32704161
DOI: 10.1038/s41375-020-0990-y -
Journal of Veterinary Internal Medicine Nov 2021Differentiation of low-grade intestinal T-cell lymphoma (LGITL) from lymphoplasmacytic enteritis (LPE) in cats is a diagnostic challenge for pathologists.
BACKGROUND
Differentiation of low-grade intestinal T-cell lymphoma (LGITL) from lymphoplasmacytic enteritis (LPE) in cats is a diagnostic challenge for pathologists.
OBJECTIVE
Characterize histologic, immunohistochemical, and molecular features of LGITL and LPE.
ANIMALS
Forty-four client-owned cats, 22 diagnosed with LGITL and 22 with LPE.
METHODS
Prospective, cohort study. Clinical suspicion of LGITL or LPE was based on persistent gastrointestinal signs, unresponsive to empirical treatments. All cats underwent a standardized diagnostic evaluation, including biopsy (preferentially full-thickness), and were diagnosed with LGITL or LPE after review of clinical, laboratory, sonographic, histologic, immunohistochemical, and clonality results.
RESULTS
A monomorphic lymphocytic population (22/22, 100%) and in-depth mucosal infiltration (15/22, 68%) were hallmarks of LGITL. Epithelial patterns (nests and plaques) were significantly more frequent in LGITL (11/22, 50%) than in LPE (1/22, 5%) cases (P = .001). A CD3+ lymphocytic apical-to-basal gradient was observed in 9/22 (41%) of LGITL vs 1/22 (5%) of LPE cases (P = .004). Most LPE cases (17/18, 94%) featured marked fibrosis in the superficial part of the lamina propria. The Ki-67 20%- and 30%-thresholds discriminated between LGITL and LPE within both the epithelium (specificity >95%) and lamina propria (specificity >95%), respectively. All LGITL cases were CD3+ pSTAT3- and pSTAT5+. T-cell receptor gamma chain gene rearrangements indicated monoclonality in 86% of LGITL cases. Surprisingly, 70% of LPE cases featured monoclonality (40%) or monoclonality on a polyclonal background (30%).
CONCLUSIONS AND CLINICAL IMPORTANCE
We identified new histologic, immunohistochemical, and clonality criteria to distinguish LGITL from LPE.
Topics: Animals; Cat Diseases; Cats; Cohort Studies; Enteritis; Intestines; Lymphoma, T-Cell; Prospective Studies
PubMed: 34374109
DOI: 10.1111/jvim.16231 -
Journal of Veterinary Internal Medicine Nov 2021Low-grade intestinal T-cell lymphoma (LGITL) is the most common intestinal neoplasm in cats. Differentiating LGITL from lymphoplasmacytic enteritis (LPE) is challenging...
BACKGROUND
Low-grade intestinal T-cell lymphoma (LGITL) is the most common intestinal neoplasm in cats. Differentiating LGITL from lymphoplasmacytic enteritis (LPE) is challenging because clinical signs, laboratory results, diagnostic imaging findings, histology, immunohistochemistry, and clonality features may overlap.
OBJECTIVES
To evaluate possible discriminatory clinical, laboratory and ultrasonographic features to differentiate LGITL from LPE.
ANIMALS
Twenty-two cats diagnosed with LGITL and 22 cats with LPE based upon histology, immunohistochemistry, and lymphoid clonality.
METHODS
Prospective, cohort study. Cats presented with clinical signs consistent with LGITL or LPE were enrolled prospectively. All data contributing to the diagnostic evaluation was recorded.
RESULTS
A 3-variable model (P < .001) consisting of male sex (P = .01), duration of clinical signs (P = .01), and polyphagia (P = .03) and a 2-variable model (P < .001) including a rounded jejunal lymph node (P < .001) and ultrasonographic abdominal effusion (P = .04) were both helpful to differentiate LGITL from LPE.
CONCLUSIONS AND CLINICAL IMPORTANCE
Most clinical signs and laboratory results are similar between cats diagnosed with LGITL and LPE. However, male sex, a longer duration of clinical signs and polyphagia might help clinicians distinguish LGITL from LPE. On ultrasonography, a rounded jejunal lymph node, and the presence of (albeit small volume) abdominal effusion tended to be more prevalent in cats with LGITL. However, a definitive diagnosis requires comprehensive histopathologic and phenotypic assessment.
Topics: Animals; Cat Diseases; Cats; Cohort Studies; Enteritis; Laboratories; Lymphoma, T-Cell; Male; Prospective Studies
PubMed: 34687072
DOI: 10.1111/jvim.16272 -
Blood Mar 2022
Topics: Humans; Immunomodulating Agents; Lymphoma, T-Cell; Multiple Myeloma
PubMed: 35357480
DOI: 10.1182/blood.2021015119 -
International Journal of Molecular... Feb 2021T-cell clonality testing is integral to the diagnostic work-up of T-cell malignancies; however, current methods lack specificity and sensitivity, which can make the... (Review)
Review
T-cell clonality testing is integral to the diagnostic work-up of T-cell malignancies; however, current methods lack specificity and sensitivity, which can make the diagnostic process difficult. The recent discovery of a monoclonal antibody (mAb) specific for human TRBC1 will greatly improve the outlook for T-cell malignancy diagnostics. The anti-TRBC1 mAb can be used in flow cytometry immunophenotyping assays to provide a low-cost, robust, and highly specific test that detects clonality of immunophenotypically distinct T-cell populations. Recent studies demonstrate the clinical utility of this approach in several contexts; use of this antibody in appropriately designed flow cytometry panels improves detection of circulating disease in patients with cutaneous T-cell lymphoma, eliminates the need for molecular clonality testing in the context of large granular lymphocyte leukemia, and provides more conclusive results in the context of many other T-cell disorders. It is worth noting that the increased ability to detect discrete clonal T-cell populations means that identification of T-cell clones of uncertain clinical significance (T-CUS) will become more common. This review discusses this new antibody and describes how it defines clonal T-cells. We present and discuss assay design and summarize findings to date about the use of flow cytometry TRBC1 analysis in the field of diagnostics, including lymph node and fluid sample investigations. We also make suggestions about how to apply the assay results in clinical work-ups, including how to interpret and report findings of T-CUS. Finally, we highlight areas that we think will benefit from further research.
Topics: Gene Expression Regulation, Neoplastic; Humans; Lymphoma, T-Cell; Neoplasm Proteins; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes
PubMed: 33673033
DOI: 10.3390/ijms22041817 -
Annals of Oncology : Official Journal... Mar 2022
Topics: Humans; Lymphoma, T-Cell
PubMed: 35017032
DOI: 10.1016/j.annonc.2021.12.011