Anaplastic Large T-cell Lymphoma Research Articles

Recurrence of an erythrodermic mycosis fungoides as a biologically indolent anaplastic large T-cell lymphoma initially misdiagnosed as being of donor origin.

Recurrence of an erythrodermic mycosis fungoides as a biologically indolent anaplastic large T-cell lymphoma initially misdiagnosed as being of donor origin.

Primary cutaneous anaplastic large T-cell lymphoma: From a lesion peculiar to its diagnosis

The authors present a clinical case of a 42-year-old woman presented to the Emergency Department for a non-pruritic skin lesion in the left lower limb with a few months of evolution.

Synchronous anaplastic large T-cell lymphoma of the eyelid

Synchronous anaplastic large T-cell lymphoma of the eyelid

Implant-associated anaplastic large T-cell lymphoma (BIA-ALCL): case report

Implant-associated anaplastic large T-cell lymphoma (BIA-ALCL): case report

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Epidemiology, Clinical Features and Outcomes of Peripheral T-Cell Lymphoma in Latin America

INTRODUCTION: Peripheral T-cell lymphomas (PTCL) represent a rare and heterogenous group of mature T-cell lymphomas often characterized by aggressive behavior. Previous studies evaluating the distribution of PTCL subtypes across Latin America (LATAM) were limited in their representation of most countries in the region. Additionally, a lack of standardized management for several subtypes and the absence of comprehensive lymphoma registries in LATAM suggests exploring real-world treatment patterns and clinical outcomes. We conducted an international pooled analysis to assess the distribution of PTCL across LATAM countries and report treatment outcomes. METHODS: We compiled data from patients aged ≥18 years with newly diagnosed PTCL from the retrospective registry of the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL, n=988, 1975-2023), the Brazilian T-cell Project (Brazilian TCP, 2015-2017, 168 cases retrospective; 2017-2023, 425 cases prospective) and the prospective registry of the International T cell Project (ITCP, n=529, 2006-2023). Data were abstracted from medical records in a standardized form. Survival data was only available from the GELL and Brazilian TCP. Overall survival (OS) was estimated from diagnosis to death from any cause, while progression-free survival (PFS) was defined from diagnosis to relapse, progression, or death from any cause. We used the Kaplan-Meier method and Log-rank test to estimate and compare survival probabilities. RESULTS: We enrolled 2110 patients from 11 LATAM countries. Overall, the median age at diagnosis was 54 years (range 18-95 years), most were male (59%), present with advanced stage disease (Ann Arbor III-IV, 67%), and had good performance status (ECOG ≤1, 71%) (Table 1). After PTCL not otherwise specified (NOS, 39%), adult T-cell leukemia/lymphoma (ATL, 18%) and extranodal NK/T cell lymphoma (ENKTL, 16%) were the most frequently diagnosed PTCL subtypes with varying distribution across LATAM countries. Peru had a higher prevalence of ATL (39%) and ENKTL was frequently diagnosed in Central America (43%). In contrast, ALK-negative (ALK-) anaplastic large T-cell lymphoma (ALCL) was the second more frequent subtype in Brazil (18%), Chile (16%), and Argentina (9%). The percentage of mature T-cell NOS was 27% in Argentina and 28% in Chile. A total of 1620 received chemotherapy. First-line chemotherapy varied across subtypes. Patients with ENKTL were frequently treated with asparaginase/platinum-based therapy (62%), while CHOP was more commonly used for ATL or PTCL NOS (46% for both). Chemotherapy with CHOEP/EPOCH was frequent for patients with ALK- ALCL (45%), ALK+ (ALCL 47%), or AITL (48%). With a median follow-up of 33 months, the 3-year OS and PFS for the overall cohort were 40% and 30%, respectively. ALK+ ALCL had superior survival estimates, with a 3-year OS of 77% and a 3-year PFS of 73%. The 3-year OS for patients with ENKTL was 48% and the PFS was 45%. Patients with ATL experienced the lowest survival rates (OS and PFS of 23% and 16% at 3 years, respectively). The use of asparaginase/platinum or CHOP-based therapy was associated with superior 3-year OS (61% and 52%, respectively; p=0.011) and PFS (57% and 49%, respectively; p=0.017) among patients with ENKTL. For ATL, the use of CHOEP/EPOCH was associated with improved 3-year OS (21%, p=0.009) and PFS (15%, p=0.024), but outcomes remained dismal. CONCLUSION: To our knowledge, we report the largest pooled cohort of PTCL subtypes across LATAM by leveraging the retrospective registry of the GELL consortium and data from the Brazilian TCP and ITCP. Our findings suggest a distinct distribution of PTCL subtypes across LATAM countries, with a higher prevalence of ATL and ENKTL compared to the epidemiological patterns in Western countries. This distribution underscores a unique opportunity to increase trial enrollment and accrual of rarer PTCL subtypes. The relatively high percentage of mature T-cell NOS suggests difficulties in providing specific lymphoma diagnoses in the region. The low survival rates for some subtypes indicate the need to develop novel therapies to improve patient outcomes. A larger prospective assessment of PTCL epidemiology and treatment outcomes is being planned to expand the ascertainment of cases, improve pathological classification of the different PTCL subtypes, and validate our results in the LATAM region.

Coexistence of ALK-negative anaplastic large T-cell lymphoma and plasmablastic lymphoma in the same patient: A case report

Alk-negative anaplastic lymphoma and plasmablastic lymphoma are both rare lymphoid neoplasms, and usually have poor prognosis. We present the case of a patient who was diagnosed with both diseases within a short time from each other.

Phosphorylated STAT3 as a potential diagnostic and predictive biomarker in ALK- ALCL vs. CD30high PTCL, NOS.

The differential diagnosis between ALK-negative anaplastic large cell lymphoma (ALK- ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with high expression of CD30 (CD30high) are essential. However, no reliable biomarker is available in daily practice except CD30. STAT3 is characteristically activated in ALCL. We aimed to investigate whether the status of STAT3 phosphorylation could help the differential diagnosis. The status of phosphorylation of STAT3 was examined using two antibodies against pSTAT3-Y705 and pSTAT3-S727 by immunohistochemistry in ALK+ ALCL (n=33), ALK- ALCL (n=22) and PTCL, NOS (n=34). Ten PTCL, NOS with diffuse CD30 expression were defined as CD30high PTCL, NOS. Flowcytometric analysis were performed to evaluate the expression of pSTAT3-Y705/S727 in PTCL, NOS (n=3). The median H-scores of pSTAT3-Y705 and S727 were 280 and 260 in ALK+ ALCL, 250 and 240 in ALK- ALCL, and 45 and 75 in CD30high subgroup, respectively. Using H score of 145 as the cutoff value, pSTAT3-S727 alone distinguished between ALK- ALCL and CD30high PTCL, NOS with a sensitivity of 100% and specificity of 83%. Additionally, pSTAT3-S727, but not pSTAT3-Y705, was also expressed by background tumor-infiltrating lymphocytes (S727TILs) in PTCL, NOS. PTCL, NOS patients with high S727TILs H score had a favorable prognosis than those with no TILs (3-year OS rate: 43% vs. 0, p=0.013) or low S727TILs (3-year OS rate: 43% vs. 0, p=0.099). Flowcytometric analysis revealed that of the three patients investigated, two had enhanced pSTAT-S727 signals in neoplastic cell populations, and all three patients were negative for pSTAT3-Y705 expression in both tumor cells and background lymphocytes. pSTAT3-Y705/S727 can be used to help distinguish ALK- ALCL from CD30high PTCL, NOS and pSTAT3-S727 expression by TILs predicts the prognosis of a subset of PTCL, NOS.

Breast Implant-Associated Tumors.

In addition to anaplastic large T-cell lymphomas (BIA-ALCL), other implant-related tumors have been described for some years. Squamous cell carcinoma (SSC) and B-cell lymphomas occurred in very rare cases. The unexplained pathogenesis as well as the unclear individual risk profile is an ongoing source of uncertainty for patients and physicians. The pathogenesis of the tumors is still largely not understood. While BIA-ALCL occurs more frequently with textured breast implants, other tumors were also observed with smooth implants and at other implant sites. Multiple potential mechanisms are discussed. It is suspected that the etiology of a chronic inflammatory response and subsequently immunostimulation is multifactorial and appears to play a key role in the malignant transformation. Since there are currently no sufficiently valid data for a specific risk assessment, this must be done with caution. This article presents the incidence, pathogenesis, as well as the level of evidence according to the current state of knowledge, and evaluates and discusses the current literature.

Cutaneous anaplastic large T-cell lymphoma in a cat - case report

Cutaneous anaplastic large T-cell lymphoma in a cat - case report

Thirty Years of Experience With Ocular Adnexal T-Cell Lymphoma.

To evaluate the disease characteristics and survival of patients with ocular adnexal T-cell lymphoma. A retrospective, observational study of patients with a histopathological diagnosis of T-cell lymphoma of the ocular adnexa seen between 1992 and 2022. Demographic data, clinical presentation, imaging, histology, immunohistochemistry, treatment, and outcomes were reviewed. Fifteen patients were included in the study with the mean age at diagnosis of 50 years old (range 7-85). The most common presenting symptoms were ulcerated eyelid skin lesions (40%) followed by eyelid swelling (13.3%), and lacrimal passageways obstruction (13.3%). The anaplastic large cell lymphoma (33%) and primary cutaneous T-cell lymphoma (33%) were the most diagnosed peripheral T-cell lymphoma subtypes, followed by the nasal type natural killer/T-cell lymphoma (27%) and peripheral T-cell lymphoma not otherwise specified (7%). The most prevalent stage of disease progression was stage I and stage IV (Ann Arbor classification) with seven (47%) patients each. Eight (53%) patients succumbed to the disease process of which three (37.5%) deceased in the first six months and six (75%) within the first year of diagnosis. We identified a strong statistical association between stage and disease-related death ( p = 0.003). Peripheral T-cell lymphoma occurring in the orbit and ocular adnexa is extremely rare. Advanced stage at diagnosis leads to almost certain death from the disease despite aggressive local and systemic treatment. Early diagnosis improves the chances of survival but can be hindered by this condition's ability to simulate benign inflammatory conditions both clinically and histologically.

SBNO2 is a critical mediator of STAT3-driven hematological malignancies

AbstractGain-of-function mutations in the signal transducer and activator of transcription 3 (STAT3) gene are recurrently identified in patients with large granular lymphocytic leukemia (LGLL) and in some cases of natural killer (NK)/T-cell and adult T-cell leukemia/lymphoma. To understand the consequences and molecular mechanisms contributing to disease development and oncogenic transformation, we developed murine hematopoietic stem and progenitor cell models that express mutated STAT3Y640F. These cells show accelerated proliferation and enhanced self-renewal potential. We integrated gene expression analyses and chromatin occupancy profiling of STAT3Y640F-transformed cells with data from patients with T-LGLL. This approach uncovered a conserved set of direct transcriptional targets of STAT3Y640F. Among these, strawberry notch homolog 2 (SBNO2) represents an essential transcriptional target, which was identified by a comparative genome-wide CRISPR/Cas9-based loss-of-function screen. The STAT3-SBNO2 axis is also present in NK-cell leukemia, T-cell non-Hodgkin lymphoma, and NPM-ALK-rearranged T-cell anaplastic large cell lymphoma (T-ALCL), which are driven by STAT3-hyperactivation/mutation. In patients with NPM-ALK+ T-ALCL, high SBNO2 expression correlates with shorter relapse-free and overall survival. Our findings identify SBNO2 as a potential therapeutic intervention site for STAT3-driven hematopoietic malignancies.

Outcome of limited-stage peripheral T-Cell lymphoma after CHOP(-like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group.

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8cycles of CHOP(-like) therapy and 22% received 3-4cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4cycles vs. 6-8cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4cycles versus 6-8cycles of CHOP(-like) therapy were comparable.

Comparing Survival Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Patients with Relapsed/Refractory Nodal Peripheral T-Cell Lymphoma

Background Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma and carries a poor prognosis. The four most common types are PTCL-NOS, angioimmunoblastic T cell lymphoma (AITL), and anaplastic large T cell lymphoma (ALCL) with or without ALK and together are grouped as nodal PTCL. In relapsed/refractory disease (r/r), the survival outcomes are poor and estimated to be approximately 13.7 months (Mak, Hamm et al. 2013). Hematopoietic cell transplantation (HCT) has been used to consolidate response and improve outcomes. However, the role of autologous HCT (auto HCT) and allogeneic HCT (allo HCT) remains controversial. Here we aim to compare the survival outcomes of auto HCT and allo HSCT in r/r PTCL. Methods We retrospectively reviewed clinical data on 53 patients at Moffitt Cancer Center who developed r/r nodal PTCL and received HCT from 12/2007 to 12/2021. Patients who had auto HCT during the first remission were excluded. Physician discretion, donor availability, among others, were the factors that influenced transplant type allocation. Clinical data were abstracted in accordance with institutional review board-approved protocol. Patients were divided into two subgroups: cohort A) auto HCT and cohort B) allo HCT. The baseline clinical data of two cohorts were summarized using descriptive statistics and compared using Kruskal-Wallis tests for continuous variables and Chi-squared tests for categorical variables. Overall survival (OS) was calculated from the date of HCT to death or censored to the last follow-up. Median OS was calculated using the Kaplan Meier method and compared two cohorts with a log-rank test. Univariate and multivariate Cox proportional hazard (PH) using the backward elimination method were used to evaluate the association between OS and types of transplants. Results Out of 53 patients, 30 (57%) patients received auto HCT (cohort A), while 23 (43%) patients received allo HCT (cohort B). All patients achieved either partial response (PR) or complete response (CR) prior to transplant. The patients in allo cohort B were younger at the time of transplant (median age: 60 years vs. 50 years for cohort A and B, respectively, p=0.06), had a higher proportion of refractory disease (27% vs. 65% for cohort A and B, respectively, p=0.005), and had a higher proportion of PTCL-NOS (33% vs. 65% for cohort A and B, respectively, p=0.006) (table 1). ECOG status at transplant and IPI at the time of diagnosis were not significantly different between the two groups. Median OS was 40 months in cohort A compared to 57 months in cohort B, however, no statistical difference was present (p=0.49) (Figure 1). In the univariate analysis, HR for allo HCT was 0.77 (p=0.5). When adjusted for ECOG status at transplant, histology subtypes, IPI score at diagnosis in the multivariate analysis, allo HCT was associated with prolonged OS with an HR of 0.41 (p=0.045). At the study cutoff with a median follow-up of 57 months in cohort A, 18 patients died. Out of 12 patients with a known cause of death in cohort A, 7 patients (38%) died from relapse disease. With a median follow-up of 73 months in cohort B, 10 patients died. Out of 10 patients with a known cause of death, 2 patients (20%) died from the relapsed disease. Conclusion Our data showed that allo HCT in r/r PTCL is associated with improved survival compared to auto HCT in multivariate analysis. Our result supports the use of allo HCT, especially in the younger/fit population and in refractory disease. Larger studies are needed to validate our results. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA CD30+ IN ITS EXTENSIVE FORM: ABOUT A CASE

Primary cutaneous anaplastic large T-cell lymphoma CD30+ is a rare cutaneous lymphoma, which belongs to the group of cutaneous T-cell lymphoproliferations CD30+. It is characterized by an excellent prognosis and the treatment is therefore not very aggressive. However, its histological and molecular characteristics have many similarities with lymphoproliferative diseases whose prognosis is completely different. For this reason, it is important to study the patient from the anamnestic and clinical point of view in order to reach a correct diagnosis.

TCL-307 Epidemiological Data on T-Cell Lymphoma in the Republic of Kosovo During the Period of 2016-2021.

T-cell lymphomas consist of a wide variety of uncommon diseases that can be indolent or aggressive and consists of 12% of all NHL. T-cell lymphoma is an uncommon hematological malignancy in Kosovo compared to the other lymphoid malignancies. There are a variety of subtypes of the disease present with anaplastic large T-cell lymphoma being the most common. The diagnosis of this disease has increased in the last few years and the treatment with chemotherapy and other supportive care has many challenges. With this study, we want to better understand the disease so we can improve the quality of care for the patients. Cross-sectional retrospective epidemiological study. The data was collected during the period of February 2016 to January 2021. The data was collected from the chemotherapy treatment protocol books and patient files in the Hematology Clinic of the University Clinical Center of Kosovo. Adults, age 18 and older, of both genders, diagnosed the treated with T-cell lymphoma in the Hematology clinic of Kosovo. The diagnosis was made based on histopathological and immunohistochemical analysis of lymphoid tissue mostly in the Republic of Kosovo. During the period specified above, 47 patients were diagnosed and treated with T-cell lymphoma, the most common was anaplastic large T-cell lymphoma with 11(23.40%) then enteropathy associated T-cell lymphoma with 8(17.02%), NK/T-cell lymphoma with 5(10.63%). One rare example of T-cell lymphoma was a patient diagnosed with gamma/delta T-cell lymphoma, which was the only such case in our clinic. Of the patients diagnosed with T-cell lymphoma during this period, 33 were treated with the CHOP protocol as first-line chemotherapy. The majority of patients were treated with the CHOP chemotherapy protocol as the first-line therapy. The results of the treatments were successful in achieving remissions in a small number of patients. The patients that did not achieve remission received a second treatment protocol with mixed results.

Linfoma de células grandes T anaplásico: experiencia de 10 años en el Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú

Introduction: Anaplastic Large T-Cell Lymphoma is an infrequent pathology, determined by the expression of CD30, with different characteristics in its presentation and being more aggressive according to the expression of ALK. Objectives: The present study seeks to determine the epidemiological, clinicopathological and prognostic characteristics of patients with Anaplastic Large T-Cell Lymphoma. Methods: Descriptive, retrospective study of patients diagnosed with Anaplastic Large T-Cell Lymphoma of the National Institute of Neoplastic Diseases (INEN) between 2006 and 2016. Results: The pathology of 86 patients was analyzed and reviewed, 57% were men and 33% women, of the total population 21.9% were positive for ALK. 48 of the patients were found in CD I and II and 36 between stages III and IV. 57 patients had low or low-intermediate risk, while 26 had high-intermediate and high risk. The estimated overall survival was 40.8% at 5 years, in the group of patients with ALK + it was 67.4% and in the group with ALK- it was estimated at 30.2%. Conclusions: Anaplastic Large T-Cell Lymphoma is an aggressive disease, with a heterogeneous distribution with respect to age and slightly more frequent in males, with ALK and the international prognostic index as important prognostic factors.

T-cell-derived Hodgkin lymphoma has motility characteristics intermediate between Hodgkin and anaplastic large cell lymphoma.

Classic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T‐cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T‐cell lymphoma (ALCL). Since we recently observed differences in the motility of ALCL and cHL tumour cells, here, we aimed to obtain a better understanding of T‐cell‐derived cHL by investigating their global proteomic profiles and their motility. In a proteomics analysis, when only motility‐associated proteins were regarded, T‐cell‐derived cHL cell lines showed the highest similarity to ALK− ALCL cell lines. In contrast, T‐cell‐derived cHL cell lines presented a very low overall motility, similar to that observed in conventional cHL. Whereas all ALCL cell lines, as well as T‐cell‐derived cHL, predominantly presented an amoeboid migration pattern with uropod at the rear, conventional cHL never presented with uropods. The migration of ALCL cell lines was strongly impaired upon application of different inhibitors. This effect was less pronounced in cHL cell lines and almost invisible in T‐cell‐derived cHL. In summary, our cell line‐derived data suggest that based on proteomics and migration behaviour, T‐cell‐derived cHL is a neoplasm that shares features with both cHL and ALCL and is not an ALCL with low tumour cell content. Complementary clinical studies on this lymphoma are warranted.

Dermoscopy of Primary Cutaneous Anaplastic Lymphoma Kinase Negative Large T-Cell Lymphoma.

Dermoscopy of Primary Cutaneous Anaplastic Lymphoma Kinase Negative Large T-Cell Lymphoma.

Lack of PRAME Expression in Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphomas (CTCLs) are rare tumors with no established markers that can reliably distinguish between benign and malignant lesions. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is found in many solid and hematologic malignancies. PRAME overexpression typically portends a poor prognosis and lower chemotherapeutic response. To date, no studies have established a role for PRAME in CTCL. An analysis was performed on 47 cases definitively diagnosed as CTCL: 25 cases of mycosis fungoides, 2 of Sezary syndrome, 5 of CD30+ lymphoproliferative disorder, 7 of primary cutaneous anaplastic large T-cell lymphoma, 3 of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, 1 of subcutaneous panniculitis-like T-cell lymphoma, and 4 of angiocentric T-cell lymphoma. PRAME immunohistochemistry was completely negative in all cases. PRAME expression was not found in any CTCL subtypes, suggesting that the pathogenesis of CTCL is not mediated by PRAME. Further study is required to identify biomarkers that might aid in the diagnosis and prognostication of CTCLs.