RESUMEN
A 5 yr old female spayed pit bull terrier mix was evaluated for development of multiple dermal nodules over the previous 2 wk with concurrent weight loss and lethargy. A definitive diagnosis of cutaneous epitheliotropic T-cell lymphoma was obtained through histopathology and immunohistochemistry. Treatment was initiated with 32.9 mg/m2 (1.2 mg/kg) of oral verdinexor twice per week, according to label guidance. One week after treatment initiation, clinical remission was noted with complete resolution of the cutaneous nodules. The dog has continued twice-weekly treatments without any interruption and remains in complete remission 17 mo following initiation of verdinexor therapy. This case provides evidence for the utility of verdinexor in the treatment of canine cutaneous epitheliotropic T-cell lymphoma.
Asunto(s)
Enfermedades de los Perros , Neoplasias Cutáneas , Animales , Perros , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Femenino , Neoplasias Cutáneas/veterinaria , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/veterinaria , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Antineoplásicos/uso terapéuticoAsunto(s)
Anticuerpos Monoclonales Humanizados , Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Exantema/inducido químicamente , Exantema/patología , Inducción de Remisión , Masculino , Femenino , Persona de Mediana Edad , Respuesta Patológica CompletaRESUMEN
The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.
Asunto(s)
Neoplasias Cutáneas , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Estudios Retrospectivos , República de Corea/epidemiología , Persona de Mediana Edad , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/epidemiología , Prevalencia , Adulto , Anciano , Linfoma Cutáneo de Células T/mortalidad , Linfoma Cutáneo de Células T/epidemiología , Linfoma Cutáneo de Células T/patología , Adulto Joven , Anciano de 80 o más Años , Adolescente , Linfoma de Células B/mortalidad , Linfoma de Células B/epidemiología , Linfoma de Células B/patología , Niño , Análisis de SupervivenciaRESUMEN
ABSTRACT: Primary cutaneous gamma/delta T-cell lymphoma (PCGD-TCL) is a rare yet highly aggressive subtype of primary cutaneous lymphoma. Characterized by its challenging diagnosis and poor prognosis, PCGD-TCL presents unique clinical and histopathological features that distinguish it from other primary cutaneous lymphoma subtypes. Here, we report the case of a 75-year-old man who initially presented with multiple erythematous indurated plaques over his back and bilateral lower extremities. The initial biopsy suggested primary cutaneous T-cell lymphoma (PCTCL) with a CD30-negative phenotype. However, within a 2-month interval, the disease progressed rapidly, manifesting as extensive skin involvement across the chest and upper extremities. A repeat skin biopsy was performed, revealing dermal atypical lymphocytes without epidermotropism. Immunohistochemical analysis demonstrated positivity for CD3, CD5, and CD4, as well as T-cell receptor delta (TCR delta) expression, along with the loss of CD8 and CD30 expression. These findings were consistent with a diagnosis of PCGD-TCL. Despite therapeutic interventions, including systemic treatments, the patient's condition deteriorated rapidly, ultimately leading to his demise within a month of receiving the PCGD-TCL diagnosis. This case highlights the diagnostic complexities associated with PCGD-TCL, emphasizing the importance of careful histopathological examination and immunophenotypic characterization. Given its aggressive nature and propensity for rapid dissemination, early recognition of PCGD-TCL is paramount for initiating appropriate therapeutic interventions. However, effective treatment options for PCGD-TCL remain limited, and the disease typically carries an unfavorable prognosis. Further research is needed to elucidate the underlying molecular mechanisms driving the pathogenesis of PCGD-TCL, to identify novel therapeutic targets, and to improve patient outcomes. In addition, increased awareness among clinicians and pathologists regarding the clinical presentation and diagnostic criteria of PCGD-TCL is crucial for facilitating timely diagnosis and management of this challenging malignancy.
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Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Humanos , Masculino , Anciano , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/diagnóstico , Resultado Fatal , Receptores de Antígenos de Linfocitos T gamma-delta , Biomarcadores de Tumor/análisis , Biopsia , Progresión de la EnfermedadRESUMEN
BACKGROUND AND OBJECTIVE: Cutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. MATERIALS AND METHODS: All cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. RESULTS: A total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. CONCLUSIONS: Stage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients' survival and was closely associated with tumor skin involvement and stage IIB.
Asunto(s)
Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Masculino , Femenino , Anciano , Síndrome de Sézary/mortalidad , Síndrome de Sézary/patología , Micosis Fungoide/mortalidad , Micosis Fungoide/patología , Micosis Fungoide/diagnóstico , Adulto , Anciano de 80 o más Años , Linfoma Cutáneo de Células T/mortalidad , Linfoma Cutáneo de Células T/patología , Análisis de Supervivencia , Adulto Joven , Supervivencia sin Progresión , Progresión de la EnfermedadRESUMEN
Cutaneous T-cell lymphoma is a group of non-Hodgkin T-cell lymphomas that develop in and affect the skin but can potentially spread to other organs. There are many subtypes, the most common of which are mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary cutaneous anaplastic large cell lymphoma. Cutaneous lymphoma is a common cause of recalcitrant chronic skin rash and notoriously mimics other dermatologic and hematologic conditions, often resulting in diagnostic delays of months to years. This review provides an introduction to cutaneous T-cell lymphoma, with a primary focus on the clinical presentation, diagnosis, immunopathogenesis, and management of the condition.
Asunto(s)
Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Manejo de la Enfermedad , Micosis Fungoide/diagnóstico , Micosis Fungoide/terapia , Micosis Fungoide/patologíaRESUMEN
BACKGROUND: Primary cutaneous lymphomas are a distinct group of rare lymphoid neoplasms with absence of extracutaneous lymphomas at the time of presentation. They are rare in Nepal and no data on cutaneous lymphoma have been published from this country till date. METHODS: This retrospective study included 15 cases of cutaneous lymphomas retrieved from the records of department of Dermatopathology, DI Skin Hospital and Referral Centre, Bansbari, Kathmandu, Nepal. Patients were diagnosed according to the current WHO classification for cutaneous lymphoma. RESULTS: A total of 15 cases were studied with median age of 45 years (range: 22 to 81 years) and male to female ratio of 1.5:1. Primary cutaneous lymphomas constituted 13 cases out of 15 and the most common type of cutaneous lymphoma was mycosis fungoides and variants 5 (33%), followed by CD30 positive primary cutaneous anaplastic large cell lymphoma constituting 2 (13%). T-cell cutaneous lymphoma constituted 13 (87%) and B-cell cutaneous lymphoma 2 (13%). CONCLUSIONS: Cutaneous T-cell lymphomas were more frequent than cutaneous B-cell lymphomas in Nepalese patients. Mycosis fungoides and variants are commonest type of primary cutaneous lymphomas.
Asunto(s)
Neoplasias Cutáneas , Centros de Atención Terciaria , Humanos , Nepal/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Anciano de 80 o más Años , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Adulto Joven , Linfoma Cutáneo de Células T/epidemiología , Linfoma Cutáneo de Células T/patología , Micosis Fungoide/epidemiología , Micosis Fungoide/patología , Linfoma de Células B/epidemiología , Linfoma de Células B/patologíaAsunto(s)
Linfoma Extranodal de Células NK-T , Necrosis , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/complicaciones , Masculino , Pie/patología , Persona de Mediana Edad , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/diagnóstico , FemeninoRESUMEN
Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management.
Asunto(s)
Brentuximab Vedotina , Erupciones por Medicamentos , Exantema , Linfoma Cutáneo de Células T , Humanos , Brentuximab Vedotina/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Erupciones por Medicamentos/patología , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/diagnóstico , Anciano , Exantema/inducido químicamente , Exantema/patología , Adulto , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/tratamiento farmacológico , Inmunoconjugados/efectos adversos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Biopsia , Secuenciación de Nucleótidos de Alto Rendimiento , Anciano de 80 o más Años , Piel/patología , Piel/efectos de los fármacos , Piel/inmunología , Diagnóstico DiferencialRESUMEN
Comparison of the 2007 EORTC/ISCL and the 2022 EORTC/ISCL/USCLC blood staging guidelines for cutaneous T-cell lymphoma at a single institution reveals the newer guidelines fail to detect a subset of patients with Sézary syndrome with low blood burden.
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Linfoma Cutáneo de Células T , Estadificación de Neoplasias , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Síndrome de Sézary/patología , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/sangre , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/sangre , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Guías de Práctica Clínica como AsuntoRESUMEN
Psoriasis is a long-known skin pathology, the incidence of which is constantly rising, though it is not possible to clearly establish the trend due to the differences in the research design. In recent years, the number of cases among children and adolescents has increased. Psoriasis becomes more aggressive, severe forms are more common. It can be combined with other diseases but is rarely complicated. Isolated cases of the transformation of psoriatic plaques into skin cancer have already been described in the literature. Probable causes were the long-term use of photosensitizers and phototherapy, naphthalene, and tar. However, in general, the risk of the malignant recurrence in patients with psoriasis does not increase significantly. We present a clinical observation of the transformation of psoriasis into cutaneous T-cell lymphoma in a patient with more than 37 years of psoriasis experience, where on the background of typical psoriatic rashes, fungal growths of doughy consistency appeared, which were initially misinterpreted as a warty form of psoriasis. Based on the data of additional methods of examination and the results of histological examination, the diagnosis was clarified. Specific treatment was prescribed, which proved its effectiveness. The probable causes of degeneration, in our opinion, are prolonged irritating external therapy and excessive insolation.
Asunto(s)
Linfoma Cutáneo de Células T , Psoriasis , Neoplasias Cutáneas , Humanos , Psoriasis/patología , Psoriasis/complicaciones , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Masculino , Transformación Celular Neoplásica/patologíaRESUMEN
Mogamulizumab is a humanized antibody targeting CC chemokine receptor 4 (CCR4). This post-marketing surveillance was conducted in Japan as a regulatory requirement from 2014 to 2020 to ensure the safety and effectiveness of mogamulizumab in patients with relapsed or refractory (r/r) CCR4-positive peripheral T-cell lymphoma (PTCL) or r/r cutaneous T-cell lymphoma (CTCL). Safety and effectiveness data were collected for up to 31 weeks after treatment initiation. A total of 142 patients were registered; safety was evaluated in 136 patients. The median number of doses was 8.0 (range, 1-18). The main reasons for treatment termination were insufficient response (22.1%) and adverse events (13.2%). The frequency of any grade adverse drug reaction was 57.4%, including skin disorders (26.5%), infections and immune system disorders (16.2%), and infusion-related reactions (13.2%). Graft-versus-host disease, grade 2, developed in one of two patients who underwent allogeneic-hematopoietic stem cell transplantation after receiving mogamulizumab. Effectiveness was evaluated in 131 patients (103 with PTCL; 28 with CTCL). The best overall response rate was 45.8% (PTCL, 47.6%; CTCL, 39.3%). At week 31, the survival rate was 69.0% (95% confidence interval, 59.8%-76.5%) [PTCL, 64.4% (54.0%-73.0%); CTCL, 90.5% (67.0%-97.5%)]. Safety and effectiveness were comparable between patients <70 and ≥ 70 years old and between those with relapsed and refractory disease. The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials. Clinical Trial Registration.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Linfoma Cutáneo de Células T , Linfoma de Células T Periférico , Receptores CCR4 , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Anciano , Persona de Mediana Edad , Receptores CCR4/antagonistas & inhibidores , Adulto , Japón , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Linfoma de Células T Periférico/tratamiento farmacológico , Anciano de 80 o más Años , Vigilancia de Productos Comercializados , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Adulto Joven , Resistencia a AntineoplásicosRESUMEN
INTRODUCTION: Current treatment guidelines for cutaneous T cell lymphoma (CTCL) advocate a stage-driven approach, considering clinical presentation, symptom burden, and patient comorbidities. Therapy selection hinges on factors like disease subtype, severity, and treatment availability. The primary goal is to enhance the quality of life by mitigating symptoms, as achieving lasting complete remission is infrequent. AREAS COVERED: Over the past decade (2013-2023), the therapeutic landscape of CTCL has experienced substantial transformation with the introduction of innovative therapies. This review explores the main pivotal developments in traditional treatment schedules and recently introduced drugs, aiming to offer clinicians and researchers a thorough perspective on the decade's progress in the field. EXPERT OPINION: Despite the progress made in CTCL therapeutics, ranging from topical chemotherapeutics to immunomodulatory agents, several unmet needs persist. Firstly, there is a pressing need for the incorporation of readily available predictors for treatment response, encompassing clinical, pathological, and molecular features. Secondly, a more profound comprehension of the tumor microenvironment is imperative to optimize the landscape of targetable molecules. Lastly, the undertaking of studies on combination regimens should be encouraged as it enhances therapy efficacies by synergistically combining agents with diverse modes of action.
Asunto(s)
Antineoplásicos , Linfoma Cutáneo de Células T , Calidad de Vida , Neoplasias Cutáneas , Microambiente Tumoral , Humanos , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Antineoplásicos/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Agentes Inmunomoduladores/uso terapéuticoRESUMEN
BACKGROUND: Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients. METHODS: A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months. RESULTS: The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months (N = 22), 75.0% at 9 months (N = 24), and 60.0% at 12 months (N = 15) after ECP initiation. CONCLUSIONS: Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.
Asunto(s)
Linfoma Cutáneo de Células T , Fotoféresis , Neoplasias Cutáneas , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Estados Unidos , Resultado del Tratamiento , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Síndrome de Sézary/terapia , Síndrome de Sézary/patología , Micosis Fungoide/terapia , Micosis Fungoide/patología , Estadificación de NeoplasiasRESUMEN
Brentuximab vedotin (BV), a conjugate of anti-CD30 antibody and monomethyl auristatin E, has emerged as a promising treatment option for refractory CD30+ mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL). BV has been shown to be safe and effective in treating Hodgkin's lymphoma and peripheral T-cell lymphoma. This multicenter, prospective, single-arm phase I/II study evaluated the efficacy of BV in Japanese patients with CD30+ cutaneous lymphomas, namely CD30+ cutaneous T-cell lymphoma. Participants were divided into two groups: those with CD30+ MF or pcALCL (cohort 1, n = 13) and those with CD30+ lymphoproliferative disorders other than those in cohort 1 (cohort 2, n = 3). The studied population included the full analysis set (FAS), modified FAS (mFAS), and safety analysis set (SAF). These sets were identified in cohorts 1 and 1 + 2 and labeled FAS1 and FAS2, mFAS1 and mFAS2, and SAF1 and SAF2, respectively. Each treatment cycle lasted 3 weeks, and BV was continued for up to 16 cycles after the third cycle based on treatment response. The primary endpoint was the 4-month objective response rate (ORR4) determined by the Independent Review Forum (IRF). ORR4 was 69.2% for FAS1 and 62.5% for FAS2 (P < 0.0001). Secondary endpoints of ORR, assessed using the global response score (53.8% in FAS1) and modified severity-weighted assessment tool (62.5% in FAS1), using the IRF, provided results comparable to the primary findings. The incidence of ≥grade 3 adverse events (≥15%) in SAF1 was peripheral neuropathy in three patients (23%) and fever and eosinophilia in two patients (15%). In conclusion, BV showed favorable efficacy, tolerability, and safety profile in Japanese patients with relapsed or refractory CD30+ primary cutaneous T-cell lymphoma. The trial was registered with University Hospital Medical Information Network Clinical Trials Registry, Japan (protocol ID: UMIN000034205).
Asunto(s)
Brentuximab Vedotina , Antígeno Ki-1 , Neoplasias Cutáneas , Humanos , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/uso terapéutico , Masculino , Persona de Mediana Edad , Antígeno Ki-1/inmunología , Antígeno Ki-1/análisis , Femenino , Anciano , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Estudios Prospectivos , Japón , Adulto , Anciano de 80 o más Años , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/patología , Micosis Fungoide/inmunología , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Resultado del Tratamiento , Pueblos del Este de AsiaRESUMEN
Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.
Asunto(s)
Linfohistiocitosis Hemofagocítica , Linfoma de Células T , Paniculitis , Humanos , Masculino , Biopsia , Diagnóstico Diferencial , Resultado Fatal , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/complicaciones , Linfoma de Células T/patología , Linfoma de Células T/complicaciones , Linfoma de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/complicaciones , Linfoma Cutáneo de Células T/diagnóstico , Paniculitis/patología , Paniculitis/diagnóstico , Piel/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/complicaciones , Adulto JovenRESUMEN
The etiology of CTCL is a subject of extensive investigation. Researchers have explored links between CTCL and environmental chemical exposures, such as aromatic hydrocarbons (eg, pesticides and benzene), as well as infectious factors, including various viruses (eg, human T-lymphotropic virus [HTLV]-I and HTLV-II) and bacteria (eg, Staphylococcus aureus). There has been growing emphasis on the role of malignant inflammation in CTCL development. In this review, we synthesize studies of environmental and infectious exposures, along with research on the aryl hydrocarbon receptor and the involvement of pathogens in disease etiology, providing insight into the pathogenesis of CTCL.
Asunto(s)
Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Humanos , Linfoma Cutáneo de Células T/microbiología , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/microbiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/etiología , Inflamación/microbiología , Exposición a Riesgos Ambientales/efectos adversos , Receptores de Hidrocarburo de Aril/metabolismo , AnimalesRESUMEN
Cutaneous T-cell lymphomas (CTCL) are a diverse group of malignant blood disorders characterized by initial skin infiltration, and sometimes, tumor spreading to lymph nodes, blood, and viscera. Mycosis fungoides is the most common form. Sézary syndrome is a distinctive form of CTCL marked by a significant presence of circulating tumor cells in peripheral blood. These diseases are characterized by the plasticity and heterogeneity of the tumor cells in the different tissue compartments, and a difficulty in identifying these tumor cells for diagnostic purposes and therapeutic monitoring. Progress has been made in the understanding of the pathophysiology of these diseases in recent years, and we provide here a review of these advancements.
Asunto(s)
Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/inmunología , Linfoma Cutáneo de Células T/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/diagnóstico , Francia , Síndrome de Sézary/patología , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/inmunología , Micosis Fungoide/diagnóstico , Micosis Fungoide/patología , Micosis Fungoide/inmunología , Derivación y ConsultaAsunto(s)
Fenotipo , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Masculino , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/inmunología , Femenino , Persona de Mediana Edad , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/inmunología , Anciano , Linfocitos T CD4-Positivos/inmunología , Mutación , Adulto , Células T Auxiliares Foliculares/inmunología , Diagnóstico Diferencial , Análisis Mutacional de ADN , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/inmunologíaRESUMEN
Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in CTCL cells. KPT-330 reduces cell proliferation, induces G1 cell cycle arrest and apoptosis. RNA-sequencing was used to explore the underlying mechanisms. Genes associated with the cell cycle and the p53 pathway were significantly enriched with KPT-330 treatment. KPT-330 suppressed XPO1 expression, upregulated p53, p21WAF1/Cip1, and p27Kip1 and their nuclear localization, and downregulated anti-apoptotic protein (Survivin). The in vivo efficacy of KPT-330 was investigated using a bioluminescent xenograft mouse model of CTCL. KPT-330 blocked tumor growth and prolonged survival (p < 0.0002) compared to controls. These findings support investigating the use of KPT-330 and next-generation XPO1 inhibitors in CTCL.