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Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma. The overall risk of developing DLBCL is increased in patients with other lymphomas, such as mycosis fungoides (MF). In this report, we present an 81-year-old female with early-stage MF who simultaneously progressed to tumor stage, large-cell transformed (LCT) MF and developed a primary DLBCL in a lymph node (LN). She presented with a tumor on her leg and new lymphadenopathy in her right axilla. Skin biopsy of the tumor revealed infiltration of large atypical CD3+, CD4+, and CD30+ cells, and a smaller portion of CD8+ cells in the dermis, consistent with LCT MF. Biopsy of the axillary LN revealed diffuse sheets of CD20+, BCL-2+, c-MYC+, and CD10- cells, highly suggestive of double expressor DLBCL. High-throughput sequencing revealed monoclonal T cells in the skin tumor and a monoclonal B-cell population in the LN. The above findings led to simultaneous diagnoses of LCT MF and nodal double expressor DLBCL. Our case demonstrates the importance of performing a full pathological workup in cutaneous T-cell lymphoma patients presenting with lymphadenopathy.
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ABSTRACT: Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received a single infusion of 1 of 4 escalating doses of a product containing 68.5% SARS-CoV-2-specific CD8+ CTLs/total cells. Symptom improvement and resolution in these patients was compared with an observational group of 18 patients lacking HLA-A∗02:01 who could receive standard of care. No dose-limiting toxicities were observed at any dosing level. Nasal swab polymerase chain reaction testing showed ≥88% and >99% viral elimination from baseline in all patients at 4 and 14 days after infusion, respectively. The CTLs did not interfere with the development of endogenous anti-SARS-CoV-2 humoral or cellular responses. T-cell receptor ß analysis showed persistence of donor-derived SARS-CoV-2-specific CTLs through the end of the 6-month follow-up period. Interventional patients consistently reported symptomatic improvement 2 to 3 days after infusion, whereas improvement was more variable in observational patients. SARS-CoV-2-specific CTLs are a potentially feasible cellular therapy for COVID-19 illness. This trial was registered at www.clinicaltrials.gov as #NCT04765449.
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COVID-19 , SARS-CoV-2 , Linfocitos T Citotóxicos , Humanos , COVID-19/inmunología , COVID-19/terapia , Linfocitos T Citotóxicos/inmunología , Persona de Mediana Edad , Masculino , SARS-CoV-2/inmunología , Femenino , Anciano , Adulto , Estudios de Factibilidad , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Resultado del Tratamiento , Antígeno HLA-A2/inmunologíaRESUMEN
Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, prognosis, and ultimately clinical practice.
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Anaplastic large cell lymphoma (ALCL) is a CD30+ peripheral T-cell lymphoma with a clinical spectrum including cutaneous and systemic presentations. While primary cutaneous ALCL (pcALCL) has a favorable prognosis, systemic ALCL (sALCL) has poorer survival outcomes. Expression of anaplastic lymphoma kinase (ALK) by malignant cells has been suggested to distinguish sALCL from pcALCL. However, there have been documented cases of ALK-positive ALCL confined to the skin. The present study reviewed characteristics of published cutaneous ALK-positive ALCL cases to distinguish between these two entities. In 23 identified adults with ALK-positive pcALCL, 26% developed systemic involvement and 74% had skin-limited disease. In 14 pediatric patients, 36% had both cutaneous and systemic involvement and 64% had cutaneous disease only. This analysis revealed that pcALCL and sALCL could not reliably be distinguished by ALK expression or nuclear vs. cytoplasmic localization. Localized treatment with frequent monitoring may be sufficient in ALK-positive pcALCL until there is evidence of progression. Physicians should be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK positivity and disease with skin recurrence.
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Neoplasias Pulmonares , Melanoma , Neoplasias de la Próstata , Programa de VERF , Neoplasias Cutáneas , Neoplasias de la Tiroides , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Programa de VERF/estadística & datos numéricos , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Incidencia , Melanoma/epidemiología , Melanoma/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/diagnóstico , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/diagnóstico , Estados Unidos/epidemiología , Femenino , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/diagnóstico , Persona de Mediana Edad , Neoplasias Renales/epidemiología , Neoplasias Renales/diagnóstico , Anciano , Linfoma de Células B/epidemiología , Linfoma de Células B/diagnóstico , Adulto , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/diagnósticoRESUMEN
BACKGROUND: Work-related musculoskeletal disorders (WRMSDs) is a multi-factorial disorder in most occupational setting and it has increased significantly in recent years. OBJECTIVE: This study aimed to investigate the relationship between physical, cognitive, and environmental factors of ergonomics with the prevalence of WRMSDs in a car-parts manufacturing industry. METHODS: This cross-sectional study was performed among 220 workers in a milling unit of a car parts manufacturing company in 2021-2022. The prevalence of WRMSDs was assessed using the Extended Version of the Nordic Musculoskeletal Questionnaire. Noise exposure was evaluated using dosimetry method. Mental and physical workload were evaluated by the NASA-TLX and key index methods (KIM-MHO and KIM-LHC), respectively. Data analysis was performed using SPSS version 25.0. RESULTS: The subjects' mean age and work experience were 36.3±6.5 and 8.35±6.41 years, respectively. Eighty-five percent of the subjects reported WRMSDs in at least one area of the body. The results of mental workload assessment revealed a high workload mean range (73.23±14.89) in all of the subjects. Mean score of KIM-LHC and KIM-MHO were 738.18±336.42 and 201.86±36.41, respectively with odds ratio of 1.32 for KIM-LHC in creating the WRMSDs. There was a significant relationship between the noise exposure, mental and physical workload and the prevalence of WRMSDs (p-valueâ< â0.05). CONCLUSION: The results of the present study revealed that environmental, physical and cognitive factors can simultaneously be effective in the prevalence of WRMSDs. Therefore, performing effective control measures requires comprehensive attention to physical, environmental, and cognitive ergonomics in the algorithm of ergonomics management in the workplace.
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Alopecia , Negro o Afroamericano , Humanos , Alopecia/diagnóstico , Cabello , Industria de la BellezaRESUMEN
INTRODUCTION: Chlormethine (CL) gel was approved for treatment of mycosis fungoides based on the pivotal 201 trial (NCT00168064). Data visualization from individual patients is a powerful tool for discovery of hidden treatment trends. Here, we present a post hoc analysis of individual patient data from the pivotal trial to provide a more granular depiction of treatment and response changes over time, with an emphasis on end of treatment status. MATERIALS AND METHODS: Individual patient response data were plotted over a 12-month treatment period to visualize patient experiences while using CL gel. Responder status was assigned according to end-of-treatment Composite Assessment of Index Lesion Severity (CAILS) score, and patients were classified as early (≤4 months) or late responders based on timing of response. Baseline and active treatment characteristics were compared between early and late responders, and baseline body surface area (BSA) was compared between responders and patients with stable or progressive disease. RESULTS: Data from 123 patients with baseline and postbaseline results were included. At the end of treatment, 64.2%/55.3% were responders, 30.9%/34.1% had stable disease, and 4.9%/10.6% had progressive disease by CAILS and mSWAT, respectively. Among patients who responded to treatment, 64.6% and 35.4% were early and late responders, respectively. Response pattern analysis also identified patients with an intermittent response or initial progressive disease. Baseline BSA was not associated with responder status. Late responders had longer treatment duration and higher postbaseline plaque elevation, while early responders had a higher frequency of dermatitis. CONCLUSIONS: Results presented here can facilitate optimal treatment experiences for patients starting CL gel.
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Micosis Fungoide , Neoplasias Cutáneas , Humanos , Mecloretamina/uso terapéutico , Micosis Fungoide/diagnóstico , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
BACKGROUND: The hazardous material release has frequently occurred worldwide. As a respiratory stimulant and a toxic substance, ammonia has numerous adverse effects on human health. OBJECTIVE: The purpose of this study was to evaluate the human vulnerability and toxic effects of both chronic and acute respiratory exposure to ammonia. METHODS: This study was conducted in an ice factory. Ammonia reservoirs were selected as the danger center. The scenarios were evaluated from the perspective of the worst-case. The Emergency Response Planning Guidelines 1-3 was used to predict the dangerous concentrations in acute exposure. The probability of human vulnerability was estimated using the Probit model. PHAST 7.2 software was used to model consequences. As a measure of chronic exposure to ammonia, NMAM 6016 was used. A respiratory symptom questionnaire developed by the American Thoracic Society was used for collecting respiratory symptom histories. RESULTS: The ERPG3 level or concentration of 750âppm was found at a distance of 617.71 and 411.01 meters from tanks, respectively, as a result of a rupture in reservoir 1 over a period of two halves of the year. It was found that the highest probit values for tank 2 at distances of zero, 25, 50, 75, 100, 125, and 150 meters were 9.55, 5.92, 5.47, 4.82, 4.23, 3.56 and 2.96, respectively. The prevalence of pulmonary symptoms, which include coughing, dyspnea, phlegm, and wheezing, was 28%, 19%, 15%, and 26% in the chronic exposure group. CONCLUSION: In the event that an ammonia reservoir ruptures catastrophically, it may cause human injury at ERPG-2 or ERPG-3 levels. Results revealed that exposure to this substance can impose many pulmonary symptoms on the respiratory system of workers in industries. In order to reduce the vulnerability of humans to potential release scenarios, control measures must be implemented. Also, preventive and mitigation measures can be designed to enhance safety and resilience against the release of hazardous materials.
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Amoníaco , Exposición Profesional , Humanos , Amoníaco/efectos adversos , Amoníaco/análisis , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Hielo , Encuestas y CuestionariosRESUMEN
Introduction: Neutrophilic panniculitis (NP) is a rare subtype of neutrophilic dermatosis, a group of neutrophil-rich inflammatory skin disorders that can present in association with myeloid neoplasms. NP is defined by the presence of a neutrophilic infiltrate in the fat lobules of the subcutis in the absence of either infection or vasculitis. We herein describe a 65-year-old woman with a recent diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) who abruptly developed painful, pruritic nodules consistent with NP. Case presentation: A 65-year-old woman with MDS/MPN presented for evaluation of painful and pruritic nodules on her upper and lower extremities. A biopsy revealed a lobular neutrophilic infiltrate in the subcutis without evidence of microorganisms or vasculitis. The patient was diagnosed with NP and treated with oral prednisone. Within 1 month of treatment, she reported complete resolution of the nodules. Discussion: Similar to other neutrophilic dermatoses, NP may arise in association with hematologic malignancies of myeloid origin, such as MDS/MPN. A literature review revealed that most cases of NP associated with MDS occur after the onset of MDS and respond to systemic corticosteroids, not antibiotics. Infection should be ruled out before initiating treatment with systemic steroids. Conclusion: Although the mechanism is still unknown, it is important for clinicians to be aware that NP is associated with MDS; thus, hematological malignancies should be investigated upon diagnosis of NP. Once diagnosed, NP is easily treated and has an excellent response to systemic corticosteroids.
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ABSTRACT: We report a 48-year-old man with CD30+ large cell transformation of mycosis fungoides (tMF) with distinctive anaplastic morphology. The patient initially presented with folliculotropic and syringotropic mycosis fungoides (MF) manifested as occipital scalp plaque and trunk and extremities patches. Six years later, he progressed to the tumor stage from his scalp lesion and developed cervical lymphadenopathy. Lymph node and scalp biopsies showed diffuse infiltration of CD30+ anaplastic cells with multinucleated, hallmark-like, Hodgkin-Reed-Sternberg-like, histiocytoid forms, indistinguishable from anaplastic large cell lymphoma (ALCL). T-cell receptor gamma gene (TCRg) rearrangement studies revealed identical clones in the initial MF scalp lesion and nodal anaplastic lesion, confirming the transformation. Ancillary studies showed absence of IRF4/DUSP22 and ALK rearrangements and positive RB1, SMARCA4, SOCS1, and TP53 mutations. The patient achieved partial response with systemic chemotherapy. Our case is an example of tMF presenting as the morphology and phenotype of ALCL. Because clinical behavior and therapeutic options of tMF and primary cutaneous ALCL may be different, it is clinically relevant to differentiate these 2 entities. The proof of clonal relationship may be useful in diagnostically challenging cases with features overlapping between tMF and primary cutaneous ALCL.
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Micosis Fungoide , Neoplasias Cutáneas , Masculino , Humanos , Micosis Fungoide/genética , Biopsia , Células Clonales , Extremidades , Neoplasias Cutáneas/genética , ADN Helicasas , Proteínas Nucleares , Factores de TranscripciónRESUMEN
INTRODUCTION: Lymphedema often presents as progressive, unremitting swelling and skin changes that are extremely distressing to patients. Hereditary lymphedema (HL) constitutes a type of primary lymphedema that is passed down through generations. OBJECTIVES: The primary aims of this narrative review are to illustrate a framework to distinguish lymphedema from other causes of swelling and to differentiate the hereditary lymphedemas from each other. RESULTS: A literature search was undertaken using relevant search terms. The articles were evaluated to generate a diagnostic algorithm to approach the swelling of an extremity using clinical and laboratory data. First, the stemmer sign should be evaluated. If it is negative, other causes should be considered. History and additional physical exam findings suggest either a primary or secondary cause of lymph-edema. CONCLUSIONS: The hereditary lymphedemas have been classified by age of onset and then stratified by clinical criteria and genetic testing.
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BACKGROUND: Occupational noise exposure is a significant health problem. In addition to hearing impairments, noise as a stressor may cause cardiovascular problems. OBJECTIVE: This study aimed to investigate the effect of exposure to workplace noise on cardiovascular disease risk factors. METHODS: This case-control study was conducted in 2021 in a power plant in Iran. In this study, the health status of 406 employees in both exposed (nâ=â203) and non-exposed (nâ=â203) to noise groups was examined for cardiovascular disease risk factors. Also, the trend of changes in the studied variables from 2012 to 2020 in exposed employees was examined. Data were collected from participants' annual physical examinations and occupational noise exposure measurements. To measure the noise in the present study, the KIMO-DB300 noise level meter was used. Data were analyzed in SPSS-26 software. RESULTS: The results revealed that mean fasting blood sugar (FBS), triglyceride, liver enzyme (SGOT), blood pressure, and body mass index were significantly different in the two groups (p-value<0.05). There was no significant difference in the mean of creatinine, cholesterol, and liver enzyme (SGPT) between the two groups (p-value>0.05). In the exposed group, the mean of all studied variables except diastolic blood pressure was statistically different during the study years (p-value<0.05). CONCLUSION: This study demonstrates that exposure to noise above the permissible level can affect the cardiovascular disease risk factors, so it is recommended to apply engineering and management measures like using Hearing Conservation Programme (HCP) to reduce the risk of these diseases with periodically assessing the health status of employees and timely diagnosis.
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Enfermedades Cardiovasculares , Ruido en el Ambiente de Trabajo , Enfermedades Profesionales , Exposición Profesional , Humanos , Estudios de Casos y Controles , Enfermedades Profesionales/etiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/complicaciones , Ruido en el Ambiente de Trabajo/efectos adversos , Lugar de Trabajo , Exposición Profesional/efectos adversos , Centrales Eléctricas , Factores de RiesgoRESUMEN
Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management. We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis. Case presentation: We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms. Discussion: The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy. Conclusion: Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.
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This case report describes 3 patients with mycosis fungoides with CDR3 variants.
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Micosis Fungoide , Neoplasias Cutáneas , Humanos , Linfocitos T/patología , Micosis Fungoide/diagnóstico , Micosis Fungoide/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
Introduction: The increased incidence of cutaneous melanoma (CM) and Merkel cell carcinoma (MCC) in patients with hematologic malignancies (HM) is well established. While the risk of CM has been assessed in some subtypes of HM including cutaneous T-cell lymphoma, the incidence in patients with primary cutaneous B-cell lymphoma (PCBCL) has not been interrogated. Methods: Here we evaluated the standardized incidence ratio (SIR) of CM and MCC in 5,179 PCBCL patients compared to approximately 1.5 billion individuals in the general population using the Surveillance, Epidemiology and End Results (SEER) database. Among patients with PCBCL, we identified subgroups that were at increased risk for CM or MCC as a second primary cancer. Results: We found 36 cases of CM in the PCBCL cohort (SIR, 1.35; 95% CI, 0.94-1.86), among which SIR was significantly elevated for non-Hispanic White patients compared to the general population (SIR, 1.48; 95% CI, 1.03-2.06). Males had a significantly increased risk of developing CM after a diagnosis of PCBCL (SIR, 1.60; 95% CI, 1.10-2.26). We found that males in the age group of 50-59 were at increased risk for CM development (SIR, 3.02; 95% CI, 1.11-6.58). Males were at increased risk of CM 1-5 years after PCBCL diagnosis (SIR, 2.06; 95% CI, 1.18-3.34). Patients were at greater risk of developing MCC within 1 year of diagnosis of PCBCL (SIR, 23.60; 95% CI, 2.86-85.27), particularly in patients who were over the age of 80 (SIR, 46.50; 95% CI, 5.63-167.96). Males aged 60-69 with PCBCL, subtype marginal zone, were also at increased risk for MCC (SIR, 42.71; 95% CI, 1.08-237.99). Conclusion: There is an increased incidence of CM in White, middle-aged males within 5 years of diagnosis of PCBCL and an increased risk of MCC in elderly patients within 1 year of PCBCL diagnosis. These data suggest that certain subgroups of patients with PCBCL may require more rigid surveillance for CM and MCC.