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BACKGROUND: Mycosis fungoides (MF), the most common subtype of Cutaneous T-cell lymphomas, is caused by malignant T-cell proliferations in the skin that can invade blood, lymph nodes, or viscera. Currently, data on efficacy of maintenance therapies in MF are lacking. We developed a unique protocol to use chlormethine/mechlorethamine 0.016% gel formulation as maintenance regimen for MF patients in remission. PURPOSE: To determine progression-free survival and efficacy of chlormethine/mechlorethamine as maintenance and active treatment regimens for MF. MATERIALS AND METHODS: A retrospective review of MF patients seen at Thomas Jefferson University from 2012 to 2020 was conducted. Patients of all stages treated with chlormethine/mechlorethamine as maintenance or active treatment with 2 consecutive mSWATs (modified Severity Weighted Assessment Tool) documented were included. Treatment outcomes were assessed by change in mSWAT and progression-free survival. Dermatology Life Quality Index surveys before and after treatment were analyzed. RESULTS: Of 186 MF patients, 44 met inclusion criteria. Patients on maintenance therapy had a 65.22% progression-free survival rate with median time to progression of 29.45 months. By-time analysis for responders on active and maintenance treatment showed an increased response over time. Peak responses were seen at last mSWAT recorded. Both cohorts experienced improved quality-of-life scores from initiation to discontinuation of chlormethine/mechlorethamine. CONCLUSION: Patients on maintenance and active chlormethine/mechlorethamine treatment regimens demonstrated improvement in mSWAT and quality-of-life. Chlormethine/mechlorethamine treatment showed progression-free survival for a median of 29.45 months, indicating this therapy may be an effective maintenance regimen.
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Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Humanos , Mecloretamina/efeitos adversos , Mecloretamina/uso terapêutico , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Mycosis fungoides with large-cell transformation (MF-LCT) is associated with an aggressive clinical course, yet data comparing treatment outcomes in MF-LCT are sparse. OBJECTIVE: To compare treatment outcomes and to determine disease prevalence and characteristics associated with survival in MF-LCT. METHODS: A retrospective review was conducted of mycosis fungoides patients from 2012 to 2020 treated at Thomas Jefferson University. Patients with histopathologic diagnosis of MF-LCT were included. Treatment outcomes were assessed by mean changes in the modified Severity Weighted Assessment Tool (mSWAT) and stage. RESULTS: Of 171 patients with mycosis fungoides, 23 (13.4%) had histologic diagnosis of MF-LCT. The overall 5-year survival rate for MF-LCT was 74% and was not significantly associated with sex, age, or initial stage at the time of MF-LCT diagnosis. Brentuximab vedotin showed the greatest mean decrease in mSWAT (-20.53) and stage progression (change in Δ stage: -0.4) in MF-LCT compared to oral bexarotene (ΔmSWAT: +4.51; Δstage: +0.27), skin-directed therapy (ΔmSWAT: -5.93; Δstage: -0.08), and chemotherapy (ΔmSWAT: +4.97; Δstage: +0.85). LIMITATIONS: Single-center retrospective design, and patients often on multiple treatment modalities. CONCLUSIONS: We report superior treatment outcomes for brentuximab vedotin compared to oral bexarotene, skin-directed therapy, and chemotherapy in MF-LCT in both early and advanced disease.
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Micose Fungoide , Neoplasias Cutâneas , Bexaroteno/uso terapêutico , Brentuximab Vedotin , Transformação Celular Neoplásica/patologia , Humanos , Micose Fungoide/diagnóstico , Micose Fungoide/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Topical corticosteroids alone or in combination with other therapies are widely used to treat mycosis fungoides (MF), but data on response rates to their use as monotherapy in MF are limited. OBJECTIVE: To evaluate the efficacy of topical corticosteroid monotherapy in MF; compare sex, age, stage distributions, and histopathologic features between responders and nonresponders. METHODS: A retrospective cross-sectional review of patients with MF from 2013 to 2019 treated at Thomas Jefferson University was conducted. Patients with biopsy-proven MF, all stages, who received topical corticosteroid monotherapy were included. Response rates were determined by percent change in body surface area (BSA) involvement and modified Severity-Weighted Assessment Tool (mSWAT). RESULTS: Of the 163 patients with MF in our database, 23% (37/163) initially received topical steroid monotherapy. Of these, 73% (27/37) improved, with an average 65% decrease in BSA (67% in mSWAT); 27% (10/37) did not respond/progressed, with an average 51.6% increase in BSA (57% in mSWAT); and 33% (12/37) had a complete response (BSA, 0%) with prolonged topical steroid use. Early-stage MF and female sex were more represented in responders. LIMITATIONS: Single-center retrospective design. CONCLUSIONS: Topical steroid monotherapy in early-stage MF can produce measurable improvements in BSA and mSWAT scores and achieve complete remission in a limited subset of patients.
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Glucocorticoides/administração & dosagem , Micose Fungoide/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Administração Cutânea , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Estadiamento de Neoplasias , Indução de Remissão/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Low-dose total skin electron beam therapy (TSEBT) for mycosis fungoides is popular because of reduced toxicity with effective palliation. We condensed TSEBT, reducing visits by half and overall treatment length by one third. OBJECTIVE: To determine the efficacy and safety of a novel condensed low-dose TSEBT for mycosis fungoides. METHODS: We conducted a cohort study (2014-2018) with a median follow-up of 22.8 months. We delivered 12 Gy per 6 fractions with the modified Stanford technique, 3 fractions per week, with boosts to shadowed sites at risk between treatments, completing in 2 weeks. Primary outcomes included clinical response, duration of and time to response, and toxicity. Secondary outcomes included patient-reported quality of life (pain, pruritus, and Dermatology Life Quality Index) and physician-scored disease burden (body surface area involvement and Modified Skin Weighted Assessment Tool). RESULTS: Of 25 patients, stage IB was most common at the time of TSEBT (36%). The overall response rate was 88%. Most common was a near complete response (36%), and complete response was achieved in 6 (24%) patients. The median duration of response was 17.5 months (3.5-44.2), and the median time to response was 2 months (range, 0.9-4.1). No patients had toxicity of grade 3 or greater. QOL and disease burden showed significant benefit after TSEBT (P < .001). LIMITATIONS: Cohort study with limited sample size. CONCLUSIONS: Condensed, low-dose TSEBT has favorable outcomes and toxicity with logistical convenience.
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Efeitos Psicossociais da Doença , Micose Fungoide/radioterapia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Elétrons/efeitos adversos , Elétrons/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoAssuntos
Antibacterianos/administração & dosagem , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/imunologia , Infecções por Mycobacterium/tratamento farmacológico , Mycobacterium haemophilum/isolamento & purificação , Dermatopatias Bacterianas/tratamento farmacológico , Antibacterianos/uso terapêutico , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mycobacterium haemophilum/patogenicidade , Transplante de Células-Tronco/efeitos adversosRESUMO
B-cell lymphoblastic lymphoma (B-LBL) is a malignant neoplasm of immature B cells that accounts for only 10% of all cases of lymphoblastic lymphoma. Most commonly, B-LBL presents as bony lesions, but in rare cases, the disease manifests cutaneously. We present a case of simultaneous cutaneous and systemic presentation of B-LBL in an otherwise healthy 28-year-old man in which the lymphoblastic infiltrate stained positive for CD79a, Tdt, CD10, and CD20. A diagnosis of cutaneous B-LBL was made, and systemic work-up revealed widespread involvement of the skin, bone, and lymph nodes. Review of all currently described cases of cutaneous B-LBL with or without systemic involvement revealed that the most frequently positive tumor markers were CD79a (92.3%), Tdt (90.6%), and CD10 (83.3%). Systemic involvement of B-LBL was found in nearly half of all cases with cutaneous presentation.
Assuntos
Leucemia Linfoide/diagnóstico , Linfoma de Células B/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Antígenos CD20/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biópsia , Antígenos CD79/análise , DNA Nucleotidilexotransferase/antagonistas & inibidores , Fracionamento da Dose de Radiação , Transplante de Células-Tronco Hematopoéticas , Humanos , Imuno-Histoquímica , Leucemia Linfoide/imunologia , Leucemia Linfoide/patologia , Leucemia Linfoide/terapia , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Masculino , Neprilisina/análise , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Resultado do TratamentoRESUMO
Mycosis fungoides is the most common form of cutaneous T cell lymphoma. Although normally presenting to physicians at an early stage and with an indolent course, mycosis fungoides can have a varied presentation. The National Comprehensive Cancer Network (NCCN) has created guidelines for the treatment and staging of mycosis fungoides. Although comprehensive, in practice these guidelines do not provide specific treatment regimens for lesions located in difficult locations and those recalcitrant to the recommended therapy. Because of this, suggestions based on the practices and decisions made at the multidisciplinary cutaneous lymphoma clinic at the Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA, are presented here. Lesions located in areas such as the face and intertriginous zones are often challenging to treat because first-line therapies are often inappropriate, with the locations increasing the possibility of side effects. Additionally, lesions located in the bathing suit distribution are often nonresponsive to first-line therapies for reasons still undetermined. Finally, although well-described, erythroderma secondary to mycosis fungoides is challenging to treat, with controversy surrounding various methods of control. This article both highlights difficult clinical scenarios and reviews the recommended treatment as provided by the NCCN guidelines and provides alternative therapy for lesions that are either difficult to treat because of the location or are recalcitrant to the recommended therapy. With suggestions for the apparent gaps in guidelines, providers can better treat patients who present with more complicated conditions.
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Dermatite Esfoliativa/terapia , Micose Fungoide/terapia , Neoplasias Cutâneas/terapia , Adulto , Antineoplásicos/administração & dosagem , Biópsia , Nádegas , Terapia Combinada/métodos , Dermatite Esfoliativa/etiologia , Fármacos Dermatológicos/administração & dosagem , Dermatologia/normas , Fracionamento da Dose de Radiação , Face , Feminino , Humanos , Masculino , Oncologia/normas , Pessoa de Meia-Idade , Micose Fungoide/complicações , Micose Fungoide/patologia , Guias de Prática Clínica como Assunto , Pele/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Terapia Ultravioleta/métodosRESUMO
BACKGROUND: Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, remains a challenge for clinicians to stage and manage. Classically, MF is determined through histopathologic evidence of a neoplastic infiltrate within the epidermis. In certain patients, however, the infiltrate extends into the hair follicles and sweat glands. The objective of this study is to determine the utility of expanding the analysis of histopathology reports to include the reporting of folliculotropism and syringotropism. METHODS: This is a prospective, observational study conducted in a single facility from 2012-2018. All patients with MF, excluding those treated at this facility for less than six months with the exception of those with incomplete pruritus documentation, or absence of initial biopsy analysis were studied. Modified severity weighted assessment tool (mSWAT) quantified body surface area and treatments attempted per patient were continuously charted. Patients were surveyed for presence and degree of pruritus and pain. Evaluation of these parameters were charted at the initial patient visit and correlated with their primary biopsy for presence or absence of folliculotropism and syringotropism. RESULTS: Of the 87 patients examined, 70 patients (80%) exhibited syringotropism in their original biopsy and 68 patients (78%) exhibited folliculotropism. Presence of both findings concurrently was present in 56 patients (64.4%), while neither finding was present in 5 patients (5.8%). The singular finding of folliculotropism was found in 12 patients (13.8%), while the singular finding of syringotropism was exhibited in 14 patients (16.1%). A significant association between the presence of folliculotropism and pruritus was established (P=0.043, α=0.05). The general trend towards increase in mSWAT score and pruritus in patients in regard to the mean and median values suggest that increasing the sample population of the study might yield a significant value in the future. CONCLUSIONS: These presentations are more prevalent than previously recognized and have findings indicative of more severe disease. We propose that MF histopathology reports document the presence of folliculotropism and syringotropism and that these findings be added to the NCCN guidelines as they may aid in predicting severity and progression risk.
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Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Feminino , Folículo Piloso , Humanos , Masculino , Estudos ProspectivosRESUMO
Koebnerization of pemphigus vulgaris (PV) is an infrequently reported reaction. We present a 65-year-old man with Koebnerized pemphigus vulgaris after Mohs microscopic surgery for a basal cell carcinoma. We present this case to heighten awareness of the phenomenon in the dermatological community.
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Carcinoma Basocelular/cirurgia , Cirurgia de Mohs , Pênfigo/patologia , Complicações Pós-Operatórias/patologia , Neoplasias Cutâneas/cirurgia , Idoso , Humanos , Masculino , Pênfigo/diagnóstico , Complicações Pós-Operatórias/diagnóstico , OmbroRESUMO
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma within the general population. Low dose total skin electron beam therapy (TSEBT) and topical nitrogen mustard (Valchlor) are two treatment modalities that have been proven to be efficacious in the treatment of MF. While each have been studied independently in various clinical trials, the use of Valchlor as maintenance therapy after completion of low dose TSEBT is rarely implemented due to the lack of evidence in the literature. The Jefferson multidisciplinary cutaneous lymphoma clinic has found great success with this combination of treatment and it was the goal of the authors to provide further evidence to its efficacy. The authors conducted a retrospective review of eight patients at the Jefferson multidisciplinary cutaneous lymphoma clinic period. In this study, they were initiated on a regimen of Valchlor as a maintenance therapy after completion of low dose TSEBT. The median MSWAT score before low dose TSEBT was found to be 25.25 with a mean of 39.76. A reduction was found in MSWAT score after low dose TSEBT to a median of 7.68 and a mean of 17.31. Median scores for pruritus were decreased from 3.43 before TSEBT to 1.88 after low dose TSEBT and a decreased in quality of life score median from 6.60 to a median of 2.75. Valchlor proved to be a useful maintenance therapy prolonging time to stage increase by 22.7351 months. Overall this study provides further evidence to the efficacy of Valchlor used as a maintenance therapy after completion of low dose TSEBT.
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Mecloretamina/uso terapêutico , Micose Fungoide/tratamento farmacológico , Micose Fungoide/radioterapia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Mecloretamina/farmacologia , Pessoa de Meia-Idade , Micose Fungoide/patologia , Resultado do TratamentoRESUMO
Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated Stat3 in all nine samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, in both an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical hedgehog signaling downstream of Ptc1 to promote BCC development through the activation of phosphorylated Stat3 and regulation of Gli1 expression.
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Síndrome do Nevo Basocelular/patologia , Desmogleína 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Cutâneas/patologia , Animais , Síndrome do Nevo Basocelular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Receptor Patched-1/genética , Fosforilação , Fator de Transcrição STAT3/antagonistas & inibidores , Pele/patologia , Neoplasias Cutâneas/genética , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
Immunogenic cell death is characterized by the emission of danger signals that facilitate activation of an adaptive immune response against dead-cell antigens. In the case of cancer therapy, tumor cells undergoing immunogenic death promote cancer-specific immunity. Identification, characterization, and optimization of stimuli that induce immunogenic cancer cell death has tremendous potential to improve the outcomes of cancer therapy. In this study, we show that non-thermal, atmospheric pressure plasma can be operated to induce immunogenic cell death in an animal model of colorectal cancer. In vitro, plasma treatment of CT26 colorectal cancer cells induced the release of classic danger signals. Treated cells were used to create a whole-cell vaccine which elicited protective immunity in the CT26 tumor mouse model. Moreover, plasma treatment of subcutaneous tumors elicited emission of danger signals and recruitment of antigen presenting cells into tumors. An increase in T cell responses targeting the colorectal cancer-specific antigen guanylyl cyclase C (GUCY2C) were also observed. This study provides the first evidence that non-thermal plasma is a bone fide inducer of immunogenic cell death and highlights its potential for clinical translation for cancer immunotherapy.
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Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors. We report that driver mutations were shared with spontaneous, ultraviolet (UV) light-induced cutaneous SCC (UV SCC) and head and neck SCC (HNSCC) and did not explain the early presentation or aggressive nature of RDEB SCC. Instead, endogenous mutation processes associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases dominated RDEB SCC. APOBEC mutation signatures were enhanced throughout RDEB SCC tumor evolution, relative to spontaneous UV SCC and HNSCC mutation profiles. Sixty-seven percent of RDEB SCC driver mutations was found to emerge as a result of APOBEC and other endogenous mutational processes previously associated with age, potentially explaining a >1000-fold increased incidence and the early onset of these SCCs. Human papillomavirus-negative basal and mesenchymal subtypes of HNSCC harbored enhanced APOBEC mutational signatures and transcriptomes similar to those of RDEB SCC, suggesting that APOBEC deaminases drive other subtypes of SCC. Collectively, these data establish specific mutagenic mechanisms associated with chronic tissue damage. Our findings reveal a cause for cancers arising at sites of persistent inflammation and identify potential therapeutic avenues to treat RDEB SCC.
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Desaminases APOBEC/genética , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Citosina Desaminase/genética , Epidermólise Bolhosa Distrófica/enzimologia , Epidermólise Bolhosa Distrófica/genética , Mutação/genética , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Variações do Número de Cópias de DNA/genética , Reparo do DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Mutagênese/genética , Taxa de Mutação , Transcriptoma/genéticaRESUMO
Progressive macular hypomelanosis (PMH) is a skin disorder that historically has been described as having a predominantly truncal distribution. We report 4 adult cases of PMH with facial involvement. The diagnosis was made for all 4 patients after excluding other hypopigmented diseases. This report underscores the importance of considering PMH as part of the differential for hypopigmented lesions on the face.
Assuntos
Hipopigmentação/diagnóstico , Adulto , Face , Feminino , Humanos , Hipopigmentação/patologia , Masculino , Pessoa de Meia-IdadeAssuntos
Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Idoso , Axila/patologia , Humanos , MasculinoRESUMO
BACKGROUND: Syringocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal proliferation. There have been several reports describing collision lesions of SCAP and verruca, although little is known about the frequency of this association. Molecular testing has revealed the BRAFV600E mutation in a large proportion of SCAP cases, although its expression pattern has not been previously evaluated. METHODS: In this retrospective analysis, we explored the potential histopathological association between verruca and SCAP. We also evaluated mutation-specific BRAFV600E expression in these lesions by immunohistochemistry. Cases of SCAP diagnosed over a 7-year period were closely reviewed for the presence of contiguous verrucous proliferations. Additional sections were cut and stained using the BRAFV600E-specific clone VE1 antibody. RESULTS: Contiguous verrucous proliferations were identified in 9 out of 12 identified cases. Furthermore, expression of the BRAFV600E mutation was identified in 7 out of 12 cases. Interestingly, in SCAP associated with endophytic verrucous proliferations (n = 4), expression of BRAFV600E was found in both the glandular and the contiguous hyperplastic squamous epithelium. CONCLUSION: Overall, these findings suggest that contiguous verrucous proliferations in SCAP are common. Both components of the neoplasm may express the BRAFV600E mutation, which is suggestive of a common origin.