RESUMEN
The arrival of immunotherapy has revolutioned the management of patients with metastatic Merkel cell carcinoma (MCC). We conducted an observational, retrospective study of 14 cases treated with avelumab. The response rate was 57%: complete response was reached in 29% of patients, and partial responses in 29%. The drug proved effective in 83% (5/6) of the patients with a single metastatic site. However, the disease progressed in 75% (3/4) of the patients with bone metastases. PD1-L expression, MCC polyomavirus (MCPyV) positivity, and an impaired neutrophil-to-lypmhocyte ratio (NLR) could not be associated with responses to the therapy. Avelumab is an effective and safe drug for the management of advanced MCC, and its effectiveness appears to be impacted by the number and location of metastases.
RESUMEN
BACKGROUND AND OBJECTIVE: Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. MATERIAL AND METHODS: Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. RESULTS: In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). CONCLUSIONS: PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness.
Asunto(s)
Neoplasias Óseas , Sarcoma , Neoplasias Cutáneas , Humanos , Neoplasias Óseas/complicaciones , Necrosis/complicaciones , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Estudios Retrospectivos , Sarcoma/patología , Neoplasias Cutáneas/patologíaRESUMEN
Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Humanos , Inmunoterapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.
Asunto(s)
Carcinoma de Células de Merkel , Poliomavirus de Células de Merkel , Trasplante de Órganos , Infecciones por Polyomavirus , Neoplasias Cutáneas , Infecciones Tumorales por Virus , Carcinoma de Células de Merkel/patología , Humanos , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Serina-Treonina Quinasas TOR , Infecciones Tumorales por Virus/complicacionesRESUMEN
Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Humanos , Inmunoterapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.
Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Antineoplásicos/efectos adversos , Compuestos de Bifenilo , Carcinoma Basocelular/tratamiento farmacológico , Proteínas Hedgehog/uso terapéutico , Humanos , Piridinas , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Necrobiosis lipoidica is a rare chronic granulomatous disease. Multiple treatment approaches are available, but results are generally minimal and inconsistent. Some publications report variable results with photodynamic therapy (PDT) as a second line of treatment for refractory cases. We report 4 cases of necrobiosis lipoidica treated satisfactorily with conventional PDT using methyl aminolevulinate or 5-aminolevulinic acid BF-200 as the photosensitizing agent. All 4 patients were women with diabetes mellitus who had undergone treatment at least twice in the past, with little improvement. The lesions resolved completely with PDT, leaving only residual atrophy after a mean of 3.2 sessions per lesion.
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Necrobiosis Lipoidea , Fotoquimioterapia , Femenino , Humanos , Necrobiosis Lipoidea/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Oral contraceptives combine estrogen and progesterone to suppress ovulation. Synthetic forms are usually used. In dermatology, oral contraceptives are prescribed for 2 main reasons: to prevent pregnancy when teratogenic drugs must be taken and to treat skin manifestations of hyperandrogenism. Most oral contraceptives improve both acne and hirsutism, but the androgenic effect of progestogens - particularly if the contraceptive contains first- or second-generation progestogens- can trigger or exacerbate acne. One of the most serious side effects of oral contraceptives, thrombosis, is mainly caused by the estrogen component and its dose. If we mainly consider a contraceptive's thrombotic profile when prescribing, the choice would be to have 30µg or less of ethinyl estradiol combined with levonorgestrel. On the other hand, if our main objective is to treat signs of androgenization, we would prefer contraceptives containing progestogens with antiandrogenic effects.
Asunto(s)
Anticonceptivos Orales , Dermatología , Etinilestradiol/efectos adversos , Femenino , Humanos , Levonorgestrel , Embarazo , ProgesteronaRESUMEN
BACKGROUND: There are no large series describing cutaneous histologic changes during treatment with vismodegib in locally advanced basal cell carcinoma (BCC). OBJECTIVE: To analyze histologic changes in skin biopsy specimens from patients with locally advanced BCC treated with vismodegib. METHODS: A descriptive, retrospective study of patients with locally advanced BCC treated with vismodegib between June 2012 and December 2017 at the Instituto Valenciano de Oncología, Spain. Nineteen patients were biopsied before and during the treatment with vismodegib, and we compared histologic changes observed. RESULTS: Seven patients (37%) achieved complete response, which was characterized by replacement of tumor stroma with a hyaline scar, lymphocytic inflammatory infiltrate, keratin formation, and infundibular cysts. Twelve patients (63%) achieved partial response; 5 showed no phenotypic changes, whereas 7 showed histologic changes; 5 cases showed metatypical differentiation; and 2 cases presented squamous differentiation. We observed no cases of squamous cell carcinoma arising at vismodegib treatment sites and no association between initial histologic subtype and clinical response. LIMITATIONS: Many biopsy specimens were obtained by punch biopsy and may not be representative of the full tumors. We studied histologic changes only in complete and partial responses. CONCLUSION: Vismodegib can induce histologic changes toward metatypical or squamous differentiation of BCC in patients with partial response. Keratinizing phenomena were frequent, both in partial and complete response groups.
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Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Piridinas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaAsunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Fístula Cutánea/tratamiento farmacológico , Fístula/tratamiento farmacológico , Enfermedades de las Parótidas/tratamiento farmacológico , Glándula Parótida/patología , Anciano , Biopsia/efectos adversos , Fístula Cutánea/etiología , Femenino , Fístula/etiología , Humanos , Enfermedades de las Parótidas/etiología , Fotograbar , Sialorrea/tratamiento farmacológico , Sialorrea/etiologíaRESUMEN
There are 3 types of leiomyosarcoma of the skin: dermal, subcutaneous, and metastatic cutaneous. Dermal leiomyosarcoma arises from smooth muscle fibers in arrector pili muscles, genital dartos muscles, and the nipple-areola complex. It is an intermediate-grade tumor associated with a tendency for local recurrence (24%) and low metastatic potential (4%). Subcutaneous leiomyosarcoma originates from smooth muscle in blood vessel walls and has higher rates of local recurrence (37%) and metastasis (43%). Plemorphic dermal sarcoma typically affects elderly patients and arises in sun-exposed areas (e.g., the scalp). Its histologic and immunohistochemical characteristics are similar to those of atypical fibroxanthoma, but it is more aggressive (metastasis rate of 10-20%). Histologically, it can be distinguished from atypical fibroxanthoma by the observation of subcutaneous tissue invasion, perineural invasion, and foci of necrosis.
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Leiomiosarcoma/diagnóstico , Leiomiosarcoma/terapia , Sarcoma/diagnóstico , Sarcoma/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Algoritmos , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
Postirradiation morphea is an uncommon entity that has been mostly described in women with breast cancer. The increasing use of radiotherapy to treat breast cancer and the clinical similarities between morphea and other conditions, such as radiodermatitis, postirradiation fibrosis, and tumor recurrence, highlights the need for dermatologists to be familiar with this entity. We present a series of 6 women with a mean age of 64.2 years and a mean latency of 9.5 years between radiotherapy for breast cancer and onset of morphea. Four of the patients had a history of autoimmune disease: rheumatoid arthritis, Sjögren syndrome, vitiligo, and Crohn disease. No specific risk factors for postirradiation morphea have been identified to date, although it would appear that a history of autoimmune disease could be associated with an increased risk of morphea in patients treated with radiation therapy.
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Enfermedades Autoinmunes/complicaciones , Neoplasias de la Mama/radioterapia , Traumatismos por Radiación/complicaciones , Esclerodermia Localizada/etiología , Anciano , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Sarcomas comprise a broad group of tumors, many of whose biological behavior and aggressiveness differ from one type to another. The therapeutic approach is generally multidisciplinary and often complex. Developments in surgical and oncological dermatology during the last few decades have positioned dermatologists as specialists in the diagnosis and treatment of skin cancer. The aim of this article is to review the main soft tissue sarcomas that typically affect the skin. Dermatofibrosarcoma protuberans is a low-grade malignant sarcoma. It exhibits slow-growth, is locally invasive, and has low metastatic potential (<3%). Mohs micrographic surgery is the treatment of choice. The COL1A1-PDGFB translocation should be analyzed in cases of unclear diagnosis and when it is necessary to identify candidates for tyrosine kinase inhibitors. Imatinib is indicated for the treatment of locally advanced and metastatic dermatofibrosarcoma protuberans.
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Dermatofibrosarcoma/diagnóstico , Dermatofibrosarcoma/terapia , Guías de Práctica Clínica como Asunto , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Antineoplásicos/uso terapéutico , Terapia Combinada , Dermatofibrosarcoma/genética , Dermatofibrosarcoma/patología , Humanos , Mesilato de Imatinib/uso terapéutico , Cirugía de Mohs , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas de Fusión Oncogénica/genética , Radioterapia Adyuvante , Sarcoma/clasificación , Sarcoma/diagnóstico , Sarcoma/patología , Sarcoma/terapia , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
Kaposi sarcoma is a vascular sarcoma with 4 clinical variants: classic Kaposi sarcoma, which mainly affect the extremities of elderly patients and follows a chronic, generally indolent course; African Kaposi sarcoma; immunosuppression-associated Kaposi sarcoma; and AIDS-associated Kaposi sarcoma. Type8 human herpesvirus is the etiologic agent in all 4variants. Cutaneous angiosarcoma is a cutaneous neoplasm with a very poor prognosis. It carries a high probability of local relapse and has a 10% to 15% survival rate at 5years. There are 3 main variants of cutaneous angiosarcoma: idiopathic angiosarcoma of the face and scalp; Stewart-Treves syndrome; and postradiation angiosarcoma. The only potentially curative treatment is surgery with or without radiotherapy. However, its indistinct borders and multicentric nature mean that treatment is often palliative with chemotherapy, radiotherapy, or both.
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Hemangiosarcoma/diagnóstico , Hemangiosarcoma/terapia , Guías de Práctica Clínica como Asunto , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/terapia , Distribución por Edad , Terapia Combinada , Femenino , Hemangiosarcoma/patología , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Linfangiosarcoma/diagnóstico , Linfangiosarcoma/patología , Linfangiosarcoma/terapia , Masculino , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/terapia , Radioterapia/efectos adversos , Sarcoma de Kaposi/clasificación , Sarcoma de Kaposi/virología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/virologíaAsunto(s)
Ácido Aminolevulínico/análogos & derivados , Queratosis Actínica/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Administración Cutánea , Anciano , Ácido Aminolevulínico/administración & dosificación , Ácido Aminolevulínico/efectos adversos , Eritema/diagnóstico , Eritema/etiología , Cara , Femenino , Humanos , Queratosis Actínica/patología , Masculino , Dolor/diagnóstico , Dolor/etiología , Satisfacción del Paciente , Fotoquimioterapia/efectos adversos , Fármacos Fotosensibilizantes/efectos adversos , Estudios Prospectivos , Cuero Cabelludo , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiación , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
INTRODUCTION AND OBJECTIVES: Vismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years. MATERIAL AND METHODS: We analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences. RESULTS: We treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment. CONCLUSIONS: With a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency.
Asunto(s)
Anilidas/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Piridinas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
INTRODUCTION AND OBJECTIVES: Imiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. PATIENTS AND METHODS: We included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ2 test and the Spearman rank correlation test. RESULTS: Sixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ2 test and the Spearman rank correlation test. CONCLUSIONS: A 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response.