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INTRODUCTION: Since the field of dermatopathology is not an exact science, it is prone to personal subjectivity, which sometimes causes disagreements on the diagnosis and assessment of some histological features. In the case of melanoma, some variables such as regression are associated with low interobserver agreement. On the contrary, other variables such as the measurement of Breslow thickness show high reproducibility. OBJECTIVE: The main objective of our study was to investigate multiple features of 60 consecutive cases of melanoma to establish interobserver reproducibility. METHODS AND MAIN RESULTS: We conducted an observational and descriptive study at Hospital de Manises, Valencia, Spain, IVO Foundation, Valencia, Spain, and Hospital 12 de Octubre, Madrid, Spain. The mean level of agreement of all study variables was moderate (Cohen's kappa coefficient statistic = 0.5). The highest agreement corresponded to polypoid morphology, pigmentation, ulceration, and solar elastosis. On the other hand, the lowest level agreement was reached for the presence of cellular pleomorphism and tumor necrosis. CONCLUSIONS: Our mean level of agreement was moderate, which reflects that some of the measured characteristics such as cellular pleomorphism or the presence of necrosis cannot be used for future studies or must be redefined and their reproducibility, reestablished. When conducting a research study, it is necessary to analyze the study variables to demonstrate their validity to measure or classify a certain feature. It is also advisable to warrant that that the variables are reproducible to be able to use them for other studies or in the routine clinical practice.
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BACKGROUND AND OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. MATERIAL AND METHOD: We conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. RESULTS: A total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. CONCLUSIONS: The mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.
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Carcinoma de Células Escamosas , Progressão da Doença , Metástase Linfática , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Idoso , Estudos Longitudinais , Pessoa de Meia-Idade , Metástase Linfática/patologia , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia/epidemiologia , AdultoRESUMO
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.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Espanha , Masculino , Feminino , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.
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Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Idoso , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Antineoplásicos/efeitos adversos , Anilidas/efeitos adversosRESUMO
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.
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Neoplasias Ósseas , Sarcoma , Neoplasias Cutâneas , Humanos , Neoplasias Ósseas/complicações , Necrose/complicações , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.
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Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Idoso , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Antineoplásicos/efeitos adversos , Anilidas/efeitos adversosRESUMO
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.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Imunoterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
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.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Imunoterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Familiarity with predictors of more aggressive behavior is crucial to the management of basal cell carcinoma (BCC). Risk factors for aggressive BCC are essentially divided into clinical and histopathologic factors. In this review we examine histopathologic features predictive of aggressiveness in BCC. The morpheaform, infiltrative, micronodular, metatypical, and basosquamous subtypes and BCC with sarcomatoid differentiation are classically considered predictive of aggressive behavior. However, 2 other features associated with aggressive BCC are perineural invasion (invasion of nerves below the dermis or nerves larger than 0.1mm in caliber) and subgaleal extension. While the former is well known and widely described in the literature, the latter is not generally recognized as a risk factor, even though it is predictive of highly aggressive behavior. In this review, we draw attention to its importance.
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Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/patologia , Humanos , Fatores de Risco , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologiaRESUMO
Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists.
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This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.
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Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. The causes of vascular occlusion are also highly variable, ranging from thrombi triggered by the uncontrolled activation of coagulation mechanisms, on the one hand, to endothelial dysfunction or occlusion by material extrinsic to the coagulation system on the other. In a 2-part review, we look at the main causes of vascular occlusion and the key clinical and histopathologic findings. In this first part, we focus on vascular occlusion involving thrombi.
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Trombose , Coagulação Sanguínea , Humanos , Trombose/etiologiaRESUMO
Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion.
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Transtornos da Coagulação Sanguínea/complicações , Embolia/complicações , Dermatopatias Vasculares/etiologia , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/patologia , Calciofilaxia/complicações , Calciofilaxia/patologia , Cocaína/efeitos adversos , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/patologia , Humanos , Isquemia/etiologia , Isquemia/patologia , Levamisol/efeitos adversos , Livedo Reticular/etiologia , Livedo Reticular/patologia , Masculino , Papulose Atrófica Maligna/patologia , Necrose , Neoplasias/complicações , Neoplasias/patologia , Paraproteinemias/complicações , Paraproteinemias/patologia , Pele/irrigação sanguínea , Dermatopatias Vasculares/induzido quimicamente , Dermatopatias Vasculares/patologia , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Síndrome de Sneddon/patologiaRESUMO
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.
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Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Antineoplásicos/efeitos adversos , Compostos de Bifenilo , Carcinoma Basocelular/tratamento farmacológico , Proteínas Hedgehog/uso terapêutico , Humanos , Piridinas , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVES: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. MATERIAL AND METHODS: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. RESULTS: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter >4cm or thickness >6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (>6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. CONCLUSIONS: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays.
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Betacoronavirus , Carcinoma de Células Escamosas/patologia , Infecções por Coronavirus/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Pneumonia Viral/epidemiologia , Neoplasias Cutâneas/patologia , Carga Tumoral , Fatores Etários , Algoritmos , COVID-19 , Carcinoma de Células Escamosas/mortalidade , Diagnóstico Tardio/efeitos adversos , Diagnóstico Tardio/estatística & dados numéricos , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Melanoma/mortalidade , Pandemias , Vigilância em Saúde Pública/métodos , Quarentena , Estudos Retrospectivos , SARS-CoV-2 , Fatores Sexuais , Neoplasias Cutâneas/mortalidade , Espanha/epidemiologia , Fatores de Tempo , Tempo para o TratamentoRESUMO
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans and its incidence is both underestimated and on the rise. cSCC is referred to in the literature as high-risk cSCC, locally advanced cSCC, metastatic cSCC, advanced cSCC, and aggressive cSCC. These terms can give rise to confusion and are not always well defined. In this review, we aim to clarify the concepts underlying these terms with a view to standardizing the description of this tumor, something we believe is necessary in light of the new drugs that have been approved or are in development for cSCC.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/diagnóstico , Humanos , Estadiamento de Neoplasias , Neoplasias Cutâneas/diagnósticoRESUMO
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 terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/patologiaRESUMO
Although the arrival of new chemotherapy drugs and combinations has brought progress in terms of cancer patient survival, they entail many adverse effects that can compromise treatment, and hence prognosis, of the disease. Cytostatic agents can cause dermatological toxicity, among other side effects. The most familiar adverse effect of chemotherapy is alopecia. Although not serious, this changes the outward appearance of cancer patients. Other adverse effects include hypersensitivity and photosensitivity reactions, hand-foot syndrome, epidermal necrolysis, recall reactions, scleroderma-like reactions, Raynaud's phenomenon, eccrine squamous syringometaplasia, neutrophilic eccrine hidradenitis, nail abnormalities, pigmentation changes and extravasation injuries. Onset of these adverse effects often causes dose reduction and/or delayed treatment, which can affect patient survival and quality of life. It is therefore important to prevent their occurrence and treat them promptly, which requires cooperation between medical oncologists and dermatologists. This article reviews chemotherapy-associated dermatological toxicity, along with its diagnosis and therapeutic management.