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BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.
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Doença de Paget Extramamária , Humanos , Estudos Retrospectivos , Doença de Paget Extramamária/cirurgia , Cirurgia de Mohs , Análise de Sobrevida , Margens de Excisão , Resultado do Tratamento , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6â cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36â months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6â months could be considered an appropriate therapeutic strategy for EMPD patients.
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BACKGROUND: The survival benefit of sentinel lymph node biopsy (SLNB) in immunocompetent and immunosuppressed patients with high-risk cutaneous squamous cell carcinoma (cSCC) has not been established. OBJECTIVE: To determine whether SLNB improves disease-specific survival (DSS) in high-risk cSCC. Secondary objectives were to analyse disease-free survival, nodal recurrence-free survival and overall survival (OS). METHODS: Multicentre, retrospective, observational cohort study comparing survival outcomes in immunosuppressed and immunocompetent patients treated with SLNB or watchful waiting. Inverse probability of treatment weighting was used to adjust for possible confounding effects. RESULTS: We studied 638 tumours in immunocompetent patients (SLNB n = 42, observation n = 596) and 173 tumours in immunosuppressed patients (SLNB n = 28, observation n = 145). Overall, SLNB was positive in 15.7% of tumours. SLNB was associated with a reduced risk of nodal recurrence (NR) (hazard ratio [HR], 0.05 [95% CI, 0.01-0.43]; p = 0.006), disease specific mortality (HR, 0.17 [95% CI, 0.04-0.72]; p = 0.016) and all-cause mortality (HR, 0.33 [95% CI, 0.15-0.71]; p = 0.004) only in immunocompetent patients. CONCLUSIONS: SLNB was associated with improvements in NR, DSS and OS in immunocompetent but not in immunosuppressed patients with high-risk cSCC.
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Carcinoma de Células Escamosas , Hospedeiro Imunocomprometido , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Masculino , Estudos Retrospectivos , Feminino , Idoso , Pessoa de Meia-Idade , Imunocompetência , Idoso de 80 Anos ou mais , Conduta Expectante , Intervalo Livre de DoençaRESUMO
BACKGROUND: Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic constraints. OBJECTIVE: To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins ≥1 mm. METHODS: Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. RESULTS: In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio [SHR] 1.96 [95% CI 0.87-4.41]). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 [1.24-10.01]). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 [1.68-14.97]). LIMITATIONS: Retrospective observational study based on pathology reports. CONCLUSION: Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.
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BACKGROUND: Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. OBJECTIVE: To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific-death. METHODS: A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. RESULTS: Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P = .003], 2.32 [95% CI, 1.13-4.77; P = .021], and 2.863 [95% CI, 1.25-6.55; P = .013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P = .023]). LIMITATIONS: Retrospective study and heterogeneity of treatments. CONCLUSION: The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Estudos Retrospectivos , Prognóstico , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Fatores de Risco , Recidiva , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. OBJECTIVES: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. METHODS: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. RESULTS: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. CONCLUSION: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment.
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Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Basocelular/patologia , Anilidas/uso terapêuticoRESUMO
Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4-year-old boy and review the literature.
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Síndrome do Hamartoma Múltiplo , Nevo Sebáceo de Jadassohn , Nevo , Masculino , Humanos , Pré-Escolar , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndrome do Hamartoma Múltiplo/genética , Nevo Sebáceo de Jadassohn/diagnóstico , Nevo Sebáceo de Jadassohn/genética , Nevo/genética , Nevo/patologia , Mosaicismo , PTEN Fosfo-Hidrolase/genéticaRESUMO
The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.
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COVID-19 , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/cirurgia , Controle de Doenças Transmissíveis , Humanos , Melanoma/epidemiologia , Melanoma/cirurgia , Pandemias , SARS-CoV-2 , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia , Carga TumoralRESUMO
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCCs) when compared with non-metastasizing cSCCs (non-MSCCs). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NF-κB signaling pathway. Accordingly, non-MSCCs display higher levels of membranous pS176-inhibitor of NF-kB kinase, and their stroma is enriched in neutrophils and eosinophils when compared with MSCCs. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb-depleted cSCC cells. Altogether, these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high-risk cSCCs could benefit from clinical therapies addressed to harness the immune response.
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Carcinoma de Células Escamosas/imunologia , Proteína Potenciadora do Homólogo 2 de Zeste/imunologia , Complexo Repressor Polycomb 1/imunologia , Neoplasias Cutâneas/imunologia , Evasão Tumoral/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética/imunologia , Feminino , Humanos , Vigilância Imunológica/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Complexo Repressor Polycomb 1/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Dermal neurofibromas are characteristic of neurofibromatosis type one (NF1), and their developmental origin still unsolved. Although NF1 loss is required for neurofibroma initiation, some features of these benign tumors resemble a skin injury state and cutaneous trauma or other insults might support tumor development. Since adult terminal Schwann cells ensheathing nerve endings are able to dedifferentiate into a progenitor-like state in response to nerve crushing, we hypothesized that dedifferentiation of NF1-/- Schwann cells could be at the origin of human dermal neurofibromas. In support of this, here we show that CDH19 (a marker specific of Schwann cell precursors) and Schwann cell dedifferentiation marker SOX2 are significantly upregulated in NF1 tumors. We posit that onset of nerve regeneration might have a role in dermal neurofibroma initiation via dedifferentiation of NF1-/- Schwann cells.
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Desdiferenciação Celular , Neurofibroma/etiologia , Células de Schwann/fisiologia , Neoplasias Cutâneas/etiologia , HumanosAssuntos
Carcinoma de Células Escamosas/patologia , Nervos Periféricos/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Achados Incidentais , Masculino , Margens de Excisão , Invasividade Neoplásica/diagnóstico , Prognóstico , Estudos Retrospectivos , Pele/inervação , Pele/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Carga TumoralRESUMO
Cetuximab and panitumumab are epidermal growth factor receptor (EGFR) inhibitors used in metastatic colorectal cancer (mCRC). Most patients develop a papulopustular rash that may predict tumor response to treatment. EGFR gene polymorphisms may also determine tumor response and appearance of skin rash. We hypothesized an association between EGFR gene polymorphisms, papulopustular rash and response to anticancer treatment. Four EGFR polymorphisms (-216, -191, CA-SSR, R521K) were analysed in 51 patients with mCRC receiving anti-EGFR. Severity of cutaneous rash and tumor response was measured following standard scales. We report an association between SNP-216 and tumor response (P = 0.003): no tumor progression occurred in TT genotype. Moreover, 92.3% of the responder patients developed skin rash, 62.9% of them presenting a grade ≥2 (P = 0.015). Thus, although underpowered, our preliminary data suggest that SNP-216 polymorphism of the EGFR gene could be useful in predicting tumor response and the appearance of severe skin rash might also be associated.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Receptores ErbB/antagonistas & inibidores , Exantema/etiologia , Genes erbB-1 , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Cetuximab/efeitos adversos , Cetuximab/uso terapêutico , Neoplasias Colorretais/secundário , Receptores ErbB/genética , Exantema/genética , Feminino , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Modelos Genéticos , Panitumumabe , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Resultado do TratamentoRESUMO
Cutaneous squamous cell carcinoma (cSCC) is the second most common subtype of skin cancer. The scalp is one of the most frequently affected locations and is associated with a higher rate of complications, compared to other locations. In addition, it has a characteristic thickness and anatomical structure that may influence both growth pattern and treatment of primary cSCC; while clinical peripheral margins may be easily achieved during the surgery, vertical excision of the tumor is limited by the skull. Despite having a unique anatomy, current guidelines do not contemplate specific recommendations for scalp cSCC, which leads to inconsistent decision-making in multidisciplinary committees when discussing tumors with high risk factors or with close margins. This article provides specific recommendations for the management of patients with scalp cSCC, based on current evidence, as well as those aspects in which evidence is lacking, pointing out possible future lines of research. Topics addressed include epidemiology, clinical presentation and diagnosis, imaging techniques, surgical and radiation treatments, systemic therapy for advanced cases, and follow-up. The primary focus of this review is on management of primary cSCC of the scalp with localized disease, although where relevant, some points about recurrent cSCCs or advanced disease cases are also discussed.
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INTRODUCTION: Lentigo maligna is a subtype of melanoma in situ that typically affects the head and neck region with an increasing incidence. Margin-controlled techniques, such as spaghetti technique (ST), have gained popularity over wide local excision (WLE) with a margin of 5 mm. OBJECTIVES: To evaluate the outcomes of lentigo maligna cases in the head and neck area treated by either WLE or ST in a tertiary referral hospital. The secondary goal was to describe the demographic and clinical characteristics of our series. METHODS: Cohort study of patients diagnosed with lentigo maligna on the head and neck region between January 2014 and February 2022 in a tertiary hospital. RESULTS: In total, 79 lentigo maligna were studied, corresponding to 77 patients. Fifty-three lesions (67%) were treated with WLE and 26 (33%) with ST. The mean age of the patients was 73 years and 58% were men. Most of the tumors were located on the cheek (50%) and mean lesion diameter was 2.2 cm for the ST group and 1.2 cm for the WLE group. Mean duration follow-up was 44 months. There were two local recurrences in the WLE group (2/53; 3.7%) and none in the ST group. CONCLUSIONS: Both WLE and ST are appropriate surgical approaches for lentigo maligna. ST offers an efficient alternative to Mohs surgery for treating lentigo maligna in the head and neck area, especially when guided by reflectance confocal microscopy.
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Neoplasias Faciais/cirurgia , Histiocitoma Fibroso Benigno/cirurgia , Cirurgia de Mohs , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Neoplasias Faciais/patologia , Feminino , Histiocitoma Fibroso Benigno/patologia , Humanos , Masculino , Inclusão em Parafina , Neoplasias Cutâneas/patologiaRESUMO
Introduction: In vivo reflectance confocal microscopy (RCM) is a useful tool for assessing pre-surgical skin tumor margins when performed by a skilled, experienced user. The technique, however, poses significant challenges to novice users, particularly when a handheld RCM (HRCM) device is used. Objectives: To evaluate the performance of an HRCM device operated by a novice user to delineate basal cell carcinoma (BCC) margins before Mohs micrographic surgery (MMS). Methods: Prospective study of 17 consecutive patients with a BCC in a high-risk facial area (the H zone) in whom tumor margins were assessed by HRCM and dermoscopy before MMS. Predicted surgical defect areas (cm2) were calculated using standardized photographic digital documentation and compared to final defect areas after staged excision. Results: No significant differences were observed between median HRCM-predicted and observed surgical defect areas (2.95 cm2 [range: 0.83-17.52] versus 2.52 cm2 [range 0.71-14.42]; P = 0.586). Dermoscopy, by contrast, produced significantly underestimated values (median area of 1.34 cm2 [0.41-4.64] versus 2.52 cm2 [range 0.71-14.42]; P < 0.001). Confounders leading to poor agreement between predicted and observed areas were previous treatment (N = 5), a purely infiltrative subtype (N = 1), and abundant sebaceous hyperplasia (N = 1). Conclusions: Even in the hands of a novice user, HRCM is more accurate than dermoscopy for delineating lateral BCCs margins in high-risk areas and performs well at predicting final surgical defects.
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Diltiazem is a calcium channel blocking agent used for the treatment of hypertension. Cutaneous adverse effects are uncommon. The most frequently reported are itching, urticaria, and maculopapular eruption. A peculiar, cutaneous photodistributed reticulated hyperpigmentation secondary to diltiazem has been recently reported. A 66-year-old white woman with a 2 year history of pruritic hyperpigmented lesions on her face was seen in the clinic. Past medical history was remarkable for hypertension, which had been treated with diltiazem. Physical examination showed slate-gray to brown reticulated hyperpigmentation in the photo-exposed areas of the face and neck. Histological examination revealed interface dermatitis with liquefactive degeneration of the basal layer, necrotic keratinocytes, lymphocytic inflammatory infiltrate, and melanophages in the superficial dermis. A diagnosis of diltiazem-induced hyperpigmentation was established and diltiazem was stopped. Gradual resolution of the hyperpigmentation was observed over the following months. Although diltiazem has been marketed for over 20 years, the first cases of this particular type of reticulated hyperpigmentation were described in 2001. Since then, to our knowledge, only 17 cases have been reported in the literature. In all cases, cutaneous lesions appeared at least 6 months after this treatment had been started. Hyperpigmentation was controlled by means of photoprotection and discontinuation of diltiazem. Diltiazem can produce a characteristic lichenoid dermatitis with reticulated hyperpigmentation on sun-exposed areas.