RESUMEN
Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers of the Caucasian population and accounts for 20% of all skin tumours. An S3 guideline of the German Guideline Program in Oncology has been available since 2019. The diagnosis is based on the clinical examination. Excision and histological confirmation is required for all clinically suspicious lesions to allow prognostic assessment and correct treatment. The therapy of first choice is complete excision with histological control of the surgical margin. In cSCC with risk factors such as tumor thickness >6â¯mm, sentinel lymph node biopsy may be discussed, but there is currently no clear evidence of its prognostic and therapeutic relevance. Adjuvant radiation therapy may be considered in cases of high risk of recurrence and should be tested in cases of inoperable tumors. The indication for electrochemotherapy should also be considered in the treatment of local or locoregional recurrence. The immune checkpoint inhibitor cemiplimab is approved for the treatment of inoperable or metastasized cSCC. In case of contraindications, chemotherapeutic agents, epidermal growth factor receptor (EGFR) inhibitors or palliative radiotherapy can be used. Since the evidence is low in these cases, a systemic therapy should be used preferentially within clinical studies. Follow-up care should be risk-adapted and includes a dermatological control, supplemented by ultrasound examinations in high-risk patients.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Procedimientos Quirúrgicos Dermatologicos/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/cirugía , Carcinoma de Células Escamosas/patología , Humanos , Recurrencia Local de Neoplasia , Guías de Práctica Clínica como Asunto , Pronóstico , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Risk factors for primary non-melanoma skin cancer (NMSC) in organ transplant recipients (OTR) have been well described. Data for subsequent NMSC and dynamics in their occurrence in OTR are limited. OBJECTIVE: To study long-term risks of primary and subsequent NMSC and associated risk factors in OTR. METHODS: A retrospective single-centre cohort study analysing medical records from a dermato-oncological specialty clinic. RESULTS: Of 464 OTR 110 (23.7%) developed at least one, 73 (15.7%) two and 51 (11%) three NMSC during a median follow-up of 9.6 years. Cumulative incidences at 5, 10 and 15 years were 14.7%, 23.5% and 34.5% for the first and 75.8%, 86.5% and 93.3% for the second. Median time-to-diagnosis declined from 22 years (95% CI 19-25) to 2 years (1-3) and about 1 year (0-2) for the first, second and third NMSC. Risk for subsequent NMSC only partially related to risk factors for the primary NMSC. Histologic type of the first NMSC predicted subtype and time-to-diagnosis of the subsequent NMSC. CONCLUSIONS: A first post-transplant NMSC, particularly a SCC, confers a high risk for subsequent NMSC arising with accelerated dynamics. Risk-adapted dermato-oncologic surveillance is advisable for all OTR.
Asunto(s)
Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Trasplante de Órganos , Neoplasias Cutáneas/epidemiología , Adulto , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/patología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: The inflammatory tumour microenvironment is crucial for effective tumour control, and long-term immunosuppression has been identified as a major risk factor for skin carcinogenesis. In solid organ transplant recipients (OTRs) undergoing long-term pharmacological immunosuppression, an increased incidence of cutaneous squamous cell carcinoma (SCC) and more aggressive tumour growth compared with immunocompetent patients has been reported. OBJECTIVES: To determine the density and phenotype of immune cells infiltrating SCC and surrounding skin in OTRs, and to characterize the microanatomical distribution patterns in comparison with immunocompetent patients. METHODS: We analysed immune cell infiltrates within SCC and at defined regions of interest (ROIs) of tumour-surrounding skin in formalin-fixed paraffin-embedded tissue of 20 renal transplant patients and 18 carefully matched immunocompetent patients by high-resolution semiautomated microscopy on complete tissue sections stained for CD4, CD8, CD20 and CD68. RESULTS: The overall immune cell density of SCC arising in OTRs was significantly reduced compared with immunocompetent patients. Particularly CD4+ infiltrates at the directly invasive margin and tumour vicinity, intratumoral CD8+ T-cell densities and the overall density of CD20+ tumour-infiltrating B cells were significantly reduced in the tissue of OTRs. CONCLUSIONS: Immune cell infiltrates within SCC and at defined ROIs of tumour-surrounding skin in OTRs differ markedly in their composition and microanatomical distribution compared with tumours arising in immunocompetent patients. Our findings substantially broaden the understanding of how long-term systemic immunosuppression modulates the local inflammatory microenvironment in the skin and at the site of invasive SCC.
Asunto(s)
Carcinoma de Células Escamosas/inmunología , Terapia de Inmunosupresión/efectos adversos , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Cutáneas/inmunología , Piel/citología , Anciano , Anciano de 80 o más Años , Linfocitos B/inmunología , Carcinoma de Células Escamosas/patología , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Huésped Inmunocomprometido , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Piel/inmunología , Piel/patología , Neoplasias Cutáneas/patología , Linfocitos T/inmunología , Receptores de Trasplantes , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
BACKGROUND: Several autosomal dominant disorders may manifest in mosaic patterns with cutaneous involvement. Genomic mosaicism results from postzygotic autosomal mutations, giving rise to clonal proliferation of two genetically distinct cell groups, which clinically present as lesions following the lines of Blaschko. OBJECTIVE: To increase the awareness of the clinical variability of mosaic manifestations in autosomal dominant skin disorders in order to avoid delayed diagnosis. METHODS: Clinicopathologic correlation in a case series including three patients with mosaic manifestations of different autosomal dominant skin diseases. RESULTS: Here, we describe a patient with type 1 segmental mosaicism of epidermolytic ichthyosis (case 1) and two patients with either type 1 (case 2) or type 2 (case 3) segmental neurofibromatosis 1 (NF1). CONCLUSION: Dermatologists should be familiar with mosaic manifestations of autosomal dominant skin diseases to ensure appropriate guidance of the affected patient. Genetic counselling is mandatory as even limited forms of mosaicism may involve the patient's germline with a moderately increased risk to transmit the mutation to their offspring, resulting in a more severe, generalized form of the respective disease.
Asunto(s)
Genes Dominantes , Mosaicismo , Enfermedades de la Piel/patología , Adolescente , Niño , Femenino , Humanos , Masculino , Enfermedades de la Piel/genéticaRESUMEN
Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. A risk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients.
Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Procedimientos Quirúrgicos Dermatologicos/métodos , Radioterapia Conformacional/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Animales , Antineoplásicos/administración & dosificación , Terapia Combinada/métodos , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Resultado del TratamientoRESUMEN
Skin cancer constitutes the most frequently reported post-transplant malignancy in solid organ transplant recipients (OTR) worldwide. Whereas the risk for malignant melanoma is only moderately increased, non-melanoma skin cancers (NMSC) seem to thrive on chronic immunosuppression and account for up to 95% of post-transplant cutaneous malignancies. Compared to the general population cutaneous squamous cell carcinoma (SCC) and actinic keratoses (AK) characteristically show even higher incidences than basal cell carcinoma (BCC) and act as an indicator for the development of multiple primary cutaneous neoplasias and locally recurrent cancers (field cancerization). Early diagnosis and therapy of pre-malignant cutaneous lesions is crucial for the secondary prophylaxis of further invasive and highly aggressive skin cancers. High quality interdisciplinary care and prophylactic modalities, including consistent and sufficient UV protection, topical immunmodulatory therapies of UV-damaged skin areas, retinoid chemoprevention as well as tapering immunosuppressive treatment or the selection of immunosuppressants with proposed antiangiogenic properties like mTor-inhibitors may help to reduce the multiplicity of subsequent primary skin cancers in high-risk patients. Apart from the continuous need for educational intervention of OTR in the primary prophylaxis of post-transplant skin cancers, dermatologic care occupies a central position within the field of transplantation medicine in terms of pre- and post-transplantation dermatologic evaluation and therapy as well as the implication of timely and effective secondary preventive approaches in the management of this high-risk patient population.
Asunto(s)
Antineoplásicos/administración & dosificación , Inmunosupresores/administración & dosificación , Trasplante de Órganos/efectos adversos , Prevención Primaria/métodos , Prevención Secundaria/métodos , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/prevención & control , HumanosRESUMEN
Eczema is one of the most common skin diseases in dermatological practice. The broad medical definition of eczema includes any acute but non-infectious inflammatory reaction of the skin. The relative homogeneity of both the clinical and histological manifestations of eczema is in stark contrast to the profound pathogenetic differences of its various forms. The group of contact dermatitis can be divided into two main categories: irritant and allergic. Irritant contact dermatitis is due to a principally non- immunological inflammatory reaction of the skin to various physical or chemical irritants. In sharp contrast, allergic contact dermatitis is an antigen-specific cellular immune response of the skin, which in general requires prior antigen-recognition and priming of immune cells. A comprehensive understanding of the complex interactions between immune cells, inflammatory mediators and adhesion molecules in the underlying pathogenesis of allergic contact dermatitis is key for a better functional understanding and the development of new therapeutic strategies.