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Cell Jul 2020To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and...
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Clustered Regularly Interspaced Short Palindromic Repeats; Genomics; Humans; Keratinocytes; Mice; RNA-Seq; Single-Cell Analysis; Skin; Skin Neoplasms; Transcriptome; Transplantation, Heterologous
PubMed: 32579974
DOI: 10.1016/j.cell.2020.05.039 -
The New England Journal of Medicine Jun 2023
Review
Topics: Humans; Carcinoma, Squamous Cell; Skin; Skin Neoplasms
PubMed: 37314707
DOI: 10.1056/NEJMra2206348 -
International Journal of Dermatology Jun 2020Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp,... (Review)
Review
Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp, neck, hands, and forearms. AKs must be considered an early squamous cell carcinoma (SCC) for their probable progression into invasive SCC. For this reason, all AK should be treated, and clinical follow-up is recommended. The aims of treatment are: (i) to clinically eradicate evident and subclinical lesions, (ii) to prevent their evolution into SCC, and (iii) to reduce the number of relapses. Among available treatments, it is possible to distinguish lesion-directed therapies and field-directed therapies. Lesion-directed treatments include: (i) cryotherapy; (ii) laser therapy; (iii) surgery; and (iv) curettage. Whereas, field-directed treatments are: (i) 5-fluorouracil (5-FU); (ii) diclofenac 3% gel; (iii) chemical peeling; (iv) imiquimod; and (v) photodynamic therapy (PDT). Prevention plays an important role in the treatment of AKs, and it is based on the continuous use of sunscreen and protective clothing. This review shows different types of available treatments and describes the characteristics and benefits of each medication, underlining the best choice.
Topics: Aftercare; Carcinoma, Squamous Cell; Chemexfoliation; Cryotherapy; Curettage; Dermoscopy; Diclofenac; Disease Progression; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Laser Therapy; Photochemotherapy; Practice Guidelines as Topic; Protective Clothing; Skin; Skin Neoplasms; Sunlight; Sunscreening Agents
PubMed: 32012240
DOI: 10.1111/ijd.14767 -
European Journal of Cancer (Oxford,... Mar 2020In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a...
In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for non-surgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics.
Topics: Aftercare; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Carcinoma, Squamous Cell; Chemoradiotherapy; Clinical Decision-Making; Consensus; Dermatologic Surgical Procedures; Dermatology; Humans; Lymph Node Excision; Lymph Nodes; Margins of Excision; Medical Oncology; Neoplasm Staging; Palliative Care; Patient Care Team; Patient Education as Topic; Skin; Skin Neoplasms; Societies, Medical; Sunlight
PubMed: 32113942
DOI: 10.1016/j.ejca.2020.01.008 -
European Journal of Cancer (Oxford,... Mar 2020Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors...
Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women's Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography-computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.
Topics: Carcinoma, Squamous Cell; Consensus; Dermatology; Humans; Lymph Nodes; Magnetic Resonance Imaging; Medical Oncology; Neoplasm Staging; Patient Education as Topic; Positron Emission Tomography Computed Tomography; Protective Clothing; Risk Assessment; Skin; Skin Neoplasms; Societies, Medical; Sunlight; Sunscreening Agents; Ultrasonography
PubMed: 32113941
DOI: 10.1016/j.ejca.2020.01.007 -
Dermatologic Clinics Jul 2023Skin cancer is often associated with greater morbidity and mortality in skin of color patients because most medical literature and research on skin cancer to date has... (Review)
Review
Skin cancer is often associated with greater morbidity and mortality in skin of color patients because most medical literature and research on skin cancer to date has been predominantly focused on lighter skin types. It is crucial that dermatologic providers be able to recognize different presentations of skin cancer in skin of color patients to optimize the early detection of these tumors and ensure equitable outcomes. This article details the epidemiology, risk factors, clinical features, and disparities in the treatment of melanoma, squamous cell carcinoma, basal cell carcinoma, and mycosis fungoides subtype of cutaneous T-cell lymphoma in skin of color patients.
Topics: Humans; Carcinoma, Basal Cell; Mycosis Fungoides; Skin; Skin Neoplasms; Racial Groups
PubMed: 37236716
DOI: 10.1016/j.det.2023.02.013 -
Journal of Cutaneous Medicine and... 2023Verrucous carcinoma (VC) is a relatively rare locally aggressive, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential and is most... (Review)
Review
Verrucous carcinoma (VC) is a relatively rare locally aggressive, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential and is most frequent in the mucosa. Although rarely reported on the skin, cutaneous verrucous carcinomas (CVC) can appear anywhere, most commonly on the feet. However, clinical and pathologic diagnosis of CVC has been confusing and challenging. It can easily be mistaken for benign or more malignant conditions such as giant condyloma acuminata, keratoacanthoma, and pseudoepithelioma-like hyperplasia or squamous cell carcinoma, resulting in inappropriate management. In this review, we describe the different aspects associated with CVC, including its pathogenesis and clinicopathologic features. The available evidence for the differential diagnosis and treatment of CVC is discussed, and specific management recommendations are made. After the treatment, careful follow-up examinations of the excised area should be performed at regular intervals.
Topics: Humans; Carcinoma, Verrucous; Carcinoma, Squamous Cell; Buschke-Lowenstein Tumor; Skin Neoplasms; Skin
PubMed: 36789508
DOI: 10.1177/12034754231155895 -
Dermatologic Clinics Jan 2023Patients with immunosuppressive conditions experience an increased frequency and severity of cutaneous malignancies. This article highlights management of keratinocyte... (Review)
Review
Patients with immunosuppressive conditions experience an increased frequency and severity of cutaneous malignancies. This article highlights management of keratinocyte carcinoma, melanoma, Merkel cell carcinoma, and Kaposi sarcoma in the setting of lymphoproliferative disorders, acquired immunodeficiencies, and organ transplantation. Advances in the safety of organ transplant recipient immunosuppression, early identification of risk factors, and new targeted therapies are improving skin cancer outcomes in immunocompromised populations.
Topics: Humans; Immunocompromised Host; Skin; Skin Neoplasms; Carcinoma, Merkel Cell; Immunosuppression Therapy
PubMed: 36410975
DOI: 10.1016/j.det.2022.07.012 -
Cancer Radiotherapie : Journal de La... Jun 2023Skin adnexal carcinomas are rare skin cancer, developing from pilosebaceous, eccrine and apocrine unit. Treatment of localised tumours usually includes surgery and... (Review)
Review
Skin adnexal carcinomas are rare skin cancer, developing from pilosebaceous, eccrine and apocrine unit. Treatment of localised tumours usually includes surgery and radiotherapy. Indications and modalities of radiotherapy depend on the pathological subtype with a lack of consensus for some histologies. This review summarises the place of radiotherapy in terms of indication, dose and fractionation, volumes to irradiate and discuss ongoing studies.
Topics: Humans; Skin; Skin Neoplasms; Neoplasms, Adnexal and Skin Appendage; Carcinoma
PubMed: 37080860
DOI: 10.1016/j.canrad.2022.12.003 -
Der Hautarzt; Zeitschrift Fur... Apr 2021Skin is commonly affected by neuroendorine paraneoplastic syndromes (PNS). This is due to the expression of receptors in the skin by which abnormally secreted... (Review)
Review
Skin is commonly affected by neuroendorine paraneoplastic syndromes (PNS). This is due to the expression of receptors in the skin by which abnormally secreted neuroendocrine hormones and mediators elicit directly, and indirectly, cutaneous key signs and thus facilitate early diagnosis of these diseases. In acromegaly, induction of the growth hormone-insulin-like growth factor‑1 axis results in trophic changes of the acral portions of the skin and mucosal membranes including cutis verticis gyrata. The skin signs of non-iatrogenic Cushing syndrome are identical with those of exogenous prolonged intake of glucocorticoids: centripetal accumulation of adipose tissue, plethora and striae distensae. Episodic flushing of the face and trunk (together with explosive diarrhea) is a key feature of carcinoid tumors. Fibrotic remodeling of the heart and retroperitoneal space, and less commonly of the skin, are important complications mediated by abnormally secreted 5‑hydroxytryptamine (serotonin, 5‑HT), the latter eliciting profibrotic responses on HT-receptor-expressing fibroblasts. Androgen-secreting tumors lead to well-established receptor-mediated cutaneous signs of peripheral hyperandrogenisms: seborrhea, acne, hirsutism, and androgenetic alopecia. In contrast, the pathogenesis of necrolytic migratory erythema as a key feature of glucagonoma remains incompletely understood and is thought to be related to hypoaminoacidemia. This review summarizes the clinical features of neuroendocrine PNS with skin involvement, elucidates its underlying pathophysiology, lists differential diagnoses, and explains key diagnostic steps and principal therapeutic options. An interdisciplinary approach is essential to provide the best care of all patients with neuroendocrine PNS.
Topics: Glucagonoma; Hirsutism; Humans; Pancreatic Neoplasms; Paraneoplastic Syndromes; Skin
PubMed: 33661337
DOI: 10.1007/s00105-021-04778-5