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Acta Dermato-venereologica Apr 2019Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically... (Review)
Review
Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically predisposed to skin cancer and this article is intended as a diagnostic tool when encountering patients with multiple skin cancer lesions. The disorders are described with clinical characteristics, genetics and management. The most common syndromes associated with basal cell carcinoma are: Gorlin-Goltz syndrome, Rombo syndrome, and Bazex-Dupré-Christol syndrome. Multiple squamous cell carcinomas can be related to: xeroderma pigmentosum, Ferguson-Smith, Muir-Torre syndrome, Mibelli-type porokeratosis, keratitis-ichthyosis-deafness syndrome, Rothmund-Thomson syndrome, Bloom syndrome, and epidermodysplasia verruciformis. Malignant melanoma can be inherited, as in familial atypical multiple mole melanoma syndrome.
Topics: Adolescent; Adult; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Male; Melanoma; Middle Aged; Mutation; Neoplastic Syndromes, Hereditary; Phenotype; Risk Assessment; Risk Factors; Skin; Skin Neoplasms; Treatment Outcome; Young Adult
PubMed: 30653245
DOI: 10.2340/00015555-3123 -
Archives of Pathology & Laboratory... Nov 2017- Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally... (Review)
Review
CONTEXT
- Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment.
OBJECTIVE
- To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction.
DATA SOURCES
- Review of pertinent literature on BCC immunohistochemistry and differential diagnosis.
CONCLUSIONS
- In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.
Topics: Adenocarcinoma, Sebaceous; Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Hamartoma; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Immunophenotyping; Skin; Skin Neoplasms
PubMed: 29072946
DOI: 10.5858/arpa.2017-0222-RA -
Current Treatment Options in Oncology Sep 2018Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used... (Review)
Review
Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used routinely for all pigmented and non-pigmented cutaneous neoplasms. It is especially useful for the early stage of melanoma when melanoma-specific criteria are invisible to the unaided eye. Preselection by the unaided eye is therefore not recommended. The increased availability of polarized dermatoscopes, and the extended use of dermatoscopy in non-pigmented lesions led to the discovery of new criteria, and we recommend that lesions should be examined with polarized and non-polarized dermatoscopy. The "chaos and clues algorithm" is a good starting point for beginners because it is easy to use, accurate, and it works for all types of pigmented lesions not only for those melanocytic. Physicians, who use dermatoscopy routinely, should be aware of new clues for acral melanomas, nail matrix melanomas, melanoma in situ, and nodular melanoma. Dermatoscopy should also be used to distinguish between different subtypes of basal cell carcinoma and to discriminate highly from poorly differentiated squamous cell carcinomas to optimize therapy and management of non-melanoma skin cancer. One of the most exciting areas of research is the use of dermatoscopic images for machine learning and automated diagnosis. Convolutional neural networks trained with dermatoscopic images are able to diagnose pigmented lesions with the same accuracy as human experts. We humans should not be afraid of this new and exciting development because it will most likely lead to a peaceful and fruitful coexistence of human experts and decision support systems.
Topics: Adult; Aged; Algorithms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermoscopy; Female; Humans; Keratosis, Actinic; Male; Melanoma; Sensitivity and Specificity; Skin; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 30238167
DOI: 10.1007/s11864-018-0573-6 -
JCI Insight Mar 2019Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown.
METHODS
We performed a blinded prospective cohort study on participants of a randomized double-blind clinical trial in which a 4-day course of topical calcipotriol plus 5-FU combination was compared to Vaseline plus 5-FU (control) for AK treatment. SCC and basal cell carcinoma (BCC) incidences were assessed at 1, 2, and 3 years after trial. Tissues were analyzed for calcipotriol plus 5-FU-induced T cell immunity in the skin.
RESULTS
Calcipotriol plus 5-FU-induced tissue-resident memory T (Trm) cell formation in face and scalp skin associated with significantly higher erythema scores compared with control (P < 0.01). Importantly, more participants in the test cohort remained SCC-free over the more than 1,500-day follow-up period (P = 0.0765), and significantly fewer developed SCC on the treated face and scalp within 3 years (2 of 30 [7%] versus 11 of 40 [28%] in control group, hazard ratio 0.215 [95% CI: 0.048-0.972], P = 0.032). Accordingly, significantly more epidermal Trm cells persisted in the calcipotriol plus 5-FU-treated face and scalp skin compared with control (P = 0.0028). There was no significant difference in BCC incidence between the treatment groups.
CONCLUSION
A short course of calcipotriol plus 5-FU treatment on the face and scalp is associated with induction of robust T cell immunity and Trm formation against AKs and significantly lowers the risk of SCC development within 3 years of treatment.
FUNDING
This research was supported by internal academic funds and by grants from the Burroughs Wellcome Fund, Sidney Kimmel Foundation, Cancer Research Institute, and NIH.
Topics: Adaptive Immunity; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Double-Blind Method; Female; Fluorouracil; Humans; Immunotherapy; Male; Middle Aged; Prospective Studies; Skin; Skin Neoplasms
PubMed: 30895944
DOI: 10.1172/jci.insight.125476 -
International Journal of Molecular... Jun 2017Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as... (Review)
Review
Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as well as an economic load to the health care system; yet treatments of these preventable cancers remain ineffective. Studies estimate that there has been a 2-fold increase in the incidence of NMSCs between the 1960s and 1980s. The increase in cases of NMSCs, as well as the lack of effective treatments, makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgently required. Research over the past few years has provided data supporting both a "bottom up" and "top down" mechanism of tumourigenesis. The "bottom up" concept involves a cancer stem cell originating in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. The "top down" concept involves a more differentiated cell undergoing genetic modifications leading to dedifferentiation, giving rise to cancer initiating cells (CICs). This review explores both concepts, to paint a picture of the skin SCC cell of origin, the underlying biology, and also how this knowledge might be exploited to develop novel therapies.
Topics: Animals; Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Dedifferentiation; DNA-Binding Proteins; Epidermis; Gene Expression Regulation, Neoplastic; Humans; Neoplastic Stem Cells; Skin; Skin Neoplasms; Transcription Factors
PubMed: 28654000
DOI: 10.3390/ijms18071369 -
Science (New York, N.Y.) May 2015How somatic mutations accumulate in normal cells is central to understanding cancer development but is poorly understood. We performed ultradeep sequencing of 74 cancer...
How somatic mutations accumulate in normal cells is central to understanding cancer development but is poorly understood. We performed ultradeep sequencing of 74 cancer genes in small (0.8 to 4.7 square millimeters) biopsies of normal skin. Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the burden of somatic mutations averaged two to six mutations per megabase per cell, similar to that seen in many cancers, and exhibited characteristic signatures of exposure to ultraviolet light. Remarkably, multiple cancer genes are under strong positive selection even in physiologically normal skin, including most of the key drivers of cutaneous squamous cell carcinomas. Positively selected mutations were found in 18 to 32% of normal skin cells at a density of ~140 driver mutations per square centimeter. We observed variability in the driver landscape among individuals and variability in the sizes of clonal expansions across genes. Thus, aged sun-exposed skin is a patchwork of thousands of evolving clones with over a quarter of cells carrying cancer-causing mutations while maintaining the physiological functions of epidermis.
Topics: Carcinoma, Squamous Cell; Clonal Evolution; Epidermis; Eyelids; Genes, Neoplasm; Humans; Mutation; Neoplasms, Radiation-Induced; Selection, Genetic; Skin Neoplasms; Tumor Burden; Ultraviolet Rays
PubMed: 25999502
DOI: 10.1126/science.aaa6806 -
Clinical Medicine (London, England) Feb 2016Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy...
Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy among Caucasians and its incidence continues to rise annually. Exposure to UV radiation initiates approximately 90% of NMSC, causing malignant transformation of keratinocytes and suppression of the inflammatory response. Risk factors include sun exposure and immunosuppression. There are several subtypes of BCC, although histological overlap is common. Surgery has traditionally been regarded as the 'gold-standard' treatment, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (radiotherapy, curettage and cautery, and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Skin; Skin Neoplasms
PubMed: 26833519
DOI: 10.7861/clinmedicine.16-1-62 -
Neoplasia (New York, N.Y.) Aug 2022Non-melanoma carcinoma has high incidence rates and has two most common subtypes: basal cell carcinoma and squamous cell carcinoma. This type of carcinoma is usually not... (Review)
Review
Non-melanoma carcinoma has high incidence rates and has two most common subtypes: basal cell carcinoma and squamous cell carcinoma. This type of carcinoma is usually not fatal; however, it can destroy sensory organs such as the nose, ears, and lips. The treatment of these injuries using non-invasive methods is thus strongly recommended. Some treatments for non-melanoma carcinoma are already well defined, such as surgery, cryosurgery, curettage and electrode section, and radiotherapy; however, these conventional treatments cause inflammation and scarring. In the non-surgical treatment of non-melanoma carcinoma, the topical administration of chemotherapeutic drugs contributes for an effective treatment with reduced side effects. However, the penetration of anticancer drugs in the deeper layers of the skin is required. Lipid delivery systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers) have been developed to overcome epidermal barrier of the skin and to allow the drugs to reach tumor cells. These lipid nanoparticles contribute to control the release profile of the loaded chemotherapeutic drugs, maintaining their stability and increasing death of tumor cells. In this review, the characteristics of non-melanoma carcinoma will be discussed, describing the main existing treatments, together with the contribution of lipid delivery systems as an innovative approach to increase the effectiveness of topical therapies for non-melanoma carcinomas.
Topics: Carcinoma; Drug Delivery Systems; Humans; Lipids; Liposomes; Nanoparticles; Skin; Skin Absorption; Skin Neoplasms
PubMed: 35649306
DOI: 10.1016/j.neo.2022.100810 -
Actas Dermo-sifiliograficas Dec 2017
Topics: Alopecia; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Clinical Trials as Topic; Cryotherapy; Female; Hair Follicle; Humans; Observational Studies as Topic; Quality of Life; Scalp; Skin Neoplasms; Vasoconstriction
PubMed: 28676145
DOI: 10.1016/j.ad.2017.04.014 -
Journal of Biomedical Optics Jun 2013Optical coherence tomography (OCT) is a noninvasive diagnostic method that offers a view into the superficial layers of the skin in vivo in real-time. An infrared... (Comparative Study)
Comparative Study Review
Optical coherence tomography (OCT) is a noninvasive diagnostic method that offers a view into the superficial layers of the skin in vivo in real-time. An infrared broadband light source allows the investigation of skin architecture and changes up to a depth of 1 to 2 mm with a resolution between 15 and 3 μm, depending on the system used. Thus OCT enables evaluation of skin lesions, especially nonmelanoma skin cancers and inflammatory diseases, quantification of skin changes, visualization of parasitic infestations, and examination of other indications such as the investigation of nails. OCT provides a quick and useful diagnostic imaging technique for a number of clinical questions and is a valuable addition or complement to other noninvasive imaging tools such as dermoscopy, high-frequency ultrasound, and confocal laser scan microscopy.
Topics: Carcinoma, Basal Cell; Dermatology; Dermoscopy; Humans; Keratosis, Actinic; Luminescent Measurements; Melanoma; Microscopy, Confocal; Optical Phenomena; Skin; Skin Diseases; Skin Neoplasms; Tomography, Optical Coherence
PubMed: 23314617
DOI: 10.1117/1.JBO.18.6.061224