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Advances in Experimental Medicine and... 2020Cutaneous melanoma is one of the most aggressive types of cancer, presenting the highest potential to form metastases, both locally and distally, which are associated... (Review)
Review
Cutaneous melanoma is one of the most aggressive types of cancer, presenting the highest potential to form metastases, both locally and distally, which are associated with high death rates of melanoma patients. A high somatic mutation burden is characteristic of these tumours, with most common oncogenic mutations occurring in the BRAF, NRAS and NF1 genes. These intrinsic oncogenic pathways contribute to the metabolic switch between glycolysis and oxidative phosphorylation metabolisms of melanoma, facilitating tumour progression and resulting in a high plasticity and adaptability to unfavourable conditions. Moreover, melanoma microenvironment can influence its own metabolism and reprogram several immune cell subset functions, enabling melanoma to evade the immune system. The knowledge of the biology, molecular alterations and microenvironment of melanoma has led to the development of new targeted therapies and the improvement of patient care. In this work, we reviewed the impact of melanoma metabolism in the resistance to BRAF and MEK inhibitors and immunotherapies, emphasizing the requirement to evaluate metabolic alterations upon development of novel therapeutic approaches. Here we summarized the current understanding of the impact of metabolic processes in melanomagenesis, metastasis and microenvironment, as well as the involvement of metabolic pathways in the immune modulation and resistance to targeted and immunocheckpoint therapies.
Topics: Cell Survival; Drug Resistance, Neoplasm; Humans; Immunotherapy; Melanoma; Molecular Targeted Therapy; Protein Kinase Inhibitors; Skin Neoplasms; Tumor Microenvironment
PubMed: 32130701
DOI: 10.1007/978-3-030-34025-4_11 -
European Journal of Cancer (Oxford,... Sep 2023Convolutional neural networks (CNNs) have outperformed dermatologists in classifying pigmented skin lesions under artificial conditions. We investigated, for the first...
Diagnostic performance of augmented intelligence with 2D and 3D total body photography and convolutional neural networks in a high-risk population for melanoma under real-world conditions: A new era of skin cancer screening?
BACKGROUND
Convolutional neural networks (CNNs) have outperformed dermatologists in classifying pigmented skin lesions under artificial conditions. We investigated, for the first time, the performance of three-dimensional (3D) and two-dimensional (2D) CNNs and dermatologists in the early detection of melanoma in a real-world setting.
METHODS
In this prospective study, 1690 melanocytic lesions in 143 patients with high-risk criteria for melanoma were evaluated by dermatologists, 2D-FotoFinder-ATBM and 3D-Vectra WB360 total body photography (TBP). Excision was based on the dermatologists' dichotomous decision, an elevated CNN risk score (study-specific malignancy cut-off: FotoFinder >0.5, Vectra >5.0) and/or the second dermatologist's assessment with CNN support. The diagnostic accuracy of the 2D and 3D CNN classification was compared with that of the dermatologists and the augmented intelligence based on histopathology and dermatologists' assessment. Secondary end-points included reproducibility of risk scores and naevus counts per patient by medical staff (gold standard) compared to automated 3D and 2D TBP CNN counts.
RESULTS
The sensitivity, specificity, and receiver operating characteristics area under the curve (ROC-AUC) for risk-score-assessments compared to histopathology of 3D-CNN with 95% confidence intervals (CI) were 90.0%, 64.6% and 0.92 (CI 0.85-1.00), respectively. While dermatologists and augmented intelligence achieved the same sensitivity (90%) and comparable classification ROC-AUC (0.91 [CI 0.80-1.00], 0.88 [CI 0.77-1.00]) with 3D-CNN, their specificity was superior (92.3% and 86.2%, respectively). The 2D-CNN (sensitivity: 70%, specificity: 40%, ROC-AUC: 0.68 [CI 0.46-0.90]) was outperformed by 3D CNN and dermatologists. The 3D-CNN showed a higher correlation coefficient for repeated measurements of 246 lesions (R = 0.89) than the 2D-CNN (R = 0.79). The mean naevus count per patient varied significantly (gold standard: 210 lesions; 3D-CNN: 469; 2D-CNN: 1324; p < 0.0001).
CONCLUSIONS
Our study emphasises the importance of validating the classification of CNNs in real life. The novel 3D-CNN device outperformed the 2D-CNN and achieved comparable sensitivity with dermatologists. The low specificity of CNNs and the lack of automated counting of TBP nevi currently limit the use of augmented intelligence in clinical practice.
Topics: Humans; Reproducibility of Results; Prospective Studies; Dermatologists; Early Detection of Cancer; Skin Neoplasms; Melanoma; Neural Networks, Computer; Nevus; Nevus, Pigmented; Risk Factors; Photography
PubMed: 37453242
DOI: 10.1016/j.ejca.2023.112954 -
Journal of Cosmetic Dermatology Dec 2022Basal cell carcinoma (BCC) is the most common skin cancer and originates from the basal layer of the epidermis. It is most common in the head and neck region. It usually...
BACKGROUND
Basal cell carcinoma (BCC) is the most common skin cancer and originates from the basal layer of the epidermis. It is most common in the head and neck region. It usually grows slowly and rarely metastasizes. The gold standard treatment is surgical excision.
AIMS
In this study, it was aimed to discuss the demographic and medical data of patients treated with the diagnosis of BCC.
PATIENTS/METHODS
Sixty-seven tumors of 55 patients who were operated for BCC in our clinic between 2016 and 2020 were retrospectively analyzed. Demographic and medical data were analyzed.
RESULTS
The tumor was most commonly localized to the nose. The most common (50%) histological type was the nodular type. Recurrence occurred in one of our patients (1.5%). Surgical margin positivity was observed in six patients.
CONCLUSIONS
Basal cell carcinomas are most common in the head and neck region. Its frequency increases with age and is more common in men. In our patients, 98.5% of the tumors were located in the head and neck, and 89.5% were over 60 years of age. Nodular is the most common type of BCC, and the most common nodular type was detected in our study. Surgical margin positivity is observed between 9% and 37.2% after surgery, and the recurrence rate is around 5%. In our study, surgical margin positivity was 9% and recurrence was 1.5%. Evaluating the excision margins carefully in a well-lit environment and taking into account cosmetic concerns, obtaining an adequately intact surgical margin in one go may lead to the ideal treatment result.
Topics: Male; Humans; Middle Aged; Aged; Retrospective Studies; Margins of Excision; Carcinoma, Basal Cell; Skin Neoplasms; Nose; Neoplasm Recurrence, Local
PubMed: 36208006
DOI: 10.1111/jocd.15441 -
Open Veterinary Journal Jan 2024Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender.
BACKGROUND
Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender.
AIM
An important objective of this work was to give a full account of the clinical, pathological, and immune-histochemical features of several skin tumors in dogs.
METHODS
This study was a case series in the hospital clinic, Faculty of Veterinary Medicine, Zagazig University, Egypt. Twenty-five dogs (14 males and 11 females) were examined clinically during the period from March 2022 to October 2023. The skin swelling was collected from affected animals and then subjected to a detailed histopathological study to record the different gross and microscopic findings and confirm the diagnosis by immunohistochemistry.
RESULTS
Skin neoplasia in dogs was exposed to various clinical signs, and the dogs' ages ranged between 3 and 11 years. Concerning tumor features, the majority of neoplasms were malignant (65.52%) more than benign (34.48%). The study revealed the presence of 29 cases of dogs showed neoplasia with different prevalence rates including squamous cell carcinoma (13.79%), mast cell tumor (6.89%), basal cell tumors (10.34%), histiocytoma (6.89%), trichoepithelioma (10.34%), transmissible venereal tumor (10.34%), trichilemmoma (3.44%), scalp paraganglioma (3.44%), pilomatricoma (10.34%), malignant melanomas (17.24%), and miscellaneous cases as fat necrosis (6.89%), in males and females dogs with different histopathological lesions and immunohistochemistry expressions for pan-cytokeratin (CK), melanocyte-differentiation antigens (S100 protein), and synaptophysin.
CONCLUSION
Malignant melanomas (17.24%) are the extremely common cutaneous tumors diagnosed in this study. Meanwhile, benign tumors such as trichilemmoma, trichoepithelioma, pilomatricoma, and paraganglioma are less frequent in dogs.
Topics: Humans; Male; Female; Dogs; Animals; Melanoma; Pilomatrixoma; Egypt; Skin Neoplasms; Paraganglioma; Mammals; Dog Diseases
PubMed: 38633166
DOI: 10.5455/OVJ.2024.v14.i1.44 -
Clinical and Translational Medicine Mar 2023Cutaneous melanoma is a lethal form of skin cancer with morbidity and mortality rates highest amongst European, North American and Australasian populations. The... (Review)
Review
BACKGROUND
Cutaneous melanoma is a lethal form of skin cancer with morbidity and mortality rates highest amongst European, North American and Australasian populations. The developments of targeted therapies (TTs) directed at the oncogene BRAF and its downstream mediator MEK, and immune checkpoint inhibitors (ICI), have revolutionized the treatment of metastatic melanoma, improving patient outcomes. However, both TT and ICI have their limitations. Although TTs are associated with high initial response rates, these are typically short-lived due to resistance. Conversely, although ICIs provide more durable responses, they have lower initial response rates. Due to these distinct yet complementary response profiles, it has been proposed that sequencing ICI with TT could lead to a high frequency of durable responses whilst circumventing the toxicity associated with combined ICI + TT treatment. However, several questions remain unanswered, including the mechanisms underpinning this synergy and the optimal sequencing strategy. The key to determining this is to uncover the biology of each phase of the therapeutic response.
AIMS AND METHODS
In this review, we show that melanoma responds to TT and ICI in three phases: early response, minimal residual disease (MRD) and disease progression. We explore the effects of ICI and TT on melanoma cells and the tumour immune microenvironment, with a particular focus on MRD which is predicted to underpin the development of acquired resistance in the third phase of response.
CONCLUSION
In doing so, we provide a new framework which may inform novel therapeutic approaches for melanoma, including optimal sequencing strategies and agents that target MRD, thereby ultimately improving clinical outcomes for patients.
Topics: Humans; Melanoma; Skin Neoplasms; Neoplasm, Residual; Immunotherapy; Tumor Microenvironment
PubMed: 36967556
DOI: 10.1002/ctm2.1197 -
Experimental Dermatology May 2020The protective effect of ultraviolet (UV) light against a host of malignancies is well characterised. It was recognised by WHO in their 2006 publication on the global...
The protective effect of ultraviolet (UV) light against a host of malignancies is well characterised. It was recognised by WHO in their 2006 publication on the global burden of UV-mediated disease. The mechanism by which this oncoprotective effect occurs remains unclear. Vitamin D has been mooted as a potential mediator. However, the evidence does not support this. I suggest that UV irradiation of the skin produces nascent malignant and premalignant cells with associated generic tumor-specific antigens. These are eliminated by immunosurveillance resulting in adaptive immunity. The clonal expansion of these immune cells protects against tumors in other viscera, effectively immunising the host. The evidence for this "heliovaccination" is very strong. Childhood UV exposure protects against cancer in adulthood. Tumor naïve individuals possess anti-tumor antibodies. Antigen-presenting cells mobilise to the skin following specifically UVB skin irradiation. It is time to rethink the link between UV light and cancer.
Topics: Adaptive Immunity; Adult; Animals; Antigens, Neoplasm; Child; Humans; Models, Theoretical; Mutation; Neoplasms; Phagocytosis; Skin; Skin Neoplasms; Sunlight; Ultraviolet Rays; Vitamin D
PubMed: 32073173
DOI: 10.1111/exd.14087 -
Plastic and Reconstructive Surgery Apr 2022Nail unit squamous cell carcinoma and melanoma are the most common malignancies of the nail apparatus. Compared to their cutaneous counterparts, they are diagnosed later... (Review)
Review
Nail unit squamous cell carcinoma and melanoma are the most common malignancies of the nail apparatus. Compared to their cutaneous counterparts, they are diagnosed later and perceived as more aggressive. This may result in overzealous management, including radiographic imaging with poor sensitivity and specificity, interventional nodal staging by sentinel lymph node biopsy, amputation over digit-sparing tumor resections, and elaborate reconstructions after tumor extirpation. In this review article, the authors evaluate the evidence behind several misconceptions in nail malignancy management and provide evidence-based guidance for more conservative care.
Topics: Conservative Treatment; Humans; Melanoma; Nails; Neoplasm Staging; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 35157617
DOI: 10.1097/PRS.0000000000008968 -
International Journal of Molecular... Apr 2021Neoplasms derived from follicular tissue are extremely rare. Clinically, they are reported as non-symptomatic, slow-growing nodules. These lesions are mainly benign, but... (Review)
Review
Neoplasms derived from follicular tissue are extremely rare. Clinically, they are reported as non-symptomatic, slow-growing nodules. These lesions are mainly benign, but the malignant type can occur. Mainly middle-aged people (50-60 years of age) are affected. These carcinomas are mainly localized on the head and neck or torso. They can be locally aggressive and infiltrate surrounding tissue and metastasize to regional lymph nodes. In the minority of cases, distant metastases are diagnosed. Quick and relevant diagnosis is the basis of a treatment for all types of tumors. The patient's life expectancy depends on multiple prognostic factors, including the primary tumor size and its mitotic count. Patients should be referred to a specialized skin cancer center to receive optimal multidisciplinary treatment. This article tries to summarize all the information that is currently available about pathogenesis, diagnosis, and treatment methods of follicular tumors.
Topics: Animals; Carcinogenesis; Disease Management; Humans; Neoplasms, Glandular and Epithelial; Skin; Skin Neoplasms
PubMed: 33946233
DOI: 10.3390/ijms22094759 -
Surgical Oncology Clinics of North... Jul 2020Stage IV melanoma has a 5-year survival rate of 6%, but considerable advances have been made in systemic therapies. Systemic immunotherapy has achieved durable responses... (Review)
Review
Stage IV melanoma has a 5-year survival rate of 6%, but considerable advances have been made in systemic therapies. Systemic immunotherapy has achieved durable responses in up to 40% of patients, with similar improvements with targeted therapies. This has reshaped the landscape for surgery in stage IV melanoma. Metastasectomy can be considered in patients on systemic immunotherapy or targeted therapy with responding, stable, or isolated progressing lesions, oligometastatic disease, or long disease-free intervals. Surgery plays a role in providing tumor tissue for preparation of tumor-infiltrating lymphocytes for adoptive cell therapy. Surgical palliation plays a role in patients with symptomatic metastases.
Topics: Humans; Melanoma; Metastasectomy; Neoplasm Staging; Skin Neoplasms
PubMed: 32482322
DOI: 10.1016/j.soc.2020.02.010 -
Pediatric Radiology Oct 2021Cutaneous lesions present a diagnostic challenge to radiologists and clinicians alike. Pilomatricoma is the second most common skin neoplasm in childhood, yet there are...
BACKGROUND
Cutaneous lesions present a diagnostic challenge to radiologists and clinicians alike. Pilomatricoma is the second most common skin neoplasm in childhood, yet there are limited reports in the literature focusing on imaging in pediatric patients.
OBJECTIVE
To characterize the typical and atypical US features of pilomatricoma in pediatric patients and to determine the performance of the adult-based Solivetti classification for assessing pilomatricomas in children.
MATERIALS AND METHODS
We retrospectively reviewed 169 US scans of pathologically proven pilomatricomas in 156 children performed over a period of 66 months. We evaluated images for the size of the lesion, borders, morphology, content, calcification, location on the skin and Doppler characteristics.
RESULTS
Most of the pilomatricomas presented as single dermohypodermic lesions with peripheral vascularity on color Doppler interrogation. The cheek was the most common location, followed by the arm. Solivetti type 2 US pattern was the most frequent, and peripheral hypoechoic halo was only observed in this type. One child had an anetodermic pilomatricoma, and 11 children had multiple lesions.
CONCLUSION
We showed that pilomatricomas exhibit variable sonographic patterns. In our cohort, less than 50% of the lesions showed the characteristic hypoechoic rim and less than 30% of the cases presented as diffusely hyperechoic masses with posterior acoustic shadowing. Our results show that the Solvetti classification for the US assessment of pilomatricomas can be of value in children.
Topics: Adult; Child; Hair Diseases; Humans; Pilomatrixoma; Retrospective Studies; Skin Neoplasms; Ultrasonography
PubMed: 34255110
DOI: 10.1007/s00247-021-05124-6