Guidelines of care for the management of primary cutaneous melanoma Bichakjian, Christopher K., MD; Halpern, Allan C., MD (Co-chair); Johnson, Timothy M., MD (Co-chair) ...
Journal of the American Academy of Dermatology,
11/2011, Letnik:
65, Številka:
5
Journal Article
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The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer–related deaths, but treatment is nearly always ...curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.
Do inflammatory pathways drive melanomagenesis? Schneider, Samantha L.; Ross, Andrew L.; Grichnik, James M.
Experimental dermatology,
February 2015, Letnik:
24, Številka:
2
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Inflammatory pathways serve to protect the host and promote tissue healing/repair; however, over‐activation or dysregulation can be pathological with unintended consequences including malignant ...progression. A correlation between inflammation and cancer has been well established, and anti‐inflammatory medications have been shown to be chemopreventive in certain malignancies. Data are now becoming available that outline an inflammatory pathway that may have a critical role in melanomagenesis. ATP‐regulated membrane channels/receptors P2X7 and PANX1 have been directly implicated in melanoma tumor growth. Among other potential effects, opening of the P2X7/PANX1 channel results in activation of the NALP3 inflammasome, which in turn leads to caspase‐1 activation and increased levels of activated IL‐1β. Elevated levels of caspase‐1 and IL‐1β have been correlated with melanoma progression, and inhibitors of the inflammasome, caspase and IL‐1β activity have all been shown to inhibit melanoma growth. Among many other potential actions, IL‐1β increases cyclooxygenase‐2 expression leading to local increases in inflammatory mediators such as prostaglandin E2 (PGE2). Anti‐inflammatory medications targeting the end of this pathway have had positive results for certain cancers but overall remain mixed for melanoma. A better understanding of the pathways and appropriate intervention points may help direct future therapies. In this viewpoint, we will review data and attempt to model an inflammatory pathway that may be critical for melanomagenesis and propose future directions for exploration.
Background: As a result of advances in skin imaging technology and the development of suitable image processing techniques, during the last decade, there has been a significant increase of interest ...in the computer‐aided diagnosis of melanoma. Automated border detection is one of the most important steps in this procedure, because the accuracy of the subsequent steps crucially depends on it.
Methods: In this article, we present a fast and unsupervised approach to border detection in dermoscopy images of pigmented skin lesions based on the statistical region merging algorithm.
Results: The method is tested on a set of 90 dermoscopy images. The border detection error is quantified by a metric in which three sets of dermatologist‐determined borders are used as the ground‐truth. The proposed method is compared with four state‐of‐the‐art automated methods (orientation‐sensitive fuzzy c‐means, dermatologist‐like tumor extraction algorithm, meanshift clustering, and the modified JSEG method).
Conclusion: The results demonstrate that the method presented here achieves both fast and accurate border detection in dermoscopy images.
Background Acral lentiginous melanoma has increased mortality compared with other melanoma subtypes and disproportionately affects ethnic minorities. Acral melanocytic lesions have not been well ...studied in diverse populations of the United States. Objective We sought to assess the prevalence, awareness, and dermoscopic patterns of acral melanocytic lesions in skin-of-color and non-Hispanic white patients. Methods We prospectively examined the palms and soles of 1052 patients presenting to dermatology clinics in New York, NY, and Miami, FL, from October 2013 to April 2015. Results Acral melanocytic lesions were observed in 36% of our cohort. Skin-of-color patients were more likely to have acral melanocytic lesions than non-Hispanic white patients ( P < .01). Acral melanocytic lesions correlated with increased mole counts, particularly on non-Hispanic white patients. The majority of lesions demonstrated benign dermoscopic patterns. We observed 2 lesions with the parallel ridge pattern in our cohort, both found to be atypical nevi on biopsy specimen. Patients often lacked awareness of the presence of their lesions. Limitations Interobserver variability in assessing dermoscopic patterns is a limitation. Conclusions Melanocytic lesions of the palms and soles are common, particularly in a cohort of multiple ethnicities from the United States. Dermoscopy of acral lesions is an important clinical tool for diagnosis and management of these lesions.
Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15% L-ascorbic acid and 1% α-tocopherol improved chemical stability of the vitamins (C+E) and ...doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer.
Hair graying holds psychosocial importance and serves as an excellent model for studying human pigmentation and aging in an accessible miniorgan. Current evidence suggests that graying results from ...an interindividually varying mixture of cumulative oxidative and DNA damage, excessive mTORC1 activity, melanocyte senescence, and inadequate production of pigmentation-promoting factors in the hair matrix. Various regulators modulate this process, including genetic factors (DNA repair defects and IRF4 sequence variation, peripheral clock genes, P-cadherin signaling, neuromediators, HGF, KIT ligand secretion, and autophagic flux. This leads to reduced MITF- and tyrosinase-controlled melanogenesis, defective melanosome transfer to precortical matrix keratinocytes, and eventual depletion of hair follicle (HF) pigmentary unit (HFPU) melanocytes and their local progenitors. Graying becomes irreversible only when bulge melanocyte stem cells are also depleted, occurring later in this process. Distinct pigmentary microenvironments are created as the HF cycles: early anagen is the most conducive phase for melanocytic reintegration and activation, and only during anagen can the phenotype of hair graying and repigmentation manifest, whereas the HFPU disassembles during catagen. The temporary reversibility of graying is highlighted by several drugs and hormones that induce repigmentation, indicating potential target pathways. We advise caution in directly applying mouse model concepts, define major open questions, and discuss future human antigraying strategies.
Melanocytic neoplasms are a diverse group of benign and malignant tumors with variable clinical features. While some models still promote the epidermal melanocyte as the origin of melanocytic ...neoplasms, clinical findings are inconsistent with this theory for the majority of tumors. Despite advances in naevus and melanoma biology, the location and differentiation status of the cell of origin remains undefined. Germ line genetics, biological state and cellular location of the mutated cell, as well as local environmental factors all likely play a role in the development of melanocytic neoplasms. Herein, we will review potential models for melanocytic neoplasia and discuss research challenges and opportunities.
Background: Virtually all plants and animals protect themselves from the sun using vitamins C and E. Objective: The purpose of this study was to see if a combination of topical vitamins C and E is ...better for UV protection to skin than an equivalent concentration of topical vitamin C or E alone. Methods: We developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1% α-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5× minimal erythema dose) control- and antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter. On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and thymine dimers. Results: The combination of 15% L-ascorbic acid and 1% α-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% α-tocopherol alone also was protective but the combination was superior. Application during 4 days provided progressive protection that yielded an antioxidant protection factor of 4-fold. In addition, the combination of vitamins C and E provided protection against thymine dimer formation. Conclusion: Appreciable photoprotection can be obtained from the combination of topical vitamins C and E. We suggest that these natural products may protect against skin cancer and photoaging. (J Am Acad Dermatol 2003;48:866-74.)
Molecular Nevogenesis Ross, Andrew L.; Sanchez, Margaret I.; Grichnik, James M.
Dermatology Research and Practice,
01/2011, Letnik:
2011
Journal Article
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Despite recent advances, the biology underlying nevogenesis remains unclear. Activating mutations in NRAS, HRAS, BRAF, and GNAQ have been identified in benign nevi. Their presence roughly correlates ...with congenital, Spitz, acquired, and blue nevi, respectively. These mutations are likely to play a critical role in driving nevogenesis. While each mutation is able to activate the MAP kinase pathway, they also interact with a host of different proteins in other pathways. The different melanocytic developmental pathways activated by each mutation cause the cells to migrate, proliferate, and differentiate to different extents within the skin. This causes each mutation to give rise to a characteristic growth pattern. The exact location and differentiation state of the cell of origin for benign moles remains to be discovered. Further research is necessary to fully understand nevus development given that most of the same developmental pathways are also present in melanoma.
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