Melanocytic neoplasms are a diverse group of benign and malignant tumors with variable clinical f... more 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.
Embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells expanded in vitro... more Embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells expanded in vitro exhibit genomic instability. Commonly reported abnormalities include aneuploidy, deletions and duplications (including regions also amplified in cancer). Genomic instability confers an increased risk of malignant transformation that may impact the safety of cultured stem cell transplantation. Possible mechanisms responsible for this genomic instability include DNA repair mechanism abnormalities, telomere crisis, mitotic spindle abnormalities and inappropriate induction of meiotic pathways. Prior to widespread use of these cells in regenerative medicine, it will be critical to gain an understanding of the mechanisms responsible for genomic instability to develop strategies to prevent the accrual of chromosomal defects during expansion in vitro.
Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution ... more 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
The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few da... more The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. A consensus statement by the PLS of the MPWG following review of the ...
Mutations driving melanoma growth have diagnostic, prognostic, and therapeutic implications. Trad... more Mutations driving melanoma growth have diagnostic, prognostic, and therapeutic implications. Traditional classification systems do not correlate optimally with underlying melanoma growth-promoting mutations. Our objective was to determine whether unique dermoscopic growth patterns directly correlate with driving mutations. We evaluated common driving mutations in 4 different dermoscopic patterns (rhomboidal, negative pigmented network, polygonal, and dark homogeneous streaks) of primary cutaneous melanomas; 3 melanomas per pattern were tested. Three of the 4 patterns lacked common mutations in BRAF, NRAS, KIT, GNAQ, and HRAS. One pattern, the dark homogeneous streaks pattern, had unique KIT mutations in the second catalytic domain of KIT in exon 17 for all 3 samples tested. Two tumors with the dark homogeneous streaks pattern turned out to be different primary melanomas from the same patient and had different sequence mutations but had an impact on the same KIT domain. While future ...
Mission Statement: The Archives of Dermatology publishes information concerning the skin, its dis... more Mission Statement: The Archives of Dermatology publishes information concerning the skin, its diseases, and their treatment. Its mission is to explicate the structure and function of the skin and its diseases and the art of using this information to deliver optimal medical and surgical care to the patient .W e attempt to enhance the understanding of cutaneous pathophysiology and improve
Journal of the American Academy of Dermatology, 2003
There is a need for better standardization of the dermoscopic terminology in assessing pigmented ... more There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.
Melanocytic neoplasms are a diverse group of benign and malignant tumors with variable clinical f... more 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.
Embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells expanded in vitro... more Embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells expanded in vitro exhibit genomic instability. Commonly reported abnormalities include aneuploidy, deletions and duplications (including regions also amplified in cancer). Genomic instability confers an increased risk of malignant transformation that may impact the safety of cultured stem cell transplantation. Possible mechanisms responsible for this genomic instability include DNA repair mechanism abnormalities, telomere crisis, mitotic spindle abnormalities and inappropriate induction of meiotic pathways. Prior to widespread use of these cells in regenerative medicine, it will be critical to gain an understanding of the mechanisms responsible for genomic instability to develop strategies to prevent the accrual of chromosomal defects during expansion in vitro.
Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution ... more 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
The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few da... more The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. A consensus statement by the PLS of the MPWG following review of the ...
Mutations driving melanoma growth have diagnostic, prognostic, and therapeutic implications. Trad... more Mutations driving melanoma growth have diagnostic, prognostic, and therapeutic implications. Traditional classification systems do not correlate optimally with underlying melanoma growth-promoting mutations. Our objective was to determine whether unique dermoscopic growth patterns directly correlate with driving mutations. We evaluated common driving mutations in 4 different dermoscopic patterns (rhomboidal, negative pigmented network, polygonal, and dark homogeneous streaks) of primary cutaneous melanomas; 3 melanomas per pattern were tested. Three of the 4 patterns lacked common mutations in BRAF, NRAS, KIT, GNAQ, and HRAS. One pattern, the dark homogeneous streaks pattern, had unique KIT mutations in the second catalytic domain of KIT in exon 17 for all 3 samples tested. Two tumors with the dark homogeneous streaks pattern turned out to be different primary melanomas from the same patient and had different sequence mutations but had an impact on the same KIT domain. While future ...
Mission Statement: The Archives of Dermatology publishes information concerning the skin, its dis... more Mission Statement: The Archives of Dermatology publishes information concerning the skin, its diseases, and their treatment. Its mission is to explicate the structure and function of the skin and its diseases and the art of using this information to deliver optimal medical and surgical care to the patient .W e attempt to enhance the understanding of cutaneous pathophysiology and improve
Journal of the American Academy of Dermatology, 2003
There is a need for better standardization of the dermoscopic terminology in assessing pigmented ... more There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.
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Papers by James Grichnik