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Melanoma: HELP
Articles by David E. Elder
Based on 73 articles published since 2010
(Why 73 articles?)
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Between 2010 and 2020, D. Elder wrote the following 73 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Guidelines of care for the management of primary cutaneous melanoma. 2019

Swetter, Susan M / Tsao, Hensin / Bichakjian, Christopher K / Curiel-Lewandrowski, Clara / Elder, David E / Gershenwald, Jeffrey E / Guild, Valerie / Grant-Kels, Jane M / Halpern, Allan C / Johnson, Timothy M / Sober, Arthur J / Thompson, John A / Wisco, Oliver J / Wyatt, Samantha / Hu, Shasa / Lamina, Toyin. ·Department of Dermatology, Stanford University Medical Center and Cancer Institute, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California. Electronic address: sswetter@stanford.edu. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Wellman Center for Photomedicine, Boston, Massachusetts. · Department of Dermatology, University of Michigan Health System, Ann Arbor, Michigan; Comprehensive Cancer Center, Ann Arbor, Michigan. · Division of Dermatology, University of Arizona, Tucson, Arizona; University of Arizona Cancer Center, Tucson, Arizona. · Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. · AIM at Melanoma Foundation, Plano, Texas. · Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut; Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut; Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut. · Department of Dermatology, Memorial Sloan-Kettering Cancer Center, New York, New York. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Division of Oncology, University of Washington, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington. · Department of Dermatology, Oregon Health and Science University, Portland, Oregon. · Decatur Dermatology, Decatur, Alabama. · Department of Dermatology, University of Miami Health System, Miami, Florida. · American Academy of Dermatology, Rosemont, Illinois. ·J Am Acad Dermatol · Pubmed #30392755.

ABSTRACT: The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.

2 Editorial Melanoma Screening and Mortality. 2018

Elder, David E. ·Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA. ·J Natl Cancer Inst · Pubmed #29618115.

ABSTRACT: -- No abstract --

3 Editorial Point: What's in a name? 2015

Elder, David E. ·Anatomic Pathology, University of Pennsylvania Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. ·J Am Acad Dermatol · Pubmed #26282798.

ABSTRACT: -- No abstract --

4 Review Pathology of melanoma. 2015

Elder, David E. ·Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA. Electronic address: David.Elder@uphs.upenn.edu. ·Surg Oncol Clin N Am · Pubmed #25769708.

ABSTRACT: The pathology of melanoma is discussed in relation to surgical diagnosis and management. Pitfalls that may result in problems of clinicopathologic communication are emphasized. A compelling vision for the future is that all tumors will be characterized by their driving oncogenes, suppressor genes, and other genomic factors. The success of targeted therapy directed against individual oncogenes, despite its limitations, suggests that a repertoire of targeted agents will be developed that can be used against a variety of different tumors, depending on the results of genetic testing. Nevertheless, histopathologic diagnosis and surgical therapy will remain mainstays of management for melanoma.

5 Review Pathological staging of melanoma. 2014

Elder, David E. ·Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. ·Methods Mol Biol · Pubmed #24258986.

ABSTRACT: Staging of cancer is a shorthand system of describing the extent of disease. Pathological staging, often called microstaging, uses the methods of histopathology to achieve this goal. Microstaging for melanoma utilizes attributes that are associated with outcome, generally in association with prognostic models that allow for estimation of survival rates, based on large groups of patients with similar tumors. Microstaging can be performed on primary tumors and to a lesser extent on metastases. Attributes that are important in microstaging in primary tumors include, in particular, those that are utilized in the AJCC/UICC staging system. These are, more or less in order of importance, Breslow's thickness, ulceration, and mitogenicity (the presence or absence of mitoses). Other attributes that have relevance to prognosis at least in some well-conducted studies include tumor-infiltrating lymphocytes, lymphovascular invasion, perineural invasion, Clark's level of invasion, the presence or absence of vertical growth phase and of regression, and other attributes. The pathologic interpretation and significance of these "prognostic variables" are discussed in this chapter. In addition, prognostic models including the AJCC staging system are presented in some detail.

6 Review Thin melanoma. 2011

Elder, David E. ·Department of Pathology and Laboratory Medicine, Division of Anatomic Pathology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA. elder@mail.med.upenn.edu ·Arch Pathol Lab Med · Pubmed #21366458.

ABSTRACT: CONTEXT: The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies. OBJECTIVE: To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas. DATA SOURCES: Selected literature. CONCLUSIONS: About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing thickness, modified by ulceration, mitotic rate, and other attributes.

7 Review Prognostic models for melanoma. 2010

Elder, David E. ·Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. David.Elder@uphs.upenn.edu ·J Cutan Pathol · Pubmed #20482678.

ABSTRACT: -- No abstract --

8 Review Dysplastic naevi: an update. 2010

Elder, David E. ·Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. David.Elder@uphs.upenn.edu ·Histopathology · Pubmed #20055909.

ABSTRACT: Dysplastic naevi are clinically atypical and histologically are characterized by architectural disorder and cytological atypia. Their diagnosis is reproducible if criteria and thresholds are agreed upon. They are significant only in relation to melanoma, as simulants of melanoma, as markers of individuals at increased risk of developing melanoma, and as potential and occasional actual precursors of melanoma. Morphologically and biologically, they are intermediate between common naevi and melanoma. Individuals with dysplastic naevi may have deficient DNA repair, and dysplastic naevi lesions are associated with overexpression of pheomelanin, which may lead to increased oxidative damage and increased potential for DNA damage and tumour progression.

9 Clinical Trial The self-reported use of immunostains and cytogenetic testing in the diagnosis of melanoma by practicing U.S. pathologists of 10 selected states. 2016

Zhao, Ge / Lee, Kachiu C / Kwon, Gina / Frederick, Paul D / Onega, Tracy L / Piepkorn, Michael W / Knezevich, Stevan / Barnhill, Raymond L / Elder, David E / Elmore, Joann G. ·Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. · Department of Dermatology, Massachusetts General Hospital, Harvard University, Boston, MA, USA. · Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. · Department of Biomedical Data Science, Norris Cotton Cancer Center, Lebanon, NH, USA. · Department of Epidemiology, Norris Cotton Cancer Center, Lebanon, NH, USA. · Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH, USA. · Dermatopathology Northwest, Bellevue, WA, USA. · Pathology Associates, Clovis, CA, USA. · Department of Pathology, Faculty of Medicine, University of Paris Descartes, Paris, France. · Institut Curie, Paris, France. · Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA. ·J Cutan Pathol · Pubmed #26968847.

ABSTRACT: BACKGROUNDS: The diagnosis of melanoma can be challenging, especially in lesions for which the histopathologic criteria bridge two or more taxonomic categories. Newer genomic analytical methods of fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have been introduced as ancillary techniques to differentiate benign and malignant melanocytic proliferations. METHODS: We evaluated how pathologists perceive and are incorporating these new cytogenetic testing technologies into their practices. We conducted a study of 207 U.S. pathologists who interpret melanocytic lesions in clinical practice in 10 SEER states. Pathologists were surveyed regarding perceptions and utilization of FISH and/or CGH in their clinical practices. RESULTS: Results showed that 38% of pathologists use FISH and/or CGH in interpreting melanocytic lesions. Pathologists reporting FISH and/or CGH use were significantly younger (p < 0.05), were fellowship trained or board certified in dermatopathology (p < 0.001) and were affiliated with an academic institute (p < 0.001). Pathologists reporting that their colleagues consider them an expert in the assessment of melanocytic lesions were more likely to employ FISH and/or CGH in their practices than non-experts. CONCLUSIONS: Early users of cytogenetic testing technologies in cutaneous pathology are more likely to be younger, affiliated with an academic institution and fellowship trained or board certified in dermatopathology.

10 Clinical Trial Clark level risk stratifies patients with mitogenic thin melanomas for sentinel lymph node biopsy. 2014

Bartlett, Edmund K / Gimotty, Phyllis A / Sinnamon, Andrew J / Wachtel, Heather / Roses, Robert E / Schuchter, Lynn / Xu, Xiaowei / Elder, David E / Ming, Michael / Elenitsas, Rosalie / Guerry, DuPont / Kelz, Rachel R / Czerniecki, Brian J / Fraker, Douglas L / Karakousis, Giorgos C. ·Department of Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA, Edmund.Bartlett@uphs.upenn.edu. ·Ann Surg Oncol · Pubmed #24121883.

ABSTRACT: BACKGROUND: The role for sentinel lymph node biopsy (SLNB) in patients with thin melanoma (≤1 mm) remains controversial. We examined a large cohort of patients with thin melanoma to better define predictors of SLN positivity. METHODS: From 1995 to 2011, 781 patients with thin primary melanoma and evaluable clinicopathologic data underwent SLNB at our institution. Predictors of SLN positivity were determined using univariate and multivariate regression analyses, and patients were risk-stratified using a classification and regression tree (CART) analysis. RESULTS: In the study cohort (n = 781), 29 patients (3.7%) had nodal metastases. In the univariate analysis, mitotic rate [odds ratio (OR) = 8.11, p = 0.005], Clark level (OR 4.04, p = 0.003), and thickness (OR 3.33, p = 0.011) were significantly associated with SLN positivity. In the multivariate analysis, MR (OR 7.01) and level IV-V (OR 3.45) remained significant predictors of SLN positivity. CART analysis initially stratified lesions by mitotic rate; nonmitogenic lesions (n = 273) had a 0.7% SLN positivity rate versus 5.6% in mitogenic lesions (n = 425). Mitogenic lesions were further stratified by Clark level; patients with level II-III had a 2.9% SLN positivity rate (n = 205) versus 8.2% with level IV-V (n = 220). With median follow-up of 6.3 years, five SLN-negative patients developed nodal recurrence and four SLN-positive patients died of disease. CONCLUSIONS: SLN positivity is low in patients with thin melanoma (3.7%) and exceedingly so in nonmitogenic lesions (0.7%). Appreciable rates of SLN positivity can be identified in patients with mitogenic lesions, particularly with concurrent level IV-V regardless of thickness. These factors may guide appropriate selection of patients with thin melanoma for SLNB.

11 Clinical Trial Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma. 2012

Xu, Xiaowei / Chen, Lianjun / Guerry, DuPont / Dawson, Peter R / Hwang, Wei-ting / VanBelle, Patricia / Elder, David E / Zhang, Paul J / Ming, Michael E / Schuchter, Lynn / Gimotty, Phyllis A. ·Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ·Clin Cancer Res · Pubmed #22096024.

ABSTRACT: PURPOSE: Lymphatic invasion (LI) in primary cutaneous melanomas was recently found to be common. In this study, we evaluated LI as an independent prognostic factor. EXPERIMENTAL DESIGN: This study included 251 patients with vertical growth phase (VGP) primary cutaneous melanomas who had paraffin-fixed lesional tissue and were in a prospective cohort seen between 1972 and 1991, had no clinical evidence of regional nodal disease at diagnosis, and had at least ten years of follow-up. Dual immunohistochemical staining was used to detect lymphatic endothelium (podoplanin) and melanoma cells (S-100). Multivariate logistic regression for ten-year metastasis was used to define independent prognostic factors, and a prognostic tree was developed to characterize and discriminate risk groups. Kaplan-Meier disease-free survival curves for those with and without LI within current American Joint Committee on Cancer stages were compared using the log-rank statistic. RESULTS: LI was observed in 43% (108 of 251) of the study melanomas. The multivariate model for ten-year metastasis identified four independent prognostic factors: tumor thickness, mitotic rate, LI, and anatomic site. The prognostic tree identified a group of patients with thin (≤1 mm thick) melanomas and poor prognosis: stage IB melanomas with LI. Survival curves for time to first metastasis showed significantly poorer prognosis for patients with LI compared with those without it for both stages IB and IIA. CONCLUSIONS: LI is common across the range of tumor thicknesses in primary VGP melanomas. It is an independent prognostic factor and significantly increases the risk of metastasis in patients in clinical stages IB and IIA.

12 Clinical Trial Sunbeds and sunlamps: who used them and their risk for melanoma. 2011

Fears, Thomas R / Sagebiel, Richard W / Halpern, Allan / Elder, David E / Holly, Elizabeth A / Guerry, Dupont / Tucker, Margaret A. ·Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ·Pigment Cell Melanoma Res · Pubmed #21362155.

ABSTRACT: Sunbed/sunlamp use was recently classified as carcinogenic. This report considers characteristics of those who use sunbeds/sunlamps and the effect of sunbed/sunlamp use on their risk for melanoma within a large case-control study carried out in 1991-1992. Females were more likely than males to have used sunbeds/sunlamps. Use by females increased strongly and significantly with younger ages and with the perceived ability to tan. For females, the individual risk for melanoma increased with typical session time and frequency of sessions. Use before age 20, current use and years of use were not significant. The use patterns of occasional and frequent users were very different. We estimate that typical 5-min sessions would increase the risk for melanoma by 19% for frequent users (10+ sessions) and by 3% for occasional users (1-9 sessions). Body sites that are not generally exposed to sunlight were more common sites of primary melanomas for frequent sunbed/sunlamp users. For males, measures of sunbed/sunlamp use were not significantly associated with melanoma risk.

13 Article Factors associated with use of immunohistochemical markers in the histopathological diagnosis of cutaneous melanocytic lesions. 2020

May, Caitlin J / Piepkorn, Michael W / Knezevich, Stevan R / Elder, David E / Barnhill, Raymond L / Lee, Annie C / Flores, Martiniano J / Kerr, Kathleen F / Reisch, Lisa / Elmore, Joann G. ·Dermatopathology Northwest, Bellevue, WA, USA. · ivision of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. · Pathology Associates, Clovis, California, USA. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Departments of Pathology and Translational Research, Institut Curie, University of Paris Descartes, Paris, France. · Division of General Internal Medicine and Health Services Research, UCLA David Geffen School of Medicine, Los Angeles, California, USA. · Edwards Lifesciences, Irvine, California, USA. · Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA. · Division of Dermatology, UCLA David Geffen School of Medicine, Los Angeles, California, USA. ·J Cutan Pathol · Pubmed #32383301.

ABSTRACT: BACKGROUND: Melanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized. METHODS: A test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions. RESULTS: Of 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1-6 cases, and 81 (43%) requested testing for ≥ six cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board-certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH-Dx classes 2-4. The median intra-observer concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%-90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39). CONCLUSION: Substantial variability exists amongst pathologists in utilizing IHC. This article is protected by copyright. All rights reserved.

14 Article Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain. 2020

Sargen, Michael R / Calista, Donato / Elder, David E / Massi, Daniela / Chu, Emily Y / Potrony, Míriam / Pfeiffer, Ruth M / Carrera, Cristina / Aguilera, Paula / Alos, Llucia / Puig, Susana / Elenitsas, Rosalie / Yang, Xiaohong R / Tucker, Margaret A / Landi, Maria Teresa / Goldstein, Alisa M. ·Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. Electronic address: michael.sargen@nih.gov. · Department of Dermatology, Maurizio Bufalini Hospital, Cesena, Italy. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA. · Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy. · Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, PA. · Dermatology Department, Melanoma Unit, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. · Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. · Pathology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain. · Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. · Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. · Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. ·J Am Acad Dermatol · Pubmed #32283231.

ABSTRACT: BACKGROUND: CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes. OBJECTIVE: We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1. METHODS: We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and non-carriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family. RESULTS: Histologic slides were evaluated for 290 melanomas (139 from 132 non-carriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in the majority of invasive melanomas from POT1 carriers (10 of 15 [67%], P<.0001 vs. non-carriers). This finding was independently confirmed by three expert melanoma dermatopathologists in 9 of 15 (60%) invasive melanomas. In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from non-carriers. LIMITATIONS: Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1) CONCLUSION: Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to Spitzoid differentiation in melanocytic tumors.

15 Article Pathologists' agreement on treatment suggestions for melanocytic skin lesions. 2020

Jafry, Mustufa A / Peacock, Sue / Radick, Andrea C / Shucard, Hannah L / Reisch, Lisa M / Piepkorn, Michael W / Knezevich, Stevan R / Weinstock, Martin A / Barnhill, Raymond L / Elder, David E / Kerr, Kathleen F / Elmore, Joann G. ·Department of Medicine, University of Washington School of Medicine, Seattle, Washington. · Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Dermatopathology Northwest, Bellevue, Washington. · Pathology Associates, Clovis, California. · Center for Dermatoepidemiology, Providence VA Medical Center, Providence, Rhode Island; Departments of Dermatology and Epidemiology, Brown University, Providence, Rhode Island. · Department of Pathology, Institut Curie, Paris Sciences and Lettres Research University; Faculty of Medicine, University of Paris Descartes, Paris, France. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Biostatistics, University of Washington, Seattle, Washington. · Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California. Electronic address: jelmore@mednet.ucla.edu. ·J Am Acad Dermatol · Pubmed #31862403.

ABSTRACT: BACKGROUND: Although treatment guidelines exist for melanoma in situ and invasive melanoma, guidelines for other melanocytic skin lesions do not exist. OBJECTIVE: To examine pathologists' treatment suggestions for a broad spectrum of melanocytic skin lesions and compare them with existing guidelines. METHODS: Pathologists (N = 187) completed a survey and then provided diagnoses and treatment suggestions for 240 melanocytic skin lesions. Physician characteristics associated with treatment suggestions were evaluated with multivariable modeling. RESULTS: Treatment suggestions were concordant with National Comprehensive Cancer Network guidelines for the majority of cases interpreted as melanoma in situ (73%) and invasive melanoma (86%). Greater variability of treatment suggestions was seen for other lesion types without existing treatment guidelines. Characteristics associated with provision of treatment suggestions discordant with National Comprehensive Cancer Network guidelines were low caseloads (invasive melanoma), lack of fellowship training or board certification (melanoma in situ), and more than 10 years of experience (invasive melanoma and melanoma in situ). LIMITATIONS: Pathologists could not perform immunohistochemical staining or other diagnostic tests; only 1 glass side was provided per biopsy case. CONCLUSIONS: Pathologists' treatment suggestions vary significantly for melanocytic lesions, with lower variability for lesion types with national guidelines. Results suggest the need for standardization of treatment guidelines for all melanocytic lesion types.

16 Article Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure. 2019

Cust, A E / Drummond, M / Bishop, D T / Azizi, L / Schmid, H / Jenkins, M A / Hopper, J L / Armstrong, B K / Aitken, J F / Kefford, R F / Giles, G G / Demenais, F / Goldstein, A M / Barrett, J H / Kanetsky, P A / Elder, D E / Mann, G J / Newton-Bishop, J A. ·Cancer Epidemiology and Prevention Research, Sydney School of Public Health, The University of Sydney, Sydney, Australia. · Melanoma Institute Australia, The University of Sydney, Sydney, Australia. · Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. · School of Mathematics and Statistics, The University of Sydney, Sydney, Australia. · Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. · Viertel Centre for Research in Cancer Control, Cancer Council Queensland, Brisbane, Australia. · Macquarie University Health Sciences Centre, Macquarie University, Sydney, Australia. · Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. · Genetic Variation and Human Diseases Unit, UMR-946, INSERM, Université Paris Diderot, Université Sorbonne Paris Cité, Paris, France. · Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. · Cancer Epidemiology Program, Moffitt Cancer Center, Tampa, FL, USA. · Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. ·J Eur Acad Dermatol Venereol · Pubmed #31087403.

ABSTRACT: BACKGROUND: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. OBJECTIVE: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure. METHODS: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. RESULTS: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. CONCLUSIONS: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

17 Article Stromal inflammatory cells are associated with poorer prognosis in primary cutaneous melanoma. 2019

Yun, Sook Jung / Liu, Shujing / Buckley, Meghan / Wang, Tao / Jin, Suna / Karakousis, Giorgos / Peters, Madalyn G / Elder, David E / Gimotty, Phyllis A / Xu, Xiaowei. ·Department of Dermatology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea. · Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, USA. · Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: pgimotty@mail.med.upenn.edu. · Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: xug@mail.med.upenn.edu. ·Hum Pathol · Pubmed #30965022.

ABSTRACT: We observed that non-tumor-infiltrating inflammatory cells are often present in the stroma of melanoma. The role of these stromal inflammatory cells (SIC) in cancer has not been studied. We evaluated the prognostic significance of SIC in 299 patients with vertical growth phase primary melanomas with at least 10 years of clinical follow-up. Lymphatic density and lymphatic invasion in the areas with SIC was quantified. The prognostic significance of these factors was evaluated using univariable and multivariable Cox models for melanoma-specific death and the time to first recurrence. Of the 299 melanomas, 161 exhibited areas with SIC. Percentages of vertical growth phase tumor-infiltrating lymphocytes and radial growth phase regression were significantly higher in cases with SIC compared to those without SIC (P = .005); lymphatic invasion was also detected more frequently in cases with SIC (P = .001). Lymphatic density in SIC areas was higher than that in other areas of the melanomas. Patients with SIC had poorer clinical outcome. Vascular endothelial growth factor-C (VEGFC) staining in a subset of these melanoma patients showed that VEGFC expression in the stromal macrophages was associated with lymphatic invasion in SIC areas. In conclusion, SIC in melanoma is associated with poorer prognosis, and the prognostic effect is partially mediated through induction of lymphangiogenesis with increased lymphatic invasion.

18 Article Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT. 2019

Taylor, Nicholas J / Mitra, Nandita / Qian, Lu / Avril, Marie-Françoise / Bishop, D Timothy / Bressac-de Paillerets, Brigitte / Bruno, William / Calista, Donato / Cuellar, Francisco / Cust, Anne E / Demenais, Florence / Elder, David E / Gerdes, Anne-Marie / Ghiorzo, Paola / Goldstein, Alisa M / Grazziotin, Thais C / Gruis, Nelleke A / Hansson, Johan / Harland, Mark / Hayward, Nicholas K / Hocevar, Marko / Höiom, Veronica / Holland, Elizabeth A / Ingvar, Christian / Landi, Maria Teresa / Landman, Gilles / Larre-Borges, Alejandra / Mann, Graham J / Nagore, Eduardo / Olsson, Håkan / Palmer, Jane M / Perić, Barbara / Pjanova, Dace / Pritchard, Antonia L / Puig, Susana / Schmid, Helen / van der Stoep, Nienke / Tucker, Margaret A / Wadt, Karin A W / Yang, Xiaohong R / Newton-Bishop, Julia A / Kanetsky, Peter A / Anonymous3411133. ·Department of Epidemiology and Biostatistics, Texas A&M University, College Station, Texas. · Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Assistance Publique-Hôpitaux de Paris, Hôpital Cochin et Université Paris Descartes, Paris, France. · Section of Epidemiology and Biostatistics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom. · Gustave Roussy, Université Paris-Saclay, Département de Biopathologie and Institut National de la Santé et de la Recherche Médicale U1186, Villejuif, France. · Department of Internal Medicine and Medical Specialties, University of Genoa and Istituto de Ricovero e Cura a Carattere Scientifico AOU San Martino-IST, Genoa, Italy. · Dermatology Unit, Maurizio Bufalini Hospital, Cesena, Italy. · Melanoma Unit, Dermatology Department, Hospital Clinic Barcelona, Institut de Investigacions Biomediques August Pi Sunyer, Universitat de Barcelona, Barcelona, Spain. · Sydney School of Public Health, The University of Sydney, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, Australia. · Institut National de la Santé et de la Recherche Médicale UMR-946, Genetic Variation and Human Disease Unit, Université Paris Diderot, Paris, France. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark. · Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. · Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. · Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands. · Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. · QIMR Berghofer Medical Research Institute, Herston, Australia. · Institute of Oncology Ljubljana, Zaloska, Ljubljana, Slovenia. · Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Westmead Institute for Medical Research, University of Sydney, Sydney, Australia. · Department of Clinical Sciences, Lund University Hospital Lund, Sweden; Department of Surgery, Lund University Hospital, Lund, Sweden. · Department of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil. · Unidad de Lesiones Pigmentadas, Cátedra de Dermatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay. · Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain. · Latvian Biomedical Research and Study Centre, Riga, Latvia. · Melanoma Unit, Dermatology Department, Hospital Clinic Barcelona, Institut de Investigacions Biomediques August Pi Sunyer, Universitat de Barcelona, Barcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain. · Department of Clinical Genetics, Leiden University Medical Center Leiden, the Netherlands. · Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address: peter.kanetsky@moffitt.org. ·J Am Acad Dermatol · Pubmed #30731170.

ABSTRACT: BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. METHODS: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. RESULTS: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. CONCLUSION: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.

19 Article NRAS Q61R and BRAF G466A mutations in atypical melanocytic lesions newly arising in advanced melanoma patients treated with vemurafenib. 2019

Parekh, Vishwas / Sobanko, Joseph / Miller, Christopher J / Karakousis, Giorgos / Xu, Wei / Letrero, Richard / Elenitsas, Rosalie / Xu, Xiaowei / Elder, David E / Amaravadi, Ravi / Schuchter, Lynn M / Nathanson, Katherine L / Wilson, Melissa A / Chu, Emily Y. ·Department of Pathology, City of Hope Medical Center, Duarte, CA. · Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. ·J Cutan Pathol · Pubmed #30552700.

ABSTRACT: BACKGROUND: BRAF inhibition has improved overall survival in patients with BRAF mutant melanoma, but this is associated with a range of known and predictable cutaneous side effects, including squamous cell carcinomas associated with RAS mutations. METHODS: We identified three severely dysplastic nevi, one atypical intraepidermal melanocytic proliferation, and four melanoma in situ lesions, newly arising in four patients undergoing treatment with vemurafenib. To characterize mutations in these atypical melanocytic lesions, we used a custom iPlex panel detecting 74 mutations in 13 genes known to play a role in melanoma pathogenesis. RESULTS: We identified an NRAS mutation at codon 61 (Q61R) and a rare BRAF exon 11 mutation (G466A) in atypical melanocytic lesions that arose in patients treated with vemurafenib. CONCLUSION: There appears to be development or accelerated growth of atypical melanocytic lesions in the setting of BRAF inhibition. Our results underscore the need for careful surveillance for melanocytic lesions in patients on BRAF inhibitor therapy and shed light on potential mechanisms for melanoma pathogenesis in the context of BRAF pathway blockade. Further studies are warranted to show a causal relationship.

20 Article Relationship between age and likelihood of lymph node metastases in patients with intermediate thickness melanoma (1.01-4.00 mm): A National Cancer Database study. 2019

Hanna, Andrew N / Sinnamon, Andrew J / Roses, Robert E / Kelz, Rachel R / Elder, David E / Xu, Xiaowei / Pockaj, Barbara A / Zager, Jonathan S / Fraker, Douglas L / Karakousis, Giorgos C. ·Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Surgery, Mayo Clinic in Arizona, Phoenix, Arizona. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: giorgos.karakousis@uphs.upenn.edu. ·J Am Acad Dermatol · Pubmed #30165160.

ABSTRACT: BACKGROUND: There is large variability in the risk of sentinel lymph node (SLN) positivity among patients with intermediate thickness melanoma (ITM), with a subgroup of patients exhibiting a low risk of nodal disease. OBJECTIVE: To identify a group of patients with ITM for whom the risk of nodal disease is low. METHODS: A retrospective cohort of patients with ITM who underwent wide excision and nodal evaluation from 2010 to 2013 was identified by using the National Cancer Database and analyzed for the presence of nodal disease. Classification and regression tree analysis identified the most important factors used in a model to identify groups at low risk of SLN positivity. RESULTS: Of 23,440 patients, 14.7% were found to have nodal metastasis. On classification and regression tree analysis, patients older than 55 years without lymphovascular invasion and with a lesion thickness less than 1.7 mm had an SLN positivity rate of 4.9%. A model using age and thickness in nonulcerated patients identified a low-risk subgroup with a corresponding SLN positivity rate of 4.7%. LIMITATIONS: This was a retrospective study, and the model developed requires prospective validation. CONCLUSIONS: Patient age is an important factor in estimating risk of SLN in patients with ITM and may help identify patients without ulceration who may be safely spared an SLN biopsy.

21 Article Concordance and Reproducibility of Melanoma Staging According to the 7th vs 8th Edition of the 2018

Elmore, Joann G / Elder, David E / Barnhill, Raymond L / Knezevich, Stevan R / Longton, Gary M / Titus, Linda J / Weinstock, Martin A / Pepe, Margaret S / Nelson, Heidi D / Reisch, Lisa M / Radick, Andrea C / Piepkorn, Michael W. ·Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (Elmore) · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia (Elder) · Department of Pathology, Institut Curie, Paris, France (Barnhill) · Paris Sciences and Lettres Research University, Paris, France (Barnhill) · Faculty of Medicine, University of Paris Descartes, Paris, France (Barnhill) · Pathology Associates, Clovis, California (Knezevich) · Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, Washington (Longton, Pepe) · Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (Titus) · Department of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (Titus) · Norris Cotton Cancer Center, Lebanon, New Hampshire (Titus) · Center for Dermatoepidemiology, Providence Veterans Affair Medical Center, Providence, Rhode Island (Weinstock) · Department of Dermatology, Brown University, Providence, Rhode Island (Weinstock) · Department of Epidemiology, Brown University, Providence, Rhode Island (Weinstock) · Department of Medical Informatics and Clinical Epidemiology, School of Medicine, Oregon Health and Science University, Portland (Nelson) · Department of Medicine, School of Medicine, Oregon Health and Science University, Portland (Nelson) · Department of Medicine, University of Washington School of Medicine, Seattle (Reisch, Radick, Piepkorn) · Dermatopathology Northwest, Bellevue, Washington (Piepkorn). ·JAMA Netw Open · Pubmed #30556054.

ABSTRACT: IMPORTANCE: The recently updated American Joint Committee on Cancer (AJCC) classification of cancer staging, the OBJECTIVE: To compare DESIGN SETTING AND PARTICIPANTS: In this diagnostic study conducted as part of the national Melanoma Pathology Study across US states, 187 pathologists interpreting melanocytic skin lesions in practice completed 4342 independent case interpretations of 116 invasive melanoma cases. A consensus reference diagnosis and participating pathologists' interpretations were classified into the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis class IV (T1a) or class V ( T1b) using both the MAIN OUTCOMES AND MEASURES: Concordance with consensus reference diagnosis, interobserver reproducibility, and intraobserver reproducibility. RESULTS: For T1a diagnoses, participating pathologists' concordance with the consensus reference diagnosis increased from 44% (95% CI, 41%-48%) to 54% (95% CI, 51%-57%) using CONCLUSIONS AND RELEVANCE: Melanoma staging in

22 Article Characteristics and diagnostic performance of pathologists who enjoy interpreting melanocytic lesions. 2018

Radick, Andrea C / Phipps, Amanda I / Piepkorn, Michael W / Nelson, Heidi D / Barnhill, Raymond L / Elder, David E / Reisch, Lisa M / Frederick, Paul D / Elmore, Joann G. ·Department of Medicine, University of Washington School of Medicine, Seattle, Washington. radica@uw.edu. ·Dermatol Online J · Pubmed #30142708.

ABSTRACT: Diagnostic discrepancy among pathologists interpreting melanocytic skin lesions (MSL) is an ongoing concern for patient care. Given that job satisfaction could impact patient care, this study aimed to characterize which pathologists enjoy interpreting MSL and estimate the association between enjoyment and diagnostic accuracy. Pathologists' demographics, training, and experience were obtained by a cross-sectional survey. Associations between these characteristics and self-reported enjoyment when interpreting MSL were estimated by Pearson's Chi-square tests. Diagnostic accuracy was determined by comparing pathologists' MSL interpretations with reference standard diagnoses. Associations between enjoyment and diagnostic accuracy were evaluated by generalized estimating equations (GEE) models. One hundred and eighty-seven (90%) pathologists completed the study. Seventy percent agreed that interpreting MSL is enjoyable. Pathologists who enjoyed interpreting MSL were more likely to be board certified and/or fellowship trained in dermatopathology (P=0.008), have ?10 years of experience (P=0.010) and have an MSL caseload of ?60 per month (P=<0.001). After adjustment, there was no association between enjoyment and diagnostic accuracy. Our data suggest that job dissatisfaction does not adversely affect diagnostic accuracy in the interpretation of melanocytic lesions, which is of importance given the progressive increase in annual biopsy rates and the attendant work demands imposed on pathologists.

23 Article Accuracy of Digital Pathologic Analysis vs Traditional Microscopy in the Interpretation of Melanocytic Lesions. 2018

Onega, Tracy / Barnhill, Raymond L / Piepkorn, Michael W / Longton, Gary M / Elder, David E / Weinstock, Martin A / Knezevich, Stevan R / Reisch, Lisa M / Carney, Patricia A / Nelson, Heidi D / Radick, Andrea C / Elmore, Joann G. ·Departments of Medicine and Community and Family Medicine, The Dartmouth Institute for Health Policy and Clinical Practice, Hanover, New Hampshire. · Geisel School of Medicine at Dartmouth, Hanover, New Hampshire. · Norris Cotton Cancer Center, Lebanon, New Hampshire. · Department of Pathology, Institut Curie, Paris Sciences and Lettres Research University, and Faculty of Medicine University of Paris Descartes, Paris, France. · Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle. · Dermatopathology Northwest, Bellevue, Washington. · Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, Washington. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia. · Center for Dermatoepidemiology, Providence VA Medical Center, Providence, Rhode Island. · Departments of Dermatology and Epidemiology, Brown University, Providence, Rhode Island. · Pathology Associates, Clovis, California. · Department of Medicine, University of Washington School of Medicine, Seattle. · Department of Family Medicine, School of Medicine, Oregon Health & Science University, Portland. · Department of Medical Informatics and Clinical Epidemiology, School of Medicine, Oregon Health & Science University, Portland. · Department of Medicine, School of Medicine, Oregon Health & Science University, Portland. · Providence Cancer Center, Providence Health and Services, Portland, Oregon. · Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California. ·JAMA Dermatol · Pubmed #30140929.

ABSTRACT: Importance: Use of digital whole-slide imaging (WSI) for dermatopathology in general has been noted to be similar to traditional microscopy (TM); however, concern has been noted that WSI is inferior for interpretation of melanocytic lesions. Since approximately 1 of every 4 skin biopsies is of a melanocytic lesion, the use of WSI requires verification before use in clinical practice. Objective: To compare pathologists' accuracy and reproducibility in diagnosing melanocytic lesions using Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) categories when analyzing by TM vs WSI. Design, Setting, and Participants: A total of 87 pathologists in community-based and academic settings from 10 US states were randomized with stratification based on clinical experience to interpret in TM format 180 skin biopsy cases of melanocytic lesions, including 90 invasive melanoma, divided into 5 sets of 36 cases (phase 1). The pathologists were then randomized via stratified permuted block randomization with block size 2 to interpret cases in either TM (n = 46) or WSI format (n = 41), with each pathologist interpreting the same 36 cases on 2 separate occasions (phase 2). Diagnoses were categorized as MPATH-Dx categories I through V, with I indicating the least severe and V the most severe. Main Outcomes and Measures: Accuracy with respect to a consensus reference diagnosis and the reproducibility of repeated interpretations of the same cases. Results: Of the 87 pathologists in the study, 46% (40) were women and the mean (SD) age was 50.7 (10.2) years. Except for class III melanocytic lesions, the diagnostic categories showed no significant differences in diagnostic accuracy between TM and WSI interpretation. Discordance was lower among class III lesions for the TM interpretation arm (51%; 95% CI, 46%-57%) than for the WSI arm (61%; 95% CI, 53%-69%) (P = .05). This difference is likely to have clinical significance, because 6% of TM vs 11% of WSI class III lesions were interpreted as invasive melanoma. Reproducibility was similar between the traditional and digital formats overall (66.4%; 95% CI, 63.3%-69.3%; and 62.7%; 95% CI, 59.5%-65.7%, respectively), and for all classes, although class III showed a nonsignificant lower intraobserver agreement for digital. Significantly more mitotic figures were detected with TM compared with WSI: mean (SD) TM, 6.72 (2.89); WSI, 5.84 (2.56); P = .002. Conclusions and Relevance: Interpretive accuracy for melanocytic lesions was similar for WSI and TM slides except for class III lesions. We found no clinically meaningful differences in reproducibility for any of the diagnostic classes.

24 Article Prediction of Residual Nodal Disease at Completion Dissection Following Positive Sentinel Lymph Node Biopsy for Melanoma. 2018

Sinnamon, Andrew J / Song, Yun / Sharon, Cimarron E / Yang, Yu-Xiao / Elder, David E / Zhang, Paul J / Xu, Xiaowei / Roses, Robert E / Kelz, Rachel R / Fraker, Douglas L / Karakousis, Giorgos C. ·Department of Surgery, Endocrine and Oncologic Surgery Division, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. andrew.sinnamon@uphs.upenn.edu. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. andrew.sinnamon@uphs.upenn.edu. · Department of Surgery, Endocrine and Oncologic Surgery Division, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. · Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. ·Ann Surg Oncol · Pubmed #30043316.

ABSTRACT: INTRODUCTION: While recent trial data have demonstrated no survival benefit to immediate completion lymph node dissection (CLND) for positive sentinel lymph node (SLN) disease in melanoma, prediction of non-SLN disease may help risk-stratify patients for more intensive observation of the nodal basin. PATIENTS AND METHODS: A retrospective cohort of patients with positive SLN biopsy (SLNB) who underwent CLND was identified (1996-2016). A risk score for likelihood of CLND-positive disease was developed based on factors associated with presence of CLND metastases identified on logistic regression. Survival outcomes were analyzed. RESULTS: Among 312 patients with positive SLN, 192 underwent CLND and had complete pathologic data for evaluation. The median age of the study cohort was 53 years [interquartile range (IQR) 43-66 years], and 112 (58%) were male. Thirty-one (16%) had non-SLN metastatic disease on CLND. The four factors independently associated with CLND positivity and thus included in the risk score were Breslow thickness ≥ 3 mm [odds ratio (OR) 2.56, p = 0.047], presence of primary tumor-infiltrating lymphocytes (OR 0.33, p = 0.013), ≥ 2/3 positive-to-total SLN ratio (OR 4.35, p = 0.003), and combined subcapsular and parenchymal metastatic SLN location or metastatic deposit ≥ 1 mm (OR 4.45, p = 0.013). The four-point risk score predicted CLND positivity well with area under the curve of 0.82 (0.80-0.85). Increasing risk score was independently associated with increasingly worse melanoma-specific survival [hazard ratio (HR) = 1.54, p = 0.001]. CONCLUSIONS: Likelihood of residual nodal disease after positive SLNB and survival can be predicted from primary tumor and SLN characteristics. High-risk patients may warrant more intensive surveillance of the nodal basin to reduce risk of loss of regional control.

25 Article Malpractice Concerns, Defensive Medicine, and the Histopathology Diagnosis of Melanocytic Skin Lesions. 2018

Titus, Linda J / Reisch, Lisa M / Tosteson, Anna N A / Nelson, Heidi D / Frederick, Paul D / Carney, Patricia A / Barnhill, Raymond L / Elder, David E / Weinstock, Martin A / Piepkorn, Michael W / Elmore, Joann G. ·Department of Epidemiology and Pediatrics, Norris Cotton Cancer Center, Hanover, NH. · Department of Medicine, Norris Cotton Cancer Center, Hanover, NH. · Departments of Medicine and Community and Family Medicine, Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Hanover, NH. · Departments of Medical Informatics and Clinical Epidemiology and Medicine, Portland. · Department of Family Medicine, Oregon Health and Science University, Portland. · Department of Pathology, Institut Curie, Paris Sciences and Letters Research University, University of Paris Descartes, Paris, France. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia. · Center for Dermatoepidemiology, VA Medical Center, Providence Department of Dermatology, Rhode Island Hospital, Providence. · Departments of Dermatology and Epidemiology, Brown University, Providence, RI. · Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle. · Dermatopathology Northwest, Bellevue, WA. · Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA. ·Am J Clin Pathol · Pubmed #30007278.

ABSTRACT: Objectives: The impact of malpractice concerns on pathologists' use of defensive medicine and interpretations of melanocytic skin lesions (MSLs) is unknown. Methods: A total of 207 pathologists interpreting MSLs responded to a survey about past involvement in malpractice litigation, influence of malpractice concerns on diagnosis, and use of assurance behaviors (defensive medicine) to alleviate malpractice concerns. Assurance behaviors included requesting second opinions, additional slides, additional sampling, and ordering specialized tests. Results: Of the pathologists, 27.5% reported that malpractice concerns influenced them toward a more severe MSL diagnosis. Nearly all (95.2%) pathologists reported practicing at least one assurance behavior due to malpractice concerns, and this practice was associated with being influenced toward a more severe MSL diagnosis (odds ratio, 2.72; 95% confidence interval, 1.41-5.26). Conclusions: One of four US skin pathologists upgrade MSL diagnosis due to malpractice concerns, and nearly all practice assurance behaviors. Assurance behaviors are associated with rendering a more severe MSL diagnosis.

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