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Melanoma: HELP
Articles by David E. Elder
Based on 77 articles published since 2008
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Between 2008 and 2019, D. Elder wrote the following 77 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
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 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 --

3 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.

4 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.

5 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.

6 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 --

7 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.

8 Review Selection criteria for genetic assessment of patients with familial melanoma. 2009

Leachman, Sancy A / Carucci, John / Kohlmann, Wendy / Banks, Kimberly C / Asgari, Maryam M / Bergman, Wilma / Bianchi-Scarrà, Giovanna / Brentnall, Teresa / Bressac-de Paillerets, Brigitte / Bruno, William / Curiel-Lewandrowski, Clara / de Snoo, Femke A / Debniak, Tadeusz / Demierre, Marie-France / Elder, David / Goldstein, Alisa M / Grant-Kels, Jane / Halpern, Allan C / Ingvar, Christian / Kefford, Richard F / Lang, Julie / MacKie, Rona M / Mann, Graham J / Mueller, Kurt / Newton-Bishop, Julia / Olsson, Håkan / Petersen, Gloria M / Puig, Susana / Rigel, Darrell / Swetter, Susan M / Tucker, Margaret A / Yakobson, Emanuel / Zitelli, John A / Tsao, Hensin. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA. sancy.leachman@hci.utah.edu ·J Am Acad Dermatol · Pubmed #19751883.

ABSTRACT: Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.

9 Review Angiomatoid Spitz nevus: a clinicopathological study of six cases and a review of the literature. 2009

Tetzlaff, Michael T / Xu, Xiaowei / Elder, David E / Elenitsas, Rosalie. ·Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. tetzlafm@uphs.upenn.edu ·J Cutan Pathol · Pubmed #19278435.

ABSTRACT: Angiomatoid Spitz nevus is a recently described subtype of desmoplastic Spitz nevus. Six cases have been described in the literature thus far. Here, we describe six additional cases of angiomatoid Spitz nevus and provide a review of the literature on this entity. The features of classic angiomatoid Spitz nevus are described in the context of important differential diagnostic considerations, particularly regressed malignant melanoma.

10 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.

11 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.

12 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.

13 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.

14 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.

15 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.

16 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.

17 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.

18 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.

19 Article Influence of variability in assessment of Breslow thickness, mitotic rate and ulceration among US pathologists interpreting invasive melanoma, for the purpose of AJCC staging. 2018

Taylor, Laura / Hood, Kyle / Reisch, Lisa / Elmore, Joann / Piepkorn, Michael / Barnhill, Raymond / Knezevich, Stevan / Radick, Andrea / Elder, David. ·Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Bureau of Economic Analysis, Suitland, Maryland. · Department of Medicine, University of Washington School of Medicine, Seattle, Washington. · David Geffen School of Medicine at UCLA, Los Angeles, California. · Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington. · Dermatopathology Northwest, Bellevue, Washington. · Department of Pathology, Institut Curie Paris Sciences and Lettres Research University, and Faculty of Medicine University of Paris Descartes, Paris, France. · Pathology Associates, Clovis, California. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. ·J Cutan Pathol · Pubmed #29717800.

ABSTRACT: BACKGROUND: Melanoma staging has depended on depth of invasion (Breslow thickness, BT), mitotic rate (MR) and ulceration. In anticipation of the AJCC's eighth edition, variability in pathologists' assessment of these factors and consequently in tumor staging was assessed. METHODS: One-hundred and fifteen cases of invasive melanoma, established by a consensus panel, were assessed by 187 pathologists. Variation was studied in BT, the detection of mitotic figures, and ulceration. The sources of this variation and its effect on tumor staging are considered. RESULTS: On average, participant assessments closely approached consensus BT. Greater variation was identified in the classification of mitogenicity, which (like ulceration) upstages a T1 melanoma from T1a to T1b in the seventh but not eighth edition. In cases with a T1a diagnosis by the consensus panel, 15.6% of participants identified one or more mitotic figures (indicative of a false positive); and in cases diagnosed asT1b by the consensus panel, 32.0% of participants failed to find mitotic figures (false negative). CONCLUSION: Variability in the staging of T1 melanoma among pathologists when using the AJCC seventh edition criteria is closely related to the detection of mitotic figures, with BT playing a less prominent role. Decreased variability is expected after implementation of the eighth edition.

20 Article Pathologist characteristics associated with accuracy and reproducibility of melanocytic skin lesion interpretation. 2018

Elder, David E / Piepkorn, Michael W / Barnhill, Raymond L / Longton, Gary M / Nelson, Heidi D / Knezevich, Stevan R / Pepe, Margaret S / Carney, Patricia A / Titus, Linda J / Onega, Tracy / Tosteson, Anna N A / Weinstock, Martin A / Elmore, Joann G. ·Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Dermatopathology Northwest, Bellevue, Washington. · Department of Pathology, Institut Curie, Paris, France; University of Paris Descartes, Paris, France. · Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, Washington. · Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon; Department of Medicine, Oregon Health and Science University, Portland, Oregon. · Pathology Associates, Clovis, California. · Department of Family Medicine, Oregon Health and Science University, Portland, Oregon. · Department of Epidemiology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire. · Department of Biomedical Data Science, Department of Epidemiology, Norris Cotton Cancer Center, Lebanon, New Hampshire; Geisel School of Medicine at Dartmouth, The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire. · Department of Medicine, The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire; Department of Community and Family Medicine, The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire. · Center for Dermatoepidemiology, VA Medical Center, Providence Department of Dermatology, Rhode Island Hospital, Providence, Rhode Island; Department of Dermatology, Brown University, Providence, Rhode Island; Department of Epidemiology, Brown University, Providence, Rhode Island. · Department of Medicine, University of Washington School of Medicine, Seattle, Washington. Electronic address: jelmore@uw.edu. ·J Am Acad Dermatol · Pubmed #29524584.

ABSTRACT: BACKGROUND: Diagnostic interpretations of melanocytic skin lesions vary widely among pathologists, yet the underlying reasons remain unclear. OBJECTIVE: Identify pathologist characteristics associated with rates of accuracy and reproducibility. METHODS: Pathologists independently interpreted the same set of biopsy specimens from melanocytic lesions on 2 occasions. Diagnoses were categorized into 1 of 5 classes according to the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis system. Reproducibility was determined by pathologists' concordance of diagnoses across 2 occasions. Accuracy was defined by concordance with a consensus reference standard. Associations of pathologist characteristics with reproducibility and accuracy were assessed individually and in multivariable logistic regression models. RESULTS: Rates of diagnostic reproducibility and accuracy were highest among pathologists with board certification and/or fellowship training in dermatopathology and in those with 5 or more years of experience. In addition, accuracy was high among pathologists with a higher proportion of melanocytic lesions in their caseload composition and higher volume of melanocytic lesions. LIMITATIONS: Data gathered in a test set situation by using a classification tool not currently in clinical use. CONCLUSION: Diagnoses are more accurate among pathologists with specialty training and those with more experience interpreting melanocytic lesions. These findings support the practice of referring difficult cases to more experienced pathologists to improve diagnostic accuracy, although the impact of these referrals on patient outcomes requires additional research.

21 Article The prognostic significance of tumor-infiltrating lymphocytes for primary melanoma varies by sex. 2018

Sinnamon, Andrew J / Sharon, Cimarron E / Song, Yun / Neuwirth, Madalyn G / Elder, David E / Xu, Xiaowei / Chu, Emily Y / Ming, Michael E / Fraker, Douglas L / Gimotty, Phyllis A / Karakousis, Giorgos C. ·Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: andrew.sinnamon@uphs.upenn.edu. · Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania. ·J Am Acad Dermatol · Pubmed #29518458.

ABSTRACT: BACKGROUND: The immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored. METHODS: Patients who had clinically localized primary melanoma with a Breslow thickness of 0.76 mm or more and underwent sentinel lymph node (SLN) biopsy at our institution were identified. The association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated by using logistic regression. Overall survival (OS) was evaluated by TIL status and sex. RESULTS: Among 1367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (P = .71). SLN positivity was associated with TILs among men (brisk, 3.8%; nonbrisk, 16.9%; and absent, 26.6% [P < .001]). In contrast, there was no association between SLN positivity and TILs among women (P = .49). Interaction between brisk TILs and sex on SLN positivity was significant (P = .029). Among men, presence of brisk TILs was associated with prolonged OS (P = .038) but not after adjustment for SLN status (P = .42). There was no association between TIL status and OS among women. LIMITATIONS: Findings from this single-institution study have yet to be validated by other research groups. CONCLUSIONS: The implications of TILs in predicting SLN positivity appear to be more relevant for men than for women.

22 Article Risks of Melanoma and Other Cancers in Melanoma-Prone Families over 4 Decades. 2018

Tucker, Margaret A / Elder, David E / Curry, Michael / Fraser, Mary C / Pichler, Virginia / Zametkin, Deborah / Yang, Xiaohong R / Goldstein, Alisa M. ·Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: tuckerp@mail.nih.gov. · Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Information Management Services, Inc, Silver Spring, Maryland. · Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Westat, Inc, Rockville, Maryland, USA. ·J Invest Dermatol · Pubmed #29408205.

ABSTRACT: Since 1976, melanoma-prone families have been followed at the National Cancer Institute to identify etiologic factors for melanoma. We compared risks of melanoma and other cancers in 1,226 members of 56 families followed for up to 4 decades with population rates in the Surveillance, Epidemiology, and End Results program. All families were tested for mutations in CDKN2A and CDK4; 29 were mutation-positive and 27 mutation-negative. We compared rates of invasive melanomas, both first and second, by family mutation status, with Surveillance, Epidemiology, and End Results program. Comparing three calendar periods of the study, risk of first primary melanoma decreased slightly. Risks of melanoma after first examination, however, were approximately one-third the risks prior to the first examination in both mutation-positive and mutation-negative families. Among patients with melanoma, risk of a second melanoma was increased 10-fold in all families; risk was somewhat higher in mutation-positive families. Risks of other second cancers were increased only for pancreatic cancer after melanoma in mutation-positive families. Over 4 decades, prospective risk of melanoma has decreased substantially in both mutation-positive and mutation-negative families, when melanoma has greatly increased in the general population. TRIAL REGISTRATION: NCI 02-C-0211, ClinicalTrials.gov ID NCT00040352.

23 Article Population-Based Analysis of Histologically Confirmed Melanocytic Proliferations Using Natural Language Processing. 2018

Lott, Jason P / Boudreau, Denise M / Barnhill, Ray L / Weinstock, Martin A / Knopp, Eleanor / Piepkorn, Michael W / Elder, David E / Knezevich, Steven R / Baer, Andrew / Tosteson, Anna N A / Elmore, Joann G. ·Cornell Scott-Hill Health Center, New Haven, Connecticut. · Kaiser Permanente Washington Health Research Institute, Seattle. · Departments of Pharmacy and Epidemiology, University of Washington, Seattle. · Department of Pathology, Institut Curie, and Faculty of Medicine, University of Paris Descartes, Paris, France. · Departments of Dermatology and Epidemiology, Brown University, Providence, Rhode Island. · Center for Dermatoepidemiology, Department of Veterans Affairs Medical Center, Providence, Rhode Island. · Department of Dermatology, Rhode Island Hospital, Providence, Rhode Island. · Division of Dermatology, Department of Medicine, University of Washington, Seattle. · Group Health Capitol Hill Campus, Seattle, Washington. · Dermatopathology Northwest, Bellevue, Washington. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia. · Pathology Associates, Clovis, California. · The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire. · Department of Medicine Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire. · Norris Cotton Cancer Center, Lebanon, New Hampshire. · Department of Medicine, University of Washington School of Medicine, Seattle. ·JAMA Dermatol · Pubmed #29094145.

ABSTRACT: Importance: Population-based information on the distribution of histologic diagnoses associated with skin biopsies is unknown. Electronic medical records (EMRs) enable automated extraction of pathology report data to improve our epidemiologic understanding of skin biopsy outcomes, specifically those of melanocytic origin. Objective: To determine population-based frequencies and distribution of histologically confirmed melanocytic lesions. Design, Setting, and Participants: A natural language processing (NLP)-based analysis of EMR pathology reports of adult patients who underwent skin biopsies at a large integrated health care delivery system in the US Pacific Northwest from January 1, 2007, through December 31, 2012. Exposures: Skin biopsy procedure. Main Outcomes and Measures: The primary outcome was histopathologic diagnosis, obtained using an NLP-based system to process EMR pathology reports. We determined the percentage of diagnoses classified as melanocytic vs nonmelanocytic lesions. Diagnoses classified as melanocytic were further subclassified using the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema into the following categories: class I (nevi and other benign proliferations such as mildly dysplastic lesions typically requiring no further treatment), class II (moderately dysplastic and other low-risk lesions that may merit narrow reexcision with <5-mm margins), class III (eg, melanoma in situ and other higher-risk lesions warranting reexcision with 5-mm to 1-cm margins), and class IV/V (invasive melanoma requiring wide reexcision with ≥1-cm margins and potential adjunctive therapy). Health system cancer registry data were used to define the percentage of invasive melanoma cases within MPATH-Dx class IV (stage T1a) vs V (≥stage T1b). Results: A total of 80 368 skin biopsies, performed on 47 529 patients, were examined. Nearly 1 in 4 skin biopsies were of melanocytic lesions (23%; n = 18 715), which were distributed according to MPATH-Dx categories as follows: class I, 83.1% (n = 15 558); class II, 8.3% (n = 1548); class III, 4.5% (n = 842); class IV, 2.2% (n = 405); and class V, 1.9% (n = 362). Conclusions and Relevance: Approximately one-quarter of skin biopsies resulted in diagnoses of melanocytic proliferations. These data provide the first population-based estimates across the spectrum of melanocytic lesions ranging from benign through dysplastic to malignant. These results may serve as a foundation for future research seeking to understand the epidemiology of melanocytic proliferations and optimization of skin biopsy utilization.

24 Article Pathologists' Use of Second Opinions in Interpretation of Melanocytic Cutaneous Lesions: Policies, Practices, and Perceptions. 2018

Geller, Berta M / Frederick, Paul D / Knezevich, Stevan R / Lott, Jason P / Nelson, Heidi D / Titus, Linda J / Carney, Patricia A / Tosteson, Anna N A / Onega, Tracy L / Barnhill, Raymond L / Weinstock, Martin A / Elder, David E / Piepkorn, Michael W / Elmore, Joann G. ·Department of Family Medicine, College of Medicine, University of Vermont, Burlington, Vermont. · Department of Medicine, University of Washington School of Medicine, Seattle, Washington. · Pathology Associates, Clovis, California. · Dermatology, Bayer Healthcare LLC, Whippany, New Jersey. · Providence Cancer Center, Providence Health and Services Oregon, and Departments of Medical Informatics and Clinical Epidemiology and Medicine, Oregon Health and Science University, Portland, Oregon. · Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth and the Norris Cotton Cancer Center, Lebanon, New Hampshire. · Departments of Family Medicine and Public Health and Preventative Medicine, Oregon Health and Science University, Portland, Oregon. · Department of Medicine and The Dartmouth Institute for Health Policy and Clinical Practice and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire. · Departments of Biomedical Data Science, and. · Epidemiology, Norris Cotton Cancer Center, Lebanon, New Hampshire. · Department of Pathology, Institut Curie, and Faculty of Medicine, University of Paris Descartes, Paris, France. · Center for Dermatoepidemiology, VA Medical Center, Providence Department of Dermatology, Rhode Island Hospital Departments of Dermatology and Epidemiology, Brown University, Providence, Rhode Island. · Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington. · Dermatopathology Northwest, Bellevue, Washington. ·Dermatol Surg · Pubmed #28858936.

ABSTRACT: BACKGROUND: Research examining the role of second opinions in pathology for diagnosis of melanocytic lesions is limited. OBJECTIVE: To assess current laboratory policies, clinical use of second opinions, and pathologists' perceptions of second opinions for melanocytic lesions. MATERIALS AND METHODS: Cross-sectional data collected from 207 pathologists in 10 US states who diagnose melanocytic lesions. The web-based survey ascertained pathologists' professional information, laboratory second opinion policy, use of second opinions, and perceptions of second opinion value for melanocytic lesions. RESULTS: Laboratory policies required second opinions for 31% of pathologists and most commonly required for melanoma in situ (26%) and invasive melanoma (30%). In practice, most pathologists reported requesting second opinions for melanocytic tumors of uncertain malignant potential (85%) and atypical Spitzoid lesions (88%). Most pathologists perceived that second opinions increased interpretive accuracy (78%) and protected them from malpractice lawsuits (62%). CONCLUSION: Use of second opinions in clinical practice is greater than that required by laboratory policies, especially for melanocytic tumors of uncertain malignant potential and atypical Spitzoid lesions. Quality of care in surgical interventions for atypical melanocytic proliferations critically depends on the accuracy of diagnosis in pathology reporting. Future research should examine the extent to which second opinions improve accuracy of melanocytic lesion diagnosis.

25 Article A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma. 2017

Krepler, Clemens / Sproesser, Katrin / Brafford, Patricia / Beqiri, Marilda / Garman, Bradley / Xiao, Min / Shannan, Batool / Watters, Andrea / Perego, Michela / Zhang, Gao / Vultur, Adina / Yin, Xiangfan / Liu, Qin / Anastopoulos, Ioannis N / Wubbenhorst, Bradley / Wilson, Melissa A / Xu, Wei / Karakousis, Giorgos / Feldman, Michael / Xu, Xiaowei / Amaravadi, Ravi / Gangadhar, Tara C / Elder, David E / Haydu, Lauren E / Wargo, Jennifer A / Davies, Michael A / Lu, Yiling / Mills, Gordon B / Frederick, Dennie T / Barzily-Rokni, Michal / Flaherty, Keith T / Hoon, Dave S / Guarino, Michael / Bennett, Joseph J / Ryan, Randall W / Petrelli, Nicholas J / Shields, Carol L / Terai, Mizue / Sato, Takami / Aplin, Andrew E / Roesch, Alexander / Darr, David / Angus, Steve / Kumar, Rakesh / Halilovic, Ensar / Caponigro, Giordano / Jeay, Sebastien / Wuerthner, Jens / Walter, Annette / Ocker, Matthias / Boxer, Matthew B / Schuchter, Lynn / Nathanson, Katherine L / Herlyn, Meenhard. ·Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA. · Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA. · Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. · Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA 90404, USA. · Helen F. Graham Cancer Center at Christiana Care, Newark, DE 19713, USA. · Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA 19107, USA. · Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107. · Department of Dermatology, University Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany; German Consortium of Translational Cancer Research, Heidelberg, Germany. · Lineberger Cancer Center, University of North Carolina Chapel Hill, NC 27514, USA. · Glaxosmithkline, Collegeville, PA 19426, USA. · Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA. · Bayer Pharma AG, Berlin 13353, Germany. · National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850, USA. · Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: herlynm@wistar.org. ·Cell Rep · Pubmed #29141225.

ABSTRACT: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups.

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