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Melanoma: HELP
Articles by Pedram Gerami
Based on 79 articles published since 2008
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Between 2008 and 2019, P. Gerami wrote the following 79 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Review Usefulness of dermoscopy to improve the clinical and histopathologic diagnosis of skin cancers. 2019

Yélamos, Oriol / Braun, Ralph P / Liopyris, Konstantinos / Wolner, Zachary J / Kerl, Katrin / Gerami, Pedram / Marghoob, Ashfaq A. ·Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York; Dermatology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. Electronic address: oyelamos@gmail.com. · Department of Dermatology, University Hospital Zürich, Zürich, Switzerland. · Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Dermatology, Feinberg School of Medicine, The Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois. · Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York; Dermatology Service, Memorial Sloan Kettering Cancer Center, Hauppauge, New York. ·J Am Acad Dermatol · Pubmed #30321580.

ABSTRACT: Multiple studies have shown that dermoscopy increases the sensitivity and specificity for the detection of skin cancers compared with examination by the naked eye. Dermoscopy can also lead to the detection of thinner and smaller cancers. In addition, dermoscopy leads to the more precise selection of lesions requiring excision. In essence, dermoscopy helps clinicians differentiate benign from malignant lesions through the presence or absence of specific dermoscopic structures. Therefore, because most dermoscopic structures have direct histopathologic correlates, dermoscopy can allow the prediction of certain histologic findings present in skin cancers, thus helping select management and treatment options for select types of skin cancers. Visualizing dermoscopic structures in the ex vivo specimens can also be beneficial. It can improve the histologic diagnostic accuracy by targeted step-sectioning in areas of concern, which can be marked by the clinician before sending the specimen to the pathologist, or by the pathologist on the excised specimen in the laboratory. In addition, ex vivo dermoscopy can also be used to select tumor areas with genetic importance because some dermoscopic structures have been related to mutations with theragnostic relevance. In the second article in this continuing medical education series, we review the impact of dermoscopy on the diagnostic accuracy of skin cancer, how dermoscopy can affect the histopathologic examination, and which dermoscopic features may be more relevant in terms of histologic and genetic prediction.

2 Review Pigmented onychomatricoma: a rare mimic of subungual melanoma. 2018

Isales, M C / Haugh, A M / Bubley, J / Zarkhin, S / Bertler, D / Hanson, E / Verzi, A E / Brieva, J / Guitart, J / Gerami, P. ·Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · Marian University College of Osteopathic Medicine, Indianapolis, IN, USA. · Forefront Dermatology, De Pere, WI, USA. ·Clin Exp Dermatol · Pubmed #29473193.

ABSTRACT: -- No abstract --

3 Review Genotypic and Phenotypic Features of BAP1 Cancer Syndrome: A Report of 8 New Families and Review of Cases in the Literature. 2017

Haugh, Alexandra M / Njauw, Ching-Ni / Bubley, Jeffrey A / Verzì, Anna Elisa / Zhang, Bin / Kudalkar, Emily / VandenBoom, Timothy / Walton, Kara / Swick, Brian L / Kumar, Raj / Rana, Huma Q / Cochrane, Sarah / McCormick, Shelley R / Shea, Christopher R / Tsao, Hensin / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Massachusetts General Hospital Cancer Center, Boston. · Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Boston. · Department of Dermatology, University of Iowa Hospitals and Clinics, and Iowa City VAMC, Iowa City. · Dana Farber Cancer Institute, Boston, Massachusettss. · Section of Dermatology, University of Chicago Medicine, Chicago, Illinois. · The Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois. ·JAMA Dermatol · Pubmed #28793149.

ABSTRACT: Importance: Patients with germline mutations in BAP1 may develop several flesh-colored melanocytic BAP1-mutated atypical intradermal tumors (MBAITs). These tumors generally develop earlier than other BAP1-associated tumors, highlighting an important role for dermatologists in identifying and screening patients with a history suggestive of a germline mutation. Objective: To describe 8 new families with germline mutations in BAP1 and provide a comprehensive review of reported cases. Design, Settings and Participants: Patients were identified in an outpatient dermatology clinical setting over a 6-month period (10 mutation carriers from 8 families) and through a literature review using PubMed (205 patients). Exposures: Mutations were identified through next-generation sequencing of saliva or blood samples, and RNA was extracted from fibroblasts cultured from a patient with an intronic variant to determine the impact of the mutation on the coding sequence. Main Outcomes and Measures: All 215 patients were assessed for personal and/or family history and genotype. These findings were compiled and assessed for any association between genotype and phenotype. Results: Overall, this study included 215 patients (108 women, 91 men, and 16 gender unspecified; median [range] age, 46.5 [10.0-79.0] years). Nine of the 10 patients who were identified in the outpatient dermatology setting were found to have MBAITs on clinical examination. Forty of 53 patients (75%) identified in the literature review who underwent total-body skin examinations (TBSE) were found to have MBAITs, suggesting a high penetrance in patients who have undergone TBSE. The most prevalent malignancies among BAP1 mutation carriers were uveal melanoma (n =  60 [28%]), mesothelioma (n = 48 [22%]), cutaneous melanoma (n = 38 [18%]), and renal cell carcinoma (n = 20 [9%]). A total of 71 unique mutations in BAP1 have been reported. Conclusions and Relevance: Our results indicate that germline mutations in both coding and noncoding regions throughout the BAP1 gene can impair protein function, leading to an increased risk for several associated malignancies. Four of the 8 probands we present had no history of BAP1-associated malignancies and were assessed for germline mutations when found to have MBAITs on dermatologic examination. Dermatologists can identify patients with a high likelihood of the BAP1 cancer syndrome through personal and family history and TBSE for the presence of possible MBAITs.

4 Review Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features. 2017

Merkel, Emily A / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · The Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, USA. ·Lab Invest · Pubmed #28092366.

ABSTRACT: In most cases of cutaneous melanoma, ultraviolet (UV) radiation is recognized as a prominent risk factor. Less is known regarding the mechanisms of mutagenesis for melanoma arising in sun-protected sites, such as acral and mucosal melanoma. Acral and mucosal melanoma share many common features, including a late age of onset, a broad radial growth phase with prominent lentiginous growth, the presence of field cancerization cells, and, in most cases, lack of a precursor nevus. In addition to early chromosomal instability, many of the same genes are also involved in these two distinct melanoma subtypes. To better understand non-UV-mediated pathogenesis in melanoma, we conducted a joint literature review of clinical, histological, and molecular features in acral and mucosal melanoma. We also reviewed the current literature regarding aberrations in KIT, PDGFRA, TERT, and other commonly involved genes. By comparing common features of these two subtypes, we suggest potential mechanisms underlying acral and/or mucosal melanoma and offer direction for future investigations.

5 Review Nonoverlapping Clinical and Mutational Patterns in Melanomas from the Female Genital Tract and Atypical Genital Nevi. 2016

Yélamos, Oriol / Merkel, Emily A / Sholl, Lauren Meldi / Zhang, Bin / Amin, Sapna M / Lee, Christina Y / Guitart, Gerta E / Yang, Jingyi / Wenzel, Alexander T / Bunick, Christopher G / Yazdan, Pedram / Choi, Jaehyuk / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. Electronic address: pgerami1@nm.org. ·J Invest Dermatol · Pubmed #27220476.

ABSTRACT: Genital melanomas (GM) are the second most common cancer of the female external genitalia and may be confused with atypical genital nevi (AGN), which exhibit atypical histological features but have benign behavior. In this study, we compared the clinical, histological, and molecular features of 19 GM and 25 AGN. We described chromosomal copy number aberrations and the mutational status of 50 oncogenes and tumor suppressor genes in both groups. Our study showed that a pigmented lesion occurring in mucosal tissue, particularly in postmenopausal women, was more likely to be a melanoma than a nevus. GM had high levels of chromosomal instability, with many copy number aberrations. Furthermore, we found a completely nonoverlapping pattern of oncogenic mutations when comparing GM and AGN. In GM, we report somatic mutations in KIT and TP53. Conversely, AGN had frequent BRAF V600E mutations, which were not seen in any of the GM. Our results show that GM and AGN have distinct clinical and molecular changes and that GM have a different mutational pattern compared with AGN.

6 Review Molecular techniques for predicting behaviour in melanocytic neoplasms. 2016

Lee, Christina Y / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: pgerami1@nm.org. ·Pathology · Pubmed #27020386.

ABSTRACT: Molecular tools are rapidly emerging as novel tools for clinicians caring for cancer patients. Roles for these assays in melanocytic neoplasms include diagnosis for histologically ambiguous tumors, prognosis for conventional melanoma, and theragnosis for advanced disease. The introduction of these molecular strategies is timely, as different therapeutic options are rapidly developing to treat melanoma. With the development of new and effective therapeutic options, it is more critical than ever to improve the discrimination between patients with aggressive disease and those with more indolent tumours. In this review, we will evaluate the traditional staging of melanoma and what are the likely greatest opportunities for improvement with molecular strategies. We will explore a number of molecular assays that are now commercially available for the assessment of melanocytic neoplasms, which include techniques such as fluorescence in situ hybridisation, comparative genomic hybridisation, mRNA expression profiling and next generation sequencing, and discuss the optimal utilisation of each of these assays.

7 Review Molecular diagnostics for ambiguous melanocytic tumors. 2012

Shahbain, Hilmy / Cooper, Chelsea / Gerami, Pedram. ·College of Science, Benedictine University, Lisle, IL, USA. ·Semin Cutan Med Surg · Pubmed #23174498.

ABSTRACT: Certain subsets of melanocytic neoplasms are difficult to classify because of conflicting histologic features and the existence of a poorly defined intermediate grade of melanocytic tumors. The integration of molecular diagnostic information with a histologic impression may contribute significantly toward improving classification. This review discusses the development of and advances in molecular techniques, including comparative genomic hybridization and fluorescence in situ hybridization (FISH) as diagnostic and prognostic tools for melanocytic neoplasms. Further, we discuss how specific molecular aberrations identified via FISH correlate with certain morphologies in melanocytic neoplasms. We also examine the prognostic value of FISH in intermediate-grade melanocytic tumors, particularly atypical Spitz tumors.

8 Review Update in molecular diagnostics in melanocytic neoplasms. 2012

Cooper, Chelsea / Sorrell, Jennifer / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. ·Adv Anat Pathol · Pubmed #23060066.

ABSTRACT: Future classification systems for melanocytic neoplasms will likely include the integration of molecular aberrations. A number of studies have shown that many gene mutations and chromosomal copy number aberrations may correlate with characteristic clinical and morphologic features for melanocytic neoplasms. This review discusses newly described familial germline mutations such as the BRCA1-associated protein-1 familial melanoma syndrome, recently described somatic mutations, and chromosomal copy number aberrations recently described in melanoma. Further, we discuss how these specific molecular aberrations correlate with specific clinical and morphologic features in melanocytic neoplasm and their implications for prognosis and molecular diagnostics. In addition, we discuss state of the art advancements in molecular diagnostics for melanocytic neoplasms and newly developed fluorescence in situ hybridization assays including the utility of fluorescence in situ hybridization for 9p21 in spitzoid melanocytic neoplasms. Lastly, we discuss a phenomenon known as paradoxical activation of wild-type BRAF seen in patients treated with vemurafenib and some potential clinical presentations of this process.

9 Review Fluorescence in situ hybridization for ambiguous melanocytic tumors. 2012

Gammon, B / Gerami, P. ·Northwestern University, Department of Dermatology, Chicago, IL 60611, USA. bryan.gammon@gmail.com ·Histol Histopathol · Pubmed #23059884.

ABSTRACT: The large majority of melanocytic lesions can be reliably classified as either benign or malignant based upon morphology alone, but a minority of lesions remains difficult to classify by traditional histologic methods. Recently, a panel of fluorescence in situ hybridization (FISH) probes targeting loci on chromosomes 6 and 11 has emerged as a powerful tool to discriminate melanoma from nevi. This has been validated in numerous difficult diagnostic scenarios. In addition, this same FISH panel has been shown to provide independent prognostic information in traditional melanomas. There is accumulating evidence that FISH targeting these loci as well as several other key chromosomal loci such as 9p21 and 8q24 can provide valuable prognostic information in histologically ambiguous melanocytic tumors. However, since the vast majority of atypical spitz tumors have an indolent course, larger studies including adequate numbers of cases with adverse events is necessary to provide sufficient proof of its role in clinically relevant cases. In this review, we discuss the current literature and studies to date on this topic.

10 Review Cytogenetic and mutational analyses of melanocytic tumors. 2012

Gerami, Pedram / Busam, Klaus J. ·Department of Dermatology, Northwestern University, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. ·Dermatol Clin · Pubmed #23021045.

ABSTRACT: Analyses of genetic and genomic alterations of melanocytic tumors have not only led to a better understanding of the pathogenesis of melanocytic tumors but also created new opportunities for improvements in diagnostic accuracy in distinguishing nevus from melanoma, and more effective treatments for patients affected by melanoma. Cytogenetic tests have emerged as a promising ancillary method for the workup of diagnostically problematic melanocytic tumors with ambiguous light microscopic features. Mutation analysis not only is important in treatment decision making but also can be used for improved diagnostic accuracy, staging, and prognosis.

11 Review Update on fluorescence in situ hybridization in melanoma: state of the art. 2011

Gerami, Pedram / Zembowicz, Artur. ·Department of Dermatology, Northwestern University and the Feinberg School of Medicine, Chicago, Illinois, USA. ·Arch Pathol Lab Med · Pubmed #21732770.

ABSTRACT: CONTEXT: Recent advances in understanding the molecular basis of melanoma have resulted in development of fluorescence in situ hybridization (FISH) protocols designed to detect genetic abnormalities discriminating melanoma from nevi. The most extensively studied is a 4-probe multicolor FISH probe panel targeting chromosomes 6 and 11. Validation studies showed promising sensitivity and specificity for distinguishing benign nevi and malignant melanoma by FISH. Recent studies show that a melanoma FISH assay has great potential for becoming an important diagnostic adjunct in classification of melanocytic lesions and in diagnosis of melanoma. OBJECTIVE: To present a comprehensive review of the science and practical aspects of FISH in melanoma for pathologists considering the use of melanoma FISH in their practice. DATA SOURCES: Review of the literature and personal experience of the authors. CONCLUSIONS: Judicious use of a 4-probe multicolor melanoma FISH procedure can enhance accuracy for diagnosis of melanoma and improve classification of melanocytic proliferations.

12 Article The role of TERT promoter mutations in differentiating recurrent nevi from recurrent melanomas: A retrospective, case-control study. 2019

Walton, Kara E / Garfield, Erin M / Zhang, Bin / Quan, Victor L / Shi, Katherine / Mohan, Lauren S / Haugh, Alexandra M / VandenBoom, Timothy / Yazdan, Pedram / Isales, Maria Cristina / Panah, Elnaz / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: pgerami1@nm.org. ·J Am Acad Dermatol · Pubmed #30287318.

ABSTRACT: BACKGROUND: Repigmentation at previous biopsy sites pose a significant diagnostic dilemma given clinical and histologic similarities between recurrent nevi and locally recurrent melanoma. Though common in melanoma, the role of TERT promoter mutations (TPMs) in recurrent nevi is unknown. OBJECTIVE: We investigated the role of TPMs in recurrent nevi and whether the presence of hotspot TPM distinguishes recurrent nevi from locally recurrent melanoma. We also characterized clinical and histologic features differentiating these lesions. METHODS: We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and melanoma and nevus controls to determine TPM status. We also assessed clinical and histologic features of the recurrent groups. RESULTS: Hotspot TPMs were more common in recurrent melanomas than recurrent nevi (P = .008). Recurrent melanomas were more likely to have solar elastosis (P = .0047), multilayering of melanocytes in the epidermis (P = .0221), adnexal involvement (P = .0069), and epidermal consumption (P = .0204). Recurrent nevi had intra-epidermal atypia limited to the area above the scar (P < .0001) and occurred earlier after the original biopsy (P < .0008). Solar elastosis, months to recurrence, and hotspot TPMs were independently associated with recurrent melanoma in multivariate analysis. LIMITATIONS: This was a retrospective study. CONCLUSION: Hotspot TPMs are significantly more frequent in recurrent melanomas and could serve as a diagnostic clue in histologically ambiguous cases.

13 Article Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. 2019

Gastman, Brian R / Gerami, Pedram / Kurley, Sarah J / Cook, Robert W / Leachman, Sancy / Vetto, John T. ·Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Skin Cancer Institute, Northwestern University Lurie Comprehensive Cancer Center, Chicago, Illinois. · Castle Biosciences, Inc, Friendswood, Texas. · Castle Biosciences, Inc, Friendswood, Texas. Electronic address: rcook@castlebiosciences.com. · Department of Dermatology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon. · Division of Surgical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon. ·J Am Acad Dermatol · Pubmed #30081113.

ABSTRACT: BACKGROUND: A substantial number of patients who relapse and die from cutaneous melanoma (CM) are categorized as being at low risk by traditional staging factors. The 31-gene expression profile (31-GEP) test independently stratifies metastatic risk of patients with CM as low (Class 1, with 1A indicating lowest risk) or high (Class 2,with 2B indicating highest risk). OBJECTIVE: To assess risk prediction by the 31-GEP test within 3 low-risk (according to the American Joint Committee on Cancer) populations of patients with CM: those who are sentinel lymph node (SLN) negative, those with stage I to IIA tumors, and those with thin (≤1 mm [T1]) tumors. METHODS: A total of 3 previous validation studies provided a nonoverlapping cohort of 690 patients with 31-GEP results, staging information, and survival outcomes. Kaplan-Meier and Cox regression analysis were performed. RESULTS: The results included the identification of 70% of SLN-negative patients who experienced metastasis as Class 2, the discovery of reduced recurrence-free survival for patients with thin tumors and Class 2B biology compared with that of those with Class 1A biology (P < .0001); and determination of the 31-GEP test as an independent predictor of risk compared with traditional staging factors in patients with stage I to IIA tumors. LIMITATIONS: Diagnoses spanned multiple versions of pathologic staging criteria. CONCLUSIONS: The 31-GEP test identifies high-risk patients who are likely to experience recurrence or die of melanoma within low-risk groups of subpopulations of patients with CM who have SLN-negative disease, stage I to IIA tumors, and thin tumors.

14 Article National practice patterns of completion lymph node dissection for sentinel node-positive melanoma. 2018

Hewitt, D Brock / Merkow, Ryan P / DeLancey, John Oliver / Wayne, Jeffrey D / Hyngstrom, John R / Russell, Maria C / Gerami, Pedram / Balch, Charles M / Bilimoria, Karl Y. ·Surgical Outcomes and Quality Improvement Center (SOQIC), Department of Surgery and Center for Healthcare Studies, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Northwestern Institute for Comparative Effectiveness Research in Oncology (NICER-Onc), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. · Division of General Surgery, Huntsman Cancer Institute, University of Utah Health Care, Salt Lake City, Utah. · Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia. · Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas. ·J Surg Oncol · Pubmed #30098302.

ABSTRACT: BACKGROUND AND OBJECTIVES: Close observation may be an appropriate alternative to completion lymph node dissection (CLND) for selected patient populations, especially those with minimal tumor burden in the sentinel lymph node (SLN). In this study, we examined the practice patterns of CLND utilization. METHODS: Using the National Cancer Database, we examined CLND utilization in SLN-positive patients diagnosed with clinically node-negative Stage III melanoma from 2012 to 2015. Hierarchical logistic regression models were constructed to assess the factors associated with observation after positive SLN biopsy (SLNB). RESULTS: Of the 131 171 patients identified, 55 688 (42.5%) underwent SLNB and 7200 (12.9%) had an SLN with a metastatic disease. CLND was performed in 57.0% of the patients with a positive SLNB. Patients were more likely to forgo CLND if the primary tumor was located on the lower extremity (odds ratio [OR], 1.65, 95% confidence interval [CI], 1.40-1.94), were older (P < 0.001), had multiple comorbidities (OR, 1.61, 95% CI, 1.19-2.20), or were diagnosed with melanoma in 2015 (OR, 1.33, 95% CI, 1.13-1.56 vs 2012). CONCLUSIONS: CLND utilization varied based on patient factors and decreased over time. As evidence supports close observation in selected patient populations with low SLN tumor burden, monitoring is needed to ensure that CLND is performed in the appropriate patient populations. However, this will require improvements in the data collected by cancer registries.

15 Article Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. 2018

Ferris, Laura K / Gerami, Pedram / Skelsey, Maral K / Peck, Gary / Hren, Catherine / Gorman, Christopher / Frumento, Tana / Siegel, Daniel M. ·Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania. · Department of Dermatology, Northwestern University, Chicago, Illinois. · Department of Dermatology, Georgetown University School of Medicine, Washington, District of Columbia. · Dermatologic Surgery Center of DC, Chevy Chase, Maryland. · Cary Dermatology Center, Cary, North Carolina. · Avenues Dermatology, Richmond, Virginia. · Phoenix Skin, Phoenix, Arizona. · SUNY Downstate Medical Center, New York City, New York, USA. ·Melanoma Res · Pubmed #30004988.

ABSTRACT: About 3 million surgical pigmented skin lesion biopsies are performed each year in the USA alone to diagnose fewer than 200 000 new cases of invasive melanoma and melanoma in situ using the current standard of care that includes visual assessment and histopathology. A recently described noninvasive adhesive patch-based gene expression rule-out test [pigmented lesion assay (PLA)] may be helpful in identifying high-risk pigmented skin lesions to aid with surgical biopsy decisions. The main objective of this utility study was to determine the real-world clinical performance of PLA use and assess how the PLA changes physician behavior in an observational cohort analysis of 381 patients assessed with the PLA. All (100%) of 51 PLA(+) test results were clinically managed with surgical biopsy. Of these, 19 (37%) were melanomas, corresponding to a number needed to biopsy of 2.7 and a biopsy ratio of 1.7. All melanomas were histopathologically classified as melanoma in situ or stage 1. Nearly all (99%) of 330 PLA(-) test results were clinically managed with surveillance. None of the three follow-up biopsies performed in the following 3-6 months, were diagnosed as melanoma histopathologically. The estimated sensitivity and specificity of the PLA from these data sets are 95 and 91%, respectively. Overall, 93% of PLA results positive for both LINC00518 and PRAME were diagnosed histopathologically as melanoma. PRAME-only and LINC00518-only lesions were melanomas histopathologically in 50 and 7%, respectively. The PLA alters clinical management of pigmented lesions and shows high clinical performance. The likelihood of positive histopathologic diagnosis of melanoma is higher in PLA results that are positive for both LINC00518 and PRAME.

16 Article Immunohistochemical and molecular analysis of spitzoid neoplasms with pulverocyte subclones. 2018

Amin, S M / Haugh, A M / Bubley, J A / Verzì, A E / Merkel, E A / Lee, C Y / Quan, V L / Garfield, E M / Sholl, L M / Zhang, B / Gerami, P. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · The Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, USA. ·Clin Exp Dermatol · Pubmed #29779219.

ABSTRACT: BACKGROUND: Clonal naevi are characterized by a focal proliferation of pigmented melanocytes in an otherwise banal naevus. These subclones are often composed of aggregates of larger, epithelioid melanocytes with nuclear atypia and dusty-grey cytoplasmic pigmentation, which are referred to as 'pulverocytes', and this finding may lead to a misdiagnosis of malignant melanoma (MM). AIM: To characterize the significance of subclones of dusty-grey pigmented epithelioid melanocytes within spitzoid neoplasms. METHODS: We studied the histological and molecular features of a series of 20 spitzoid neoplasms with pulverocyte subclones encountered in our practice, including both atypical Spitz tumours (ASTs) and invasive MMs. RESULTS: Pulverocytes were predominantly dermal, and the percentage of subclones ranged from 2% to 40%, with a median of 10% in ASTs and 25% in lesions we classified as MM. In cases with > 10% subclones, there was an increased odds of fluorescence in situ hybridization positivity (OR = 12; 95% CI 1.2-293.4; P = 0.03) and an increased odds of homozygous 9p21 deletion (OR = 3.6; 95 CI 0.28-89.82; P = 0.33), although the latter did not reach statistical significance. CONCLUSIONS: We consider spitzoid lesions with a small subclone population to be a variant of a clonal naevus with indolent behaviour, whereas lesions with larger pulverocyte populations are more likely to have chromosomal copy number aberrations and in some cases may represent malignant transformation.

17 Article Histomorphologic spectrum of germline-related and sporadic BAP1-inactivated melanocytic tumors. 2018

Garfield, Erin M / Walton, Kara E / Quan, Victor L / VandenBoom, Timothy / Zhang, Bin / Kong, Betty Y / Isales, Maria Cristina / Panah, Elnaz / Kim, Gene / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: pgerami1@nm.org. ·J Am Acad Dermatol · Pubmed #29753057.

ABSTRACT: BACKGROUND: BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) are often the earliest sign of the BAP1 tumor predisposition syndrome. Identification of BIMTs and selection of patients for germline testing affect the lives of patients with germline BAP1 mutations. OBJECTIVE: To describe the spectrum of histomorphologic findings in BAP1-inactivated melanocytic lesions to improve their recognition. We determined the frequency of sporadic versus germline cases in our cohort, assessing whether any features were statistically linked to germline status. METHODS: Histomorphologic features of BAP1-inactivated melanocytic lesions were analyzed by comparing cases with germline mutations with those with unknown or negative status. Available clinical follow-up data were reported. RESULTS: The histomorphologic spectrum of BAP1-inactivated melanocytic lesions is broad; it includes cases with spitzoid cytomorphology (69%), smaller epithelioid cells without spitzoid features (31%), and rhabdoid cytologic features (58%). BIMTs from patients with germline mutations were statistically more likely to have an extensive junctional component of BAP1-inactivated melanocytes (P = .0177). All 11 patients with suspected or confirmed germline mutations had a history of cutaneous melanoma or multiple BIMTs. LIMITATIONS: The unknown germline status of 77 patients. CONCLUSION: Approximately 12% of patients with BIMTs have germline mutations. Extensive junctional involvement in a BIMT and a personal history of melanoma or previous BIMT may be additional indications for germline testing.

18 Article Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. 2018

Zager, Jonathan S / Gastman, Brian R / Leachman, Sancy / Gonzalez, Rene C / Fleming, Martin D / Ferris, Laura K / Ho, Jonhan / Miller, Alexander R / Cook, Robert W / Covington, Kyle R / Meldi-Plasseraud, Kristen / Middlebrook, Brooke / Kaminester, Lewis H / Greisinger, Anthony / Estrada, Sarah I / Pariser, David M / Cranmer, Lee D / Messina, Jane L / Vetto, John T / Wayne, Jeffrey D / Delman, Keith A / Lawson, David H / Gerami, Pedram. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 N. McKinley Drive room 4123, Tampa, FL, 33612, USA. · Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR, 97239, USA. · Department of Medical Oncology, University of Colorado School of Medicine, 12801 E. 17th Avenue, Aurora, CO, 80045, USA. · Department of Surgical Oncology, The University of Tennessee Health Science Center, 910 Madison, Suite 303, Memphis, TN, 38163, USA. · Department of Dermatology, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Pittsburgh, PA, 15213, USA. · Department of Pathology, University of Pittsburgh Medical Center, 3708 Fifth Avenue, Suite 500.94, Pittsburgh, PA, 15213, USA. · START Center for Cancer Care, 4383 Medical Drive, San Antonio, TX, 78229, USA. · Castle Biosciences, Inc., 820 S. Friendswood Drive, Suite 201, Friendswood, TX, 77546, USA. · Dermatology North Palm Beach, 840 U.S. Highway Number One, North Palm Beach, FL, 33408, USA. · Research & Development, Kelsey Research Foundation, 5615 Kirby Drive, Suite 660, Houston, TX, 77005, USA. · Affiliated Dermatology, 20401 North 73rd Street, Suite 230, Scottsdale, AZ, 85255, USA. · Pariser Dermatology Specialists, Virginia Clinical Research, Inc., 6160 Kempsville Circle, Suite 200A, Norfolk, VA, 23502, USA. · Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA, 23501-1980, USA. · Department of Sarcoma Medical Oncology, Seattle Cancer Care Alliance, 825 Eastlake Avenue E, Seattle, WA, 98109, USA. · Department of Anatomic Pathology, Moffitt Cancer Center, 10920 N. McKinley Drive, Tampa, FL, 33612, USA. · Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR, 97239, USA. · Department of Surgical Oncology, Northwestern University Feinberg School of Medicine, 251 East Huron Street, Chicago, IL, 60611, USA. · Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1600, Chicago, IL, 60611, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, 420 East Superior Street, Chicago, IL, 60611, USA. · Department of Surgery, Emory University Winship Cancer Institute, 1364 Clifton Road NE, Atlanta, GA, 30322, USA. · Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, 550 Peachtree Street NE, Atlanta, GA, 30308, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, 420 East Superior Street, Chicago, IL, 60611, USA. pgerami1@nm.org. · Departments of Dermatology and Pathology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Arkes 1600, Chicago, IL, 60611, USA. pgerami1@nm.org. ·BMC Cancer · Pubmed #29402264.

ABSTRACT: BACKGROUND: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. METHODS: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. RESULTS: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). CONCLUSIONS: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

19 Article The diagnostic value and histologic correlate of distinct patterns of shiny white streaks for the diagnosis of melanoma: A retrospective, case-control study. 2018

Verzi, Anna Eliza / Quan, Victor L / Walton, Kara E / Martini, Mary C / Marghoob, Ashfaq A / Garfield, Erin M / Kong, Betty Y / Isales, Maria Cristina / VandenBoom, Timothy / Zhang, Bin / West, Dennis P / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Dermatology Service, Memorial Sloan Kettering Cancer Center, Hauppage, New York, New York. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: pgerami1@nm.org. ·J Am Acad Dermatol · Pubmed #29138058.

ABSTRACT: BACKGROUND: Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. OBJECTIVE: We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. METHODS: Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. RESULTS: Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007). LIMITATIONS: This study was retrospective. CONCLUSION: Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma.

20 Article Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure. 2018

Haugh, Alexandra M / Zhang, Bin / Quan, Victor L / Garfield, Erin M / Bubley, Jeffrey A / Kudalkar, Emily / Verzi, Anna Elisa / Walton, Kara / VandenBoom, Timothy / Merkel, Emily A / Lee, Christina Y / Tan, Timothy / Isales, Maria Cristina / Kong, Betty Y / Wenzel, Alexander T / Bunick, Christopher G / Choi, Jaehyuk / Sosman, Jeffrey / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Dermatology, Yale University, New Haven, Connecticut, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, Illinois, USA. · Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. Electronic address: pgerami1@nm.org. ·J Invest Dermatol · Pubmed #28870692.

ABSTRACT: Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.

21 Article A single-institution assessment of superficial spreading melanoma (SSM) in the pediatric population: Molecular and histopathologic features compared with adult SSM. 2017

Verzì, Anna Elisa / Bubley, Jeffrey A / Haugh, Alexandra M / Zhang, Bin / Wagner, Annette / Kruse, Lacey / West, Dennis P / Wayne, Jeffrey / Guitart, Joan / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois. · Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois. Electronic address: pgerami1@nm.org. ·J Am Acad Dermatol · Pubmed #28754310.

ABSTRACT: BACKGROUND: The epidemiology of pediatric melanoma is distinct from that seen in adults. This is more distinguishable when pediatric patients are separated into prepubertal and adolescent groups. OBJECTIVE: In this study, we compared epidemiologic, clinical, histologic, and molecular characteristics of pediatric superficial spreading melanoma (SSM) in prepubertal and adolescent patients to that in adults. METHOD: We reviewed our database for pediatric melanomas, comparing SSM data between pediatric and adult cases for pathologic stage at presentation, ratio of radial to vertical growth phase, average Breslow depth and mitotic index, and frequency of fluorescence in situ hybridization (FISH) positivity. RESULTS: Of 84 pediatric melanomas, 38 were SSM, and 5 of the latter (6%) were prepubertal. There were no significant differences when pediatric and adult SSM were compared for stage at presentation, ratio of radial to vertical growth phase, average Breslow depth and mitotic count, or frequency of FISH positivity. A significant difference was detected for SSM arising from a precursor nevus (80% of pediatric cases versus 30% of adult cases). LIMITATIONS: Follow-up time was limited for both cohorts. CONCLUSIONS: SSM melanoma is infrequent in childhood, particularly in the prepubertal years. Features such as tumor stage, Breslow depth, mitotic activity, and FISH positivity suggest morphologic and molecular characteristics similar to those of adult SSM.

22 Article Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy. 2017

Ferris, Laura K / Jansen, Burkhard / Ho, Jonhan / Busam, Klaus J / Gross, Kenneth / Hansen, Doyle D / Alsobrook, John P / Yao, Zuxu / Peck, Gary L / Gerami, Pedram. ·Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania. · DermTech, Inc, La Jolla, California. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. · Skin Surgery Medical Group, San Diego, California. · East County Dermatology Medical Group, El Cajon, California. · Dermatologic Surgery Center of Washington, Chevy Chase, Maryland. · Department of Dermatology, Northwestern University, Chicago, Illinois. ·JAMA Dermatol · Pubmed #28445578.

ABSTRACT: Importance: Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated. Objective: To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions. Design, Setting, and Participants: In this secure web-based, multiple-reader-multiple-case study, 45 board-certified dermatologists each evaluated 60 clinical and dermoscopic images of clinically atypical pigmented lesions, first without and then with PLA gene expression information and were asked whether the lesions should be biopsied. Data were collected from March 24, 2014, through November 13, 2015. Interventions: Participants were given a report for each lesion, which included the results of an assay for expression of LINC00518/PRAME and a PLA score with data on the predictive values of the information provided. Main Outcomes and Measures: Biopsy sensitivity and specificity with vs without PLA data. Results: Forty-five dermatologists (29 male and 16 female) performed the evaluation. After incorporating the PLA into their decision as to whether to biopsy a pigmented lesion suggestive of melanoma, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to 56.9% (P < .001) with PLA data. Conclusions and Relevance: The noninvasive PLA enables dermatologists to significantly improve biopsy specificity while maintaining or improving sensitivity. This result may increase the number of early melanomas biopsied and reduce the number of benign lesions biopsied, thereby improving patient outcomes and reducing health care costs.

23 Article Identification of high-risk cutaneous melanoma tumors is improved when combining the online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31-gene expression profile-based classification. 2017

Ferris, Laura K / Farberg, Aaron S / Middlebrook, Brooke / Johnson, Clare E / Lassen, Natalie / Oelschlager, Kristen M / Maetzold, Derek J / Cook, Robert W / Rigel, Darrell S / Gerami, Pedram. ·Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: ferrlk@upmc.edu. · National Society for Cutaneous Medicine, New York, New York. · Castle Biosciences Inc, Friendswood, Texas. · Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. ·J Am Acad Dermatol · Pubmed #28110997.

ABSTRACT: BACKGROUND: A significant proportion of patients with American Joint Committee on Cancer (AJCC)-defined early-stage cutaneous melanoma have disease recurrence and die. A 31-gene expression profile (GEP) that accurately assesses metastatic risk associated with primary cutaneous melanomas has been described. OBJECTIVE: We sought to compare accuracy of the GEP in combination with risk determined using the web-based AJCC Individualized Melanoma Patient Outcome Prediction Tool. METHODS: GEP results from 205 stage I/II cutaneous melanomas with sufficient clinical data for prognostication using the AJCC tool were classified as low (class 1) or high (class 2) risk. Two 5-year overall survival cutoffs (AJCC 79% and 68%), reflecting survival for patients with stage IIA or IIB disease, respectively, were assigned for binary AJCC risk. RESULTS: Cox univariate analysis revealed significant risk classification of distant metastasis-free and overall survival (hazard ratio range 3.2-9.4, P < .001) for both tools. In all, 43 (21%) cases had discordant GEP and AJCC classification (using 79% cutoff). Eleven of 13 (85%) deaths in that group were predicted as high risk by GEP but low risk by AJCC. LIMITATIONS: Specimens reflect tertiary care center referrals; more effective therapies have been approved for clinical use after accrual. CONCLUSIONS: The GEP provides valuable prognostic information and improves identification of high-risk melanomas when used together with the AJCC online prediction tool.

24 Article A clinical, histologic, and follow-up study of genital melanosis in men and women. 2017

Haugh, Alexandra M / Merkel, Emily A / Zhang, Bin / Bubley, Jeffrey A / Verzì, Anna Elisa / Lee, Christina Y / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois. Electronic address: pgerami1@nm.org. ·J Am Acad Dermatol · Pubmed #27986395.

ABSTRACT: BACKGROUND: Genital melanosis may clinically mimic melanoma. Little is known about the potential risk for genital and nongenital melanoma in these patients. OBJECTIVE: In this retrospective cohort study, we analyzed clinical and histologic data from patients with genital melanosis to better characterize these lesions and the risk they confer for genital and nongenital melanoma. METHODS: In all, 41 patients were identified for a retrospective chart review and histologic analysis. RESULTS: Genital melanosis can clinically mimic melanoma but the typical age of onset is younger than for genital melanoma. A majority of lesions were found to stabilize or regress over time. Five patients were found to have a history of melanoma, only 1 of which was in the genital region. Lesions from these patients were more likely to show melanocytes with suprabasal movement (P = .0101) and to have a higher melanocyte count (P < .0462). LIMITATIONS: We present a relatively small cohort of patients with an average follow-up of only 30.5 months. CONCLUSION: Patients with genital melanosis, and in particular those with any level of histologic atypia in the genital melanosis lesion, may require careful total body skin examinations for the possibility of melanoma in any body site.

25 Article Reduced H3K27me3 Expression Is Common in Nodular Melanomas of Childhood Associated With Congenital Melanocytic Nevi But Not in Proliferative Nodules. 2017

Busam, Klaus J / Shah, Kara N / Gerami, Pedram / Sitzman, Thomas / Jungbluth, Achim A / Kinsler, Veronica. ·*Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY †Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, OH ‡Department of Dermatology, Northwestern University, Chicago, IL §Great Ormond Street Hospital for Children ∥UCL Institute of Child Health, London, UK. ·Am J Surg Pathol · Pubmed #27849631.

ABSTRACT: The formation of a nodule within a congenital melanocytic nevus (CMN) raises concerns about possible melanoma. Most new nodular growths that develop during childhood, however, are benign proliferative nodules (PN); melanoma is very rare. The distinction of melanoma from PN can at times be difficult clinically and histopathologically, requiring ancillary molecular tests for diagnosis. Although the application of molecular methods has revealed new insights into the mutational and genomic landscape of childhood melanomas, little is known about epigenetic events that may drive the growth of a melanoma or PN in a CMN. In this study we compared the expression of H3K27me3, a key regulator in chromatin remodelling-controlled transcription, in PNs and pediatric nodular melanomas arising within medium-sized to large CMN by immunohistochemistry. Significant loss of H3K27me3 expression was seen in 4 of 5 melanomas, but not in any of the 20 PNs. This observation suggests that epigenetic events likely play a role in the pathogenesis of melanoma developing in the dermis or subcutis of CMN. Furthermore, assessing for H3K27me3 expression by immunohistochemistry may be diagnostically useful for problematic cases.

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