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Melanoma: HELP
Articles by Pedram Gerami
Based on 84 articles published since 2010
(Why 84 articles?)
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Between 2010 and 2020, P. Gerami wrote the following 84 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Advancements in unresectable melanoma: a multidisciplinary perspective. 2016

Malecek, Mary-Kate / Robinson, June K / Bilimoria, Karl / Choi, Jennifer N / Choi, Jaehyuk / Gerami, Pedram / Kruser, Timothy / Kuzel, Timothy / Martini, Mary / Strauss, Jonathan B / Wayne, Jeffrey / Sosman, Jeffrey / Chandra, Sunandana. ·Department of Medicine, Northwestern University Feinberg School of Medicine, 251 East Huron Street, Galter Pavilion Suite 3-150, Chicago, IL 60611, USA. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Division of Surgical Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Division of Medical Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ·Melanoma Manag · Pubmed #30190886.

ABSTRACT: -- No abstract --

2 Review The role of gene fusions in melanocytic neoplasms. 2019

Quan, Victor L / Panah, Elnaz / Zhang, Bin / Shi, Katherine / Mohan, Lauren S / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. ·J Cutan Pathol · Pubmed #31152596.

ABSTRACT: Recent advances in next generation sequencing (NGS) have allowed for efficient whole transcriptome sequencing, leading to the identification of important kinase fusions as the primary driver in some melanocytic neoplasms. These fusions typically occur mutually exclusively of one another and other well-known initiating mutations such as BRAF, NRAS, NF1, KIT, and GNAQ. Fusions are found in over 50% of Spitz neoplasms, including ALK, BRAF, NTRK1, NTRK3, ROS1, MET, MAP3K8, and RET. Familiarity with the typical morphologic features of certain fusion-driven melanocytic neoplasms can help with classification, diagnosis, and identification of targeted molecular therapies in malignant cases. Spitz tumors with ALK, NTRK1, and NTRK3 fusions have characteristic morphologic features. BRAF and MAP3K8 fusions, in particular, tend to be epithelioid, high grade, and more frequent in Spitz melanoma than other fusion subtypes. Sporadic cases of pigmented epithelioid melanocytoma may have PRKCA fusions and sheets of monomorphic epithelioid melanocytes. Fusion events are also enriched among melanomas without the key mutations BRAF, NRAS, or NF1. Although NGS is the most reliable method to detect fusions, immunohistochemistry and fluorescence in situ hybridization are cost-effective alternatives in some cases. We describe recent discoveries regarding the role of kinase fusions in melanocytic neoplasms and their associated morphologies.

3 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.

4 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 --

5 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.

6 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.

7 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.

8 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.

9 Review Predicting the outcome of melanoma: can we tell the future of a patient's melanoma? 2015

Yélamos, Oriol / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, The Robert H Lurie Cancer Center, Northwestern University, 676 N. St Clair Street, Suite 1765, Chicago, IL 60611, USA. ·Melanoma Manag · Pubmed #30190851.

ABSTRACT: Cutaneous melanoma is responsible for the greatest number of skin cancer related deaths. For many years there were few therapeutic options. However, in the last years a number of new therapeutic options have emerged showing improved survival rates for advanced melanoma patients. A significant question based on these findings is whether identification and treatment of patients with biologically aggressive melanomas at an earlier clinical stage offer an opportunity for even greater improvement in overall survival. In this review, we will discuss the recent advancements in molecular strategies beyond traditional staging to identify biologically aggressive melanomas, and which are their implications in terms of predicting the prognosis of patients with melanoma.

10 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.

11 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.

12 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.

13 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.

14 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.

15 Article Incorporation of dermoscopy improves inter-observer agreement among dermatopathologists in histologic assessment of melanocytic neoplasms. 2020

Shi, Katherine / Compres, Elsy / Walton, Kara E / Mohan, Lauren S / Zhang, Bin / Panah, Elnaz / Quan, Victor L / Garfield, Erin M / Khan, Ayesha U / Kim, Daniel / Yazdan, Pedram / Robinson, June K / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. pgerami1@nm.org. · Department of Dermatopathology, Northwestern University, 676 N. St. Clair Street, Suite 1765, Chicago, IL, 60611, USA. pgerami1@nm.org. ·Arch Dermatol Res · Pubmed #32338293.

ABSTRACT: Histopathologic assessment of melanocytic neoplasms is the current gold standard of diagnosis. However, there are well recognized limitations including inter-observer diagnostic discordance. This study aimed to determine if integrating dermoscopy with histopathology of melanocytic neoplasms impacts diagnosis and improves inter-observer agreement. We conducted a prospective cohort study in a pigmented lesion clinic. Consecutive melanocytic lesions were identified for biopsy based on atypical gross or dermoscopic features. Standardized immunohistochemistry and levels were ordered on each specimen. The cases were randomized. Three dermatopathologists blinded to the clinical impression assessed each lesion. The cases were then re-randomized and re-assessed with addition of gross clinical and dermoscopic images. Inter-rater reliability (IRR) using Fleiss' kappa statistic revealed an increase from 0.447 without to 0.496 with dermoscopy amongst all dermatopathologists. The kappa increased from 0.495 before to 0.511 with dermoscopy in separating high-grade atypia or melanoma from moderate atypia or less. In 16 of 136 cases, at least 2 of 3 dermatopathologists favored a diagnosis of melanoma only after dermoscopy. In total, the consensus grade of atypia changed in 24.3% (33/ 136) of cases thereby representing changes to excisional margins and patient follow up. This study is limited by the cohort size. Dermoscopy significantly impacts diagnosis and improves identification of early melanomas in high risk populations and improves inter-observer agreement.

16 Article Keratinocyte cadherin desmoglein 1 controls melanocyte behavior through paracrine signaling. 2020

Arnette, Christopher R / Roth-Carter, Quinn R / Koetsier, Jennifer L / Broussard, Joshua A / Burks, Hope E / Cheng, Kathleen / Amadi, Christine / Gerami, Pedram / Johnson, Jodi L / Green, Kathleen J. ·Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. ·Pigment Cell Melanoma Res · Pubmed #31563153.

ABSTRACT: The epidermis is the first line of defense against ultraviolet (UV) light from the sun. Keratinocytes and melanocytes respond to UV exposure by eliciting a tanning response dependent in part on paracrine signaling, but how keratinocyte:melanocyte communication is regulated during this response remains understudied. Here, we uncover a surprising new function for the keratinocyte-specific cell-cell adhesion molecule desmoglein 1 (Dsg1) in regulating keratinocyte:melanocyte paracrine signaling to promote the tanning response in the absence of UV exposure. Melanocytes within Dsg1-silenced human skin equivalents exhibited increased pigmentation and altered dendrite morphology, phenotypes which were confirmed in 2D culture using conditioned media from Dsg1-silenced keratinocytes. Dsg1-silenced keratinocytes increased melanocyte-stimulating hormone precursor (Pomc) and cytokine mRNA. Melanocytes cultured in media conditioned by Dsg1-silenced keratinocytes increased Mitf and Tyrp1 mRNA, TYRP1 protein, and melanin production and secretion. Melanocytes in Dsg1-silenced skin equivalents mislocalized suprabasally, reminiscent of early melanoma pagetoid behavior. Together with our previous report that UV reduces Dsg1 expression, these data support a role for Dsg1 in controlling keratinocyte:melanocyte paracrine communication and raise the possibility that a Dsg1-deficient niche contributes to pagetoid behavior, such as occurs in early melanoma development.

17 Article Distinct Genomic Features in a Retrospective Cohort of Mucosal, Acral and Vulvovaginal Melanomas. 2019

Shi, Katherine / Zhang, Bin / Kong, Betty Y / Zhang, Yongzhan / Igartua, Catherine / Mohan, Lauren S / Quan, Victor L / Panah, Elnaz / Isales, Maria Cristina / Beaubier, Nike / Taxter, Timothy J / White, Kevin P / Zou, Lihua / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL. · Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL. · Tempus Labs, Inc., Chicago, IL. · Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL. · Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, IL. Electronic address: zoul@northwestern.edu. · Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL; Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address: pgerami1@nm.org. ·J Am Acad Dermatol · Pubmed #31306728.

ABSTRACT: BACKGROUND: Compared to sun-exposed melanomas, less is known regarding the pathogenesis of sun-protected melanomas. Sun-protected melanomas share many epidemiologic factors but their genetic heterogeneity is not well studied. OBJECTIVE: We investigated the genomic profile of acral, mucosal and vulvovaginal melanomas. We hypothesize that mucosal melanomas, recognized for their uniquely aggressive clinical behavior, have distinct genomic features. METHODS: We performed whole transcriptome mRNA and DNA (1711 genes) sequencing, mRNA expression profiling, TMB, UV signature and CNV analysis on 29 volar/digital acral, 7 mucosal and 6 vulvovaginal melanomas. RESULTS: There was significant genetic heterogeneity, particularly in acral melanomas with 36% having BRAF alterations while other melanomas had none (p = 0.0159). Nonzero UV signatures were more frequent in acral melanomas, suggesting greater UV involvement. Mucosal melanomas formed a distinct group with increased expression of cell cycle and proliferation genes. Various targetable aberrations were identified such as AURKA and ERBB2 in mucosal and acral melanomas, respectively. LIMITATIONS: There was a small sample size. CONCLUSION: There is significant genetic heterogeneity among sun-protected melanomas. Mucosal melanomas have upregulation in cell cycle and proliferation genes, which may explain their aggressive behavior. Ultraviolet radiation plays some role in a subset of acral but not other melanomas.

18 Article Performance of a 31-gene expression profile test in cutaneous melanomas of the head and neck. 2019

Gastman, Brian R / Zager, Jonathan S / Messina, Jane L / Cook, Robert W / Covington, Kyle R / Middlebrook, Brooke / Gerami, Pedram / Wayne, Jeffrey D / Leachman, Sancy / Vetto, John T. ·Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida. · Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida. · Research & Development, Castle Biosciences, Inc., Friendswood, Texas. · 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. · Department of Surgical Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. · Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. ·Head Neck · Pubmed #30694001.

ABSTRACT: BACKGROUND: We report the performance of a gene expression profile test to classify the recurrence risk of cutaneous melanoma tumors of the head and neck as low-risk Class 1 or high-risk Class 2. METHODS: Of note, 157 primary head and neck cutaneous melanoma tumors were identified. Survival analyses were performed using Kaplan-Meier and Cox methods. RESULTS: Gene expression profile class and node status stratified tumors into significantly different 5-year survival groups by Kaplan-Meier method (P < .0001 for all end points), and both were independent predictors of recurrence in multivariate analysis. Overall, 74% of distant metastases and 88% of melanoma-specific deaths had Class 2 risk. CONCLUSION: The gene expression profile test identifies cases at increased risk for metastasis and death independent of a clinically or pathologically negative nodal status, suggesting that incorporation of this molecular tool could improve clinical management of patients with head and neck cutaneous melanoma, especially in those with a negative sentinel lymph node biopsy.

19 Article Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling. 2019

Vetto, John T / Hsueh, Eddy C / Gastman, Brian R / Dillon, Larry D / Monzon, Federico A / Cook, Robert W / Keller, Jennifer / Huang, Xin / Fleming, Andrew / Hewgley, Preston / Gerami, Pedram / Leachman, Sancy / Wayne, Jeffrey D / Berger, Adam C / Fleming, Martin D. ·Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA. · Department of Surgery, St Louis University, St Louis, MO 63110, USA. · Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44915, USA. · Larry D Dillon Surgical Oncology & General Surgery, Colorado Springs, CO 80907, USA. · Castle Biosciences, Inc., Friendswood, TX 77546, USA. · Division of Surgical Oncology, Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago IL 60611, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA. · Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago IL 60611, USA. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA. · Department of Surgical Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. · Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA 19017, USA. ·Future Oncol · Pubmed #30691297.

ABSTRACT: AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy.

20 Article Noninvasive Analysis of High-Risk Driver Mutations and Gene Expression Profiles in Primary Cutaneous Melanoma. 2019

Ferris, Laura K / Moy, Ronald L / Gerami, Pedram / Sligh, James E / Jansen, Burkhard / Yao, Zuxu / Cockerell, Clay J. ·Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: ferrlk@upmc.edu. · RodeoDerm Moy Fincher Chips, Beverly Hills, California, USA. · Department of Dermatology, Northwestern University, Chicago, Illinois, USA. · Southern Arizona Veterans Affairs Healthcare System and University of Arizona, Tucson, Arizona, USA. · DermTech, Inc., La Jolla, California, USA. · Cockerell Dermatopathology, Dallas, Texas, USA. ·J Invest Dermatol · Pubmed #30500343.

ABSTRACT: Tools that help reduce the number of surgical biopsies performed on benign lesions have the potential to improve patient care. The pigmented lesion assay (PLA) is a noninvasive tool validated against histopathology that helps rule out melanoma and the need for surgical biopsies of atypical pigmented skin lesions. Genetic information is collected using adhesive patches and the expression of two genes, LINC and PRAME, is measured. By using genetic material collected noninvasively and to further validate the PLA, somatic hotspot mutations in genes known to be drivers of early melanoma development (BRAF other than V600E, NRAS, and the TERT promoter) can also be identified. The frequency of these hotspot mutations in samples of early melanoma was 77%, which is higher than the 14% found in nonmelanoma samples (P < 0.0001). TERT promoter mutations were the most prevalent mutation type in PLA-positive melanomas; 82% of PLA-negative lesions had no mutations, and 97% of histopathologically confirmed melanomas were PLA and/or mutation positive (cohort 1, n = 103). Mutation frequencies were similar in prospectively collected real-world PLA samples (cohort 2, n = 519), in which 88% of PLA-negative samples had no mutations. Combining gene expression and mutation analyses enhances the ability to noninvasively detect early cutaneous melanoma.

21 Article Distinct Genomic Patterns in Pigmented Epithelioid Melanocytoma: A Molecular and Histologic Analysis of 16 Cases. 2019

Isales, Maria C / Mohan, Lauren S / Quan, Victor L / Garfield, Erin M / Zhang, Bin / Shi, Katherine / Arva, Nicoleta / Beaubier, Nike / Yazdan, Pedram / White, Kevin / Taxter, Timothy J / Gerami, Pedram. ·Departments of Pathology. · Dermatology, Feinberg School of Medicine, Northwestern University. · Tempus Labs Inc., Chicago, IL. ·Am J Surg Pathol · Pubmed #30475255.

ABSTRACT: Pigmented epithelioid melanocytoma (PEM) is considered an intermediate grade melanocytic lesion that is histologically indistinguishable from epithelioid blue nevi associated with Carney complex. PEM are characterized by an intradermal population of heavily pigmented epithelioid-shaped melanocytes along with some spindled and dendritic melanocytes with frequent melanophages. These melanocytic tumors occasionally involve regional lymph nodes but only rarely result in distant metastases. Recent studies have demonstrated a variable but limited number of specific genomic aberrations including protein kinase A regulatory subunit alpha (PRKAR1A), BRAF, GNAQ, and MAP2K1 mutations as well as protein kinase C alpha isoform (PRKCA) fusions. We performed an 8-year retrospective review of our database and identified 16 cases of PEM. Using targeted DNA sequencing and RNA-seq to assess 1714 cancer-related genes, we detected gene fusions involving PRKCA in 31% of cases (5/16) with 5' partners SCARB1(12q24) in 2 cases, CD63 (12q13) in 1 case, ATP2B4 (1q32) in 1 case, and MAP3K3 (17q23) in 1 case. Additional fusions were identified in TPR-NTRK1 (1/16), ALK (1/16), and MYO5A-NTRK3 (1/16). PRKCA fusion lesions tended to occur in younger-aged patients and histologic examination demonstrated sheets of monomorphic epithelioid-shaped melanocytes, moderate to high-grade nuclear atypia, and higher mitotic activity (P=0.037). Our gene panel also identified previously described mutations in PRKAR1A, GNAQ, MAP2K1, BRAF, NF1. To our knowledge, this is the largest and most comprehensive study of PEM integrating molecular data with histologic features that can be utilized in future studies for improved subclassification and prognostication of heavily pigmented melanocytic neoplasms.

22 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.

23 Article Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: Results of a multicenter case-control study by the International Dermoscopy Society. 2019

Yélamos, Oriol / Navarrete-Dechent, Cristián / Marchetti, Michael A / Rogers, Tova / Apalla, Zoe / Bahadoran, Philippe / Blázquez-Sánchez, Nuria / Busam, Klaus / Carrera, Cristina / Dusza, Stephen W / de la Fouchardière, Arnaud / Ferrara, Gerardo / Gerami, Pedram / Kittler, Harald / Lallas, Aimilios / Malvehy, Josep / Millán-Cayetano, José F / Nelson, Kelly C / Quan, Victor Li / Puig, Susana / Stevens, Howard / Thomas, Luc / Marghoob, Ashfaq A. ·Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Dermatology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, and CIBER de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain. Electronic address: oyelamos@gmail.com. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Dermatology, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · First Department of Dermatology, Aristotle University, Thessaloniki, Greece. · Dermatology Department, Centre Hospitalier Universitaire de Nice, Nice, France. · Dermatology Department, Hospital Costa del Sol, Marbella, Spain. · Pathology Department, Memorial Sloan Kettering Cancer Center, New York, New York. · Dermatology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, and CIBER de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain. · Département de Biopathologie, Centre Léon Bérard, Lyon, France. · Anatomic Pathology Unit, Hospital of Macerata, Macerata, Italy. · Dermatology Department, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. · Dermatology Department, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Skin Care Network, Barnet, London, United Kingdom. · Department of Dermatology, Lyon 1 University, Centre Hospitalier Lyon Sud and Lyon's Cancer Research Center INSERM U1052 - CNRS UMR5286, Lyon, France. ·J Am Acad Dermatol · Pubmed #30244062.

ABSTRACT: BACKGROUND: Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1. OBJECTIVES: We sought to describe the clinical and dermoscopic features of BIMTs. METHODS: This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients. RESULTS: The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P < .0001 and P = .001, respectively). LIMITATIONS: Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs. CONCLUSIONS: Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.

24 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.

25 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.

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