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355. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

Author

Rindi, Guido, Klimstra, David S., Abedi-Ardekani, Behnoush, Asa, Sylvia L., Bosman, Frederik T., Brambilla, Elisabeth, Busam, Klaus J., de Krijger, Ronald R., Dietel, Manfred, El-Naggar, Adel K., Fernandez-Cuesta, Lynnette, McCluggage, W. Glenn, Moch, Holger, Ohgaki, Hiroko, Rakha, Emad A., Reed, Nicholas S., Rous, Brian A., Sasano, Hironobu, Scarpa, Aldo, Scoazec, Jean Yves, Travis, William D., Tallini, Giovanni, Trouillas, Jacqueline, van Krieken, J. Han, and Cree, Ian A.

Subjects
Pathology and Forensic Medicine
Abstract

© 2018, United States & Canadian Academy of Pathology. The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.

Published
2018

356. Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A

Author

Pourmaleki, Maryam, primary, Young, Jonathan H., additional, Socci, Nicholas D., additional, Chiang, Sarah, additional, Edelweiss, Marcia, additional, Li, Yanyun, additional, Zhang, Mianlei, additional, Roshal, Lev, additional, Chi, Dennis S., additional, Busam, Klaus J., additional, Mellinghoff, Ingo K., additional, and Hollmann, Travis J., additional

Published
2019
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361. Relationship of Chromosome Arm 10q Variants to Occurrence of Multiple Primary Melanoma in the Population-Based Genes, Environment, and Melanoma (GEM) Study

Author

Miles, Jonathan A., primary, Orlow, Irene, additional, Kanetsky, Peter A., additional, Luo, Li, additional, Cust, Anne E., additional, Armstrong, Bruce K., additional, Kricker, Anne, additional, Anton-Culver, Hoda, additional, Gruber, Stephen B., additional, Gallagher, Richard P., additional, Zanetti, Roberto, additional, Rosso, Stefano, additional, Sacchetto, Lidia, additional, Dwyer, Terence, additional, Gibbs, David C., additional, Busam, Klaus J., additional, Mavinkurve, Vikram, additional, Ollila, David W., additional, Begg, Colin B., additional, Berwick, Marianne, additional, Thomas, Nancy E., additional, Begg, Colin, additional, Roy, Pampa, additional, Leong, Siok, additional, Corrales-Guerrero, Sergio, additional, Sadeghi, Keimya, additional, Reiner, Anne, additional, Boyce, Tawny W., additional, Venn, Alison, additional, Tucker, Paul, additional, Lai, Agnes, additional, Marrett, Loraine D., additional, From, Lynn, additional, Huang, Shu-Chen, additional, Conway, Kathleen, additional, Groben, Pamela A., additional, Edmiston, Sharon N., additional, Hao, Honglin, additional, Parrish, Eloise, additional, Frank, Jill S., additional, Rebbeck, Timothy R., additional, Lee Taylor, Julia, additional, and Madronich, Sasha, additional

Published
2019
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362. Massively parallel sequencing analysis of benign melanocytic naevi

Author

Lozada, John R, primary, Geyer, Felipe C, additional, Selenica, Pier, additional, Brown, David, additional, Alemar, Barbara, additional, Merghoub, Taha, additional, Berger, Michael F, additional, Busam, Klaus J, additional, Halpern, Allan C, additional, Weigelt, Britta, additional, Reis‐Filho, Jorge S, additional, and Hollmann, Travis J, additional

Published
2019
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364. Therapeutic implications of a novel driver classification system for cutaneous and unknown primary melanomas.

Author

Shoushtari, Alexander Noor, primary, Sanchez-Vega, Francisco, additional, Kantheti, Havish, additional, Callahan, Margaret K., additional, Postow, Michael A., additional, Barker, Christopher Andrew, additional, Chatila, Walid K., additional, Jonsson, Philip, additional, Ariyan, Charlotte Eielson, additional, Brady, Mary Susan, additional, Coit, Daniel G., additional, Nair, Suresh, additional, Chapman, Paul B., additional, Busam, Klaus J., additional, Solit, David B., additional, Wolchok, Jedd D., additional, and Schultz, Nikolaus, additional

Published
2019
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368. Defining Novel DNA Virus-Tumor Associations and Genomic Correlates Using Prospective Clinical Tumor/Normal Matched Sequencing Data

Author

Vanderbilt, Chad M., Bowman, Anita S., Middha, Sumit, Petrova-Drus, Kseniya, Tang, Yi-Wei, Chen, Xin, Wang, Youxiang, Chang, Jason, Rekhtman, Natasha, Busam, Klaus J., Gupta, Sounak, Hameed, Meera, Arcila, Maria E., Ladanyi, Marc, Berger, Michael F., Dogan, Snjezana, and Zehir, Ahmet

Abstract

This study is the largest analysis of DNA viruses in solid tumors with associated genomics. To achieve this, a novel method for discovery of DNA viruses from matched tumor/normal next-generation sequencing samples was developed and validated. This method performed comparably to reference methods for the detection of high-risk (HR) human papilloma virus (HPV) (area under the receiver operating characteristic curve = 0.953). After virus identification in 48,148 consecutives samples from 42,846 unique patients, novel virus tumor associations were established by segregating tumor types to determine whether each DNA virus was enriched in each of the tumor types compared with the remaining cohort. All firmly established solid tumor-virus associations (eg, HR HPV in cervical cancer) were confirmed, and the novel associations discovered included: human herpes virus 6 in neuroblastoma, human herpes virus 7 in esophagogastric cancer, and HPV42 in digital papillary adenocarcinoma. These associations were confirmed in an independent validation cohort. HR HPV– and Epstein-Barr virus–associated tumors showed newly discovered genomic associations, including a lower tumor mutation burden. The study demonstrated the ability to study the role of DNA viruses in human cancer from clinical genomics data and established the largest cohort that can be utilized as a validation set for future discovery efforts.

Published
2022
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371. Dermal melanocytic tumor with CRTC1‐TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity.

Author

Parra, Ourania, Bridge, Julia A., Busam, Klaus J., Shalin, Sara C., and Linos, Konstantinos

Subjects
MELANOMA, ADULTS, ENGLISH literature, METASTASIS
Abstract

"Cutaneous melanocytic tumor with CRTC1‐TRIM11 fusion" (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100‐protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow‐up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65‐year‐old female and the other on the arm of a 33‐year‐old female in addition to a comprehensive literature review are reported. [ABSTRACT FROM AUTHOR]

Published
2021
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380. Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Author

Thomas, Nancy E., primary, Edmiston, Sharon N., additional, Orlow, Irene, additional, Kanetsky, Peter A., additional, Luo, Li, additional, Gibbs, David C., additional, Parrish, Eloise A., additional, Hao, Honglin, additional, Busam, Klaus J., additional, Armstrong, Bruce K., additional, Kricker, Anne, additional, Cust, Anne E., additional, Anton-Culver, Hoda, additional, Gruber, Stephen B., additional, Gallagher, Richard P., additional, Zanetti, Roberto, additional, Rosso, Stefano, additional, Sacchetto, Lidia, additional, Dwyer, Terence, additional, Ollila, David W., additional, Begg, Colin B., additional, Berwick, Marianne, additional, Conway, Kathleen, additional, Begg, Colin, additional, Roy, Pampa, additional, Reiner, Anne, additional, Leong, Siok, additional, Guerrero, Sergio Corrales, additional, Sadeghi, Keimya, additional, Boyce, Tawny W., additional, Venn, Alison, additional, Tucker, Paul, additional, Marrett, Loraine D., additional, From, Lynn, additional, Huang, Shu-Chen, additional, Thomas, Nancy E., additional, Groben, Pamela A., additional, Parrish, Eloise, additional, Frank, Jill S., additional, Rebbeck, Timothy R., additional, Lee Taylor, Julia, additional, and Madronich, Sasha, additional

Published
2018
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381. Tumor Board Conferences for Multidisciplinary Skin Cancer Management: A Survey of US Cancer Centers

Author

Mori, Shoko, primary, Navarrete-Dechent, Cristian, additional, Petukhova, Tatyana A., additional, Lee, Erica H., additional, Rossi, Anthony M., additional, Postow, Michael A., additional, Dunn, Lara A., additional, Roman, Benjamin R., additional, Yin, Vivian T., additional, Coit, Daniel G., additional, Hollmann, Travis J., additional, Busam, Klaus J., additional, Nehal, Kishwer S., additional, and Barker, Christopher A., additional

Published
2018
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385. Tumor mutational burden, clinical features, and outcomes to PD-1 mono- and combination therapy in patients with cutaneous and unknown primary melanoma.

Author

Shoushtari, Alexander Noor, primary, Armenia, Joshua, additional, Arora, Arshi, additional, Rojas-Zamalloa, Jorge, additional, Betof Warner, Allison, additional, Derr, Megan, additional, Postow, Michael A., additional, Callahan, Margaret K., additional, Momtaz, Parisa, additional, Coit, Daniel G., additional, Brady, Mary Susan, additional, Ariyan, Charlotte Eielson, additional, Nair, Suresh, additional, Busam, Klaus J., additional, Chapman, Paul B., additional, Schultz, Nikolaus, additional, and Wolchok, Jedd D., additional

Published
2018
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387. Guidelines of care for the management of basal cell carcinoma

Author

Kim, John Y.S., primary, Kozlow, Jeffrey H., additional, Mittal, Bharat, additional, Moyer, Jeffrey, additional, Olencki, Thomas, additional, Rodgers, Phillip, additional, Bichakjian, Christopher, additional, Armstrong, April, additional, Baum, Christian, additional, Bordeaux, Jeremy S., additional, Brown, Marc, additional, Busam, Klaus J., additional, Eisen, Daniel B., additional, Iyengar, Vivek, additional, Lober, Clifford, additional, Margolis, David J., additional, Messina, Jane, additional, Miller, Alexander, additional, Miller, Stanley, additional, Mostow, Eliot, additional, Mowad, Christen, additional, Nehal, Kishwer, additional, Schmitt-Burr, Kristi, additional, Sekulic, Aleksandar, additional, Storrs, Paul, additional, Teng, Joyce, additional, Yu, Siegrid, additional, Huang, Conway, additional, Boyer, Kevin, additional, Begolka, Wendy Smith, additional, and Alam, Murad, additional

Published
2018
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388. Guidelines of care for the management of cutaneous squamous cell carcinoma

Author

Kim, John Y.S., primary, Kozlow, Jeffrey H., additional, Mittal, Bharat, additional, Moyer, Jeffrey, additional, Olenecki, Thomas, additional, Rodgers, Phillip, additional, Alam, Murad, additional, Armstrong, April, additional, Baum, Christian, additional, Bordeaux, Jeremy S., additional, Brown, Marc, additional, Busam, Klaus J., additional, Eisen, Daniel B., additional, Iyengar, Vivek, additional, Lober, Clifford, additional, Margolis, David J., additional, Messina, Jane, additional, Miller, Alexander, additional, Miller, Stanley, additional, Mostow, Eliot, additional, Mowad, Christen, additional, Nehal, Kishwer, additional, Schmitt-Burr, Kristi, additional, Sekulic, Aleksandar, additional, Storrs, Paul, additional, Teng, Joyce, additional, Yu, Siegrid, additional, Huang, Conway, additional, Boyer, Kevin, additional, Begolka, Wendy Smith, additional, and Bichakjian, Christopher, additional

Published
2018
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398. Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.

Author

Thomas, Nancy E, Thomas, Nancy E, Edmiston, Sharon N, Orlow, Irene, Kanetsky, Peter A, Luo, Li, Gibbs, David C, Parrish, Eloise A, Hao, Honglin, Busam, Klaus J, Armstrong, Bruce K, Kricker, Anne, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Dwyer, Terence, Ollila, David W, Begg, Colin B, Berwick, Marianne, Conway, Kathleen, GEM Study Group, Thomas, Nancy E, Thomas, Nancy E, Edmiston, Sharon N, Orlow, Irene, Kanetsky, Peter A, Luo, Li, Gibbs, David C, Parrish, Eloise A, Hao, Honglin, Busam, Klaus J, Armstrong, Bruce K, Kricker, Anne, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Dwyer, Terence, Ollila, David W, Begg, Colin B, Berwick, Marianne, Conway, Kathleen, and GEM Study Group

Abstract

BRAF and NRAS mutations arise early in melanoma development, but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma Study, 1,223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms identified as low-penetrant melanoma-risk variants. We used multinomial logistic regression to simultaneously examine each single-nucleotide polymorphism's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features. IRF4 rs12203592*T was associated with BRAF V600E (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.43-0.79) and V600K (OR = 0.65, 95% CI = 0.41-1.03), but not BRAF other or NRAS+ melanoma. A global test of etiologic heterogeneity (Pglobal = 0.001) passed false discovery (Pglobal = 0.0026). PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma. The test for etiologic heterogeneity (Pglobal) was 0.005. The IRF4 rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6 rs132985 associations were independent of phenotypes. IRF4 and PLA2G6 inherited genotypes may influence melanoma BRAF/NRAS subtype development.

Published
2018

399. Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma

Author

Taylor, Nicholas J, Thomas, Nancy E, Anton-Culver, Hoda, Armstrong, Bruce K, Begg, Colin B, Busam, Klaus J, Cust, Anne E, Dwyer, Terence, From, Lynn, Gallagher, Richard P, Gruber, Stephen B, Nishri, Diane E, Orlow, Irene, Rosso, Stefano, Venn, Alison J, Zanetti, Roberto, Berwick, Marianne, Kanetsky, Peter A, and GEM Study Group

Subjects
Adult, Male, Skin Neoplasms, Oncology and Carcinogenesis, Kaplan-Meier Estimate, phenotypic characteristics, Pigmented, Risk Factors, Clinical Research, Odds Ratio, melanoma, Humans, disease-specific survival, Climate-Related Exposures and Conditions, Oncology & Carcinogenesis, Nevus, Proportional Hazards Models, Aged, Cancer, GEM Study Group, Middle Aged, Prognosis, Phenotype, Population Surveillance, Case-Control Studies, nevi, Female
Abstract

Although nevus count is an established risk factor for melanoma, relationships between nevus number and patient and tumor characteristics have not been well studied and the influence of nevus count on melanoma-specific survival is equivocal. Using data from the Genes, Environment and Melanoma (GEM) study, a large population-based study of primary cutaneous melanoma, we evaluated associations between number of nevi and patient features, including sun-sensitivity summarized in a phenotypic index, and tumor characteristics. We also assessed the association of nevus count with melanoma-specific survival. Higher nevus counts were independently and positively associated with male gender and younger age at diagnosis, and they were inversely associated with lentigo maligna histology. We observed a borderline significant trend of poorer melanoma-specific survival with increasing quartile of nevus count, but little or no association between number of nevi and pigmentary phenotypic characteristics or prognostic tumor features.

Published
2016

400. Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways

Author

Gibbs, David C, Orlow, Irene, Bramson, Jennifer I, Kanetsky, Peter A, Luo, Li, Kricker, Anne, Armstrong, Bruce K, Anton-Culver, Hoda, Gruber, Stephen B, Marrett, Loraine D, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Dwyer, Terence, Sharma, Ajay, La Pilla, Emily, From, Lynn, Busam, Klaus J, Cust, Anne E, Ollila, David W, Begg, Colin B, Berwick, Marianne, Thomas, Nancy E, and GEM Study Group

Subjects
Adult, Male, Principal Component Analysis, Skin Neoplasms, Genotype, European Continental Ancestry Group, Oncology and Carcinogenesis, GEM Study Group, Middle Aged, Polymorphism, Single Nucleotide, Logistic Models, Phenotype, Interferon Regulatory Factors, Odds Ratio, Sunlight, Humans, Genetic Predisposition to Disease, Female, Oncology & Carcinogenesis, Age of Onset, Melanoma, Aged
Abstract

Solar elastosis and neval remnants are histologic markers characteristic of divergent melanoma pathways linked to differences in age at onset, host phenotype, and sun exposure. However, the association between these pathway markers and newly identified low-penetrance melanoma susceptibility loci remains unknown.In the Genes, Environment and Melanoma (GEM) Study, 2103 Caucasian participants had first primary melanomas that underwent centralized pathology review. For 47 single-nucleotide polymorphisms (SNPs) previously identified as low-penetrant melanoma risk variants, we used multinomial logistic regression to compare melanoma with solar elastosis and melanoma with neval remnants simultaneously to melanoma with neither of these markers, excluding melanomas with both markers. All statistical tests were two-sided.IRF4 rs12203592 was the only SNP to pass the false discovery threshold in baseline models adjusted for age, sex, and study center. rs12203592*T was associated positively with melanoma with solar elastosis (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.18 to 1.82) and inversely with melanoma with neval remnants (OR = 0.65, 95% CI = 0.48 to 0.87) compared with melanoma with neither marker (P global = 3.78 x 10(-08)). Adjusting for phenotypic characteristics and total sun exposure hours did not materially affect rs12203592's associations. Distinct early- and late-onset age distributions were observed in patients with IRF4 rs12203592 [CC] and [TT] genotypes, respectively.Our findings suggest a role of IRF4 rs12203592 in pathway-specific risk for melanoma development. We hypothesize that IRF4 rs12203592 could underlie in part the bimodal age distribution reported for melanoma and linked to the divergent pathways.

Published
2016
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