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Jessica S.W. Borgers, Richard P. Tobin, Robert J. Torphy, Victoria M. Vorwald, Robert J. Van Gulick, Carol M. Amato, Dasha T. Cogswell, Tugs-Saikhan Chimed, Kasey L. Couts, Adrie Van Bokhoven, Christopher D. Raeburn, Karl D. Lewis, Joshua Wisell, Martin D. McCarter, Rao R. Mushtaq, and William A. Robinson

Background: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands. Patients and Methods: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti–PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis. Results: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells. Conclusions: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland–directed therapies or surgical resection.

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Christopher K. Bichakjian, Thomas Olencki, Sumaira Z. Aasi, Murad Alam, James S. Andersen, Daniel Berg, Glen M. Bowen, Richard T. Cheney, Gregory A. Daniels, L. Frank Glass, Roy C. Grekin, Kenneth Grossman, Susan A. Higgins, Alan L. Ho, Karl D. Lewis, Daniel D. Lydiatt, Kishwer S. Nehal, Paul Nghiem, Elise A. Olsen, Chrysalyne D. Schmults, Aleksandar Sekulic, Ashok R. Shaha, Wade L. Thorstad, Malika Tuli, Marshall M. Urist, Timothy S. Wang, Sandra L. Wong, John A. Zic, Karin G. Hoffmann, and Anita Engh

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

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Christopher K. Bichakjian, Thomas Olencki, Sumaira Z. Aasi, Murad Alam, James S. Andersen, Rachel Blitzblau, Glen M. Bowen, Carlo M. Contreras, Gregory A. Daniels, Roy Decker, Jeffrey M. Farma, Kris Fisher, Brian Gastman, Karthik Ghosh, Roy C. Grekin, Kenneth Grossman, Alan L. Ho, Karl D. Lewis, Manisha Loss, Daniel D. Lydiatt, Jane Messina, Kishwer S. Nehal, Paul Nghiem, Igor Puzanov, Chrysalyne D. Schmults, Ashok R. Shaha, Valencia Thomas, Yaohui G. Xu, John A. Zic, Karin G. Hoffmann, and Anita M. Engh

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

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Christopher K. Bichakjian, Thomas Olencki, Murad Alam, James S. Andersen, Daniel Berg, Glen M. Bowen, Richard T. Cheney, Gregory A. Daniels, L. Frank Glass, Roy C. Grekin, Kenneth Grossman, Alan L. Ho, Karl D. Lewis, Daniel D. Lydiatt, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Clifford S. Perlis, Ashok R. Shaha, Wade L. Thorstad, Malika Tuli, Marshall M. Urist, Timothy S. Wang, Andrew E. Werchniak, Sandra L. Wong, John A. Zic, Nicole McMillian, Karin Hoffman, and Maria Ho

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

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Christopher K. Bichakjian, Thomas Olencki, Murad Alam, James S. Andersen, Daniel Berg, Glen M. Bowen, Richard T. Cheney, Gregory A. Daniels, L. Frank Glass, Roy C. Grekin, Kenneth Grossman, Alan L. Ho, Karl D. Lewis, Daniel D. Lydiatt, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Clifford S. Perlis, Ashok R. Shaha, Wade L. Thorstad, Malika Tuli, Marshall M. Urist, Timothy S. Wang, Andrew E. Werchniak, Sandra L. Wong, John A. Zic, Karin G. Hoffmann, Nicole R. McMillian, and Maria Ho

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.