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David M. Brizel, William Lydiatt and A. Dimitrios Colevas

Head and neck cancer (HNC) is a heterogeneous combination of various sites and types of disease. This manuscript elaborates on 3 important and current issues: the emerging role of human papilloma virus (HPV) in oropharyngeal cancer (OPC), current considerations in systemic therapy for advanced disease, and evolving treatment of the neck. Exogenous carcinogens, most notably tobacco, have classically been implicated in the development of HNC. A large increase in the incidence of OPC has occurred in the past few decades, predominantly in nontobacco users, and is caused by HPV. This disease is unique in many respects and presents an opportunity for novel therapeutic approaches. Because the prognosis for HPV-related HNC is better, regardless of whether surgery or radiation is used as the primary therapy, the reduction of treatment-related morbidity has assumed increasing importance and provides unique opportunities and challenges for de-escalation of therapies. Radiotherapy (RT) and concurrent cisplatin is the most commonly used nonsurgical platform for locally advanced disease. New data suggest that viable alternatives exist to the typical 3 cycles of bolus high-dose cisplatin. The role of RT and concurrent taxanes remains less understood. Similarly, the value of integrating epidermal growth factor inhibition and concurrent chemoradiation is under continuing investigation. The use of PET scanning is changing the traditional use of adjuvant neck dissection after RT or chemoradiation. Recent data support the use of surgery in the presence of a positive posttreatment PET, and observation in the setting of a negative posttreatment scan.

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Richard D. Carvajal, Sharon A. Spencer and William Lydiatt

Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made more challenging by its relative rarity. Because of the rarity of MM as a whole, and because of the unique biology and clinical challenges of MM arising from each anatomic location, understanding of this disease and its optimal management remains limited. The impact of various treatment strategies on disease control and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, the retrospective nature of most series, and the lack of a uniform comprehensive staging system for this disease. This article summarizes the clinical, pathologic, and molecular features, and the diagnostic and therapeutic considerations for the management of MM, underscoring the similarities and differences from cutaneous melanoma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces of the head and neck, the anorectal region, and the female genital tract are highlighted.

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Stanley J. Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K. Bichakjian, Glen Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Dennis E. Hallahan, Anne Kessinger, Nancy Y. Lee, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Allan R. Oseroff, Clifford S. Perlis, E. William Rosenberg, Ashok R. Shaha, Marshall M. Urist and Linda C. Wang

Merkel Cell Carcinoma Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative non-melanoma skin cancer along with the regional and distant metastatic rates of thick melanoma.1–16 Several large reviews document the development of local recurrence in 25% to 30% of all cases of MCC, regional disease in 52% to 59%, and distant metastatic disease in 34% to 36%.1,16,17 MCC has a mortality rate that exceeds that of melanoma;18 overall 5-year survival rates range from 30% to 64%.3,19 A history of extensive sun exposure is a risk factor for MCC. Older white men (≥ 65 years) are at higher risk for MCC, which tends to occur on the areas of the skin that are exposed to sun.20 The NCCN Non-Melanoma Skin Cancer Panel has developed guidelines outlining treatment of...
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Stanley J. Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K. Bichakjian, Glen Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Anne Kessinger, Nancy Y. Lee, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Clifford S. Perlis, E. William Rosenberg, Ashok R. Shaha, Marshall M. Urist, Linda C. Wang and John A. Zic

Overview Basal and squamous cell skin cancers, collectively known as non-melanoma skin cancers (NMSC), are the most common skin cancers.1,2 More than 1 million cases of NMSC are estimated to be diagnosed each year in the United States and their incidence is rising rapidly.3,4 Basal cell carcinomas are approximately 4 to 5 times more common than squamous cell carcinomas. Although rarely metastatic, basal and squamous cell cancers can produce substantial local destruction along with disfigurement, and may involve extensive areas of soft tissue, cartilage, and bone. The estimated annual cost of treating these 2 diseases in the United States Medicare population exceeds $400 million.5 However, NMSCs generally have a good prognosis. The most significant environmental carcinogen for NMSC is sunlight.6 Thus, individuals in Hawaii are at much greater risk than those in the northern parts of the United States. Fair-skinned individuals who have received too much sun exposure are at the greatest risk for these cancers. Most of these tumors develop on sun-exposed skin sites. The most common sites are on the head and neck area. According to a report from the Childhood Cancer Survivor Study, long-term survivors of childhood and adolescent cancers who have undergone prior radiation therapy are also at risk for developing NMSC.7 Actinic keratoses are sun-induced precancerous lesions.8,9 Bowen's disease is characterized by squamous cell carcinoma in situ lesions that occur predominantly in older persons.10 Both types of lesions, if untreated, can progress to invasive squamous cell carcinoma with the potential for metastasis. Skin cancer preventive...
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R. Michael Tuttle, Douglas W. Ball, David Byrd, Gilbert H. Daniels, Raza A. Dilawari, Gerard M. Doherty, Quan-Yang Duh, Hormoz Ehya, William B. Farrar, Robert I. Haddad, Fouad Kandeel, Richard T. Kloos, Peter Kopp, Dominick M. Lamonica, Thom R. Loree, William M. Lydiatt, Judith McCaffrey, John A. Olson Jr., Lee Parks, John A. Ridge, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang and Lori J. Wirth

Overview There are 3 main histologic types of thyroid carcinoma: differentiated (including papillary, follicular, and Hürthle), medullary, and anaplastic (aggressive undifferentiated tumor). Of 53,856 patients treated for thyroid carcinoma between 1985 and 1995, 80% had papillary, 11% had follicular, 3% had Hürthle cell, 4% had medullary, and 2% had anaplastic thyroid carcinoma.1 These NCCN guidelines focus on medullary thyroid carcinoma (MTC). Another NCCN guideline addresses papillary, follicular, Hürthle cell, and anaplastic thyroid carcinomas (see NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma [to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org]). MTC derives from the neuroendocrine parafollicular calcitonin-producing (C) cells of the thyroid.2–4 Sporadic MTC accounts for approximately 80% of all cases of the disease. The remaining cases consist of inherited tumor syndromes, such as multiple endocrine neoplasia type 2A (MEN 2A), which is the most common type; MEN 2B; or familial MTC.5,6 Sporadic disease typically presents in the fifth or sixth decade. Familial forms of the disease tend to present at earlier ages.2 Because the C cells are predominantly located in the upper portion of each thyroid lobe, patients with sporadic disease typically present with upper pole thyroid nodules. Metastatic cervical adenopathy appears in approximately 50% of patients at initial presentation. Symptoms of upper aerodigestive tract compression or invasion are reported by up to 15% of patients with sporadic disease.7 Symptoms from distant metastases in the lungs or bones occur in 5% to 10% of patients. The ability of the tumor to...
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R. Michael Tuttle, Douglas W. Ball, David Byrd, Raza A. Dilawari, Gerard M. Doherty, Quan-Yang Duh, Hormoz Ehya, William B. Farrar, Robert I. Haddad, Fouad Kandeel, Richard T. Kloos, Peter Kopp, Dominick M. Lamonica, Thom R. Loree, William M. Lydiatt, Judith C. McCaffrey, John A. Olson Jr., Lee Parks, John A. Ridge, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang and Lori J. Wirth

OverviewEpidemiologyThyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of approximately 5% in the United States population aged 50 years and older.1–3 Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using ultrasonography, and 50% of these have nodules, which are almost always benign.2,4 New nodules develop at a rate of approximately 0.1% per year beginning in early life, but at a much higher rate (∼2% per year) after exposure to head and neck irradiation.5,6By contrast, thyroid carcinoma is uncommon. For the United States population, the lifetime risk of being diagnosed with thyroid carcinoma is less than 1% (0.83% for women and 0.33% for men).7 Approximately 37,200 new cases of thyroid carcinoma were diagnosed in the United States in 2009.8As with thyroid nodules, thyroid carcinoma occurs 2 to 3 times more often in women than in men. With the incidence increasing by 6.2% per year, thyroid carcinoma is currently the sixth most common malignancy diagnosed in women.8 Among persons age 15 to 24 years, thyroid carcinoma accounts for 7.5% to 10% of all diagnosed malignancies.9–11 The disease is also diagnosed more often in white North Americans than in African Americans. Although thyroid carcinoma can occur at any age, the peak incidence from 2004 to 2006 was near age 45 to 49 years in women and 65 to 69 years in men.7Thyroid carcinoma has...
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Robert I. Haddad, William M. Lydiatt, Douglas W. Ball, Naifa Lamki Busaidy, David Byrd, Glenda Callender, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, Judith C. McCaffrey, Jeffrey F. Moley, Lee Parks, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Robert C. Smallridge, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Karin G. Hoffmann and Miranda Hughes

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.

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Stanley J. Miller, Murad Alam, James S. Andersen, Daniel Berg, Christopher K. Bichakjian, Glen M. Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Alan L. Ho, Anne Kessinger, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Clifford S. Perlis, Ashok R. Shaha, Malika Tuli, Marshall M. Urist, Linda C. Wang and John A. Zic

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David G. Pfister, Kie-Kian Ang, David M. Brizel, Barbara A. Burtness, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks Jr., Ying J. Hitchcock, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Sandeep Samant, Giuseppe Sanguineti, David E. Schuller, Jatin P. Shah, Sharon Spencer, Andy Trotti III, Randal S. Weber, Gregory T. Wolf and Frank Worden

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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.