<unk>  is rare and expedient referral to radiation oncology is critical.<unk>  will quickly relapse following any attempted excisional biopsy. Surgery The first step and primary goal of surgical treatment is to obtain negative histologic margins with 1-cm to 2-cm margins. Retrospective analyses of data from the National Comprehensive Database (NCDB) suggest no difference in the overall and relative survival of patients with stage I to II<unk>  who were treated with wide local excision versus MMS. Radiation Radiation therapy is the primary management of<unk>  <unk> . The largest series we have are from Australia and have demonstrated that radiotherapy alone achieves equal outcomes with upfront or neoadjuvant surgery followed by radiation therapy. The role of surgery is largely historical and relegated to biopsy. There have been no head-to-head trials comparing the two treatment strategies, and in the absence of this, surgeons tend to most commonly perform excisional biopsy prior to referring for radiation therapy to eradicate<unk> .<unk>  is exquisitely radiosensitive. The conclusion amongst published studies in the Radiation Oncology community is that<unk>  should be managed ideally with radiation therapy alone. Chemotherapy Because of its significant adverse effects, traditional chemotherapy has been saved for late-stage highly metastasized cases of<unk> . While some chemotherapeutic regiments have been shown to have transient effects, studies have not found any significant long-term effect on recurrence rate or life expectancy. As of 2015, there were no FDA-approved standard chemotherapy regimens for<unk>  treatment. The most recent American guidelines do not recommend adjuvant chemotherapy, citing a lack of evidence to suggest improved outcomes. Instead, consideration of the need for chemotherapy on a case-by-case basis is recommended. Drug therapy Immunotherapies, namely inhibitors of the PD1-PDL1 checkpoint signaling pathway, are novel anticancer agents that have shown benefit in advanced-stage<unk>  or chemotherapy-resistant<unk> . The PD-1 pathway is responsible for regulating the balance between T-cell activation and over-activation leading to T-cell exhaustion or autoimmunity. However, over-expression of PD-1 ligands (PDL1) have been observed in tumors as a method of evading immune attack. PD-1 inhibition therefore enhances the body's immune response, enabling it to target cancer<unk> s for destruction. Due to their side effects, however, National Comprehensive Cancer Network guidelines recommend PD-1 inhibitors for people with disseminated rather than early-stage<unk> . PD1/PDL1 pathway inhibitors approved or in clinical trials for use in<unk>  treatment include: * In March 2017, the U.S. Food and Drug Administration granted accelerated approval to Avelumab, a PDL1 inhibitor, to treat adults and children above 12 years with metastatic<unk> . * In December 2018, the U.S. Food and Drug Administration granted accelerated approval to Pembrolizumab (KEYTRUDA®, Merck & Co. Inc.) for all ages (adults and pediatrics) with recurrent locally advanced or metastatic<unk>  * Nivolumab (brand name Opdivo, Bristol-Myers Squibb) is in phase III/IV clinical trials * Ipilimumab (brand name Yervoy, Bristol-Myers Squibb) is in phase II clinical trials for use in adults with metastatic<unk> . Studies to date have shown a clinical response rate between 50 and 65% for<unk>  treated with PD-1 pathway inhibitors. Suggestions for further immunotherapy research areas have included therapeutic vaccines or epigenetic modification of HLA-receptors.
Merkel-cell carcinoma
Basal-cell carcinoma
Lymphoepithelioma
Trichoepithelioma
Angiokeratoma
Onychomatricoma
Sebaceous carcinoma
Generalized trichoepithelioma