Due to their side effects, however, National Comprehensive Cancer Network guidelines recommend PD-1 inhibitors for people with disseminated rather than early-stage MCC.PD1/PDL1 pathway inhibitors approved or in clinical trials for use in MCC 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 MCC. 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 Merkel cell carcinoma
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 MCC.Studies to date have shown a clinical response rate between 50 and 65% for MCC treated with PD-1 pathway inhibitors. Suggestions for further immunotherapy research areas have included therapeutic vaccines or epigenetic modification of HLA-receptors. Prognosis
According to the American Joint Committee on Cancer (AJCC), the natural course of MCC is "variable and depends heavily on the stage at diagnosis". Staging of MCC is classified according to the TNM staging system, a notation system that describes the stage of cancer according to the size of the primary tumor (T), the degree of spread to regional lymph nodes (N), and the presence of distant metastasis (M). A combination of T, N, and M stages dictate the final clinical stage group (0, I, IIA, IIB, IIIA, IIIB, IV). Advanced stage (i.e.
MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Merkel cell carcinomas have been described in children, however pediatric cases are very rare.Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels to many organs, particularly to liver, lung, brain, and bone. Pathophysiology
Cell of origin
Although MCC was initially named for the Merkel cell due to histologic and physiologic similarities between MCC and Merkel cells, the cellular progenitor of MCC has been a heavily debated question. Merkel cells are highly specialized cells that act as pressure receptors in the epidermis. The origin of Merkel cells themselves is debated and proposed to be derived from neural crest cells or epidermal progenitors. MCC is similar to Merkel cells in its histological appearance (see below: Diagnosis) and shares many immunohistochemical markers with Merkel cells, including epidermal marker cytokeratin 20 and neuroendocrine markers synaptophysin and chromogranin A. Furthermore, the ion channel Piezo2 and transcription factor Atoh1, both specific to Merkel cells, are also expressed by MCC. However, Merkel cells are post-mitotic cells with a low probability of cancerous transformation.