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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: J Am Acad Dermatol. 2018 Aug 27;80(6):1758–1760. doi: 10.1016/j.jaad.2018.08.021

One in a hundred million: Merkel cell carcinoma in pediatric and young adult patients is rare but more likely to present at advanced stages based on US registry data

Kelly G Paulson 1, Paul Nghiem 1,*
PMCID: PMC6487227  NIHMSID: NIHMS1022356  PMID: 30165170

To the Editor:

Published data for pediatric and young adult patients with Merkel cell carcinoma (MCC) are scarce. Case reports from the US and Europe1–3 suggest MCC can occur in young persons and may be more aggressive in this setting. We sought to determine the frequency of pediatric/young adult MCC and establish whether MCC is more likely to present at advanced stages in younger people. To minimize referral bias and maximize available data, we used the National Program of Cancer Registries-Surveillance Epidemiology and End-Results (NPCR-SEER)4 database that captures incident cancer cases in >98% of the US population.

From 2001–2015, there were 27,105 incident cases of MCC (ICD-0–3 code 8247/3) reported to NPCR-SEER with defined age at diagnosis, of which only 20 (0.07%) were in persons younger than 30. Among these young individuals, 75% were 20 to 29 years old. Over this 15-year period, crude (unadjusted) MCC incidence rates were more than 7,000 times higher in individuals ≥85 years than in those younger than 30 (1 in 13,186 person-years vs. 1 in 93,023,545 person-years respectively; Figure 1). The demographics of persons with MCC <30 years old were otherwise similar to those >30 years of age, with a modest male predominance (60%) and the majority (85%) non-Hispanic white.

Figure 1: Incidence Rates of MCC and Melanoma Across the Age Spectrum.

Figure 1:

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Cases per person-year are shown for the indicated age brackets; crude (unadjusted) incidence rates calculated across the 15 year period from 2001–2015. Note logarithmic scale. Merkel cell carcinoma (ICD-o-3 8247/3; n=27,105 cases) is shown as red circles and invasive melanoma (ICD-O-3 codes 8720–3/3, 8730/3, 8740/3, 8742–6/3, 8760–1/3; n= 975,396 cases) is shown as brown squares.

Having established the low incidence rate of MCC in individuals <30 years, we next sought to determine whether patients in this subset have more advanced disease. Information on extent of disease at presentation was available for 90% of patients <30 years and 87% of those aged 30+. All MCC patients younger than 30 had a defined skin primary, most commonly on the head and neck (44%); this is similar to those 30+ years, where 99% had a defined skin primary of which 43% were on the head and neck. However, extent of disease at presentation differed, with younger individuals 3 times more likely to present with distant metastatic disease (33% vs. 10%) (p = 0.01; Chi-squared with Yates correction) (Figure 2). The high fraction of young patients presenting with metastatic disease supports a more aggressive course in these younger patients, consistent with prior case reports; delayed diagnosis also potentially could have contributed.

Figure 2: Extent of Disease at Merkel cell carcinoma Diagnosis, by Age.

Figure 2:

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The fraction of patients presenting with early/late disease is shown as a function of age at diagnosis. Those less than 30 (n=18 persons) are on the left, while those 30 or older are on the right (n=23,666). A significantly higher fraction of pediatric and young adult patients (33%) had distant metastatic disease at diagnosis as compared with older persons (10%; p=0.01).

Here we describe that MCC can very rarely occur in young individuals. The extremely low rate of MCC in the young differs dramatically from invasive melanoma, which is ~11 times more common than MCC in elderly adults, but >2000 times more common than MCC in individuals <30 years of age (Figure 1). This discrepancy suggests that MCC and melanoma have different age-related risk factors beyond UV-exposure alone. Furthermore, the lack of MCC in young individuals is not solely explained by Merkel cell polyomavirus (MCPyV) infection: population seroprevalence studies report MCPyV infection usually occurs before age 5 years,5 and infections with the virologically-similar human papillomavirus result in increased cancer incidence with only a 10–20 year latency.6 Limitations of this study include absence of survival/outcomes information, inability to calculate adjusted incidence due to small number of young cases, and lack of information in the NPCR-SEER database regarding the MCC risk factors MCPyV7 or immunosuppression.8 Although MCC is only rarely diagnosed in individuals under the age of 30 years (<1% of cases), it is more likely to have spread beyond the primary site at diagnosis, and consideration should be given to thorough staging including cross-sectional imaging in young patients. Further research is needed to determine the reason(s) for the markedly pronounced relationship between age and MCC risk.

Acknowledgments

Funding: This research was supported in part by NIH/NCI grants T32CA009515, K24-CA139052, and the MCC Gift Fund at the University of Washington

Conflicts of Interest: P.N. declares honoraria from EMD Serono, Merck Sharp and Dohne, Pfizer, Mallinckrodt, Amgen, Incyte, Takeda and grants/research funding to his institution from EMD Serono, Bristol Myers Squibb. K.P. receives research funding to her institution from Merck.

Footnotes

IRB Status Statement: De-identified National Registry Data/Exempt

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