Malignant melanoma after treatment for Merkel cell carcinoma^☆,☆☆

Dear Editor,

A 98-year-old male was referred complaining of a mass on his left cheek. He had never received immunosuppressive therapy. Physical examination showed a solid, dome-shaped, reddish tumor, 35 mm in diameter, on his left cheek. Microscopic examination of a biopsy specimen revealed an infiltrative tumor in the dermis. The tumor was composed of sheets and trabeculae of atypical cells with scant cytoplasm, and round nuclei with stippled chromatin (Fig. 1). Immunohistochemistry results revealed that the tumor cells stained positive for cytokeratin 20 and neuron specific enolase. The patient underwent total resection of the tumor. However, because of the patient’s advanced age, neither the patient nor his family wished further treatment, including radiotherapy, choosing follow-up visits only. Two years later, he presented again with erosion of the right hallux. Physical examination showed widespread erosion of his right hallux, which in part had a reddish nodule. The nail had completely disappeared (Fig. 2). Histological examination revealed many atypical cells infiltrating irregularly from the epidermis to the dermis (Fig. 3). These atypical cells were immunoreactive for MART-1 and HMB-45. For the same reason as before, the patient and his family wanted only local symptomatic treatments at a nearby hospital.

Figure 1
Microscopic examination of a biopsy specimen from a mass on patient’s left cheek. There was an infiltrative tumor in the dermis. The tumor was composed of sheets and trabeculae of atypical cells with scant cytoplasm, and round nuclei with stippled chromatin (Hematoxylin & eosin, ×200).

Figure 2
Physical examination revealed widespread erosion of the right hallux, which in part had a reddish nodule. The nail had completely disappeared.

Figure 3
Histological examination showed many atypical cells infiltrating irregularly from the epidermis to the dermis (Hematoxylin & eosin, ×200).

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine cancer that is known to be a highly aggressive malignancy with frequent metastasis and a high mortality rate. A previous review article revealed increased risk of a second primary cancer after the diagnosis of MCC, and cutaneous malignant melanoma (MM) is one of the most common cancers after MCC.¹ Miller and Rabkin reported that occurrences of MM and MCC were similarly increased with sun exposure and immunosuppression.² Considering that ultra violet (UV) rays attenuate systemic immune responses via the induction of regulatory T-cells, systemic immunosuppression may be an essential factor in the development of both conditions in a patient.³ In the present case, MCC occurred on the left cheek, and MM occurred on the right hallux. In Japan, the majority of MM cases occur on the edges of limbs that are not directly affected by UV rays, and external irritation has been considered one of the risk factors.⁴ However, systemic immunosuppression associated with aging and/or UV irradiation may be a common cause of both conditions in the present case. According to previous articles, several cases in which MCC and MM developed in a patient have been reported from countries other than Japan; however, to the best of the authors’ knowledge, this is the first report of its type from Japan. Interestingly, there was a report of a case of MCC that developed in a patient during treatment with immune checkpoint inhibitors for MM.^2,5 Given the increase of immune checkpoint inhibitors used to treat MM, the number of cases in which both MCC and MM develop in a patient may increase in Japan, as well as around the world.

• ☆
  How to cite this article: Ishikawa M, Yamamoto T. Malignant melanoma after treatment for Merkel cell carcinoma. An Bras Dermatol. 2020; 95. https://doi.org/10.1016/j.abd.2020.02.013.
• ☆☆
  Study conducted at the Fukushima Medical University, Fukushima, Japan.
• Financial support
  None declared.

References

• ¹
  Saxena A, Rubens M, Ramamoorthy V, Khan H. Risk of second cancers in Merkel cell carcinoma: a meta-analysis of population based cohort studies. J Skin Cancer. 2014;2014:184245.
• ²
  Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma etiological similarities and differences. Cancer Epidemiol Biomarkers Prev. 1999;8:153-8.
• ³
  Milliken SV, Wassall H, Lewis BJ, Logie J, Barker RN, Macdonald H, et al. Effects of ultraviolet light on human serum 25-hydroxyvitamin D and systemic immune function. J Allergy Clin Immunol. 2012;129:1554-61.
• ⁴
  Ishihara K, Saida T, Otsuka F, Yamazaki N. Prognosis and Statistical Investigation Committee of the Japanese Skin Cancer Society. Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update. Int J Clin Oncol. 2008;13:33-41.
• ⁵
  Hajar T, Hill EE, Leitenberger JJ. Development of Merkel cell carcinoma and squamous cell carcinoma during treatment with pembrolizumab for metastatic mucosal melanoma. Dermatol Surg. 2019;1 [Epub ahead of print].

Publication Dates

• Publication in this collection
  16 Nov 2020
• Date of issue
  Sep-Oct 2020

History

• Received
  12 Dec 2019
• Accepted
  12 Feb 2020