Merkel cell carcinoma associated with chronic treatment with hydroxyurea: a case report

Saulo Esteves Saraiva, Virgínia Mareco, André Florindo, Diogo Delgado, Maria Filomena de Pina


Merkel cell carcinoma is a rare neuroendocrine tumour of the skin, that shows a quickly and aggressive behaviour and carries a poor prognosis. Surgery is the standard primary treatment modality, while radiotherapy plays a role in postoperative treatment. Radiotherapy is also an alternative to unresectable lesions or patients who are unfit to surgery. Here we report a 90-year-old male with polycythemia vera that was chronically treated with hydroxyurea for about 30 years. The patient presented a purple and exophytic frontal scalp lesion, which had recurred after primary wide excision. This recurrence had been considered inoperable and the patient was treated with external beam radiotherapy to the lesion and locoregional lymph nodes, showing a complete clinical response after 12 weeks. However, disease progressed rapidly, and the patient died from distant metastasis 4 months later. This report is the second described case in literature of Merkel cell carcinoma as complication of chronic hydroxyurea and highlights the need for these patients to undergo regular and close dermatological evaluation.


Merkel cell carcinoma, Hydroxyurea, Non-melanoma skin cancer, Radiotherapy, Immunosuppression, Risk factor

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Schadendorf D, Lebbé C, zur Hausen A, Avril M, Hariharan S, Bharmal M, et al. Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs. Eur J Cancer. 2017;71:53-69.

Koljonen V. Merkel cell carcinoma. World J Surg Oncol. 2006;4:1-11.

Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: Prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23:2300-9.

Jaeger T, Ring J, Andres C. Histological, Immunohistological, and Clinical Features of Merkel Cell Carcinoma in Correlation to Merkel Cell Polyomavirus Status. J Skin Cancer. 2012;2012:1-5.

Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096-100.

Lebbe C, Becker JC, Grob JJ, Malvehy J, Marmol V, Pehamberger H, et al. Diagnosis and treatment of Merkel Cell Carcinoma. European consensus-based interdisciplinary guideline. Eur J Cancer. 2015;51:2396-403.

Paulson KG, Iyer JG, Blom A, Warton EM, Sokil M, Yelistratova L, et al. Systemic immune suppression predicts diminished merkel cell carcinoma-specific survival independent of stage. J Invest Dermatol. 2013;133:642-6.

Bouldouyre M-A, Avril M-F, Gaulier A, Sigal-Grinberg M. Association of cutaneous side-effects of hydroxyurea and neuroendocrine carcinoma. Eur J Dermatol. 2005;15:268-70.

Singh A, Xu YJ. The cell killing mechanisms of hydroxyurea. Genes (Basel). 2016;7.

Madaan K, Kaushik D, VerM.A. T. Hydroxyurea: A key player in cancer chemotherapy. Expert Rev Anticancer Ther. 2012;12:19-29.

Steinberg MH, McCarthy WF, Castro O, Ballas SK, Armstrong D, Smith W, et al. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. Am J Hematol. 2010;85:403-8.

Cantisani C, Kiss N, Naqeshbandi AF, Tosti G, Tofani S, Cartoni C, et al. Nonmelanoma skin cancer associated with Hydroxyurea treatment: Overview of the literature and our own experience. Dermatol Ther. 2019;32:1-7.

Disdier P, Harle JR, Grob JJ, Weiller-Merli C, Magalon G, Waller PJ. Rapid development of multiple squamous-cell carcinomas during chronic granulocytic leukemia. Dermatology. 1991;183:47-8.

Soltani-Arabshahi R, Tristani-Firouzi P. Chemoprevention of nonmelanoma skin cancer. Facial Plast Surg. 2013;29:373-83.

Raju S, Vazirnia A, Totri C, Hata TR. Treatment of Merkel cell carcinoma of the head and neck: A systematic review. Dermatologic Surg. 2014;40:1273-83.

Petrelli F, Ghidini A, Torchio M, Prinzi N, Trevisan F, Dallera P, et al. Adjuvant radiotherapy for Merkel cell carcinoma: A systematic review and meta-analysis. Radiother Oncol. 2019;134:211-9.

Hasan S, Liu L, Triplet J, Li Z, Mansur D. The role of postoperative radiation and chemoradiation in Merkel cell carcinoma: A systematic review of the literature. Front Oncol. 2013;3:1-10.

Goff PH, Bierma M, Lachance K, Schaub SK, Tseng YD, Liao JJ, et al. Primary Tumor Location As a Potential Risk Factor for Local Recurrence in Resected, Low-risk Merkel Cell Carcinoma: Implications for Postoperative Radiotherapy. Int J Radiat Oncol. 2020;108:S132.

Gunaratne DA, Howle JR, Veness MJ. Definitive radiotherapy for Merkel cell carcinoma confers clinically meaningful in-field locoregional control: A review and analysis of the literature. J Am Acad Dermatol. 2017;77:142-8.

Song Y, Azari FS, Tang R, Shannon AB, Miura JT, Fraker DL, et al. Patterns of Metastasis in Merkel Cell Carcinoma. Ann Surg Oncol. 2021;28:519-29.