Merkel Cell Carcinoma Presenting as a Solitary Facial Nodule in a 59-Year-Old Woman

To the Editor: A 59-year-old Kuwaiti woman presented to the dermatology clinic with an asymptomatic skin lesion on her left cheek of 8 months duration. The lesion had a gradual onset and slowly progressive course. There was no associated pain, ulceration, or bleeding noted. Her medical history was significant for type 2 diabetes mellitus and hypertension. There was no personal or family history of malignancy or other dermatologic diseases. On examination, a solitary, well-defined erythematous nodule measuring approximately 1 × 1 cm was observed on the left cheek (Fig. 1). The lesion was indurated and firm in consistency with a smooth surface and clear borders. No evidence of ulceration, crusting, or other secondary changes. No cervical or regional lymphadenopathy was observed. General and systemic examinations were normal.FIGURE 1.: A solitary erythematous, indurated nodule measuring approximately 1 × 1 cm located on the left cheek. The lesion demonstrates a firm consistency and well-defined borders without ulceration or secondary changes.A skin biopsy from the facial nodule was performed, and histopathologic and immunohistochemical evaluations were performed (Figs. 2–4) to investigate the possibility of a primary cutaneous neoplasm or an infiltrative inflammatory process. The clinical differential diagnoses included lymphocytoma cutis, B-cell lymphoma, granuloma faciale, follicular mucinosis, adnexal tumor, vascular tumor, Merkel cell carcinoma, basal cell carcinoma, amelanotic melanoma, and metastatic carcinoma. Written informed consent was obtained from the patient.FIGURE 2.: Pan-dermal infiltrate of small round blue cells arranged in nests, sheets, and trabeculae. The tumor is separated from the overlying epidermis by a clear Grenz zone (H&E, ×4).FIGURE 3.: Tumor cells with a high nuclear-to-cytoplasmic ratio, round to oval nuclei with finely dispersed chromatin, indistinct nucleoli, and scant cytoplasm. Frequent mitotic figures and apoptotic bodies are evident (H&E, ×20).FIGURE 4.: Immunohistochemical staining showing strong cytoplasmic CK20 positivity with a characteristic paranuclear dot-like pattern in the tumor cells and diffuse cytoplasmic positivity for synaptophysin, confirming neuroendocrine differentiation (CK20 and synaptophysin, ×40).Hematoxylin and eosin staining of the skin biopsy specimen revealed pan-dermal infiltration of small, round, blue cells arranged in nests, sheets, and trabeculae with scant intervening stroma. The tumor was separated from the epidermis by a Grenz zone (Fig. 2). At higher magnification, the cells exhibited a high nuclear-to-cytoplasmic ratio, round-to-oval nuclei with finely dispersed chromatin, indistinct nucleoli, and scant cytoplasm. Conspicuous mitotic figures, apoptotic bodies, variable nuclear molding, and crush artifacts were noted (Fig. 3). Immunohistochemical staining revealed that the tumor cells were positive for cytokeratin 20, showing a characteristic paranuclear dot-like pattern, and were also positive for synaptophysin (Fig. 4). The tumor cells were negative for thyroid transcription factor-1 (TTF-1), CD45, CDX2, cytokeratin 7, and S100. Additional testing for Merkel cell polyomavirus was negative. Inflammatory, lymphoproliferative, melanocytic, adnexal, vascular, and metastatic neoplasms were considered as differential diagnoses. Based on the histopathologic findings and the lack of a reactive inflammatory infiltrate, inflammatory diseases, including granuloma faciale and lymphocytoma cutis, were ruled out. Morphologic and negative lymphoid immunohistochemical marker analyses excluded lymphoproliferative diseases, including B-cell lymphoma. The absence of melanocytic markers ruled out melanocytic tumors, including amelanotic melanoma. Based on histomorphology and the absence of supporting immunophenotypic characteristics, adnexal and vascular tumors were ruled out. The remaining consideration was a neuroendocrine malignancy, and the characteristic morphology and immunohistochemical profile supported a diagnosis of Merkel cell carcinoma rather than metastatic carcinoma. The possibility of metastatic neuroendocrine carcinoma from a different primary location was considered, despite the immunohistochemical profile was supporting Merkel cell cancer. The diagnosis of primary cutaneous Merkel cell carcinoma was supported by clinical evaluation and radiologic imaging, which showed no signs of a primary cancer in the lung or gastrointestinal system. Based on the histopathologic and immunohistochemical findings, a diagnosis of MCC was established. The patient was referred to the Kuwait Cancer Control Center for further staging and full treatment. MCC is a rare and highly aggressive primary cutaneous neuroendocrine carcinoma. It typically arises in sun-exposed areas, particularly the head and neck, and predominantly affects elderly and immunocompromised individuals. Although MCC has been described worldwide, it is rarely reported in Kuwait.1 Chronic ultraviolet radiation exposure and Merkel cell polyomavirus infection are the main etiologic factors implicated in its pathogenesis.2,3 Clinically, MCC often presents as a painless, firm, erythematous, or violaceous nodule with a rapid growth pattern. Owing to its nonspecific appearance, it is frequently mistaken for benign lesions or other cutaneous malignancies, such as basal cell carcinoma, squamous cell carcinoma, or cutaneous lymphoma.4 In the present case, the diagnosis was confirmed by histopathologic and immunohistochemical findings, while testing for Merkel cell polyomavirus was negative, indicating a virus-independent pathogenesis, which is reported in approximately 20%–30% of MCC cases and is often associated with a higher mutational burden and aggressive clinical behavior.5 Histopathologically, MCC is characterized by dermal and subcutaneous infiltrates of small, round blue cells with scant cytoplasm, finely dispersed chromatin, and frequent mitotic figures. A Grenz zone separating the tumor from the epidermis is a typical histopathologic finding. Immunohistochemistry is essential for diagnosis, because MCC shares morphologic features with other “small round blue cell” tumors. CK20 positivity with a distinctive paranuclear dot-like pattern, together with neuroendocrine markers such as synaptophysin and chromogranin, confirms the diagnosis. Negative staining for TTF-1 helps differentiate MCC from metastatic small cell lung carcinoma, while CD45 negativity excludes lymphoma.6,7 MCC is an aggressive tumor with a high propensity for local recurrence, regional lymph node involvement, and distant metastasis. Management typically involves wide local excision with sentinel lymph node biopsy, often followed by adjuvant radiotherapy to improve local control.8 In advanced or metastatic disease, immune checkpoint inhibitors targeting PD-1/PD-L1 have shown significant survival benefits.9 Early recognition and prompt histopathologic evaluation are important for improving the outcomes. In the present case, the clinical presentation of a solitary erythematous cheek nodule with histopathologic findings of small round blue cells and a CK20-positive immunoprofile confirmed MCC. The absence of lymphadenopathy and normal imaging suggested localized disease, underscoring the importance of early biopsy of suspicious cutaneous lesions.