Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor associated with Merkel cell polyomavirus and ultraviolet light exposure. MCC typically affects older individuals, and it also influences young patients with immunosuppressive conditions. We report a case of lower eyelid MCC in a non-immunocompromised 37-year-old woman. Case Presentation: A 37-year-old woman presenting with suspected MCC on her right lower eyelid was referred to our hospital for further resection. The patient underwent wide excision with clear margins followed by reconstruction and radiation therapy. The patient has shown no signs of recurrence after 5 months of follow-up. Conclusion: MCC needs to be considered as a possible diagnosis when examining an eyelid tumor in a young patient.

Merkel cell carcinoma (MCC) is a malignant skin tumor of neuroendocrine origin, which was first reported by Toker in 1972 [1]. It is thought to be associated with Merkel cell polyomavirus and the effects of ultraviolet light [2, 3]. It frequently occurs in exposed areas of sunlight such as the head, and 2.5% of the cases are found in periocular area [4]. Patients with eyelid MCC have a poor prognosis, with a metastatic rate ranging from 10% to 30% [5]. The 5-year survival rate varies depending on the extent of the disease; for localized disease, it is 51%, whereas for lymph node metastases, it drops to 35%, and for systemic metastases, it further decreases to 14% [6]. Treatment is based on a combination of surgical resection and radiation therapy, with or without the use of immune checkpoint inhibitors in progressive cases [7]. MCC is more common in the elderly, with few cases in younger patients associated with immunosuppressive conditions such as HIV/AIDS and solid organ transplantation [4, 8]. We report a case of lower eyelid MCC in a non-immunocompromised 37-year-old woman and provide a literature review and discussion of younger patients with MCC.

A 37-year-old woman presenting with suspected MCC on her right lower eyelid was referred to our hospital for further resection. This diagnosis followed an incisional biopsy performed by her previous physician. Her occupation as an office worker meant she was not in a particularly sun-exposed environment. She had no known history of conditions or factors that could lead to immunocompromise such as diabetes, HIV/AIDS, cancer in other parts of the body, or organ transplantation. At first presentation, her best-corrected visual acuity was 20/16 in both eyes. A slight subconjunctival hemorrhage was noted in the right eye with no lid malposition. The tumor was 12 mm × 10 mm in size and had a purple-red surface. It was non-tender, firm and non-movable (Fig. 1). A wide excision with a 5 mm margin was performed followed by reconstruction of the posterior lamella of the lower eyelid using the Hughes procedure. Reconstruction of the anterior lamella of the right lower lid was done using a retroauricular full-thickness skin graft. Pathology showed clear margins. Hematoxylin and eosin staining revealed a sheet-like small round cell tumor infiltrate in the subepithelial layer and a prominent lymphocytic infiltrate around the tumor (Fig. 2a). Immunohistology was positive for synaptophysin (Fig. 2b), chromogranin A (Fig. 2c), and cytokeratin 20 (Fig. 2d), and negative for thyroid transcription factor-1 (Fig. 2e). These pathological findings led to the diagnosis of MCC. Postoperative positron emission tomography-computed tomography scan of the entire body revealed accumulations in the right parotid gland and uterus, which were subsequently biopsied and found to be benign lesions. A sentinel lymph node biopsy (SLNB) was not performed because the patient did not wish to undergo the procedure. Two months after the surgery, the patient received radiation therapy consisting of volumetric modulated arc therapy delivering 8,000 Gy in 40 fractions, and proton beam therapy delivering 200 Gy in 20 fractions, targeted to the lesion site and regional lymph nodes. Five months after the extensive resection, there is no evidence of MCC recurrence, and positron emission tomography-computed tomograph shows no metastases. However, there is severe dry eye in the right eye due to radiation therapy (Fig. 3).

Fig. 1.

Preoperative frontal view photograph of MCC on the lower eyelid.

Fig. 1.

Preoperative frontal view photograph of MCC on the lower eyelid.

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Fig. 2.

a Hematoxylin and eosin staining (magnification, ×400) with tumor cells with scant cytoplasm, round nucleus, finely dispersed chromatin, and frequent mitotic figures. Positivity for synaptophysin (b), chromogranin A (c), and cytokeratin 20 (d) and negativity for thyroid transcription factor-1 (e).

Fig. 2.

a Hematoxylin and eosin staining (magnification, ×400) with tumor cells with scant cytoplasm, round nucleus, finely dispersed chromatin, and frequent mitotic figures. Positivity for synaptophysin (b), chromogranin A (c), and cytokeratin 20 (d) and negativity for thyroid transcription factor-1 (e).

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Fig. 3.

Frontal view 5 months post-surgery.

Fig. 3.

Frontal view 5 months post-surgery.

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We report a rare case of lower eyelid MCC in a non-immunocompromised 37-year-old woman who underwent wide excision and reconstruction with the Hughes procedure. Eyelid MCC is an aggressive and potentially fatal malignancy that usually affects older patients with 71.4% of cases occurring in those over 70 years old [4]. The incidence of MCC in younger patients is very low, accounting for less than 4% of the cases [8]. Previous studies have suggested that immunosuppression, viral infection, and excessive exposure to sunlight may play a role in the development of MCC in younger patients [8‒10]. Although an association between MCC and Merkel cell polyomavirus has been suggested, we did not perform a test for virus detection. The decision not to perform virus investigation was based on the widely observed lifetime prevalence of Merkel cell polyomavirus infection in most individuals [11], where a positive test result might not significantly contribute to defining a treatment strategy.

MCC is an uncommon but aggressive skin cancer that spreads quickly and painlessly. It is easily misdiagnosed, especially in young patients, due to its low incidence and its presentation, like benign lesions such as cysts and chalazia [8, 9]. Based on the AEIOU features of MCC [8], the following three factors are applicable to this case: asymptomatic or lack of tenderness, rapid expansion (within 3 months), and location on a UV-exposed site. In light of these findings, it may be appropriate to consider a biopsy. We emphasize the importance of biopsy or referral to a specialist when there is doubt about the diagnosis of eyelid lesions.

Treatment strategies for MCC in young patients are similar to those in older patients with a combination of surgical resection and radiation therapy. However, for younger patients with limited excess tissue, the treatment approach aims to preserve as much healthy tissue as possible, such as Mohs micrographic surgery or local excision. We adopted the surgical margin of 5 mm according to the report by Peters et al. [9] in keeping with management guidelines for other aggressive malignant eyelid lesions [9, 10]. As well, a full thickness skin graft from the posterior auricular region was required, while excess eyelid skin can be utilized to secure a skin flap in older patients. Adjuvant radiation therapy has been reported as effective in preventing local recurrence and is recommended for regional lymph nodes and local irradiation [12]. We commenced post-operative radiotherapy 2 months after the surgery, ensuring a robust blood supply for the graft, in line with the suggested delay of 6–7 weeks by the previous report [13].

Chemotherapy was not used in this case since the efficacy of chemotherapy is not well established. However, previous reports suggest that chemoradiation therapy may confer a survival advantage over radiation therapy alone in high-risk patients with tumors larger than 3 cm in diameter, men, and those with positive surgical margins [14]. Available immune checkpoint inhibitors, such as avelumab (an anti-programmed cell death protein ligand 1 antibody) and pembrolizumab (an anti-programmed cell death protein 1 antibody), are primarily used in metastatic cases and have demonstrated response rates of 32% and 56%, respectively [15, 16]. As this was not a metastatic case, we did not utilize immune checkpoint inhibitors.

Recent research highlights the crucial role of SLNB in staging MCC, with a 24% positive rate reported even among patients with no clinically palpable lymph nodes [17]. This has led to a growing consensus among experts to recommend SLNB as a standard diagnostic step for all MCC patients [18]. However, the procedure has its drawbacks, including a 17.1% rate of false negatives in MCC cases [19]. To counteract this, some clinicians advocate for nodal adjuvant radiotherapy as a safeguard against nodal recurrence, even when SLNB results are negative [19]. In our specific case, the patient chose to decline SLNB, leading us to opt for adjuvant radiotherapy targeting both the lesion and regional lymph nodes.

In conclusion, we have presented a rare case of MCC of the lower eyelid in a young female patient. The diagnosis was confirmed by immunohistology and then treated with wide excision and radiation therapy. The patient has shown no signs of recurrence after 5 months of follow-up. This case highlights the importance of considering MCC for differential diagnosis of eyelid tumors even in young age groups. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material at https://doi.org/10.1159/000536098.

Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. Ethical approval is not required for this study in accordance with local or national guidelines.

The authors have no conflicts of interest to declare.

The authors have no funding to declare.

Yoshifumi Komatsu reviewed the medical records, prepared the manuscript of case reports, and revised the intellectual content. Dr. Yoshiyuki Kitaguchi made critical revisions of the manuscript and intellectual content. Masako Kurashige conducted critical revisions of the manuscript and a review of the manuscript to ensure pathological content accuracy. Takeshi Morimoto and Kohji Nishida performed critical revisions of the manuscript and provided final approval for the version to be published.

All data used during this study are included in this article. Further inquiries can be directed to the corresponding author.

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