Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin, with a reported 3-year disease-specific mortality rate of approximately 33%, exceeding that of melanoma [1-3]. At initial diagnosis, regional lymph node metastasis is identified in approximately 26% of patients, and distant metastasis in about 8%, underscoring the tumor’s aggressive biological behavior [4]. Despite apparently complete surgical excision, local or regional recurrence develops in nearly 40% of cases, emphasizing the importance of early diagnosis and appropriate adjuvant therapy [5].

Clinically, MCC most often presents as a rapidly enlarging, firm, violaceous nodule on sun-exposed skin of elderly or immunocompromised individuals. The tumor usually originates in the dermis and may extend into the subcutaneous tissue with progression [6,7]. In contrast, MCC arising in the submandibular region without associated cutaneous involvement is extremely rare [8,9]. We report a distinctive case of a presumed primary submandibular gland MCC and describe its clinical features, diagnostic evaluation, surgical management, and early postoperative course.

An 86-year-old man with a medical history of hypertension and gout presented with a rapidly enlarging, painful mass in the right anterior neck that had progressed over 3 months. Ultrasonography demonstrated a suspicious malignant lesion adjacent to the right submandibular gland, and the patient was referred to the department of plastic and reconstructive surgery for further evaluation. Physical examination revealed a soft, palpable mass measuring approximately 7×5 cm in the right submandibular region (Fig. 1). Contrast-enhanced computed tomography (CT) of the neck and chest showed a well-enhancing mass centered in the right submandibular gland region without definite cervical lymphadenopathy. Core needle biopsy confirmed the diagnosis of MCC. Positron emission tomography–CT demonstrated intense fluorodeoxyglucose uptake limited to the primary lesion. Magnetic resonance imaging revealed a 7.2×4.0×5.5 cm homogeneously enhancing mass and a single indeterminate right level II lymph node (Figs. 2, 3).

The patient underwent wide local excision of the tumor with cervical lymph node biopsy under general anesthesia. The excised mass measured 7.2×4.0×5.5 cm (Fig. 4). Intraoperative frozen-section analysis confirmed negative surgical margins and absence of nodal metastasis. Because of marked age-related skin laxity, the defect was closed primarily without excessive tension. Bilateral Hemovac drains were placed. For airway protection and close monitoring, the patient was transferred to the intensive care unit (ICU) with endotracheal intubation and was successfully extubated on postoperative day (POD) 2. No postoperative hematoma or airway compromise occurred. Sentinel lymph node biopsy and evaluation of cervical lymph node levels I–IV revealed no metastatic involvement. Histopathological examination showed a dermal-based malignant neoplasm composed of uniform small round blue cells arranged in diffuse sheets [1,10]. The tumor cells exhibited scant cytoplasm, a high nuclear-to-cytoplasmic ratio, finely granular (“salt-and-pepper”) chromatin, and inconspicuous nucleoli. Numerous mitotic figures and apoptotic bodies were present, with focal tumor necrosis. A characteristic crush artifact was observed [10,11]. Notably, there was no significant epidermal involvement, supporting a predominantly dermal and subdermal origin (Fig. 5). Postoperatively, the right-sided drain produced approximately 20 mL/day and was removed on POD 5 after output decreased to 15 mL/day. The left-sided drain continued to drain more than 20 mL/day and was removed on POD 7 to reduce the risk of infection (Fig. 6). Hemoglobin levels decreased from 14.8 g/dL preoperatively to 12.0 g/dL postoperatively, without clinical sequelae. After 2 days of ICU care, the patient was transferred to the general ward and discharged on POD 10 following suture removal. Considering the patient’s advanced age and negative lymph node status following complete resection, close observation without additional adjuvant therapy was selected.

At a 3-month postoperative outpatient follow-up, the wound healed without any specific complications, and there was no evidence of recurrence on CT imaging. The patient is scheduled for outpatient follow-up every 3 months for the next 3 years.

MCC is an uncommon but highly aggressive neuroendocrine malignancy that predominantly arises in sun-exposed cutaneous sites. Primary non-cutaneous MCC is exceptionally rare, and involvement of the salivary glands, particularly the submandibular gland, has been reported only sporadically. This case represents an uncommon presentation of MCC involving the submandibular region without cutaneous involvement and emphasizes that MCC should be considered in the evaluation of rapidly enlarging cervical masses, even in the absence of skin lesions.

The pathogenesis of MCC is multifactorial, involving ultraviolet radiation, Merkel cell polyomavirus (MCPyV) infection, immunosuppression, and advanced age [4,7,8,12]. Two principal oncogenic pathways—ultraviolet radiation-induced mutagenesis and MCPyV-driven carcinogenesis—have been well described [8]. Because MCC typically originates in the skin, the absence of any detectable cutaneous lesion in the present case raises the possibility of either a primary submandibular origin or complete regression of a cutaneous primary tumor, a phenomenon that has been documented but remains uncommon.

The differential diagnosis of a head and neck mass suspicious for MCC includes salivary gland neoplasms, lymphoma, squamous cell carcinoma, myofibroblastic tumor, and other neuroendocrine tumors [13-15]. Therefore, histopathological and immunohistochemical evaluation is essential for accurate diagnosis. MCC characteristically demonstrates small round blue cells with high mitotic activity and typically shows immunoreactivity for cytokeratin 20 in a perinuclear dot-like pattern, as well as positivity for neuroendocrine markers such as chromogranin A and synaptophysin [12].

Management of MCC requires a multimodal approach. Wide local excision with histologically negative margins is the cornerstone of treatment for localized disease, although achieving adequate margins may be challenging in the head and neck region. Sentinel lymph node biopsy is recommended because of the high incidence of occult nodal metastasis. In the present case, nodal evaluation was negative despite the large tumor size, suggesting disease confined to the primary site. Adjuvant radiotherapy was recommended because MCC is highly radiosensitive and associated with a substantial risk of locoregional recurrence [1,16,17]. According to the ESMO-EURACAN Clinical Practice Guideline, adjuvant systemic therapy has not demonstrated a clear survival benefit in localized, resectable MCC and is not recommended as standard treatment. For advanced or unresectable MCC, immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have become the preferred systemic therapy, demonstrating more durable responses than conventional chemotherapy [1,18,19]. In the present case, considering the patient’s advanced age and negative lymph node status following complete resection, close observation without additional adjuvant therapy was selected.

This case represents a rare presentation of MCC as a deep mass without cutaneous involvement, which may complicate the differential diagnosis and result in suboptimal diagnostic and therapeutic decision-making. Prognosis in MCC is closely related to disease stage at presentation; however, even early-stage disease carries a significant risk of recurrence. Accordingly, thorough initial evaluation and differential diagnosis, together with long-term surveillance using clinical examination and periodic imaging, are essential [4,5,10].