Salivary gland tumors are commonly encountered in the parotid gland. The vast majority of these tumors are benign (80%), with only 25% of them being malignant [1]. Most cases of parotid melanomas are reported as metastatic lesions from cutaneous malignant melanoma (MM), typically originating from skin neoplasms of the head and neck region [2]. Primary malignant melanoma of the parotid gland (PMMPG) is extremely rare, making up less than 0.7% of all parotid gland malignancies [3]. Distinguishing PMMPG and metastatic parotid involvement is a crucial step, as the latter accounts for most parotid melanomas and has different prognosis and treatment implications. Melanomas affecting the parotid gland are often metastases from cutaneous sources, most commonly the scalp, face, and ear, or, less frequently, from mucosal sites such as the oral or nasal cavities [4,5]. The frequent prevalence of intraparotid nodal metastases from cutaneous melanoma is explained by the parotid gland’s role as a regional lymphatic basin for these regions [6]. PMMPG poses a considerable diagnostic challenge. When found in the parotid gland without an identified primary location, they are regarded as exceptionally rare [7]. This case describes a 66-year-old man with a PMMPG in a specialized tertiary hospital in Saudi Arabia.

A 66-year-old man with a medical background of diabetes mellitus type II, rheumatoid arthritis, and a 20-year history of smoking (ex-smoker), presented to Otolaryngology–Head and Neck Surgery Clinic, at King Fahad Specialist Hospital complaining of a 6-month history of a painless, progressively enlarging right facial swelling, with no associated facial asymmetry, trismus, or other masses. On physical examination, a 3×3 cm firm, mobile mass was noted in the right parotid region. Thorough oral, dermatological, ophthalmic, neck, and cranial nerve examinations were all unremarkable with fully intact function.

Upon further evaluation, a contrasted computed tomography (CT) scan of the neck revealed a lesion involving the superficial lobe of the right parotid gland and an enlarged lymph node in level IIa (Fig. 1). Fine-needle aspiration confirmed the presence of malignant cells that were positive for S100, Melan A, and HMB45 immunohistochemical stains consistent with melanoma. The patient was then further investigated with a CT scan of the chest, abdomen, and pelvis and a positron emission tomography (PET)-CT, which identified small, indeterminate pulmonary nodules, an intensely FDG (fluorodeoxyglucose)-avid right parotid mass, and similarly avid parotid and right level IIb lymph nodes, all suggestive of metastatic disease (Fig. 2). No significant distant metastases were detected, leading to a diagnosis of primary parotid melanoma with regional metastatic involvement. The oncology service was consulted regarding his PET-CT findings of pulmonary nodules and advised for interval follow-up.

Three weeks following confirmation of the diagnosis, the patient underwent a right total parotidectomy with a right neck dissection (levels II, III, IV, and V). Partial sacrifice of the lower two branches (marginal mandibular and cervical) of the facial nerve was necessary, as they were inseparable from the tumor, with preservation of Cranial Nerve XI, the internal jugular vein, and the sternocleidomastoid muscle. Intraoperative frozen section evaluation of the surgical margins was negative for tumor. Subsequent microscopic examination of the resection specimen showed an intraparotid well-circumscribed tumor composed of sheets of epithelioid cells with pleomorphic nuclei, prominent cherry-red-like nucleoli, and an abundant amount of eosinophilic cytoplasm (Fig. 3). The tumor cells were positive for Melan A and HMB45 immunohistochemical stains, confirming the diagnosis of melanoma. Metastatic melanoma was identified in two out of 59 lymph nodes from levels II and III. Postoperatively, the patient had mild lower facial weakness, with partial preservation of upper branches and satisfactory recovery of facial symmetry. After multidisciplinary tumor board review, adjuvant radiotherapy was initiated 4 weeks postoperatively. Intensity-modulated radiotherapy was delivered to the parotid bed and upper cervical nodes at a total dose of 60 Gy in 30 fractions over 6 weeks. Subsequently, the oncology service commenced pembrolizumab 200 mg diluted in 50 mL of 0.9% normal saline intravenously every 3 weeks, planned for 35 cycles, as adjuvant immunotherapy. Follow-up PET-CT scans demonstrated stable indeterminate pulmonary nodules and no evidence of local recurrence at 6 months.

Since 1986, there have been approximately 12–15 well-documented reports of PMMPG worldwide, highlighting its extreme rarity. In these case reports, the prevalence of the male-to-female ratio was almost equal (5:6). All patients presented with unilateral swellings, and almost 70% of them were over 50 years of age [8,9]. According to Aung et al. [10], undiagnosed PMMPG may have a more favorable prognosis than primary cutaneous MM, with a 5-year survival rate of over 50%. PMMPG diagnosis necessitates satisfying certain criteria according to Woodwards et al. [11], who first proposed the classic histological criteria in 1993. These consist of (1) the tumor’s primary location being within the parotid gland parenchyma, (2) the tumor’s absence of detectable intraparotid lymph node tissue, (3) the non-existence of any additional cutaneous, mucosal, or ocular melanoma lesions, and (4) not having any history of previous melanoma excision. Adherence to these criteria helps avoid misdiagnosis, since metastatic melanoma commonly mimics the primary tumor visually and immunohistochemically. In the presented case, a meticulous dermatologic and ophthalmologic examination found no cutaneous or mucosal melanoma, and PET-CT indicated no further primary lesions. All four of Woodwards et al.’s diagnostic criteria for primary parotid melanoma were fulfilled [11].

A complete diagnostic evaluation should include thorough dermatologic and ophthalmologic assessments, as well as whole-body PET-CT to rule out occult primary sites [7,9]. On the other hand, emerging evidence showed that molecular testing could become of greater significance in differentiation. For example, PMMPG rarely exhibits NRAS and BRAF V600E mutations, which are common in cutaneous melanomas, although KIT mutations, which are more common in mucosal melanomas, may occasionally be seen [6]. Magnetic resonance imag-ing could yield useful information due to the usual hyperintense T1 signal seen by melanomas, which is associated with the paramagnetic effect of melanin and accompanying bleeding [1]. CT imaging reveals well-defined margins with homogeneous or heterogeneous attenuation, making it difficult to distinguish from benign salivary gland tumors [10]. Intracellular melanin pigmentation is the gold standard for diagnosing melanoma, but it is only seen in 40%–60% of instances [12]. Hence, confirming the diagnosis requires immunohistochemical identification, especially the presence of S100 and HMB45 proteins [13]. In addition, clear cell sarcoma (CCS) and MM exhibit similar morphological and immunohistochemical characteristics, making distinction difficult [14]. Although CCS usually affects the deep soft tissues of the extremities, it may arise from uncommon locations like the skin or gastrointestinal system [15]. The primary difference between CCS and cutaneous melanoma is the presence of a t(12;22)(q13;q12) chromosomal translocation, which causes EWS/ATF1 fusion [16]. Molecular methods like reverse transcription–polymerase chain reaction and fluorescence in situ hybridization are necessary to confirm the diagnosis [17]. Studies have demonstrated that some patients initially classified as MM in atypical locations actually had CCS upon molecular investigation [15]. As a result, accurate differentiation is essential for proper patient management and prognosis.

The management of PMMPG is controversial. Although the effectiveness is questionable considering the poor prognosis, total parotidectomy appears to be the best surgical method. A selective neck dissection should always be performed in the N0 neck due to the significant incidence of lymph node metastases [4]. Adjuvant postoperative radiation may aid in the management of microscopic disease and has demonstrated a better prognosis, with 5-year survival rate and local control estimated to be 46% and 94%, respectively [18]. When compared to more conventional methods, recent developments in immunotherapy and targeted therapy have greatly enhanced the treatment of MM, providing better outcomes. Immune checkpoint inhibitors, notably pembrolizumab and nivolumab, which target the programmed death-1 receptor, have shown promising improvement of the overall survival rates and long-term disease control among patients with metastatic or unresectable melanoma. Combined checkpoint inhibition with nivolumab and ipilimumab has also been linked to better intracranial and extracranial response rates in mucosal melanoma, despite increased immune-related toxicity [6]. Case-based evidence showed that PMMPG could be successfully treated with surgery combined with Sintilimab immunotherapy, chemotherapy, and radiotherapy, leading to a progression-free survival of more than 19 months [19]. In comparison with previous PMMPG reports, this case shows a favorable early result with pembrolizumab-based immunotherapy after surgery and adjuvant radiation, indicating that checkpoint inhibitors may provide significant disease control in particular patients. Unfortunately, patients with PMMPG continue to have a negative prognosis despite the most effective therapeutic approaches, having a high risk of metastases (67%) [10]. In a study by Prayson and Sebek [20] that included twelve different cases of parotid gland melanoma, six patients died from the tumor at a median follow-up of 11 months following surgery, while only two patients survived extended follow-up periods with no signs of residual tumor. PMMPG management continues to be difficult, and the standard treatment is surgery, followed by adjuvant methods. Although aggressive intervention offers the best outcomes, prognoses remain guarded despite multimodal management, with high recurrence and metastasis rates. Future studies are encouraged to focus on molecular profiling of PMMPG and assessing immunotherapeutic drugs’ effectiveness in this rare parotid malignancy.