Orbital and Parotid Metastases from Nasopharyngeal Carcinoma: A Rare Case Presentation and Review of the Literature

Abstract

Introduction

Nasopharyngeal carcinoma (NPC) is a rare, yet aggressive malignancy characterized by various clinical presentations. Metastasis to the orbital and parotid regions presents diagnostic challenges and adds complexity to the management.

Case Presentation

Herein, we present a case of a 23-year-old male diagnosed with non-keratinizing undifferentiated NPC, initially presenting with orbital metastasis followed by parotid gland involvement shortly after completion of chemoradiotherapy. The patient underwent surgical intervention preceded by chemoradiotherapy, resulting in complete remission without recurrence over a 12-month follow-up period.

Conclusion

This case reinforces the critical importance of vigilant long-term surveillance in high-risk NPC patients with symptom-directed and risk-adapted surveillance approaches.

Introduction

Nasopharyngeal carcinoma (NPC) is a highly aggressive form of cancer arising from the epithelial cells that line the nasopharynx [1]. According to the World Health Organization (WHO), NPC is considered a rare type of tumor, accounting for only 0.7% of all cancer cases worldwide [1]. Nevertheless, NPC constituted 30% of all reported head-and-neck tumors in Saudi Arabia, indicating a significant incidence of the disease in the region [2]. It is 3 times more prevalent in males than females aged between 40 and 60 years [2, 3].

NPC can be categorized into two primary subtypes: keratinizing and nonkeratinizing subtypes. These subtypes may overlap, with patients potentially exhibiting characteristics of both. Moreover, the non-keratinizing NPC subtype can be subclassified into differentiated or undifferentiated forms, each characterized by unique histological features and varying levels of cellular differentiation [3]. Clinical presentation of NPC includes a variety of symptoms depending on its anatomical site and local invasiveness [1]. This type of cancer can extend within or out of the nasopharynx toward the opposing lateral wall and/or posteriorly to the palate, oropharynx, nasal cavity, or skull base [1]. It usually metastasizes to adjacent cervical lymph nodes. Thus, many patients diagnosed with NPC initially present with cervical lymphadenopathy or mass. Other symptoms related to the primary tumor include pain, trismus, otitis media, hearing loss, cranial nerves deficits, and nasal regurgitation [1, 3]. In this report, we describe a rare case of orbital and parotid regions metastases from nasopharyngeal carcinoma in a young male.

Case Presentation

A 23-year-old male, a known smoker consuming one pack per day, presented to the otorhinolaryngology head and neck clinic with left eyelid swelling, which he had noticed 1 month prior to this visit. The swelling had subsided in size following a left exploratory orbitotomy with biopsy performed 2 weeks earlier. He denied any nasal symptoms or constitutional symptoms. His medical history included a prior diagnosis of nasopharyngeal carcinoma (T3N2Mx), specifically undifferentiated non-keratinizing subtype, originating from the left fossa of Rosenmüller which was found to be EBV seropositive and negative to p16 on immunohistochemistry, and completion of chemoradiotherapy 2 years ago. Upon physical examination, a left supraorbital scar was noted, with normal visual acuity, intraocular pressure, and ocular motility, with no exophthalmos. All cranial nerves were grossly intact, and neck examination revealed no palpable masses. Nasal endoscopy showed a clear nasal cavity and nasopharynx without any signs of recurrence.

Orbital magnetic resonance imaging (MRI), conducted 1 month ago, revealed a heterogeneously enhancing soft tissue mass involving the region of the left lacrimal gland with patchy diffusion restriction. Thickening of the periorbital soft tissues was also observed. Additionally, focal dural enhancement was noted along the adjacent left frontal and anterior temporal convexities (Fig. 1). Orbital computed tomography (CT) was then requested due to query of orbital roof periosteal involvement seen intraoperatively, revealing subperiosteal bone resorption of superolateral aspect of the orbit (Fig. 2). An urgent neck MRI with contrast was determined and came back negative. The pathology report of the left upper orbital mass confirmed undifferentiated non-keratinizing nasopharyngeal carcinoma (Fig. 3, 4). Subsequently, he underwent chemoradiotherapy, completing a total of 30 sessions of intensity modulated radiation therapy and was given platinum-based chemotherapy with cisplatin in 6 weekly doses. Four months later, on ophthalmologic examination, the corrected visual acuity was 20/20 in the right eye (OD) and counting fingers at 2 feet in the left eye (OS). Intraocular pressure was 16 mm Hg OD and 10 mm Hg OS. Pupils were round, regular, and reactive to light with no afferent pupillary defect. Ocular motility was full without limitations OU. External examination of the OD was normal. The OS revealed mild upper eyelid swelling, an S-shaped ptosis, and a lower eyelid ectropion with symblepharon formation. The conjunctiva and sclera showed diffuse +2 injection. The cornea exhibited mild diffuse edema, a poor ocular surface with mucus filaments, and two small infiltrates inferiorly at 6 o’clock measuring 1 × 2 mm and 1 × 1 mm, with an improving corneal epithelial defect. The anterior chamber was deep with no hypopyon, and the lens was clear. A head and neck positron emission tomography (PET)/CT was ordered post-treatment to assess recurrence and distant metastasis, revealing the development of a new hypermetabolic nodular density in the left parotid space, measuring 1.5 cm, with no abnormal hypermetabolic activity in the nasopharyngeal region and no evidence of other disease metastasis or osseous lesions (Fig. 5).

Fig. 1.

An orbital MRI showing a heterogeneously hyperintense left upper orbital mass seen in T2W FSE (a) and T2 (b).

Fig. 2.

A non-contrasted orbital CT showing a left subperiosteal bone resorption of the superolateral orbital aspect.

Fig. 3.

Histologic features. Panoramic view of the submitted material showing a fragment of tumor (a) and a fragment of unremarkable lacrimal gland lobules (b) (H&E* stain, original magnification, ×10). b Solid sheets of large pleomorphic neoplastic cells with round to oval dark nuclei, a prominent nucleolus, and frequent mitotic figures (arrow). The tumor cells are intermingled with lymphocytes and plasma cells (H&E* stain, original magnification, ×400). *Hematoxylin and eosin.

Fig. 4.

Immunohistochemical findings. a Tumor cells show nuclear reactivity to p63 (original magnification, ×200). b EBV in situ hybridization showing diffuse block staining of the tumor cells (original magnification, ×200).

Fig. 5.

A PET-CT study showing a transaxial cut of a left parotid space hypermetabolic lesion with 7.3 SUV of 18F-FDG.

He returned to the clinic for evaluation, presenting with left parotid swelling, measuring 2 × 2 cm, which felt rubbery, with a red edematous left eye. Otherwise, he had no active nasal, orbital, or constitutional complaints. Nasal endoscopy revealed a clear nasal cavity and nasopharynx. An ultrasound-guided fine-needle aspiration of the parotid mass was performed, and pathology confirmed the metastasis of non-keratinizing undifferentiated nasopharyngeal carcinoma (NK-UNPC). Following that, the patient was offered medical versus surgical intervention; however, he preferred surgical removal over radiation therapy. Thus, he underwent left superficial parotidectomy and left supraomohyoid neck dissection levels Ib, 2a, and 3. Intraoperative surgical pathology confirmed parotid metastasis with one positive intraparotid lymph node, while other lymph nodes of the parotid and neck were negative for malignancy. Operative course was smooth with no intraoperative complications, and all neurovascular structures encountered were preserved. The patient made an uneventful postoperative recovery and was discharged on the following day of the surgery in a stable condition.

The patient had an overall good prognosis, and he had follow-up visits with regular imaging follow-ups for more than 1 year, which showed no evidence of disease recurrence. He also underwent two conjunctival biopsies to check for any orbital recurrence, which all came negative for malignancy. His performance status using Karnofsky scale is 90. He experienced post-orbital radiation red eye, madarosis, and dermatitis as complications of radiotherapy, managed with ophthalmic solutions and lubricants. Table 1 demonstrates the chronological events of the case, while Table 2 lists cases of NPC with parotid and orbital metastasis.

Table 1.

Chronological events of the case

May 28, 2019	First emergency department visit
	CT with contrast
	EBV-IgG (+) and EBV-EA (+)
	Admission for further workup
May 30, 2019	Right cervical lymph node biopsy
June 3, 2019	Patient was discharged
June 23, 2019	Lymph node biopsy report confirmed the diagnosis of NK U-NPC
June 24, 2019	First ENT outpatient department follow-up visit
June 27, 2019	Whole-body PET/CT scan and neck CT
September 4, 2019	Completion of chemoradiotherapy
January 1, 2020	Neck MRI showing significant regression of the disease
June 21, 2020	Neck CT revealed no evidence of recurrence
February 5, 2021	Orbital MRI
February 21, 2021	Exploratory orbitotomy of left upper eyelid with incisional biopsy
March 2, 2021	ENT follow-up visit
March 5, 2021	Neck MRI
April 4, 2021	Left orbital mass biopsy pathology result of confirmed the metastasis of NK U-NPC
September 29, 2021	Completion of chemoradiotherapy
January 3, 2022	Head and neck PET/CT
January 18, 2022	ENT presentation of left preauricular parotid mass
January 25, 2022	FNA pathology result of left parotid mass biopsy confirmed the metastasis of NK U-NPC
March 21, 2022	Left superficial parotidectomy and left supraomohyoid neck dissection levels Ib, 2a, and 3
	Surgical pathology results confirmed parotid metastasis with one positive intraparotid lymph node
April 21, 2022	ENT follow-up visits
June 28, 2022	Physical examination without palpable neck masses, clear nasopharynx upon examination with nasopharyngoscope, and follow-up PET/CT head and neck with no evidence of FDG-avid local recurrence, nodal or distant metastasis
December 12, 2023
January 17, 2024	Conjunctival biopsy was negative for malignancy
October 16, 2024	Follow-up imaging studies of PET/CT remain with no evidence of FDG-avid local recurrence, nodal or distant metastasis
April 28, 2025
November 20, 2025
December 16, 2025	Follow-up ENT visit the patient remains in metabolic remission for continuous surveillance

CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; FNA, fine-needle aspiration; NK U-NPC, non-keratinizing undifferentiated nasopharyngeal carcinoma.

Table 2.

Summary of nasopharyngeal carcinoma cases with orbital and parotid metastasis

Author/year	Age/gender	Presentation	Prognosis	Management
Wang et al. [4]	50/Male	Left parotid lump, intermittent nasal obstruction	No recurrence with 3-year follow-up	Total parotidectomy with selective neck dissection, radiotherapy, and chemotherapy
Van et al. [5]	57/Male	Left parotid mass measuring 1.5 cm, bilateral enlarged lymph nodes	No recurrence or metastasis with 2-year follow-up	Parotid mass excision, followed by radiotherapy and chemotherapy
	42/Male	Right cheek movable, firm, and painless mass measuring 0.5 cm	No signs of recurrence or metastasis with 3-year follow-up	Radiotherapy, chemotherapy, and lymphadenectomy
Amin et al. [6]	16/Male	Growing painful cervical lump below right ear, bleeding from mouth and nose, and several lymphadenopathy	Deterioration and slow progression of the mass	7 sessions of radiation with chemoradiation (cisplatin, fluorouracil, paclitaxel, and granulocyte colony-stimulating factor)
Kamio et al. [7]	54/Male	Left eye acute visual loss, left serous otitis media, left facial pain mimicking trigeminal neuralgia, no light perception, disturbed eye movement in all directions	1 recurrence (Karnofsky scale 80%)	Radiotherapy
				Chemotherapy and cervical lymphadenectomy
Marrero et al. [8]	60/Female	Progressively enlarging left forehead lesion, painless nodule which became tender later overtime, bilateral headaches	Deterioration, significant reduction in functional capacity and ultimately transferred to palliative services	Surgical excision of calvarial lesion, followed by palliative radiation and systemic therapy with immune checkpoint inhibitor toripalimab and bone-modifying agent denosumab to manage skeletal metastases

Discussion

NK-UNPC represents a histopathological subtype of NPC distinguished by the lack of keratinization, syncytial cellular growth, and large cells round to oval in shape with prominent nucleoli [3]. The incidence of NK-UNPC varies across different geographic regions. According to the American Association for Cancer Registry, in highly endemic areas such as south and Southeast Asia, NK-UNPC constitutes the majority of NPC cancers [9]. A study conducted by Argirion et al. [10] revealed that the incidence of NK-UNPC in different regions of Thailand ranged from 0.8% to 8.9% of all NPCs.

Several factors have been linked to the etiology of NK-UNPC, including tobacco smoking, alcohol consumption, and dietary habits such as the consumption of salted fish [11]. Tobacco smoke is a complex mixture containing over 4,000 compounds, many of which are known to act as mutagens and DNA-damaging agents associated with various cancers, including NPC [11, 12]. The carcinogenic effects of tobacco smoke influence the reactivation of the Epstein-Barr virus (EBV), with nicotine exposure promoting NPC cell proliferation and EBV replication, thereby inducing the expression of lytic gene products [12]. This relationship is supported by several studies that have demonstrated a correlation between cigarette smoking and EBV seropositivity [11–13]. Our case demonstrated smoking associated with a strong positivity on EBV testing, these findings are consistent with a recent study by Li et al. [14], which suggests that the combination of cumulative smoking consumption and pretreatment EBV DNA levels serves as an independent prognostic indicator for male NPC, with an associated increased risk of disease progression, distant metastases, and death.

Common sites of metastasis in NPC include regional lymph nodes, with cervical lymph nodal involvement being prevalent across various subtypes [3]. In many cases, cervical lymphadenopathy typically presents as the initial complaint, as observed in our patient, who initially presented with right progressive neck swelling. NPC can also metastasize to other sites such as bone, liver, and lungs, or to rarer sites like orbit and distant lymph nodes [3]. Metastasis to orbit is rare, occurring in only 2–3% among all cancer patients [15]. Orbital involvement typically results from direct extension invading pterygopalatine fossa and inferior orbital fissure or from apical invasion of the orbit through the paranasal sinuses [16]. The clinical presentation of orbital metastasis may include eyelid swelling, sudden diplopia, change in visual acuity, painful eye with or without movement, and proptosis [16]. Similar to our case, eyelid mass was the presenting symptom of recurrence that upon thorough investigation revealed orbital involvement.

Similarly, the parotid gland is an unusual site of metastasis, with reported incidence of lymph node metastasis in the parotid gland ranges from 0.6 to 3% in the literature [17]. The literature reveals only a handful of documented cases [4, 5, 18]. In Wang et al.’s [4] study, 14 cases of parotid gland lymph node metastasis from NPC were reported. Among these, three patients experienced uncontrolled disease progression, with recurrence observed within 3 months following radiotherapy. On the other hand, delayed parotid metastases manifested in the remaining patients, with an average interval of 55.9 months between primary tumor treatment and metastatic involvement diagnosis. Clinically palpable masses were detected in all cases during physical examinations, typically localized to the inferior or superficial parotid nodes. In our patient’s case, he presented with uncontrolled metastasis that occurred within 3 months post-chemoradiotherapy, with the mass predominantly situated in the superficial parotid lymph nodes. This rapid parotid metastasis was within a short interval after completion of orbital treatment, all of which were subsequent to completed chemoradiotherapy for a prior primary NPC 2 years ago. The putative pathological mechanism of NPC metastasis to parotid gland is not fully understood; however, the prevailing evidence hypothetically suggests retrograde retropharyngeal nodal spread, which may be due to a disrupted natural lymphatic drainage secondary to obstruction, prior surgical intervention, or radiation therapy [19]. In our case, it is speculated that previous radiotherapy affected regional parotid physiological lymphatic system which in turn promoted seeding of tumor cells through alternative pathways.

Various imaging modalities are utilized in the evaluation and staging of NPC, including CT, magnetic resonance, and PET. CT is often the initial imaging modality of choice due to its excellent visualization of bony involvement [20]. On the other hand, MRI is preferred for local staging, aiding in better soft tissue delineation [20]. PET, typically combined with CT, plays an essential role in assessing nodal involvement and detecting distant metastases by identifying metabolically active disease [20]. Additionally, immunohistochemistry, in conjunction with EBV testing, contributes significantly to the precise diagnosis of NPC subtypes [3]. In the presented case, the strong staining with pan-cytokeratin, P63, Ck5/6, P40, and EBV facilitated the diagnosis of NK-UNPC.

The cornerstone of NPC management is radiotherapy. NPC, particularly the non-keratinizing type, demonstrates radiosensitivity, making it a primary treatment modality [21]. However, the incorporation of concurrent chemotherapy has become crucial for managing locally advanced NPC [22]. While the role of surgical intervention is limited, cases of locoregional disease recurrence may necessitate surgery [22]. In our case, we opted for a combined approach, performing a superficial parotidectomy and selective neck dissection along with chemoradiotherapy. Multiple factors contribute to the prognosis of NPC. Stepan et al. [23] found variations in prognosis based on histological subtypes, with the non-keratinizing undifferentiated subtype demonstrating the most significantly favorable prognosis for survivability among different ethnic groups.

Conclusion

NPC is a rare and aggressive malignancy with diverse clinical presentations. Early detection and staging by imaging play a crucial role in effective management. While NPC generally demonstrates radiosensitivity, the complexities involved in treatment decision-making and the potential for recurrence or metastasis highlight the importance of multidisciplinary approaches. Histological subclassification has proved to be critical in both diagnostic and prognostic values.

Statement of Ethics

The authors are accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the Institutional and/or National Research Committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal upon request. The Institutional Review Board approval was not required complying with national and local guidelines where written informed consent is sufficient. The CARE Checklist has been completed by the authors for this case report and attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000551478).

Conflict of Interest Statement

The work was not supported or funded by any drug company. This article (or any part of its contents) was not presented in any conference and was not published in any journal. The authors have no conflicts of interest to declare.

Funding Sources

The authors confirm that the research project is not funded.

Author Contributions

Shmokh Alsalamah and Sultan Alsumairi: conceptualization, investigation, data curation, writing – original draft and assisting in making tables and figures. Malak Almalki: conceptualization, writing – review and editing, and project administration. Majed Pharaon: investigation, formal analysis (pathology), visualization (photomicrographs), and writing – review and editing. Mohammed Alessa: conceptualization, investigation, intervention, writing – review and editing, project administration.

Funding Statement

The authors confirm that the research project is not funded.

Data Availability Statement

Data are not publicly available due to privacy reasons. The data used to support the findings of this study are available from the corresponding author upon request.