Nasopharyngeal carcinoma in a 15-year-old: A rare pediatric tumor

Abstract

The unique challenges of diagnosing, treating, and managing pediatric nasopharyngeal carcinoma (NPC) in a lower-middle-income African country, Tanzania, are presented. Also, Computed Tomography (CT) imaging features that can distinguish NPC from other pediatric head and neck tumors are highlighted.

Introduction

Nasopharyngeal carcinoma (NPC) is rare in children and adolescents, constituting less than 1% of all pediatric malignancies [1,2]. NPC is more prevalent in specific geographic areas, particularly Southeast Asia, North Africa, and parts of the Middle East [3,4]; with a peak incidence among adolescents (ages 10-19 years). In Africa, lymphoma (including Hodgkin, non-Hodgkin, and Burkitt lymphoma) is the most prevalent pediatric head and neck tumor, making up 52.15% of all pediatric head and neck tumors [4]. NPC is a distant second (16.7%), and rhabdomyosarcoma is the third (15.9%) most common pediatric head and neck tumor [4].

NPC is closely associated with Epstein-Barr virus (EBV) infection. In endemic areas, it is linked to about 95% of NPC cases [5]. EBV is universally present in WHO type 2 (nonkeratinizing squamous cell carcinoma) and WHO type 3 (undifferentiated) NPC [5]. The clinical presentation of NPC in the pediatric population is nonspecific, which makes early diagnosis difficult. Children with NPC may present with some of the following symptoms: nasal obstruction, epistaxis, dyspnea, headaches, tinnitus, trigeminal or abducens nerve palsy, and neck mass [6].

The challenges of diagnosing and managing pediatric NPC in a lower-middle-income-African country, and the CT imaging findings that can distinguish NPC from other pediatric head and neck tumors are presented.

Case presentation

A 15-year-old previously healthy patient was referred from a rural hospital in Tanzania for bilateral neck mass evaluation. The neck masses were first noticed about 14 months earlier. The patient reported worsening neck pain, epistaxis, hoarseness, dysphagia and dyspnea. Despite these symptoms, the patient only presented for evaluation after an episode of generalized weakness, near syncope, and blurry vision. On physical exam, the patient appeared pale. Nontender, nonmobile, firm, smooth bilateral neck masses were also noted (Fig. 1). The patient had a BMI of 16.8 kg/m². Otherwise, all other vital signs were within normal limits.

Fig. 1.

Bilateral neck masses on presentation. Nontender, nonmobile, nonulcerated, firm, smooth bilateral neck masses. The mass in the right neck was approximately 12 × 8 cm, while that in the left measured 12 × 10 cm.

Laboratory evaluation included complete blood count (CBC), serum electrolytes, prothrombin time (PT), partial thromboplastin time (PTT), renal function tests (RFT), international normalized ratio (INR), serology, and uric acid levels. The patient was noted to be anemic with a hemoglobin of 6.4 g/dL. Other laboratory values were within normal limits.

On imaging, Computed Tomography (CT) with contrast of the neck showed a moderately enhancing 6.1 cm ill-defined nasopharyngeal mass with bilateral lymphadenopathy (Fig. 2). Differential diagnosis for the CT findings included NPC, lymphoma, and rhabdomyosarcoma.

Fig. 2.

Computer tomography (CT) of the neck with contrast. Moderately enhancing ill-defined mass obliterating the Fossa of Rosenmuller (posterolateral pharyngeal recess) and the torus tubarius, measuring approximately 6.0 × 4.8 × 6.1 cm, yellow arrow (A). The mass extended into the nasal cavity, obstructing the nasopharynx, red arrow (A). Opacified ethmoid air cells and sphenoid sinuses, suggesting obstruction due to mucous retention or tumor extension, orange arrows (B). Multiple enlarged heterogeneously enhancing lymph nodes within the bilateral submandibular regions, black arrows (C); left retropharyngeal, blue arrow (C); bilateral cervical regions, green arrows (D and E).

Ultrasound guided fine needle aspiration of the neck masses showed cohesive sheets and islands of epithelioid cells with large vesicular nuclei and prominent nucleoli (Fig. 3). Immunochemistry stain showed strong positivity for AEI/AE3 keratins (Fig. 4). In addition, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) immunochemistry stain was also positive.

Fig. 3.

Low (A) and high (B) magnification images of fine needle aspiration. Cohesive sheets of cells (A) characterized by moderate abundant cytoplasm (red arrows, B) and enlarged hyperchromatic nuclei (yellow arrow, B). The high nucleus to cytoplasm (N/C) ratio is consistent with poorly differentiated NPC cells [7].

Fig. 4.

AEI/AE3 keratin immunochemistry stain. Diffusely strong positive staining with AE1/AE3 indicates the presence of epithelial tumor cells, supporting a diagnosis of poorly differentiated nasopharyngeal carcinoma.

With a tissue diagnosis of NPC, the patient was started on a comprehensive treatment regimen. The patient first received Amoxicillin and Clavulanate potassium (Augmentin, USA antibiotics, Bristol, TN, USA) 625 mg twice daily for 5 days to address potential infection. Diclofenac potassium 50 mg 3 times a day for pain for a total of 7 days was also administered. The patient was optimized for chemoradiotherapy with 2 units of blood to address her severe anemia. In addition, Dexamethasone (Decadron, Merck & Co., Inc., Whitehouse Station, NJ, USA) 5 mg twice a day, and Allopurinol (Aloprim, NerPharMaSrl, V.le Pasteur 10, Nerviano, Italy) 200 mg twice a day were administered for 5 days before initiation of chemotherapy. The patient had 3 cycles of chemotherapy consisting of Cisplatin (WG Critical Care, Paramus, NJ, USA), Folinic acid (Fisher Scientific, Reagent Lane, Fair Lawn, NJ, USA), and 5-Fluorouracil (Fresenius Kabi, Lake Zurich, IL, USA). Upon completing chemotherapy, the patient received intensity-modulated radiation therapy (IMRT) delivered to the nasopharynx and involved cervical lymph nodes. A total 70 Gray (Gy) dose in 35 fractions was administered.

During treatment, the patient exhibited expected acute toxicities, including mucositis, xerostomia, and mild hematological toxicity. These side effects were effectively managed with sodium bicarbonate mouthwash, BMX syrup, antacids and xylocaine plus miconazole oral gel. Frequent clinical assessments were performed during and after treatment to monitor response and toxicity. At the end of chemoradiotherapy, local disease improved markedly (Fig. 5) and the bilateral neck swelling resolved completely (Fig. 6).

Fig. 5.

Postcontrast enhanced CT of the neck obtained 12 weeks postchemoradiation therapy. Near complete resolution of moderately enhancing ill-defined mass in the Fossa of Rosenmuller, white arrows (A). Moderately enhancing small soft tissue mass within the nasal cavity, orange arrow (B). Mucosal thickening involving the bilateral maxillary sinuses, worse on the left, yellow arrow (A) and left ethmoid air cells, green arrow (C). Interval size decrease of multilevel bilateral cervical lymphadenopathy within the left level IV lymph node chain, red arrows (D and E). Irregularities and bone destruction involving the clivus, blue arrow (F).

Fig. 6.

Post-treatment resolution of bilateral neck swelling. Markedly decreased bilateral neck swelling after 3 cycles of chemotherapy (A). Complete resolution of bilateral neck swelling with associated skin desquamation postradiation therapy (B).

A post-treatment CT of the neck, acquired 12 weeks after treatment completion, showed significant improvement of the nasopharyngeal mass and lymphadenopathy. However, a moderately enhancing small soft tissue mass within the nasal cavity was seen, concerning for residual tumor, although postradiation changes could not be excluded (Fig. 5).

Post treatment completion, patient and family received palliative counselling and discharged home with Etoposide (Etopophos, Bristol-Myers Squibb, Princeton, NJ, USA) and Cyclophosphamide (Amneal Oncology Pvt. Ltd., Telangana, India).

Discussion

The standard of care for locally advanced nasopharyngeal cancer is chemoradiotherapy [8,9]. This therapeutic strategy merges the strengths of chemotherapy and radiation therapy to optimize treatment effectiveness and enhance patient outcomes. Despite the curative potential of pediatric NPC with chemoradiation, the overall survival rate of pediatric NPC in Africa is significantly lower compared to high-income countries. The 2-year survival rate in Kenya is 36% [10] compared to a 5-year survival rate of 91% in the USA [11]. Pediatric NPC in Africa is often diagnosed at an advanced stage, leading to a poorer prognosis. For example, our patient did not present for evaluation until about 2 years after initial symptoms onset. While curative treatment is possible with chemoradiotherapy, limited access to specialized care and delayed diagnosis contribute to lower survival rates in Africa [12].

Early diagnosis and treatment of NPC is crucial for favorable outcomes. Ultrasound, CT, PET-CT and MRI all play a role in diagnosis (Table 1). Ultrasound and CT are usually the initial imaging modalities for neck masses. Ultrasound can also be utilized for cervical lymph node biopsy and post treatment surveillance of cervical lymphadenopathy. CT assesses local regional tumor burden and bone involvement. PET-CT and MRI provide complementary information that guides accurate diagnosis, treatment planning, and follow-up. PET-CT is essential in detecting regional nodal involvement and distant metastases. It also aids in evaluating treatment response and identifying residual or recurrent disease post-therapy. MRI provides superior soft-tissue contrast and can precisely delineate tumor margins. Thus, MRI is essential for radiation therapy planning and post treatment evaluation. However, in resource limited areas CT and ultrasound are often the only available imaging modalities.

Table 1.

Imaging modalities utilized in pediatric NPC diagnosis and management [13,14].

Modality	Utility in pediatric NPC	Strengths	Limitations
Ultrasound	Initial evaluation of cervical lymphadenopathy and mass. FNA and core lymph node biopsy guidance.	Safe, no radiation, cheap and portable.	Cannot assess primary nasopharyngeal tumor or skull base involvement.
CT	Assessment of regional spread and bone involvement.	Rapid imaging, excellent for detecting skull base erosion and lymph node calcifications.	Radiation exposure; limited soft tissue resolution.
PET-CT	Whole-body staging and treatment response evaluation.	Detects distant metastases and residual disease; useful in surveillance.	High radiation dose; less anatomic detail for local tumor margins.
MRI	Gold standard for local tumor extent and treatment planning.	Superior soft-tissue contrast; detailed evaluation of skull base, intracranial, and perineural spread. No ionizing radiation.	Longer scan times; may require sedation in young children; less effective for detecting distant metastases. Expensive to acquire and maintain.

The superior soft tissue contrast of MRI makes it the gold standard for local tumor extent evaluation. However, the high cost of acquiring and running an MRI scanner limits availability in most low-income areas. Therefore, the work horse for NPC imaging in most low-income areas is CT. Yet, ionizing radiation from the use of CT in pediatric patients increases the risk of developing other head and neck cancers later in life, such as leukemia, brain tumors, and thyroid cancer [15].

In our case, the patient could not afford MRI imaging. Also, PET-CT was not established in Tanzania at the time. Therefore, the only imaging modalities utilized were ultrasound and CT. Distinguishing NPC from other head and neck tumors like lymphoma and Rhabdomyosarcoma with CT alone can be challenging. Table 2 highlights distinguishing CT findings for common pediatric head and neck tumors.

Table 2.

Distinguishing CT imaging findings of common pediatric head and neck tumors.

	Nasopharyngeal carcinoma (NPC)	Lymphoma	Rhabdomyosarcoma
Common location	Lateral nasopharyngeal wall (Fossa of Rosenmüller).	Tonsils, oropharynx, and nasopharynx (Waldeyer’s ring).	Orbit, parameningeal sites (nasal cavity, middle ear), neck.
Enhancement pattern	Moderate to intense, often heterogeneous enhancement.	Homogeneous soft-tissue density, mild to moderate enhancement.	Variable; often heterogeneous, especially with necrosis.
Mass effect	Often causes local invasion, skull base erosion.	Minimal despite large mass size.	Pronounced; may displace adjacent structures.
Bone involvement	Frequently invades skull base and adjacent foramina.	Typically spares bone early.	Commonly invades bone (especially parameningeal types).
Necrosis/Cystic change	Can show central necrosis in advanced cases.	Rare	Common, especially in larger or aggressive tumors.
Calcification	Rare	Uncommon	Rare
Lymphade- nopathy	Common, with necrosis or ring enhancement.	Common, often bulky, bilateral, non-necrotic.	Possible, may be necrotic.
Soft tissue invasion	Frequently invades parapharyngeal, masticator spaces.	Often limited.	Aggressive invasion, depending on site and subtype.

Lower soft tissue contrast with CT compared to MRI limits adequate distinction of various head and neck cancers with CT alone. However, a constellation of CT findings including tumor location, mass effect, enhancing pattern, bone involvement, and soft tissue invasion can be used to adequately differentiate common head and neck tumors [[16], [17]].

Bilateral cervical lymphadenopathy is more common in lymphoma than NPC, however several additional CT findings made NPC more likely in our case [16,17]. The presence of a moderately enhancing mass in the fossa of Rosenmüller, invasion of the nasopharyngeal space and sinuses, and erosive changes of the anterior clivus; all suggested a primary malignancy of the nasopharynx making NPC the most likely diagnosis (Fig. 2). The absence of MRI limited radiotherapy planning since definite tissue delineation is limited on CT. Post treatment soft tissue in the tumor bed with moderate enhancement on CT (Fig. 5) could not be definitively characterized as either residual tumor or post radiation changes without MRI. Additionally, the spread of disease to distant organs and lymph nodes was limited without PET-CT.

Given the potential for recurrence and long-term complications in pediatric NPC survivors, it is recommended to maintain a vigilant follow-up regimen lasting more than 5 years [18]. However, financial constraints and lack of adequate infrastructure limits optimal comprehensive post treatment follow up in low resource settings.

Conclusion

Chemoradiation therapy is curative for pediatric NPC. Yet, the outcomes and post-treatment survival rates are significantly lower in Africa compared to high income countries. Lack of adequate medical infrastructure, delayed diagnosis, poverty, and poor post treatment follow-up all contribute to poorer outcomes. Improving early detection, treatment infrastructure, and multidisciplinary care is essential to enhance outcomes for children with NPC in Africa.

Patient consent

Written informed consent was obtained from the patient’s parents for photos, laboratory, pathology, CT images and publication of this case report. A copy of the consent is available on request.