Diagnostic Delay in Pediatric Nasopharyngeal Burkitt Lymphoma Presenting With Chronic Otalgia and Multiple Cranial Nerve Palsies: A Case Report

ABSTRACT

Persistent unilateral otalgia, especially when refractory to treatment and associated with cranial nerve signs, should prompt early imaging and nasopharyngeal evaluation to avoid delayed diagnosis of aggressive malignancies such as Burkitt lymphoma.

1. Introduction

Burkitt's lymphoma is marked by its highly aggressive nature. The mandible, facial bones, kidneys, gastrointestinal tract, ovaries, breast, and other extranodal sites are frequently involved. The neck is not as commonly involved as other areas. Instances of Burkitt's lymphoma have been recorded in the sinonasal and orbital areas, along with less conventional locations like the nasopharynx, postnasal area, parapharyngeal region, mastoid, and mouth [1, 2].

We will present an unusual case of a 12‐year‐old girl initially mistaken as acute otitis media based on the ear pain which was the first complaint. Then symptoms progressed toward damaging the cranial nerves to suffer from strabismus and tongue deviation. After the necessary investigations, she was diagnosed with Burkitt's lymphoma of the nasopharynx.

2. Case History

A 12‐year‐old girl presented to the Children's Hospital with a two‐month history of right‐sided ear pain that was initially responsive to analgesics but progressively worsened over time. No hearing loss, rhinorrhea, or epistaxis were mentioned. Snoring and weight loss were noted by her family. Medical history, family history, and immunodeficiency history were unremarkable.

Over a period of 1 week, she developed additional neurological symptoms, including right‐sided facial numbness, excessive tearing from the right eye, and dysphagia. Prior to her admission at our institution, she had undergone multiple evaluations; an otolaryngologist initially diagnosed acute otitis media, prescribing amoxicillin‐clavulanate and dexamethasone without clinical improvement. Subsequent consultations with a neurologist and an endocrinologist led to diagnoses of trigeminal neuralgia and facial nerve palsy, respectively, but treatments with vitamins proved ineffective. Upon clinical examination at our hospital, the patient exhibited significant cranial nerve involvement, characterized by right esotropia, right‐sided tongue deviation, and a leftward deviation of the uvula. The rest of the cranial nerves examination was normal.

3. Differential Diagnosis, Investigations and Treatment

Refractory otitis media, mastoiditis, trigeminal neuralgia, skull base lesion, nasopharyngeal carcinoma, rhabdomyosarcoma, lymphoma, and infectious or inflammatory cranial neuropathy were considered as differential diagnoses.

Baseline laboratory investigations in our patient demonstrated leukocytosis (WBC 10,800/μL) with neutrophilic predominance, microcytic anemia (Hb 9.7 g/dL, MCV 72 fL), elevated uric acid (13.9 mg/dL), and elevated ESR (79 mm/h). Renal and liver function tests were largely within acceptable limits, although creatinine was mildly elevated (1.5 mg/dL). Infectious screening, including HBsAg, anti‐HIV, HCV PCR, and anti‐HAV IgM, was negative. CSF analysis showed no white blood cells and normal protein levels, with no evidence of central nervous system involvement. Brain computed tomography (CT) scan ordered by a neurologist revealed a suspicious nasopharyngeal mass. Subsequent magnetic resonance imaging (MRI) of the brain (Video 1) demonstrated a lesion centered in the nasopharynx extending toward the right temporal fossa, partially obstructing the right eustachian tube and reaching the medial wall of the right maxillary sinus with evident bone erosion. Nasopharyngeal endoscopy was then performed to obtain a biopsy for definitive diagnosis. Histopathological examination confirmed Burkitt lymphoma, with H&E staining showing sheets of monotonous intermediate‐sized cells with round nuclei and finely clumped chromatin. Immunohistochemical analysis revealed that the neoplastic cells were positive for LCA (Figure 1), CD20 (Figure 2), and CD10 (Figure 3), while testing negative for CD3 (Figure 4). Furthermore, a bone marrow biopsy revealed large, atypical cells compatible with Burkitt lymphoma infiltration (Figure 5). Our patient was treated according to the BFM‐NHL protocol, including the COP regimen (prednisolone, vincristine, and cyclophosphamide) followed by Block AA (dexamethasone, vincristine, etoposide, cyclophosphamide, cytarabine, methotrexate, and leucovorin rescue). Intrathecal therapy with cytarabine, methotrexate, and hydrocortisone was also administered. On presentation, the patient had tumor lysis syndrome and was managed with aggressive hydration and allopurinol; although hemodialysis was considered, it was ultimately not required. Following Block AA chemotherapy, the patient developed febrile neutropenia, which was treated with filgrastim and broad‐spectrum antimicrobial therapy, including ceftazidime, vancomycin, ciprofloxacin, and fluconazole.

VIDEO 1.

Download video file ^{(11.9MB, mp4)}

MRI of the brain demonstrated a lesion centered in the nasopharynx extending toward the right temporal fossa. Video content can be viewed at https://onlinelibrary.wiley.com/doi/10.1002/ccr3.73588.

FIGURE 1.

LCA (CD45) immunohistochemical stain showing diffuse membranous positivity in neoplastic lymphoid cells (×40).

FIGURE 2.

CD20 immunohistochemical stain showing strong diffuse membranous positivity in B‐cell population (×20).

FIGURE 3.

CD10 immunohistochemical stain demonstrating positive membranous staining in neoplastic cells (×10). Bone marrow biopsy revealed large, atypical cells compatible with Burkitt lymphoma.

FIGURE 4.

CD3 immunohistochemical stain negative in neoplastic cells (×20).

FIGURE 5.

Bone marrow biopsy revealed large, atypical cells compatible with Burkitt lymphoma.

4. Conclusion and Results (Outcome and Follow‐Up)

After the 12‐month follow‐up after the initial diagnosis, the patient demonstrated a significant regression in esotropia and ear pain, with no reported treatment complications. Additionally, a noticeable improvement in tongue mobility was observed. A follow‐up MRI revealed a reduction in tumor size compared to the baseline scan, with no signs of metastasis.

5. Discussion

Burkitt Lymphoma (BL) stands out among B‐cell malignancies for its remarkably aggressive clinical course, driven by an almost unparalleled rate of cellular proliferation [3].

While the abdomen is the most common site for sporadic BL, primary involvement of the nasopharynx—specifically within Waldeyer's ring—is a clinical rarity, occurring in less than 15% of head and neck presentations [4].

The pathogenesis is further complicated by the role of the Epstein–Barr Virus (EBV). In the endemic variant, EBV is present in virtually all tumor cells, where it is thought to promote genomic instability and provide critical survival signals to B‐cells during the early stages of oncogenesis [3, 5]. In sporadic cases, the prevalence of EBV is lower, ranging from 20% to 30%. In African populations, chronic Plasmodium falciparum malaria serves as a necessary co‐factor, inducing B‐cell hyperplasia and suppressing the T‐cell‐mediated surveillance of EBV‐infected cells, thereby creating an environment ripe for MYC translocation [6].

The clinical manifestations of nasopharyngeal BL are predominantly influenced by its rapid doubling time, generally ranging from 24 to 48 h [5]. This rapid growth can cause symptoms to appear suddenly, which can easily be mistaken for mild inflammatory conditions like chronic rhinosinusitis or adenoid hypertrophy. Patients primarily exhibit progressive nasal obstruction, reported in nearly 100% of nasopharyngeal cases [7]. This is often accompanied by hyponasal speech, snoring, and persistent rhinorrhea.

The anatomical position of the nasopharyngeal mass often dictates the initial clinical presentation. Specifically, mechanical compression of the torus tubarius frequently results in Eustachian tube dysfunction; this, in turn, may precipitate secondary serous otitis media and persistent conductive hearing loss [8]. In more aggressive scenarios where the malignancy infiltrates the parapharyngeal space or the skull base, the clinical picture often shifts toward neurological involvement. In these cases, it is not uncommon to observe cranial nerve palsies—most notably involving the abducens (VI) or oculomotor (III) nerves—which clinically present as diplopia or noticeable proptosis [7]. Despite the nasopharynx being a frequent subsite for head and neck BL—involved in 40% of rhinologic cases—its symptoms often mimic benign conditions, causing diagnostic delays. Statistically, the most common presentations include nasal obstruction (29%), facial swelling (24%), headache (21%), and proptosis (19%) [9]. In contrast, our patient presented atypically with severe ear pain as the primary symptom; this highlights how atypical manifestations within a common subsite can easily mislead clinicians and delay diagnosing this aggressive malignancy.

Because Burkitt's lymphoma is marked by a high proliferation index (Ki‐67 about 100%) and certain immunohistochemistry markers, such as CD20, CD10, and BCL‐6, histological investigation is essential. These distinct characteristics are essential for precise diagnosis and suitable treatment planning. CT and MRI‐based imaging aids in determining the expansion toward nearby structures. When diagnosing bone degeneration, CT scans are better than MRIs because they reveal soft‐tissue density mass with or without bony erosion. When assessing soft tissue and bone marrow extensions, MRI performs better [2]. In our patient, the diagnosis was delayed due to not considering the red flags, which is the main aim of our case. A study of Swain et al. [4], showed that this tumor was more common in males and the most common symptoms were nasal blockage and nasal bleeding. Our patient was a female with ear pain as a main symptom. BL is extremely sensitive to chemotherapy, and complicated chemotherapy consisting of methotrexate, prednisone, vincristine, and cyclophosphamide is the basis for its treatment. However, surgery and radiation therapy are not advised and have been shown to raise morbidity without improving survival. Even in localized forms, surgery is not recommended. Its application is limited to issues like bowel obstruction that call for immediate attention [2].

Author Contributions

Sultaneh Haddad: writing – original draft, data curation, investigation. Abdulwahhab Al‐Shaikhli: writing – original draft. Fehmat Hallak: writing – original draft. Halima Hamdan: writing – original draft. Ahmed Farag: writing – original draft. Ranim Nakhal: writing – original draft. Sameh Alramdani: writing – review and editing. Mohammad Obada Alsadi: writing – review and editing, project administration. Rawad Hamza: writing – review and editing. Othman Hamdan: supervision.

Funding

The authors have nothing to report.

Disclosure

Guarantor: Mohammad Obada Alsadi.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient's parents to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.