Bilateral jaw involvement of Burkitt's lymphoma in a 5-year-old: Rare pediatric case with review of the literature

Abstract

Introduction and importance

Burkitt lymphoma (BL) is a rapidly progressing tumor that requires urgent diagnosis and treatment. It is the first human neoplasm linked to a viral cause and is classified into three subtypes: sporadic, endemic, and immunodeficiency-associated.

Case presentation

We report a rare case of a 5-year-old boy who presented to the Oral and Maxillofacial Surgery Department with a two-month history of bilateral maxillary swelling and pain. He had no significant medical history. An incisional biopsy confirmed the diagnosis of Burkitt's lymphoma. The patient underwent chemotherapy following the R-COPADM protocol. Despite stage III diffuse lymph node involvement, treatment was successful.

Clinical discussion

Oral and maxillofacial involvement of BL in pediatric patients are extremely rare, with an estimated prevalence of 0.5 % to 6 %. In this case, the disease extended beyond the jaws to involve the maxillary sinuses, orbit, and zygomatic bone. Histologically, the classic “starry-sky” pattern was notable in most tissue sections.

Conclusion

This case highlights the importance of early recognition and prompt multidisciplinary intervention in pediatric Burkitt lymphoma to prevent widespread disease progression and improve survival outcomes.

Highlights

• •Burkitt lymphoma rarely presents with bilateral jaw involvement in pediatric patients.
• •This case involved extensive maxillofacial spread, including the orbit, sinuses, and zygomatic bone.
• •Histopathology and immunohistochemistry were essential for definitive diagnosis.
• •Early multidisciplinary management led to successful treatment despite advanced-stage disease.

1. Introduction

Burkitt's lymphoma (BL) is a highly aggressive tumor B-cell lymphoma, which is classified under non-Hodgkin lymphoma (NHL). Moreover, it accounts for 3–5 % of all lymphomas [1,2]. BL is a rapidly growing human neoplasm and the first to be associated with a virus [2,3].

The WHO categorization of BL describes three epidemiological variants: endemic, sporadic (the most common variety found in regions with non-malaria) and immunodeficiency-associated or AIDS-associated [3]. The endemic type most frequently presents with facial involvement in approximately 86 % of cases, or with abdominal involvement in about 9 % of cases [4,5]. Jaw involvement is infrequent in the sporadic type, whereas abdominal involvement is common, presenting in 91 % of cases [[6], [7], [8]]. Sporadic Burkitt's lymphoma (SBL) is not related to geographical region, accounts for about 30 to 40 % of lymphomas in children [7,8]. The AIDS-associated type is often interrelated with extranodal involvement, forasmuch as the gastrointestinal tract and bone marrow are the most prevalent extranodal sites of disease [3,9]. These types are analogous to each other in morphology, immunophenotype, and genetic features [3]. The National Comprehensive Cancer Network (NCCN) views the following investigations as crucial for determining a diagnosis of Burkitt lymphoma in addition to its general guidelines on lymphoma diagnosis: an Immunohistochemistry panel including CD45, CD20, CD3, CD10, Ki-67, BCL2, BCL6, TdT with or without cell surface marker analysis by flow cytometry for kappa/lambda, CD45, CD20, CD3, CD5, CD19, CD10, TdT in peripheral blood and/or a biopsy specimen Karyotype with or without fluorescence in situ hybridization (FISH): t (8;14) or variants; MYC, BCL2; BCL6 rearrangement [9]. In this paper we present a rare case of Burkitt's lymphoma in a 5-year-old boy with manifestation in the oral cavity.

2. Case presentation

A 5-year-old boy was referred to the Department of Oral and Maxillofacial Surgery, Damascus University, with complaints of intermittent bilateral maxillary swelling, accompanied by acute pain and occasional bleeding. The patient reported a history of pain and swelling for 2 months and had previously been diagnosed with a dental abscess by his general dental practitioner. The patient's medical history was reviewed, but no significant findings were noted in relation to the current issue. The extraoral examination revealed facial asymmetry and exophthalmos due to bilateral swelling of the maxilla. The surface of the swelling was well defined, smooth and erythematous (Fig. 1). The intraoral examination revealed noticeable swelling in the oral vestibule and hard palate, with no signs of ulceration. The overlying soft tissue appeared pinkish-white in color. The panoramic radiograph revealed loss of lamina dura in mandibular molar region and displacement of the permanent tooth buds in the maxilla (Fig. 2). Initial swelling was also observed on the left side of the mandible (Fig. 1). Computed tomography (CT) scans revealed necrosis and osteolysis involving the bones of both jaws, the zygomatic bone, the maxillary sinus, and the orbital floor (Fig. 3). An incisional biopsy was performed, and histopathological analysis revealed complete replacement of the normal tissue structure by proliferating white blood cells (WBCs), with a characteristic “starry sky” appearance clearly observed (Fig. 5). Immunohistochemically, the tumor cells were positive for CD20 (Fig. 6), with a 100 % proliferative index and showed Ki67 staining in approximately 70 % of malignant cells (Fig. 7). The tumor was negative for both CD5 and Bcl-2 (Fig. 8, Fig. 9). (See Fig. 4.)

Fig. 1.

BL involving the maxilla and causing bilateral facial swelling and exophthalmos.

Fig. 2.

The panoramic radiograph reveals a radiolucent lesion in both the left mandibular and maxillary molar regions. Additionally, there is noted displacement of the temporary tooth buds and a loss of lamina dura in the posterior region.

Fig. 3.

(a, b, c) Axial, (d) 3D CT, of cone-beam computed tomography images reveals ill-defined destructive radiolucency in the mandibular and maxillary posterior regions. Thinning and destruction of the vestibule and oral cortex. The coronal slices indicate the destruction of the zygomatic bone and orbital floor.

Fig. 5.

Photomicrography showing the starry sky pattern (H/E stain).

Fig. 6.

tumor cells were 100 % positive for CD20 (immunohistochemically staining).

Fig. 7.

Positivity for Ki-67 in 70 % in neoplastic cells (immunohistochemically staining).

Fig. 8.

The tumor cells were negative for CD5 (immunohistochemically staining).

Fig. 9.

The tumor cells were negative for Bcl2 (immunohistochemically staining).

Fig. 4.

replacement of normal structure with proliferating white blood cell (WBC) with the “starry sky” appearance (H/E stain).

Following the completion of diagnostic investigations, the patient was referred to the pediatric Oncology Department. Treatment was initiated according to the R-COPADM protocol (Rituximab, Cyclophosphamide, Oncovin [Vincristine], Prednisone, Adriamycin [Doxorubicin], Dexamethasone, and Methotrexate), in line with contemporary pediatric mature B-cell lymphoma protocols. Rituximab was administered in accordance with the R-COPADM schedule, and chemotherapy was delivered in inpatient cycles with appropriate supportive care and methotrexate monitoring. A PET-CT scan was performed to evaluate the response to therapy. The scan demonstrated significant improvement in the patient's condition (Fig. 10). This work has been reported in line with the SCARE 2025 criteria [10].

Fig. 10.

PET CT scan shows density filling the maxillary sinuses, with no evidence of pathological filling for radiopaque material. Additionally, no active metabolic lesions are observed.

3. Discussion

Oral and maxillofacial malignancies are extremely infrequent in the pediatric population, with a reported prevalence ranging between 0.5 % and 6 % [11]. Burkitt lymphomas (BLs) can be classified as endemic, sporadic, or immunodeficient-associated. While they share identical histopathological features, they differ in epidemiology, clinical presentation, and genetic characteristics. Although the microscopic findings are the same across all three types, they vary clinically in terms of age distribution and geographic predominance. [12,13]. The endemic type, which is common in equatorial Africa, is generally documented to occur in early childhood, with a peak age of 6 years, and has a close relationship with the Epstein-Barr virus (EBV); in contrast, the sporadic variant has only a 20 % relationship with EBV and is mostly found in Europe and North America and mostly affects children and adolescents [12,13]. Several studies have strongly demonstrated the involvement of Epstein-Barr virus (EBV) in Burkitt lymphoma (BL), as EBV slows cell death and contributes to the development and persistence of the disease. The endemic type frequently affects the jaw bones and abdomen, leading to tooth displacement, jaw enlargement, and the formation of abdominal masses. In contrast, jaw involvement is rare in the sporadic type. Immunodeficiency-associated variants are more commonly observed in patients with AIDS or other immune-compromising conditions [12,13]. In our case, the patient was not investigated for the presence of EBV, and a definitive classification is not possible. Also, more 89 % of pediatric patients reviewed by Rodrigues-Fernandes et al. [1] do not have information on the identification of EBV in these tumors. Additionally, the incidence of Burkitt's lymphoma cases has been considered intermediate (between endemic and sporadic) in different regions of the world, including South America [1].

Boys have been affected more severely by Burkitt's lymphoma, despite the fact that girls are more prone to maxillofacial lesions [1,3]. Depending on the tumor's severity and anatomic location, symptoms might range from none to life-threatening airway blockage [14]. Clinical signs involving the jaws and surrounding structures may include face swelling, discomfort, exophytic growth, gingival hyperplasia, tooth mobility or displacement, premature tooth eruption and pain. The inferior alveolar nerve or other facial nerves could experience paraesthesia [14,15]. In several reports, a regional hard swelling was observed, with or without pain symptoms [[16], [17], [18]]. When the tumor involved the mandible, hypoesthesia of the lower lip—particularly on the right side—was occasionally reported. In two cases, lip anesthesia and chin numbness were the only presenting symptoms of sporadic Burkitt's lymphoma [19,20]. In maxillary cases, progressive tumor enlargement sometimes led to orbital swelling, proptosis, diplopia, and pruritus [16]. Our case exhibits several typical features of this neoplasm, including male sex, young age, and rare findings such as bilateral jaw involvement and aggressive growth extending to the maxillary sinus, orbit, and zygomatic bone.

Dental inflammation is the most common cause of radiolucent lesions in the periapical area. Non-Hodgkin's Lymphoma can mimic common dental lesions such as periodontitis, chronic periapical periodontitis, pericoronitis, and osteomyelitis on imaging studies. Acute dentoalveolar abscess, osteomyelitis, rhabdomyosarcoma, periapical lesions, ameloblastoma, eosinophilic granuloma, multiple myeloma, leukemia, and other fibro-osseous lesions should thus also be included in the differential diagnosis of BL [14,15]. In the present case, swelling was the primary clinical manifestation of the disease. This observation aligns with the findings of Rodrigues-Fernandes et al. [1], who reported that maxillofacial swelling is the most frequent clinical sign in pediatric patients with this malignancy. Although bilateral jaw involvement in Burkitt's lymphoma is rare [21], as seen in this case, it played a crucial role in ruling out the possibility of an infectious or inflammatory lesion.

Among the 163 reported cases with radiological findings, the majority exhibited radiolucent images indicative of bone resorption or loss. Radiographically, intraosseous lesions often appear as radiolucent areas either unilocular or multilocular with poorly defined, diffuse borders [22]. In our panoramic image, we observed the loss of the lamina dura in the molar region and displacement of the temporary tooth buds in the maxilla. A computed tomography (CT) scan revealed necrosis and destruction of the bone in both jaws, as well as involvement of the zygomatic bone, sinus, and orbital floor (Fig. 3).

The destruction of the cortical bone in both the maxilla and mandible was a significant finding in the imaging examination of this case. The tumor mass extended into regions including the zygomatic bone, maxillary sinuses, and the orbital floor. Similar involvement of these regions by Burkitt's lymphoma has been previously reported in the literature [18,23].

The accurate diagnosis of this malignancy is challenging, but it avoids complications in the management and treatment of the patient [21,24]. In association with routine morphological analysis, the development of an immunohistochemical panel is essential to obtain the definitive diagnosis [24,25]. In our case, the presence of immunoexpression for CD20 and Ki-67, along with negative results for CD5 and Bcl-2, was critical in establishing a conclusive diagnosis of Burkitt's lymphoma.

The chemotherapy cycles to treat Burkitt's lymphoma, as in this case, allow the complete remission of the disease. The chemotherapy treatment adopted in pediatric patients provides a relative survival rate of 90.4 % in five years of follow-up [26]. Additionally, radiotherapy can be indicated for patients with a potential risk of involvement of the central nervous system or in cases that require rapid decompression of structures of the same system due to the disease's involvement [2]. Our patient underwent chemotherapy following the R-COPADM protocol and was successfully treated for stage III diffuse lymph node involvement.

The occurrence of maxillary malignancy in children is rare and in conditions of rapid tumor growth, as in the case reported, the patient showed a good prognosis due to prompt diagnosis and intensive chemotherapy. Early diagnosis and referral for treatment can prevent the development of BL. The microscopic analysis in association with immunohistochemistry allows for accurate diagnosis, as well as providing adequate management.

4. Conclusions

BL in the head and neck is quite uncommon. Even less common is the involvement of both maxilla and mandible. A strong index of suspicion for BL must be present when there is an unexplained aggressive clinical presentation. Therefore, early diagnosis and urgent treatment are life-saving in patient.

Consent

Written informed consent was obtained from the patient's parents for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

Ethical approval was waived by the authors' institution, Damascus University, as this manuscript reports solely on a routine surgical intervention. No research was conducted on the patient or on the histological samples obtained.

Funding

We have no sponsor.

Author contribution

All authors have viewed and agreed to submit this article.

Prof. Dr. Nabil Kochaji: pathological study.

Bakr Haddad and Hadi Hamandoush: surgical procedure and patient follow up.

Rami Alissa: literature review and paper writing.

Guarantor

Corresponding author is the guarantor for this case report.

Research registration number

This paper is case report. The authors don't need to register this work.

Patient perspective

Patient was quite happy with the surgical procedure and overall treatment.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Conflict of interest statement

N/A, there is no conflicts of interest.