Atypical presentation of oral Burkitt lymphoma in an adult: a case report

Abstract

Introduction

Burkitt lymphoma is an aggressive form of non-Hodgkin B cell lymphoma. Oral lesions often are a component of the disseminated disease process that may involve regional lymph nodes or may at times represent the primary extranodal form of the disease. However, isolated oral Burkitt lymphoma in adults is extremely rare.

Case report

We report the case of a 26-years-old Caucasian Moroccan woman with oral Burkitt lymphoma without any other general symptoms. It presented as swelling of the left mandibular and maxillary soft tissue progressing for 1 month. The unilateral location in both maxilla and mandible is an atypical feature. The diagnosis was based on clinical and radiographic features. Furthermore, the histopathological examination and immunochemistry was of paramount importance for making the final diagnosis of oral Burkitt lymphoma.

Conclusion

BL is considered an emergency. Early diagnosis and rapid referral are needed, and consequently, the role of the dentist in the diagnosis is important and crucial.

Introduction

Burkitt’s lymphoma (BL) is a malignant tumor of B cell lymphocytes and is categorized as a subtype of non-Hodgkin’s lymphoma (NHL). It is a highly aggressive lymphoma and is considered one of the fastest growing human tumors [1]. BL occurs predominantly in the first decades of life; it accounts for 50% of malignant tumors affecting children and 70% of all NHL [2]. BLs are estimated to account for only 1–5% of all non-Hodgkin Lymphoma (NHL) in adults. Mostly in men and with high preference for gnathic bones, notably the maxilla, presented on imaging as a radiolucent image and, histologically, is characterized by a diffuse growth pattern and uniform medium-sized cells, with coarsely clumped nuclear chromatin and nucleoli. This tumor may develop in the mouth extremely quickly, presenting as an exophytic mass affecting the maxillary bones or as a facial tumor [3]. We report an isolated oral presentation of BL in an adult female patient, which is very rare. The oral presentation was unilateral affecting both maxilla and mandible, which are unusual and uncommon clinical features.

Case report

A 26-year-old healthy young Caucasian Moroccan woman presented at the oral surgery department of consultation and treatment center of Rabat, with a chief complaint of a painless swelling on the left side of the face that had appeared 4 days ago. The patient reported weight loss and tiredness in the last 1 month.

Extraoral examination revealed a left swelling causing a facial asymmetry, involving both the maxillary and mandibular regions (Fig. 1). The swelling was soft on palpation with normal skin color. Examination of the cervical lymph node areas showed a mobile, medium-sized and painless lymphadenopathy. Furthermore, paresthesia of the left mandible and left lower lip was noted. The patient mentioned that the paresthesia had appeared 1 month prior, and it was gradually getting better.

Fig. 1

Extraoral views showed a left jugal swelling. a Frontal view. b Profil view

Intraoral examination revealed an asymptomatic tumor-like mass that was reddish in color, ulcerated in some places, and firm on palpation. It was located in both the vestibular and lingual portions of the left mandible ridge and extends from tooth 38 to tooth 43, without involving the floor of the mouth (Fig. 2a). A similar mass was observed on the maxillary ridge involving both vestibular and palatine sides, extending from tooth 28 to tooth 24, recovering the all-vestibular side of the teeth and the left hard palate (Fig. 2b). Dental examination revealed no caries or mobilities, except for palatal displacements of 23, 24, and 25. A limited mouth-opening was also noted (one finger and a half) (Fig. 3).

Fig. 2

a Intraoral view showed an ulcerated mass at incisor region and involving vestibular side of the mandible. b Intraoral view showed a palatal mass

Fig. 3

Mouth opening limitation

Radiographically, orthopantomography (Fig. 4) showed a widening of the periodontal ligament space of teeth 25, 26, 28, 38, 35, and 44. Radiopacity of maxillary sinus occupying almost entire sinus on the right side. Computed tomography (CT) showed on sagittal reconstruction soft tissue windows (Fig. 5), an almost total filling of the right maxillary sinus extended to the homolateral nasal fossa delivered through the ostium of the maxillary sinus, which was enlarged, realizing a bissac filling in favor of an antrochoanal polyp. There was also significant mucosal thickening at the floor of the left maxillary sinus. A complete blood analysis was performed including red blood cell (RBC), hemoglobin, hematocrit, leukocyte, neutrophils, monocytes, eosinophils, basophils, lymphocytes, and platelets; the results were normal, except for the polymorphonuclear eosinophil count, which was higher than normal (453 mm³). The rapid growth of the tumor, its appearance, widening of the periodontal ligament space, and paresthesia led us to a probable diagnosis of malignant tumor.

Fig. 4

Orthopantomography showing radiolucent images at 25, 26, 28, 38

Fig. 5

Coronal view of the computed tomography showing the involvement of the left soft tissue (red arrow A) and an hypodensity occupying almost the entire right maxillary sinus (red arrow B)

An incisional biopsy was performed by a maxillofacial surgeon, leading to a histopathological diagnosis of BL characterized by diffuse proliferation of intermediate-sized cells with many macrophages resulting in a starry sky appearance (Fig. 6a). Immunophenotyping showed a high proliferative index (PI) of 100%, as measured by Ki-67 staining (Fig. 6b), and a positive response for cell markers CD10 (Fig. 7a) and CD20 (Fig. 7b). In addition, translocation of the MYC oncogene, which is a proto-oncogene associated with BL, was positive (Fig. 8). The patient was referred to the oncology hospital, and they affirmed that there were no other disease locations and that this lesion is not associated with Epstein–Barr virus (EBV). Treatment consisted of chemotherapy with cyclophosphamide 300 mg/m² (500 cc SG5% every 2 hours) and vincristine 2 mg intravenous. After 1 year of the chemotherapy treatment beginning, the lesion has completely disappeared on the maxillary vestibular side (Fig. 9a), palatal side (Fig. 9b), and the mandible (Fig. 9c) Then, the patient was referred to periodontology service for gingival care.

Fig. 6

a Diffuse proliferation of intermediate-sized cells with many macrophages giving a starry sky appearance. Hemalun phloxiline (×10). b Immunochemistry showed a high proliferative index 100% measured by Ki-67 (×20)

Fig. 7

a Positive immunophenotype for cell markers CD10 (× 20). b Positive immunophenotype for cell markers CD20 (×20)

Fig. 8

Immunophenotypically view showing translocations involving MYConcogene (×10)

Fig. 9

Follow up after one year after treatment a Vestibular view of the right maxilla showing the regression of the lesion. b Palatal view of the maxilla showing the regression of the lesion. c Mandible view showing the regression of the lesion

Discussion

Burkitt lymphoma (BL), first described by Denis Burkitt in African children, is a rare and highly aggressive B cell lymphoma. In his original publication, published more than 50 years ago, Denis Burkitt discovered atypical jaw tumors associated with a distinct distribution pattern of anatomic sites in 38 Ugandan infants [4].

This endemic variety, the first to be reported, is found in equatorial Africa and certain other specific locations of the world. Its occurrence peaks in children are between the ages of 4 and 7 years old. In around 90% of cases, it is linked to the Ebstein–Barr virus (EBV) genome in malignant cells. Patients frequently exhibit with extranodal locations of disease (e.g., testes, ovary, jaw, and orbit) [5].

Two other epidemiologic variants were recognized. Sporadic BL is also called American or idiopathic lymphoma, but it is not related to geographical region. It usually affects young people and children, presents worldwide, and is the most prevalent variety in the western world. Typically, it takes the shape of an intra-abdominal mass. This subtype is rarely associated with Epstein–Barr virus (EBV) around 20% of cases. The maxillofacial location of sporadic BL, such as the jaw and sinuses, can be seen in approximately 12–30% of cases [6]. Immunodeficiency-associated BL is a condition that is linked to HIV infection and is almost 1000 times more common in HIV-infected individuals than in people that are HIV-negative [4, 5]. In our case, it occurred in an adult female patient, but we could not determine whether it was a sporadic or immunodeficiency-associated BL because we considered it an emergency, and we promptly referred the patient for treatment. The incidence of BL in the Moroccan population remains unknown. In their study in 2005, Madani et al. found that the sporadic BL is the most common variant present in Moroccan patients with 9.5% of jaw location and 73.5% of abdominal location [7].

Clinical manifestations in oral cavity include increased tooth mobility, tooth loss [6], mucosal swelling resembling to a periapical abscess [8], or swelling of the mucosa with a firm, nonfluctuant mass [9]. It may also be present as an ulcerative mass, as in this case, or as a fungating mass [10]. The case presented below showed ulcerative mucosal swelling, firm and nonfluctuant in palpation, along with tooth displacements, fully covering the vestibular side without any tooth mobilities. In multiple cases, localized hard swellings were noted either in the presence or absence of pain symptoms [3, 9].

The mandible is the most frequent location. The posterior region of the jaw is the most affected area [11]. Presentations in both the maxilla and mandible, as in the present case, are extremely rare. Oral Burkitt lymphoma can have unilateral or bilateral presentation, as reported by Freitas Filho et al. and Boffano et al. [12, 13]. However, unilateral involvement is uncommon [12].

Paresthesia of the right lower lip was also occasionally noted when the tumor was placed in the mandible, which was similar to what was observed in this case. An expanding mass involving the maxilla occasionally resulted in orbital enlargement, proptosis, diplopia, and pruritus, which was not observed in our case [6, 14]. Cervical lymphadenopathy is often seen in patients with oral BL [15].

In literature, it is clear that the rate of malignant cell mitosis in BL is so fast that the tumor can double in size in less than 24 h, which is why we consider BL to be the fastest growing malignancy in humans. Our case showed rapid progression of the lesion, similar to other reported cases [16, 17]. In their study, Otmani et al. [18] reported that the median delay to diagnosis of BL was 41 days (10 days, 2 months), in the present case, the delay was 1 month.

Radiographic findings of BL in the craniofacial region can vary depending on the technique utilized and the area of interest. Commonly used two-dimensional X-ray modalities, such as retroalveolar and panoramic X-rays, can reveal areas of diffuse radiolucency without a regular trabecular pattern, a widening of the periodontal space. Radiologically, teeth can also appear to be “floating in the air”. On the other hand, when the lesion is in the lateral region of the maxillary alveolar bone, panoramic imaging may not be very helpful. Even though the lesion is clearly present clinically, the superimposition of anatomical structures in this area may conceal its existence. Computed tomography is one of the three-dimensional techniques used to diagnose BL in the facial region. Examination of the mandible and maxilla may reveal osteolytic lesions with ill-defined margins and a mottled, permeative pattern of bone destruction. Occasionally, balloon-like bone expansion is seen, with thinning or destruction of the cortical plates and a spiculated periosteal response [6].

In our patient, the oral manifestations were limited to the gingival soft tissues with only a few widenings of the periodontal ligament space, which is atypical for oral BL. The maxillary sinuses and nasal cavity can be invaded by BL as the case of Atikah et al. [19]; however, in this case, the left maxillary sinus was not invaded and the maxillary sinus floor was preserved.

Regarding biological examinations, blood cell count disorder is not a constant feature. Kissi et al. [2] reported a case of oral BL with normal blood cell count. In the case presented below, the blood cell count was normal except for the polymorphonuclear eosinophil count, which was a little higher than normal. Furthermore, human immunodeficiency virus (HIV) testing is a pertinent investigation for patients presenting with oral lesions suspicious for BL.

The microscopic features of BL include a diffuse monomorphic infiltration of medium-sized cells with squared-off cytoplasmatic borders, round nuclei, and multiple paracentrally located nucleoli. Typically, the so-called “starry sky” appearance is observed because of the presence of numerous tingible body macrophages containing apoptotic debris. Neoplastic cells are positive for B cell markers, such as CD20, CD79a, and PAX5, and coexpression of germinal center markers CD10 and Bcl-6 [20]. Another important pathological feature of classic Burkitt lymphoma is the positivity for Ki-67 (nearly 100%) and negativity for Bcl-2 [15]. Moreover, MYC is the proto-oncogene classically associated with BL located at chromosomal locus 8q24. The deregulation of the MYC proto-oncogene is a characteristic feature of BL [11]. This immunochemical profile is similar to that in this case.

Differential diagnosis of BL includes carcinomas it interests only one clinical location. Also, it includes sarcoma, leukemia, and other non-Hodgkin’s lymphomas, which can present the same clinical and radiographical features as BL but differs in histopathological characteristics [3].

The primary therapeutic modality for BL is chemotherapy because of its fast growth rate and high mitotic index. Monoclonal antibodies, such as rituximab, have recently been added to the regimen [13]. The prognosis of Burkitt lymphoma is based on the patient’s age, the extent of the disease, and the timing of diagnosis [15].

Conclusion

Burkitt lymphoma is a severe emergency due to its rapid growth and associated consequences, such as tumor lysis, infection, and invasion of the central nervous system. This emphasizes the significance of implementing advanced supportive treatment promptly and thoughtfully. As a result, it is impossible to overstate the importance of dentists in the early diagnosis and timely referral of patients with Burkitt lymphoma.