Primary B-Cell lymphoma of the mandible: a potentially difficult diagnosis

Case report

A 34-year-old fit and well male presented initially to the Emergency Department complaining of pain from his ‘mouth, gums and ear’, and he had also observed a complete numbness of his right lip and chin. The Emergency Department staff attributed the cause to trigeminal neuralgia. The patient was discharged with analgesia, and advised to see his GMP to arrange for a prescription of carbamazepine and an outpatient MRI investigation.

The patient was first seen by Oral and Maxillofacial Surgery (OMFS) following an urgent referral from his dentist. He described pain and complete absence of sensation in the right mandibular division of the trigeminal nerve. An OPG radiograph was taken, which failed to demonstrate a clear cause of the patient's symptoms (Figure 1).

An MRI brain scan was ordered to identify any central cause for numbness, however, it concluded that there was a normal appearance of the trigeminal nerves. Following the MRI scan, a second urgent referral was received, this time from the patient's GMP. The patient now presented with a bony firm lump that had arisen in the right mandible (Figure 2). An urgent CT scan was arranged, demonstrating a 45 x 15 x 23 mm lesion in the right mandible which appeared to have breached the buccal and lingual cortices (Figure 3). An MRI scan with contrast was advised, which demonstrated an area of abnormal signal from the right mandibular bone marrow.

A new OPG radiograph was taken, which appeared to show a peri-apical radiolucency associated with LR3. The patient had previously undergone orthodontic treatment, and it was provisionally diagnosed that his symptoms were associated with an osteomyelitic inflammatory process from a canine devitalized by orthodontic tooth movement (Figure 4).

A biopsy was planned of the lesion in the right mandible, however, on the day of the procedure, the patient presented with a reduction in paraesthesia and spontaneous resolution of the mass. After discussion, the patient was still keen to proceed with a biopsy. Intra-operatively, an incision was made lateral to LR6, where it was found that there was an approximately 5 mm breach of the buccal cortex. This was extended with a fissure bur to allow curettage of the cancellous bone to send to histopathology. The overlying soft tissue and mucosa was unaffected. Clinically, this was felt to be an inflammatory process, and the patient was started on 100 mg of Doxycycline daily.

The biopsy demonstrated large lymphocytes strongly positive for CD20, CD45 with weaker variable staining for BCL2, BCL6 and PAX5. These features are consistent with a diagnosis of high grade large B-cell lymphoma (LBCL). The specimen was negative for staining to CD10, CD5, MUM1, TDT, CD30, ALK1, Cyclin D, CD15, AE1/3 and CD23.

A PET scan demonstrated that the LBCL was confined to the mandible only. The patient was discussed at a haematology MDT, and a plan was agreed for three sessions of Rituximab, Cyclophosphamide, Hydroxydaunomycin, Vincristine and Prednisolone (R-CHOP) chemotherapy.

Discussion

Large B-cell lymphoma is the most common type of Non–Hodgkin's lymphomas (NHL), a neoplasia of lymphocytes and their precursors. Primary LBCL of the mandible accounts for only 0.6% of all NHLs, with the mandibular body being the most frequent site of occurrence within the mandible.¹ NHLs predominantly arise within lymph nodes although, in approximately 24% of cases, there are extra-nodal presentations, typically within skin, the GI tract, lungs or the CNS.²

The most common extra-nodal sites for NHL within the oral cavity are the gingiva and palate. In the head and neck, NHL is most commonly seen in salivary gland tissue and Waldeyer's ring, comprising the palatine, nasopharyngeal and the lingual tonsils.³

Head and neck lymphomas typically present in males (M:F, 3:2) between the fifth and seventh decades. Primary intra-osseous lymphomas constitute approximately 3% of all bone malignancies and around 5% of extra-nodal lymphomas. Oropharyngeal lymphomas are often associated with HIV-affected or other immunocompromised individuals.² The patient presented here is an immunocompetent 34-year-old, which appears to contrast with other case reports reviewed.

High grade LBCL of the mandible responds well to chemotherapy and, in localized disease without widespread involvement, the prognosis is excellent,⁴ especially when compared to other malignancies of the mandible. Squamous cell carcinoma and osteosarcoma of the mandible have a disease specific five-year survival rate of 30–40%⁵ and 62%, respectively.⁶ For a Stage 1 NHL (well-localized lesion at one site) the five-year survival is 70%. A combination of chemo/radiotherapy may also be used in high grade LBCL. Low grade LBCL may be treated by radiotherapy alone. There is little place for surgical intervention of LBCL other than a biopsy for diagnosis.⁷

Common with other case reports of LBCL of the mandible, there was a difficulty in ascertaining a diagnosis prior to biopsy. Patients progress through various non-specific characteristics, such as vague pain, swelling, numbness, radiolucency on OPG/CT imaging, mobility of teeth and lymphadenopathy. Tumours can increase in size rapidly leading to advanced destruction of bone.³ A mean interval from presentation to diagnosis/treatment was found to be 3.9 months, with reported cases of up to 7 months' delay.⁸ For our patient, it was approximately 4 months after he first presented to OMFS before determining a histopathological diagnosis.

The non-specific clinical and radiographic signs present clinicians with a broad differential, including odontogenic infections, osteomyelitis, cysts, odontogenic tumours, jaw metastases, sarcoma or carcinoma of the mandible. Clinical/histopathological correlation and communication is key if the correct diagnosis is to be reached.³

A number of points are to be reflected upon from this interesting case. Firstly, liaison with emergency departments and medically trained colleagues for their understanding of symptoms for common orofacial conditions is invaluable. In the case presented here, the Emergency Department staff felt trigeminal neuralgia was the diagnosis, despite the patient's symptoms, which delayed the presentation to OMFS by 4 weeks.

This case highlights the importance of ascertaining a diagnosis early to implement the correct treatment modality, which is especially pertinent in the case of LBCL which requires, uncommonly for head and neck lesions, chemotherapy as the first line treatment. A very unusual feature of this case that the authors have not come across in the literature, was the spontaneous resolution of the mandibular mass within a two-week period. Despite this, a biopsy confirmed the diagnosis and ensured that the correct treatment was prescribed.

Conclusion

Numbness should be treated with a high degree of suspicion, with urgent imaging, biopsy and specialist histopathology staining to exclude malignancy. This is a particularly interesting case given the initial diagnosis in the emergency department, the rarity of the diagnosis itself, combined with spontaneous resolution of a mandibular mass which could have led to a further delay in establishing a definitive diagnosis.