Primary Diffuse Large B‐Cell Lymphoma Mimicking a Dental Abscess: A Case Report

ABSTRACT

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma, yet its presentation in the maxillofacial region can pose diagnostic challenges, particularly in patients with confounding medical histories. We report the case of a 40‐year‐old Iranian male with a history of ulcerative colitis on mesalazine therapy, who presented with progressive left facial swelling. Symptoms persisted for over a year, during which initial fine‐needle aspiration (FNA) of a cervical lymph node showed only chronic lymphadenitis. This result prompted repeated empiric treatments with antibiotics and anti‐inflammatory medications, without lasting improvement and leading to significant diagnostic delay. Upon referral to the Department of Oral and Maxillofacial Medicine at Tabriz Faculty of Dentistry, the presentation initially mimicked an odontogenic abscess or other dental pathology, a common consideration in cases of unilateral facial swelling evaluated in a dental setting. However, a panoramic radiography revealed no dental or periodontal source of infection, effectively ruling out an odontogenic origin and prompting further investigation. Clinical examination disclosed firm, fixed, nontender lymphadenopathy involving the left submandibular and cervical nodes. Subsequent referral to a hematologist and excisional lymph node biopsy with immunohistochemistry confirmed DLBCL. Treatment was promptly initiated, and a CT scan performed 10 months later demonstrated complete response to therapy. This case underscores the critical importance of maintaining a high index of suspicion for lymphoproliferative disorders, such as DLBCL, in patients with persistent cervicofacial swelling and inconclusive initial investigations (including misleading FNA results). It also highlights how such malignancies can closely mimic odontogenic infections in the dental setting, where early panoramic radiography and precise examination of teeth and periodontium can help exclude dental sources and accelerate referral for non‐odontogenic causes. Early consideration of excisional biopsy in refractory cases can prevent prolonged diagnostic delays and enable timely intervention.

Key Clinical Message.

Persistent cervicofacial swelling unresponsive to antibiotics, even with benign FNA and no dental pathology, warrants early suspicion of DLBCL/NHL. Timely hematology referral and excisional biopsy prevent diagnostic delays (> 1 year in this case) and enable complete response to therapy.

1. Introduction

Lymphomas include a diverse group of malignancies derived from uncontrolled growths of lymphoid cells, such as lymphocytes and histiocytes. This malignancy is the second‐most common primary tumor affecting the head and neck region. It is classified into Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL). The oral cavity is affected very scarcely; hence, only 3%–5% of reported NHL cases have arose initially in this area [1, 2, 3]. This case report describes a 40‐year‐old man with DLBCL arising primarily in the head and neck region which was misdiagnosed as chronic lymphadenitis for about a year and referred to an Oral and Maxillofacial specialist upon a possible dental origin.

2. Case History/Examination

The case involved a 40‐year‐old Iranian male with a history of ulcerative colitis, who was receiving treatment with mesalazine. He had no history of smoking or alcohol consumption. In October 2024, he was referred to the Department of Oral and Maxillofacial Medicine at the Faculty of Dentistry, Tabriz University of Medical Sciences, with a chief complaint of swelling in the left side of his face. The patient had first noticed this swelling approximately one year earlier. After consulting a general surgeon, he underwent fine‐needle aspiration (FNA) biopsy of a left cervical lymph node, which was reported as chronic lymphadenitis. The histopathologic examination showed an abundant polymorphic population of lymphoid cells, consisting of numerous benign‐appearing lymphocytes, plasma cells, centroblasts, immunoblasts, and rare tingible‐body macrophages in a hemorrhagic background. Scattered mitotic figures were present, but no malignant cells were identified. The patient was therefore treated for presumed chronic inflammation with a course of azithromycin and naproxen. However, there was no response to this therapy, and the swelling continued to enlarge. He was subsequently referred to another surgeon and received antibiotic treatment consisting of parenteral penicillin in September 2024. The swelling showed mild initial reduction in size following the injections but began enlarging again after approximately one month. At that point, he was referred to the Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences. Clinical examination revealed swelling in the left submandibular region accompanied by diffuse pain in the area (Figure 1). Additionally, the left submandibular, anterior deep cervical, and superficial cervical lymph nodes were palpable; all were firm, fixed to the underlying tissues, nontender, and measured approximately 3 cm in diameter (Figure 2). A panoramic radiograph was obtained, which showed no evidence of a dental origin for the swelling. Notably, tooth #19 had been recently retreated successfully, and the periapical radiolucency associated with its mesial root was in the healing process (as confirmed by prior radiographs), with no signs or symptoms of active apical pathology (Figure 3).

FIGURE 1.

Diffuse persistent swelling in the left submandibular region for over a year.

FIGURE 2.

Left cervical lymphadenopathy.

FIGURE 3.

Panoramic image of the patient without any evidence of dental or periodontal pathoses.

3. Differential Diagnosis, Investigations and Treatment

The patient was referred to a hematologist with a suspected diagnosis of non‐Hodgkin lymphoma, given the exclusion of dental‐related pathology. An excisional biopsy of a cervical lymph node was performed, revealing complete effacement of the normal nodal architecture by diffuse proliferation of large atypical lymphoid cells. These neoplastic cells exhibited large round‐to‐oval vesicular nuclei, prominent nucleoli, and moderate basophilic cytoplasm, with numerous mitotic figures and occasional foci of necrosis (Figure 4). The overall histopathologic features were consistent with a high‐grade lymphoid neoplasm, prompting confirmatory immunohistochemistry (IHC). The IHC profile supported a diagnosis of DLBCL (Table 1). To assess for distant metastasis, a contrast‐enhanced CT scan of the neck, thorax, abdomen, and pelvis was obtained, which showed no identifiable metastatic lesions; only mild splenomegaly was noted (Figure 5). CT scan complete series are included in Appendix 1.

FIGURE 4.

Histopathologic view indicating large atypical neoplastic lymphoid cells with round‐to‐oval vesicular nuclei, prominent nucleoli, moderate basophilic cytoplasm, numerous mitotic figures, and occasional foci of necrosis, compatible with high‐grade lymphoid neoplasia (IHC staining, Magnification ×10).

TABLE 1.

Immunohistochemistry [IHC] results which are consistent of DLBCL.

CD20	Positive
CD5	Negative
KI‐67	70%
PAX5	Positive
CD30	Negative
CD10	Negative
BCL2	Positive
BCL6	Negative
CD23	Negative
CyclinD1	Negative
EMA	Negative
CD3	Negative

FIGURE 5.

CT scan in favor of lymphoma with no distant metastasis.

Chemotherapy was initiated promptly thereafter. Following 6 months of treatment, a PET‐CT scan demonstrated a reduction in size and an increase in density of the left submandibular and parotid glands, findings suggestive of radiation‐induced sialadenitis or post‐treatment changes (noting that DLBCL treatment is typically systemic chemotherapy like R‐CHOP, these glandular changes may reflect therapy‐related effects or inflammation). Treatment continued, and a subsequent CT scan performed 4 months later (10 months post‐initiation) confirmed complete response to therapy, with resolution of previously noted abnormalities.

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

The patient was followed‐up regularly regarding the outcome of chemotherapy, and the maintenance phase is ongoing. He was advised to return to our department promptly if he developed any signs of mucositis or xerostomia as potential side effects of chemotherapy. Additionally, he was instructed to resume or continue his dental treatment plan only after completion of chemotherapy, once his white blood cell (WBC) and platelet counts had been confirmed to be within acceptable ranges via a differential complete blood count (CBC).

NHL, particularly DLBCL, represents one of the more common malignancies in the head and neck region. These lymphomas often present with nonspecific clinical and imaging features, posing a significant diagnostic challenge for oral and maxillofacial specialists, who are frequently the first healthcare providers to encounter the disease. An effective diagnostic approach—including a thorough medical history, meticulous clinical examination, appropriate imaging modalities, targeted biopsies from representative sites (with repetition if initial results are inconclusive), and precise histopathologic evaluation with ancillary studies such as immunohistochemistry—can substantially streamline the diagnostic process and facilitate timely intervention.

5. Discussion

NHLs, a diverse group of lymphoproliferative malignancies, are far more likely to involve extranodal sites than HL. Approximately 25%–40% of NHL cases present initially at extranodal locations [4]. In the head and neck region, the most commonly affected extranodal sites include Waldeyer's ring (particularly the palatine tonsils), salivary glands, base of the tongue, and oropharynx. Intraorally, the most frequent sites are the palatal mucosa, gingiva, tongue, buccal mucosa, floor of the mouth, lips, and jaw bones. The majority (85%–90%) of NHL cases originate from B lymphocytes, while only about 10% arise from T lymphocytes or natural killer (NK) cells [1, 2, 5, 6, 7]. Key etiological factors include immunosuppression—particularly T‐cell dysfunction—as the primary driver, along with latent Epstein–Barr virus (EBV) infection and chronic antigen stimulation [1].

DLBCL is the most common subtype of NHL and frequently presents as an extranodal disease, with the oral cavity being one of the most commonly involved sites. Advanced age is a major risk factor for DLBCL development, and the disease shows a higher incidence among White men [2, 8]. Major risk factors for DLBCL include severe immune deficiencies (e.g., HIV/AIDS, hereditary immunodeficiency syndromes, and post‐organ transplantation immunosuppression), family history of NHL or DLBCL, prior malignancy, and genetic predisposition. Additional contributors encompass chronic immune dysregulation from autoimmune disorders (such as Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis), infections with viruses like KSHV/HHV‐8, HCV, HBV, and EBV, and obesity. Prolonged exposure to certain environmental chemicals—such as trichloroethylene, benzene, pesticides, herbicides, and glyphosate—also increases susceptibility [8].

DLBCL exhibits a wide range of nonspecific symptoms and often appears indeterminate on imaging, making diagnosis challenging. Extranodal DLBCL rarely originates in the jaws, and distinguishing it from other tumors or inflammatory conditions is difficult because it frequently mimics their presentations. Suggestive features in jaw involvement include pathologic tooth mobility, paresthesia of the chin or buccal area, pain or discomfort, and ulcerative or erosive lesions. “B symptoms” (fever, night sweats, and unexplained weight loss) are uncommon. Most patients are asymptomatic in the early stages, with symptoms emerging only as the tumor enlarges, which can contribute to diagnostic delays and errors [9]. In the neck, DLBCL typically manifests as enlarged, painful or painless lymph nodes, as observed in the present case. When involving the nasal cavity or paranasal sinuses, it may mimic sinusitis, presenting with nasal obstruction, rhinorrhea, headache, and anosmia, complicating differentiation. A high index of suspicion for DLBCL is warranted in cases of early symptoms such as lacrimation, diplopia, exophthalmos, or isolated maxillary sinus swelling that extends to the orbit and face, especially when unresponsive to standard anti‐inflammatory treatments [9, 10]. Elevated serum lactate dehydrogenase (LDH) and soluble interleukin‐2 receptor (sIL‐2R) levels can serve as supportive diagnostic markers in malignant lymphoma [11].

Systemic chemotherapy is the mainstay of treatment, with the R‐CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) commonly administered until complete remission is achieved [12, 13]. Prognosis depends primarily on age, disease stage, and the extent of extranodal involvement. Adverse factors include age over 60 years, advanced stage (III/IV), and more than one extranodal site, all of which are associated with poorer outcomes [14].

Author Contributions

Haniyeh Najafi Aghdam: conceptualization, data curation, investigation, writing – review and editing. Ladan Paya: project administration, supervision, validation, visualization, writing – review and editing. Mina Zohrabi: investigation, methodology, resources, writing – original draft, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

This study was approved by the Regional Ethics Committee. (IR.TBZMED.DENTISTRY.REC.1404.065).

Consent

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

Conflicts of Interest

The authors declare no conflicts of interest.

Appendix A.

Full set of CT scans obtained from the patient confirmed the diagnosis of lymphoma with no evidence of distant metastasis.

Additionally, a 12‐mm calcified focus was noted in segment IV of the liver. The spleen showed mild enlargement, with a craniocaudal (cephalocaudal) height of 140 mm, consistent with mild splenomegaly.

Data Availability Statement

The data that support the findings of this study are available in this article and the supplementary files.