Rare Clinical Presentation of Diffuse Large B-Cell Lymphoma as Otitis Media and Mastoiditis
Article information
Abstract
Lymphomas originating in the ear are extremely rare. As with other malignancies of the temporal bone, diagnosis of lymphoma in the middle ear and temporal bone is often delayed, negatively impacting treatment and prognosis. The delay in diagnosis is primarily due to its clinical presentation overlapping with benign infectious conditions of the middle ear. Here, we present a rare case of a 46-year-old woman with prolonged otorrhea, hearing disturbances, intermittent vertigo, and headache. She underwent surgery to investigate suspected chronic otomastoiditis, and subsequent pathological examination revealed diffuse large B-cell lymphoma. Severe and persistent middle ear symptoms should raise red flags and warrant thorough and detailed investigations, including pathological confirmation.
Introduction
Lymphoma is a cancer of the reticuloendothelial system and is one of the most common non-epithelial malignancies of the head and neck region [1]. Lymphomas account for approximately 10% of all head and neck tumors and are classified into two main subtypes: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma [2]. About 15% of all non-Hodgkin’s lymphomas arise in the head and neck area [3].
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphoma, characterized by extranodal involvement, most frequently in the stomach and gastrointestinal tract [1]. While lymphoma can arise in various tissues, involvement of the temporal bone is extremely rare and the clinical features remain unknown. In this report, we present the clinical characteristics of a rare case of DLBCL involving the middle ear and mastoid, along with a review of the relevant literature.
Case Report
A 46-year-old Mongolian woman visited to the otology clinic with a 35-year history of left otorrhea and hearing disturbance. She also reported intermittent tinnitus in the left ear, non-whirling vertigo, and headaches. Otoscopic examination revealed a moderate perforation of the left tympanic membrane with purulent otorrhea (Fig. 1). She was clinically diagnosed with chronic otitis media in the left ear and was initially managed with antibiotics and dressing. High-resolution computed tomography scan of the temporal bones revealed soft tissue density in the left mastoid air cells, mastoid antrum, and middle ear cavity, without evidence of intracranial extension. No definite bony erosion of the left ossicles was observed, and the inner ear structures appeared intact (Fig. 2). Pure tone audiometry revealed left conductive hearing loss, with bone conduction at 8 dB HL and air conduction at 43 dB HL. Air conduction in the right ear was within normal limits. Consequently, left tympanomastoidectomy was planned.
Otoscopic findings at the initial outpatient visit. A: Right intact tympanic membrane. B: Left tympanic membrane with perforation and purulent otorrhea.
High-resolution computed tomography scan (A: axial view; B: coronal view) of the temporal bone. The left epi- and mesotympanum show complete opacification by soft tissue density. The mastoid air cells on the left are reduced with sclerotic changes. The left inner ear structures, middle ear ossicles, and scutum remain intact. The right middle ear cavity is normally aerated, with intact ossicles and unremarkable mastoid air cells.
During the left tympanomastoidectomy, the mastoid air cells were found to be sclerotic, and the mastoid antrum and epitympanum were filled with a large amount of granulation tissue, which was removed and sent for biopsy. The eroded incus was removed, and the fixed malleus head was cut. Ossicular reconstruction was performed using a titanium partial ossicular replacement prosthesis (2.0 mm), and temporalis muscle fascia and cartilage was harvested for the tympanic membrane graft (Fig. 3).
Intraoperative findings during left canal wall-up mastoidectomy with tympanoplasty and ossiculoplasty. A: The middle ear cavity was filled with granulation tissue (arrow), and significant bleeding occurred during the dissection. B: The mastoid bone was sclerotic, and the antrum was filled with granulation tissue (arrow), which was removed and sent for biopsy. C: Ossiculoplasty was performed following the removal of incus. D: Tympanoplasty was completed using temporalis muscle fascia.
Fig. 4 shows microphotographs and immunohistochemical findings of the biopsied tissue. Histopathological assessment of the left mastoid antrum mucosa revealed a diffuse proliferation of large neoplastic lymphoid cells. These cells were positive for CD19, CD20, and Bcl-6, but negative for CD3, CD5, CD10, and MUM-1. A c-MYC gene translocation was identified, consistent with malignant lymphoma, B-cell type, classified as DLBCL. The proliferative fraction, as detected by Ki-67 immunostaining, was high (70% positivity).
Microphotographs and immunohistochemical findings. A and B: Hematoxylin and eosin staining shows diffuse infiltration of atypical large neoplastic lymphoid cells at 200× (A) and 400× (B) magnification. C-G: Immunohistochemistry results: The tumor cells are positive for CD19 (C), CD20 (D), and Bcl-6 (E), but negative for CD10 (F) and MUM-1 (G) (all at 200× magnification). H: Fluorescence in situ hybridization (FISH) confirms the presence of c-MYC gene translocation. I: Ki-67 immunostaining shows high proliferation index (70%, ×200).
Postoperative whole-body positron emission tomography (PET) revealed mild hypermetabolic soft tissue lesions in the left ear canal and mastoidectomy site, suggesting the possibility of residual malignant lymphoma. However, no additional lymphoma lesions were detected, and blood and bone marrow evaluations were unremarkable, indicating that the temporal bone lesion was likely the primary site. The patient underwent three cycles of R-CHOP chemotherapy (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone) in the oncology department. Symptoms improved significantly, and the postoperative wound healed cleanly. There has been no recurrence during the 7 months following surgery, and the patient was diagnosed with a complete metabolic response on follow-up PET scans.
Discussion
Malignancies of the temporal bone are rare, accounting for only 0.2% of all head and neck malignancies [4]. Among temporal bone malignancies, squamous cell carcinoma (39%) is the most common neoplasm, followed by basal cell carcinoma (14%), adenoid cystic carcinoma (7%), ceruminous adenocarcinoma, and middle ear adenocarcinoma [4,5].
There are only a few reported cases in which the middle ear or temporal bone was identified as the primary lesion of lymphoma [3,6]. According to cases that have been described, it seems that a wide variety of lymphoma subtypes can occur in the ear. Lymphoma of the middle ear can originate from the mucosa of the mastoid antrum, tympanum, or the tympanic orifice of the Eustachian tube [3]. Additionally, it can arise primarily from the temporal bone. Since the normal middle ear cavity lacks lymphoid tissue, Schuknecht hypothesized that a layer of lymphoid tissue might exist beneath the epithelium and could serve as the site of primary lymphoma [7]. It has also been suggested that small numbers of circulating lymphocytes may naturally “home” to areas of the body that are not typically considered secondary lymphoid organs [8]. Furthermore, Li, et al. [9] proposed that small numbers of lymphocytes may “slip” into the middle ear from the Eustachian tube via a system known as “mucosa-associated lymphoid tissue.”
Middle ear and mastoid malignancies are rarely diagnosed an early stage [1]. The primary reason is the unique anatomy of the middle ear and mastoid, as well as the fact that many benign conditions, such as otitis media and its complications, present with similar clinical features, including otorrhea, otalgia, hearing loss, and earfullness. Presentation with otoneurological signs before systemic involvement of a lymphoproliferative disease is both nonspecific and unusual. In previous case reports, facial nerve palsy was the most common initial symptom, and mastoiditis was associated with approximately half of the cases [2,6,10]. A rare case reported by Saito, et al. [6] presented with cerebral venous thrombosis, diagnosed by surgery.
Our patient had a 35-year history of left otorrhea, initially suspected to be intractable otitis media. There were no palpable lymph nodes, and the patient did not exhibit any systemic symptoms. A significant proportion of lymphoma patients develop systemic symptoms, particularly B symptoms such as fever, weight loss, and night sweats, before lymphadenopathy becomes apparent. These symptoms are present in up to 50% of patients with advanced lymphoma [6,11]. Although the initial presentation suggested a middle ear infection, the key distinguishing factor was the lack of response to antibiotics. Definitive diagnosis of DLBCL was established through a proper tissue biopsy obtained during surgery and pathological examinations.
In summary, we report a case of DLBCL of the middle ear and mastoid, which was successfully managed with intensive chemotherapy. Otologists should recognize that surgery has its place as a diagnostic procedure and the chemotherapy is the treatment of choice. This rare and serious, yet potentially treatable, entity requires a multidisciplinary approach for both diagnosis and management. Furthermore, a diagnosis of infectious ear disease should be questioned when there is a lack of response to standard therapies.
Lymphoma of the ear is extremely rare. In patients with chronic otomastoiditis that is refractory to initial antibiotic therapy, a high index of suspicion for primary neoplasms of the middle ear and temporal bone, such as lymphoma, should be maintained, and a proactive biopsy is required. Early diagnosis and appropriate treatment result in favorable therapeutic outcomes and minimize further complications.
Notes
Ethics Statement
This study was exempt from the Institutional Review Board’s approval (No. 2025-0213), with the requirement for patient consent waived.
Conflicts of Interest
The authors have no financial conflicts of interest.
Author Contributions
Conceptualization: Hye Ah Joo, Hong Ju Park. Data curation: Hye Ah Joo. Formal analysis: Hong Ju Park. Investigation: Hye Ah Joo. Methodology: Hye Ah Joo, Hong Ju Park. Project administration: Hong Ju Park. Resources: Hong Ju Park. Supervision: Hong Ju Park. Writing—original draft: Hye Ah Joo. Writing—review & editing: Hye Ah Joo. Approval of final manuscript: Hye Ah Joo, Hong Ju Park.
Funding Statement
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Acknowledgments
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