Abstract
Bilateral sudden sensorineural hearing loss (BSSHL) is an uncommon otologic emergency that may occur as the initial manifestation of relapsed B-cell non-Hodgkin lymphoma complicated by hyperviscosity syndrome (HVS). Systemic Bruton tyrosine kinase (BTK) inhibition can reduce IgM levels but may be insufficient to reverse cochlear dysfunction. We present a 74-year-old woman with a history of small B-cell non-Hodgkin lymphoma who developed simultaneous bilateral profound sudden hearing loss secondary to clinically presumed Waldenström macroglobulinemia (WM). Serum IgM peaked at 53.21 g/L, and fundoscopic examination showed typical hyperviscosity retinopathy. Despite four weeks of treatment with zanubrutinib, hearing showed no improvement. Bilateral intratympanic dexamethasone (IT-Dex) injections (5 mg daily for 6 consecutive days) were administered as salvage therapy.
The patient began to perceive sound on day 3 and showed significant hearing improvement by day 6. Pure-tone average thresholds improved by 15 dB in the right ear and 20 dB in the left ear. This case demonstrates that IT-Dex injection is an effective salvage intervention for refractory HVS-related BSSHL that is unresponsive to systemic BTK inhibitor therapy. Multidisciplinary collaboration between otolaryngologists and hematologists is essential for timely diagnosis and intervention.
Keywords
Introduction
Sudden sensorineural hearing loss (SSHL) is generally defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies within 72 hours and constitutes an otologic emergency. The reported annual incidence ranges from 5 to 20 per 100,000,1,2 with bilateral cases accounting for only 4.9–8.6%.3,4 Bilateral Sudden Sensorineural Hearing Loss (BSSHL) usually shows more severe threshold shifts and a poorer prognosis than unilateral disease. To facilitate both research and clinical discussion, BSSHL is further subdivided into Simultaneous BSSHL (Si-BSSHL, interval ≤72 h) and Sequential BSSHL (Se-BSSHL, interval >72 h) subtypes. 5
Although most episodes remain idiopathic, recognised triggers include viral infection, metabolic disturbance, ototoxic drugs or labyrinthine membrane rupture; In patients with bilateral involvement, autoimmune and hematological diseases are particularly important considerations and require comprehensive laboratory evaluation. 6
Waldenström macroglobulinemia (WM) is a distinct subtype of B-cell non-Hodgkin lymphoma characterized by excessive production of monoclonal immunoglobulin M (IgM). Hyperviscosity syndrome (HVS) and free light chain toxicity are well-known complications that can induce microcirculatory dysfunction and tissue injury in multiple organs, including the inner ear. Characteristic manifestations of HVS include visual disturbances, mucosal bleeding, and neurological abnormalities. 7 However, hearing loss and vestibular symptoms are relatively rare and often underrecognized. Only a small number of case reports have described SSHL or BSSHL as the presenting feature of WM or relapsed lymphoma.8-11
We present a rare case of relapsed B-cell NHL with clinically presumed WM presenting with BSSHL that progressed to profound deafness: a 5-year history of follicular marginal zone non-Hodgkin lymphoma, with dizziness followed by progressive hearing loss as the presenting manifestation of NHL relapse—a rare presentation pattern not previously described. Despite one month of targeted therapy with Zanubrutinib, hearing did not improve. We then performed bilateral intratympanic dexamethasone (IT-Dex) injections, a treatment approach not previously described in lymphoma-associated hearing loss.
Case Presentation
A 74-year-old woman presented to the emergency department with acute vertigo, near syncope, fatigue, and subjective bilateral hearing loss. Within one week, her hearing deteriorated to profound bilateral deafness (Figure 1). Pure-tone audiometry confirmed severe-to-profound sensorineural hearing loss in both ears. All audiometric tests were performed by an audiologist who was blinded to the patient’s clinical data and diagnostic information to reduce detection bias. Brain magnetic resonance imaging (MRI) demonstrated scattered ischemic foci but no space-occupying lesions, hemorrhage, or structural abnormalities in the internal auditory canals or inner ear structures. Pure-tone audiograms before and after treatment.
Past Medical History: Five years prior, the patient was evaluated for a right breast mass. After right breast quadrantectomy, pathological examination showed atypical B-lymphoid hyperplasia, suspicious for small B-cell lymphoma. Fine-needle aspiration of a right axillary mass confirmed B-cell non-Hodgkin lymphoma (NHL). Immunohistochemistry (HI20-5312) revealed CD20+, CD10−, partial weak Bcl-6+, Bcl-2+, MUM1−, MNDA+, CD3−, focal CD5−/+, CD43+, CD23+, CyclinD1−, and Ki-67+ (20–40%). Flow cytometry demonstrated B cells with restricted surface immunoglobulin light chain expression, mostly CD10−, CD5−/+, FMC7−, and minor CD23+, with small-to-medium cell size. A diagnosis of small B-cell NHL was established, but precise subclassification (marginal zone lymphoma vs. small lymphocytic lymphoma/chronic lymphocytic leukemia) was not achieved. She was treated with 6 cycles of R-CHOP immunochemotherapy followed by maintenance rituximab and remained in complete remission thereafter.
The laboratory tests in this episode showed mild anemia, lymphocytosis, elevated creatinine, proteinuria, and hematuria. Two weeks later, further oncological work-up identified severe anemia, extreme lymphocytosis, and markedly elevated serum IgM (53.21 g/L). Serum immunofixation confirmed an IgM λ monoclonal protein, and free light chain analysis showed a severely inverted κ/λ ratio. Fundoscopic examination demonstrated diffuse retinal hemorrhages and dilated, tortuous veins consistent with hyperviscosity retinopathy.
Hyperviscosity syndrome (HVS) is a clinical diagnosis based on the triad of visual disturbances, mucosal bleeding, and neurologic abnormalities. 11 Serum viscosity measurement is not mandatory. In this case, markedly elevated IgM, typical hyperviscosity retinopathy, and bilateral sudden sensorineural hearing loss fulfilled the clinical criteria for HVS. IgM multiple myeloma was excluded due to the absence of osteolytic lesions, normal renal function, and lack of hypercalcemia. Thus, clinically presumed Waldenström’s macroglobulinemia (WM) complicated by HVS was diagnosed. The patient’s family declined further testing, including bone marrow biopsy and MYD88 mutation analysis. Although histopathological and genetic confirmation was not available, the clinical and laboratory features were highly consistent with Waldenström’s macroglobulinemia, and the diagnostic uncertainty was acknowledged. During this period, the patient developed transient visual obscuration and epistaxis, and targeted therapy with zanubrutinib 320 mg daily was initiated for suspected lymphoma relapse.
After four weeks of systemic treatment, IgM decreased partially to 46.9 g/L and anemia improved; however, profound bilateral hearing loss remained unchanged. Otomicroscopic findings were unremarkable. Auditory brainstem response testing showed elevated thresholds and prolonged latencies (Figure 1), consistent with severe cochlear or retrocochlear dysfunction.
Salvage bilateral intratympanic dexamethasone (IT-Dex) injections (5 mg daily) were administered for six consecutive days. The patient regained initial sound perception on day 3 and was able to understand loud speech by day 6. Post-treatment audiometry showed clinically meaningful improvements in pure-tone averages: 15 dB in the right ear and 20 dB in the left ear (Figure 1). Hearing improvement remained stable at the one-month follow-up. The patient reported significant relief of vertigo, aural fullness, and tinnitus after treatment, and expressed clear subjective improvement in hearing ability and quality of life. The intratympanic dexamethasone injections were well tolerated without obvious discomfort.
Fundoscopic and optical coherence tomography findings showed persistent intraretinal fluid despite partial systemic response. The patient reported subjective improvement in blurred vision but declined further ophthalmic evaluation.
Discussion
Waldenström Macroglobulinemia (WM)-Associated Hyperviscosity Syndrome With Bilateral Sudden Sensorineural Hearing Loss: A Review of Our Case and Previously Reported Literature Cases
Abbreviations: BSSHL: Bilateral sudden sensorineural hearing loss; Si-BSSHL: Simultaneous bilateral sudden sensorineural hearing loss; Se-BSSHL: Sequential bilateral sudden sensorineural hearing loss; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye); VA: Visual acuity; SRD: Serous retinal detachment; SPE: Serum protein electrophoresis; NR: Not reported (data not mentioned in the original literature); N/A: Not applicable (indicator irrelevant or not tested for the case); IT-Dex: Intratympanic dexamethasone; IVB: Intravitreal bevacizumab; SRT: Speech recognition threshold; PTA: Pure-tone average; OCT: Optical coherence tomography; FA: Fluorescein angiography; BR: Bendamustine + Rituximab; RVD: Rituximab + Bortezomib + Dexamethasone; BiCROS: Bilateral contralateral routing of signals (hearing aid system).
HVS is widely recognized as the principal pathogenic mechanism underlying WM-associated hearing loss, yet the precise pathophysiology remains controversial. Table 1 shows that in previously reported cases, fewer than half of the patients showed any hearing improvement after IgM and serum viscosity were lowered, and many were left with severe to profound deafness.6,10 An initial hemorrhagic mechanism was proposed on the basis of associated coagulopathy. 9 However, mounting evidence now supports hemorheological disturbances. Wells 19 identified reversible hearing impairment attributable to cochlear venous stasis secondary to hyperviscosity, findings subsequently validated by Ruben. 20 Notably, Platia and Saral 10 described a patient with hearing loss and lower extremity thrombophlebitis in the absence of marked hyperviscosity, where long-term anticoagulation stabilized auditory function, suggesting that inner ear venous thrombosis may constitute an independent mechanism. The unique vascular anatomy of the inner ear—supplied by end-arteries with limited collateral circulation—renders it particularly vulnerable to such microcirculatory disturbances. Furthermore, MRI studies by Shibata 6 have confirmed intralabyrinthine hemorrhage in select cases, while temporal bone pathology by Wells et al. demonstrated that hemorrhage can cause irreversible destruction of the Organ of Corti and stria vascularis. These mechanisms may operate independently or coexist, collectively contributing to the clinical heterogeneity of auditory manifestations in WM.
In the present case, the markedly elevated serum IgM (53.21 g/L) and characteristic hyperviscosity retinopathy (diffuse retinal hemorrhages and venous tortuosity), coupled with the absence of intralabyrinthine hemorrhage on MRI, suggest that cochlear venous stasis secondary to hyperviscosity constituted the primary mechanism of hearing loss. Current clinical practice guidelines for SSHL include the administration of oral, systemic corticosteroids and/or salvage intratympanic (IT) steroid injections.2,3,21 Although four weeks of systemic Zanubrutinib reduced IgM levels (to 46.9 g/L), hearing failed to recover, indicating that IgM reduction alone was insufficient to reverse cochlear injury. Given the patient’s poor physical condition and the approximately one-month duration of hearing loss, we administered bilateral IT-Dex 5 mg daily for 6 days as salvage therapy. Within 72 hours, the patient perceived sound; by day 6, she could understand loud speech, with significant audiometric improvement (right ear +15 dB, left ear +20 dB). To our knowledge, this is the first reported use of IT-Dex as salvage therapy for WM-associated BSSHL refractory to Bruton’s tyrosine kinase (BTK) inhibitor therapy, suggesting that combination therapy (systemic treatment plus local anti-inflammatory intervention) is necessary and effective for this condition.
In summary, BSSHL can be the opening clue to lymphoma relapse, especially the subtype evolving into WM. Combined systemic therapy and early IT-Dex may rescue hearing even when IgM has only partially fallen.
Limitations
Several limitations of this case report should be acknowledged. First, serum viscosity was not routinely measured in this patient. Second, therapeutic plasmapheresis was not performed during hospitalization. Third, due to the combined use of zanubrutinib and intratympanic dexamethasone, it is difficult to separately distinguish the independent therapeutic effect of IT-Dex. Fourth, the follow-up period after treatment was relatively short. Finally, definitive bone marrow biopsy and MYD88 genetic testing were not completed, leading to inevitable diagnostic uncertainty.
Conclusion
Given the potential irreversible risk of hearing loss caused by HVS associated with WM, urgent intervention targeting both the underlying hematological disease and auditory dysfunction is necessary. In the differential diagnosis of BSSHL, hyperviscosity should be prioritized as a contributing factor, especially in elderly patients with a history of lymphoma or hematological disorders.
For otolaryngologists, recognizing lymphoma as a rare yet critical cause of sudden hearing loss is crucial—particularly when patients present with concurrent manifestations such as anemia, elevated total protein, or evidence of systemic microcirculatory disturbances (e.g., renal impairment, visual abnormalities). Early collaboration with hematology teams to promptly assess monoclonal protein levels and serum viscosity, initiate targeted therapy, and supplement with salvage intratympanic steroid injections can maximize the potential for hearing recovery and improve the patient’s overall prognosis.
Footnotes
Acknowledgments
We express our sincere gratitude to all medical staff in our department for their invaluable support throughout the diagnosis and treatment of this patient. We also extend our heartfelt appreciation to the patient and her family for their informed consent and cooperation with this case report.
Ethical Considerations
This case report was granted an exemption from ethical approval by the Institutional Review Board of Minhang Branch, Zhongshan Hospital, Fudan University. Our institution does not require ethical approval for reporting individual cases or case series.
Consent to Participate
Written informed consent was obtained from participant prior to the study, for the purpose of publication in accordance with ethical guidelines.
Consent for Publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Author Contributions
Yuhui Deng: Conceptualization, Methodology, Investigation, Data curation, Writing – original draft, Visualization. Qing Xiao: Investigation, Resources, Writing – review & editing. Yangyang Ji: Conceptualization, Methodology, Validation, Supervision, Writing – review & editing, Project administration. Linglan Gu: Conceptualization, Methodology, Validation, Investigation, Writing – original draft, Visualization.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Disclosure
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.