Marinelli, John P.

ObjectiveTo ascertain the relationship among vestibular schwannoma (VS) tumor volume, growth, and hearing loss.Study DesignRetrospective cohort study.SettingSingle tertiary center.Subjects and MethodsAdults with observed VS and serviceable hearing at diagnosis were included. The primary outcome was the development of nonserviceable hearing as estimated using the Kaplan‐Meier method. Associations of tumor volume with baseline hearing were assessed using Spearman rank correlation coefficients. Associations of volume and growth with the development of nonserviceable hearing over time were assessed using Cox proportional hazards models and summarized with hazard ratios (HRs).ResultsOf 230 patients with VS and serviceable hearing at diagnosis, 213 had serial volumetric tumor data for analysis. Larger tumor volume at diagnosis was associated with increased pure‐tone average (PTA) (P <. 001) and decreased word recognition score (WRS) (P =. 014). Estimated rates of maintaining serviceable hearing at 6 and 10 years following diagnosis were 67% and 49%, respectively. Larger initial tumor volume was associated with development of nonserviceable hearing in a univariable setting (HR for 1‐cm3 increase: 1.36, P =. 040) but not after adjusting for PTA and WRS. Tumor growth was not significantly associated with time to nonserviceable hearing (HR, 1.57; P =. 14), although estimated rates of maintaining serviceable hearing during observation were poorer in the group that experienced growth.ConclusionLarger initial VS tumor volume was associated with poorer hearing at baseline. Larger initial tumor volume was also associated with the development of nonserviceable hearing during observation in a univariable setting; however, this association was not statistically significant after adjusting for baseline hearing status.

Objective: Closely paralleling previous radiologic studies, recent population-based prevalence data suggest sporadic vestibular schwannoma (VS) affects over one in 2,000 adults and up to one in 500 in those aged 70 years or older. Attributable to increased utilization of magnetic resonance imaging and screening protocols for asymmetrical sensorineural hearing loss, the increasing detection rate of sporadic VS fundamentally changes the perception of VS as a whole. The primary objective of the current study was to contextualize modern epidemiological trends in neurofibromatosis type 2 (NF2) in light of these recent advancements in the understanding of sporadic VS. Study Design: Population-based study. Setting: Olmsted County, Minnesota. Population size on January 1, 2017: 159,689 people. Patients: All patients with NF2 diagnosed between Jan 1, 1966 and Dec 31, 2016, identified using the Rochester Epidemiology Project. Main Outcome Measures: Incidence, prevalence. Results: Six incident cases were identified over the past 50 years. From 1966 to 2016, the age- and sex-adjusted incidence rate was 0.10 per 100,000 person-years. The incidence rate remained at 0.12 over the most recent decade. Five cases met disease prevalence criteria, and the age- and sex-adjusted prevalence of NF2 on Jan 1, 2017 was 3.1 per 100,000 persons. All prevalent cases were women, and the resultant prevalence among women only was 6.0 per 100,000 persons. Conclusions: The modern age- and sex-adjusted incidence rate and prevalence of NF2 is 0.10 per 100,000 person-years and 3.1 per 100,000 persons, respectively. In contrast to trends in incidence rates of sporadic VS over the last half-century, this study demonstrates that the incidence of NF2 has remained relatively stable since 1966. This divergence in epidemiological trends is likely attributed to the nature of NF2, with early clinical manifestations resulting in diagnosis regardless of modern advances, whereas the increased incidence of sporadic VS is heavily influenced by improved detection in a greater population of patients with minimally symptomatic or asymptomatic tumors.

Objective: Several reports have suggested that the incidence of otosclerosis is declining. However, due to the limitations of epidemiologic databases within the United States, little is known about the incidence of congenital stapes footplate fixation (CSFF), much less epidemiological trends over the past 50 years. The current study was conceived to characterize the epidemiology of CSFF over the past five decades using the unique resources of the Rochester Epidemiology Project (REP). Study Design: Population-based study. Patients: The medical records of every resident of Olmsted County, Minnesota who was diagnosed with CSFF was reviewed from January 1, 1970 to December 12, 2017 using the REP. The population of Olmsted County on January 1, 2017 was 159,689 persons. Main Outcome Measure: Incidence of CSFF. Results: Sixteen cases of CSFF were identified at a median age at diagnosis of 8 years (IQR, 6–17), eight of whom confirmed by exploratory tympanotomy. Three of the 16 (19%) cases were bilateral, and the median pure-tone average (500, 1k, 2k, 3k Hz) at time of diagnosis was 37 dB (IQR, 31–48). Two (13%) cases were identified in patients bearing a syndromic condition and one (6%) case demonstrated a malformed external ear on physical examination. The incidence rate of surgically confirmed cases among residents of Olmsted County was 0.31 per 100,000 person-years from 1970 to 1979 and 0.28 from 2000 to 2009. No incident cases among residents of Olmsted County were identified since 2010. Conclusions: CSFF constitutes a rare disease. Unlike epidemiological trends in otosclerosis, the incidence of surgically confirmed cases of CSFF remained stable over the past 50 years.

AbstractEsthesioneuroblastoma (ENB) is a rare olfactory malignancy that can present with locally advanced disease. At our institution, patients with ENB in whom the treating surgeon believes that a margin-negative resection is initially not achievable are selected to undergo induction with chemotherapy with or without radiotherapy prior to surgery. In a retrospective review of 61 patient records, we identified six patients (10%) treated with this approach. Five of six patients (83%) went on to definitive surgery. Prior to surgery, three of five patients (60%) had a partial response after induction therapy, whereas two of five (40%) had stable disease. Microscopically margin-negative resection was achieved in four of five (80%) of the patients who went on to surgery, while one patient had negative margins on frozen section but microscopically positive margins on permanent section. Three of five patients (60%) recurred after surgery; two of these patients died with recurrent/metastatic ENB. In summary, induction therapy may facilitate margin-negative resection in locally advanced ENB. Given the apparent sensitivity of ENB to chemotherapy and radiotherapy, future prospective studies should investigate the optimal multidisciplinary approach to improve long-term survival in this rare disease.

ObjectiveIgG4‐related disease (IgG4‐RD) is a recently recognized disease characterized by fibroinflammatory infiltrates rich in IgG4+ plasma cells that can present as isolated tumor‐like lesions of the head and neck. The objective of the current study was to describe the cranial base manifestations of IgG4‐RD.MethodsReview of all cases at three tertiary‐referral centers since disease description in 2003.ResultsEleven patients were identified at a median age at presentation of 58 years (IQR, 38–65; 55% male). Ten (91%) patients had isolated skull base masses without systemic disease. Cranial neuropathies were commonly observed in the abducens (45%), trigeminal (18%), and facial nerves (18%). Lesions frequently involved the cavernous sinus (55%; 6/11) with extension to the petroclival junction in 50% (3/6). Infiltration of the internal auditory canal was present in 27% (3/11) with one case demonstrating erosion of the bony labyrinth. Preliminary clinical diagnoses commonly included nasopharyngeal cancer, pituitary macroadenoma, cholesteatoma, and meningioma / multiple meningioma syndrome. Local biopsy demonstrated >30 IgG4‐positive plasma cells per high‐powered field or an IgG4:IgG ratio greater than 40% in all cases. Rapid and durable clinical improvement was seen in 91% following corticosteroid and rituximab therapy.ConclusionsIgG4‐RD nonspecifically presents as a rare cause of the skull base mass. Often presenting without concomitant systemic disease, local diagnostic biopsies are required. Obtaining adequate tissue specimen is complicated by densely fibrotic cranial base lesions that are frequently in close proximity to critical neurovascular structures. Primary medical therapy with corticosteroids and rituximab is effective in most patients.Level of Evidence4 Laryngoscope, 130:2574–2580, 2020

Objective: The majority of research influencing our understanding of vestibular schwannoma (VS) comes from large tertiary referral centers, and as a consequence, is inherently prone to referral bias. The objective of the current study was to characterize tertiary referral center bias in VS research. Study design: Single-institution retrospective clinical, audiometric, and radiologic review. Setting: One tertiary referral center. Patients: One hundred twenty-three patients with sporadic VS treated at our institution, consisting of a local cohort of all 41 VS patients residing in the same US county as our medical center and a referral cohort of 82 patients from outside counties matched 2:1 based on age, sex, and year of diagnosis. Intervention: Surgical resection, stereotactic radiosurgery (SRS), observation. Main outcome measures: Clinical manifestations, audiometric and radiologic findings, elected treatment modality. Results: Local patients had significantly longer follow-up after initial presentation compared to referral patients (median 4.0 vs 2.2 yr; p = 0.007). Referral patients were significantly less likely to have an incidental VS diagnosis (1% vs. 29%; p < 0.001) and presented with worse symptomatology such as hearing loss (80% vs. 54%; p = 0.002), dizziness (72% vs. 44%; p = 0.002), headache (29% vs. 15%; p = 0.075), and other cranial nerve dysfunction (11% vs. 0%; p = 0.029). Audiometrically, referral patients had significantly poorer word recognition scores at presentation (median 70% vs. 90%; p = 0.043). Local patients were more likely to have tumors confined to the IAC compared with referral patients, and had significantly smaller tumors when restricted to this region (median 4.0 vs 6.5 mm; p = 0.005). Referral patients were significantly more likely to undergo definitive management with either radiosurgery or microsurgery following primary evaluation compared to local patients (48% vs. 24%; p = 0.013). Conclusion: These data suggest that the majority of existing literature surrounding VS likely suffers from referral bias, whereby disease characteristics and management decisions are distinct from that of the general VS patient population.

Objective: Previous research has shown that tumor growth during observation of small-to-medium sized sporadic vestibular schwannomas (VSs) occurs almost exclusively within 3 to 5 years following diagnosis. This has led some to consider ending surveillance after this interval. This study seeks to characterize a cohort of patients with tumors that exhibited late growth. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Adults with sporadic VSs who initially elected observation with serial magnetic resonance imaging (MRI) surveillance. Intervention(s): None. Main Outcome Measure(s): Linear tumor growth was measured in accordance with AAO-HNS reporting guidelines. Delayed growth was defined as growth ≥2 mm in linear diameter that was first detected 5 years or more from the initial MRI. Results: From a total of 361 patients, 172 experienced tumor growth during the interval of observation. Fourteen of these 172 patients (8.1%) experienced late growth occurring at 5 years or beyond. Among patients with delayed growth, the fastest growth rate after extended quiescence was 1.33 mm/yr, and the longest delay before tumor growth detection was 11.1 years. Additional treatment was recommended for six (42.9%) of the patients with delayed growth. Of 68 tumors that remained in the IAC, 11 (16.2%) demonstrated delayed growth. Of 66 tumors that presented in the CPA, 2 (3.0%) demonstrated delayed growth. Initial size was larger for tumors demonstrating early growth compared with those with delayed growth. For tumors within the IAC, those with early growth had a significantly higher median growth rate than those with delayed growth (1.40 vs. 0.45 mm/yr, p < 0.001). Conclusions: Delayed growth encompassed 8.1% of growing VSs and 3.9% of all observed tumors. Patients with delayed growth exhibited slower growth rates compared with those who were diagnosed with growth early in their observation course. These findings support the need for lifelong surveillance of untreated VSs given the possibility of clinically significant delayed growth. Increasing the time interval between MRI studies after 5 years is a reasonable concession to balance practicalities of cost and convenience with risk of delayed of tumor growth.