Carlson, Matthew L.

Objective: To date, less than 150 cases of middle ear adenomatous neuroendocrine tumors (MEANTs) have been reported in the English literature. The objective of this study was to provide a contemporary analysis of these rare lesions and develop a consensus-driven staging system. Study Design: Multi-institutional retrospective histopathologic, radiologic, and clinical review. Setting: Six tertiary referral centers. Patients: Thirty-two patients with pathologically confirmed MEANT. Intervention: Surgical resection, adjuvant therapy. Main Outcome Measures: Clinical manifestations, outcomes, staging system. Results: Patients commonly presented with progressive conductive or mixed hearing loss (90%), aural fullness (50%), and tonal tinnitus (46%). Pulsatile tinnitus (16%), carcinoid syndrome (4%), and facial nerve paresis (4%) were less commonly observed. MEANTs frequently mimicked temporal bone paraganglioma (31%) and cholesteatoma (15%) at presentation. According to a novel T/N/M/S staging system (S = secretory tumor) proposed herein, there were 6 (19%) T1, 19 (59%) T2, and 7 (22%) T3 MEANTs. T3 tumors were significantly more likely to undergo subtotal or near total resection compared with lower staged tumors secondary to adherence to critical neurovascular structures such as the petrous internal carotid artery and facial nerve (p = 0.027). Patients with T3 MEANTs were more likely to experience multiple recurrences, require adjuvant therapy with a somatostatin analogue, or develop permanent facial nerve paresis compared with lower staged tumors. At last follow up, no patients with T1 MEANTs had developed recurrence, whereas 37% (7/19) of patients with T2 MEANT and 57% (4/7) of patients with T3 MEANT experienced either disease recurrence after gross total resection (GTR) or regrowth of known residual tumor requiring additional surgery at a median duration of 72 months (95% CI, 24–84). Conclusions: Patients with MEANTs can present with nonspecific symptomatology that overlaps with more commonly encountered middle ear lesions. MEANT exhibits a proclivity for recurrence according to T-stage and long-term clinical follow up is necessary, particularly for advanced stage tumors.

Objective: To describe the incidence of intralabyrinthine schwannoma (ILS) utilizing the Rochester Epidemiology Project (REP), a unique medical consortium in the United States that covers a complete population of all ages in a well-defined geographic area over the past half-century. Patients: All patients with ILS diagnosed between January 1, 1966 and December 31, 2016 in Olmsted County, Minnesota, identified using the REP medical records-linkage system. Main Outcome Measures: Incidence of ILS. Results: Fourteen incident cases of ILS were identified in Olmsted County since 1966—a period spanning 5.9 million person-years. Over the past decade, the incidence rate of ILS was 0.81 per 100,000 person-years and 1.1 over the last 5 years. Since 1966, the cumulative incidence rate of ILS over the past 50 years was 0.26 per 100,000 person-years. The median age at diagnosis was 60 years (interquartile ranges, 39–70). Incidence increased with age: over the last 5 years, those aged 60 to 69 exhibited an incidence rate of 2.7 per 100,000 person-years and those 70+ displayed a rate of 4.1. All patients had varying levels of asymmetrical sensorineural hearing loss with 64% of patients presenting with class D hearing. Four (29%) patients had a history of sudden sensorineural hearing loss, five (36%) reported imbalance and/or vertigo, and four (29%) reported aural fullness. Three of the 14 (21%) patients had neurofibromatosis type 2. Conclusion: The incidence of ILS exceeds 1 per 100,000 person-years with modern diagnostic imaging. The rising incidence of ILS in recent years most likely reflects improved capacity for disease detection rather than a true increase in tumor development. Given the reputability of the REP consortium, these data suggest that ILS comprises a more common entity than previously considered.

Background Cahan's criteria have been utilized since 1948 to establish causality between prior radiation treatment and the development of secondary malignancy. One major criterion specifies that histological and radiographic evidence collected before and after radiation treatment must confirm separate tumor types; however, pretreatment biopsy is rarely obtained prior to radiosurgery for vestibular schwannoma and many other skull base and cranial lesions. Therefore, in these cases Cahan's criteria cannot be validly applied. Objective This article proposes an update to Cahan's criteria using modern molecular genetic analysis for cases lacking baseline histopathology. Methods Mate-pair sequencing and whole exome sequencing of a cerebellopontine angle undifferentiated high-grade pleomorphic sarcoma (UHGPS) that developed after stereotactic radiosurgery of a presumed benign vestibular schwannoma. Results Mate-pair sequencing and whole exome sequencing of the sarcoma revealed complex chromosomal aberrations. Notably, the tumor contained a deletion in the NF2 gene at 22q12 and an in-frame deletion on exon 5 of the remaining copy of NF2. Biallelic events impacting NF2 are atypical for UHGPS but are characteristic for vestibular schwannoma. These findings help support the conclusion that the UHGPS arose from a benign vestibular schwannoma all along. Conclusions Next-generation sequencing can be successfully applied to a radiation-induced sarcoma when both the original and malignant tumors harbor separate signature genetic markers. As our understanding of the genetic profile of various tumors expand, we believe that next-generation sequencing and other genomic tools will play an increasingly important role in establishing causality between radiation and the development of secondary malignancy.