Malignant peripheral nerve sheath tumors of the eighth cranial nerve arising without prior irradiation

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OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) of the eighth cranial nerve (CN) are exceedingly rare. To date the literature has focused on MPNSTs occurring after radiation therapy for presumed benign vestibular schwannomas (VSs), while MPNSTs arising without prior irradiation have received little attention. The objectives of the current study are to characterize the epidemiology, clinical presentation, disease course, and outcome using a large national cancer registry database and a systematic review of the English literature. Additionally, a previously unreported case is presented.

METHODS

The authors conducted an analysis of the Surveillance, Epidemiology, and End Results (SEER) database, a systematic review of the literature, and present a case report. Data from all patients identified in the SEER database with a diagnosis of MPNST involving the eighth CN, without a history of prior radiation, were analyzed. Additionally, all cases reported in the English literature between January 1980 and March 2015 were reviewed. Finally, 1 previously unreported case is presented.

RESULTS

The SEER registries identified 30 cases between 1992 and 2012. The average incidence was 0.017 per 1 million persons per year (range 0.000–0.0687 per year). The median age at diagnosis was 55 years, and 16 (53%) were women. Thirteen cases were diagnosed upon autopsy. Of the 17 cases diagnosed while alive, the median follow-up was 118 days, with 3 deaths (18%) observed. When compared with the incidence of benign VS, 1041 VSs present for every 1 MPNST arising from the eighth CN. Including a previously unreported case from the authors' center, a systematic review of the English literature yielded 24 reports. The median age at diagnosis was 44 years, 50% were women, and the median tumor size at diagnosis was 3 cm. Eleven patients (46%) reported isolated audiovestibular complaints typical for VS while 13 (54%) exhibited facial paresis or other signs of a more aggressive process. Treatment included microsurgery alone, microsurgery with adjuvant radiation, or microsurgery with chemoradiation. Sixty-one percent of patients receiving treatment experienced recurrence, 22% of which were diagnosed with drop metastases to the spine. Ultimately, 13 patients (54%) died of progressive disease at a median of 3 months following diagnosis. The ability to achieve gross-total resection was the only feature that was associated with improved disease-specific survival.

CONCLUSIONS

MPNSTs of the eighth CN are extremely rare and portend a poor prognosis. Nearly half of patients initially present with findings consistent with a benign VS, often making an early diagnosis challenging. In light of these data, early radiological and clinical follow-up should be considered in those who elect nonoperative treatment, particularly in patients with a short duration of symptoms or atypical presentation. These data also provide a baseline rate of malignancy that should be considered when estimating the risk of malignant transformation following stereotactic radiosurgery for VS.

ABBREVIATIONSCN = cranial nerve; GTR = gross-total resection; ICD-O-3 = International Classification of Diseases for Oncology-Third Edition; MPNST = malignant peripheral nerve sheath tumors; NF, NF1, NF2 = neurofibromatosis, NF Type 1, NF Type 2; NOS = not otherwise specified; NTR = near-total resection; SEER = Surveillance, Epidemiology, and End Results; STR = subtotal resection; VS = vestibular schwannoma.

OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) of the eighth cranial nerve (CN) are exceedingly rare. To date the literature has focused on MPNSTs occurring after radiation therapy for presumed benign vestibular schwannomas (VSs), while MPNSTs arising without prior irradiation have received little attention. The objectives of the current study are to characterize the epidemiology, clinical presentation, disease course, and outcome using a large national cancer registry database and a systematic review of the English literature. Additionally, a previously unreported case is presented.

METHODS

The authors conducted an analysis of the Surveillance, Epidemiology, and End Results (SEER) database, a systematic review of the literature, and present a case report. Data from all patients identified in the SEER database with a diagnosis of MPNST involving the eighth CN, without a history of prior radiation, were analyzed. Additionally, all cases reported in the English literature between January 1980 and March 2015 were reviewed. Finally, 1 previously unreported case is presented.

RESULTS

The SEER registries identified 30 cases between 1992 and 2012. The average incidence was 0.017 per 1 million persons per year (range 0.000–0.0687 per year). The median age at diagnosis was 55 years, and 16 (53%) were women. Thirteen cases were diagnosed upon autopsy. Of the 17 cases diagnosed while alive, the median follow-up was 118 days, with 3 deaths (18%) observed. When compared with the incidence of benign VS, 1041 VSs present for every 1 MPNST arising from the eighth CN. Including a previously unreported case from the authors' center, a systematic review of the English literature yielded 24 reports. The median age at diagnosis was 44 years, 50% were women, and the median tumor size at diagnosis was 3 cm. Eleven patients (46%) reported isolated audiovestibular complaints typical for VS while 13 (54%) exhibited facial paresis or other signs of a more aggressive process. Treatment included microsurgery alone, microsurgery with adjuvant radiation, or microsurgery with chemoradiation. Sixty-one percent of patients receiving treatment experienced recurrence, 22% of which were diagnosed with drop metastases to the spine. Ultimately, 13 patients (54%) died of progressive disease at a median of 3 months following diagnosis. The ability to achieve gross-total resection was the only feature that was associated with improved disease-specific survival.

CONCLUSIONS

MPNSTs of the eighth CN are extremely rare and portend a poor prognosis. Nearly half of patients initially present with findings consistent with a benign VS, often making an early diagnosis challenging. In light of these data, early radiological and clinical follow-up should be considered in those who elect nonoperative treatment, particularly in patients with a short duration of symptoms or atypical presentation. These data also provide a baseline rate of malignancy that should be considered when estimating the risk of malignant transformation following stereotactic radiosurgery for VS.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare and heterogeneous group of neoplasms composing 5%–10% of all soft-tissue sarcomas with an incidence of approximately 1 per million people per year.30,42,44 MPNSTs may arise de novo unrelated to a major nerve, within normal peripheral neural tissue, or from precursor lesions such as plexiform neurofibromas or less commonly, schwannomas.42 The majority of MPNSTs arise in the deep tissues of the proximal upper and lower extremities commonly involving the sciatic nerve, brachial plexus, or sacral plexus, while less than 5% involve the cranial base.2,17,42 Of the cranial nerve (CN) and intracranial MPNSTs, the seventh-eighth CN bundle is most commonly affected.30,44

Primary risk factors for MPNST development include neurofibromatosis Type 1 (NF1) and a prior history of radiation therapy.30,42,44 The majority of the literature on eighth CN MPNSTs has focused on cases that developed following radiation therapy, while very little attention has been given to lesions arising without a prior history of ionizing radiation.8,40,45,46 Given the paucity of data describing the latter, the authors sought to characterize the epidemiology, disease presentation, and clinical course of eighth CN MPNSTs, using a large national cancer registry, as well as a systematic review of the English literature. Furthermore, we include 1 previously unreported case treated at the authors' center within the last year.

Methods

Tumor Registry Analysis

The Surveillance, Epidemiology, and End Results (SEER) database includes a set of 20 population-based tumor registries covering approximately 28% of the US. Cases were selected by coding for International Classification of Diseases for Oncology-Third Edition (ICD-O-3) codes for 9540/3 (malignant peripheral nerve sheath tumor), 9560/3 (neurilemmoma, malignant), and 8561/3 (triton tumor, malignant) with associated topography code (C72.4) for auditory and vestibular nerve. Cases with a prior history of radiation were excluded, as were cases with a prior history of vestibular schwannoma (VS) that received radiation therapy. As SEER is a set of population-based registries, incidence may be calculated. The annual population denominators for the registries were taken from SEER-Stat, and the incidence from 1992 to 2012 was plotted. Additionally, to draw a comparison of the incidence of eighth CN MPNST and benign VS, data were extracted using the ICD-0-3 code 9560/0 (benign schwannoma) with associated topography code C72.4 (auditory and vestibular nerve) from 2004 to 2012, the years SEER began cataloguing benign VS.

Systematic Review of the Literature

The PubMed database (National Library of Medicine, http://www.ncbi.nlm.nih.gov) was searched from January 1, 1980, to March 1, 2015, using MPNST- and VS-relevant MeSH (Medical Subject Headings) and non-MeSH search terms. “Malignant” AND “nerve” combined with other more specific terms including “vestibular,” “acoustic,” “intracranial,” “cranial,” “cerebellopontine,” AND “internal auditory canal” were queried. Potential references were then hand-searched based on the titles and abstracts to exclude laboratory-only studies and titles not relevant to the topic. Links to “related citations in PubMed” and the bibliography from highly relevant studies were explored to ensure all relevant studies were captured. Individual entries were cross-checked to eliminate duplicate publications reported by more than 1 journal. Reports describing MPNSTs involving other CNs or generically located in the cerebellopontine angle without data regarding nerve of origin were excluded.7 There were 7 excluded cases that were labeled highly proliferative, atypical, or melanotic without an explicit diagnosis of malignancy.4,20,26,36,51

A total of 43 malignant tumors of the eighth CN were identified. After excluding 16 cases of eighth CN MPNSTs that occurred following radiation,1,3,10,11,19,27,29,32,33,39,41,44,47,52,54,55 a total of 27 reports remained. Two were subsequently excluded based on non-English publication language.43,56 Finally, 1 case was published twice and was tallied only a single time in analysis.28,34 Thus, when including the current case report, 24 unique cases met inclusion criteria and were analyzed (Fig. 1).5,9,12–16,18,22–25,28,31,34,35,37,44,48,50,53 Data including patient demographics, presence of NF1 or NF2, presenting symptoms, tumor size, treatment strategy, histopathology, recurrence, survival, and duration of clinical follow-up were extracted and presented in tabular form. For cases that developed after resection of a benign VS, details regarding follow-up used the time of diagnosis of malignancy as the starting point. Maximum dimension was used for tumor size. Data were summarized with means, medians, and ranges, or frequency counts and percentages.

FIG. 1.
FIG. 1.

Flow diagram outlining the search strategy for systematic review of the literature on the topic of MPNSTs of the eighth CN arising without prior irradiation.

Because the SEER database samples 28% of the US population, and within the systematic review of the literature there were 10 reports published by US centers between 1992 and 2012, it can be estimated that approximately 2–3 cases from the systematic literature review were also included in the SEER analysis. However, this overlap should not skew study results because these 2 data sets were analyzed and presented separately.

Results

Case Report

A 25-year-old man presented to a local care facility after experiencing a 3-month history of progressive left-sided hearing loss and tinnitus, nonvertiginous imbalance, and worsening of baseline headaches. An audiogram demonstrated mild sensorineural hearing loss with only 40% speech discrimination on the left and normal hearing on the right, and MRI revealed a 1.4-cm left-sided internal auditory canal mass consistent with a VS (Fig. 2). The patient denied a history of facial nerve symptomatology and reported no personal history of ionizing radiation or family history of NF1 or NF2.

FIG. 2.
FIG. 2.

Pre- (left) and postcontrast (right) T1-weighted axial MR images demonstrating a 1.4-cm lesion (arrow) involving the left internal auditory canal and cerebellopontine angle typical for a VS.

The patient was subsequently referred to the authors' center for management. On examination the patient had normal facial nerve function and there were no stigmata of NF1 or NF2. After reviewing the options, the patient and family elected to pursue resection. The patient subsequently underwent an uncomplicated translabyrinthine approach with gross-total tumor resection. Postoperatively, the patient had normal facial nerve function, and surprisingly experienced no acute postoperative vertigo and was without nystagmus. Intraoperative frozen section pathology revealed a spindle cell neoplasm. However, permanent sections revealed a highly cellular tumor composed of spindle-shaped and epithelioid cells, showing moderate cytological anaplasia and brisk mitotic activity. On immunohistochemical staining, these cells diffusely and strongly expressed S100 protein, showed retained INI-1 expression, and were negative for the melanocytic markers HMB-45 and Melan-A. The combined histological and immunophenotypic features were considered consistent with an epithelioid MPNST (Fig. 3).

FIG. 3.
FIG. 3.

Photomicrographs from the case report. A: The histological sections show a cellular neoplasm, composed of areas showing elongated and spindle-shaped cells arranged as fascicles, merging with areas of epithelioid cells. H & E, original magnification ×100. B: The neoplastic cells show moderate cytological atypia, with nuclear pleomorphism, coarse chromatin, and prominent nucleoli. Mitotic activity is very brisk, with 3 mitotic figures (arrows) noted in this field alone. H & E, original magnification ×400. C and D: According to immunohistochemical analysis, there was diffuse and strong positive staining with S100 (C), and INI-1 expression was retained in the tumor cells (D). Original magnification ×100. Figure is available in color online only.

Following final histopathological review, the patient underwent postoperative MRI of the head and whole-body PET CT for initial staging. MRI confirmed gross-total resection (GTR) and nuclear medicine imaging revealed no evidence for local, regional, or distant metastasis (Fig. 4). It was recommended that the patient receive adjuvant intensity-modulated radiotherapy without chemotherapy; however, after reviewing his options the patient and family elected to forgo planned postoperative radiation and the patient is currently being followed closely with serial MRI. At the time of writing this paper, 3 months following surgery, the patient had no evidence of clinical or radiological recurrence.

FIG. 4.
FIG. 4.

Early postoperative MRI and PET CT. A and B: Fast imaging employing steady-state acquisition (A) and postcontrast fat-subtracted T1-weighted MRI (B) reveal GTR (arrows). C and D: Axial (C) and whole-body PET CT (D) reveals no evidence of residual or metastatic disease (arrows). Figure is available in color online only.

Analysis of National Tumor Registry Data

The SEER database contained 30 cases between 1992 and 2012. The average incidence was 0.017 per 1 million persons per year (range 0.000–0.0687 per year). Utilizing the SEER database, it was determined that 1041 VSs present for every 1 case of an eighth CN MPNST. The median age at diagnosis was 55 years (mean 55.3 years, range 28–79 years), and 16 (53.3%) were women. Most patients reported non-Hispanic white ethnicity (n = 21, 70.0%), followed by Hispanic (n = 5, 16.7%), non-Hispanic black (n = 3, 10.0%) and other or unknown (n = 1, 3.3%). Thirteen patients (43.3%) were diagnosed upon autopsy and therefore did not receive treatment, 12 (40.0%) received GTR, 3 (10.0%) subtotal resection (STR), and 2 (6.6%) surgery not otherwise specified (NOS) or status of surgery unknown. Of the 17 cases diagnosed while alive, the median follow-up was 118 days, with 3 deaths observed.

Systematic Review of the Literature

Including the above-described case report, a total of 24 unique cases met inclusion criteria and were analyzed.5,9,12–16,18,22–25,28,31,34,35,37,44,48,50,53 The median age of these 24 patients was 44 years (mean 43.3 years, range 1.5–77 years) and 12 (50%) were women. Two patients (8.3%) had NF2, while 1 (4.2%) had NF1. Thirteen patients (54.2%) presented with varying severities of facial paresis, hearing loss was universally present (20 of 20 cases) in cases where hearing status was documented, and dizziness, imbalance, or ataxia was reported in 13 cases (54.2%). The rate of audiological deterioration could not be analyzed secondary to incomplete reporting in the literature. In 11 reports (45.8%) the patient initially presented with symptoms typical for a benign VS, while the remaining exhibited clinical features suggesting a more aggressive process, including facial weakness; trigeminal neuropathy; lower CN dysfunction; diplopia from third, fourth, or sixth CN involvement; or global neurological decline (Table 1). There were no published cases of spinal metastasis at primary presentation. Primary tumor size was available in 14 reports; the median tumor size prior to treatment was 3 cm (mean 3.2 cm, range 1.5–5.4 cm). Nine cases (37.5%) had features to suggest the possibility that the MPNST arose from a benign VS precursor. Specifically, 4 tumors demonstrated coexisting portions of benign schwannoma background; 4 patients had prior resection documenting VS; and 1 had undergone imaging 10 years earlier, which documented a small lesion consistent with a VS. Twenty-three (95.8%) of 24 cases underwent resection, 7 (29.2%) received adjuvant radiation therapy following resection via a variety of radiation delivery techniques, and 2 (8.3%) also received adjuvant chemotherapy. One patient died within 2 months of presentation without treatment. Fourteen (60.9%) of 23 patients receiving treatment experienced disease recurrence; 5 (35.7%) of these 14 had evidence of spinal metastasis. Ultimately 13 (54.2%) of 24 published cases reported death from progressive disease at a median of 3 months (mean 5.5 months, range 1–27 months) following initial diagnosis (Table 2). When analyzing age, sex, treatment modality, and symptomatology at presentation, the only feature that was found to be statistically significantly associated with improved disease-specific survival was GTR versus incomplete resection (p = 0.004, 2-tailed Fisher's exact test; Fig. 5).

TABLE 1.

Summary of demographic features and disease presentation of 24 cases of eighth CN MPNSTs arising without prior irradiation

Case No.Primary Author & YearAge (yrs), SexSyndromeFrom Prior VSFacial ParalysisHearing LossDizziness, Imbalance, or AtaxiaHAsHydrocephalusOther Symptoms
1Kudo et al., 1983; Matsumoto et al., 199054, MNoNoYesYesYesNSNSCN V
2Hernanz-Schulman et al., 19861.5, FNoNoYesYesNSNSNS
3Best, 198724, FNoNoYesYesYesNSNoCN V, VI, slurred speech
4McLean et al., 199075, MNoYesYesYesNoNSNS
5Han et al., 199247, FNoYesNoYesYesYesYesCN V, X
6Maeda et al., 199338, MNoNoYesYesYesYesNS
7Earls et al., 199477, MNSNoNoYesYesNSNSCN X, XI
8Gruber et al., 199461, FNoNoNoYesYesNSNS
9Mrak et al., 199440, MNoNoYesNSYesYesNSCN V
10Higami et al., 199845, FNF2NoNoYesNSNSNSIncontinence, shoulder & leg weakness
11Son et al., 200133, FNoYesNoYesYesYesNS
12Suresh et al., 200346, FNF2NoYesNSNSNSNSCN III, IV, IX, X, paraplegia
13Gonzalez et al., 200743, FNoYesYes (HB Grade II)YesYesNSYes
14Chen et al., 200862, FNoNoYesYesNSNSNSCN V, IX, X
15Scheithauer et al., 200967, MNoYesNoYesNSNSNSNeurological decline
1656, MNSYesNSNSNSNSNS
1732, MNF1NoNoNSNSNSNSNeurological decline
185, MNoYesYesYesNSNSNS
19Gousias et al., 201064, MNoYesNoYesYesYesNS
20Karami et al., 201123, FNoNoYes (HB Grade VI)YesYesNSYesCN V, X
21Gong et al., 201255, FNSNoYesYesNSNSNSCN V
22Wei et al., 201241, FNoYesYes (HB Grade III)YesNSNSNSCN V
23Hong et al., 201425, MNoNoNoYesYesNSNSCN V
24Current case25, MNoNoNoYesYesYesNo

HA = headache; HB = House-Brackmann; NS = not specified.

TABLE 2.

Summary of treatment and outcome of 24 cases of eighth CN MPNSTs arising without prior irradiation

Case No.Primary Author & YearInitial Treatment of MPNSTRadiationChemoFrom Prior VSRecurrenceFollow-up (mos)Death From Disease
1Kudo et al., 1983; Matsumoto et al., 1990Surgery (STR)NoNoNoYes4Yes
2Hernanz-Schulman et al., 1986Surgery (GTR)Yes (55 Gy)NoNoYes24No
3Best, 1987Surgery (STR)NoNoNoYes1.5Yes
4McLean et al., 1990Surgery (STR)NoNoYesYes2Yes
5Han et al., 1992Surgery (NTR)RefusedNoYesYes (w/DM)10Yes
6Maeda et al., 1993Surgery (STR)NoNoNoYes3Yes
7Earls et al., 1994Surgery (NOS)NSNSNoNSNSNS
8Gruber et al., 1994Surgery (GTR)NoNoNoNo24No
9Mrak et al., 1994Surgery (GTR)Yes (fractionated NOS)NoNoYes (w/DM)39NS
10Higami et al., 1998Surgery (NOS)NoYesNoYes (w/DM)4Yes
11Son et al., 2001Surgery (GTR)Yes (fractionated NOS)NoYesYes12No
12Suresh et al., 2003NoneNoNANoNA2Yes
13Gonzalez et al., 2007Surgery (GTR)Yes, multipleYesYesYes (w/DM)8Yes
14Chen et al., 2008Surgery (GTR)NoNoNoYes4Yes
15Scheithauer et al., 2009Surgery (GTR)NSNSYesYes1Yes
16Surgery (STR)NSNSYesYes2Yes
17Surgery (STR)NoNoNoNS3Yes
18Surgery (NOS)NSNSYesNSNSNo
19Gousias et al., 2010Surgery (GTR)Yes (60 Gy)NoYesNo12No
20Karami et al., 2011Surgery (STR)Yes, multipleNoNoYes (w/DM)27Yes
21Gong et al., 2012Surgery (NOS)NoNoNoNo5No
22Wei et al., 2012Surgery (NOS)NSNSYesNSNSNS
23Hong et al., 2014Surgery (GTR)Yes, multipleYesNoNo24No
24Current caseSurgery (GTR)RefusedNoNoNA3NA

Chemo = chemotherapy; DM = drop metastasis; NA = not applicable.

FIG. 5.
FIG. 5.

Kaplan-Meier plot comparing disease-specific survival following GTR versus near-total resection (NTR) or STR of MPNSTs of the eighth CN arising without prior irradiation. Tick marks designate censored data.

Discussion

Intracranial and CN MPNSTs are rare, representing less than 5% of all reported cases of MPNSTs overall.2,17,42 Prior studies have demonstrated that intracranial MPNSTs are divergent from MPNSTs elsewhere with respect to pathogenesis and risk factors.30,44 In the trunk and limbs approximately half of all MPNSTs are associated with NF1 and most frequently arise from a preexisting plexiform neurofibroma. In contrast, intracranial lesions are more likely to develop from normal neural tissue, precursor schwannoma, and in patients with NF2. Notably, of the 24 unique cases reported in the literature, 2 occurred in patients with NF2. Thus, NF2-associated eighth CN tumors appear to have a slightly higher rate of malignancy than sporadic tumors, a finding that parallels reports from the postradiation literature.8

Given the increasing number of patients receiving primary stereotactic radiosurgery worldwide for benign intracranial lesions, much of the literature over the past 2 decades has focused on so-called radiation-induced or radiation-associated secondary malignancies, while eighth CN MPNSTs arising without prior irradiation have received much less attention. The authors recently treated a young man with microsurgical resection for a presumed benign VS, without prior history of radiation, only to discover an epithelioid MPNST on permanent section pathological analysis. Notably, this is the first occurrence of an eighth CN MPNST occurring in a patient without prior radiation therapy that the senior author has observed in more than 600 VS surgeries. Given the paucity of literature on this subject, we sought to review all prior published cases and to use the SEER database to further elucidate the epidemiology of this rare malignancy.

Including the recent case managed at our institution, we identified 24 unique accounts of eighth CN MPNSTs occurring without prior irradiation in the English literature. There was an equal distribution of sex, and the median age at diagnosis was 44 years, which is more than 10 years younger than the average age at presentation for benign sporadic VS.49 Prior to data analysis, the authors posited that the great majority of patients with eighth CN MPNSTs would present with atypical symptoms such as facial paralysis or telling radiological features such as ill-defined margins, brainstem edema, or internal necrosis; rather, these data demonstrate that approximately half of patients present with symptoms and findings consistent with typical VS. The SEER database estimated an average annual incidence of 0.017 per 1 million persons per year. When comparing this to the average estimated incidence of VSs that present to medical attention, we found that 1 in every 1041 eighth CN tumors is malignant. While rare, this information should be considered when determining radiological follow-up for patients who elect initial nonoperative therapy. Specifically, it would be reasonable to consider earlier MRI, such as 3 months following initial imaging, in patients with a short duration of symptoms or particularly for those with an atypical presentation such as facial paresis or lower CN dysfunction.

This review demonstrates that the overall prognosis of eighth CN MPNSTs is poor. Over half of published cases reported death from progressive disease at a median of 3 months, a finding that has been corroborated by other studies.15,30,44 It is very likely that disease-specific mortality estimates would only increase if this cohort had been followed longer. In a 2010 review, Gousias reviewed 42 cases of intracranial MPNSTs and found that on univariate analysis, GTR, radiotherapy, and female sex were beneficial prognostic factors; however, GTR was the only independent predictor of prolonged overall survival.15 Similarly, we found that the frequency of disease-specific mortality was lower in those treated with GTR compared with STR. Given the high-grade infiltrative nature of MPNSTs and the inability to achieve wide negative margins in the cerebellopontine angle and skull base without significant morbidity, resection combined with adjuvant radiation with or without chemotherapy is warranted in most cases.15,30,44 Disease surveillance should include frequent MRI of the complete neuraxis to detect early local recurrence or spinal drop metastasis.

As an aside, this issue raises an interesting question regarding the true risk of secondary malignancy following stereotactic radiosurgery. Because we found that nearly half of the patients in our systematic review of the literature presented with features typical of VS, it very likely that at least several MPNSTs have been treated with primary radiosurgery for presumed benign VSs. In 1 such published case, the authors suspected this scenario given the atypical behavior of the tumor immediately following radiosurgery.29 In another publication, Comey et al. reported a case of an MPNST that was diagnosed 5 years following primary radiosurgery.10 After experiencing rapid tumor growth the patient underwent microsurgery, and pathological analysis demonstrated a malignant tumor without any background features of benign schwannoma. In both cases, the authors surmised that the patient had received radiosurgery for what was, in fact, a malignant tumor all along. However, it would have been just as logical to conclude that both cases were radiation-induced without histological evidence at the time of initial treatment, particularly the latter case with a latency period of 5 years in accordance with Cahan et al.'s criteria.6 Several studies have estimated the risk of malignant transformation following radiosurgery for VS to be between approximately 1 in 500 to 1 in 2000.21,38,45 Interestingly, this is very similar to the rate of MPNSTs developing without prior irradiation in the current study. While there has been a rise in the number of published cases of eighth CN MPNSTs since 2000, only approximately half occur in patients without prior radiation treatment.11,38,46 While clearly radiation induction is a real phenomenon, particularly in the NF2 population, these data would suggest that we are likely overestimating the risk of malignant transformation following low-dose stereotactic radiation for nonsyndromic VSs.8

Conclusions

Eighth CN MPNSTs arising without a history of prior radiation therapy are exceptionally rare. In contrast to MPNSTs found elsewhere that are commonly associated with NF1 and preexisting plexiform neurofibroma, MPNSTs of the eighth CN are more frequently associated with preexisting schwannoma, NF2, or de novo tumorigenesis. Epidemiological estimates derived from national tumor registry data demonstrate that approximately 1 MPNST involving the vestibulocochlear nerve will present for every 1041 VSs or an incidence of 0.017 per million population per year. Approximately half of the cases will initially present with symptoms and radiological features congruent with benign schwannoma. In light of these data, early radiological and clinical follow-up should be considered after initial evaluation in those who elect nonoperative treatment, particularly in patients with a short duration of symptoms or atypical presentation. These results also provide a baseline rate of malignancy that should be considered when estimating the risk of malignant transformation following stereotactic radiosurgery for VS.

References

  • 1

    Akamatsu YMurakami KWatanabe MJokura HTominaga T: Malignant peripheral nerve sheath tumor arising from benign vestibular schwannoma treated by gamma knife radiosurgery after two previous surgeries: a case report with surgical and pathological observations. World Neurosurg 73:7517542010

  • 2

    Bailet JWAbemayor EAndrews JCRowland JPFu YSDawson DE: Malignant nerve sheath tumors of the head and neck: a combined experience from two university hospitals. Laryngoscope 101:104410491991

  • 3

    Bari MEForster DMKemeny AAWalton LHardy DAnderson JR: Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature. Br J Neurosurg 16:2842892002

  • 4

    Benhaiem-Sigaux NRicolfi FKeravel YPoirier J: Epithelioid schwannoma of the acoustic nerve. Clin Neuropathol 15:2312331996

  • 5

    Best PV: Malignant triton tumour in the cerebellopontine angle. Report of a case. Acta Neuropathol 74:92961987

  • 6

    Cahan WGWoodard HQHiginbotham NLStewart FWColey BL: Sarcoma arising in irradiated bone: report of eleven cases. 1948 Cancer 82:8341998

  • 7

    Caporlingua FLapadula GAntonelli MMissori P: Pleomorphic rhabdomyosarcoma of the cerebellopontine angle in an adult: a review of literature. BMJ Case Rep 2014. bcr20132032572014

  • 8

    Carlson MLBabovic-Vuksanovic DMessiaen LScheithauer BWNeff BALink MJ: Radiation-induced rhabdomyosarcoma of the brainstem in a patient with neurofibromatosis type 2. J Neurosurg 112:81872010. (Erratum in J Neurosurg 112: 209 2010)

  • 9

    Chen LMao YChen HZhou LF: Diagnosis and management of intracranial malignant peripheral nerve sheath tumors. Neurosurgery 62:8258322008

  • 10

    Comey CHMcLaughlin MRJho HDMartinez AJLunsford LD: Death from a malignant cerebellopontine angle triton tumor despite stereotactic radiosurgery. Case report. J Neurosurg 89:6536581998

  • 11

    Demetriades AKSaunders NRose PFisher CRowe JTranter R: Malignant transformation of acoustic neuroma/vestibular schwannoma 10 years after gamma knife stereotactic radiosurgery. Skull Base 20:3813872010

  • 12

    Earls JPRobles HAMcAdams HPRao KC: General case of the day. Malignant melanotic schwannoma of the eighth cranial nerve. Radiographics 14:142514271994

  • 13

    Gong LLiu XYZhang WDHan XJYao LZhu SJ: A rare case of malignant triton tumor in the cerebellopontine angle. Diagn Pathol 7:432012

  • 14

    Gonzalez LFLekovic GPEschbacher JCoons SSpetzler RF: A true malignant schwannoma of the eighth cranial nerve: case report. Neurosurgery 61:E421E4222007

  • 15

    Gousias KBoström JKovacs ANiehusmann PWagner IKristof R: Factors of influence upon overall survival in the treatment of intracranial MPNSTs. Review of the literature and report of a case. Radiat Oncol 5:1142010

  • 16

    Gruber BPetchenik LWilliams MThomas CLuken MG: Malignant vestibular schwannoma. Skull Base Surg 4:2272311994

  • 17

    Guccion JGEnzinger FM: Malignant Schwannoma associated with von Recklinghausen's neurofibromatosis. Virchows Arch A Pathol Anat Histol 383:43571979

  • 18

    Han DHKim DGChi JGPark SHJung HWKim YG: Malignant triton tumor of the acoustic nerve. Case report. J Neurosurg 76:8748771992

  • 19

    Hanabusa KMorikawa AMurata TTaki W: Acoustic neuroma with malignant transformation. Case report. J Neurosurg 95:5185212001

  • 20

    Harada KNishizaki TAdachi NSuzuki MIto H: Pediatric acoustic schwannoma showing rapid regrowth with high proliferative activity. Childs Nerv Syst 16:1341372000

  • 21

    Hasegawa TKida YKato TIizuka HKuramitsu SYamamoto T: Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery. J Neurosurg 118:5575652013

  • 22

    Hernanz-Schulman MWelch KStrand ROrdia JI: Acoustic neuromas in children. AJNR Am J Neuroradiol 7:5195211986

  • 23

    Higami YShimokawa IKishikawa MOkimoto TOhtani HTomita M: Malignant peripheral nerve sheath tumors developing multifocally in the central nervous system in a patient with neurofibromatosis type 2. Clin Neuropathol 17:1151201998

  • 24

    Hong WCheng HWang XHu XFeng C: Study of malignant peripheral nerve sheath tumor in cerebellopontine angle. J Craniofac Surg 25:6997012014

  • 25

    Karami KJKelkar PSVerdon MPGrills ISBojrab DIPieper DR: Malignant peripheral nerve sheath tumor of the vestibulocochlear nerve and brainstem: multimodality treatment with survival of 27 months. A case report and review of the literature. Neurosurgery 69:E1152E11652011

  • 26

    Kroh HMatyja EMarchel A: Epithelioid schwannomas of the acoustic nerve. Folia Neuropathol 38:23272000

  • 27

    Kubo OChernov MIzawa MHayashi MMuragaki YMaruyama T: Malignant progression of benign brain tumors after gamma knife radiosurgery: is it really caused by irradiation?. Minim Invasive Neurosurg 48:3343392005

  • 28

    Kudo MMatsumoto MTerao H: Malignant nerve sheath tumor of acoustic nerve. Arch Pathol Lab Med 107:2932971983

  • 29

    Kuzmik GAMichaelides EMChiang VLNonaka YFukushima TVortmeyer AO: Rapidly progressive epithelioid malignant peripheral nerve sheath tumor of the vestibular nerve. Otol Neurotol 34:173917422013

  • 30

    L'heureux-Lebeau BSaliba I: Updates on the diagnosis and treatment of intracranial nerve malignant peripheral nerve sheath tumors. Onco Targets Ther 6:4594702013

  • 31

    Maeda MJozaki TBaba SMuro HShirasawa HIchihashi T: Malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve. Acta Pathol Jpn 43:1982031993

  • 32

    Maire JPHuchet AMilbeo YDarrouzet VCausse NCélérier D: Twenty years' experience in the treatment of acoustic neuromas with fractionated radiotherapy: a review of 45 cases. Int J Radiat Oncol Biol Phys 66:1701782006

  • 33

    Markou KEimer SPerret CHuchet AGoudakos JLiguoro D: Unique case of malignant transformation of a vestibular schwannoma after fractionated radiotherapy. Am J Otolaryngol 33:1681732012

  • 34

    Matsumoto MSakata YSanpei KOnagi ATerao HKudo M: [Malignant schwannoma of acoustic nerve: a case report.]. No Shinkei Geka 18:59621990. (Jpn)

  • 35

    McLean CALaidlaw JDBrownbill DSGonzales MF: Recurrence of acoustic neurilemoma as a malignant spindle-cell neoplasm. Case report. J Neurosurg 73:9469501990

  • 36

    Miller RTSarikaya HSos A: Melanotic schwannoma of the acoustic nerve. Arch Pathol Lab Med 110:1531541986

  • 37

    Mrak REFlanigan SCollins CL: Malignant acoustic schwannoma. Arch Pathol Lab Med 118:5575611994

  • 38

    Nicolli EARuckenstein M: What is the risk of malignant transformation of vestibular schwannoma following radiosurgery?. Laryngoscope 125:176117622015

  • 39

    Norén G: Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg 70:Suppl 165731998

  • 40

    Patel TRChiang VL: Secondary neoplasms after stereotactic radiosurgery. World Neurosurg 81:5945992014

  • 41

    Puataweepong PJanwityanujit TLarbcharoensub NDhanachai M: Radiation-induced peripheral malignant nerve sheath tumor arising from vestibular schwannoma after Linac-based stereotactic radiation therapy: a case report and review of literatures. Case Rep Med 2012:6481912012

  • 42

    Rodriguez FJFolpe ALGiannini CPerry A: Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 123:2953192012

  • 43

    Saito TOki SMikami TKawamoto YYamaguchi SKuwamoto K: [Malignant peripheral nerve sheath tumor with divergent cartilage differentiation from the acoustic nerve: case report.]. No To Shinkei 52:7347392000. (Jpn)

  • 44

    Scheithauer BWErdogan SRodriguez FJBurger PCWoodruff JMKros JM: Malignant peripheral nerve sheath tumors of cranial nerves and intracranial contents: a clinicopathologic study of 17 cases. Am J Surg Pathol 33:3253382009

  • 45

    Schmitt WRCarlson MLGiannini CDriscoll CLLink MJ: Radiation-induced sarcoma in a large vestibular schwannoma following stereotactic radiosurgery: case report. Neurosurgery 68:E840E8462011

  • 46

    Seferis CTorrens MParaskevopoulou CPsichidis G: Malignant transformation in vestibular schwannoma: report of a single case, literature search, and debate. J Neurosurg 121:Suppl1601662014

  • 47

    Shin MUeki KKurita HKirino T: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. Lancet 360:3093102002

  • 48

    Son EIKim IMKim SP: Vestibular schwannoma with malignant transformation: a case report. J Korean Med Sci 16:8178212001

  • 49

    Stangerup SECaye-Thomasen P: Epidemiology and natural history of vestibular schwannomas. Otolaryngol Clin North Am 45:257268vii2012

  • 50

    Suresh TNMahadevan AChandrashekhar Sagar BSantosh VYasha TCShankar SK: Unusual case of multiple cellular and malignant schwannomas of the cranial and spinal nerves. Clin Neuropathol 22:23292003

  • 51

    Tan TCLam PW: Epithelioid schwannoma of the vestibular nerve. Singapore Med J 45:3933962004

  • 52

    Tanbouzi Husseini SPiccirillo ETaibah APaties CTRizzoli RSanna M: Malignancy in vestibular schwannoma after stereotactic radiotherapy: a case report and review of the literature. Laryngoscope 121:9239282011

  • 53

    Wei CHeman-Ackah SENewman KZagzag DGolfinos JGRoland JT Jr: Temporal bone histopathology case of the month: Malignant peripheral nerve sheath tumor arising within vestibular schwannoma. Otol Neurotol 33:e83e842012

  • 54

    Wilkinson JSReid HArmstrong GR: Malignant transformation of a recurrent vestibular schwannoma. J Clin Pathol 57:1091102004

  • 55

    Yanamadala VWilliamson RWFusco DJEschbacher JWeisskopf PPorter RW: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. World Neurosurg 79:593.e1593.e82013

  • 56

    Zouari IBChtourou IGhariani MMakni SKhabir AGouiaa N: [Epithelioid schwannoma of the acoustic nerve: a case report.]. Ann Pathol 26:4504532006. (Fr)

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Carlson, Habermann, Glasgow, Link. Acquisition of data: Carlson, Jacob, Habermann, Glasgow, Raghunathan. Analysis and interpretation of data: all authors. Drafting the article: Carlson, Habermann, Glasgow, Raghunathan. Critically revising the article: Jacob, Glasgow, Link. Reviewed submitted version of manuscript: Carlson, Jacob, Glasgow, Raghunathan, Link. Approved the final version of the manuscript on behalf of all authors: Carlson. Statistical analysis: Carlson, Glasgow. Study supervision: Carlson.

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Article Information

INCLUDE WHEN CITING Published online January 8, 2016; DOI: 10.3171/2015.7.JNS151056.

Correspondence Matthew L. Carlson, Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. email: carlson.matthew@mayo.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Flow diagram outlining the search strategy for systematic review of the literature on the topic of MPNSTs of the eighth CN arising without prior irradiation.

  • View in gallery

    Pre- (left) and postcontrast (right) T1-weighted axial MR images demonstrating a 1.4-cm lesion (arrow) involving the left internal auditory canal and cerebellopontine angle typical for a VS.

  • View in gallery

    Photomicrographs from the case report. A: The histological sections show a cellular neoplasm, composed of areas showing elongated and spindle-shaped cells arranged as fascicles, merging with areas of epithelioid cells. H & E, original magnification ×100. B: The neoplastic cells show moderate cytological atypia, with nuclear pleomorphism, coarse chromatin, and prominent nucleoli. Mitotic activity is very brisk, with 3 mitotic figures (arrows) noted in this field alone. H & E, original magnification ×400. C and D: According to immunohistochemical analysis, there was diffuse and strong positive staining with S100 (C), and INI-1 expression was retained in the tumor cells (D). Original magnification ×100. Figure is available in color online only.

  • View in gallery

    Early postoperative MRI and PET CT. A and B: Fast imaging employing steady-state acquisition (A) and postcontrast fat-subtracted T1-weighted MRI (B) reveal GTR (arrows). C and D: Axial (C) and whole-body PET CT (D) reveals no evidence of residual or metastatic disease (arrows). Figure is available in color online only.

  • View in gallery

    Kaplan-Meier plot comparing disease-specific survival following GTR versus near-total resection (NTR) or STR of MPNSTs of the eighth CN arising without prior irradiation. Tick marks designate censored data.

References

  • 1

    Akamatsu YMurakami KWatanabe MJokura HTominaga T: Malignant peripheral nerve sheath tumor arising from benign vestibular schwannoma treated by gamma knife radiosurgery after two previous surgeries: a case report with surgical and pathological observations. World Neurosurg 73:7517542010

  • 2

    Bailet JWAbemayor EAndrews JCRowland JPFu YSDawson DE: Malignant nerve sheath tumors of the head and neck: a combined experience from two university hospitals. Laryngoscope 101:104410491991

  • 3

    Bari MEForster DMKemeny AAWalton LHardy DAnderson JR: Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature. Br J Neurosurg 16:2842892002

  • 4

    Benhaiem-Sigaux NRicolfi FKeravel YPoirier J: Epithelioid schwannoma of the acoustic nerve. Clin Neuropathol 15:2312331996

  • 5

    Best PV: Malignant triton tumour in the cerebellopontine angle. Report of a case. Acta Neuropathol 74:92961987

  • 6

    Cahan WGWoodard HQHiginbotham NLStewart FWColey BL: Sarcoma arising in irradiated bone: report of eleven cases. 1948 Cancer 82:8341998

  • 7

    Caporlingua FLapadula GAntonelli MMissori P: Pleomorphic rhabdomyosarcoma of the cerebellopontine angle in an adult: a review of literature. BMJ Case Rep 2014. bcr20132032572014

  • 8

    Carlson MLBabovic-Vuksanovic DMessiaen LScheithauer BWNeff BALink MJ: Radiation-induced rhabdomyosarcoma of the brainstem in a patient with neurofibromatosis type 2. J Neurosurg 112:81872010. (Erratum in J Neurosurg 112: 209 2010)

  • 9

    Chen LMao YChen HZhou LF: Diagnosis and management of intracranial malignant peripheral nerve sheath tumors. Neurosurgery 62:8258322008

  • 10

    Comey CHMcLaughlin MRJho HDMartinez AJLunsford LD: Death from a malignant cerebellopontine angle triton tumor despite stereotactic radiosurgery. Case report. J Neurosurg 89:6536581998

  • 11

    Demetriades AKSaunders NRose PFisher CRowe JTranter R: Malignant transformation of acoustic neuroma/vestibular schwannoma 10 years after gamma knife stereotactic radiosurgery. Skull Base 20:3813872010

  • 12

    Earls JPRobles HAMcAdams HPRao KC: General case of the day. Malignant melanotic schwannoma of the eighth cranial nerve. Radiographics 14:142514271994

  • 13

    Gong LLiu XYZhang WDHan XJYao LZhu SJ: A rare case of malignant triton tumor in the cerebellopontine angle. Diagn Pathol 7:432012

  • 14

    Gonzalez LFLekovic GPEschbacher JCoons SSpetzler RF: A true malignant schwannoma of the eighth cranial nerve: case report. Neurosurgery 61:E421E4222007

  • 15

    Gousias KBoström JKovacs ANiehusmann PWagner IKristof R: Factors of influence upon overall survival in the treatment of intracranial MPNSTs. Review of the literature and report of a case. Radiat Oncol 5:1142010

  • 16

    Gruber BPetchenik LWilliams MThomas CLuken MG: Malignant vestibular schwannoma. Skull Base Surg 4:2272311994

  • 17

    Guccion JGEnzinger FM: Malignant Schwannoma associated with von Recklinghausen's neurofibromatosis. Virchows Arch A Pathol Anat Histol 383:43571979

  • 18

    Han DHKim DGChi JGPark SHJung HWKim YG: Malignant triton tumor of the acoustic nerve. Case report. J Neurosurg 76:8748771992

  • 19

    Hanabusa KMorikawa AMurata TTaki W: Acoustic neuroma with malignant transformation. Case report. J Neurosurg 95:5185212001

  • 20

    Harada KNishizaki TAdachi NSuzuki MIto H: Pediatric acoustic schwannoma showing rapid regrowth with high proliferative activity. Childs Nerv Syst 16:1341372000

  • 21

    Hasegawa TKida YKato TIizuka HKuramitsu SYamamoto T: Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery. J Neurosurg 118:5575652013

  • 22

    Hernanz-Schulman MWelch KStrand ROrdia JI: Acoustic neuromas in children. AJNR Am J Neuroradiol 7:5195211986

  • 23

    Higami YShimokawa IKishikawa MOkimoto TOhtani HTomita M: Malignant peripheral nerve sheath tumors developing multifocally in the central nervous system in a patient with neurofibromatosis type 2. Clin Neuropathol 17:1151201998

  • 24

    Hong WCheng HWang XHu XFeng C: Study of malignant peripheral nerve sheath tumor in cerebellopontine angle. J Craniofac Surg 25:6997012014

  • 25

    Karami KJKelkar PSVerdon MPGrills ISBojrab DIPieper DR: Malignant peripheral nerve sheath tumor of the vestibulocochlear nerve and brainstem: multimodality treatment with survival of 27 months. A case report and review of the literature. Neurosurgery 69:E1152E11652011

  • 26

    Kroh HMatyja EMarchel A: Epithelioid schwannomas of the acoustic nerve. Folia Neuropathol 38:23272000

  • 27

    Kubo OChernov MIzawa MHayashi MMuragaki YMaruyama T: Malignant progression of benign brain tumors after gamma knife radiosurgery: is it really caused by irradiation?. Minim Invasive Neurosurg 48:3343392005

  • 28

    Kudo MMatsumoto MTerao H: Malignant nerve sheath tumor of acoustic nerve. Arch Pathol Lab Med 107:2932971983

  • 29

    Kuzmik GAMichaelides EMChiang VLNonaka YFukushima TVortmeyer AO: Rapidly progressive epithelioid malignant peripheral nerve sheath tumor of the vestibular nerve. Otol Neurotol 34:173917422013

  • 30

    L'heureux-Lebeau BSaliba I: Updates on the diagnosis and treatment of intracranial nerve malignant peripheral nerve sheath tumors. Onco Targets Ther 6:4594702013

  • 31

    Maeda MJozaki TBaba SMuro HShirasawa HIchihashi T: Malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve. Acta Pathol Jpn 43:1982031993

  • 32

    Maire JPHuchet AMilbeo YDarrouzet VCausse NCélérier D: Twenty years' experience in the treatment of acoustic neuromas with fractionated radiotherapy: a review of 45 cases. Int J Radiat Oncol Biol Phys 66:1701782006

  • 33

    Markou KEimer SPerret CHuchet AGoudakos JLiguoro D: Unique case of malignant transformation of a vestibular schwannoma after fractionated radiotherapy. Am J Otolaryngol 33:1681732012

  • 34

    Matsumoto MSakata YSanpei KOnagi ATerao HKudo M: [Malignant schwannoma of acoustic nerve: a case report.]. No Shinkei Geka 18:59621990. (Jpn)

  • 35

    McLean CALaidlaw JDBrownbill DSGonzales MF: Recurrence of acoustic neurilemoma as a malignant spindle-cell neoplasm. Case report. J Neurosurg 73:9469501990

  • 36

    Miller RTSarikaya HSos A: Melanotic schwannoma of the acoustic nerve. Arch Pathol Lab Med 110:1531541986

  • 37

    Mrak REFlanigan SCollins CL: Malignant acoustic schwannoma. Arch Pathol Lab Med 118:5575611994

  • 38

    Nicolli EARuckenstein M: What is the risk of malignant transformation of vestibular schwannoma following radiosurgery?. Laryngoscope 125:176117622015

  • 39

    Norén G: Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg 70:Suppl 165731998

  • 40

    Patel TRChiang VL: Secondary neoplasms after stereotactic radiosurgery. World Neurosurg 81:5945992014

  • 41

    Puataweepong PJanwityanujit TLarbcharoensub NDhanachai M: Radiation-induced peripheral malignant nerve sheath tumor arising from vestibular schwannoma after Linac-based stereotactic radiation therapy: a case report and review of literatures. Case Rep Med 2012:6481912012

  • 42

    Rodriguez FJFolpe ALGiannini CPerry A: Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 123:2953192012

  • 43

    Saito TOki SMikami TKawamoto YYamaguchi SKuwamoto K: [Malignant peripheral nerve sheath tumor with divergent cartilage differentiation from the acoustic nerve: case report.]. No To Shinkei 52:7347392000. (Jpn)

  • 44

    Scheithauer BWErdogan SRodriguez FJBurger PCWoodruff JMKros JM: Malignant peripheral nerve sheath tumors of cranial nerves and intracranial contents: a clinicopathologic study of 17 cases. Am J Surg Pathol 33:3253382009

  • 45

    Schmitt WRCarlson MLGiannini CDriscoll CLLink MJ: Radiation-induced sarcoma in a large vestibular schwannoma following stereotactic radiosurgery: case report. Neurosurgery 68:E840E8462011

  • 46

    Seferis CTorrens MParaskevopoulou CPsichidis G: Malignant transformation in vestibular schwannoma: report of a single case, literature search, and debate. J Neurosurg 121:Suppl1601662014

  • 47

    Shin MUeki KKurita HKirino T: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. Lancet 360:3093102002

  • 48

    Son EIKim IMKim SP: Vestibular schwannoma with malignant transformation: a case report. J Korean Med Sci 16:8178212001

  • 49

    Stangerup SECaye-Thomasen P: Epidemiology and natural history of vestibular schwannomas. Otolaryngol Clin North Am 45:257268vii2012

  • 50

    Suresh TNMahadevan AChandrashekhar Sagar BSantosh VYasha TCShankar SK: Unusual case of multiple cellular and malignant schwannomas of the cranial and spinal nerves. Clin Neuropathol 22:23292003

  • 51

    Tan TCLam PW: Epithelioid schwannoma of the vestibular nerve. Singapore Med J 45:3933962004

  • 52

    Tanbouzi Husseini SPiccirillo ETaibah APaties CTRizzoli RSanna M: Malignancy in vestibular schwannoma after stereotactic radiotherapy: a case report and review of the literature. Laryngoscope 121:9239282011

  • 53

    Wei CHeman-Ackah SENewman KZagzag DGolfinos JGRoland JT Jr: Temporal bone histopathology case of the month: Malignant peripheral nerve sheath tumor arising within vestibular schwannoma. Otol Neurotol 33:e83e842012

  • 54

    Wilkinson JSReid HArmstrong GR: Malignant transformation of a recurrent vestibular schwannoma. J Clin Pathol 57:1091102004

  • 55

    Yanamadala VWilliamson RWFusco DJEschbacher JWeisskopf PPorter RW: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. World Neurosurg 79:593.e1593.e82013

  • 56

    Zouari IBChtourou IGhariani MMakni SKhabir AGouiaa N: [Epithelioid schwannoma of the acoustic nerve: a case report.]. Ann Pathol 26:4504532006. (Fr)

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