Intraparotid Facial Nerve Schwannoma in a Nine-Year-Old Patient: Diagnosis, Classification, and Surgical Approach Stages.

Intraparotid facial nerve schwannoma (IFNS) is rarely observed in children compared with adults. Only a few cases have been reported in the literature. After radiological imaging and fine needle aspiration biopsy, an IFNS diagnosis may be skipped and confused with pleomorphic adenoma, which has a high prevalence among patients who have a mass in the parotid gland. The probability of IFNS can be recognized by a close relation between the mass and the facial nerve during the application of parotidectomy and by the frozen biopsy of the mass. The surgeon evaluates the mass and faces with surgical mass excison and facial nerve reconstruction according to the relation between the mass and the facial nerve because there is no diagnostic method for the presurgery diagnosis of IFNS. Therefore, the surgeon should be prepared for the possibility of functional lossin the facial nerve during parotidectomy. This article presents the case of a 9-year-old patient with an IFNS diagnosis who had a surgical operation in our clinic, and the algorithm designed according to the literature for the diagnosis and surgical classification of IFNS, as well as the approaches to facial nerve reconstruction.

Sporadic Schwannomatosis: A Systematic Review Following the 2005 Consensus Statement.

AIMS: To identify the frequency of reports of sporadic schwannomatosis, the types of patients affected, and the nerves affected. PATIENTS AND METHODS: We identified all case reports and case series that reported on patients with sporadic schwannomatosis according to established criteria. RESULTS: The initial search yielded 1,597 studies, of which 15 were included. A total of 38 of 55 individuals met the inclusion criteria. The mean age of the patients was 48 years; 41% were male. Thirty-three patients had peripheral nerve tumors, and 17 had spinal tumors. Twelve had tumors in both locations. Tumor distribution was unilateral in 25 of 30 cases (83.3%) and segmental (limited to one limb or five or fewer contiguous segments of the spine) in 28 of 38 cases (73.7%). CONCLUSION: This systematic review quantified the number of individuals who meet the criteria for sporadic schwannomatosis and better described this population to facilitate the classification of neurofibromatosis in regard to the 2005 consensus statement. Unilateral or segmental distribution of nerve tumors are key aspects when dealing with multiple noncutaneous schwannomas without involvement of the vestibular nerve.

Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview.

Patients with neurofibromatosis 1 (NF1) develop multiple neurofibromas, with 8% to 15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, after a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant transformation of neurofibromas. Nuclear atypia alone is generally insignificant. However, with atypia, loss of neurofibroma architecture, high cellularity, and/or mitotic activity >1/50 but <3/10 high-power fields, the findings are worrisome for malignancy. We propose the term "atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)" for lesions displaying at least 2 of these features. This diagnosis should prompt additional sampling, clinical correlation, and possibly, expert pathology consultation. Currently, such tumors are diagnosed inconsistently as atypical neurofibroma or low-grade MPNST. Most MPNSTs arising from neurofibromas are high-grade sarcomas and pose little diagnostic difficulty, although rare nonnecrotic tumors with 3-9 mitoses/10 high-power fields can be recognized as low-grade variants. Although neurofibromas contain numerous S100 protein/SOX10-positive Schwann cells and CD34-positive fibroblasts, both components are reduced or absent in MPNST. Loss of p16/CDKN2A expression, elevated Ki67 labeling, and extensive nuclear p53 positivity are also features of MPNST that can to some degree already occur in atypical neurofibromatous neoplasms of uncertain biologic potential. Complete loss of trimethylated histone 3 lysine 27 expression is potentially more reliable, being immunohistochemically detectable in about half of MPNSTs. Correlated clinicopathological, radiologic, and genetic studies should increase our understanding of malignant transformation in neurofibromas, hopefully improving diagnosis and treatment soon.

[Maxillary trigeminal schwannoma. Presentation of a case and review of literature]. / Schwannoma trigeminal maxilar. Presentación de un caso y revisión de la literatura.

INTRODUCTION: Schwannomas are benign tumours that are relatively common in the head, however the involvement of the sinunasal region is rare and there are only 5 cases reported in the maxilla in current literature, representing less than 1% of bone tumours. CLINICAL CASE: We report the case of a woman with a right maxillary schwannoma who underwent a complete resection of the lesion. Emphasis is placed on the rarity of the lesion in terms of its location and includes a review of clinical behaviour, diagnosis and current treatment options. CONCLUSIONS: Maxillary trigeminal schwannoma must be suspected if vague sinunasal symptoms, paranasal mass or, as in this case, trigeminal neuralgia present. Surgical treatment is indicated, and approaches vary according to location and tumour size.

Methylation-based classification of benign and malignant peripheral nerve sheath tumors.

The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss of H3K27me3 was exclusively seen in MPNST of the main methylation cluster, which defines it as an additional useful marker for the differentiation of cellular schwannoma and MPNST.

Clinical and radiological guidance in managing facial nerve schwannomas.

OBJECTIVE: To present a review of all patients diagnosed with a facial nerve schwannoma (FNS) managed in our center over almost two decades, and suggest guidelines for their classification and management. STUDY DESIGN: Retrospective case review SETTING: Tertiary referral center PATIENTS: Twenty-eight patients with a facial nerve schwannoma INTERVENTION: Conservative or surgical management depending on clinical and radiological features MAIN OUTCOME MEASURE: Patient demographics, site of tumor, and clinical symptoms, including facial nerve function (House-Brackmann score) at baseline and follow-up. In those managed surgically, operative approach and surgical outcomes were also recorded. RESULTS: Of 28 patients, 16 were male. Mean age at presentation was 46 years. The majority presented with either facial weakness or hearing loss. The internal auditory canal segment of the facial nerve was the most commonly affected (19/28, 68%). Multi-segmental lesions were found in almost half (46%) of patients. Facial weakness was most commonly associated with involvement of the labyrinthine segment (89%). Overall, 16 (57%) patients were managed surgically. CONCLUSION: FNS may be difficult to distinguish on both clinical and imaging grounds from other cerebellopontine pathologies on the basis of audiovestibular symptoms alone. The presence of facial weakness in combination with imaging findings suggestive of FNS is highly suggestive for FNS. In patients with brainstem compression, rapid tumor growth, or House-Brackmann greater than 4, we suggest a surgical approach based on preoperative audiovestibular status, helping optimize long-term facial function and minimize morbidity. Facial nerve reanimation at the time of primary surgery is preferred.

Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles.

Melanotic tumors of the nervous system show overlapping histological characteristics but differ substantially in their biological behavior. In order to achieve a better delineation of such tumors, we performed an in-depth molecular characterization. Eighteen melanocytomas, 12 melanomas, and 14 melanotic and 14 conventional schwannomas (control group) were investigated for methylome patterns (450k array), gene mutations associated with melanotic tumors and copy number variants (CNVs). The methylome fingerprints assigned tumors to entity-specific groups. Methylation groups also showed a substantial overlap with histology-based diagnosis suggesting that they represent true biological entities. On the molecular level, melanotic schwannomas were characterized by a complex karyotype with recurrent monosomy of chromosome 22q and variable whole chromosomal gains and recurrent losses commonly involving chromosomes 1, 17p and 21. Melanocytomas carried GNAQ/11 mutations and presented with CNV involving chromosomes 3 and 6. Melanomas were frequently mutated in the TERT promoter, harbored additional oncogene mutations and showed recurrent chromosomal losses involving chromosomes 9, 10 and 6q, as well as gains of 22q. Together, melanotic nervous system tumors have several distinct mutational and chromosomal alterations and can reliably be distinguished by methylome profiling.

[Mesenchymal gastric tumor--not always GIST]. / Mesenchymaler Magentumor--nicht immer GIST.

The correct histopathological classification of a gastric mesenchymal tumor as a schwannoma is essential because in contrast to gastrointestinal stromal tumors (GIST) it is a definitive benign neoplasm which can be sufficiently treated by in sano (R0) resection. A (partial) gastrectomy is unnecessary. A clear radiological or sonographical differentiation between a schwannoma and GIST is not possible. The histomorphological and immunohistochemical features of this tumor entity are described.

Schwannomas and their pathogenesis.

Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney's complex. Schwannomas have a variety of morphological appearances, but they behave as World Health Organization (WHO) grade I tumors, and only very rarely undergo malignant transformation. Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. The genetic pathways and morphological features of schwannomas associated with different genetic syndromes will be discussed. Merlin has multiple functions, including within the nucleus and at the cell membrane, and this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention.

Dumbbell-shaped abducens schwannoma: case report.

Schwannomas of the abducens nerve are uncommon. Nineteen cases have been reported in the literature and are classified into two types: Type 1, in the cavernous sinus, and Type 2, in the prepontine area. However, a dumbbell-shaped type has not yet been reported. Here we report the first case of a dumbbell-shaped abducens schwannoma and classify this type into a new category (Type 3). A 36-year-old woman presented with left hearing disturbance for 4 years, dizziness for 2 years, and dysphagia for 6 months. Neurological examination showed left sensorineural hearing impairment, hypesthesia in the distribution of the left first and second branches of the trigeminal nerve, left curtain sign, and gait disturbance. Computed tomography and magnetic resonance imaging revealed a dumbbell-shaped tumor located in the cavernous sinus that extended to the right cerebellopontine angle. She underwent a two-staged operation; the first operation was via ananterior transpetrosal approach for the lesion in the middle fossa and the upper part in the posterior fossa, and the second surgery was via alateral suboccipital approach for the lower part in the posterior fossa. In the first operation, the abducens nerve was sacrificed. Histological examination confirmed schwannoma. Postoperatively, hearing disturbance and ataxia were improved and complete abducens nerve paresis appeared. The dumbbell-shaped abducens schwannoma has novel clinical features, difficulty of sixth nerve preservation, and unique surgical approach.

Malignant melanotic schwannian tumor: a clinicopathologic, immunohistochemical, and gene expression profiling study of 40 cases, with a proposal for the reclassification of "melanotic schwannoma".

Melanotic schwannomas (MSs), variably associated with the Carney complex, are rare tumors that usually involve spinal nerve roots but may occur in other locations. Clinicopathologic evaluation poorly predicts the behavior of MS. Fewer than 200 cases have been reported. We report a series of 40 well-characterized MSs, one of the largest series to date. The tumors were comprehensively evaluated, and clinical follow-up was obtained. Immunohistochemistry for S100 protein, Melan-A, HMB45, tyrosinase, glial fibrillary acidic protein (GFAP), EMA, SMARCB1, Ki-67 antigen, ASMTL, and the Carney complex-associated PRKAR1A gene product was performed using commercially available antibodies and the Ventana Ultraview detection system. Gene microarray study was conducted on formalin-fixed, paraffin-embedded blocks from 10 MSs and the results compared with previous data from melanoma and schwannoma. Differentially expressed genes were selected at >3-fold and P<0.001. The Fisher exact test was used for statistical analysis. The tumors occurred in 18 male and 22 female patients (mean age 41 y; range, 11 to 84 y) and involved the paravertebral nerve roots (N=31), mediastinum (N=3), sacrum, cauda equina, para-aortic region, fifth cranial nerve, buttock, and cerebellum (N=1 each). Two patients had known Carney complex, and 1 patient also had a cutaneous myxoma, suggestive of Carney complex. The tumors expressed S100 protein (21/25, 84%), Melan-A (23/25, 92%), HMB45 (25/25, 100%), tyrosinase (25/25, 100%), GFAP (0/24, 0%), EMA (0/9, 0%), SMARCB1 (retained in 25/25, 100%), and ASMTL (5/19, 26%); PRKAR1A expression was lost in 7/20 cases (35%). Ki-67-labeling index was <5% in 23/25 cases (92%) and 5% to 10% in 2/25 cases (8%). Gene expression profiling showed significant differences between MS, melanoma, and conventional schwannoma. Clinical follow-up (26/40, 65%; mean 55 mo; range, 1 to 300 mo) showed local recurrences in 9/26 (35%) and metastases in 11/26 (44%) patients. Fourteen patients were alive without disease, 5 were alive with disease, and 7 had died of disease. Only a mitotic rate >2/10 HPF correlated with metastases (P=0.008). The clinicopathologic features of tumors with and without psammoma bodies were identical. We conclude that MSs are distinctive malignant tumors, rather than benign neoplasms with occasionally unpredictable behavior, and propose their reclassification as "malignant melanotic schwannian tumors." Loss of PRKAR1A expression suggests a link to Carney complex, even when this history is absent.

[Airway granular cell tumor].

The paper describes the clinical, morphological, and immunohistochemical characteristics of 13 granular cell tumors of the upper airway. These tumors are shown to have virtually the same histological and immunohistochemical features as granular cell tumors at another site. The histogenesis of these tumors is discussed. There are currently a number of more or less solid grounds for considering them as neurogenic tumors to be close to schwannomas. At the same time one cannot ignore the fact that there is morphological and immunohistochemical evidence for that the granular cell tumors have rather cytotypical than histotypical properties, which cannot implicitly assign them to nerve tissue tumors. Most likely, the granular cell tumors belong to a histogenetically heterogeneous mixed group, in this connection their place in the classification of tumors needs further investigation, by applying the criteria developed by Russian histologists and oncomorphologists.

Hybrid schwannoma/perineurioma: report of 10 Chinese cases supporting a distinctive entity.

Hybrid schwannoma/perineurioma is a recently described benign nerve sheath tumor that typically manifests as a dermal tumor on the extremities and trunk. Occurrence outside the skin is uncommon. This article describes 10 cases of hybrid schwannoma/perineurioma arising in diverse anatomic locations. They all occurred in adult patients (age range 27-81 years, median 35 years) with a marked female predominance (2 males and 8 females). Of the 10 tumors, 7 were situated in the subcutis of trunk (n = 3), extremities (n = 2), neck (n = 1), and labium majus (n = 1) and 3 in the submucosa of nasal cavity, sigmoid colon, and rectum, respectively. Histologically, they were composed of intimately admixed plump spindle cells and elongated slender spindle cells forming storiform, lamellar or fascicular architecture. By immunohistochemistry, the tumor showed dual differentiation of schwannian cells (plump-spindled) and perineurial cells (slender-spindled), characterized by strong S100 protein expression in the former component and variable immunoreactivity of epithelial membrane antigen, claudin-1, and CD34 in the latter. Awareness of its morphological characteristics and potential occurrence in diverse sites may aid in the recognition of this rare tumor type.

Schwanoma retroperitoneal de localización pelviana: reporte de un caso / Benign retroperitoneal schwannoma of pelvic location: case report

Se reporta un caso de schwanoma benigno de localización retroperitoneal, pelviana, en una paciente de 38 años de edad que consultó por dolor pelviano inespecífico de un mes de evolución, derivada a nuestra institución con el diagnóstico de blastoma anexial derecho para confirmación de su diagnóstico y tratamiento. Se efectuaron ecografía transvaginal, tomografía computada, y resonancia magnética diagnosticándose un tumor no ginecológico de origen retroperitoneal cuya anatomía patológica determinó el diagnóstico de schwanoma benigno.

Schwanoma retroperitoneal de localización pelviana: reporte de un caso / Benign retroperitoneal schwannoma of pelvic location: case report

Se reporta un caso de schwanoma benigno de localización retroperitoneal, pelviana, en una paciente de 38 años de edad que consultó por dolor pelviano inespecífico de un mes de evolución, derivada a nuestra institución con el diagnóstico de blastoma anexial derecho para confirmación de su diagnóstico y tratamiento. Se efectuaron ecografía transvaginal, tomografía computada, y resonancia magnética diagnosticándose un tumor no ginecológico de origen retroperitoneal cuya anatomía patológica determinó el diagnóstico de schwanoma benigno.(AU)

Natural history of intradural-extramedullary spinal cord tumors.

The objective of the present study was to investigate the natural history of intradural-extramedullary spinal cord tumors. Nine cases of intradural-extramedullary tumors were observed over the 2 years. The physical and magnetic resonance imaging (MRI) examination were performed in the first examination and every other year. Tumors were classified as the schwannoma type and the meningioma type based on the MRI findings. The tumor volume was calculated by the craniocaudal length on a sagittal image and maximum transverse diameter on an axial image of MRI, every year. The annual growth rate, which was defined as the change in the volume each year compared to the volume of the previous year, was examined. There were six cases in the schwannoma type and three cases in the meningioma type. The schwannoma type tumors presented several growth patterns: unchanging, continuous slight growth, and initial slight growth followed by rapid growth during the observation period (6.7 ± 2.7 years), while the meningioma type tumors presented the continuous growth pattern during the observation period (4.3 ± 2.5 years). The average annual growth rate was 2.3 ± 5.5% in the schwannoma type and 7.0 ± 8.5% in the meningioma type. Schwannoma type tumors showed relatively less change in their size and would be observed for a longer time.

Intralabyrinthine schwannomas: imaging diagnosis and classification.

BACKGROUND AND PURPOSE: ILS is a rare lesion that has a different management from the more common "acoustic" schwannoma. To date, only 137 cases have been reported. We present a classification scheme based on labyrinthine anatomy to describe and localize these lesions. Treatment and prognosis hinge on the appropriate localization of these tumors; thus, a concise terminology that can be used by both the otolaryngologist and radiology communities is desirable. MATERIALS AND METHODS: After approval of the institutional review board, a retrospective study of all patients with the diagnosis of ILS imaged between 1996 and 2010 was performed. Clinical and imaging data were collected. Patients were imaged with thin-section high-resolution T2 and contrast-enhanced MR imaging. RESULTS: There were 45 patients with a diagnosis of ILS. Forty-three had complete histories. There were 18 male and 25 female patients with an age range of 21-78 years with a mean age of 53 years. The most common presenting symptom was progressive sensorineural hearing loss. Lesions were characterized on the basis of their location. Intracochlear was most common (14/45) followed by transmodiolar (13/45), intravestibular (7/45), vestibulocochlear (5/45), transmacular (4/45), and transotic (2/45). Sixteen patients underwent surgical resection. The remaining patients were followed clinically and by serial MR imaging. CONCLUSIONS: ILS is an uncommon but under-reported tumor. We characterized the MR imaging appearance of these tumors by using high-resolution techniques. In addition, an anatomically based classification system is presented that will help the radiologist accurately describe ILS within the inner ear and help the surgeon determine which tumors are potential surgical candidates.

Triple dumbbell-shaped jugular foramen schwannomas.

PURPOSE: Triple dumbbell-shaped jugular foremen schwannomas (DSJFSs) have high cervical extension according to Bulsara's classification. One-stage, single-discipline, total removal of triple DSJFSs is not always possible due to their both intracranial and cervical extensions. We evaluated our experience in one-stage resection of triple DSJFSs by using a combined neurosurgical and head and neck approach. METHODS: Between October 2004 and May 2009, eight patients with triple DSJFSs were treated surgically at our institute. The clinical and radiological features, operative procedures and outcomes are retrospectively reviewed. RESULTS: Total tumour removal was achieved in seven patients and near total in one. New cranial nerve (CN) paresis occurred after surgery in one patient and worsening of preoperative CN deficits was noted in three. Two patients experienced cerebrospinal fluid leakage and one of them had a repeated operation with closure of the dural deficit. Follow-up period ranged from 23 to 60 months (mean 38 months). All CN dysfunction had improved considerably at the last follow-up examination. There have been no clinical or radiological signs of tumour recurrence. CONCLUSIONS: One-stage total resection of triple DSJFSs can be achieved by a multidisciplinary cranial base team composed of neurosurgeons and head and neck surgeons via a craniocervical approach.

Simultaneously occurring tumours within the same cerebello-pontine angle: refining literature definitions and proposal for classification.

We report on an unusual case of a patient, not affected by neurofibromatosis, harbouring two radiologically spatially contiguous tumours within the same cerebello-pontine angle. Pathological findings were consistent with the diagnosis of two spatially distinct primary tumours, namely a meningioma and a schwannoma. We proposed a classification of tumours occurring at the same location consistent with the different spatial arrangement and histological nature of these conditions. The correct classification of these nosological entities will allow further more accurate evaluations of these cases in order to clarify the pathogenesis, prognosis and best treatment of each one.