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Ancient schwannoma (AS) is a subtype of schwannoma characterized by slow progression despite degenerative changes in pathology. Although it is considered a benign tumor, most previous reports have focused on extracranial AS; therefore, the clinical characteristics of intracranial AS is not clear. We included 174 patients who underwent surgery for sporadic intracranial schwannoma, and 13 patients (7.5%) were diagnosed with AS. Cysts were significantly more common in patients with AS than conventional schwannomas (92.3% vs. 44.7%, p < 0.001), as was bleeding (38.5% vs. 6.9%, p = 0.003) and calcification (15.4% vs. 1.3%, p = 0.029). The maximum tumor diameter was also larger in patients with AS (35 mm vs. 29 mm, p = 0.017). The median duration from symptom onset to surgery (7.0 vs. 12.5 months, p = 0.740) did not significantly differ between groups, nor did the probability of postoperative recurrence (p = 0.949). Intracranial AS was strongly associated with cyst formation and exhibited a benign clinical course with a lower rate of recurrence and need for salvage treatment. Extracranial AS is reportedly characterized by a slow progression through a long-term clinical course, whereas intracranial AS did not progress slowly in our study and exhibited different clinical features to those reported for extracranial AS., (© 2024. The Author(s).)

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.

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., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

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., (Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.)

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., (Published by Elsevier Inc.)

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.

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 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., (© 2014 International Society of Neuropathology.)

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 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., (© 2014 International Society of Neuropathology.)

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.

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.

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 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.

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.

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., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

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.

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.

Study Design: A retrospective study of a new classification and surgical approach of cervical dumbbell tumors., Objective: To evaluate PUTH classification., Summary of Background Data: The high recurrence rate and postoperative deformity are unsolved problems. Asazuma's landmark classification could not cover all cases and could not provide clear suggestion for the surgical approach. The ideal classification should be comprehensive, easily understood and of practical value., Methods: PUTH classification for cervical dumbbell tumors includes 7 categories (types 1-7) and 2 foraminal modifiers. Posterior approach is appropriate for type 1, 2 and 5 tumors, anterior and anterolateral approach is an ideal choice for type 4 and 6 tumors. Type 7 tumors need combined anterior and posterior approach., Results: Forty-four consecutive patients with cervical dumbbell tumor were surgically treated. The pathology included schwannoma in 31 cases, neurofibroma in 9 and ganglioneuroma in 4. Based on PUTH classification, type 3 was diagnosed in 13 cases, type 5 in 17, type 6 in 8, and type 7 in 6. Tumors were unilateral in 41 cases, and bilateral in 3 cases. Five were tumor revision cases. Thirty patients underwent posterior approach, 7 had anterior approach, 1 had anterolateral approach, and 6 had combined approach. Gross total resection was achieved in all the patients. Tumors involved nerve roots were transected in 12 cases. Single vertebral artery was ligated in 3. The complications included cerebrospinal fluid leakage in 18 cases, esophagus injury in 1, Horner syndrome in 1, dysphagia in 2, dyspnea in 1 and deep infection in 1. Thirty-six cases (81.1%) had an average 61-month follow-up. Recurrence was found in only one case (2.8%)., Conclusion: PUTH classification covers all tumor types and is easier to remember. It is practical and useful for determining the surgical approach. The recurrence rate decreases significantly after radial tumor resection. Revision surgeries are associated with more complications.

Schwannoma is a well-described, benign nerve sheath tumor of the soft tissue, but is rare in the gastrointestinal tract. Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions. In this report, we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts. Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein. To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes, it is better to use the designation "mucosal Schwann hamartoma".

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

Objectives: To review the literature on glossopharyngeal schwannomas with a focus on clinical presentation, radiologic/audiologic characteristics, and management options, and to propose a mechanism explaining the nature of vestibulocochlear dysfunction seen with these tumors., Study Design: Contemporary review., Methods: English literature search for cases of primary isolated glossopharyngeal schwannomas and chart review of two new cases., Results: A total of 42 glossopharyngeal schwannoma cases between 1908-2008 were reviewed. Of these 84% presented with vestibulocochlear symptoms whereas only 30% presented with glossopharyngeal symptoms. Tumors can occur anywhere along the CNIX; however, the majority of symptomatic cases are intracranial/intraosseous, which present with vestibulocochlear dysfunction. Reviewed cases typically described the caliber of CNVII and VIII on CT/MRI as normal. We present a case where notching and displacement of CNVIII by the tumor can be appreciated on MRI, allowing for the first correlation between clinical symptoms and imaging findings. Mid frequency SNHL was prevalent in contrast to the high-frequency pattern typical of vestibular schwannomas. Tonotopic studies of CNVIII mapped low-to-mid frequency fibers along the posterior medial surface corresponding to the area of greatest compression by glossopharyngeal schwannomas., Conclusion: Glossopharyngeal schwannomas usually present with vestibulocochlear rather than glossopharyngeal symptoms, likely due to CNVIII compression and displacement by tumor, which can be better appreciated with modern imaging. The tumor's location posterior and medial to CNVIII combined with the complex CNVIII tonotopic organization may account for the preferential mid-frequency hearing loss seen in these patients.

Object: Due to the proximity and involvement of critical neurovascular structures, the resection of jugular foramen schwannomas can pose a formidable challenge. The authors review their experience in the microsurgical management of jugular foramen schwannomas and propose a modified grading scale to guide surgical management., Methods: All jugular foramen schwannoma cases treated by the senior author (T.F.) between 1980 and 2004 were retrospectively reviewed. The average age at presentation, surgical approach, tumor characteristics, cranial nerve (CN) deficits, and tumor recurrence rates were assessed. The authors present the following modified grading scale: Type A, intradural tumors; Type B, dumbbell-shaped tumors; and Type C, triple dumbbell tumors with a high cervical extension., Results: The authors treated jugular foramen tumors in 129 patients during the study period. Of these, 53 patients (41%) had jugular foramen schwannomas. The mean patient age was 52 years (range 14-74 years); there were 12 male and 41 female patients. The mean follow-up period was 8.4 years. Patients presented most commonly with deficits of the vagus nerve, followed by vestibular/cochlear nerve and glossopharyngeal nerve deficits. Gross-total resection of the tumor was achieved in 48 patients (90.5%). New postoperative paresis in a previously normal CN was not seen; however, worsening of preoperative CN deficits was frequently noted. The highest incidence occurred with the glossopharyngeal and vagus nerves (30%), with 26% of the deficits being permanent. There were no deaths related to surgery in this series. Three patients (5.7%) experienced tumor recurrence., Conclusions: The microsurgical resection of jugular foramen schwannomas carries a risk of worsening preoperative CN deficits; however, these are often transient. Based on their experience, the authors have formulated a grading scale that predicts the optimal surgical approach to these lesions. Considerable technical training and microneuroanatomical knowledge of the region is required. The modified grading scale presented facilitates preoperative planning.

Latent class models provide a useful framework for clustering observations based on several features. Application of latent class methodology to correlated, high-dimensional ordinal data poses many challenges. Unconstrained analyses may not result in an estimable model. Thus, information contained in ordinal variables may not be fully exploited by researchers. We develop a penalized latent class model to facilitate analysis of high-dimensional ordinal data. By stabilizing maximum likelihood estimation, we are able to fit an ordinal latent class model that would otherwise not be identifiable without application of strict constraints. We illustrate our methodology in a study of schwannoma, a peripheral nerve sheath tumor, that included 3 clinical subtypes and 23 ordinal histological measures.

Microarray gene expression profiling is a high throughput system recently used in basic and applied research. It provides a large amount of data -at molecular level- that once acquired, must be functionally integrated in order to find common patterns within a defined group of biological samples. In addition to identification of differentially expressed genes and the establishment of gene regulation patterns, microarrays may also allow us to discover new tumor markers that could have a great impact on the improvement of clinical practice and therapeutics for cancer. The classification method used for cancer is currently based on the morphological characteristics of the biological samples. The information obtained with this method is limited, omitting many important tumor characteristics like the proliferation rate, the capacity of invasion and metastases, as well as the possible development of mechanisms of cellular resistance to treatment. Microarrays can be used in combination with conventional diagnostics as a helpful complement. In this review we focus on how this technology has contributed to our knowledge of the molecular pathogenesis of meningiomas and schwannomas, its potential role as a useful tool for tumor classification and its application in clinical practice.

Objective: The aim of this review was to assess and describe the pathological characteristics of intraparotid facial nerve schwannoma, in order to facilitate correct prognostic evaluation and appropriate therapeutic decision making., Study Design and Setting: The literature was reviewed regarding involvement of the various portions of the facial nerve. A classification is proposed, based on anatomical and pathological evaluations, which can supply important information on facial functional outcomes., Results: From this study, two important characteristics of facial nerve schwannoma emerged: the schwannoma may be capable of surgical dissection from the facial nerve, leaving the latter anatomically preserved; or it may be tightly bound to the nerve, in which case it must be removed along with a variable section of nerve tract, followed by reconstruction., Conclusions: The extent of the neoplasm and the involvement of different branches of the facial nerve are very important elements to consider when evaluating prognosis and therapy., Significance: To emphasise the usefulness of a classification, based on anatomical and pathological evaluation, which can supply information about post-operative facial function.

The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

Schwannoma accounts for one of the most common benign mesenchymal neoplasms of soft tissues. Although it is well defined in the cytology literature, particular histologic subtypes such as "ancient," cellular and epithelioid variants could be a source of diagnostic difficulties. We have reviewed cytology aspirates and corresponding histologic sections from 34 schwannomas diagnosed at Institut Curie. Histologically, 24 cases were classic, 5 were "ancient," 4 were cellular, and 1 was epithelioid schwannomas. No example of melanotic schwannoma was recorded. Original cytologic diagnosis was schwannoma in 13 (38.2%) cases, benign soft tissue tumor in 11 (32.4%), pleomorphic adenoma in 2 (6%) cases, angioma in 1 (2.9%) case, nodular fasciitis in 1 (2.9%) case, suspicious in 3 (8.8%) cases, and not satisfactory in 3 (8.8%) cases. There were no major differences between classical, "ancient," cellular, and epithelioid variants on cytology smears. Myxoid stroma, mast cells, and intranuclear inclusions were limited to classical subtype. Similarly, cyto-nuclear atypia was more frequent in classical subtype than in other subtypes. Schwannoma should be differentiated from well-differentiated malignant peripheral nerve sheath tumor, neurofibroma, and pleomorphic adenoma, in the last instance particularly for head and neck lesions., ((c) 2006 Wiley-Liss, Inc.)

Gene therapy for schwannomas was evaluated in two mouse models of neurofibromatosis type 2 (NF2): (1) a transgenic model in which mice express a dominant mutant form of merlin and spontaneously develop schwannomas, and (2) a xenograft model in which human schwannoma tissue is implanted subcutaneously into immune- compromised mice. In both models, schwannoma volumes were monitored by magnetic resonance imaging (MRI) and showed strong gadolinium enhancement typical of these tumors in humans. Both types of tumor were positive for the Schwann cell marker S100, and highly infectable with herpes simplex virus (HSV) vectors. Schwannomas were injected with an oncolytic HSV-1 recombinant virus vector, G47Delta, which has deletions in genes for ribonucleotide reductase (ICP6), gamma34.5, and ICP47. In the NF2 transgenic model, schwannomas were reduced by more than half their original size by 10 days after infection. In the case of subcutaneous schwannoma xenografts, reduction in size after infection occurred more slowly, with a mean reduction of onethird by 42 days after treatment. Schwannomas injected with control vehicles continued to grow slowly over time in both schwannoma models. These studies demonstrate the ability of an oncolytic recombinant HSV vector to reduce the volume of schwannoma tumors in NF2 tumor models in mice and extend the possible therapeutic applications of oncolytic vectors for benign tumors to reduce mass while minimizing nerve damage.

Schwannomas are encapsulated benign tumours arising from nerve sheath cells, of which ancient schwannoma is one of five variants. Since the first description, only a few ancient schwannomas have been reported in different locations in the head and neck region. In the parotid gland, this tumour is very rare. In this report, a 41-year-old female patient with an ancient schwannoma of the parotid gland is presented and the data of this patient compared with other (comparable) cases described in the literature.

The cause of sciatica and low back pain associating with lumbar disc herniation has not been clearly identified until now. Inflammation has been shown to occur via immunohistochemical and biochemical methods in herniated disc tissues. The important prognostic role of E-selectin has recently been substantiated by other studies in early rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). The important role of adhesion molecules in the initiation and progression of the inflammatory response is well known for infectious diseases and autoimmune disorders. In our study, we aimed to show the role of E-selectin as an inflammatory marker and the correlation of inflammation with straight-leg raise (SLR) test findings and subtype of disc herniation. We found that the cases with positive SLR test had higher rates of immunostaining with E-selectin. This led us to think that E-selectin might play an important role in the activity status of the disease, meaning patients with more limited movement capacity might benefit from E-selectin antagonist therapy. Among the many studies performed to identify the relationship between the inflammation markers and activity of lumbar disc herniation, this is the first investigation held with E-selectin.

Peripheral nerve tumors show an interesting histologic variety despite being composed ofa limited array of cellular constituents. As we learn more about the interplay between the Schwann cells, perineurial cells, and ganglion cells that comprise these tumors, it is likely that we will better understand the biologic behavior of these important tumors. Key issues for the pathologist include distinguishing schwannomas from neurofibromas, ganglioneuromas from neurofibromas involving ganglia, and MPNSTs from cellular schwannomas or neurofibromas. The association of each of these tumors with genetic tumor disorders provides a unique window into discovering basic mechanisms of cell regulation and tumorigenesis that may ultimately shed light on the biology of a much wider array of human disease.

Cellular schwannomas are uncommon tumors of Schwann cells that can rarely have a plexiform architecture. Cellular schwannomas can be confused with low-grade malignant peripheral nerve sheath tumors (MPNST) but have been noted to have a benign clinical course. There are few published cytogenetic analyses of cellular schwannomas and, to our knowledge, there are no reports of the plexiform variant of cellular schwannoma to date. Cellular schwannomas are reported to have cytogenetic changes similar to those seen in benign schwannomas with near-diploid karyotypes having simple numerical changes often involving chromosomes 22, 7, and the sex chromosomes. MPNST are markedly different, with extensive genetic heterogeneity and complex karyotypes. We report clonal numerical changes in a cellular schwannoma with plexiform architecture: 47,XY,+17 and 48,XY,+17,+18. These findings add to the karyotypic spectrum of peripheral nerve sheath tumors.

Objective: To outline the diagnosis and management of intralabyrinthine schwannomas and to propose a new classification system to further define them., Study Design: Retrospective case review., Setting: Tertiary referral center at a university hospital., Patients: Twenty-eight patients seen at the institution with intralabyrinthine schwannomas between 1996 and 2002 were included in the study., Interventions: Diagnosis was made with magnetic resonance imaging in all but one case. Our ability to detect these tumors has been greatly enhanced by the introduction of high-resolution T2-weighted magnetic resonance imaging. Treatment options were observation with serial magnetic resonance imaging versus complete surgical removal via a translabyrinthine or transotic approach. Surgery was indicated for dizziness caused by the tumor or extralabyrinthine growth., Main Outcome Measures: Clinical features, audiology, radiology, and management outcomes were evaluated., Results: Eight patients have undergone successful surgery with removal of their tumors and resolution of symptoms. One patient chose to have stereotactic radiotherapy. Of the 20 patients who were managed with observation and serial magnetic resonance imaging, only 1 has shown significant growth requiring surgical removal., Conclusion: Intralabyrinthine schwannomas are uncommon tumors that mimic the clinical features of many other neurotologic conditions. A high index of suspicion and precise imaging are often required to detect these tumors. Surgical treatment is indicated for specific indications and will be needed in the minority of patients with this disorder. The classification system that we propose is helpful in both the diagnosis and the management of these tumors.

Unlike most soft tissue tumors, schwannoma is characterized by the presence of distinct linear, frequently duplicated external lamina (EL). Although electron microscopy remains the gold standard for demonstrating this unique feature and distinguishing its morphologic variants from mimickers, the use of two anti-EL antibodies, laminin and type IV collagen, appears to supersede electron microscopy in terms of current practice. To determine whether immunohistochemical expression correlates with ultrastructural findings, 10 cellular schwannomas, 18 classic schwannomas, and 3 melanotic schwannomas were evaluated ultrastructurally and immunohistochemically using antibodies to type IV collagen and laminin. Immunohistochemically, a moderate to strong intensity in more than 50% of tumor cells was detected using either antibody in most cases of cellular schwannomas (70%), the Antoni A areas of classic schwannomas (78%), and melanotic schwannomas (67%). Ultrastructurally, the presence of diffusely continuous, duplicated EL was observed in 30% of cellular schwannomas and 56% of classic schwannomas, while 50% of cellular schwannomas and 22% of classic schwannomas showed either continuous simple EL or discontinuous but duplicated EL alone. In addition, two cellular schwannomas (20%) and four classic schwannomas (22.2%) had only a simple layer of EL in focal areas. In contrast to the distinct immunostaining surrounding individual cells seen in the former two subtypes, all three melanotic schwannomas displayed a biphasic-staining pattern of the EL (ie, individual cell and nested), which was confirmed at the ultrastructural level. The authors found a significant difference in intensity between the Antoni A and B areas of classic schwannomas using both laminin and type IV collagen. In addition, the intensities of laminin and type IV collagen in the Antoni A areas of classic schwannomas were significantly stronger compared with those of cellular schwannomas. Nevertheless, there was no significant difference either between two antibodies or between cellular and classic variants with regard to the extent of immunoreaction. Only in classic schwannomas did the extent of immunoreaction against both laminin and type IV collagen correlate significantly with the ultrastructural EL distribution pattern (diffusely continuous vs. discontinuous). However, this association was not detected in cases of cellular schwannomas. On the other hand, the intensities of laminin and type IV collagen did not correlate with the ultrastructural thickness of EL, irrespective of the morphologic subtypes. In conclusion, both type collagen IV and laminin are still reliable markers of EL in various types of schwannomas. Schwannomas exhibiting a monolayered EL are as strong in immunoreaction as those displaying reduplicated/thickened EL, indicating that a single layer of EL is thick enough to be identified by both antibodies with sufficient sensitivity. The peculiar biphasic EL pattern seen in melanotic schwannoma remains under-recognized, which may lead to misdiagnosis as malignant melanomas, especially in limited biopsy specimens.

Nerve sheath tumors that involve the sacrum are rare. Delayed presentation is common because of their slow-growing nature, the permissive surrounding anatomical environment, and nonspecific symptoms. Consequently, these tumors are usually of considerable size at the time of diagnosis. The authors discuss a case of a sacral nerve sheath tumor. They also propose a classification scheme for these tumors based on their location with respect to the sacrum into three types (Types I-III). Type I tumors are confined to the sacrum; Type II originate within the sacrum but then locally metastasize through the anterior and posterior sacral walls into the presacral and subcutaneous spaces, respectively; and Type III are located primarily in the presacral/retroperitoneal area. The overwhelming majority of sacral nerve sheath tumors are schwannomas. Neurofibromas and malignant nerve sheath tumors are exceedingly rare. Regardless of their histological features, the goal of treatment is complete excision. Adjuvant radiotherapy may be used in patients in whom resection was subtotal. Approaches to the sacrum can generally be classified as anterior or posterior. Type I tumors may be resected via a posterior approach alone, Type III may require an anterior approach, and Type II tumors usually require combined anterior-posterior surgery.

Background: The authors present a retrospective analysis of 29 consecutive patients with trigeminal neurinomas. Modified classification based on the tumor distribution over petrous ridge is suggested to select the optimal surgical approach and to predict the outcome., Methods: Preoperative computed tomography (CT) or magnetic resonance (MR) images were analyzed to measure a long diameter of tumor axis (LD), which divided into middle and posterior fossa and a width of the petrous erosion (PW) by the tumor on axial image. The tumors were classified into four groups (M, tumor confined to middle fossa; Mp, tumor mainly in middle fossa; M = P, tumor equally distributed into both middle and posterior fossa; Pm, tumor mainly in cisternal space of posterior fossa with slender, rarely round extension into Meckel's cave), and extent of removal was compared between the groups. Long-term outcomes were based on recurrence-free survival., Results: Total removal was achieved in 16 patients including stage operation (55%). Excluding three tumors, which underwent gamma knife for residual tumor, 8 of 10 subtotally removed tumors recurred at 50 months on average. The LD and PW are significantly different among the tumor types. The M = P type is the largest in both parameter, while the M type is the smallest in LD; Pm type is the smallest in PW, respectively. The tumors with equal or lager posterior fossa component (M = P and Pm type) were more difficult to remove totally by single attempt than those with smaller or nil posterior fossa mass (Mp and M type). Also, the corrected PW (PW over the tumor diameter of minor portion) shows a tendency to influence the extent of removal as the relatively narrow PW hindered the total removal., Conclusions: Aggressive attempt for total removal using skull base approach is recommended, especially for those having dominant posterior fossa component and for those having relatively narrow PW.

The infrequent exposure of pathologists to soft tissue spindle cell neoplasms coupled with overlapping histologic patterns can often make diagnosis challenging. We reviewed all nonodontogenic spindle cell neoplasms seen between 1982 and 2002 (86,162 total accessions). Diagnoses were reclassified according to current standards supplemented with immunohistochemistry. Of the 307 neoplasms reviewed (0.36% of total accessions), neural tumors were the most common benign entities, accounting for 21% of total cases. Kaposi's sarcoma was the most common malignancy, accounting for 67% of all cases. Diagnoses were revised for 57 cases. Schwannoma and neurofibroma were most commonly revised to palisaded encapsulated neuroma. There were 8 myofibromas and 1 inflammatory myofibroblastic tumor. There were no oral leiomyomas; that is, all 4 originally reported cases were reclassified as myofibroma, palisaded encapsulated neuroma, and solitary fibrous tumor. With the exception of Kaposi's sarcoma, oral soft tissue sarcomas were rare; most benign lesions were neural in origin. The relatively high prevalence of some tumors, such as myofibroma, likely reflects the use of immunohistochemistry in the diagnosis of spindle cell tumors.

The paper analyzes the authors' experience in treating 16 patients with neurinomas and neurofibromas of the jugular foramen. A tumor was located intracranially (Type A) in 1 case, at the level of the base of the skull (Type B) in 7 cases, extracranially (type C) in 3 cases, and extra- and intracranially (Type D) in 5. All the patients were operated on. One-stage removal was performed in 15 patients, in 1 case a tumor was removed in 2 steps. By taking into account differences in the site of the tumors, the authors used the following accesses: retrosigmoid, supracondyllar, extreme lateral transcondylar, retroauricular transtemporal, extended retroauricular transtemporal, lateral cervical. While planning accesses, it is necessary to bear in mind not only the direction of growth of these tumors, but also the pathways of collateral venous blood flow.

As an anatomical interface between various tissues, the skull base harbors an exceptionally broad variety of neoplasms, some of which pose a major challenge for surgical pathology. The characterization of distinct immunohistochemical expression profiles and the identification of molecular genetic alterations associated with different tumor entities have significantly advanced this field. The new World Health Organization (WHO) classification of tumors of the nervous system lists 15 histopathological variants of meningioma. Of clinical importance are those entities that carry an increased risk of recurrence and a poor prognosis, i.e., the atypical meningioma (WHO grade II), clear-cell meningioma (WHO grade II), chordoid meningioma (WHO grade II), rhabdoid meningioma (WHO grade III), papillary meningioma (WHO grade III), and anaplastic meningioma (WHO grade III). Diagnostic criteria for atypical and anaplastic meningioma variants have now been stringently defined. The differential diagnosis of meningiomas includes hemangiopericytoma, hemangioblastoma, solitary fibrous tumor, sarcomas, and chordoid neoplasms. Recent data highlight the importance of distinguishing chordoma and chondrosarcoma of the skull base since chondrosarcomas show a significantly better clinical outcome. Among the less common, aggressive tumor entities in this anatomical region, infiltrating pituitary adenoma/pituitary carcinoma, superficial malignant gliomas, rhabdomyosarcoma, olfactory neuroblastoma, various sarcomas, and malignant lymphoma must be considered. Profiles of molecular genetic alterations have been established for several of these neoplasms and may facilitate the differential diagnosis. This review summarizes recent developments in the histopathological characterization, classification, and molecular pathology of neoplasms arising at the skull base.

Objective: A series of 51 patients with trigeminal neurillemmoma were analyzed with respect to the clinical manifestations, radiologic features, operative approaches and factors influencing tumor total resection., Methods: Three different approaches were used to remove the tumors according to the site of tumor growth. Tumors in middle fossa were removed via extended middle fossa approach or extended transpterion approach. Dumbbel tumors on petrosal bone were resected by presigmoid approach. Retrosigmoid approach was used to excise tumors in posterior fossa., Results: Tumors removed completely in 80.0% of patients, 75.0% of the patients had a normal cranial nerve function after operation. Tumors recurred in two patients 2 years after operation., Conclusion: The new operative approach increases the complete tumor resection rate.

The diagnosis of gastrointestinal stromal tumors (GIST) is generally established on histopathologic examination of surgical specimens. The present study was undertaken to characterize the cytologic appearance of these tumors and to assess the utility of fine-needle aspirates, including immunocytochemistry for the demonstration of c-kit (CD117) and CD34, in the preoperative diagnosis. The study comprised preoperative fine-needle aspirates in three cases and aspirates performed on fresh surgical specimens in eight cases. The routinely stained smears revealed a mesenchymal cell population, predominated by spindle cells. In five of six cases a strong positivity for c-kit was demonstrated and in three of five cases a strong CD34-expression was found in the tumor cells. These results show that fine-needle aspiration appears to be a useful method for the recognition and diagnosis of GISTs or ICC (interstitial cell of Cajal) tumors., (Copyright 2000 Wiley-Liss, Inc.)

Benign schwannoma (neurilemoma) has various morphologic patterns that may cause problems in differential diagnosis. Although an epithelioid variant of malignant schwannoma simulating carcinoma and melanoma is well recognized, a benign counterpart has not yet been defined. In the current study, we describe five cases of benign epithelioid schwannoma that were in the subcutis (four cases) and the neck of the urinary bladder (one case). The tumors occurred in adults 28-73 years of age, were 1-4.5 cm in diameter, were well circumscribed and cellular, and were composed of epithelioid cells arranged in cords and nests. The benign nature of the lesions was evident by a constellation of features, including small size, sharp circumscription, bland morphology, low proliferative activity (four of five had < or =1% Ki67 immunostaining), and a benign clinical course after either marginal or intralesional excision. All cases had some features of classic schwannoma light microscopically and a high degree of Schwann cell differentiation both ultrastructurally and immunohistochemically. The recognition of benign epithelioid schwannoma is important because it may be misinterpreted as a malignant neuroectodermal, mesenchymal, epithelioid, or melanocytic tumor.

Until recently, benign cutaneous neural tumours which do not fulfill criteria for either neurofibroma or schwannoma often were lumped into the broad category of benign peripheral nerve sheath tumours (PNST). However, during the last years a number of new entities of neural tumours has been described, and advances in immunohistochemistry and electronmicroscopy have helped us better to understand the cytological differentiation in these neoplasms. The knowledge of these distinctive neoplasms is necessary in order to avoid diagnostic pitfalls and misdiagnosis of more aggressive neoplasms. These distinctive lesions include: Neurothekeoma, which can be divided into classical myxoid and cellular types showing characteristic histological and immunohistochemical features. Typical neurothekeoma (nerve sheath myxoma) is a lobular or nodular dermal neoplasm composed of plump spindled or stellated S-100 positive tumour cells set in a myxoid stroma. In contrast cellular neurothekeoma is characterized as an ill-defined dermal neoplasm composed of concentric nests and fascicles of spindle-shaped and epitheloid tumour cells, which are S-100 negative but stain positively for NKIC3. The evidence of intermediate forms of neurothekeoma showing features of ordinary, hypocellular neurothekeoma and cellular neurothekeoma, as well as ultrastructural studies emphasize, that both variants represent a spectrum of neurothekeoma. Solitary circumscribed neuroma ("palisaded encapsulated neuroma") manifests mainly as a skin-colored or pink papule or nodule, and is most often located on the face. Histologically, solitary circumscribed neuroma is a well-circumscribed round or ovoid dermal neoplasm composed of interwoven fascicles of schwann cells, which stain positively for S-100 protein, and numerous neurofilament positive axons surrounded partly by fibroblasts and EMA-positive perineurial cells. Perineurioma is a rare well-circumscribed neoplasm which occurs mainly in subcutaneous tissue and only rarely in the dermis and in deep soft tissue. Perineurioma is composed of elongated bipolar spindle-shaped tumour cells which are arranged in a storiform, linear or lamellated growth pattern. The tumour cells stain positively for vimentin and EMA, and for CD34 in a number of cases, but lack positivity for S-100 protein, neurofilament and desmoplakin. In addition unusual forms of schwannoma including cellular schwannoma, solitary plexiform schwannoma, and melanocytic schwannoma are briefly discussed.

Patients with multiple schwannomas without vestibular schwannomas have been postulated to compose a distinct subclass of neurofibromatosis (NF), termed "schwannomatosis." To compare the molecular-genetic basis of schwannomatosis with NF2, we examined the NF2 locus in 20 unrelated schwannomatosis patients and their affected relatives. Tumors from these patients frequently harbored typical truncating mutations of the NF2 gene and loss of heterozygosity of the surrounding region of chromosome 22. Surprisingly, unlike patients with NF2, no heterozygous NF2-gene changes were seen in normal tissues. Examination of multiple tumors from the same patient revealed that some schwannomatosis patients are somatic mosaics for NF2-gene changes. By contrast, other individuals, particularly those with a positive family history, appear to have an inherited predisposition to formation of tumors that carry somatic alterations of the NF2 gene. Further work is needed to define the pathogenetics of this unusual disease mechanism.