[Sciatic nerve intraneural perineurioma]. / Périneuriome intraneural du nerf sciatique.

Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient.

Low-grade small round cell tumor of the cauda equina with EWSR1-WT1 fusion and indolent clinical course.

We report a case of a longstanding, large tumor involving spinal nerve roots of the cauda equina. The tumor showed small round cells arranged in nests and cords and immunophenotypic features of a glomus tumor, along with infrequent mitoses and a low Ki-67 labeling index, but exhibited some rosette-like structures, with focal CD99 and Neu-N expression. Subsequent molecular analysis showed the presence of an EWSR1-WT1 gene fusion by fluorescence in situ hybridization, which was confirmed by reverse- transcriptase polymerase chain reaction. To our knowledge, this is the first case reported with EWSR1-WT1 fusion in a small round blue cell tumor with smooth muscle differentiation and an indolent course.

Fibrolipomatous Hamartoma of the Nerve Arising in the Neck: A Case Report With Review of the Literature and Differential Diagnosis.

We report an unusual case of a fibrolipomatous hamartoma that arose in a nuchal nerve. Typically, fibrolipomatous hamartoma, otherwise known as a neural fibrolipoma or lipomatosis of nerve, arises in the median nerve, brachial plexus, cranial nerves, or plantar nerves. The differential diagnosis is broad and includes benign and malignant spindle cell lesions, such as spindle cell lipoma, perineurioma, and myxoid liposarcoma. We were able to identify the lesion based on the typical histology, including triphasic composition with spindle cell, neural, and adipocytic components and whorled architecture. Because of the atypical location in the neck, detailed immunohistochemical staining was performed. The lesional spindle cells were negative for SMA, CD10, CD68, EMA, S100, PGP9.5, CD34, CD56, and beta-catenin. Colloidal iron stain highlighted marked intralesional mucin deposition. This detailed immunohistochemical profile is a useful diagnostic aid and to our knowledge has not been previously described.

Epithelioid schwannoma of the facial nerve masquerading as pleomorphic adenoma: a case report.

Schwannomas arising in the parotid gland or peri-parotid region is frequently misdiagnosed as pleomorphic adenoma on cytologic preparations. The epithelioid variant of schwannoma is particularly susceptible to misdiagnosis because this neoplasm typically has epithelioid and spindled cells, which are associated with fibrillar stroma and mimic the epithelial, myoepithelial, and stromal components of a pleomorphic adenoma. Preoperative diagnosis of schwannoma is critical in order to plan appropriate management and to avoid inadvertent injury to the associated nerve during surgical resection. Thus, awareness of the distinct clinical, radiological, and cytomorphological features of schwannoma is important in order to guide clinical management. If the cytomorphological features are equivocal, immunohistochemical staining may provide a valuable alternative for distinguishing between pleomorphic adenoma and schwannoma.

A study of gata3 and phox2b expression in tumors of the autonomic nervous system.

Autonomic neurons and chromaffin cells, which constitute the autonomic nervous system, are derived from a common progenitor from the neural crest, and its development is controlled by a network of transcription factors, including the master regulator, Phox2b, and its downstream, Gata3. Anti-Phox2b and anti-Gata3 antibodies were applied to a total of 77 autonomic nervous system tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimics, including tumors of the small round cell tumor group, neuroendocrine carcinomas of lung and gastrointestinal tract (carcinoid tumors/neuroendocrine tumors, large cell neuroendocrine carcinomas, and small cell carcinomas), Merkel cell carcinomas, benign and malignant tumors of thyroid, parathyroid, and adrenal cortex, and malignant melanomas. A variety of nonendocrine/neuroendocrine carcinomas were also studied. Gata3 expression was seen in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, as well as in all parathyroid tumors, a majority of urothelial and mammary carcinomas, and a subset of squamous cell carcinomas, but all other tumors were negative. Phox2b expression was seen in all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas and in 40% of paragangliomas, but pheochromocytomas and all other tumors were negative. Gata3 is a highly reliable marker for paragangliomas, pheochromocytomas, and neuroblastic tumors to distinguish from their simulators. This is an additional utility for this marker, which is used for the diagnosis of urothelial and mammary carcinomas. Phox2b is also highly specific, but its low sensitivity to paragangliomas and pheochromocytomas would limit the utility only to neuroblastic tumors.

SMARCB1 deficiency in tumors from the peripheral nervous system: a link between schwannomas and rhabdoid tumors?

BACKGROUND: Inactivation of SMARCB1 tumor-suppressor gene was originally described as highly specific for rhabdoid tumors (RTs). Nevertheless, recent reports have illustrated that SMARCB1 alterations also characterize other tumors; in particular, some familial schwannomatosis and epithelioid malignant peripheral nerve sheath tumors, both from peripheral nervous system (PNS) origin, lack BAF47 expression. To document the putative role of SMARCB1 in PNS, we reviewed PNS tumors referred to our institution for a molecular analysis of SMARCB1 because of histologic features compatible with RT. METHODS: Clinicopathologic, radiologic, and molecular characteristics were detailed for the 12 cases showing loss of expression and/or biallelic inactivation of SMARCB1. The status of the NF2 gene, likely to synergize with SMARCB1 in PNS tumors, was also analyzed. RESULTS: Patients' age ranged from 0 to 45 years (median age, 6.6 y). Neurological symptoms were observed in 7/12 cases with radiologic features evoking a neuroblastic tumor in 6 cases and a peripheral nerve tumor in 4 cases. The mean delay before diagnosis was 3 months. Histologic examination revealed rhabdoid features in 11/12 tumors. All tumors showed a complete loss of SMARCB1 expression. Interestingly, adjacent nervous proliferation resembling neurofibromas were observed in 3 cases, suggesting a multistep transformation. Three tumors harbored a hemizygous deletion at the NF2 locus, but all NF2 sequences were normal. CONCLUSIONS: We report the first series of PNS RT. In patients with aggressive PNS tumors, RT should be suspected, and anti-SMARCB1 immunohistochemical analysis should be performed. SMARCB1 inactivation, occasionally associated with NF2 deletion, might have oncogenic effects in peripheral nerves.

[Standardizing a central nervous system tumor DNA biobank]. / Estandarización de un biobanco de ADN de tumores del sistema nervioso central.

BACKGROUND: Brain tumors are one of the leading cancers worldwide; in the National Institute of Neurology and Neurosurgery (INNN) these tumors are the leading cause of morbitity and mortality. OBJECTIVE: Standardize biopsies, colletion, processing and storage biologic material of molecular studies. METHODS: with a previously signed surgical consent, a tumor and blood biopsy was done to 134 patients. Their DNA was extracted and a database was filled considering technical, ethical and legal aspects. In order to have optimal biologic material the procedure was standardized between the surgical and research laboratory teams. RESULTS: The biopsy, transportation, processing and storage were standardized. 134 patients were included (67 male and 67 female) with an average age of 46.28 years (range 15-81). The most frequently biopsied tumor was the meningioma (42%). The integrity of the obtained material was determined by agarose gel electrophoretic analysis. CONCLUSION: the INNN biobank has a standardized system that biopsies, processes and stores optimum quality biologic material that will be the basis of future molecular studies.

[Morphologic and differential diagnosis of sclerosing perineurioma].

The paper discusses morphologic and immunohistochemical characteristics of sclerosing perineurioma. Generally, it is well circumscribed and consists of tiny spindle-shaped plump epitheloid cells embedded in collagenous hyalinized matrix. Immunohistochemically, it was represented by EMA+, S-100, AE1/AE3, CAM 5.2, smooth muscle actin and desmin. Being benign, tumor was identified by differential diagnosis using fibroma of tendon sheath, sclerosing one, glomal tumor, giant cell tumor and sclerosing epitheloid cell sarcoma.

[Morphologic features of reticular (retiform) perineuroma].

The report deals with 8 cases of reticular (retiform) perineuroma, a rare soft-tissue variant of the latter. It presents as a lace-like pattern of long cytoplasmic outgrowths of tumor cell clusters in myxoid or tender collagenized stroma. Despite its potential for infiltrative growth, perineuroma has a benign clinical course.

Spontaneous ganglioneuroma possibly originating from the trigeminal ganglion in a B6C3F1 mouse.

In a carcinogenicity study, a neuronal tumor in the cranial cavity was observed in a 110-week-old female B6C3F1 mouse. At necropsy, the tumor was seen at the site of the pituitary gland. Histologically, the tumor consisted of well-differentiated ganglion cells, nerve fiber/neuropil-like elements and ganglion-like cells. The tumor was composed mainly of ganglion-like cells, which were arranged in solid sheets interspersed with thin fibrovascular stroma. Nissl substance was detected at the margin in the cytoplasm of well-differentiated ganglion cells, and nerve fibers were identified by the Kluever-Barrera method. Immunohistochemically, the well-differentiated ganglion cells were positive for S-100, neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin, and chromogranin A. The nerve fiber/neuropil-like elements were positive for S-100, NF, NSE, and glial fibrillary acidic protein (GFAP), and the ganglion-like cells were strongly positive only for NSE and synaptophysin. On the other hand, there were no pituitary cells, such as prolactin-positive or adrenocorticotropic hormone (ACTH)-positive cells in the tumor tissue. Detailed histopathological examination suggested that the tumor might be a ganglioneuroma arising from the trigeminal ganglion. This report provides additional histopathological evidence of peripheral nerve neoplasms in mice.

Extraneural hemangioblastoma: a report of 5 cases.

Hemangioblastoma is a morphologically distinctive tumor that can occur sporadically or in association with von Hippel-Lindau disease, and which involves the central nervous system in the majority of the cases. Rare occurrences of hemangioblastoma in peripheral nerves and extraneural tissues have been reported. The histogenesis of this tumor remains uncertain. Various cell lineages such as vascular, glial, neural, fibrohistiocytic, and smooth muscle/myofibroblastic have been proposed for the so-called stromal cells, which are thought to represent the neoplastic component of these lesions. We report on 5 cases of hemangioblastoma arising in extraneural tissues. Two of the tumors were located in the presacral region, and one each in the maxilla, kidney, and adrenal glands. All 5 cases were morphologically indistinguishable from central nervous system hemangioblastoma. The existence of these cases suggests that the "stromal" cells of hemangioblastoma can demonstrate a variety of mature specific lineages, such as smooth muscle/myofibroblastic, or neuroendocrine, depending on the location and possibly the microenvironment.

Retroperitoneal schwannomas: diagnostic and therapeutic implications.

AIMS AND BACKGROUND: Schwannomas are a rare group of soft-tissue tumors that are derived from the peripheral nerve sheath and rarely develop in the retroperitoneum. METHODS AND STUDY DESIGN: We reviewed the clinicopathological features of 4 patients referred to our unit between October 1999 and March 2004 who on radiological examination were diagnosed with pancreatic, adrenal, psoas and retroperitoneal fat tissue tumors and subsequently underwent surgical treatment. RESULTS: The preoperative diagnosis was incorrect in all cases. At time of surgery, we found a mass probably arising from the adrenal gland in 2 patients, a lesion originating from the femoral nerve in 1 patient, and a retroperitoneal mass without a clear site of origin in 1 patient. Pathological evaluation revealed schwannomas in all cases, with no signs of malignancy. Complete surgical excision was performed in all patients without any major postoperative complications. At the time of writing all patients are alive with no evidence of local or distant recurrence. CONCLUSIONS: Radical surgical excision is considered the best treatment for these neoplasms, resulting in a very good longterm prognosis.

Oncolytic herpes simplex virus therapy for peripheral nerve tumors.

Oncolytic viruses are one of many emerging cancer therapies. The surgical management of peripheral nerve tumors carries an inherent risk of damaging the nerves involved and so the search for novel therapies with reduced risk of morbidity continues. In this review the authors discuss the use of oncolytic herpes simplex virus (HSV) in the treatment of peripheral nerve tumors. Herpes simplex virus has a number of characteristics that make it a useful oncolytic vector, including its large, sequenced genome that can accommodate multiple transgenes, its lack of insertional mutagenesis, its ability to infect a wide array of cell types in various species, and the availability of well-established antiviral therapies to treat it. The efficacy of oncolytic HSV therapy against schwannomas and malignant peripheral nerve sheath tumors has been studied in multiple experimental models both in vitro and in vivo. The virus utilizes cell pathways unique to tumors to enhance its oncolytic efficacy, preferentially and effectively targeting and destroying peripheral nerve tumor cells without harming normal cells. This effect is augmented by transgenes expressing antiangiogenic factors, such as dominant-negative fibroblast growth factor receptor and platelet factor 4, and displays synergy with chemotherapy. Different oncolytic HSV vectors have been tested, including hrR3, G207, and G47D. In addition, new animal models have been developed to test the efficacy of oncolytic HSV therapy in peripheral nerve tumors. The safety of oncolytic HSV is well established and has been tested in nonhuman primates and in human clinical trials.

Comparative proteomic expression profile in all-trans retinoic acid differentiated neuroblastoma cell line.

Neuroblastoma (NB) is an infant tumor which frequently differentiates into neurons. We used two-dimensional differential in-gel electrophoresis (2D-DIGE) to analyze the cytosolic and nuclear protein expression patterns of LAN-5 cells following neuronal differentiating agent all-trans-retinoic acid treatment. We identified several candidate proteins, from which G beta2 and Prefoldin 3 may have a role on NB development. These results strength the use of proteomics to discover new putative protein targets in cancer.

Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma? Case report.

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.

Low grade malignant peripheral nerve sheath tumour: varied cytological and histological patterns.

BACKGROUND: A small number of malignant peripheral nerve sheath tumours (MPNSTs) are low grade, and the nature of these low grade tumours has never been systematically assessed. AIMS: To describe the clinicopathological, immunohistochemical, and ultrastructural features of low grade MPNST and to discuss the main differential diagnoses. METHODS: Four cases of low grade MPNST were studied, including one coexistent with neurofibromatosis type 1. The tumours were analysed with respect to nuclear atypia, cellularity, nuclear enlargement, hyperchromasia, mitotic rate, and necrosis. Immunohistochemistry was performed by standard techniques, and an ultrastructural study was performed on one tumour. RESULTS: The ages of the patients ranged from 32 to 72 years (mean, 58). Two were male and two were female. Three tumours occurred in the deep tissue, including one in the retroperitoneum, and one was located in the dermal and subcutaneous tissue. The maximum diameters of the tumours ranged from 3.5 to 8.0 cm. Microscopically, all tumours showed moderate hypercellularity, an increased nuclear to cytoplasmic ratio, and hyperchromasia, but exhibited varied growth patterns, including those that were atypical neurofibroma-like, low grade fibromyxoid sarcoma-like, low grade epithelioid, and haemangiopericytoma-like. All tumours showed immunoreactivity for S-100 protein and vimentin. CONCLUSIONS: These findings suggest that careful clinical and histological evaluation, along with S-100 protein immunostaining, are essential for the accurate diagnosis of low grade MPNST.

Neurocytoma arising in the pelvis.

Central neurocytoma represents a rare neoplasm of the central nervous system with advanced neurocytic and sometimes focal lipomatous differentiation, a low proliferative potential and a favorable prognosis depending on the efficiency of surgical resection. This entity has been described as an intraventricular tumor near the foramen Monroi. Here, we report a case of a 21-year-old male with peripheral neurocytoma. Using computed tomography, a tumor of unknown origin was located behind the bladder. After complete surgical resection of the tumor, histologically small uniform cells, zones of fibrillarity and neuropil-like islands were seen. Immunohistochemistry revealed positivity for the neuronal markers synaptophysin, neuron-specific enolase and neurofilaments. Vimentin, pan-keratin, desmin, chromogranin, CD-99 and glial fibrillary acidic protein were immuno-negative. A low proliferation rate (1-2%) was found. Several case reports described extraventricular central neurocytomas. A sole publication documented a peripheral neurocytoma arising within a mature cystic teratoma of the ovary. To our knowledge, this is the second reported case of a neurocytoma outside the central nervous system, indicating that this entity may also occur infrequently in peripheral tissues.

Neural fibrolipoma of the superficial peroneal nerve in the ankle: a case report with immunohistochemical analysis.

This report presents a case of neural fibrolipoma arising from the superficial peroneal nerve in the ankle. A 28-year-old woman was referred with a soft tissue mass in the anterior aspect of the right ankle, which had been gradually enlarging for the past 10 years. Magnetic resonance imaging showed a mass lesion, measuring approximately 8 x 3 x 2 cm, with high to partially low signal intensity on both T1- and T2-weighted images. A band of low signal intensity within the lesion, which is indicative of coexistence with the tumor and the superficial peroneal nerve, could be detected on both T1- and T2-weighted images. The patient underwent an excisional biopsy. The specimen microscopically consisted of nerve bundles and fibro-fatty proliferation with abundant collagen fibers. Immunoreactivity for CD34 antigen antibody was detected in fibrous spindle cells. This is the first report to present an immunohistochemical profile of neural fibrolipoma. Neural fibrolipoma should be considered as a differential diagnosis when a lipomatous lesion is encountered in the foot or ankle as well as in the upper extremities.