Cytology of Extraneural Metastases of Nonhematolymphoid Primary Central Nervous System Tumors: Six Cases with Histopathological Correlation and Literature Update.

INTRODUCTION: Extraneural/-cranial metastases (ENM) of primary central nervous system (CNS) tumors are rare and may be diagnostically challenging. We describe the cytomorphological and pertinent clinical features of ENM in a case series assessed by fine-needle aspiration (FNA). A search of the laboratory information systems of 2 tertiary care centers in Toronto (2000-2015) was performed. Cases with direct extracranial/-spinal extension of CNS neoplasms were excluded. Microscopic slides of FNA and surgical specimens were reviewed. Demographic and clinicopathological data were retrieved. CASE PRESENTATION: Six cases were identified with the original diagnoses of glioblastoma, glioblastoma with primitive neuroectodermal tumor-like components, anaplastic ependymoma, myxopapillary ependymoma, atypical meningioma, and hemangiopericytoma. Median patient age at first diagnosis was 44 years (range 22-56). The time interval between initial diagnosis and first metastatic disease manifestation was 3 months to 19 years. All FNA diagnoses were rendered correctly. In 4 cases, immunohistochemistry was used to support the diagnosis. All cases had prior surgical intervention at the primary tumor site. In 4 cases, the ENM location was the ipsilateral parotid or buccal area. Two primary tumors in midline location developed ENM in the scapular area. DISCUSSION/CONCLUSION: ENM are a rare manifestation of a range of different primary CNS tumors and may involve the ipsilateral head and neck mimicking clinically a salivary gland neoplasm. FNA can rapidly discriminate ENM from other, potentially more indolent conditions. Awareness of the clinical history is paramount to avoid diagnostic confusion.

Multinodular and vacuolating neuronal tumor of the cerebrum. A rare entity. New case and review of the literature.

BACKGROUND: Multinodular and vacuolating neuronal tumor has been recently described and included in the World Health Organization Classification of Tumors of The Central Nervous System, even though its consideration as a true tumor is controversial. Patients with these lesions usually present with refractory seizures and inconclusive imaging findings that may be confused with other more common diagnoses such as dysembryoplastic neuroepithelial tumors or low-grade gliomas. Therefore, surgical resection is warranted to reach a pathologic diagnosis and seizure control. To the best of our knowledge, only 16 cases have been published in the English literature. CASE DESCRIPTION: We present the case of a 52-year-old male who presented at our institution with a 2-year-history of absence of seizures. Brain MRI showed a T2-hyperintense lesion with no contrast enhancement affecting his temporal lobe. Temporal craniotomy and microsurgical resection was scheduled. The procedure was uneventful and a grayish, gluey mass was sent for pathologic analysis. The tumor was formed by immature neuronal cells organized in nodules with a vacuolated matrix. A thorough immunohistochemical analysis showed positivity for: Protein Gene Product 9.5. ATRX. OLIG2. SOX10. p16. Nestin. Synaptophysin. The findings were consistent with multinodular and vacuolating neuronal tumor. The patient has been seizure-free after surgery and with no signs of tumor progression. CONCLUSION: We present a thorough review addressing this uncommon tumor along with a description of the 17th reported case of MVNT, a tumor that was described for the first time in 2013. Further studies and case studies are necessary to establish a well-defined morphological and immunohistochemical profile along with knowledge about its natural history.

Extracranial head and neck neurogenic tumors: report of 47 cases.

UNLABELLED: Extracranial head and neck neurogenic tumors are rare and usually revealed by histological examination. The aim of this study was to review the clinical, radiological and therapeutic particularities of these tumors. METHODS: This retrospective study concerns 47 patients with neurogenic tumors of the head and neck, operated on between 1989 and 2011 (22 years period). All patients had complete physical examination and ultrasonography was performed when a cervical extension was found. CT scan and MRI were performed in 16 cases. Minimum follow up was 4 years. RESULTS:   A sinusonasal tumor was found in 9 cases and a cervical mass was seen in 28 cases. Parapharyngeal extension was observed in two cases. Two patients had tympano-jugular glomic tumors and 8 of them had a cervical soft tissue tumor. Complete surgical resection was performed in 46 patients. Histological examination revealed a benign tumor in 91% of cases (n=43), 24 of them were schwannomas. Malignant tumors were seen in 4 cases: esthesioneuroblastoma (3 cases) and malignant schwannoma (1 case). These patients received post operative radiotherapy. After surgery, two patients had Claude Bernard Horner syndrome and one had a definitive facial nerve palsy. CONCLUSION: Extracranial head and neck neurogenic tumors may have several aspects depending on their localisation and their histological type. Surgery, when performed, should be complete with minimum complications.

Cutaneous manifestations in neuro-oncology: clinically relevant tumor and treatment associated dermatologic findings.

Skin findings are a rare but important aspect of the evaluation and management of patients with tumors of the nervous system. Skin findings have the highest prevalence in genetic tumor syndromes termed neuro-genodermatoses, which include neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and tuberous sclerosis. Skin changes are observed in patients with non-syndromic nervous system malignancy, often as a result of pharmacotherapy. The skin may also manifest findings in paraneoplastic conditions that affect the nervous system, providing an early indication of underlying neoplasm, including dermatomyosistis, neuropathic itch, and brachioradial pruritus. In this article, we review the major cutaneous findings in patients with tumors of the brain, spine, and peripheral nervous system focusing on (1) cutaneous manifestations of genetic and sporadic primary nervous system tumor syndromes, and (2) paraneoplastic neurological syndromes with prominent cutaneous features.

Soft tissue sarcoma misdiagnosed as benign peripheral neurogenic tumor.

BACKGROUND: Because of the distinctive clinical and MR findings associated with benign peripheral neurogenic tumors (BPNTs), they are commonly diagnosed without histological confirmation. As such, they are one of the most frequently misdiagnosed entities among the soft tissue sarcomas (STSs) that undergo initial unplanned excision. In this study, we investigate the characteristics of STSs misdiagnosed as BPNTs. METHODS: We present a series of nine STS patients with an initial preoperative diagnosis of BPNT (BPNT-STS), and compare their clinical and MR findings to those of the 18 genuine BPNT patients, matched for site, depth, and size of tumors as well as related nerves. RESULTS: Among the nine BPNT-STS cases, the most common histological diagnosis was synovial sarcoma (n = 4). Six patients (67 %) had deep-seated tumors; four patients (44 %) had tumors 5 cm or greater in size. BPNT-STS patients were more likely to experience pain (78 % vs. 22 %) and shorter symptom duration (9 vs. 55 months) compared to BPNT patients. A target sign on MR imaging was observed only in BPNT patients (0 % vs. 50 %), whereas peritumoral edema was found only in BPNT-STS patients (33 % vs. 0 %). CONCLUSIONS: If a tumor suggestive of a BPNT is painful, with a relatively short symptom duration, and presents with peritumoral edema without a definite target sign on MR images, the possibility of an STS must be considered.

Spectrum of superficial nerve-related tumor and tumor-like lesions: MRI features.

Superficial soft-tissue masses arising from skin appendages, metastasis, and inflammatory lesions have been widely reported. However, nerve-related superficial mass-like lesions other than peripheral nerve sheath tumors are less commonly described. High resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss the entire spectrum of these lesions and also outline a systemic diagnostic approach.

Contemporary evaluation and management of parapharyngeal space neoplasms.

OBJECTIVE: This review summarises the contemporary, multidisciplinary approach to managing parapharyngeal space neoplasms. OVERVIEW: Parapharyngeal space neoplasms are uncommon head and neck tumours and are most often benign. Most tumours are of either salivary gland or neurogenic origin. Patients tend to be asymptomatic even when tumours reach large sizes. Patients may present with a mass in the pharynx or neck, although frequently the tumour is found incidentally on an imaging study. Due to the limitations of physical examination in this anatomical area, imaging studies are essential to the evaluation of parapharyngeal space neoplasms. Cytopathology may provide additional diagnostic information. Open biopsy is rarely necessary and can be hazardous. Treatment is primarily surgical, and various surgical approaches can be tailored for a given neoplasm. Recently, a trend toward observation of select patients with asymptomatic neurogenic tumours has been advocated. CONCLUSION: The evaluation and management of parapharyngeal space tumours is best done by a multidisciplinary team. Treatment should be individualised, and the risks and benefits of surgical intervention need to be carefully weighed. Complications are best avoided by careful surgical planning.

Desmoplastic trichoepithelioma with perineural involvement: a series of seven cases.

Desmoplastic trichoepithelioma (DTE) is a benign follicular tumor occurring most commonly within facial skin of young and middle-aged women, morphologically characterized by a superficial dermal proliferation of basaloid cells growing in narrow strands embedded in a desmoplastic stroma associated with small keratinizing cysts. DTE must be distinguished from other benign epithelial proliferations such as syringoma, microcystic adnexal carcinoma and infiltrating basal cell carcinoma. Among morphological features useful in that distinction, perineural involvement is considered a feature indicative of malignancy. We present a series of seven DTEs with otherwise typical presentation and morphology, nevertheless showing epithelium present in the perineural spaces of adjacent small dermal nerves. Patients ranged in age from 14 to 66 years (mean 44 years). All seven tumors were restricted to dermis, showed strands of basaloid epithelium in desmoplastic stroma and contained CK20-positive cells. Additionally, five of five examined tumors displayed diffuse expression of p75 neurotrophin receptor. Five patients were followed up clinically (follow-up time range: 2 months-4 years). No tumor recurrence was observed in any of these patients. We postulate that perineural involvement is an unusual feature of DTE that should not be equated with malignancy or lead to unnecessary over-treatment.

Spinal glioneuronal tumor with neuropil-like islands and meningeal dissemination: histopathological and radiological study of a pediatric case.

Cerebral and spinal location of glioneuronal tumors have been recently described as a novel type of primary CNS neoplasia. A distinctive rare form of glioneuronal tumors with neuropil-like islands (GTNI) have been reported to occur in the adult cerebrum, whereas spinal GTNI localization is extremely rare. In the present report we describe a case of a 15-month-old child with a spinal GTNI of the cervical region and meningeal dissemination. Histologically the tumor was composed of round, small neurocytic-like cells arranged around eosinophilic neuropil cores and embedded in a diffuse fibrillar glial component forming prominent "rosetted" neuropil islands displaying strong immunoreactivity for neuronal markers. Cerebral GTNI shows abundant glial components not rarely exhibiting anaplastic features that justify their inclusion within the group of diffuse astrocytomas. In contrast, including our case, spinal GTNI do not show histological evidence of anaplastic features and exhibits a significant neuronal component that may imply considering these lesions in a separate group. Nevertheless, due to their exceptional rarity, the natural history of these lesions is not yet fully understood, but spinal GTNI seems to have an unfavorable clinical course despite their benign histopathological features, which must be taken into account for appropriate treatment and follow-up of the patient.

Spinal tumors in children.

Pediatric spine tumors encompass a diverse group of pathologic diagnoses that differ markedly based on the location and age of the child. Children can be affected by primary and metastatic tumors, making the differential diagnosis and treatment options extensive. This article discusses the features of spinal tumors in children based primarily on location: extradural, intradural-extramedullary, and intramedullary tumors. Because this article deals with such a broad topic, detailed descriptions and outcomes of surgical and nonsurgical treatments for each particular tumor are limited. Rather, the key clinical, diagnostic, and therapeutic features of each tumor are discussed.

Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo.

Pseudotyping of viral vectors has been widely used to enhance viral transduction efficiency. One of the most popular pseudotyping proteins has been the G-protein of the vesicular stomatitis virus, VSV-G. In the present study, we show that the 21-amino-acid ectodomain with transmembrane and cytoplasmic tail domains of VSV-G (VSV-GED) augments baculovirus-mediated gene delivery in vertebrate cells by aiding viral entry. The VSV-GED pseudotyped virus replicated efficiently in insect cells yielding high titers. Five out of six studied cell lines showed improved transduction, as measured by a number of transduced cells or transgene expression level. Nearly 15-fold increase in the transduction efficiency was detected in rat malignant glioma cells as compared to the control virus. In the rat brain, transgene expression could be detected in the walls of lateral ventricles and in subarachnoid membranes. Increased transduction efficiency was also observed in the rabbit muscle. Our results suggest that VSV-GED enhances baculoviral gene transfer by augmenting gp64-mediated endosomal release. Moreover, no cytotoxicity was associated with improved gene transfer efficiency. Thus, VSV-GED pseudotyping provides a simple means to enhance baculovirus-mediated gene transfer in vitro and in vivo.

Cancer gene therapy using a novel secretable trimeric TRAIL.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is a type II transmembrane cytokine molecule. Soluble TRAIL has been shown to induce apoptosis in a wide variety of cancer cells in vitro and to suppress tumor growth specifically without damaging normal cells and tissues in vivo. In our previous report, we have demonstrated that an artificial gene encoding the polypeptide composed of the three functional elements (a secretion signal, a trimerization domain and an apoptosis-inducing moiety of TRAIL gene sequence) expresses and secretes highly apoptotic trimeric TRAIL into the culture supernatant. Here, as an approach to TRAIL-based cancer gene therapy, we developed an adenoviral vector delivering the gene that encodes our secretable trimeric TRAIL (stTRAIL). This adenovirus (Ad-stTRAIL) potently induced apoptosis in vitro in cancer cell lines such as HeLa, MDA-MB-231, A549, HCT116 and U-87MG. In an animal xenograft tumor model bearing a human glioma cell line U-87MG, intratumoral delivery of Ad-stTRAIL dramatically suppressed tumor growth without showing detectable adverse side effects. Histological analysis revealed that Ad-stTRAIL suppresses tumor growth by inducing apoptotic cell death. Contrary to the known rapid clearance of systemically delivered TRAIL protein from the blood circulation, stTRAIL expressed by Ad-stTRAIL in tumor tissues persisted for more than 4 days. In a comparison of tumor suppressor activity between Ad-stTRAIL and Ad-flTRAIL (delivering the full-length TRAIL gene) after mixing infected cells with uninfected cells and implanting these mixed cells in nude mice, Ad-stTRAIL showed higher tumor suppressor activity than that of Ad-flTRAIL. Our data reveal that a gene therapy using Ad-stTRAIL has a promising potential to treat human cancers including gliomas.

Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management.

Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The majority of GISTs are immunohistochemically positive for c-kit protein (CD 117) and CD34. GISTs express a heterogeneous clinical course not easily predicted by standard pathological means. The most important prognostic factors are size > 5 cm, tumor necrosis, infiltration and metastasis to other sites, mitotic count > 1-5 per 10 high-powered fields, and most recently, mutation in the c-kit gene. Surgical resection remains the mainstay of treatment, as chemotherapy and radiation are ineffective. Long-term follow-up is imperative, as recurrence rates are high.

Neurogenic tumors of the mediastinum.

Neurogenic tumors can arise from neural cells in any location; however, they commonly are found in the mediastinum and, more specifically, most often are located in the posterior compartment. Neurogenic tumors can be benign or malignant, with a wide array of both clinical and pathologic features that are commonly classified by the cell type of origin. These tumors are usually detected on routine chest radiograph, and a computed tomographic scan is required to obtain more information about involvement of local structures. A magnetic resonance imaging scan may be necessary if a dumbbell-shaped component is identified or suspected. Treatment options vary depending on the presentation, but most often surgical resection is recommended. Whereas patients with benign neurogenic tumors have an excellent prognosis with complete surgical resection, patients with malignant neurogenic tumors still have poor long-term survival prospects.

Neurogenic tumors of the head and neck in children.

Soft tissue tumors make up 63% of all tumors in children. Tumors of the sympathetic chain make up 7.4% of tumors arising in children (nine new cases a year for every million children in USA) while neurofibrosarcomas make up 3.4% (2.4 new cases per year for every million children). There is a certain difference between the frequency of benign forms (rather elevated) and that of malignant forms (rather low). Diagnosis is possible by echo-scan, computed tomography, magnetic resonance imaging and fine-needle aspiration biopsy. As regards therapy, surgical resection represents the treatment of choice. In our experience, 35 neurogenic tumors in pediatric patients (8-16 years), arising in head and neck spaces, were observed and treated in the period 1976 and 1995. Twenty-six cases were schwannomas, six were neurofibromas and three were olfactory neuroblastomas. All the patients underwent surgery. Sacrifice of the affected nerve was necessary in 12 cases (all neurofibromas and eight neurinomas). In one case of olfactory aesthesioneuroblastoma a combined approach (extra-intracranial approach) was employed. Two patients are alive and disease-free with 5 and 7 years follow-up. As regards dysfunctional pathology following surgical resection, we report definitive facial nerve palsy in two cases, permanent laryngeal palsy in six cases, tongue dysfunction in one case and cheek hypoaesthesia in one case.

[Neurogenic tumors of the head and neck]. / Neurogenne guzy glowy i szyi.

The authors present case studies of 65 patients with neurogenic tumors of the head and neck treated in the Department of Otolaryngology of the Medical University of Gdansk in the years 1948-1993. Age and sex of patients, localization of tumor, symptoms, histopathology and treatment were analysed. This resulted in the noting of difficulties in diagnosis and in showing the importance of immunohistochemical examinations, CT, MRI, USG in the diagnostics of malignant neurogenic neoplasms. Patients with benign tumors, in the majority of cases, were subjected to surgery. Patients with malignant neoplasms were subjected to surgery combined with high voltage radiotherapy. The positive effect of combined chemotherapy in cases of esthesioneuroblastoma is worthy of note. The results of the treatment of benign tumors are positive, whereas in the case of malignant tumors--the results are still not satisfactory.

Neurogenic tumors of the thorax.

We have conducted a retrospective review of 134 cases of neurogenic tumors of the thorax, including 66 in infants and children and 68 in adults. Nerve cell tumors were the majority in infants and children (84.8%) and were mostly malignant (67.2%). Nerve sheath tumors were more frequent in adults (73.5%). Nerve cell tumors were the most frequent tumors in males and nerve sheath tumors in females. Nineteen tumors were associated with von Recklinghausen's disease. The tumors were symptomatic in 76.4% of children and 36.7% of adults. Spinal cord compression was observed in 8 infants and children and in 2 adults. Neo-adjuvant treatment was administrated to 3 patients. Resection was complete for 80 benign tumors out of 86 (93%) and for 26 malignant tumors out of 48 (54%). Postoperative chemo- or radiotherapy (or both) was administrated to 17 children and 8 adults. The mean followup periods were 11 years for the infants and children and 8 years, 6 months for the adults. There was one postoperative death. There were no late deaths related to benign tumor. The prognosis of spinal cord compression depended on the malignancy and staging of the tumors. At 5 years postoperatively, 21 children out of 28 with neuroblastomas and 8 out of 9 with ganglioneuroblastomas were alive. The possibility of maturation of neuroblastomas and survival with hepatic metastases was confirmed. The prognosis in cases of chemodectoma depended on the extension. Patients with malignant schwannomas had very poor prognoses, especially when associated with von Recklinghausen's disease.