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PubMed2005

A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana State University Health Sciences Center.

OBJECT: This is a retrospective review of 397 benign and malignant peripheral neural sheath tumors (PNSTs) that were surgically treated between 1969 and 1999 at the Louisiana State University Health Sciences Center (LSUHSC). The surgical techniques and adjunctive treatments are presented, the tumors are classified with respect to type and prevalence at each neuroanatomical location, and the management of malignant PNSTs is reviewed. METHODS: There were 361 benign PNSTs (91%). One hundred forty-one benign lesions were brachial plexus tumors: 54 schwannomas (38%) and 87 neurofibromas (62%), of which 55 (63%) were solitary neurofibromas and 32 (37%) were neurofibromatosis Type 1 (NF1)-associated neurofibromas. Among the brachial plexus lesions supraclavicular tumors predominated with 37 (69%) of 54 schwannomas; 34 (62%) of 55 solitary neurofibromas; and 19 (59%) of 32 NF1-associated neurofibromas. One hundred ten upper-extremity benign PNSTs consisted of 32 schwannomas (29%) and 78 neurofibromas (71%), of which 45 (58%) were sporadic neurofibromas and 33 (42%) were NF1-associated neurofibromas. Twenty-five benign PNSTs were removed from the pelvic plexus. Lower-extremity PNSTs included 32 schwannomas (38%) and 53 neurofibromas (62%), of which 31 were solitary neurofibromas and 22 were NF1-associated neurofibromas. There were 36 malignant PNSTs: 28 neurogenic sarcomas and eight other sarcomas (fibro-, spindle cell, synovial, and perineurial sarcomas). CONCLUSIONS: The majority of tumors were benign PNSTs from the brachial plexus region. Most of the benign PNSTs in all locations were neurofibromas, with sporadic neurofibromas predominating. Similar numbers of schwannomas were found in the upper and lower extremities, whereas neurofibromas were more prevalent in the upper extremities. Despite aggressive limb-ablation or limb-sparing surgery plus adjunctive therapy, malignant PNSTs continue to be associated with high morbidity and mortality rates.

Academic Medical Centers↗

PubMed2005

Association between benign and malignant peripheral nerve sheath tumors in NF1.

OBJECTIVE: People with neurofibromatosis type 1 (NF1) have a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). MPNSTs are often metastatic and are a frequent cause of death among people with NF1. Clinical evidence suggests that most MPNSTs in people with NF1 develop from preexisting plexiform neurofibromas. However, it is not known whether an individual's risk of developing an MPNST is associated with the burden of benign neurofibromas. The authors conducted a study to determine whether people with NF1 who have benign neurofibromas of various kinds are at greater risk of developing MPNSTs than patients with NF1 who lack these benign tumors. METHODS: Clinical information on 476 NF1 probands in the Henri Mondor Database was analyzed by logistic regression to examine associations between MPNSTs and internal plexiform, superficial plexiform, subcutaneous, and cutaneous neurofibromas. RESULTS: Individuals with subcutaneous neurofibromas were approximately three times more likely to have internal plexiform neurofibromas or MPNSTs than individuals without subcutaneous neurofibromas. Individuals with internal plexiform neurofibromas were 20 times more likely to have MPNSTs than individuals without internal plexiform neurofibromas. When this analysis was done with both subcutaneous and internal plexiform neurofibromas as explanatory variables, only the association of MPNSTs with internal plexiform neurofibromas remained significant. CONCLUSIONS: The observation that malignant peripheral nerve sheath tumors are strongly associated with internal plexiform neurofibromas suggests that patients with neurofibromatosis type 1 with these benign tumors warrant increased surveillance for malignancy.

Adolescent↗

PubMed2004

Analysis of neurofibromatosis 1 (NF1) lesions by body segment.

Café-au-lait spots and neurofibromas are defining features of neurofibromatosis 1 (NF1), but they vary greatly in number, size, and clinical importance from patient to patient. The cause of this variability is unknown. We tested the hypotheses that development of these lesions is influenced by local or familial factors. The presence or absence of café-au-lait spots, cutaneous neurofibromas, and diffuse plexiform neurofibromas was recorded for each of 10 divisions of the body surface in 547 NF1 patients, including 117 affected individuals in 52 families. We used stratified Mantel-Haenszel tests to look for local associations between the presence of diffuse plexiform neurofibromas, cutaneous neurofibromas, and café-au-lait spots in individual body segments of NF1 patients. We used a random effects model to obtain intrafamilial correlation coefficients for the age-adjusted number of body divisions affected with each of the three lesions. No significant association was observed between the occurrence of cutaneous and diffuse plexiform neurofibromas, between café-au-lait spots and cutaneous neurofibromas, or between café-au-lait spots and plexiform neurofibromas in the same body segment. The correlation among relatives in the number of body segments affected with café-au-lait spots was 0.45 (95% confidence interval [CI] = 0.18-0.71), with cutaneous neurofibromas, 0.37 (95% CI = 0.15-0.55), and with plexiform neurofibromas, 0.35 (95% CI = 0.15-0.57). We conclude that the development of café-au-lait spots, cutaneous neurofibromas, and plexiform neurofibromas are spatially independent in NF1 patients but that the development of all three lesions is influenced by familial factors.

Adolescent↗

PubMed2006

Serum IgE levels in neurofibromatosis 1.

A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using the IgE radioimmunosorbent test, with the reference values of 75-502 IU mL(-1). The patients were divided into groups, with 25 patients presenting plexiform neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas. The purposes of this study were to determine the serum IgE levels of patients with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas, as well as to determine possible correlations between serum IgE levels and the size of the plexiform neurofibromas and neurofibromas presented by these patients. Elevated serum IgE levels were observed in all the patient groups. We did not observe a correlation between IgE levels and age in these patients; however, we did observe correlations between IgE levels and neurofibroma and plexiform neurofibroma size. We suggest further studies to confirm these results and to investigate in greater depth the possible role of IgE in the development and growth of neurofibromas and plexiform neurofibromas in NF1.

Adolescent↗

PubMed1999

Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis.

The two main peripheral nerve sheath tumors found in patients with neurofibromatosis, type 1 (NF1), are neurofibroma, a benign tumor, and malignant peripheral nerve sheath tumor (MPNST). The tumors are related in that most MPNSTs are thought to arise by malignant transformation of neurofibromas. Such an event occurs in about 2% of NF1 patients. There are five forms of neurofibroma; three of them-localized cutaneous neurofibroma when multiple, plexiform neurofibroma, and massive soft-tissue neurofibroma-are highly specific for NF1. Only two forms of neurofibroma, plexiform and localized intraneural neurofibroma, are significant precursors of MPNST. Massive soft-tissue neurofibromas are worrisome in that they may mask MPNST arising from one of the mentioned neurofibromas. The vast majority of MPNSTs are high-grade malignant tumors with a high rate of distant metastasis. The overall 5-year survival rate for patients with MPNSTs ranges from 34% to 52%. MPNSTs generally are solitary, deep-seated globoid or fusiform tumors. They are firm, fleshy, tan, and often focally to extensively necrotic, and they invade surrounding soft tissue. On histological examination, MPNSTs are most often hypercellular, hyperchromatic, fasciculated, and mitotically active tumors. Low-grade tumors account for only about 10-15% of cases. Twenty percent of MPNSTs have unusual and potentially misleading histological features, such as epithelioid cells and divergent mesenchymal or glandular differentiation. Am. J. Med. Genet. (Semin. Med. Genet.) 89:23-30, 1999.

Humans↗

PubMed2002

Frequent genomic imbalances in chromosomes 17, 19, and 22q in peripheral nerve sheath tumours detected by comparative genomic hybridization analysis.

Comparative genomic hybridization (CGH) was used to detect changes in relative chromosome copy number in 50 cases of peripheral nerve sheath tumour (PNSTs), including nine malignant peripheral nerve sheath tumours (MPNSTs), 27 neurofibromas (with three plexiform neurofibromas) and 14 schwannomas. Chromosome imbalances were frequently detected in benign as well as malignant PNSTs. In both NF1-associated and sporadic MPNSTs, the number of gains was higher than the number of losses, suggesting proto-oncogene activation during MPNST progression. NF1-asociated MPNSTs exhibited gains of chromosomes 17q and X (2/4 cases each), whereas sporadic MPNSTs showed gains of chromosome 4q (3/5 cases). On the other hand, in benign neurofibromas and schwannomas, the number of losses was higher than the number of gains, suggesting a predominant role of tumour suppressor genes in tumourigenesis. Both sporadic and NF1-associated neurofibromas exhibited losses at chromosome 22q in more than 50% of cases. These chromosomal regions may contain common chromosomal abnormalities characteristic of both types of neurofibromas. In NF1-associated neurofibromas, most frequent losses were found in chromosomes 17 [17p11.2-p13 in nine cases (60%); 17q24-25 in 6 cases (40%)] and 19 [19p13.2 in eight cases (53%); 19q13.2-qter in eight cases (53%)], whereas in sporadic neurofibromas and schwannomas losses of chromosomes 17 and 19 were detected in less than 50% of cases. Since this 17p11.2-p13 region is known to contain the tumour suppressor gene TP53, patients with NF1 may be at high risk of malignant neoplasms including MPNSTs. Gains were more frequently detected in plexiform neurofibromas (2/3 cases) than other benign tumours, suggesting proto-oncogene activation in tumourigenesis of plexiform neurofibroma. The significance of the losses of chromosome 19 in these cases is not clear at present, but in NF1-associated neurofibromas, the presence of some as yet unknown tumour suppressor genes on chromosome 19 cannot be ruled out.

Adolescent↗

PubMed2004

Somatic mitochondrial DNA mutations in neurofibromatosis type 1-associated tumors.

Neurofibromatosis type 1 is an autosomal dominantly inherited disease predisposing to a multitude of tumors, most characteristically benign plexiform neurofibromas and diffuse cutaneous neurofibromas. We investigated the presence and distribution of somatic mitochondrial DNA (mtDNA) mutations in neurofibromas and in nontumor tissue of neurofibromatosis type 1 patients. MtDNA alterations in the entire mitochondrial genome were analyzed by temporal temperature gradient gel electrophoresis followed by DNA sequencing. Somatic mtDNA mutations in tumors were found in 7 of 19 individuals with cutaneous neurofibromas and in 9 of 18 patients with plexiform neurofibromas. A total of 34 somatic mtDNA mutations were found. All mutations were located in the displacement loop region of the mitochondrial genome. Several plexiform neurofibromas from individual patients had multiple homoplasmic mtDNA mutations. In cutaneous neurofibromas, the same mtDNA mutations were always present in tumors from different locations of the same individual. An increase in the proportion of the mutant mtDNA was always found in the neurofibromas when compared with nontumor tissues. The somatic mtDNA mutations were present in the Schwann cells of the analyzed multiple cutaneous neurofibromas of the same individual. The observed dominance of a single mtDNA mutation in multiple cutaneous neurofibromas of individual patients indicates a common tumor cell ancestry and suggests a replicative advantage rather than random segregation for cells carrying these mutated mitochondria.

Base Sequence↗

PubMed2003

MR imaging of spinal tumors in children with neurofibromatosis 1.

OBJECTIVE: The need for radiologic surveillance of spinal tumors in children with neurofibromatosis 1 is controversial and unresolved. We aimed to determine the incidence of spinal tumors in asymptomatic patients, describe the imaging findings, and evaluate the clinical usefulness of a prospective MR imaging surveillance program of the spine in children with neurofibromatosis 1. SUBJECTS AND METHODS: Of 62 children consecutively seen in a neurofibromatosis 1 clinic, 53 (85.5%) were recruited for MR imaging of the whole spine. All children satisfied the clinical criteria for diagnosis of neurofibromatosis 1. Imaging findings, clinical signs and symptoms, and subsequent clinical management were reviewed. RESULTS: The patients were 35 boys and 18 girls (age range, 11 months-18 years; mean age, 9.6 years), all of whom were asymptomatic, with no remarkable neurologic signs. Seven children (13.2%) had spinal neurofibromas: four had solitary neurofibromas (two dumbbell, one intradural, and one paraspinal tumor) and three had plexiform neurofibromas of the sacral plexus and thoracic and lumbar nerve sheaths. The incidences of scoliosis, localized cutaneous neurofibromas, and massive soft-tissue neurofibromas were 71.4%, 71.4%, and 28.6%, respectively, in the group with spinal neurofibromas (n = 7), and 30.4%, 39.1%, and 8.7%, respectively, in the group without spinal neurofibromas (n = 46). Patient clinical outcome was affected in only one patient (1.9%) in whom a solitary neurofibroma was resected. Follow-up imaging in 10 patients (mean period, 29 months) showed no evidence of tumor occurrence, progression, or recurrence. CONCLUSION: Although benign spinal neurofibromas are not uncommon in asymptomatic children with neurofibromatosis 1, the clinical usefulness of spine surveillance with MR imaging is limited in these children, making its effectiveness questionable.

Adolescent↗

PubMed1989

CT findings in orbital tumours of nerve sheath origin.

The clinical and CT features of orbital nerve sheath tumours (13 neurofibromas and 17 neurilemmomas, including one malignant neurilemmoma) have been reviewed. The commonest clinical findings were proptosis, mild impairment of visual acuity and disorders of eye movements. No significant correlation with intra- or extraconal location and these symptoms was found. The two types of tumour were morphologically similar, most being smooth retrobulbar masses, elongated in the long axis of the orbit; lobulation was slightly more common with neurofibromas. The neurilemmomas were generally larger than the neurofibromas. The distribution of neurilemmomas in the retrobulbar space, and in its intra- and extraconal compartments appeared random, but most neurofibromas occurred in the upper orbit and three quarters lay extraconally. The apex of the orbit was seen to be clear of tumour in all intraconal neoplasms (except the one case of malignant neurilemmoma); this observation may be useful in differentiation from intrinsic optic nerve tumours and pseudotumour. Focal or generalised enlargement of the bony orbit was common, being seen in four-fifths of neurilemmomas and three-quarters of neurofibromas. Tumour density was homogeneous for all the neurilemmomas and in the majority of neurofibromas: attenuation coefficients were slightly higher for the neurofibromas. Subcutaneous extension was more common in neurofibromas, occurring in approximately one third of cases but was observed in about a tenth of the neurilemmomas. Enhancement with intravenous contrast medium was variable; contrast medium was helpful in showing intracranial extension. Although the CT findings did not allow unequivocal presurgical diagnosis, they were suggestive in many cases and facilitated biopsy.

Humans↗

PubMed2003

Delayed rectifier K currents in NF1 Schwann cells. Pharmacological block inhibits proliferation.

K+(K) currents are related to the proliferation of many cell types and have a relationship to second messenger pathways implicated in regulation of the cell cycle in development and certain disease states. We examined the role of K currents in Schwann cells (SC) cultured from tumors that arise in the human disease neurofibromatosis type 1 (NF1). Comparisons were made between whole cell voltage clamp recordings from normal human SC cultures and from neurofibroma cultures and malignant peripheral nerve sheath tumor (MPNST) cell lines. The outward K currents of normal and tumor cells could be divided into three types based on pharmacology and macroscopic inactivation: (1) "A type" current blocked by 4-aminopyridine, (2) delayed rectifier (DR) current blocked by tetraethylammonium, and (3) biphasic current consisting of a combination of these two current types. The DR K current was present in MPNST- and neurofibroma-derived SC, but not in quiescent, nondividing, normal SC. DR currents were largest in MPNST-derived SC (50 pA/pF vs. 2.1-4.9 pA/pF in dividing and quiescent normal SC). Normal SC cultures had significantly more cells with A type current than cultures of MPNST and the plexiform neurofibroma. Conversely, MPNST and plexiform neurofibroma cultures had significantly more SC with DR current than did normal cultures, and these DR currents were significantly larger. In addition, the plexiform neurofibroma culture had significantly more cells with DR current than the dermal neurofibroma culture. K currents in SC from normal NF1 SC cultures had current abundances similar to GGF-exposed normal SC and the plexiform neurofibroma. We have established a link between DR K current blockade via TEA analogs and inhibition of proliferation of NF1 SC in vitro. In addition, a farnysyl transferase inhibitor (FTI), a blocker of Ras activation, blocked cell proliferation without blocking K currents in all cultures except a plexiform neurofibroma, suggesting that regulation of proliferation in neoplastic and normal SC in vitro is complex.

4-Aminopyridine↗

PubMed2005

Evaluation of skin viscoelasticity in type 1 neurofibromatosis patients.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disease characterized by cutaneous benign tumors called neurofibromas. Surgery takes an important place in managing these skin disorders. However, skin distensibility and softness of NF1 patients quickly offset the surgical benefit. The aim of this study was to determine the rheological behavior of neurofibromas and compare it with healthy skin in an attempt to comprehend what leads to this phenomenon. Thirty patients were admitted to this study. A group of 24 healthy control subjects was also included. The skin elasticity was assessed by a noninvasive in vivo suction device (Cutometer) including 5 consecutive suctions. The assessments were performed on neurofibroma skin, the supposedly healthy skin around neurofibromas and the healthy skin of control subjects. The extensibility at the first and the fifth traction in NF1 patients (neurofibromas and the supposedly healthy skin around it) was significantly different compared to the healthy skin of control subjects. The viscoelastic parameters obtained from the neurofibromas were significantly different in comparison to those obtained from the supposedly healthy skin of NF1 patients and the healthy skin of control subjects. The rheological profiles of the neurofibromas and the apparent healthy skin of NF1 patients demonstrated a hyperextensibility behavior, but in neurofibromas, the skin was unable to return to its initial position at the end of the stretch.

Adolescent↗

PubMed2000

Culture of cytogenetically abnormal schwann cells from benign and malignant NF1 tumors.

Dermal and plexiform neurofibromas are benign peripheral nerve sheath tumors that arise in neurofibromatosis type 1 (NF1). NF1 patients also have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs), thought to arise in a subset of plexiform neurofibromas. Plexiform neurofibroma pathogenesis is poorly understood, despite the serious clinical problem posed by these tumors. The Schwann cell is hypothesized to be the cell type initially mutated and clonally expanded in plexiform neurofibromas. To test this hypothesis and search for genetic alterations involved in tumorigenesis, we established Schwann cell cultures from plexiform and dermal neurofibromas. Cytogenetic abnormalities were identified in 4/6 plexiform cultures (including one from a plexiform with a sarcomatous component) and 0/7 dermal neurofibroma Schwann cell cultures. There were no consistent chromosomal regions involved in the abnormal karyotypes, suggesting that plexiform tumors are heterogeneous and may bear a variety of primary and/or secondary genetic changes. This is the first study to show successful culturing of genetically abnormal Schwann cell lineages from plexiform neurofibromas. Thus, we present the strongest evidence yet to support the theory that the Schwann cell is the central component in the development of plexiform neurofibromas. This is a key finding for NF1 research, which will lead to further studies of the genetic and biochemical pathogenesis of these Schwann cell tumors. Genes Chromosomes Cancer 27:117-123, 2000.

Cell Division↗

PubMed2002

Integrated imaging in peripheral nerve lesions in type 1 neurofibromatosis.

PURPOSE: Our aim was to evaluate the role of Ultrasonography (US) and Magnetic Resonance (MR) in the staging and follow-up of peripheral nerve lesions in type 1 Neurofibromatosis (NF1). MATERIAL AND METHODS: We evaluated forty-six NF1 patients (16 males and 30 females, age range 12-65 years, mean age 34 years) affected by 51 soft tissue lesions, clinically diagnosed as subcutaneous (18 cases) and plexiform (33 cases) neurofibromas. The lesions were studied to identify site, size, extension, relationship with surrounding structures, and any features indicating malignant transformation. All patients underwent at least one US examination performed with a 7.5 - 10 MHz linear multi-frequency probe. All subcutaneous neurofibromas larger than 2 cm, all superficial or deep plexiform neurofibromas not clearly defined at US, and all large plexiform neurofibromas with massive involvement of surrounding tissues were studied by MR using 0.2 T magnet (Artoscan) or 1.5 T magnet (Magnetom Vision Plus Siemens). Fifteen patients underwent surgery; the remaining cases (31) were followed up according to the National Institutes of Health (NIH) protocol. RESULTS: The subcutaneous neurofibromas smaller than 2 cm showed homogeneous hypoechoic echotexture (10 cases), whereas lesions equal to or larger than 2 cm showed a characteristic target pattern (peripheral hypoechoic rim with hyperechoic core). All lesions larger than 2 cm studied by MRI displayed the target pattern in T2-weighted sequences, with peripheral signal hyperintensity and central signal hypointensity. At US, the 33 plexiform neurofibromas had an irregular shape with undefined borders; the patterns were classified as follows: 1) superficial plate-like lesions (14 cases); 2) superficial lesions with deep digitations (8 cases); 3) deep multi-lobulated lesions (5 cases); 4) extensive lesions massively involving soft tissues (6 cases). MRI was performed in 11 cases, showing an isointense or moderately hyperintense signal on T1-weighted sequences, high signal intensity on T2-weighted sequences, and, after intravenous gadolinium administration, variable enhancement on T1-weighted sequences. CONCLUSIONS: The results obtained in subcutaneous neurofibromas indicate a clear relationship between lesion size and US-MR imaging, with similar local staging. Since MRI failed to provide additional information, US may be considered the first-choice, and sometimes decisive, examination in these cases. As regards plexiform neurofibromas, US only proved useful in staging superficial lesions and partly deep multi-lobulated lesions as it accurately depicted lesion size, but not local extension; MRI is therefore useful in the preoperative staging of lesions. In extensive lesions, US proved unable to provide accurate and complete local staging of the lesions, so that MRI should be systematically used in these cases.

Adolescent↗

PubMed2004

Subclassification of nerve sheath tumors by gene expression profiling.

Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1-patients, whereas plexiform neurofibromas are only observed in one-third of the patients. NF1-patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1-patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1-associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.

Adolescent↗

PubMed2000

Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Adolescent↗

PubMed2007

Radiation induced peripheral nerve tumors: case series and review of the literature.

PURPOSE: Radiation induced peripheral nerve tumors (PNT) are a rare but known complication of radiotherapy. The clinical and pathologic features of six cases of post-radiation PNT's are reported here, more than doubling the number of known cases reported in the literature. METHODS: We reviewed six cases of radiation induced PNT and performed a review of the current literature on radiation induced neurofibromas. RESULTS: Patient's ranged in age from 18 months to 49 years at the time of their original diagnosis, with radiation doses to the primary tumor ranging from 24 to 40 Gy with post radiation intervals from 10 to 50 years. The majority of PNT's identified were neurofibromas (3) and schwannomas (3). Nuclear atypia, S100 positive staining and mild-moderate cellularity were common pathologic findings. CONCLUSIONS: There are only a handful of neurofibromas in the 60 cases of PNT's thus far reported. This case series broadens the post-radiation neurofibroma literature. While the pathology of PNT induced transformation is still poorly understood, experiments and pathology are congruent on the possibility of malignant transformation, especially for the "atypical neurofibroma". On the clinical level, this case series lends its support to some, but not all, of the risk factors thought to predispose to the formation of radiation induced neurofibromas. Though rare, the complication of radiation-induced neurofibroma cannot be ignored, especially with the increasing use of focused radiosurgical techniques.

Adult↗

PubMed2002

Neurofibromatosis type 1 and the pediatric neurosurgeon: a 20-year institutional review.

Children with neurofibromatosis type 1 (NF1) undergo costly surveillance scanning for a variety of asymptomatic central nervous system lesions whose natural history is poorly understood. We performed a 20-year retrospective chart review of 25 patients with clinically proven NF1 who required surgery (group A) and contrasted this cohort with 150 NF1 patients who did not require surgery (group B). In group A, 52% of patients underwent multiple procedures for more than one lesion (p = 0.043). Group A patients were further distinguished from those in group B by exhibiting a greater number of optic gliomas (p = 0.015), nonoptic intracranial tumors (p = 0.006), cranial nerve (p = 0.000), paraspinal (p = 0.0062), craniofacial (p = 0.001) and visceral (p = 0.03) neurofibromas and moyamoya disease (p = 0.00), as well as a higher frequency of seizure disorder, sphenoid wing dysplasia and poor academic performance. Gadolinium enhancement occurred in 43% of optic gliomas, 50% of parenchymal gliomas, 100% of cranial nerve, 100% of plexus, 67% of paraspinal, 50% of craniofacial and 50% of visceral neurofibromas in group A, while only 1 group B tumor enhanced. In group A, radiological progression occurred after a median of 4 years from initial diagnosis for optic gliomas as well as cranial nerve, plexus and visceral neurofibromas, 2 years for paraspinal neurofibromas and brainstem gliomas and 2.7 years for craniofacial neurofibromas. Only 1 tumor progressed in group B. Therefore, a small subgroup of NF1 patients (12.5%) who require treatment are at risk of subsequently needing further surgical attention, whereas a larger group of NF1 patients (87.5%) carry an indolent form of the disease. We recommend imaging for asymptomatic, gadolinium-enhancing lesions every 2 years for optic pathway and parenchymal gliomas and cranial nerve and visceral neurofibromas, and every year for brainstem gliomas and paraspinal as well as craniofacial neurofibromas. Nonenhancing optic pathway lesions could be followed up radiographically much less often since they do not show progression.

Brain Neoplasms↗

PubMed1987

Tumors of the brachial plexus.

Over a 17-year period, 56 patients with 57 tumors involving the brachial plexus were operated upon. The 40 neural sheath tumors included 26 neurofibromas, 8 schwannomas, 4 malignant neural sheath tumors, 1 fibrosarcoma, and 1 meningioma. Nine of the neurofibromas were associated with von Recklinghausen's disease (VRD), and 2 others were what was termed regionalized neurofibromatosis characterized by involvement of one limb with extension along the course of one or more plexus elements. Seventeen tumors were not of neural sheath origin; 7 were benign and 10 were metastatic malignant tumors compressing or invading the plexus. Benign neurofibromas and malignant sheath tumors almost always presented with pain or functional neural deficit, whereas schwannomas often presented with a palpable mass as their only initial symptom. Patients with solitary neurofibromas were significantly older, often female, and more likely to have tumor on the right side than patients with schwannomas, malignant neural sheath tumors, or neurofibromas associated with VRD. Solitary neurofibromas could often be totally resected without added deficit by sacrificing fascicles entering and leaving tumor that were determined to be "nonfunctional" by intraoperative nerve action potential recordings. Resection of neurofibromas associated with VRD sometimes but not always resulted in significant loss. Operation is nonetheless recommended, especially when malignancy is suspected because of rapidly increasing size, when severe pain or neural deficit is present, or when compression of adjacent plexus elements is a concern. Schwannomas and benign non-neural sheath tumors can usually be extirpated without damage to plexus elements. Forequarter amputation is advised for malignant intrinsic tumors involving distal plexus elements even though gross total resection seems feasible.

Adult↗