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PubMed1997

Thoracic tumors in children with neurofibromatosis-1.

Thoracic tumors have been infrequently reported as a complication of neurofibromatosis-1 (NF1). To determine the prevalence and clinical features of thoracic tumors seen in children with NF1, we reviewed medical records and imaging studies for a group of 260 pediatric patients with NF1 followed in a multidisciplinary NF Center. Extrapleural thoracic tumors were seen in nine patients with NF1, corresponding to a prevalence of 3.5% in this hospital-based series of patients. Pathological studies of the tumors demonstrated plexiform neurofibroma in four cases and neurofibrosarcoma in one case. The remaining four cases were suspected to be plexiform neurofibroma based on clinical features but have not been confirmed histologically. Three patients presented with symptoms of chest pain, syncope, or wheezing; six patients were asymptomatic at the time of diagnosis of the tumors. Physical findings frequently found in patients with thoracic tumors were scoliosis (especially focal scoliosis) and visible plexiform neurofibromas of the neck. We conclude that NF1 patients presenting with any of these signs and symptoms should be screened for thoracic tumors with chest X-ray and magnetic resonance imaging as needed. It is unknown whether screening asymptomatic NF1 patients with chest X-rays on a regular basis will result in an improved outcome.

Adolescent↗

PubMed2005

Neurofibromatosis type 1 in a pediatric population: Ste-Justine's experience.

BACKGROUND: To date, few pediatric series of neurofibromatosis type 1 (NF-1) have been described in the literature even though it is the most frequently encountered phakomatosis. METHODS: We reviewed 987 charts of pediatric patients with a presumptive diagnosis of NF-1 who were evaluated at Ste-Justine hospital from January 1, 1991 to July 31, 2002. Patients who presented with two or more cardinal criteria were diagnosed with NF-1. Clinical and laboratory data were retrospectively collected, including: demographics, neuroimaging and presence or absence of associated symptoms or signs of NF-1. RESULTS: A total of 279 patients were diagnosed with NF-1. The mean age at diagnosis was 3.4 years. Ninety-nine percent of the patients had café au lait spots and 47% had a first degree relative with NF-1. Almost 60 percent (59.6%) of those seen by an ophthalmologist had Lisch nodules. Optic glioma was found in in 14.7%, cutaneous neurofibromas in 38.4%, plexiform neurofibromas in 24.7%, neurofibrosarcoma in 1.8%, learning disabilities in 39%, attention deficit disorder in 40.5%, osseous dysplasias in 7.2%, pseudoarthrosis in 3.6%, precocious puberty in 3.2% and short stature in 17.9%. Magnetic resonance, when performed, showed hyperintense T2 lesions in 87.1% of cases. The mean period of follow-up was 7.4 years. CONCLUSION: Neurofibromatosis type 1 is a multisystemic disorder associated with increased risk of malignancy. It can be diagnosed at a very young age and clinical follow-up is advised. To our knowledge, this is the largest single center study of NF-1 in a pediatric population.

Adolescent↗

PubMedDate not supplied

Comparison of fine-needle aspiration and surgical-tissue biopsy in the diagnosis of canine brain tumors.

OBJECTIVE: To compare the diagnoses obtained using fine-needle aspiration (FNA) and surgical-tissue biopsy of focal cerebral masses with the histologic diagnoses obtained via necropsy. STUDY DESIGN: A prospective case series. SAMPLE POPULATION: Ten client-owned adult dogs of various breeds. All dogs had clinical signs of cerebral disease and had a focal brain mass identified using magnetic resonance imaging; all were eventually euthanatized. METHODS: Immediately after euthanasia, the brains were removed en bloc from the cranial cavity. FNAs were obtained from each mass using a 22-gauge hypodermic needle and a 12-mL syringe. Cytologic preparations were made from each aspirate. A 14-gauge Tru-cut biopsy needle was used to obtain a core tissue sample from each mass. The biopsy specimens were fixed in 10% buffered formalin and submitted for histologic evaluation. The brains were similarly fixed and stained. Six-micrometer-thick transverse sections of the brain were examined microscopically. RESULTS: Neoplasia was confirmed in all dogs histologically in the 6-microm transverse sections. Four meningiomas, 2 astrocytomas, 2 oligodendrogliomas, 1 pituitary adenocarcinoma, and 1 neurofibrosarcoma were identified. FNA correctly identified all of the masses as neoplastic. Cytologic diagnoses correlated with the histologic interpretation in 5 of the masses (50%). Tru-cut biopsy specimens identified all 10 masses as neoplastic; in 9 of the 10 (90%), the diagnosis correlated with the histologic diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: FNA is a sensitive method that can be used to determine the presence of neoplasia in the brain, but is not as definitive as the Tru-cut biopsy in determining the specific type of cerebral neoplasm.

Adenocarcinoma↗

PubMed2004

[A huge malignant degenerating neurofibroma of the lower leg coexistent with type 1 Recklinghausen disease].

HISTORY: A 65-year-old man had noted a tumor of the right lower leg that had progressively grown over the last twenty years. He had a dyspnoea on insignificant movement and was relatively immobile because of the extent of the tumor. The tumor had been diagnosed as a Klippel-Trenaunay syndrome. INVESTIGATIONS: Laboratory investigations suggested a hypochromic and microcytic anaemia and an inflammatory constellation. The tumor had no av-fistulas on ultrasonography and angiography, but there were many pathological arteries and tumor nodes. The tumor nodes had been seen also on MRI-biopsy suggested a neurogenic sarcoma. DIAGNOSIS AND TREATMENT: Amputation of the leg was necessary. The histological diagnosis was neurofibrosarcoma with extensive necrotic areas and Recklinghausen disease. Investigation did not reveal any metastasis. Postoperatively the anaemia regressed and the patient learned to walk with a prosthesis. CONCLUSIONS: This history shows the problem of separating clearly the two hereditary diseases. Often there is a different clinical picture in everyday life. One must consider the definitely higher risk of malignant tumors of patients with neurofibromatosis. Ultrasonography is a non-invasive method that can provide morphological information on soft parts and pathology of the vessels. It facilitates the classification of such.

Aged↗

PubMed2001

Sciatic nerve resection in the thigh: a functional evaluation.

Patients with a soft tissue malignancy involving the sciatic nerve who present with neurologic loss generally are advised to have an amputation. Twenty patients who underwent limb-sparing procedures with complete resection of the sciatic nerve as treatment for neurofibrosarcomas (12 patients), liposarcomas (four patients), malignant fibrous histiocytomas (two patients), recurrent desmoid tumor (one patient), and epithelioid hemangioendothelioma (one patient) were reviewed retrospectively. The mean age of these nine women and 11 men at the time of surgery was 51 years (range, 28-84 years). The right sciatic nerve was affected in 12 patients. These tumors were large and high grade. A mean of 22 cm of the nerve had to be resected (range, 8-42 cm). Ten patients received preoperative radiotherapy and 16 patients had intraoperative or postoperative radiotherapy. At a mean followup of 35 months (range, 7-97 months), 14 of the 20 patients were alive. Two patients had local recurrences develop (10%), whereas 12 patients had distant metastases. The function of the 10 patients as assessed by the Toronto Extremity Salvage Score averaged 74%. Most patients indicated that walking in the house is not difficult, but walking is compromised as soon as an effort is needed. Four patients walk without a cane, four needed one cane, and two needed two canes. The patients experienced stiffness, a sense of numbness, and premature fatigue. The use of analgesics was infrequent. Generally, patients rated themselves to be mildly to moderately disabled. From this small number of patients, it is shown that a tumor involving the sciatic nerve can be treated by limb-sparing surgery, including complete nerve resection, as an alternative to hip disarticulation or hindquarter amputation because the limb salvage option provides an acceptable functional outcome.

Activities of Daily Living↗

PubMed1997

Cervical neuromas with extradural components: surgical management in a series of 57 patients.

OBJECTIVE: Cervical neuromas with extradural components (intraextradural or strictly extradural forms) are rare. Their resection raises the problems of nerve root preservation, vertebral artery (VA) control, and spinal stability. METHODS: A series of 57 patients with neuromas (29 neurofibromas, 23 schwannomas, 4 neurofibrosarcomas, and 1 plexiform neurofibroma) was treated during the period of 1980 to 1995, using one of the lateral approaches (antero- or posterolateral approach). The VA was always controlled before resection of the tumor. In cases of intraextradural forms, the intradural component was removed by a complementary laminectomy (three patients) in the early period and then by an oblique corpectomy through the same lateral approach (five patients) in the late period. A laminectomy had been performed in 15 other patients (11 patients with intraextradural neuromas) before they were referred to us. These patients included seven with recurrent neuromas, occurring after an average period of 4.1 years (1-9 yr). RESULTS: Complete resection was achieved in all except two patients, in whom the nerve root reacted positively to intraoperative stimulation and could not be separated from the tumor. One of the patients was subsequently operated on after 2 years. Another recurrence was observed in another patient at 1 year. The four patients with sarcomas died from recurrence within 2 years. The rate of root preservation included an average of 28%, including 43.5% for schwannomas, 18% for neurofibromas, 44% for lower cervical neuromas (C4-C8), and 4.5% for upper cervical neuromas (C1-C3). Worsening of preoperative neurological deficits was observed in only two patients. The VA was always preserved, except in one patient with a sarcoma that was preoperatively occluded. No instability was observed in any of the patients. CONCLUSION: Complete resection with good neurological results can be achieved in most patients harboring cervical neuromas each with an extradural component by using a lateral approach and VA control. If the root cannot be separated from the tumor, especially in patients with neurofibromas, intraoperative stimulation can help decide whether the root may be divided without incurring postoperative deficit. The lateral approach permits the resection of the extradural as well as the intradural component by a complementary oblique corpectomy. There was no morbidity in relation to VA control as well as no postoperative instability.

Adult↗

PubMed1996

A retrovirus isolated from cell lines derived from neurofibromas in bicolor damselfish (Pomacentrus partitus).

Damselfish neurofibromatosis (DNF) is a naturally occurring, neoplastic disease affecting bicolor damselfish (Pomacentrus partitus) living on coral reefs in southern Florida, USA. The disease consists of multiple neurofibromas, neurofibrosarcomas and chromatophoromas and has been proposed as an animal model for neurofibromatosis type 1 in humans. DNF is transmissible by injection of crude tumour homogenates, cell-free filtrates of homogenates or cells from tumour cell lines. An analysis of tumorigenic cell lines derived from fish with spontaneous or experimentally induced DNF revealed virus particles budding from cells and present in conditioned media. The 90-110 nm particles resembled type C retroviruses. This virus exhibited a buoyant density of 1.14-1.17 g/cm2 in sucrose, at least six virus proteins of 15 to 80 kDa and reverse transcriptase (RT) activity. RT activity was maximized with a poly(rC).oligo(dG) template.primer combination and Mn2+ at a concentration of 0.5-1.0 mM. The optimum temperature for RT was determined to be 20 degrees C, a finding consistent with the ambient temperatures encountered by this species. This retrovirus, tentatively named damselfish neurofibromatosis virus (DNFV) may be the aetiological agent of DNF. Whether DNFV or another, as yet unidentified, virus is the cause of DNF, this agent may be unique in virus oncogenesis; neoplastic transformation of the cell types involved in DNF, Schwann cells and chromatophores, has not been documented in any other transmissible tumour.

Animals↗

PubMed1996

A retrospective study of pancreatic tumors in slaughter cattle.

Sixteen primary pancreatic tumors were found in a retrospective study of bovine pancreatic lesions detected in slaughtered cattle. Eleven islet cell tumors and three pancreatic exocrine carcinomas were identified based on light microscopy and immunohistochemistry. Nine of 11 islet cell tumors were classified as malignant. Metastatic sites included iliac, mediastinal, hepatic, and mesenteric lymph nodes, peritoneum, mesentery, and liver. Six cows with multiple islet cell tumors also had pheochromocytomas. All 11 islet cell tumors had positive immunoreactivity to insulin and somatostatin. Three tumors also contained cells immunoreactive for glucagon and two tumors contained pancreatic polypeptide immunoreactive cells. Immunoreactivity of tumor cells in metastatic sites was similar to their respective primary tumors. All exocrine pancreatic carcinomas metastasized widely and were immunonegative for insulin, somatostatin, glucagon, and pancreatic polypeptide. No mixed endocrine-exocrine tumors were identified. None of the endocrine or exocrine tumors contained amyloid. Additional primary tumors of the bovine pancreas included one neurofibroma and one neurofibrosarcoma. Additional cases with lesions of the bovine pancreas included nodular hyperplasia in 15 cows, exocrine acinar atrophy and fibrosis in four cows (two of which also had pancreatic lithiasis), pancreatitis in one cow, peripancreatic fibrosis in two cows, pancreatic steatosis in one animal, and pancreatic hemorrhages in one cow.

Adenoma, Islet Cell↗

PubMedDate not supplied

Diagnosis, classification, and management of soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas are challenging to oncologists due to their unique character, the infrequency of their occurrence, and the difficulties in predicting outcomes. Advances in imaging, as well as improvements in surgical techniques and adjunctive treatment methods, have improved care for patients with these unusual disorders. METHODS: The various types of soft tissue tumors are defined, and the statistics for the Orthopaedic Oncology Group in relation to them are reviewed and compared with literature references. RESULTS: The overall survival rate for 1,220 tumors treated at our institute from June 1972 to June of 2001 was 72%, with a wide range. Patients with leiomyosarcomas, clear cell sarcomas, and malignant fibrous histiocytomas had a poorer survival rate, while those with fibrosarcomas, liposarcomas, and neurofibrosarcomas fared better. Outcome was affected by patient age, tumor anatomic site, tumor stage, and a history of recurrence. CONCLUSIONS: Competent imaging, predictive immunological and genetic studies, improved surgery, and newer methods of adjunctive and neoadjunctive treatment should result in improvements in outcomes for patients with these tumors.

Adolescent↗

PubMed1998

[Late results of radiotherapy of soft tissue sarcoma].

PURPOSE: To evaluate the effect of radiation therapy in the treatment of soft-tissue sarcomas. MATERIALS AND METHODS: Between March 1970 and January 1990, 58 patients with soft-tissue sarcoma were referred for radiation therapy. The most frequent histologic diagnoses included fibrosarcoma (n = 15), neurofibrosarcoma (n = 5) and rhabdomyosarcoma (n = 5). Central tumor sites in the trunk (n = 31) were much more frequent than in the head and neck region (n = 14) or the extremities (n = 13). Thirty-nine of 58 primary tumors were bigger than 5 centimeters. Forty-five patients were irradiated after surgery, 5 patients prior to surgery; in 8 cases only radiation therapy was used. Radiation therapy was performed with Co-60 photons and an average total dose of 58 Gy, fractionated in single doses of 2 Gy. The treatment results were obtained by actual follow-up examinations. RESULTS: Twenty-three of 58 patients survived at least 5 years (39.9%). Of 15 patients with R0 resection 11 were alive after 5 years (73.3%). Local tumor control was achieved in 34 of 58 patients (58.6%). Low 5-year-survival rates were associated with dedifferentiation of the primary tumor (three survivors in 10 patients with G3 tumor), tumor diameters over 5 cm (13 survivors of 39), R2 resection (3 survivors of 16) and tumor sites in the body trunk (11 survivors of 31). CONCLUSIONS: (1) The best results of radiation therapy were achieved after R0 resection of the primary tumor. (2) Tumors in the trunk are prognostically worse because of bigger tumor diameters due to later diagnosis.

Female↗

PubMed1998

[The clinicopathological study on 41 cases of cardiac tumors].

OBJECTIVE: To analyze the relation between the pathological changes and the prognosis of cardiac tumors through the clinicopathological study on 41 cases of cardiac tumors. METHODS: The study was carried out by using the common and special histochemical stainings. RESULTS: 39(95.1%) tumors were benign, including myxoma, fibroma, and rhabdomyoma; while 2(4.9%) tumors were malignant, including neurofibrosarcoma and malignant mesothelioma. In the myxomas group, 75% patients were female, 91.7% tumors existed in the left atrium. CONCLUSIONS: The results of the clinicopathological study showed that the cardiac tumors were quite different from the tumors in the other sites, i.e. even benign ones could cause fatal hemodynamic disturbance, hence early diagnosis and early operation are necessary. The prognosis of the malignant tumors is worst.

Female↗

PubMedDate not supplied

[Brachial plexus tumors].

The brachial plexus is a primary site of tumours originating from peripheral nervous system, such as neurilemmoma and neurofibroma. Moreover, the brachial plexus is affected by various neoplasms spreading from the neighbouring anatomic structures. Surgical treatment of neoplasms provoking plexopathy is often realised by multidisciplinary teams. The authors present the series of 7 patients operated on for brachial plexus affection between 1993-2000, the pathologic findings were as follows: neurofibroma, neurilemmoma, lymphogranulomatosis, neurofibrosarcoma, lipoma, chordoma, sarcoma neurogenes. The analysis of clinical course includes: main symptoms, diagnostic procedures and results of treatment. Surgical technique is also described.

Adult↗

PubMed2003

Metastatic disease of the proximal femur.

Since January 1999, ten patients had undergone surgical treatment for metastatic bony lesions of proximal femur at this centre. Seven of these patients were treated for complete pathological fractures, one for impending fracture and one for revision of internal fixation and loosening of hemiarthroplasty. Primary malignancies were located in breast in four cases, prostate in three and one in lung, thyroid and neurofibrosarcoma. Two patients had died within six months after surgery, four after 1 year while the remaining four were still alive. The mean duration of survival was eleven months. Nine patients had been ambulating pain free and there were no failure of reconstruction.

Adult↗

PubMed1997

A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors.

Neurofibromatosis type I (NF1) is a common disorder that predisposes to neoplasia in tissues derived from the embryonic neural crest. The NF1 gene encodes a tumor suppressor that most likely acts through the interaction of its GTPase-activating protein (GAP)-related domain (GRD) with the product of the ras protooncogene. We have previously identified a site in the NF1 mRNA, within the first half of the NF1 GRD, which undergoes base-modification editing. Editing at that site changes a C to a U, thereby introducing an in-frame stop codon. NF1 RNA editing has been detected in all cell types studied, to date. In order to investigate the role played by editing in NF1 tumorigenesis, we analyzed RNA from 19 NF1 and 4 non-NF1 tumors. We observed varying levels of NF1 mRNA editing in different tumors, with a higher range of editing levels in more malignant tumors (e.g., neurofibrosarcomas) compared to benign tumors (cutaneous neurofibromas). Plexiform neurofibromas have an intermediate range of levels of NF1 mRNA editing. We also compared tumor and nontumor tissues from several NF1 individuals, to determine the extent of variability present in the constitutional levels of NF1 mRNA editing and to determine whether higher levels are present in tumors. The constitutional levels of NF1 mRNA editing varied slightly but were consistent with the levels observed in non-NF1 individuals. In every case, there was a greater level of NF1 mRNA editing in the tumor than in the nontumor tissue from the same patient. These results suggest that inappropriately high levels of NF1 mRNA editing does play a role in NF1 tumorigenesis and that editing may result in the functional equivalent of biallelic inactivation of the NF1 tumor suppressor.

Astrocytoma↗

PubMed1977

Soft-tissue sarcoma of the head and neck after puberty.

The most frequent soft-tissue sarcomas in the head and neck are are embryonal rhabdomyosarcomas and neurofibrosarcomas. Histological grading and the staging of the lesions bear on the prognosis of the disease. The use of sequential surgical resection plus postoperative radiation therapy has considerably improved the local control of these sarcomas. The use of multiple-drug systemic chemotherapy as an adjuvant to radiation therapy is fraught with considerate complications in this seris of patients. Studies are ongoing for a better understanding of the immunologic changes that occur in patients with sarcoma.

Adult↗

PubMed1999

Tikhoff-Linberg procedure for bone and soft tissue tumors of the shoulder girdle.

OBJECTIVE: To evaluate complications and the oncological and intermediate-term functional results in patients with bone and soft tissue tumors of the shoulder girdle who were managed with interscapulothoracic resection (Tikhoff-Linberg procedure). DESIGN: Case series of 19 consecutive patients during a 10-year period at a mean follow-up of 6.3 years (range, 1-11 years). SETTING: University hospital; referral center for musculoskeletal tumor surgery. PATIENTS: The initial diagnosis in this consecutive series of patients with shoulder girdle tumors requiring the Tikhoff-Linberg procedure was chondrosarcoma in 7 patients, Ewing sarcoma in 3 patients, malignant fibrous histiocytoma in 3 patients, solitary metastasis of thyroid carcinoma in 2 patients, osteosarcoma, synovial sarcoma, angiosarcoma, ancd neurofibrosarcoma in 1 patient each. According to the Musculoskeletal Tumor Society staging system, there were 6 in surgical stage IB, 10 in stage IIB, and 3 in stage III. Nine tumors involved the proximal humerus, 8 were located in the scapula or surrounding soft tissues, 1 in the lateral clavicle, and 1 in the acromioclavicular joint. INTERVENTIONS: For reconstruction of the proximal humerus after en bloc tumor resection an isoelastic cemented shoulder tumor prosthesis was inserted in every patient to restore arm length. MAIN OUTCOME MEASURES: Complications, and oncological and intermediate-term functional results. RESULTS: Twelve patients were alive with no evidence of disease. One of these patients died of nontumorous disease 2 years after surgery. One patient is alive with pulmonary metastases after 12 months. Six patients died of metastases at a mean (SD) interval of 18 months (range, 3-35 months) postoperatively. Two of these patients had additional local recurrence. A deep infection necessitated the explantation of the prosthesis in 1 patient. The mean functional score and SD according to the rating system of the Musculoskeletal Tumor Society was 72%+/-14% (range, 33%-87%) for the 12 surviving patients evaluated. Major complications (1 infection and 2 local recurrences) that may be attributed to the procedure occurred in 3 of the 19 patients. CONCLUSION: Despite an overall complication rate of 74% the Tikhoff-Linberg procedure proved to be a valuable surgical procedure for extended tumors of the shoulder girdle for functional and oncological outcome and is superior to forequarter amputation.

Adolescent↗

PubMed1997

Fine-needle aspiration biopsy in the diagnosis and management of bone lesions: a study of 450 cases.

BACKGROUND: Fine-needle aspiration (FNA) biopsy has proved to be a cost-effective technique, with low complication risks and high diagnostic value in distinguishing neoplastic versus nonneoplastic lesions in many organs. This study was designed to determine the reliability, areas of diagnostic difficulty, and limitations of FNA in the diagnosis of bone lesions encountered in a university-affiliated tertiary care hospital. METHODS: The cytology of 450 FNA biopsies of bone lesions, performed on 427 patients between 1979 and 1996, were reviewed. The results were correlated with the corresponding histology when available, and with clinical follow-up, in an attempt to define the role of FNA in managing patients with bony lesions. RESULTS: The patients ranged in age from 5 to 94 years, with a male-to-female ratio of 1.25:1. The spine was the most frequently aspirated site (49%), followed by the ilium, sacrum, mandible, ribs, and femur. Three hundred and eighty-five aspirates (86%) were adequate for evaluation, with 215 cases diagnosed cytologically as positive for malignancy, 11 cases as suspicious but not diagnostic of malignancy, and 2 cases as inconclusive. One hundred and fifty-seven cases were interpreted as showing no evidence of malignancy. Metastatic carcinoma was present in 175 of the 215 malignant aspirates, and 67% of these were adenocarcinomas. Forty cases were primary malignant bone neoplasms, including myeloma, lymphoma, Ewing's sarcoma, chondrosarcoma, ameloblastoma, chordoma, neurofibrosarcoma, and unclassified high grade sarcoma. False-negative diagnoses were rendered in ten cases; however, on review, material representative of the bone lesion was not present in six cases. Five cases were correctly diagnosed as malignant but were misclassified with regard to the type of malignancy. CONCLUSIONS: FNA biopsy of bone lesions is a reliable and easily performed diagnostic test for metastatic and primary bone tumors. False-positive results have major therapeutic implications, hence the significance of the authors' conservative diagnostic approach, which resulted in a false-positive rate of 0.2%. Areas of difficulty were due to inadequate sampling or misclassification with regard to the exact type of malignancy. The simplicity and accuracy of this procedure, which does not require any surgical incisions (open biopsy or manipulation), supports its important role in triaging and managing bone lesions with minimum risk or morbidity.

Adolescent↗

PubMed1998

Ionic currents in normal and neurofibromatosis type 1-affected human Schwann cells: induction of tumor cell K current in normal Schwann cells by cyclic AMP.

Comparisons were made of whole cell voltage clamp recordings from cultures of normal Schwann cells (SC) from three human subjects and from three neurofibrosarcoma cell lines. The whole cell K+ (K) currents of normal and tumor cells could be divided into three types based on voltage activation range, pharmacology, and macroscopic inactivation: A type current, tetraethylammonium- (TEA-) only-sensitive current, and inward rectifier current. The most conspicuous difference between normal and tumor cells was the nature of K currents present. Normal SC K currents were inactivating, A type currents blocked by extracellular 4-aminopyridine (4-AP; 5 mM). The whole cell K currents of tumor cells were noninactivating due to the presence of non-inactivating A current, or non-inactivating, TEA-only sensitive current, or both, despite the presence of inactivating A current in some tumor cells. TEA-only-sensitive currents, which were 4-AP-insensitive and noninactivating, were common in all three tumor cell lines, but were not observed in normal SC. Inward rectifier K currents were a conspicuous feature of two of the tumor cells lines but were rarely observed in whole cell recordings of normal SC. The properties of Na+ currents recorded in both normal and tumor cells were not significantly different. Treatment of normal SC with a membrane-permeant analog of cyclic AMP (cAMP) resulted in functional expression of the TEA-only-sensitive K currents typical of tumor cells. These results establish the abnormal ion channel profile of neurofibromatosis type 1 (NF1)-tumor cells and suggest (Guo et al.: Science 276:795-798, 1997) that regulation of ionic currents by second messengers may involve the NF1 gene.

4-Aminopyridine↗