Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and synchronous development of MPNST and metastasis

Melean, Germán; Hernández, Alba; Valero, M. Carmen; Hernández-Imaz, Elisabete; Martín, Yolanda; Hernández-Chico, Concepción

doi:10.1186/1471-2407-10-407

Cited by 9 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are at least 30 published case reports of MZ twins with NF1. Many MZ twins have very similar clinical features (CAL spots, axillary and inguinal freckling, Lisch nodules, epilepsy, non-dysplastic scoliosis, renal vascular hypertension, unilateral ptosis and cutaneous neurofibromas) 2 3 14. In principle, this is explained by identical NF1 mutations, near-identical genomic backgrounds and very similar pre- and perinatal environments.…”

Section: First Clues: Natural History Studiesmentioning

confidence: 99%

“…Other non hereditary factors could also influence tumour initiation and growth, such as epigenetic changes, somatic mutations in other tumour-related genes and environmental factors. A recent report describes a pair of MZ twins with NF1 resulting from a de novo mutation, both of whom developed a left-sided sciatic plexiform neurofibroma that progressed to MPNST at a similar age, with pulmonary metastasis also occurring at the same age 14. However, data on MZ twins, although precious, should be interpreted with care.…”

Section: First Clues: Natural History Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Neurofibromatosis type 1: from genotype to phenotype

et al. 2012

View full text Add to dashboard Cite

Although neurofibromatosis 1 (NF1) is a common Mendelian disorder with autosomal-dominant inheritance, its expression is highly variable and unpredictable. Many NF1 patients have been genotyped but few allelephenotype correlations have been identified. NF1 genotype-phenotype correlations are difficult to identify because of the complexity of the NF1 phenotype, its strong age dependency, the relatedness of many clinical features and the huge heterogeneity of pathogenic NF1 mutations. Some NF1 patients with a given NF1 mutation may develop very severe disease while others with the same mutation have only mild symptoms. This phenotypic variability may be due to both modifier genes and environmental factors. Recent targeted strategies have identified several interesting candidate modifier genes.

show abstract

Section: First Clues: Natural History Studiesmentioning

confidence: 99%

Section: First Clues: Natural History Studiesmentioning

confidence: 99%

Neurofibromatosis type 1: from genotype to phenotype

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Patients with neurofibromatosis type 1 (NF1) develop more neurofibromas, at younger age, and have increased risk of MPNSTs [4]. Our patient did not show any of the typical cutaneous hallmarks of NF1 disease, and was therefore considered sporadic.…”

Section: Histological Findings and Diagnosismentioning

confidence: 93%

Intramedullary malignant peripheral nerve sheath tumor

et al. 2011

View full text Add to dashboard Cite

Primary spinal cord tumors represent 2-4% of central nervous system (CNS) tumors. Intramedullary tumors predominantly include diffuse astrocytomas and ependymomas [1]. Intramedullary schwannomas are rare and account for 0.3-1.5% of all spinal schwannomas [2]. Thus far, no primary intramedullary malignant peripheral nerve sheath tumor (MPNST) has been described. Only a postradiation intramedullary MPNST was described, in 2006, with metachronous laryngeal cancer [3].We report the case of a 56-year-old man who developed a sensory impairment in his left leg and in his right arm over a 6-month period. Cervical magnetic resonance imaging (MRI) revealed a C2-C3 intramedullary, heterogeneous, contrast-enhancing lesion (Fig. 1a, b). Neurological examination revealed sensory loss of the lower extremities and of the right arm. No significant motor defects were detected. Patellar reflexes were increased. Surgical treatment and postoperative courseSurgery was carried out with continuous sensory and motor function monitoring. The lesion was located in the posterior aspect of the spinal cord, just underneath the dura, and appeared firm and white. Posterior myelotomy was performed, and tumor removal was apparently complete.No clear margins were discernible between the tumor and the spinal cord. During the final surgical maneuvers, intraoperative motor function monitoring revealed a sudden, severe decrease of muscle motor evoked potentials (MEPs) in all extremities, especially on the right side, while D-wave showed a decrease of up to 50%. Surgery was immediately stopped before performing further samplings of the surgical field walls, because of the high risk of permanent impairment. However, resection was complete, as confirmed by postoperative MRI showing gross total resection of the lesion, and a very thin, decompressed spinal cord (Fig. 1c-e). After surgery, the patient presented with tetraparesis that gradually improved during the following weeks. Two months after surgery he could walk with cane. MRI confirmed satisfactory tumor removal. Iphosphamide was given as adjuvant chemotherapy. No recurrences were detected on cerebrospinal MRI 9 months after surgery (Fig. 1f). Histological findings and diagnosisHistopathological examination showed a malignant spindle cell neoplasm featuring extensive hypercellular areas with limited collagenous areas. No necrosis was found. Mitotic count revealed up to 6 mitoses/10 high-power fields (HPF). S100 protein was focally positive in tumor cells, whereas CKCAM 5.2, epithelial membrane antigen (EMA), collagen IV, desmin, myogenin, and human melanoma black (HMB)-45 were completely negative. Glial fibrillary acidic protein (GFAP) and neurofilament stains were limited to the underlying cord parenchyma infiltrated by the tumor (Fig. 2). Molecular immunology borstel (MIB)-1 labeling was moderate. Fluorescence in situ hybridization analysis (probe LSI SS18 Break Apart FISH probe kit, Vysis) did not reveal rearrangements in the SYT gene.

show abstract

“…Although additional molecular changes are also necessary for oncogenesis, an interesting anecdote supporting the homogeneity MPNST development is a case of monozygous twins with remarkably similar phenotypes 158. Constitutive activation of the RAS/RAF/MEK/ERK pathway through biallelic loss of function of neurofibromin is a uniform and critical event in MPNST pathogenesis 159,160.…”

Section: Mpnstmentioning

confidence: 99%

Epidemiology and therapies for metastatic sarcoma

Amankwah¹,

Conley²,

Reed³

2013

CLEP

View full text Add to dashboard Cite

Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma.

show abstract

Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and synchronous development of MPNST and metastasis

Cited by 9 publications

References 21 publications

Neurofibromatosis type 1: from genotype to phenotype

Neurofibromatosis type 1: from genotype to phenotype

Intramedullary malignant peripheral nerve sheath tumor

Epidemiology and therapies for metastatic sarcoma

Contact Info

Product

Resources

About