Neurofibromatosis 1 is one of the more common in heritable disorders that surgeons may encounter. A plethora of systemic associations, both benign and malignant, can affect these patients, and an acute awareness of these associations is essential for proper surgical care. A complete review of this disorder from the surgical perspective follows, highlighting the importance of this awareness. A brief review on the management and follow-up of surgical malignancies associated with this disorder is included.
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References
1.
National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis.Bethesda, MD, USA July 13–15, 1987.Neurofibromatosis1988; 1: 172–8.
2.
LegiusE., MarchukD.A., CollinsF.S., GloverT.W.Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumor suppressor gene hypothesis.Nat Genet1993; 3: 122–6.
3.
McCorkmickF.ras GTPase activating protein: Signal transmitter and signal terminator.Cell1989; 13: 5–8.
4.
XuG., O'ConnellP.O., ViskochilD.The neurofibromatosis 1 gene encodes a protein related to GAP.Cell1990; 62: 599–608.
5.
BallesterR., MarchukD., BoguskiM.The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.Cell1990; 63: 851–9.
6.
BosJ.L.Ras oncogenes in human cancer: A review.Cancer Res1989; 49: 4682–9.
7.
RiccardiV.M., LewisR.A.Penetrance of von Recklinghausen Neurofibromatosis: A distinction between predecessors and descendants.Am J Hum Genet1988; 42: 284–9.
8.
MulvihillJ.J., ParryD.M., ShermanJ.L.Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis): An update.Ann Intern Med1990; 113: 39–52.
9.
JadayelD., FainP., UpadhyayaM.Paternal origin of new mutations in von Recklinghausen neurofibromatosis.Nature1990; 343: 558–9.
10.
WoodruffJ.M.Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis.Sem Med Genet1999; 89: 23–30.
11.
OzonoffS.Cognitive impairment in neurofibromatosis type 1.Semin Med Genet1999; 89: 45–52.
12.
NorthK.N., RiccardiV., Samango-SprouseC.Cognitive function and academic performance in neurofibromatosis 1: Consensus statement from the NF 1 cognitive disorders task force.Neurol (Tokyo)1997; 48: 1121–7.
13.
RuggieriM.The different forms of neurofibromatosis.Childs Nerv Syst1999; 15: 295–308.
14.
PollackI.F., ShultzB., MulvihillJ.J.The management of brainstem gliomas in patients with neurofibromatosis 1.Neurol (Tokyo)1996; 46: 1652–60.
15.
MolloyP.T., BilaniukL.T., VaughanS.N.Brainstem tumors in patients with neurofibromatosis type 1.Neurol (Tokyo)1995; 45: 1897–902.
LinD., BarkerP.Neuroimaging of phakomatoses.Semin Pediatr Neurol2006; 13: 48–62.
18.
Brunetti-PierriN., DotyS., HicksJ.Generalized metabolic bone disease in Neurofibromatosis type 1.Mol Genet Metab2008; 94: 105–11.
19.
StevensonD.A., BirchP.H., FriedmanJ.M.Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1.Am J Med Genet1999; 84: 413–9.
20.
VitaleM.G., GuhaA., SkaggsD.L.Orthopaedic manifestations of neurofibromatosis in children: An update.Clin Orthop Relat Res2002; 107–18.
21.
CrozierW.C.Upper airway obstruction in neurofibromatosis.Anaesthesia1987; 42: 1209–11.
22.
RyuJ.H., ParambilJ.G., McGrannP.S., AughenbaughG.L.Lack of evidence for an association between neurofibromatosis and pulmonary fibrosis.Chest2005; 128: 2381–6.
23.
ZamoraA.C., CollardH.R., WolterP.J.Neurofibromatosis-associated lung disease: A case series and literature review.Eur Respir J2007; 29: 210–4.
24.
YokoyamaA., KohnoN., SakaiK.Distal acinar emphysema and interstitial pneumonia in a patient with von Recklinghausen's disease: Five year observation following quitting smoking.Intern Med1997; 36: 413–6.
25.
HuppmanJ.L., GathonV., BowersV.D.Neurofibromatosis and arterial aneurysm.Am Surg1996; 62: 311–31.
26.
SalyerW.R.The vascular lesions of neurofibromatosis.Angiol1974; 8: 510–9.
27.
StewartD.R., CoganJ.D., KramerM.R.Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy?Chest2007; 132: 798–808.
28.
EngelP.J., BaughmanR.P., MenonS.G.Pulmonary hypertension in neurofibromatosis.Am J Cardiol2007; 99: 1177–8.
29.
Hassen-KhodjaR., DeclemyS., BattM.Visceral artery aneurysms in von Recklinghausen's neurofibromatosis.J Vasc Surg1997; 25: 572–5.
30.
FossaliE., SignoriniE., IntermiteR.C.Renovascular disease and hypertension in children with neurofibromatosis.Pediatr Nephrol2000; 14: 806–10.
31.
TedescoM.A., DiSalvoG., RattiG.Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1.Am J Hypertens2001; 14: 559–66.
FullerC.E., WilliamsG.T.Gastrointestinal manifestations of type 1 neurofibromatosis (von Recklinghausen's disease).Histopath1991; 19: 1–11.
34.
SicaG.S., SujendranV., WarrenB., MaynardN.D.Neurofibromatosis of the esophagus.Ann Thorac Surg2006; 81: 1138–40.
35.
KimH.R., KimY.J.Neurofibromatosis of the colon and rectum combined with other manifestations of von Recklinghausen's disease.Dis Colon Rectum1998; 41: 1187–92.
36.
FeinstatT., TeslukH., SchufflerM.D.Megacolon and neurofibromatosis: A neuronal intestinal dysplasia.Gastroenterology1984; 86: 1573–9.
37.
BuckL., PerryB., RichardsM.Periampullary carcinoid tumor in a woman with neurofibromatosis.Curr Surg2006; 63: 252–4.
38.
GriffithsD.F.R., WilliamsG.T., WilliamsE.D.Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: Islet cell tumour, phaeochromocytoma and the von hippel-lindau complex: Two distinctive neuroendocrine syndromes.Q J Med1987; 64: 769–82.
39.
BauschB., BorozdinW., NeumannH.P.H.Clinical and genetic characteristics of patients with neurofibromatosis type 1 and pheochromocytoma.N Engl J Med2006; 25: 2729–31.
40.
LewJ.I., JacomeF.J., SolorzanoC.C.Neurofibromatosis-associated pheochromocytoma.J Am Coll Surg2005; 202: 550–1.
41.
PerezE.A., LivingstoneA.S., FranceschiD.Current incidence and outcomes of gastrointestinal mesenchymal tumors including gastrointestinal stromal tumors.J Am Coll Surg2006; 202: 623–9.
42.
MiettienenM., FetschJ.F., SobinL.H., LasotaJ.Gastrointestinal stromal tumors in patients with neurofibromatosis 1: A clinicopathologic and molecular study of 45 cases.Am J Surg Pathol2006; 30: 90–6.
CacevT., RadosevicS., SpaventiR.NF 1 gene loss of heterozygosity and expression analysis in sporadic colon cancer.Gut2005; 54: 1129–35.
45.
EckertL.B., RepaskyG.A., UlkuA.S.Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikis.Cancer Res2004; 64: 4585–92.
46.
SharifS., MoranA., HusonS.M.Women with neurofibromatosis 1 are at a moderately increased risk of developing breast cancer and should be considered for early screening.J Med Genet2007; 44: 481–4.
47.
DeSchepperS., BoucneauJ., LambertJ.Pigment cell-related manifestation in neurofibromatosis type 1: An overview.Pigment Cell Res2005; 18: 13–24.
48.
SchafferJ.V., ChangM.W., KovichO.I.Pigmented plexiform neurofibroma: Distinction from a large congenital melanocytic nevus.J Am Acad Dermatol2007; 56: 862–8.
49.
RiccardiV.M.Pathophysiology of neurofibromatosis. Dermatologic insights into heterogeneity and pathogenesis.J Am Acad Dermatol1980; 3: 157–66.
50.
RubbenA., BauschB., NikkelsA.Somatic deletion of the NF 1 gene in a neurofibromatosis type 1 associated malignant melanoma demonstrated by digital PCR.Mol Cancer2006; 5: 36.
51.
AndersonL.B., FountainJ.W., GutmannD.H.Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines.Nature1993; 3: 118–21.
52.
GuillotB., DalacS., DelaunayM.Cutaneous malignant melanoma and neurofibromatosis type 1.Melanoma Res2004; 14: 159–63.
53.
KarM., DeoS.V.S., ShuklaN.K.Malignant peripheral nerve sheath tumors (MPNST) Clinicopathological study and treatment outcome of twenty four cases.W J Curg Onc2006; 4: 55.
54.
FernerR.E., GutmanD.H.International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis 1.Can Resear2002; 62: 1573–5.
55.
DucatmanS.B., ScheithauerB.W., PiepgrasD.G.Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases.Cancer1986; 57: 2006–21.
CichowskiK., ShihT.S., SchmittE.Mouse models of tumor development of neurofibromatosis type 1.Science1999; 286: 2172–8.
58.
ZhuY., ParadaL.F.Neurofibromin, a tumor supressor in the nervous system.Exp Cell Res2001; 264: 19–28.
59.
NielsenG.P., Stemmer-RachamimovA.O., InoY.Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation.Am J Pathol1999; 155: 1879–84.
60.
KoureaH.P., Cordon-CardoC., DudasM.Expression of p27kip and other cell cycle regulators in malignant peripheral nerve sheath tumors and neurofibromas.Am J Pathol1999; 155: 1885–91.
61.
KoureaH.P., OrlowI., ScheithauerB.W.Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas.Am J Pathol1999; 155: 1855–9.
62.
HoltkampN., OkuducuA.F., MuchaJ.Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity.Carcinogenesis2006; 27: 664–71.
63.
KingA., DeBaunM.R., RiccardiV.M., GutmannD.H.Malignant peripheral nerve sheath tumors in eurofibromatosis.Am J Med Genet2002; 39: 311–4.
MautnerV.F., FriedrichR.E., von DeimlingA.Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma.Neuroradiology2003; 45: 618–25.
67.
FernerR.E., LucasL.D., O'DohertyM.J.Evaluation of 18 fluorodeoxyglucose positron emission tomography (18FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1.J Neurol Neurosurg Psychiatry2000; 68: 353–7.
68.
CardonaS., SchwarzbachM., HinzU.Evaluation of F 18 deoxyglucose positron emission tomography (FDG PET) to assess the nature of neurogenic tumors.Eur J Surg Oncol2003; 29: 536–41.
69.
WolkensteinP., ZaleskiI.D., MorenoJ.C.Cost evaluation of the medical management of neurofibromatosis 1: A prospective study on 201 patients.Br J Derm2000; 142: 1166–70.
70.
GutmannD.H., AylsworthA., CareyJ.C.The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2.JAMA1997; 278: 51–7.
71.
WolkensteinP., FrecheB., ZellerJ., RevuzJ.Usefulness of screening investigations in neurofibromatosis type 1. A study of 152 patients.Arch Dermatol1996; 132: 1333–6.
72.
DrappierJ.C., KhosrotehraniK., ZellerJ.Medical management of neurofibromatosis 1: A cross-sectional study of 383 patients.J Am Acad Dermatol2003; 49: 440–4.
73.
WalkerL., ThompsonD., EastonD.A prospective study of neurofibromatosis type 1 cancer incidence in the UK.Br J Cancer2006; 95: 233–8.
74.
ZollerM.E.T., RembeckB., OdenA.Malignant and benign tumours in patients with neurofibromatosis type 1 in a defined Swedish population.Cancer1997; 79: 2125–31.
75.
RasmussenS.A., YangA., FriedmanJ.M.Mortality in neurofibromatosis 1: An analysis using US death certificates.Am J Hum Genet2001; 68: 1110–8.