The authors report a rare association between cutaneous melanoma and Von Recklinghausen's disease (NF-1) and analyze the possible meaning of this occurrence. Various types of tumors have been associated with NF-1, in particular those of neuroectodermal origin, such as malignant peripheral nerve sheath tumors (MPNST) and phaeochromocytoma.
The development of malignant melanoma in NF-1 patients is rare. Data from the literature is enable to demonstrate an increased incidence of cutaneous melanoma in patients with neurofibromatosis but the association of these two disorders seems reasonable in theory, as both are abnormalities of a neural crest origin.
The cases described may represent not only a clinical report of two rarely associated disorders, but may also confirm the biological mechanisms responsible for these infrequent diseases.
AndrewA.: Apud cells, apudomas and the neural crest.S. Afr. Med. J., 50: 890–898, 1976.
2.
AntleC.M.DamjiK.F.WhiteV.A.RootmanJ.: Uveal malignant melanoma and optic nerve glioma in von Recklinghausen's neurofibromatosis.Br. J. Ophthalmol., 74: 502–504, 1990.
3.
BaderJ.L.MillerR.W.: Neurofibromatosis and childhood leukemia.J. Pediatr., 92: 925–929, 1978.
4.
BaderJ.L.: Neurofibromatosis and cancer.Ann. N.Y. Acad. Sci., 486: 57–65, 1986.
5.
BairH.L.LoveJ.G.: Acoustic neurofibroma associated with melanoepithelioma of the choroid; successful removal of both tumors.Mayo Clin. Proc, 12: 481–485, 1937.
6.
BolandeR.T.: The neurocristopathies: a unifying concept of disease arising in neural crest maldevelopment.Hum. Pathol., 5: 409–429, 1974.
7.
BolandeR.T.: Neurofibromatosis- the quintessential neuro-cristopathy: pathogenic concepts and relationships.Adv. Neurol., 29: 67–75, 1981.
8.
BrasfieldR.D.Das GuptaT.K.: Von Recklinghausen's disease: a clinico-pathological study.Ann. Surg., 175: 86–104, 1972.
9.
BuchbergA.M.ClevelandL.S.JenkinsN.A.CopelandN.G.: Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway.Nature, 347: 291–294, 1990.
10.
BusamK.J.ChenY.-T.OldL.J.: Expression of Melan-A (Mart1) in benign melanocytic nevi and primary cutaneous malignant melanoma.Am. J. Surg. Pathol., 22: 976–982, 1998.
11.
CawthonR.M.WeissR.XuG.ViskochilF.CulverM.StevensJ.: A major segment of the neurofibromatosis type-1 gene: cDNA sequence, genomic structure and point mutations.Cell, 62: 193–201, 1990.
12.
CerneaP.DobrescuG.: Mélanome malin uvéal, manifestation de la maladie de Recklinghausen.Ophthalmologica, 166: 161–171, 1973.
13.
CroweF.W.SchullG.NeelJ.V.: A clinical, pathological and genetic study of multiple neurofibromatosis.Charles G. Thomas, Springfield, Illinois, 1956.
14.
CroxattoJ.O.CharlesD.E.MalbranE.S.: Neurofibromatosis associated with nevus of Ota and choroidal melanoma.Am. J. Ophthalmol., 92: 578–580, 1981.
15.
D'AgostinoA.N.SoureE.H.MillerR.H.: Sarcomas of the peripheral nerves and somatic soft tissues associated with multiple neurofibromatosis (von Recklinghausen's disease).Cancer, 16: 1015–1027, 1963.
16.
DuveS.RakoskiJ.: Cutaneous melanoma in a patient with neurofibromatosis: a case report and review of the literature.Br. J. Dermatol., 131: 290–294, 1994.
17.
EnzingerF.M.: Soft tissue tumors, third edition.Mosby Year Book, Inc., St Louis, MO, 1995.
18.
FitzpatrickT.B.: Melanin synthesis pathways in the pathogenesis of neurofibromatosis.Adv. Neurol., 29: 209–211, 1981.
Garcia-CasasolaG.CasadoA.CinguenzaR.Gonzalez LarribbJ.L.Alvarez-SalaJ.L.: Melanoma rectal y enfermedad de von Recklinghausen.Rev. Clin. Espan., 190: 475–476, 1992.
21.
GartnerS.: Malignant melanoma of the choroid and von Recklinghausen's disease.Am. J. Ophthalmol., 23: 73–78, 1940.
22.
GreenbergJ.H.: Cranial neural crest cells: inhibition on differentation in culture.Adv. Neurol., 29: 105–113, 1981.
23.
HafezM.SharafL.Abd eL-NabiS.M.eL-WehedyG.: Evidence of chromosomal instability in neurofibromatosis.Cancer, 55: 2434–2436, 1985.
24.
HealeyF.H.Jr., MekelatosC.J.: Pheochromocytoma and neurofibromatosis.NEJM, 258: 540–543, 1958.
25.
HopeD.G.MulvihillJ.J.: Malignancy in neurofibromatosis.Adv. Neur., 29: 33–56, 1981.
26.
JohnsonB.L.CharnecoD.R.: Café au lait spot in neurofibromatosis and in normal individuals.Arch. Dermatol., 102: 442–446, 1970.
27.
JohnstonM.C.VigK.W.L.AmbroseL.J.: Neurocristopathy as a unifying concept: clinical correlations.Adv. Neurol., 29: 97–104, 1981.
28.
KaufmannD.WiandtsS.VeserJ.KroneW.: Increased melanogenesis in cultured epidermal melanocytes from patients with neurofibromatosis 1 (NF1).Human Genet., 87: 144–150, 1991.
KushnerB.HajduS.HelsonL.: Synchronous neuroblastoma and von Recklinghasen's disease. Review of the literature.J. Clin. Oncol., 3: 117–120, 1985.
31.
LedbetterD.H.RichD.C.O'ConnellP.LeppertM.CareyJ.C.: Precise localization of NF 1 to 17q112 by balanced translocation.Am. J. Hum. Genet., 44: 20–24, 1989.
32.
LeeC.W.ShulmanK.MoreckiR.CookW.A.: Malignant degeneration of thoracic neurofibromatosis.N.Y. State J. Med., 75: 347–352, 1975.
33.
MastrangeloM.J.GoeppC.E.PatelY.A.ClarkW.H.: Cutaneous melanoma in a patient with neurofibromatosis.Arch. Dermatol., 115: 864–865, 1979.
MenonA.G.AndersonK.M.RicciardiV.M.: Chromosome p17 deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis.Proc. Natl. Acad. Sci. USA, 87: 5435–5439, 1990.
36.
National Institutes of Health Consensus Development Conference: Neurofibromatosis conference statement.Arch. Neurol., 45: 575–578, 1988.
37.
NordmannJ.: Cancer de la choroide et maladie de Recklinghausen.Bull. Soc. Ophtal. Fran., 5: 322–325, 1961.
38.
NordmannJ.BriniA.RuoltJ.: Tumour mélanique de la choroide et neurinomes chez un meme suject.Bull. Soc. Ophtal. Franc, 7: 551–553, 1963.
39.
PearseA.G.E.PolakJ.M.: Endocrine tumors of neural crest origin: neurolophomas, apudomas and the APUD concept.Med. Biol., 52: 3–18, 1974.
40.
PerkinsonN.G.: Melanoma arising in a cafè au lait spot of neurofibromatosis.Am. J. Surg., 93: 1018–1020, 1957.
SayedA.K.BernhardtB.Perez AtaydeA.R.BannermannR.M.: Malignant schwannoma in siblings with neurofibromatosis.Cancer, 59: 829–835, 1987.
43.
SchlumbergerH.G.: Limbus tumors as a manifestation of von Recklinghausen's neurofibromatosis in goldfish.Arch. Dermatol., 107: 747–750, 1973.
44.
SilvermanJ.F.BlahoveM.CollinsJ.L.NorrisH.T.: Cutaneous melanoma in a black patient with neurofibromatosis (von Recklinghausen's disease).Am. J. Dermatopathol., 10: 536–540, 1988.
45.
SpechtC.S.SmithT.W.: Uveal malignant melanoma and von Recklinghausen's neurofibromatosis.Cancer, 62: 812–817, 1988.
46.
StayE.J.VawterG.: The relationship between nephroblastoma and neurofibromatosis (von Recklinghausen's disease).Cancer, 39: 2550–2555, 1977.
47.
StrakhovV.P.ShepkhalovaV.M.: Recklinghausen's disease, neurinoma of the right orbit and neoplasm of the left choroid.Vest. Oftalmol., 18: 12–16, 1941.
48.
SzeklerR.: Ein Uvealsarkom bei einem Mitglied einer Famille mit Recklinghausenscher Krankeit.Ophthalmologica, 126: 248–251, 1954.
49.
VincentR.RiccardiV.M.: Von Recklinghausen neurofibromatosis.NEJM, 305: 1617–1626, 1981.
50.
Von RecklinghausenF.: Ueber die multiplen Fibrome der Haut und ihre Beziehung zu den multiplen Neuromen.Hirschwald, Berlin, 1882.
51.
WestonJ.A.: The regulation of normal and abnormal neural crest cell development.Adv. Neurol., 29: 77–95, 1981.
52.
WizniaR.A.FreedmanJ.D.ManciniA.D.ShieldsJ.A.: Malignant melanoma of the choroid in neurofibromatosis.Am. J. Ophthalmol., 86: 684–687, 1978.
53.
XuG.O'ConnellP.ViskochilD.LawthonR.M.RobertsonM.CulverM.DunnD.: The neurofibromatosis type 1 gene encodes a protein related to GAP.Cell, 62: 599–608, 1990.
54.
YanoffM.ZimmermanL.E.: Histogenesis of malignant melanomas of the uvea. The relationship of congenital ocular melanocytosis and neurofibromatosis to uveal melanomas.Arch. Ophthalmol., 77: 331–336, 1967.
