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Nevi of Ota and Ito

  • Author: William A Berger; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 02, 2016
 

Background

Nevus of Ota, which originally was described by Ota and Tanino in 1939, is a hamartoma of dermal melanocytes. Clinically, nevus of Ota presents as a blue or gray patch on the face, which is congenital, with onset at birth or around puberty and is within the distribution of the ophthalmic and maxillary branches of the trigeminal nerve. The nevus can be unilateral or bilateral, and, in addition to skin, it may involve ocular and oral mucosal surfaces.[1, 2]

Nevus of Ito, initially described by Minor Ito[1, 2, 3] in 1954, is a dermal melanocytic condition affecting the shoulder area in the distribution of the posterior supraclavicular and lateral cutaneous brachial nerves. Nevus of Ito often occurs in association with nevus of Ota in the same patient but is much less common, although the true incidence is unknown.

Additionally, the Medscape article Melanocytic Nevi may be of interest.

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Pathophysiology

The etiology and pathogenesis of nevi of Ota and Ito are not known. Although unconfirmed, nevus of Ota and other dermal melanocytic disorders, such as nevus of Ito, blue nevus, and Mongolian spots, may represent melanocytes that have not migrated completely from the neural crest to the epidermis during the embryonic stage.[4] The variable prevalence among different populations suggests genetic influences, although familial cases of nevus of Ota are exceedingly rare. The two peak ages of onset in early infancy and in early adolescence suggest that hormones are a factor in the development of these conditions. Schwann cell precursors have been shown to be a source of melanocytes in skin.[5] The observation of dermal melanocytes in close proximity with peripheral nerve bundles in nevus of Ito suggests that the nervous system is a factor in the development of nevus of Ito, although the true pathogenesis remains unknown.

A new theory is emerging regarding the pathogenesis of nevi of Ota and Ito. It has been demonstrated that most nevi and melanomas are associated with mutations in the BRAF and NRAS genes of the MAP kinase pathway.[6, 7] However, blue nevi and nevi of Ota and Ito do not possess these mutations. Instead, it has been discovered that the melanocytes present in these lesions often contain a mutation in a G-coupled protein gene, GNAQ. This mutation causes the G-coupled protein to be constitutively turned on, resulting in increases in the melanoblast pool. These melanoblasts then migrate during embryogenesis to the skin, the uvea, and/or the meninges, creating the various manifestations of Nevus of Ota.[8, 9, 10] This would explain the association between nevus of Ota and uveal and leptomeningeal melanocytosies. GNAQ mutations have also been shown to underlie other cutaneous disorders, including phakomatosis pigmentovascularis (of which melanocytosis may be a feature),[11] nevus flammeus,[12] and Sturge-Weber syndrome.

It has also been shown that the risk of developing cutaneous, uveal, or leptomeningeal melanomas in the setting of lesions such as nevus of Ota is related to monosomy of chromosome 3. The tumor suppressor gene BAP1 (BRCA-associated protein 1) is located on this chromosome. Loss of one the BAP1 allele is linked with an adverse prognosis. Monosomy 3, coupled with loss of 1q or gain of 8q, is associated with a worse outcome. Evaluation for this abnormality in melanomas associated with nevus of Ota could aid in prognosis, treatment, and follow-up.[13]

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Epidemiology

Race

Nevi of Ota and Ito occur most frequently in Asian populations, with an estimated prevalence of 0.2-0.6% for nevus of Ota in Japanese persons. Nevus of Ito is less common than nevus of Ota, although the true incidence is unknown.

Other ethnic groups with increased prevalence include Africans, African Americans, and East Indians.

Nevi of Ota and Ito are uncommon in whites.

Sex

The male-to-female ratio is 1:4.8 for nevus of Ota.[14] The ratio for nevus of Ito is unknown.

Age

The first peak of onset of nevus of Ota occurs in infancy, with as many as 50% of nevus of Ota cases present at birth. The onset for nevus of Ito is at birth or shortly thereafter.

The second peak of onset for nevus of Ota is seen during adolescence.

Isolated cases of delayed-onset nevi of Ota that first appear in adults, including in older patients, have been reported.[15] The same has rarely been found in patients with nevus of Ito.[16]

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Prognosis

Without treatment, the skin lesions are permanent.

Nevus of Ota can cause facial disfigurement, resulting in emotional and psychologic distress.[17] In rare cases, melanoma, which can be life threatening, has been reported to arise from nevus of Ota.[18]  Glaucoma also has been associated with nevus of Ota.

Nevus of Ito usually does not have symptoms and causes little cosmetic concern to the patients; sensory changes occasionally are present in the lesion. Rarely, nevus of Ito has progressed to cutaneous melanoma.[18, 19]

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Patient Education

Make patients aware of the risk associated with the development of glaucoma. Instruct patients to schedule periodic follow-up visits with an ophthalmologist.

Instruct patients to report any unusual symptoms or changes to the lesional areas to a physician, since a small risk for malignant degeneration exists.

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Contributor Information and Disclosures
Author

William A Berger Frank H Netter, MD, School of Medicine at Quinnipiac University

William A Berger is a member of the following medical societies: American Chemical Society, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Justin J Finch, MD, FAAD Assistant Professor, Director of Clinical Photography, Director of the Center for Cutaneous Laser Surgery, Department of Dermatology, University of Connecticut Health Center

Justin J Finch, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, Society for Pediatric Dermatology, New England Dermatological Society, Connecticut Society of Dermatology and Dermatologic Surgery, Midwest Arts in Healthcare Network, Arts & Health Alliance

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Christen M Mowad, MD Professor, Department of Dermatology, Geisinger Medical Center

Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, Noah Worcester Dermatological Society, Pennsylvania Academy of Dermatology, American Academy of Dermatology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Harvey Lui, MD, FRCPC Professor and Head, Department of Dermatology and Skin Science, Vancouver General Hospital, University of British Columbia; Medical Director, The Skin Centre, Lions Laser Skin Centre and Psoriasis and Phototherapy Clinic, Vancouver General Hospital

Harvey Lui, MD, FRCPC is a member of the following medical societies: Canadian Medical Association, American Society for Photobiology, Photomedicine Society, European Academy of Dermatology and Venereology, National Psoriasis Foundation, Canadian Dermatology Association, College of Physicians and Surgeons of British Columbia, North American Hair Research Society, Canadian Dermatology Foundation, American Academy of Dermatology, American Society for Laser Medicine and Surgery

Disclosure: Received consulting fee from Astellas for review panel membership; Received consulting fee from Amgen/Wyeth for speaking and teaching; Received honoraria from LEO Pharma for speaking and teaching; Received grant/research funds from LEO Pharma for investigator; Received grant/research funds from Galderma for other.

Sungnack Lee, MD Vice President of Medical Affairs, Professor, Department of Dermatology, Ajou University School of Medicine, Korea

Sungnack Lee, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Youwen Zhou, MD, PhD, FRCPC Associate Professor, Department of Dermatology and Skin Science, University of British Columbia Faculty of Medicine; Director, Hyperhidrosis Specialty Clinic, Co-Director, Psoriasis and Phototherapy Centre, Consulting Physician, Department of Dermatology, Vancouver General Hospital; Co-Director, Vitiligo and Pigmentation Clinic, Oncologist Consultant, Skin Tumor Program, BC Cancer Agency

Youwen Zhou, MD, PhD, FRCPC is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Soodabeh Zandi, MD Fellow, Department of Dermatology and Skin Science, University of British Columbia School of Medicine

Soodabeh Zandi, MD is a member of the following medical societies: American Academy of Dermatology, Photomedicine Society, European Academy of Dermatology and Venereology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Abbvie; Celgene;LEO<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie;Celgene;LEO.

References
  1. Franceschini D, Dinulos JG. Dermal melanocytosis and associated disorders. Curr Opin Pediatr. 2015 Aug. 27 (4):480-5. [Medline].

  2. Que SK, Weston G, Suchecki J, Ricketts J. Pigmentary disorders of the eyes and skin. Clin Dermatol. 2015 Mar-Apr. 33 (2):147-58. [Medline].

  3. Ito M. Studies on melanin XXII. Nevus fuscocaeruleus acromio-deltoideus. Tohoko J Exper Med. 1954. 60:10.

  4. Mohan RP, Verma S, Singh AK, Singh U. 'Nevi of Ota: the unusual birthmarks': a case review. BMJ Case Rep. 2013 Mar 1. 2013:[Medline].

  5. Adameyko I, Lallemend F, Aquino JB, Pereira JA, Topilko P, Müller T, et al. Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell. 2009 Oct 16. 139 (2):366-79. [Medline].

  6. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27. 417 (6892):949-54. [Medline].

  7. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003 Jan. 33 (1):19-20. [Medline].

  8. Van Raamsdonk CD, Fitch KR, Fuchs H, de Angelis MH, Barsh GS. Effects of G-protein mutations on skin color. Nat Genet. 2004 Sep. 36 (9):961-8. [Medline].

  9. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009 Jan 29. 457 (7229):599-602. [Medline].

  10. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010 Dec 2. 363 (23):2191-9. [Medline].

  11. Thomas AC, Zeng Z, Rivière JB, et al. Mosaic Activating Mutations in GNA11 and GNAQ Are Associated with Phakomatosis Pigmentovascularis and Extensive Dermal Melanocytosis. J Invest Dermatol. 2016 Apr. 136 (4):770-8. [Medline].

  12. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013 May 23. 368 (21):1971-9. [Medline].

  13. Goldman-Lévy G, Rigau V, Bléchet C, Bens G, Muckensturm B, Delage M, et al. Primary melanoma of the leptomeninges with bap1 expression-loss in the setting of a nevus of ota: A clinical, morphological and genetic study of 2 cases. Brain Pathol. 2016 Feb 2. [Medline].

  14. Hidano A, Kajima H, Ikeda S, Mizutani H, Miyasato H, Niimura M. Natural history of nevus of Ota. Arch Dermatol. 1967 Feb. 95(2):187-95. [Medline].

  15. Quenan S, Strueven V, Saxer N, Laffitte E, Kaya G, Krischer J, et al. Pruritic acquired nevus of Ota. Dermatology. 2013. 227 (2):186-8. [Medline].

  16. Mataix J, López N, Haro R, González E, Angulo J, Requena L. Late-onset Ito's nevus: an uncommon acquired dermal melanocytosis. J Cutan Pathol. 2007 Aug. 34 (8):640-3. [Medline].

  17. Cho BJ, Kwon JW, Han YK, Kim JH, Wee WR, Lee JH. Cosmetic improvement of nevus of Ota by scleral allograft overlay. Can J Ophthalmol. 2011 Oct. 46(5):428-30. [Medline].

  18. Tse JY, Walls BE, Pomerantz H, Yoon CH, Buchbinder EI, Werchniak AE, et al. Melanoma arising in a nevus of Ito: novel genetic mutations and a review of the literature on cutaneous malignant transformation of dermal melanocytosis. J Cutan Pathol. 2015 Aug 11. [Medline].

  19. Martínez-Peñuela A, Iglesias ME, Mercado MR, Martínez-Peñuela JM. Malignant Transformation of a Nevus of Ito: Description of a Rare Case. Actas Dermosifiliogr. 2011 Dec. 102(10):817-820. [Medline].

  20. Solanki J, Gupta S, Sharma N, Singh M, Bhateja S. Nevus of ota"- a rare pigmentation disorder with intraoral findings. J Clin Diagn Res. 2014 Aug. 8 (8):ZD49-50. [Medline].

  21. Patel BC, Egan CA, Lucius RW, Gerwels JW, Mamalis N, Anderson RL. Cutaneous malignant melanoma and oculodermal melanocytosis (nevus of Ota): report of a case and review of the literature. J Am Acad Dermatol. 1998 May. 38(5 Pt 2):862-5. [Medline].

  22. Chen YC, Chang CH, Hsu SL, Hsu MW, Lee CL. Malignant melanoma of the choroid in the eye with oculodermal melanocytosis of a Chinese woman. Kaohsiung J Med Sci. 2010 Dec. 26 (12):673-8. [Medline].

  23. Gerami P, Pouryazdanparast P, Vemula S, Bastian BC. Molecular analysis of a case of nevus of ota showing progressive evolution to melanoma with intermediate stages resembling cellular blue nevus. Am J Dermatopathol. 2010 May. 32 (3):301-5. [Medline].

  24. Qian Y, Zakov ZN, Schoenfield L, Singh AD. Iris melanoma arising in iris nevus in oculo(dermal) melanocytosis. Surv Ophthalmol. 2008 Jul-Aug. 53 (4):411-5. [Medline].

  25. Toivonen P, Kivelä T. Unusual tumors involving the head and neck region: case 2. Malignant uveal melanoma in ocular melanocytosis. J Clin Oncol. 2001 Nov 1. 19 (21):4174-7. [Medline].

  26. Infante de German-Ribon R, Singh AD, Arevalo JF, Driebe W, Eskin T. Choroidal melanoma with oculodermal melanocytosis in Hispanic patients. Am J Ophthalmol. 1999 Aug. 128 (2):251-3. [Medline].

  27. Sharan S, Grigg JR, Billson FA. Bilateral naevus of Ota with choroidal melanoma and diffuse retinal pigmentation in a dark skinned person. Br J Ophthalmol. 2005 Nov. 89 (11):1529. [Medline].

  28. Biswas J, Krishnakumar S. Choroidal melanoma in a black patient with oculodermal melanocytosis. Retina. 2003 Feb. 23 (1):126; author reply 126. [Medline].

  29. Shields JA, Shields CL, Naseripor M, Eagle RC, Miller J. Choroidal melanoma in a black patient with oculodermal melanocytosis. Retina. 2002 Feb. 22 (1):126-8. [Medline].

  30. Nik NA, Glew WB, Zimmerman LE. Malignant melanoma of the choroid in the nevus of Ota of a black patient. Arch Ophthalmol. 1982 Oct. 100 (10):1641-3. [Medline].

  31. Mohandessan M, Fetkenhour C, O'Grady R. Malignant melanoma of choroid in a case of nevus of Ota. Ann Ophthalmol. 1979 Feb. 11 (2):189-92. [Medline].

  32. Plateroti AM, Scavella V, Abdolrahimzadeh B, Plateroti R, Rahimi S. An Update on Oculodermal Melanocytosis and Rare Associated Conditions. Semin Ophthalmol. 2016 Apr 15. 1-5. [Medline].

  33. Teekhasaenee C, Ritch R, Rutnin U, Leelawongs N. Glaucoma in oculodermal melanocytosis. Ophthalmology. 1990 May. 97(5):562-70. [Medline].

  34. Radhadevi CV, Charles KS, Lathika VK. Orbital malignant melanoma associated with nevus of Ota. Indian J Ophthalmol. 2013 Apr 10. [Medline].

  35. Wang BQ, Shen ZY, Fei Y, Li H, Liu JH, Xu H, et al. A population-based study of acquired bilateral nevus-of-Ota-like macules in Shanghai, China. J Invest Dermatol. 2011 Feb. 131(2):358-62. [Medline].

  36. Shields CL, Kaliki S, Livesey M, Walker B, Garoon R, Bucci M, et al. Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes. JAMA Ophthalmol. 2013 Aug. 131 (8):993-1003. [Medline].

  37. Hirayama T, Suzuki T. A new classification of Ota's nevus based on histopathological features. Dermatologica. 1991. 183(3):169-72. [Medline].

  38. Padilla-España L, del Boz J, Ramírez-López MB, Fernández-Sánchez ME. Camouflage therapy workshop for pediatric dermatology patients: a review of 6 cases. Actas Dermosifiliogr. 2014 Jun. 105 (5):510-4. [Medline].

  39. Anderson RR. Lasers in dermatology--a critical update. J Dermatol. 2000 Nov. 27(11):700-5. [Medline].

  40. Watanabe S, Takahashi H. Treatment of nevus of Ota with the Q-switched ruby laser. N Engl J Med. 1994 Dec 29. 331(26):1745-50. [Medline].

  41. Chan HH, Leung RS, Ying SY, Lai CF, Kono T, Chua JK, et al. A retrospective analysis of complications in the treatment of nevus of Ota with the Q-switched alexandrite and Q-switched Nd:YAG lasers. Dermatol Surg. 2000 Nov. 26(11):1000-6. [Medline].

  42. Wang HW, Liu YH, Zhang GK, Jin HZ, Zuo YG, Jiang GT, et al. Analysis of 602 Chinese cases of nevus of Ota and the treatment results treated by Q-switched alexandrite laser. Dermatol Surg. 2007 Apr. 33(4):455-60. [Medline].

  43. Liu J, Ma YP, Ma XG, Chen JZ, Sun Y, Xu HH, et al. A retrospective study of q-switched alexandrite laser in treating nevus of ota. Dermatol Surg. 2011 Oct. 37(10):1480-5. [Medline].

  44. Levin MK, Ng E, Bae YS, Brauer JA, Geronemus RG. Treatment of pigmentary disorders in patients with skin of color with a novel 755 nm picosecond, Q-switched ruby, and Q-switched Nd:YAG nanosecond lasers: A retrospective photographic review. Lasers Surg Med. 2016 Feb. 48 (2):181-7. [Medline].

  45. Hosaka Y, Onizuka T, Ichinose M, Yoshimoto S, Okubo F, Hori S, et al. Treatment of nevus Ota by liquid nitrogen cryotherapy. Plast Reconstr Surg. 1995 Apr. 95(4):703-11. [Medline].

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Table. Clinical and Histologic Features for Differential Diagnoses of Nevi of Ota and Ito
ConditionOnsetAppearanceLocationHistology
Nevi of Ota and ItoBirth or early adolescenceBlue or gray speckled coalescing macules or patchesNevus of Ota: Unilateral, rarely bilateral, on forehead, temple, zygomatic, or periorbital areas



Nevus of Ito: Shoulder and upper arm areas



Increased dermal melanocytes, with surrounding fibrosis and melanophages
Mongolian spotBirthPoorly demarcated large blue-to-gray patches that tend to spontaneously resolve by age 3-6 yMost frequently on lumbosacral areas, buttocks, and rarely, other areasIncreased dermal melanocytes; no surrounding fibrosis
Blue nevusCongenital or acquiredBlue papules or plaquesAnywhere on skinDermal nodular proliferation of heavily pigmented spindle cells
Acquired nevus of Ota-like macules (Hori nevus)Acquired, presenting in adulthoodGray macules or patchesUsually bilateral and symmetrical; over the cheeks, temples, root of the nose, alae nasi, eyelids, and foreheadDiffuse upper-dermal melanocytosis
MelasmaAcquired; may be associated with pregnancy and other estrogen excess stagesWell-to-poorly demarcated and irregularly outlined brown-to-gray brown patchesMaxillary and zygomatic areas on faceNo increase in dermal melanocytes; presence of melanophages
Lentigo malignaAcquired; presenting usually after fifth decade of lifeBrown patches, usually with pigmentary variegationPhotodistribution, particularly within zygomaticomaxillary areasAtypical melanocytes in nests at dermal-epidermal junction, with pagetoid spread
Actinic lentigoAcquired; usually after fifth decade of lifeWell-demarcated brown papules or plaquesPhotodistribution, especially on faceElongation of rete ridges; basal layer hyperpigmentation; slight increase of melanocyte number along basal layer
PhytophotodermatitisAcquired; exposure to certain plants or cosmeticsGray-to-brown macules and patchesPhotodistribution, according to sites of contact with photosensitizerDermal melanophages
Drug-induced hyperpigmentationAcquired; following drug exposure (eg, minocycline, amiodarone, gold)Variable according to offending drugsVariable according to specific offending drugsVariable but may involve presence of dermal melanophages; pigmentation of basal keratinocytes
Exogenous ochronosis (rare)Adulthood; following topical application of hydroquinoneIrregularly shaped blue-to-gray patches or maculesAreas corresponding to exposure to hydroquinoneYellow banana-shaped spindle cells in papillary dermis
Ochronosis (alkaptonuria, rare)First decade of lifeBlue-gray discoloration of ear cartilage, tip of nose, and scleraSymmetrical distribution over cartilage, nose, cheeks, and extensor tendons of hands, as well as flexural areasYellow-to-brown pigmentary granules within dermal macrophages
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