Nevi of Ota and Ito

Nevi of Ota and Ito

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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]  See the images below.

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. See the image below.

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

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]

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.

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

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]

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]

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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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].

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Nevi of Ota and Ito

Birth or early adolescence

Blue or gray speckled coalescing macules or patches

Nevus 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 spot


Poorly demarcated large blue-to-gray patches that tend to spontaneously resolve by age 3-6 y

Most frequently on lumbosacral areas, buttocks, and rarely, other areas

Increased dermal melanocytes; no surrounding fibrosis

Blue nevus

Congenital or acquired

Blue papules or plaques

Anywhere on skin

Dermal nodular proliferation of heavily pigmented spindle cells

Acquired nevus of Ota-like macules (Hori nevus)

Acquired, presenting in adulthood

Gray macules or patches

Usually bilateral and symmetrical; over the cheeks, temples, root of the nose, alae nasi, eyelids, and forehead

Diffuse upper-dermal melanocytosis


Acquired; may be associated with pregnancy and other estrogen excess stages

Well-to-poorly demarcated and irregularly outlined brown-to-gray brown patches

Maxillary and zygomatic areas on face

No increase in dermal melanocytes; presence of melanophages

Lentigo maligna

Acquired; presenting usually after fifth decade of life

Brown patches, usually with pigmentary variegation

Photodistribution, particularly within zygomaticomaxillary areas

Atypical melanocytes in nests at dermal-epidermal junction, with pagetoid spread

Actinic lentigo

Acquired; usually after fifth decade of life

Well-demarcated brown papules or plaques

Photodistribution, especially on face

Elongation of rete ridges; basal layer hyperpigmentation; slight increase of melanocyte number along basal layer


Acquired; exposure to certain plants or cosmetics

Gray-to-brown macules and patches

Photodistribution, according to sites of contact with photosensitizer

Dermal melanophages

Drug-induced hyperpigmentation

Acquired; following drug exposure (eg, minocycline, amiodarone, gold)

Variable according to offending drugs

Variable according to specific offending drugs

Variable but may involve presence of dermal melanophages; pigmentation of basal keratinocytes

Exogenous ochronosis (rare)

Adulthood; following topical application of hydroquinone

Irregularly shaped blue-to-gray patches or macules

Areas corresponding to exposure to hydroquinone

Yellow banana-shaped spindle cells in papillary dermis

Ochronosis (alkaptonuria, rare)

First decade of life

Blue-gray discoloration of ear cartilage, tip of nose, and sclera

Symmetrical distribution over cartilage, nose, cheeks, and extensor tendons of hands, as well as flexural areas

Yellow-to-brown pigmentary granules within dermal macrophages

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.

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.

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

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.

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.

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 Faculty of Medicine, Canada

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

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

Nevi of Ota and Ito

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