Nevi of Ota and Ito

Back

Background

Nevus of Ota is a dermal melanocytosis originally described by Ota and Tanino in 1939. Clinically, nevus of Ota is distributed along the ophthalmic and maxillary divisions of the trigeminal nerve and presents as a blue or gray patch on the face.[1] Around 50% of cases occur at birth, while the remaining occur during puberty and adulthood. Initial hyperpigmentation may present as light in color with continued hyperpigmentation as the individual ages. In addition to the pigmented macule observed on the skin, there have also been rare cases involving ocular and oral mucosal surfaces.[2, 3] See the images below.



View Image

Nevus of Ota. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/ota2.jpg).



View Image

Nevus of Ota. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/ota.jpg).

Nevus of Ito, initially described by Minor Ito in 1954,[2, 3, 4] is a similar dermal melanocytic condition like nevus of Ota, differing in distribution. Nevus of Ito is usually found distributed along the posterior supraclavicular and lateral cutaneous brachial nerves of the shoulder. 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. From a pathophysiological standpoint, both nevus of Ota and Ito result from failed migration of melanocytes from the neural crest to basal layer of the epidermis. See the image below.



View Image

Nevus of Ito. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/melanocytosis-ito.jpg).

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

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.[5] 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.[6] 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.

One theory 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.[7, 8] 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.[9, 10, 11] 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),[12] nevus flammeus,[13] 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.[14]

Epidemiology

Race

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

Studies have shown prevalence in other ethnic groups including Africans, African Americans, and East Indians.

Nevi of Ota and Ito are uncommon in whites.

Sex

Females are shown to be affected five times more than males, with the male-to-female ratio is 1:5 for nevus of Ota.[15] The ratio for nevus of Ito is unknown.

Age

The initial presentation of both nevus of Ota and Ito occurs in infancy, with as many as 50% of nevus of Ota cases present at birth.

Nevus of Ota may also present itself during adolescence.

Additionally, there have been rare cases of delayed-onset nevi of Ota that first appear in adults, including in older patients.[16, 17]

Prognosis

Lesions may display progressive hyperpigmentation with age, and, without treatment, lesions remain permanent.

It is important to note the psychosocial impact that Nevus of Ota can have on those affected, as disease progression can cause facial disfigurement.[18] In rare cases, melanoma, which can be life threatening, has been reported to arise from nevus of Ota.[19] Glaucoma also has been associated with nevus of Ota. Recurrence may also occur with incomplete removal of lesions.

Nevus of Ito usually does not have symptoms and causes little cosmetic concern to patients; sensory changes occasionally are present in the lesion. Rarely, nevus of Ito has progressed to cutaneous melanoma.[19, 20]

Patient Education

It is important that patients be made aware of the risk associated with the development of glaucoma as this may progress to vision loss. Periodic follow-up visits with an ophthalmologist should be encouraged.

Despite there being a rare risk of transformation into malignant melanoma, patients should be encouraged to report any changes in size and/or color to the lesional areas.

History

After onset, nevus of Ota may slowly and progressively enlarge and darken in color, and its appearance usually remains stable once adulthood is reached. The color or perception of the color of nevus of Ota may fluctuate according to personal and environmental conditions, such as fatigue, menstruation, insomnia, and cloudy, cold, or hot weather conditions. Nevus of Ota can be associated with other cutaneous disorders and ocular disease. Nevus of Ito can be associated with sensory changes in the involved skin.

Benign cutaneous and leptomeningeal conditions associated with nevus of Ota are as follows[21] :

Malignant degeneration of nevus of Ota is rare. More than 100 cases of malignant melanoma in association with nevus of Ota have been described in the literature as follows[22] :

To date, 13 cases of malignant degeneration of nevus of Ito have been described.[19]

Ocular abnormalities (ocular acuity normal) are as follows:

Physical Examination

Table. Clinical and Histologic Features for Differential Diagnoses of Nevi of Ota and Ito



View Table

See Table

Nevus of Ota most frequently presents as blue-to-gray speckled or mottled coalescing macules or patches affecting the forehead, temple, malar area, or periorbital skin.[35] Nevus of Ito presents as a patch on the shoulder or upper arms with blue, gray, or brown pigmentation. Most cases of nevus of Ota are unilateral (90%), although pigmentation is present bilaterally in 5-10%.[36] Nevus of Ito usually is unilateral. In addition to skin, pigmentation of nevus of Ota may involve oral mucosa and ocular structures such as the sclera, retrobulbar fat, cornea, and retina.

Clinically, nevus of Ito is similar to nevus of Ota, except that it typically presents over the shoulder girdle region.

Specific variants of nevus of Ota have been described in the literature under the names of nevus fuscoceruleus zygomaticus, plaque-type variant of blue nevus. Differential features of these conditions are related to the following:

Pathology and response to therapy appear similar for all forms of nevus of Ota. The pathology of nevus of Ito is similar to that of nevus of Ota.

Tanino created the following four classifications of nevus of Ota based on the extent of disease and localization of distribution:

Complications

Studies have shown that patients with dermal melanocytosis subsequently went on to develop uveal melanoma had an increased risk for metastasis double that of patients without melanocytosis.[37]

Skin biopsies are warranted if clinical changes are suspected of malignant transformation (eg, ulceration, new papular lesions, variegations in color) within the involved skin, ocular tissues, or mucosal tissues.

Ophthalmologic follow-up care is necessary for patients with increased intraocular pressure. Biannual follow up is recommended.

Other Tests

Consider ophthalmologic examination and follow-up care for nevus of Ota because of a reported 10% association of nevus of Ota with increased intraocular pressure. Iris mammillations, sometimes occurring with nevus of Ota, should not be confused with other nodular alterations of the iris, such as the Lisch nodules of neurofibromatosis, as they are associated with a higher risk of malignant transformation.[33]

Lesions should be closely observed for any changes in size or color, as there is a mild risk for melanoma.

Histologic Findings

Histologic findings for nevi of Ota and Ito have some similarities. Overlying epidermis is normal. In the papillary and upper reticular dermis, dendritic melanocytes are present and surrounded by fibrous sheaths (which are not present in other dermal melanocytosis, such as blue nevus or Mongolian spots). Dermal melanophages may be present.

Nevi of Ota have been classified histologically into 5 types based on the locations of the dermal melanocytes, which are (1) superficial, (2) superficial dominant, (3) diffuse, (4) deep dominant, and (5) deep.[38]

This histologic classification correlates clinically with the observation that the more superficial lesions tend to be located on the cheeks, while deeper lesions occur on periorbital areas, the temple, and forehead.

Approach Considerations

It is important to note that some treatment methods may result in scarring, and recurrence is a possibility.

Medical Care

Cosmetic camouflage makeup can minimize the disfiguring facial pigmentation resulting from nevus of Ota.[39] Nonsurgical methods include chemical peeling, dermabrasion, and topical hydroquinone-based bleaching products.

Surgical Care

Laser surgery is the first-line treatment.[40] Pulsed Q-switched laser surgery is the treatment of choice for nevi of Ota and Ito, and it works via selective photothermal and photomechanical destruction of dermal melanocytes and melanophages. High success rates and minimal adverse effects have been reported with the Q-switched ruby,[41] Q-switched alexandrite,[42, 43, 44] and Q-switched Nd:YAG lasers.[42, 45] After 4-8 treatments, skin pigmentation is reduced dramatically or removed in 90-100% of cases, with a less than 1% risk of scarring.

In 2016, it has been shown that similar results may be achieved using a 755-nm Q-switched picosecond laser compared with Q-switched nanosecond lasers. In a 2016 study of patients with nevus of Ota, there was no statistically significant difference in visual analog scores for six patients treated with the picosecond laser and ten patients treated with nanosecond laser. Notably, no picosecond laser‒treated patients experienced any permanent dyspigmentation, compared with 16% in the nanosecond laser group.[46]

Other surgical methods currently have been superseded by laser surgery but include the following:

Consultations

Secondary to the increased risk of ocular melanoma in patients with nevus of Ota, it is important for patients to receive consultation with ophthalmologists with biannual follow up.

Complications

Complications of surgical treatment include a risk of scarring.

Author

Omobola Onikoyi, DO, MSc, American Osteopathic Association (AOA) Internship, Manchester Memorial Hospital, Eastern Connecticut Health Network

Disclosure: Nothing to disclose.

Coauthor(s)

Chris G Adigun, MD, FAAD, Director and Physician, Dermatology and Laser Center of Chapel Hill; Senior Medical Advisor, Klara

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Celgene; Cipher; Sciton; Lumenis.

Specialty Editors

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

Disclosure: Nothing to disclose.

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

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

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

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.

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

Disclosure: Nothing to disclose.

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

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 .

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

References

  1. 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. [View Abstract]
  2. Franceschini D, Dinulos JG. Dermal melanocytosis and associated disorders. Curr Opin Pediatr. 2015 Aug. 27 (4):480-5. [View Abstract]
  3. Que SK, Weston G, Suchecki J, Ricketts J. Pigmentary disorders of the eyes and skin. Clin Dermatol. 2015 Mar-Apr. 33 (2):147-58. [View Abstract]
  4. Ito M. Studies on melanin XXII. Nevus fuscocaeruleus acromio-deltoideus. Tohoko J Exper Med. 1954. 60:10.
  5. Mohan RP, Verma S, Singh AK, Singh U. 'Nevi of Ota: the unusual birthmarks': a case review. BMJ Case Rep. 2013 Mar 1. 2013:[View Abstract]
  6. 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. [View Abstract]
  7. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27. 417 (6892):949-54. [View Abstract]
  8. 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. [View Abstract]
  9. 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. [View Abstract]
  10. 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. [View Abstract]
  11. 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. [View Abstract]
  12. 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. [View Abstract]
  13. 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. [View Abstract]
  14. 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. [View Abstract]
  15. 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. [View Abstract]
  16. 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. [View Abstract]
  17. 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. [View Abstract]
  18. 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. [View Abstract]
  19. 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. [View Abstract]
  20. 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. [View Abstract]
  21. 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. [View Abstract]
  22. 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. [View Abstract]
  23. 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. [View Abstract]
  24. 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. [View Abstract]
  25. 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. [View Abstract]
  26. 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. [View Abstract]
  27. 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. [View Abstract]
  28. 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. [View Abstract]
  29. Biswas J, Krishnakumar S. Choroidal melanoma in a black patient with oculodermal melanocytosis. Retina. 2003 Feb. 23 (1):126; author reply 126. [View Abstract]
  30. 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. [View Abstract]
  31. 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. [View Abstract]
  32. 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. [View Abstract]
  33. 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. [View Abstract]
  34. Teekhasaenee C, Ritch R, Rutnin U, Leelawongs N. Glaucoma in oculodermal melanocytosis. Ophthalmology. 1990 May. 97(5):562-70. [View Abstract]
  35. Radhadevi CV, Charles KS, Lathika VK. Orbital malignant melanoma associated with nevus of Ota. Indian J Ophthalmol. 2013 Apr 10. [View Abstract]
  36. 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. [View Abstract]
  37. 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. [View Abstract]
  38. Hirayama T, Suzuki T. A new classification of Ota's nevus based on histopathological features. Dermatologica. 1991. 183(3):169-72. [View Abstract]
  39. 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. [View Abstract]
  40. Anderson RR. Lasers in dermatology--a critical update. J Dermatol. 2000 Nov. 27(11):700-5. [View Abstract]
  41. 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. [View Abstract]
  42. 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. [View Abstract]
  43. 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. [View Abstract]
  44. 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. [View Abstract]
  45. Nam JH, Kim HS, Choi YJ, Jung HJ, Kim WS. Treatment and Classification of Nevus of Ota: A Seven-Year Review of a Single Institution's Experience. Ann Dermatol. 2017 Aug. 29 (4):446-453. [View Abstract]
  46. 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. [View Abstract]
  47. 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. [View Abstract]

Nevus of Ota. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/ota2.jpg).

Nevus of Ota. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/ota.jpg).

Nevus of Ito. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/melanocytosis-ito.jpg).

Nevus of Ota. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/ota2.jpg).

Nevus of Ota. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/ota.jpg).

Nevus of Ito. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/melanocytosis-ito.jpg).

Condition Onset Appearance Location Histology
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