Oculodermal Melanocytosis
Key Points
Oculodermal melanocytosis is a benign congenital anomalous pigmentation of deep facial skin and ocular tissues
It is a dermal melanocytic hamartoma that presents with unilateral or bilateral, brown or blue discoloration on facial skin areas that are innervated by the ophthalmic and maxillary divisions of the trigeminal nerve
It is 10 to 25 times more common among Asians than in Caucasian and black individuals
The pathogenesis is not known but is considered to be a dermal hamartoma that represents a failure of migration of melanocytes from the neural crest to the dermal-epidermal junction and subsequent arrest within the dermis
Lesions usually present as poorly defined separate or contiguous areas of pigmentation on the facial skin and nasal and oral mucosa, but in some patients only ocular involvement may be present
In addition to eyelid skin, the sclera, conjunctiva, cornea, and lens can be involved as well as orbital tissues and bone
Malignant degeneration is rare, but most cases occur in Caucasian patients
Treatment includes surgical excision with skin grafting, cryosurgery, and dermabrasion, but Q-switched laser therapy has become the treatment of choice
Laser therapy has significantly improved the prognosis with 80% to 90% of patients attaining a satisfactory cosmetic outcome
Malignant change is seen in 4% to 5% of patients
Oculodermal melanocytosis (ODM), or nevus of Ota, is a benign congenital anomalous pigmentation of deep facial skin and ocular tissues. It was first described by Hulke in 18611 in a patient with unilateral pigmentation of the face and sclera. That case was complicated by the presence of an ipsilateral choroidal malignant melanoma. In 1939, Ota2,3 described additional patients in Japan, defining the syndrome as a clinical entity. Since that time over 1000 cases have been described.
ODM is a dermal melanocytic hamartoma that presents with unilateral or bilateral, brown or blue discoloration on facial skin areas that are innervated by the ophthalmic and maxillary divisions of the trigeminal nerve.4 Approximately 50% to 55% of cases involve both the ophthalmic and maxillary divisions, 25% the maxillary division alone, and 20% the ophthalmic division alone.5 The occurrence of pigmentation in the distribution of the mandibular division of the trigeminal nerve is very rarely observed, with only one case described involving the buccal mucosa6 and another case involving the oral mucosa and the jaw.7 Several other cases of blue nevus have been described involving the buccal mucosa or oral floor,8,9,10 and some authors have grouped ODM and blue nevus together as variants of dermal dendritic melanocytic proliferations.11,12
The incidence of oculodermal melanocytosis is difficult to assess since many mild cases go unrecognized or unreported. Yoshida5 reported 110 cases among 27,082 consecutive clinic patients in Japan, an incidence of 4 per 1000 population (0.4%). Tanino13 found 26 cases among 2300 dermatologic patients in Japan, for an incidence of 11 per 1000 (1.1%). Among a series of 8680 subjects in Shanghai, Wang et al14 found acquired bilateral nevus-of-Ota-like macules in 2.5%. The only comparable figures for the United States are four affected patients among approximately 25,000 (0.016%) seen in the ophthalmology clinic at Philadelphia General Hospital.15 Gonder et al16 examined 13,150 white and black patients in an ophthalmology clinic and found an ODM incidence of 0.038% (2/5251) among white patients and 0.014% (1/6915) among black patients. Thus, oculodermal melanocytosis is at least 10 to 25 times more common among Asians than in Caucasian and black individuals.4,17
In 1939, Tanino18 observed several patients with oculodermal melanocytosis and divided them into four types according to the extent of skin involvement, and these were further divided into seven subtypes based on their location.17,19,20 These types were Ia, eyelids, periorbital and temporal areas; Ib, zygomatic area, nasolabial fold, and the lower eyelid; Ic, forehead area; Id, nostril area; II, upper and lower eyelids, zygomatic area, cheek, temple area; III, scalp, forehead, eyebrow, and nose; and IV, bilateral.
However, other authors found that Tanino’s classification failed to accurately include all affected patients. Huang et al21 reported that 19.7% of their 1079 patients with oculodermal melanocytosis were not accommodated by the Tanino classification, and Nam et al22 found an even higher rate at 35.8%. The Peking Union Medical College Hospital (PUMCH) classification is a newer system developed by a Chinese group in 2013 based on five large categories and 15 subdivisions according to the extent of involvement in the distribution of the trigeminal nerve branches.21 These are I, pigmentation involving one branch of the trigeminal nerve;
II, pigmentation involving two branches of the trigeminal nerve; III, pigmentation involving all three branches of the trigeminal nerve; IV, bilateral type; and V, melanocytosis accompanied by other cutaneous complications. In 2017, Nam et al22 introduced a three-point severity scale based on the proportion of the melanocytosis on the half-face as follows: mild, ≤one-third of the half-face; moderate, >one-third to ≤two-thirds; and severe, >two-thirds.
II, pigmentation involving two branches of the trigeminal nerve; III, pigmentation involving all three branches of the trigeminal nerve; IV, bilateral type; and V, melanocytosis accompanied by other cutaneous complications. In 2017, Nam et al22 introduced a three-point severity scale based on the proportion of the melanocytosis on the half-face as follows: mild, ≤one-third of the half-face; moderate, >one-third to ≤two-thirds; and severe, >two-thirds.
Several families have been reported in which some close relatives were affected with ODM. Hidano et al23 found a father and son in one family and two sisters in another with the syndrome. Yoshida5 reported a mother, her son, and his cousin, all similarly affected. Two families were noted by Watanabe,24 one involving a mother and daughter, and in the other, two sisters. In the Hidano et al series of 240 patients,23 15 of 208 for which family histories were obtained, were related to each other, usually as first cousins. However, they could not recognize any definite pattern of hereditary, nor was there any consistent history of consanguinity. Goyal et al25 reported a case of a brother and sister with bilateral familial nevus of Ota. Previous reports of familial cases suggest that inheritance may be autosomal recessive or autosomal dominant, with variable expressivity; however, definite hereditary patterns have not been established.26,27,28,29
Etiology and Pathogenesis
The pathogenesis of ODM is not known. It is usually considered to be a dermal hamartoma that represents a failure of migration of melanocytes from the neural crest to the dermal-epidermal junction and subsequent arrest within the dermis.4 Melanocytic cells are not normally found in deep dermal layers of adult humans, and their presence in ODM suggests an embryonic anomaly. The etiology of melanoblasts is from neuroectoderm, either directly from neural crest precursors or from dermal Schwann cells.30 In other anthropoid apes, such dermal melanocytes are normally seen in the adult,30 and they can also be found beginning in the 11- to 12-week embryonic stage in humans.31 Whether or not these dermal melanocytes gradually disappear or migrate up into the epidermis is not clear, but dermal melanocytes in adult humans are usually not present. They represent a developmental defect in which these cells persist abnormally and therefore represent an abnormal migration.30,32 In this regard, it has been suggested that the pathogenesis of blue nevus, the Mongolian spot, and oculodermal melanocytosis are all related, if not identical.30
Because the incidence of ODM is so much greater in females, a hormonal relationship has been proposed for the development of pigment in previously nonpigmented cells.33 Wang et al14 reported that, among 196 females with ODM-like pigmentation, the prevalence of the disease increased after the age of 15 years and sharply declined after the age of 50 years, with nearly half of the cases observed within ages 45 to 55 years. Age, contraceptive use, and sun exposure were independently associated with the disorder. These findings suggested that sex hormone alteration and UV exposure may independently play important roles in the pathogenesis of ODM.
Histologically, ODM shows significant overlap with a blue nevus. Blue nevi show mutations in GNAQ, a GTPase acting downstream of G protein-coupled receptors.34,35 This mutation has also been found in ODM, although at a lower frequency.35 There is a clear relationship between ODM and uveal melanoma, and about 50% of uveal melanomas also harbor the GNAQ mutation, suggesting a link between these two conditions.35 Although ODM is far more common in Asians, the risk of melanoma is mostly seen in white populations.4 In Caucasian patients with ODM, the risk of developing uveal melanoma is approximately 20 times higher than seen in the general population. The development of cutaneous malignant melanoma in ODM is less frequent.
Clinical Presentation
ODM is characterized by dermal involvement of the face and ocular tissues, but in about one-third of patients, the eye is not involved.36 In a series of 28 Chinese cases with ODM,37 the most frequent areas involved were the eyelids (82%), forehead (79%), cheek (71%), and temporal regions (64%). In 96.4% of cases, more than three regions were involved, and ocular and nasal mucosal involvement was observed in 57%. Among Japanese with ODM, pigmentation of the eustachian tube and tympanic membrane may be seen in up to 55% of patients, the nasal mucosa in 24%, and the palate and pharynx in 18%.23,38 Pigmentation may also occur in the underlying periosteum, bone, dura mater, cerebral cortex,39 the maxillary sinus,40 and the orbicularis and temporalis muscles. The condition is usually unilateral, and bilateral involvement is rare, seen in only approximately 5% to 13% of cases.2,5,37,38
Lesions of ODM usually present as areas of pigmentation on the facial skin and nasal and oral mucosa,41 and in some patients only ocular involvement may be present. The cutaneous lesions typically consist of macular, poorly defined, separate, or contiguous areas of hyperpigmentation that are not associated with increased vascularization or hair (Figure 99.1). There may be elevated nodules of denser pigmentation within it. Color varies from light brown to blue-black, to purple,5 and may be so subtle as to be missed clinically.
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