Congenital divided nevus
Nevus of Ota (Oculodermal Melanocytosis)
Oculodermal melanocytosis , known historically as the nevus of Ota, represents a disorder defined by the presence of melanocytes within the dermis which gives these lesions their characteristically bluish-gray or blue-brown color. The pigmentation occurs most likely as a mosaic phenomenon and has been associated in some cases with somatic activating mutation in genes encoding G-proteins such as GNAQ and GNA11 . Nevus of Ota is most commonly seen in the Japanese population, although it does occur in other individuals. Women are affected two  to five times as frequently as men .
The eye is involved in approximately two-thirds of cases . Approximately 95% of cases are unilateral. In the affected eye, the sclera is blue and the conjunctiva is brown. The episclera and iris are most commonly affected, followed by involvement of the anterior chamber angle and the choroid . Pigmentation may also occur on the eyelids, cornea, and optic disk. The pigmentation may be present at birth but usually manifests itself later in childhood, becoming progressively darker and persisting into adulthood. The condition may manifest itself in three different patterns. In one pattern, the skin and the eye are involved (Fig. 6.2). Other patients may have just skin involvement, while a small number of patients have only ocular involvement.
Nevus of Ota (oculodermal melanocytosis ) (Courtesy of the Section of Dermatology at the Children’s Hospital of Philadelphia, used with permission)
Children who present with oculodermal melanocytosis should have a full skin evaluation for coexisting capillary malformations (port wine stains) as part of the syndrome, phakomatosis pigmentovascularis.
Ocular complications include intraocular hypertension and, rarely, malignant melanoma [11–13]. Malignant transformation has been seen most commonly in patients with light-colored skin types, less so in darker-skinned patients, and least among patients of Asian background .
Ophthalmologic management consists primarily of periodic eye examinations to monitor for development of glaucoma and ocular melanoma. Treatment, where desired, can be performed with nanosecond or picosecond lasers (Q-switched ruby, Nd:YAG, alexandrite)  and typically requires multiple serial interventions. While earlier intervention may be associated with better response rates, eventual recurrence following laser treatment is commonplace. Dermabrasion and cryotherapy have also been reported although these modalities are accompanied by higher rates of post-therapy dyspigmentation.
Only 1% of all ocular melanomas occur in the pediatric population, and pediatric melanoma, in general, is fortunately rarely encountered . These may arise from preexisting congenital melanocytic nevi or oculodermal melanocytosis and arise as metastatic disease from elsewhere, or in the context of predisposition to malignancy, such as xeroderma pigmentosum . The presence of ocular nevi can be associated with both increased risk of ocular and cutaneous melanoma; additionally, those with atypical cutaneous nevi appear to be at higher risk of ocular melanoma . Some estimates indicate that the lifetime risk of ocular melanoma in the context of oculodermal melanocytosis is approximately 1 in 400 affected patients . Congenital ocular melanoma is an extremely rare event, with only three cases previously reported [19–21].
Dermoid cysts manifest as non-tender, firm, smooth, subcutaneous nodules (Fig. 6.3). Initially mobile, they may become fixed on palpation. They are the most common cystic tumors of the orbit in childhood, accounting for more than a third of all orbital lesions. Although dermoid cysts are present at birth, less than 25% of the lesions are evident at birth. These lesions are presumed to arise as the result of tissue sequestration at lines of embryonic closure during fetal development. As a result, dermoid cysts are most commonly found on the upper temporal quadrant, superonasally, and occasionally in the epibulbar or intraorbital locations. Histologically, dermoid cysts contain keratin and sebaceous material with a surrounding epithelial lining that can contain sebaceous glands, hair follicles, apocrine glands, and eccrine glands.
Dermoid cyst , commonly seen on lateral eyebrow area
Midline lesions may represent sites of underlying cranial dysraphism . Often, these lesions on the superonasal area manifest as a dimpled area, sometimes with small protruding hairs. Patients with midline lesions should undergo brain imaging to evaluate the extent of underlying cranial dysraphism and communication with the central nervous system.
Untreated lesions may leak contents resulting in local inflammatory subcutaneous tissue changes, and the pressure from the cyst can cause erosion of underlying bone. Prophylactic excision of identified cysts can prevent progression to these reported complications.
Epidermal (inclusion) cysts present as flesh-colored or slightly yellowish, raised, firm, slightly compressible, 0.5–5 cm dermal or subcutaneous nodules. A small black overlying punctum may be observed. They arise most commonly on the face including the periorbital area, neck, shoulders, and chest. Being slow growing and asymptomatic, some epidermal cysts may leak contents and become inflamed. When they break down, cheesy off-white and often foul-smelling material may be extruded. Histologically, these consist of a cyst wall of keratinizing epithelium filled with keratinaceous material. While some inflamed cysts may be ameliorated with intralesional steroid injection, definitive excision is typically required as these cysts recur if residual cyst lining is left behind.
Presenting as either a single or multiple small 1–2 mm yellow-white papules, milia are commonly encountered in the periorbital region. Essentially small epidermal cysts, milia consist of small cystic accumulations of keratin within the pilosebaceous unit of vellus hair follicles.
Milia are frequently encountered during the neonatal period, but may arise at any age. In children, milia tend to spontaneously regress, while in adults, lesions may be more persistent.
Milia arise at sites of trauma and are often noted following cutaneous burns, during the healing of blistered areas in mechanobullous disorders such as epidermolysis bullosa or metabolic disorders such as porphyria. Periorbital milia may be a sign of allergic rhinoconjunctivitis in association with frequent intermittent rubbing of the eyes. Milia may also be an indicator of an underlying syndromic association.
Treatment consists of either simple incision and extraction of the keratinaceous contents or therapy with a topical retinoid for lesions outside the immediate periorbital area to hasten resolution, as long as topical agents can be kept from getting into the conjunctival space and irritating the eye.
Conditions Associated with Facial Milia
Anhidrotic ectodermal dysplasia
Basal cell nevus syndrome
Congenital atrichia with papules
Epidermolysis bullosa (especially the dystrophic variety)
Hereditary trichodysplasia (Marie-Unna hypotrichosis)
Oral-facial-digital syndrome, types I and IX
Basal Cell Carcinoma
Basal cell carcinoma (BCC) has been occasionally reported on the eyelids in children and young adults, though this condition is more commonly seen in middle-aged and older adults who have experienced lifetime significant sun damage [23–26]. Rare reports have documented congenital presentation .
Clinically, early BCC lesions classically present as small pearly appearing, dome-shaped papules that are often accompanied by small overlying telangiectasias. As lesions evolve, ulceration and crusting may occur. Rarely metastatic, BCC can be locally destructive as a result of local invasion into underlying soft tissues and bone.
When encountered in the pediatric population, BCC may arise from an underlying lesion predisposed to malignant transformation (such as a nevus sebaceous), in the context of a predisposing genetic condition such as xeroderma pigmentosum or basal cell nevus syndrome, or related to a history of significant radiation exposure (as with radiation therapy or iatrogenic photosensitivity related to voriconazole administration) .
When arising as singular, isolated lesions, surgical excision with adequate margins is advised to minimize risk of recurrence. This is often performed using Mohs micrographic surgery followed by oculoplastic surgical repair and reconstruction. In cases that are not amenable to surgical excision, alternatives such as topical imiquimod application, radiation therapy, cryotherapy, or photodynamic therapy may be considered.
Hemangiomas are benign tumors characterized by the proliferation of vascular endothelial cells. While only approximately 2.5% of hemangiomas are present at birth, 90% of them are noted during the first month of life. After a rapid growth period of 3–6 months, hemangiomas stabilize and then go through a process of involution. Fifty percent of hemangiomas reach their maximal involution by 5 years of age and 90% by 9 years of age. Some residua such as telangiectasias, fibrofatty tissue, and atrophic skin may persist indefinitely once a hemangioma has involuted in between up to 2/3 of patients . Hemangiomas may present on any part of the body and are most worrisome when they occur around vital structures such as the eyes.
Hemangiomas in and around the orbit can cause amblyopia due to obstruction of the visual axis, strabismus, or anisometropia. Prompt ophthalmologic evaluation should be accompanied by consideration of appropriate strategies for intervention. During the proliferative phase, hemangiomas are highly responsive to pharmacologic therapy. Due to their favorable safety profile and degree of efficacy, beta-blockers have largely supplanted systemic corticosteroid as the mainstay of therapy. Beta-blockers are thought to exert their effect through vasoconstriction, inhibition of vascular endothelial growth factor, and induction of apoptosis . Propranolol was approved by the FDA in 2014 for the treatment of infantile hemangioma in full-term infants 5 weeks and older, at a gradually up-titrated target dosage of 3.4 mg/kg/day divided twice daily for 6 months . Approximately 90% of hemangiomas show a rapid and favorable response , and early treatment responses may be seen within 3 days of initiation. Patients treated with propranolol must be monitored for blood pressure and heart rate as well as signs and symptoms of hypoglycemia and bronchoconstriction. Variations in dosage and duration are not uncommon since the drug has been used extensively off-label since 2008 when the efficacy of propranolol was initially reported . Other systemic beta-blockers have also been reported as effective – including atenolol and nadolol, though their use remains off-label [34, 35]. Topical beta-blocker therapy also shows promise for thin, superficial hemangiomas. Topical timolol which is available in an ophthalmologic formulation can be applied two to three times daily and can slow, arrest, or even regress proliferating hemangiomas. The gel-forming solution is commonly used for this purpose until the proliferation and plateau period has ended.
Mastocytosis is a condition characterized by the accumulation of mast cells in the skin and sometimes other organs. In children, three principal types of cutaneous lesions are usually present: urticaria pigmentosa, solitary mastocytomas, and diffuse cutaneous mastocytosis.
Urticaria pigmentosa is the most common form of this disorder. It is characterized by numerous yellow to reddish-brown macules or papules that usually display a positive Darier’s sign, the development of urticaria, or blistering upon stroking the lesion. The lesions usually appear on the trunk but may be found on any part of the body, including the eyelids.
Solitary mastocytomas are reddish-tan, brown, or yellow-orange cutaneous nodules (Fig. 6.4). They also display a positive Darier’s sign in which stroking the lesion elicits urtication. They are present at birth or during early infancy with most lesions regressing within several years. Mastocytomas usually present on the arms, neck, and trunk. Blistering may occur, especially before 2 years of age. There are scant three case reports in the literature of a solitary mastocytoma involving the eyelid [36–38]. The lesion was present at birth and excised without recurrence. Solitary mastocytomas almost always regress, so excision is unnecessary except in cases where the diagnosis is in doubt, as it was in the congenital eyelid lesion.
Urticaria pigmentosa : lesions are common on the forehead and periocular areas (Courtesy of the Section of Dermatology at the Children’s Hospital of Philadelphia, used with permission)
Diffuse cutaneous mastocytosis is a very rare cutaneous variant of mastocytosis characterized by indistinct diffuse skin infiltration with mast cells. The skin has a rippled, boggy, thickened appearance with doughy consistency. These patients can be quite ill, with extensive bulla formation, flushing attacks, fainting, and diarrhea.
The symptoms and cosmetic changes of mastocytosis disappear with time. Residual pigmentation may remain if the lesions are extensive. When faced with a lesion suggestive of mastocytosis, the lesion should be stroked in an attempt to elicit Darier’s sign. Biopsy of a suspected lesion would typically show evidence of mast cells with Giemsa or other appropriate mast cell stain. In cases where one mastocytoma is identified, a total body examination to look for similar lesions is advised.
The nasal glioma is a benign lesion that may be considered a sequestered encephalocele, consisting of neuroectodermal tissue that herniates through the nasofrontal fontanelle during early fetal development and is not retracted at the time of craniofrontal suture closure [39–41]. Nasal glioma presents as a congenital lesion on the lateral aspect of the nasal bridge or occasionally as polypoid lesions within the nose or pharynx (Fig. 6.5). Typically red to purple, firm, dome-shaped nodules, nasal gliomas, measure up to approximately 3 cm in diameter though some have been larger and will grow with the child. These lesions may grow to obstruct local structures such as the ipsilateral lacrimal apparatus or, when large enough, may compromise vision . Internal nasal gliomas present as polypoid lesions in the nose or pharynx.
Nasal gliomas do not transilluminate the way fluid-filled encephaloceles do, and this may be a useful diagnostic feature. That being said, because nasal gliomas may also resemble deep hemangiomas, dermoid cysts, as well as encephaloceles [22, 42], radiologic imaging studies are often needed to define the nature and extent of the lesion prior to any surgical intervention .
Common hair follicle tumors, pilomatricomas manifest most often as solitary, firm dermal or subcutaneous nodules that often have a bluish hue. Palpation reveals a jagged, irregular border and often a stony-hard consistency due to associated calcification. Pressure to one lateral edge of the lesion produces elevation of the opposite side in what is referred to as the “teeter totter sign.” Lesions are often located on the face, including the periorbital area where the upper eyelid is more commonly seen than the lower eyelid [44, 45], as well as the neck, or upper extremity, and show gradual growth over time. Untreated lesions may ulcerate, or extrude calcium material (Fig. 6.6). Rarely, malignant transformation to a pilomatrix carcinoma has been reported.
Pilomatrixoma . Note the early extrusion of calcified material
Children who have multiple pilomatricomas may have an associated underlying disorder that predisposes to their formation. Since pilomatricomas generally persist, have the potential to ulcerate and scar, and have a low but potential for malignant change, prophylactic surgical removal is advised.
Conditions Associated with Multiple pilomatricomas
Familial Sotos syndrome
Pyogenic granulomas are bright red to brownish-red, raised, vascular-appearing papules or nodules, with a collarette of epidermis at the base (Figs. 6.7 and 6.8). They may be pedunculated or sessile and may grow to 10 mm in diameter. Pyogenic granulomas are common in children and may present on any cutaneous surface, although they most commonly occur on the face, forearms, and hands. Patients usually present with complaints of a rapidly growing lesion with recurrent bleeding.
Pyogenic granuloma (Courtesy of the Section of Dermatology at the Children’s Hospital of Philadelphia, used with permission)
Pyogenic granuloma on the conjunctiva (Courtesy of Sylvia Kodsi, MD)
When near the orbit, pyogenic granulomas occur most commonly on the eyelids, with a preference for the lower lids [46, 47]. Pyogenic granulomas have also been reported on the fornix , palpebral and bulbar conjunctiva [49, 50], lacrimal sac , and, rarely, the cornea . Their cause is unknown, although many believe them to be a reactive lesion, as a response to antecedent trauma or inflammation. A study of 100 cases of pyogenic granulomas around the eyes found that 87% were associated with a predisposing factor such as chalazion, ocular or adnexal surgery, or accidental trauma . This is in contrast to pyogenic granulomas occurring in other locations where a clear history of preceding trauma is rarely elicited.
Treatment includes curettage with gentle cautery. Larger lesions typically require excision. If the feeder vessel remains, there is a chance for recurrence. All lesions should be sent for histopathologic diagnosis, because the clinical differential diagnosis includes malignancies including but not limited to amelanotic melanoma, carcinomas, and sarcomas.
Squamous Cell Carcinoma
Persistently scaly or crusted papules or erosions may rarely indicate a squamous cell carcinoma. These lesions are extremely rare in children and are typically associated with underlying predispositions to malignancy as might be seen with DNA repair disorders (xeroderma pigmentosum)  or from severe photosensitivity related to medications (as seen with voriconazole) . Because of the potential for metastasis, prophylactic surgical excision with clear margins is advised. Mohs micrographic surgery in conjunction with oculoplastic surgical repair and reconstruction may be necessary when the periocular area is involved.
Syringomas are benign adnexal tumors that derive from eccrine duct structures. Presenting as multiple, small, 1–3 mm, monomorphic skin-colored to yellowish papules, syringomas are most commonly seen on the periorbital and especially lower eyelid areas (Fig. 6.9). When considering this diagnosis, identifying similar lesions on the neck, trunk, abdomen, and genitalia can help corroborate the diagnosis of syringoma. Patients with Down syndrome  have an increased risk for developing syringomas. While benign and generally asymptomatic, patients may wish to pursue treatment for persistent lesions for cosmetic purposes. Treatments include topical retinoid therapy, cryotherapy, electrodesiccation, or local excision.
Trichoepitheliomas manifest as benign, firm, skin-colored, slightly translucent papules that typically range in size from 2 to 5 mm, although some can grow as large as 3 cm. Lesions tend to appear on the face especially along the nasolabial folds, central face, and eyelids. Trichoepitheliomas tend to arise during the second or third decades. Lesions may be solitary or multiple and, when multiple, may arise as part of an autosomal-dominant disorder referred to epithelioma adenoides cysticum. When cylindromas are also present on the scalp in conjunction with trichoepitheliomas, Brooke-Spiegler syndrome should be considered. Clinically, trichoepitheliomas may resemble syringomas or non-ulcerated basal cell carcinomas. Rarely, trichoepitheliomas may devolve into basal cell carcinoma. While shave techniques may allow for histologic sampling, residual lesions tend to regrow and treatment typically involves excision of the lesion.
Xanthelasma or xanthoma palpebrarum are yellowish papules or plaques that are commonly found on the upper eyelids around the inner canthus. They are generally bilateral and symmetrical. While rare in children, when present, they may indicate familial hypercholesterolemia, hyperapo B syndrome, or phytosterolemia, and affected children should therefore be evaluated for an underlying lipid metabolism disorder . Xanthoma disseminatum, a proliferation of non-x histiocytes that resembles xanthelasma, may rarely occur on the eyelids along with disseminated skin and visceral disease . Adults may also develop lesions resembling xanthelasma in response to filler injections . Treatment modalities include trichloroacetic acid chemical peeling, destruction with cautery, laser ablation, or excision.
Granuloma annulare (GA) is a benign cutaneous disorder characterized by dermal granulomas that present clinically as papules or nodules in an annular configuration. The lesions usually begin at sites predisposed to trauma such as the dorsum of the hands and feet, but can occur at any site, including the eyelids (Fig. 6.10). Seventy-nine percent of cases of nodular granuloma annulare occur in people under 25 years of age . While the condition is more common in childhood, adults may be more predisposed to the more generalized form of the disorder. Variations in presentation include plaques, annular plaques, perforating papules, and subcutaneous nodules. Although their exact etiology is unknown, lesions may arise as an idiosyncratic response to trauma. Unlike in adults, this condition is rarely associated with diabetes mellitus in children.
Granuloma annulare , near medial canthus (Courtesy of the Section of Dermatology at the Children’s Hospital of Philadelphia, used with permission)
The nodular or subcutaneous form of GA is also known as pseudorheumatoid nodules because of their histologic resemblance to nodules seen in patients with rheumatoid arthritis. Seventy-nine percent of cases of nodular GA occur in people under 25 years of age. The lesions in nodular granuloma annulare most commonly occur on the extensor surface of the extremities, the dorsum of the hands and feet, the scalp, buttocks, and the eye. Nodules have been reported on the eyelid, periorbital area, lateral canthus, medial canthus, episclera, orbit, and lateral rectus muscle.
In the absence of other cutaneous lesions indicative of GA, nodules presenting in the periorbital area should be evaluated further with either imaging or biopsy. The differential diagnosis includes epidermal cysts, dermoids, neurofibromas, leukemia, lymphoma, pilomatrixomas, syringomas, sarcoidosis, and other granulomatous processes.
Most lesions do not require treatment as they typically resolve within months to years, if left untreated. Some lesions spontaneously resolve after being biopsied.
Sarcoidosis is a granulomatous disorder of unknown etiology and rarely presents during childhood. When present, it may occur in preschool-aged children, generally those of ages 4 years or younger. The presentation at this age, often referred to as Blau syndrome , is characterized by polyarthritis, uveitis, and multiple cutaneous lesions that include flesh-colored, yellow, or red infiltrated papules, reddish-brown confluent plaques, and eczematous lesions (Fig. 6.11). The infiltrated lesions may occur in the periorbital area. Other ocular findings in children include conjunctival and lacrimal gland involvement, keratitis, retinitis, and glaucoma. The chest x-ray in affected children is usually normal. A complete physical examination should be done to look for cutaneous lesions elsewhere. Sarcoidal lesions can also appear psoriasiform and lupus erythematosus-like or present as small follicular papules. A biopsy of these lesions will reveal typical sarcoidal granulomas. Sampling of the conjunctivae frequently yields sarcoidal granulomas histologically.
Juvenile xanthogranuloma (JXG) is a benign cutaneous disease of infants and children. It is now classified as a non-Langerhans cell histiocytosis and is characterized clinically by the development of one or more red to yellow-orange papules with a rubbery consistency. Lesions generally measure between 1 and 10 mm in diameter. JXGs usually develop within the first 9 months of life although 20% are present at birth. JXGs are commonly located on the face, scalp, and neck, but can also be seen on the upper trunk and proximal portions of the upper extremities (Fig. 6.12). Although JXGs usually remain localized to the skin, there are reports of extracutaneous lesions involving the eye, lungs, pericardium, testes, liver, spleen, and central nervous system.
Juvenile xanthogranuloma (Courtesy of Ruggero Caputo, MD)
The eye is the most common extraocular site affected. Ocular involvement was first reported in 1949 . Since that time, a number of cases of juvenile xanthogranuloma involving the eyelid, conjunctiva, cornea, sclera, limbus, retina, orbit, and optic nerve have been reported. A macronodular variant, where the lesions can measure several centimeters in diameter, has been reported on the eyelid . There is great variation in the color of the ocular lesions, thereby creating a large differential diagnosis and making clinical diagnosis difficult. Ocular lesions have been reported to occur in up to 10% of patients with cutaneous lesions. Juvenile xanthogranulomas of the iris are the most common, followed by eyelid involvement. Eighty-five percent of patients with intraocular involvement present during the first year of life . These patients present with spontaneous hyphemas and glaucoma [64, 65]. Most lesions regress after a year, although some may persist for longer periods.
Histologically, mature lesions are characterized by a granulomatous infiltrate containing foam cells, foreign body giant cells, Touton giant cells, histiocytes, lymphocytes, and eosinophils. The Touton giant cell is characterized by a “wreath” of nuclei surrounded by foamy cytoplasm and is quite typical for juvenile xanthogranuloma. Treatment, when indicated, includes corticosteroids, excision, and radiotherapy (see Chap. 12).