Nevus of ota
The nevus of Ota occurs in infancy or appears in adolescence as a blue-gray macule in the distribution of the trigeminal nerve. The lesion is unilateral in 90% of cases. Asian females are most commonly affected. Histologically, a benign dendritic melanocy-tosis is present in the papillary and upper reticular dermis. High-energy fluences of the Q-switched ruby laser results in lightening of the lesion, without scarring, after a few treatments.22
A malformation of epidermal melanocytes, Becker nevus occurs as a large area of hyperpigmentation and increased hair growth and is usually located on one shoulder. It appears most commonly in males during adolescence [see Figure 16]. Underlying bony and soft tissue abnormalities may be associated with this disorder.23
Light microscopy reveals hyperpigmentation of the basal layer of the epidermis, with melanin-containing phagocytes in the dermis but no nevus cells.
Congenital giant pigmented nevus
Giant pigmented nevus is an uncommon birthmark appearing sporadically in one in 20,000 live births. Its features are different from those of an ordinary acquired nevus. Lesions are often darkly pigmented, hairy, and slightly infiltrated, eventually becoming verrucous or nodular. They tend to occur in the distribution of a dermatome and may be quite extensive, as in bathing trunk nevus [see Figure 17]. Satellite lesions may be present. The condition not only is of cosmetic concern but also has a high association with malignant melanoma, with a reported 10% to 15% of nevus patients developing melanoma. Histologic features of an ordinary compound nevus, an intradermal nevus, a neural nevus, or a blue nevus may be present.1 Treatment consists of multiple operations to excise as much of the lesion as possible.
Lesions on the scalp and neck may be associated with neuro-cutaneous melanosis of the leptomeninges that can be complicated by epilepsy, mental retardation, or central nervous system melanoma. Large congenital melanocytic nevi (LCMN) carry a poor prognosis in the presence of CNS signs or symptoms such as abnormal reflexes, hydrocephalus, and papilledema. Posterior axial LCMN, especially in association with satellite nevi, is a risk factor for CNS melanosis. Magnetic resonance imaging should be considered in the evaluation of newborns with these findings. In one study, CNS involvement occurred in 33 of 289 patients with LCMN. All the patients with CNS involvement had nevi in the posterior axial location. Satellite nevi were present in 31 of the 33 patients.24 These findings suggest that melan-ocytic malformation occurs during the migration of neural crest cells that give rise to cutaneous leptomeningeal melanocytes. Malformation resulting in LCMN on the extremities occurs after migration from the neural crest and is not associated with CNS melanosis.
Neural tumors, such as neurofibromas, are of neuroectoder-mal origin, as are melanocytic tumors. Neurilemmomas (also called schwannomas) are benign nerve sheath tumors that extend subcutaneously adjacent to a peripheral nerve. They usually occur in solitary form but may occur as multiple lesions in the syndrome of neurilemmomatosis.
Figure 15 The presence of melanocytes in the middle and lower dermis is responsible for the color of the blue nevus.
Figure 16 Becker nevus, an acquired localized malformation of epidermal melanocytes that may be associated with hypertrichosis, is seen on the shoulder.
These tumors are usually painful and may be associated with nerve compression. Other benign tumors that must be considered in the differential diagnosis of painful skin nodules are neuromas, angiolipomas and angiomyolipomas, leiomyomas, eccrine spiradenomas, glomus tumors, and the blue rubber bleb nevus.
Neurofibromatosis represents a spectrum of disorders involving the skin, central and peripheral nervous systems, bones, and blood vessels. This neurocutaneous syndrome is transmitted via an autosomal dominant gene at an estimated frequency of one in 3,000 persons with almost complete penetrance.26
Diagnosis and Classification
Two distinct forms of neurofibromatosis are recognized, but variant forms also exist.
Neurofibromatosis-1 The most common form (occurring in 85% to 90% of all cases) is NF-1, or von Recklinghausen disease [see Figure 18]. This is a common autosomal disorder, with an incidence of one in 3,500 persons. It is characterized by the presence of cafe au lait spots, intertriginous freckling, multiple spinal and peripheral neurofibromas, plexiform neuromas, bilateral iris hamartomas (also known as Lisch nodules), neurologic impair-ment, and bone abnormalities.
Figure 17 This form of congenital giant pigmented hairy nevus is associated with an increased risk of malignant melanoma, which develops within the lesion.
Figure 18 Multiple neurofibromas, as seen in von Recklinghausen disease, usually appear in late childhood and increase in size and number with age.
The disease is progressive and is associated with a predisposition to a malignant state.
Sarcomatous degeneration of skin lesions is rare but may occur in extracutaneous tumors. Cafe au lait spots of NF-1 may be present at birth and may be best visualized under a Wood light. Neurofibromas begin to appear at puberty as soft, globoid, and pedunculated tumors that are skin colored or violaceous. Lesions may be large and numerous, causing complications resulting from impingement on surrounding structures.
Neurofibromatosis-2 A second form of the disease, neurofibromatosis^ (NF-2), is characterized by bilateral acoustic neuromas, which are Schwann cell tumors that arise from vestibular nerves.27 Associated features may include meningiomas, gliomas, paraspinal neurofibromas, and subcapsular cataracts. Skin tumors and cafe au lait spots are less commonly seen in NF-2 than in NF-1.
Variants Other forms of neurofibromatosis include segmental cases in which cafe au lait spots or neurofibromas are localized to a single dermatome. The gene for NF-2 is located on chromosome 22. In this autosomal dominant disorder, the merlin tumor suppressor gene encoded in chromosome band 22q12 is inactivated. This results in an alteration in DNA with substitution of tyrosine for asparagine at position 220 of the merlin cytoskeletal associated protein.28
Patients with either NF-1 or NF-2 should seek genetic counseling because there is a 50% risk that their offspring will also be affected with neurofibromatosis. In NF-1, optic glioma can appear in early childhood; patients with NF-1 may also have scoli-osis. In NF-2, bilateral acoustic neuromas can cause deafness. The genes for the two distinct forms of neurofibromatosis have been located on two separate chromosomes. This finding may lead to improved diagnosis, which would facilitate genetic counseling and enable prenatal testing.27
For treatment of selected neurofibromas, surgical excision is more successful than scalpel removal or electrodesiccation and curettage. In a preliminary study, the use of ketotifen, a benzo-cycloheptathiophene compound that acts as a mast cell stabilizer, was evaluated in the treatment of patients with neurofibromatosis.29 All treated patients showed a decrease in symptoms of pruritus, pain, or skin tenderness and experienced a decreased rate of neurofibroma growth. Long-term double-blind studies are required, however, to confirm and extend these preliminary findings.
The bilateral acoustic neuromas of NF-2 may be visualized by computed tomography or MRI. Hearing loss is an early symptom that may begin in the second or third decade of life; it can be detected by an audiologic study with brain stem auditory-evoked response. Unilateral acoustic neuromas that are not associated with neurofibromatosis and that are not inherited are more common in older persons and pose fewer management problems.27 Surgical removal of small acoustic neuromas may improve neurologic or audiologic status.
Connective Tissue Tumors
Fibroma of the skin comprises multiple conditions that may represent reactions to hemorrhage, infection, or chronic irritation.
Skin tag, also called acrochordon, commonly occurs as multiple skin-colored or tan, filiform or smooth-surfaced papules that are 2 to 3 mm in diameter. Lesions are often located on the neck or axillae but may also appear in the groin or on the extremities, often as isolated larger polypoid growths [see Figure 19]. The fibrous stalk consists of loose connective tissue with dilated capillaries. Lesions may become inflamed if they are irritated or are traumatized from twisting of the stalk. Biopsy is performed if the clinical diagnosis is uncertain. Skin tags may be removed for cosmetic reasons by using scissors to clip the pedunculate lesions at the base.
Dermatofibroma, also called histiocytoma, is a firm, skin-colored or reddish-brown sessile papule or nodule that arises spontaneously or after minor trauma, usually in adults [see Figure 20]. A dermatofibromatous lesion may occur, for example, after an insect bite on an extremity. A solitary lesion is most common, though multiple or eruptive histiocytomas have been reported. It may be necessary to perform a biopsy when the diagnosis is uncertain. Treatment is necessary only for cosmetic reasons.
Keloid and hypertrophic scar
Normal wound healing in response to tissue injury involves several integrated processes: inflammation, production of granulation tissue, formation of the extracellular matrix, wound con traction, and, finally, scar formation.
Figure 19 Skin tags, also called acrochordons or soft fibromas, are skin-colored or tan papules. They are commonly seen in such intertriginous areas as the groin or axillae.
Figure 20 Dermatofibroma appears as a firm skin-colored or reddish-brown papule and may arise spontaneously or follow minor trauma to the skin.
In the final phases of wound healing, fibroblasts degrade and produce bundles of collagen fibers. These bundles become thicker and are aligned along the lines of tension to which the tissues are exposed. As a result of these changes, wound tensile strength gradually increases. The resulting scar is relatively acellular and has fewer macrophages, blood vessels, and fibroblasts than the unwound-ed tissue.