A 25-year-old woman comes to the office for a routine skin exam. She has had an increasing number of skin-colored papules and nodules over her body since adolescence. Several members of her family have similar skin lesions. Physical examination findings are shown in the exhibit. Abnormal proliferation of cells from which of the following is the most likely cause of this patient's skin lesions?
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This patient has numerous cutaneous neurofibromas (fleshy skin nodules) and café-au-lait macules (flat, uniformly pigmented lesions), likely due to neurofibromatosis type 1, an autosomal dominant disorder (eg, her biological family members are also affected) associated with a mutation in the neurofibromin gene (NF1).
Cutaneous neurofibromas are benign nerve sheath tumors composed of diverse cells and are often found within the dermis. The dermis, the connective tissue layer between the epidermis and subcutaneous tissue (ie, hypodermis), is composed of collagen, elastic fibers, and ground substance and contains extracellular components including nerves, vasculature, hair follicles, and glands. Neurofibromas are composed of a mixture of cells normally found in peripheral nerves, including neoplastic Schwann cells, as well as non-neoplastic fibroblasts, perineural cells, and mast cells.
Cutaneous neurofibromas most commonly appear around puberty and increase in size and number with age. Café-au-lait macules represent localized areas of increased melanogenesis rather than pathologic cellular proliferation.
(Choice A) Numerous cutaneous tumors, both benign and malignant, can arise from the adnexal structures of the skin: hair follicles (eg, pilomatricomas), sebaceous glands (eg, sebaceous adenomas), and sweat glands (eg, poromas). Some cutaneous adnexal tumors present as skin-colored papules or nodules; however, they are typically not as diffuse as this patient's skin lesions and are not associated with numerous café-au-lait macules.
(Choice C) Cutaneous squamous cell carcinoma is characterized by a proliferation of atypical keratinocytes arising from the epidermis and invading the dermis. These lesions often present as discrete nodules with a scaly or ulcerated surface. In contrast, this patient's multiple lesions have normal overlying epidermis. In addition, although the epidermis contains free nerve endings, these unencapsulated neuronal receptors lack the components (eg, Schwann cells, connective tissue) that typically give rise to neurofibromas.
(Choice D) Superficial fibromatosis represents an infiltrative fibroblast proliferation within superficial fascia, which can lead to progressive fascial contracture and local deformity. A classic example is Dupuytren contracture (ie, palmar fibromatosis), which affects the palmar fascia.
(Choice E) Most skeletal muscle neoplasms are malignant. Rhabdomyosarcomas are aggressive tumors that arise from primitive mesenchymal cells with skeletal muscle differentiation rather than from mature, terminally differentiated muscle cells. They often appear during childhood or adolescence and involve locations that do not contain much skeletal muscle, most commonly the sinuses and genitourinary tract.
Educational objective:
Neurofibromas are benign nerve sheath tumors composed of cells normally found in peripheral nerves, including neoplastic Schwann cells, as well as non-neoplastic fibroblasts, perineural cells, and mast cells. Cutaneous neurofibromas often arise from small nerves in the dermis.