Chapter 363. Neoplastic and Proliferative Disorders

Dermatofibromas (fibrous histiocytomas) are red-to-brown, firm nodules, ranging in diameter from a few millimeters to 2 centimeters. These benign lesions are often located on the lower extremities and tend to persist indefinitely. Lateral pressure on the lesion produces dimpling of its surface.1 Larger lesions may be concerning for dermatofibrosarcomaprotuberans, which is a rare, more invasive lesion. Biopsy is diagnostic in both cases and may be necessary to distinguish the lesions. Biopsy of a dermatofibroma reveals prominent fibrocytes and coarse bundles of collagen in a haphazard fashion, frequently arranged in short fascicles that interweave (“storiform pattern”). There is often hyperplasia and hyperpigmentation of the overlying epidermis.2Dermatofibrosarcoma protuberans is usually located on the trunk, often has a blue hue, and may be mistaken for a vascular lesion.3 It is locally invasive and may only rarely metastasize. Wide local excision or Mohs surgery is indicated, and preoperative MRI may help delineate the extent of the lesion before surgery.4

Mastocytosis is a group of disorders in which increased numbers of mast cells infiltrate tissues and organs, especially the skin. Symptoms result from degranulation of mast cells. In contrast to adult forms of the disease, mastocytosis in children often spontaneously resolves. In the most common form of cutaneous mastocytosis, urticaria pigmentosa, a varying number of brown-to-orange macules, papules, or plaques cause a cobblestone or orange peel–like appearance over any part of the skin surface (Fig. 363-1). Spontaneous wheals, vesicles, or paroxysms of pruritus are not uncommon. The solitary mastocytoma presents as a single orange-brown nodule or plaque that may also urticate and blister with trauma, although severe pruritus is uncommon. Diffuse cutaneous mastocytosis is a rare, severe form in which there is marked and widespread infiltration of the skin with mast cells. The skin is thickened, often with a yellow-orange hue, and widespread blistering is often present. Bone, liver, spleen, gastrointestinal tract, and other organs may also be involved. Extracutaneous disease, more common in adults than in children, may be associated with flushing and tachycardia, hypotension, syncope, apnea, headache, vomiting, diarrhea, and/or abdominal pain.5 Mutations in the c-kit gene have been demonstrated in adult patients with mastocytosis, but affected children do not tend to have this mutation.6 The diagnosis of mastocytosis can usually be confirmed clinically by inducing an urticarial wheal-and-flare reaction by stroking a lesion (Darier sign); however, this sign is not entirely specific to mastocytosis. Geimsa or Toluidine blue-stained skin biopsies demonstrate increased numbers of mast cells.7 The combination of H1 and H2 antihistamines is used to decrease the frequency and severity of episodes of mast cell degranulation. Patients with severe gastrointestinal symptoms may be helped by oral disodium cromoglycate. Most children with urticaria pigmentosa follow a benign self-limited course with improvement or resolution occurring during the first decade. Exposures to medications or physical factors that induce mast cell degranulation, including aspirin, alcohol, morphine, codeine, thiamine, scopolamine, polymyxin B, and very hot or cold baths or swimming pools, may provoke acute attacks of systemic symptoms and should be avoided.8

Several skin conditions are characterized by infiltration or proliferation of histiocytes. These cells are a type of progenitor cells of monocytes/macrophages, Langerhans cells, and dermal dendritic cells. These conditions include both self-limited skin disorders and progressive infiltrative diseases that may involve multiple organ systems.

Juvenile xanthogranuloma (JXG) presents as one or more firm dome-shaped, yellow-to-orange-red papules or nodules, ranging in size from several millimeters to 1 centimeter or larger. The head and neck are the most common location for both single and multiple lesions, followed by the upper torso and extremities. Most JXG develops during the first year of life but is occasionally present at birth or develops later.9 Histologically, early lesions are composed of a monomorphous collection of ovoid cells in the dermis, whereas later ones contain foamy histiocytes, lymphocytes, and Touton giant cells. Most often, JXG resolves spontaneously within several years. Children with multiple skin lesions, children younger than 2 years, and those recently diagnosed are at highest risk of intraocular JXG, which may be associated with hyphema; therefore, ophthalmologic examination should be considered.10 Infants with JXG should be examined for evidence of neurofibromatosis (eg, multiple café-au-lait spots) because of possible increased incidence of myelogenous leukemia in this subset.11

Langerhans cell histiocytosis (LCH) refers to a group of disorders in which the basic disease process is a proliferation of Langerhans cells. LCH was previously referred to as histiocytosis X and divided into the pediatric diseases formerly referred to as Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma. These terms are now obsolete and are no longer used.12 In acute disseminated LCH flat-topped, scaly papules in the scalp or intertriginous areas are noted at birth, infancy, or early childhood (Fig. 363-2). These may coalesce to form confluent, red-to-violaceous plaques. Purpuric nodules, vesicular lesions, atrophic scars, and ulcerations may also occur. LCH should be considered in infants with an intractable diaper rash or recalcitrant, severe, seborrhealike eruption on the scalp.13 Skin biopsy is diagnostic and shows an infiltrate of S100, CD1+ cells, with characteristic Birbeck granules on electron microscopy.12 Single or multifocal bone lesions and gingival ulcerations are the most frequent extracutaneous disease, but liver, spleen, lymph node, kidney, and bone marrow are also commonly involved. Some patients with LCH present at birth with vesicles, papules, or dusky red-to-brown nodules; viscera may be involved, or the disease may be limited to the skin in the neonate. Spontaneous resolution of the neonatal disease when limited to the skin is common, but close follow-up is necessary because of recurrences.14,15 Skin may also be involved with focal lesions in the more chronic and differentiated forms of LCH, such as what was referred to as Hand-Schüller-Christian disease, which was defined by the classic triad of exophthalmos, diabetes insipidus, and bony lesions. The treatment of LCH is based on the severity of visceral disease. Chemotherapy is indicated in patients with multisystem involvement.16