Vascular Neoplasms and Malformations

Telangiectasias

Telangiectasias are such a common cutaneous finding that they are often overlooked or disregarded. In the head and neck region, the linear variety is most commonly due to solar damage or rosacea, whereas on the lower extremities telangiectasias are usually a sign of venous hypertension ( Fig. 23-1 ; Table 23-1 ). The recurrent flushing of the face and upper trunk that occurs in patients with the carcinoid syndrome may also be accompanied by linear telangiectasias, which can result in misdiagnosis as the erythematotelangiectatic form of rosacea.

In ataxia–telangiectasia, linear telangiectasias first appear on the bulbar conjunctivae during early childhood, followed over time by similar, but often more subtle, lesions in sites such as the periocular skin, ears, and antecubital and popliteal fossae. The telangiectasias are typically preceded by the onset of cerebellar ataxia when the patient began to walk. Additional skin findings may include granulomatous dermatitis, nevoid hyper- or hypopigmentation, and progeric changes. Affected individuals usually develop recurrent pulmonary infections and are at high risk of lymphoproliferative disorders. This autosomal recessive disorder is due to mutations in the ATM gene, but how this relates to the formation of telangiectasias is not well understood (see Chapter 34 ).

A rare variant of mastocytosis (see Chapter 36 ) referred to as telangiectasia macularis eruptiva perstans (TMEP) is characterized by multiple clusters of telangiectasias. Although somatic activating mutations in the KIT gene are found in most adults with urticaria pigmentosa, to date they have not been reported in patients with TMEP. Arborizing telangiectasias are a classic feature of basal cell carcinomas, and telangiectasias are also seen within cutaneous B-cell lymphomas ( Fig. 23-2 ).

One or two papular telangiectasias commonly occur on the face or hands of healthy individuals, especially women and children. Spider telangiectasias (also known as spider angiomas or spider nevi) represent dilations in ascending dermal arterioles and are characterized by both a punctum and radiating legs. The development of multiple spider telangiectasias can be a sign of hyperestrogenemia, such as occurs during pregnancy and in patients with hepatic cirrhosis.

The presence of multiple papular and stellate macular telangiectasias on the oral mucosa and lips ( Fig. 23-3, A ) as well as the face, fingers ( Fig. 23-3, B ), and nailfolds ( Fig. 23-3, C ) raises the possibility of hereditary hemorrhagic telangiectasia (HHT; Osler–Weber–Rendu syndrome). These vascular lesions most often become apparent around or after puberty, and a personal or family history of epistaxis, gastrointestinal bleeding, or cerebrovascular accidents increases suspicion of this autosomal dominant condition. The vascular lesions of HHT actually represent arteriovenous malformations (AVMs), which explains their propensity to bleed. By stretching the skin, an eccentric punctum with radiating branches can be visualized.

When the clinical diagnosis of HHT is made, it is important to screen individuals with a transthoracic echocardiogram bubble study (which assesses shunting) and a brain MRI with gadolinium enhancement to exclude pulmonary and cerebral AVMs, both of which are amenable to interventional vascular procedures, e.g., embolotherapy or surgical excision. Most patients with HHT have a mutation in ENG or ACVRL1 , genes that encode endoglin and activin A receptor type II-like 1, respectively. Patients with juvenile gastrointestinal polyposis in addition to HHT may have mutations in the SMAD4 gene, which encodes a protein that, like endoglin and ACVRL1, is involved in transforming growth factor-β signaling; these patients are at increased risk of early-onset colorectal carcinoma.

Poikiloderma is defined by the presence of (1) telangiectasias; (2) wrinkling due to epidermal atrophy; and (3) reticulated areas of hypo- and hyperpigmentation. This combination of skin findings is characteristically seen years after orthovoltage irradiation. Poikiloderma can be a feature of dermatomyositis ( Fig. 23-4, A ) and cutaneous T-cell lymphoma. In the latter condition, the lesions favor the axillae and groin ( Fig. 23-4, B ).

Telangiectasias, in particular mat and periungual variants, are an important cutaneous clue to the diagnosis of autoimmune connective tissue diseases (AI-CTD). Mat telangiectasias are flat, often have a polygonal shape, and favor the face, oral mucosa, and hands ( Fig. 23-5 ). They are a sign of scleroderma or an overlap syndrome that includes scleroderma. Of note, in the acronym for the more indolent, anticentromere antibody-positive CREST variant of scleroderma, the T stands for telangiectasias. Periungual telangiectasias are seen in systemic lupus erythematosus (SLE), dermatomyositis (DM), and scleroderma. In the latter two AI-CTD, individual telangiectasias appearing as swollen loops are admixed with avascular areas ( Fig. 23-6 ), whereas in lupus the telangiectasias have an appearance that has been likened to that of renal glomeruli. Nailfold telangiectasias are accompanied by erythema in SLE, and both erythema and ragged cuticles in DM.

Benign Vascular Tumors and Malformations

On the basis of biologic characteristics, vascular anomalies are divided into two major categories ( Table 23-2 ): vascular tumors, which arise by cellular hyperplasia; and vascular malformations, which result from errors in vascular morphogenesis during intrauterine development and have normal cellular turnover. When vascular tumors are compared to vascular malformations, there are important differences in natural history, histologic features, associated findings ( Table 23-3 ), and treatment options. However, despite the distinct processes that govern their development, occasionally vascular tumors and malformations are associated with one another, e.g., in kindreds with autosomal dominant cosegregation of infantile hemangiomas and vascular malformations. This suggests overlap in the regulation of prenatal vascular development and postnatal endothelial cell proliferation.

Vascular Tumors

Infantile hemangiomas arise during the first few months of life and are the most common tumors of infancy, with an incidence of approximately 5% by 1 year of age and a female-to-male ratio of 3–4:1. Unlike other vascular tumors and malformations, infantile hemangiomas express the placental marker glucose transporter protein-1 (GLUT-1). These hemangiomas typically mark out their territory early on and subsequently expand in volume. The proliferative phase lasts until 3 to 9 months of age, with the most rapid growth in the first few months. This is followed by slow spontaneous regression during the involutional phase, which is complete by 3 to 10 years of age. Superficial hemangiomas are initially bright red in color and then become dull red to gray during involution, whereas deep hemangiomas are light blue in color and become softer and less warm as they involute. The term “cavernous hemangioma,” which has been used to describe both hemangiomas with a deep component and venous malformations, has led to confusion and should be avoided. Infantile hemangiomas can be complicated by ulceration, interference with the function of vital structures such as the eyes or airway, high-output cardiac failure, and problems related to associated regional structural anomalies ( Table 23-3 ; see Fig. 23-16 ). Hypothyroidism occasionally occurs in infants with large-volume proliferating hemangiomas, especially hepatic lesions, because of production of iodothyronine deiodinase within the tumors. In the past decade, use of the β-blocker propranolol has revolutionized the treatment of infantile hemangiomas that would otherwise threaten vital functions or result in disfigurement.

There are a variety of benign vascular tumors and reactive proliferations other than infantile hemangiomas ( Table 23-2 ). Congenital hemangiomas represent relatively uncommon, GLUT-1-negative vascular neoplasms that are fully formed at birth and have a natural history of either rapid involution during the first year of life or proportionate growth and failure to involute. These lesions typically present as a pink to blue-violet nodule or plaque with central coarse telangiectasias and peripheral pallor.

Cherry angiomas are small, bright-red papules representing a benign proliferation of capillaries; commonly seen on the trunk of adults, they increase in number with age. Pyogenic granulomas are rapidly developing vascular lesions that typically appear as friable papules on the face, fingers ( Fig. 23-7 ), or mucous membranes. Histologically resembling granulation tissue, pyogenic granulomas frequently occur at sites of minor trauma or on the gingiva during pregnancy.

Bacillary angiomatosis primarily affects patients with AIDS and most often presents as multiple red vascular papules and nodules; internal organ involvement, e.g., liver and bone, can also occur. The causative organisms, Bartonella quintana or B. henselae , can be seen with Warthin–Starry staining of tissue specimens. Kaposiform hemangioendotheliomas and tufted angiomas are two vascular tumors that can be complicated by Kasabach–Merritt syndrome, an acute, life-threatening consumptive coagulopathy with profound thrombocytopenia ( Table 23-3 ). Spindle cell hemangiomas are unusual tumors that typically develop within existing venous malformations and may be associated with Maffucci syndrome ( Fig. 23-8 ; Table 23-3 ).