Angiosarcoma (overview) C44.-

Rare malignant tumours that occur in older people and originate from the endothelial cells of the blood or lymph vessels, which account for about 2% of all soft tissue Sarcomas. They develop mainly in the cutis/subcutis and only spread to the deep soft tissues in a secondary manner.

The following forms are important on the skin:

• Idiopathic/classical angiosarcoma in older people
• Lymphedema-associated angiosarcoma (Stewart-Trèves syndrome)
• Angiosarcoma after radiotherapy (radiation-induced angiosarcoma)
• angiosarcoma epitheloides
• Kaposi's sarcoma, see AIDS below.

A special position is taken by the hemangiendothelioma, which is classified as intermediary malignant (for details see there).

A general overview of cutaneous sarcoma and soft tissue sarcoma can be found under Cutaneous sarcoma.

Rare (about 1-2% of all soft tissue sarcomas and about 5% of cutaneous sarcomas). 50-60% of all angiosarcomas are cutaneous angiosarcomas. The incidence rates are given as 0.01/100,000 persons/year.

• Idiopathic etiology in elderly people, development in the area of long-standing lymphedema (e.g. during mastectomy and lymphadenectomy), radiating and immune defects (e.g. HIV infection) are described. If angiosarcomas occur after radiotherapy, the radiations are usually > 5-6 years ago; longer intervals are not uncommon and can be decades.
• Other predisposing factors may be: AV fistulas on the "shunt arm" after dialysis, especially after subsequent kidney transplantation and corresponding immunosuppression.
• The role of UV rays, chemical carcinogens, mutagens and foreign bodies is poorly defined for angiosarcoma of the skin. In the liver, thorotrast (X-ray contrast medium and α emitters, in use until the 1950s), arsenic and vinyl chloride gas (occurring in the plastics industry; carcinogenic DNA alkylant; induces specific ki-ras and p53 mutations) can have a predisposing effect.
• Angiosarcomas of the deep soft tissues are occasionally associated with syndromes such as neurofibromatosis, Klippel-Trénaunay syndrome and Maffucci syndrome.

• Most patients fall ill between the ages of 50-95. The peak of the manifestation lies in the 8th decade. Men are slightly more frequently affected than women (m:f = 1.6:1).
• Angiosarcomas of the deep soft tissues can occur in all age groups, including childhood and adolescence.

In principle, angiosarcomas can occur anywhere on the skin. The idiopathic or classic type occurs exclusively on the head and neck. The postradiatio type is based on the pre-irradiated area (often in women in the breast area after breast cancer). Angiosarcoma with lymphedema is mainly observed on the chronically edematous extremities after radical lymphadenectomy. The very rare deep soft tissue angiosarcomas (association with neurofibromatosis, Klippel-Trénaunay syndrome, Maffucci syndrome) prefer extremities, trunk and the body cavities. The (metastatic?) occurrence of angiosarcomas of the internal organs (liver, bones, spleen, heart) has been described.

See under the above mentioned clinical pictures.

Especially the idiopathic or classic angiosarcoma (of the scalp) offers a diverse clinical picture, whose unspectacular first symptoms are confused with inflammatory diseases (rosacea, erysipelas).

Angiosarcomas consist of proliferating atypical endothelia with varying degrees of differentiation (from hemangioma-like to anaplastic). In most cases there are net-like structured, anastomosing vascular systems with "inorganic" dissecting growth patterns. Frequently are vascular clefts with atypical endothelial cells, endothelial papillae or multicellular endothelial buds. "Multilayering", atypia and mitosis of CD31-positive (platelet endothelial cell adhesion molecule) and CD34-positive (human hematopoietic progenitor antigen) endothelial cells are typical. The lymphatic endothelial markers (podoplanin, LYVE-1, PROX-1) are also useful for diagnosis. In epithelioid angiosarcoma a large epithelioid cell type dominates. Thin, round or slit-like cavities are scattered in the cell layer; smaller cavities are initially free of erythrocytes, larger ones are blood-filled. Epithelioid angiosarcomas can express cytokeratin (in > 30% of cases) and CD31.

The following histological variants are distinguished (Kutzner 2016):

• Highly differentiated (lymphangioma-hemangioma-like)
• Classic (sieve, net, sponge)
• Pleomorphic/anaplastic (sarcoma, carcinoma-like)
• Spindle cell (kaposiform)
• Granular cell
• Epitheloid cell (see below angiosarcoma epitheloides)
• Intravascular

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