Pathogenesis and General Features

The cause of most soft tissue tumors is unknown. There are documented associations, however, between radiation therapy and rare instances in which chemical burns, thermal burns, or

trauma were associated with subsequent development of a sarcoma. Exposure to phenoxyherbicides and chlorophenols has also been implicated in some cases. Kaposi sarcoma is

causally associated with the human herpesvirus 8; however, viruses are probably not important in the pathogenesis of most sarcomas. The majority of soft tissue tumors occur

sporadically, but a small minority is associated with genetic syndromes, the most notable of which are neurofibromatosis type 1 (neurofibroma, malignant schwannoma), Gardner

syndrome (fibromatosis), Li-Fraumeni syndrome (soft tissue sarcoma), and Osler-Weber-Rendu syndrome (telangiectasia). Cytogenetic and molecular analyses of soft tissue tumors

have provided significant insight into their biology. Specific chromosomal abnormalities and genetic derangements can not only be used as diagnostic markers, but also provide

important clues about the genesis of the neoplasms.[60] For example, many of the mutations target oncogenes that encode transcription factors or cell-cycle regulators, and their

dysfunction results in uncontrolled cell proliferation ( Table 26-9 ).

Soft tissue tumors may arise in any location, although approximately 40% occur in the lower extremities, especially the thigh; 20% in the upper extremities; 10% in the head and neck;

and 30% in the trunk and retroperitoneum. Regarding sarcomas, males are affected more frequently than females (1.4:1), and the incidence generally increases with age. Fifteen per cent

arise in children; they constitute the fourth most common malignancy in this age group, following brain tumors, hematopoietic cancers, and Wilms tumor in frequency. Specific

sarcomas tend to appear in certain age groups (e.g., rhabdomyosarcoma in children, synovial sarcoma in young adulthood, and liposarcoma and malignant fibrous histiocytoma in midto

late adult life).

Several features of soft tissue tumors influence their prognosis:

• Accurate histologic classification contributes significantly to establishing the prognosis of a sarcoma. Important diagnostic features are cell morphology and architectural

arrangement ( Table 26-10 and Table 26-11 ). Often these features are not sufficient to distinguish one sarcoma

from another, particularly with poorly differentiated aggressive tumors. Great reliance must, therefore, be placed on immunohistochemistry, electron microscopy, cytogenetics, and

molecular genetics.

• Whatever the type, the grade of a soft tissue sarcoma is important for predicting its behavior. Grading, usually I to III, is based largely on the degree of differentiation, the

average number of mitoses per high-power field, cellularity, pleomorphism, and an estimate of the extent of necrosis (presumably a reflection of rate of growth). Mitotic activity

and extent of necrosis are thought to be particularly significant. The size, depth, and stage of the tumor also provide important diagnostic and prognostic information.[61]

• Staging helps determine the prognosis and chance of successful excision of a tumor. Several staging systems are utilized in treating sarcomas.

• In general, tumors arising in superficial locations (e.g., skin and subcutis) have a better prognosis than deep-seated lesions. In patients with deep-seated, high-grade sarcomas,

metastatic disease develops in 80% of those with a tumor larger than 20 cm and 30% of those with a tumor larger than 5 cm. Overall the 10-year survival rate for sarcomas is

approximately 40%.

TABLE 26-9-- Chromosomal and Genetic Abnormalities in Soft Tissue Sarcomas

Date: 2016-04-22; view: 792