Soft tissue sarcomas are a heterogeneous group of tumors that originate from mesenchymal tissues. Although they are well characterized by high-resolution magnetic resonance (MR) and computed tomography (CT) imaging, clinically important issues such as tumor grade, stage, and response to treatment cannot completely be evaluated with anatomic imaging. The variety in soft tissue sarcoma characteristics, origin, and biologic behavior make them particularly interesting for molecular imaging techniques using positron emission tomography (PET). The challenges that these tumors pose in their diagnosis and management have contributed to the definition of the role of clinical PET in sarcoma and are a developing area of PET research. With limited effective chemotherapy and radiotherapy treatment schemes available for these patients, the current emphasis in management includes identifying high-risk patients and those who may have greater sensitivity to treatment. PET imaging has made a significant contribution to these patient management issues by providing important biologic information for an individual patient tumor.

Although considered to be rare tumors, soft tissue sarcomas occur at an incidence of 1 to 2 per 100,000 people in
the United States. They are derived from mesenchymal tissues, which are the body structures that compose the soft, nonorgan, nonepithelial tissues. These tissues are muscles, connective tissue, fat, peripheral nerves, and blood vessels. Sarcomas derived from these elements show differentiation features of these tissues and retain some characteristics of the tissue of origin. Skeletal muscle is derived from myoblasts, which contain muscle fibers composed of actin and myosin. Connective tissue is composed primarily of fibroblasts, fibril structures of collagen and elastin, and ground substance, or matrix. Fat tissues are of two types. White fat, composed of lipocytes, is primarily located in the subcutaneous tissues, mediastinum, retroperitoneum, and abdomen. Brown fat is located in the neck, mediastinum, interscapular area, axillae, and the perirenal region (Fig. 33.24). Brown fat cells have many mitochondria, vacuolated cytoplasm, and a nucleus in the central location. They have a distinct microscopic and functional imaging appearance. Peripheral nerves are composed of axons, fibroblasts, perineural cells, and Schwann cells. Perineural cells originate from fibroblasts, and the Schwann cells are thought to be derived from the neuroectoderm. Blood vessels are composed of endothelial cells, pericytes, smooth muscle cells, and glomus cells. In most of today’s tumor classifications, the histologic type is determined by the type of differentiation that the cell exhibits rather than its presumed origin. On biopsy specimens, histopathologic diagnosis consists of light microscopic examination, the use of special tissue element stains, and immunocytochemistry to help characterize the cell type and level of differentiation. A list of common soft tissue sarcoma histologic types and age group associations is shown in Table 53.1. Increasingly, gene expression profiles are being used to help classify and predict the biologic behavior of soft tissue tumors (1,2,3). Standard radiologic examination consists of plain x-ray films, CT, and MRI. Benign and malignant tumors are not often easily distinguished by anatomic imaging. However, certain features such as size, structure of apparent origin, heterogeneity in density, and calcification can provide important clues as to the probability of malignancy. Patient factors such as age and tumor location are also significant for other relationships to tumor type.

Sixty percent of soft tissue sarcomas occur in the limbs. Most of these occur in the lower extremities deep to fascial tissues. They are less commonly found in superficial locations in areas such as the hand and foot. Deep soft tissue sarcomas can grow to large dimensions before coming to clinical attention. Presumably, large (>5 cm in any dimension) tumors are considered to be at least intermediate grade until subjected to further assessment, which includes biopsy.

The assessment of patients with sarcoma consists of determining the stage and grade of the tumor as accurately as possible for treatment planning. Both provide prognostic information for risk of metastasis and local recurrence. In sarcoma, the tumor stage refers to the site, size, and histologic grade of the tumor. Currently there are several systems in use for sarcoma staging. Most commonly used is the American Joint Conference on Cancer (AJCC) system, which is based on the Tumor-Node-Metastasis (TNM) assessment (4). Tumor grading systems are designed to reflect the prognosis for the sarcoma patient. The most commonly used scheme for providing histologic diagnosis and tumor grade is the French system (FNCLCC) (5). In this system, some tumors have fixed grades, such as low grade, or rarely metastasizing, or variable grade based on histologic features. The FNCLCC diagnosis and grading system for soft tissue sarcomas is shown in Table 53.2. Additional clinical grading is performed by the clinician, which is best described by an assimilation of all the clinical features of the patient. These include patient age and overall health status, symptoms, biopsy quality and tumor histologic type, tumor size, location, grade, radiologic appearance, and more recently, pattern and level of FDG uptake. In many centers, this clinical assessment is used to make the decision
for neoadjuvant chemotherapy or radiotherapy versus proceeding directly to surgical resection. A typical set of treatment guidelines for soft tissue sarcomas is presented in Table 53.3. Local variations on these guidelines are quite common.