Unlike tumors such as colorectal carcinomas that usually arise from recognized precursor lesions, the origin of sarcomas is unknown. The best guess is that the tumors arise from pluripotent mesenchymal stem cells, which acquire somatic “driver” mutations. Despite heterogeneous mechanisms of tumorigenesis among sarcomas, some generalizations can be made based on their genomic complexity:
Simple karyotype (15%–20% of sarcomas): Like many leukemias and lymphomas, sarcomas are often euploid tumors with a single or limited number of chromosomal changes that occur early in tumorigenesis and are specific enough to serve as diagnostic markers. Tumors with these features most commonly arise in younger patients and tend to have a monomorphic appearance microscopically. Examples include Ewing sarcoma, described earlier, and synovial sarcoma. In some cases, the oncogenic effect of these rearrangements is reasonably well understood. In others, the mechanisms are unknown. Oncogenic tumor-specific fusion proteins represent potential molecular targets for therapy.
Complex karyotype (80%–85% of sarcomas): These tumors are usually aneuploid or polyploid and demonstrate multiple chromosomal gains and losses, a feature that suggests underlying genomic instability. Examples http://ebooksmedicine.net include leiomyosarcoma and undifferentiated pleomorphic sarcoma. Such tumors are more common in adults and tend to be microscopically pleomorphic.
Classification of soft tissue tumors continues to evolve as new molecular genetic abnormalities are identified. Clinically, soft tissue tumors range from benign, self-limited lesions that require minimal treatment to intermediate grade, locally aggressive tumors with minimal metastatic risk to highly aggressive malignancies with significant metastatic risk and mortality. All highly aggressive malignancies are classified as sarcomas but this term is less consistently used among the locally aggressive, rarely metastasizing category. Pathologic classification integrates morphology (e.g., muscle differentiation), immunohistochemistry, and molecular diagnostics. In addition to accurate diagnosis, grade (degree of differentiation) and stage (size and depth) are important prognostic indicators.
With this as a primer, we will consider representative or especially illustrative soft tissue tumors.
Lipoma, a benign tumor of fat, is the most common soft tissue tumor in adults. The conventional lipoma is the most common subtype, from which rare variants are distinguished according to characteristic morphologic and/or genetic features. Conventional lipoma is a well-encapsulated mass of mature adipocytes. It usually arises in the subcutis of the proximal extremities and trunk, most frequently during middle adulthood. Infrequently, lipomas are large, intramuscular, and poorly circumscribed. Most lipomas are usually cured by simple excision.
Liposarcomas are malignant tumors of adipose tissue. Liposarcoma is one of the most common sarcomas of adulthood. It occurs mainly in people in their 50s to 60s in the deep soft tissues and retroperitoneum.
MORPHOLOGYLiposarcomasaredividedintothreesubtypes:
Fig.21.45A ).Thetumorsharboramplificationofchromosomeregion12q13-q15,whichincludesthegeneforMDM2.YouwillrecallMDM2encodesapotentinhibitorofp53.
Myxoidliposarcomacontainsabundantbasophilicextracellularmatrix,arborizingcapillaries,andprimitivecellsatvariousstagesofadipocytedifferentiationreminiscentoffetalfat(
Fig.21.45B ).Thet(12;16)translocationcharacterizesmyxoidliposarcoma.Theresultantfusiongenearrestsadiposedifferentiation.