Bone and Soft Tissue Tumors

Bone and Soft Tissue Tumors

• These notes cover benign and malignant bone tumors and soft tissue tumors.

Metastatic Disease

• Most common skeletal malignancy is metastatic disease
• Metastatic disease can spread through direct extension.
• It can also spread via lymphatic or hematogenous routes, in addition to intraspinal seeding.
• In adults common primary sites include prostate, breast, kidney, and lung.
• In children, common primary sites include neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma.

Bone-Forming Tumors: Osteoma

• Osteomas are benign and slow-growing lesions that do not undergo malignant transformation.
• They predominantly affect the skull or facial bones.
• Osteomas can be bosselated, and range from round to sessile in appearance.
• They can manifest as solitary or multiple tumors, the latter being associated with Gardner syndrome.
• Histologically, osteomas are made out of mature lamellar bone

Osteoid Osteoma vs. Osteoblastoma

• Osteoid osteoma is a benign bone-forming lesion within the host bone
• Osteoid osteomas feature well-circumscribed lesions on bone scans and are usually less than 2 cm in dimension.
• They are more common in patients in their 20s and have a predilection for the lower extremities
• Pain associated with osteoid osteomas is typically relieved with ASA (aspirin).
• Osteoblastomas are larger than 2 cm.
• They typically affect the axial skeleton, especially the spine
• Osteoblastomas are not responsive to ASA

Osteosarcoma

• Osteosarcoma stands as the most common primary malignant bone tumor.
• It exhibits a bimodal age distribution
• Osteosarcoma is associated with disease processes such as Paget's disease, bone infarcts, and irradiation.
• Almost 50% of cases occur around the knee (in the metaphysis).
• It could also be associated with Retinoblastoma (RB) and p53 genes.
• Characterized by malignant osteoid or bone formation by tumor cells
• A radiographic sign of osteosarcoma is the Codman triangle

Osteosarcoma Sub-types

• Osteoblastic
• Chondroblastic
• Telangiectatic
• Small cell
• Giant cell

Cartilage-Forming Tumors: Osteochondroma

• Osteochondroma is a benign cartilage-capped tumor with a bony stalk.
• Approximately 85% of osteochondromas are solitary, with the remainder associated with Multiple hereditary exostosis (AD) syndrome.
• This occurs in young patients
• Less than 1% of osteochondromas give rise to chondrosarcomas.

Chondroma

• Enchondromas arise within the medullary cavity
• Subperiosteal/juxtacortical chondromas arise on the bone surface.
• Chondromas are typically seen in individuals aged 20 to 40.
• Common locations include the short bones of the hands and feet.
• Ollier disease involves multiple enchondromas.
• Maffucci syndrome involves multiple enchondromas with soft tissue hemangiomas.
• Maffucci syndrome comes with a risk of ovarian cancer and brain gliomas.

Chondrosarcoma

• Chondrosarcoma is the second most common malignant matrix-producing tumor of bone.
• It usually affects individuals 40 years or older, more commonly males, and often occurs in the epiphyses.
• Clear cell and mesenchymal variants are seen in younger patients.
• It is most commonly seen in the central skeleton: pelvis, shoulder, and ribs.
• Chondrosarcomas can arise from a pre-existing enchondroma
• Few chondrosarcomas arise in an osteochondroma, chondroblastoma, fibrous dysplasia, or Paget disease.
• Conventional types, clear cell, dedifferentiated and mesenchymal.

Fibrous and Fibro-Osseous Tumors: Fibrous Dysplasia

• Fibrous dysplasia can be monostotic or polyostotic, affecting one or multiple bones, respectively.
• The McCune-Albright syndrome manifest as polyostotic disease, café au lait lesions, endocrine abnormalities, and precocious puberty in females.
• Fibrous dysplasia is characterized by benign tumors that can expand bones, and curvilinear trabeculae of woven bone surrounded by cellular fibroblastic proliferation ("Chinese letters").

Fibrosarcoma

• Fibrosarcoma consists of fibroblastic collagen-producing sarcoma.
• typically affects middle-aged and elderly men.
• Most fibrosarcomas arise de novo; few develop from bone infarcts, Pagetic bone, or irradiation.
• can be found in the metaphysis of long bones as well as pelvic and flat bones.

Miscellaneous Tumors: Ewing Sarcoma/Primitive Neuroectodermal Tumor (PNET)

• Ewing Sarcoma/PNET are primary malignant small round-cell tumors of bone and soft tissue.
• PNET and Ewing sarcoma are variants of the same tumor, differing only in the degree of neural differentiation.
• PNET shows neural differentiation, while Ewing sarcoma is undifferentiated.
• Translocation of the EWS gene typically happens on chromosome 22

Giant Cell Tumor (bone or tendons)

• These are multinucleated giant cell-containing tumors
• Giant cell tumors are benign but locally aggressive.
• They are most commonly seen in individuals aged 20-40
• They commonly occur in the epiphyses and metaphyses
• They are lytic on X-ray and are highly recurrent.

Soft-Tissue Tumors and Tumor-like Lesions

• These are mesenchymal proliferations classified according to the tissue they recapitulate (muscle, fat, fibrous tissue, vessels, nerves).
• Benign tumors are more common than malignant counterparts (sarcomas) by a ratio of 100:1.
• Sarcomas metastasize via hematogenous routes.

Pathogenesis and General Features

• The cause of soft-tissue tumors is unknown.
• Documented associations include radiation therapy, chemical, and thermal burns.
• Mutations in mesenchymal stem cells are suspected to play a role in the development of soft-tissue tumors.
• Kaposi sarcoma is associated with Herpesvirus 8.
• A small number of soft tissue tumors are associated to genetic syndromes like: neurofibromatosis type 1 (neurofibroma, MPNT), Gardner syndrome (fibromatosis), Li-Fraumeni syndrome (soft-tissue sarcoma), Osler-Weber-Rendu syndrome (telangiectasia)
• Prognosis depends on accurate classification, grading, staging, and location.

Adipose Tissue Tumors

• Lipomas are the most common subtype
• These are well-encapsulated masses of mature adipocytes.
• They show great variance in size
• Liposarcomas are histologically divided into well-differentiated, myxoid/round cell, and pleomorphic variants.
• Atypical cells may show increased mitosis and necrosis..
• The amplification of the MDM2 oncogene occur in well-differentiated variants (MDM2 inhibits p53).

Fibrous Tumors and Tumor-Like Lesions

• Reactive Pseudosarcomatous Proliferations include Nodular Fasciitis and Myositis ossificans.
• Nodular Fasciitis presents with a several-week history of a solitary, rapidly growing, and sometimes painful mass.
• Myositis ossificans is characterized by the presence of metaplastic bone.
• It typically develops in athletic adolescents and young adults following an episode of trauma.
• There can be Fibromatoses which can be superficial and deep.
• Fibrosarcoma is included in this category

Skeletal Muscle Tumors

• Rhabdomyosarcoma is type of skeletal muscle tumor:
• Embryonal type, being the most common subtype (60%-sarcoma botryoides)
• Alveolar type involves presence of Alveolar {t(2,13) and t(1,13)}
• Pleomorphic is the last subtype,
• Rhabdomyoblast is the diagnostic cell in all three types.

Smooth Muscle Tumors

• Leiomyomas are benign smooth muscle tumors.
• They often arise in the uterus and may cause a variety of symptoms, including infertility.
• Leiomyomas are composed of fascicles of spindle cells that intersect each other at right angles
• The tumor cells usually show minimal atypia and few mitotic figures.
• Leiomyosarcoma is defined by the presence of Atypia, increased mitoses and necrosis.