B104 Tumor and tumor like lesions of the bone Flashcards
What are the primary tumors of the bone?
Bone-forming
- Osteoma
- Osteoid osteoma
- Osteoblastoma
- Osteosarcoma
Cartilage-forming
- Osteochondroma
- Chondroma
- Chondrosarcoma
- Giant-Cell Tumor
- Ewing sarcoma, Primitive neuroectodermal tumor
Fibrous and Fibro-osseous tumors
- Fibrous cortical defect and non-ossifying fibroma
- Fibrous dysplasia
What are the metastatic tumors of bone?
Almsot any metastatic tumor can invade bone.
The most common in adults are:
- Prostate
- Breast
- Lung
- Kidney
- Thyroid
The most common in children are:
- Neuroblastoma
- Wilm’s tumor
- Osteosarcoma
- Ewing sarcoma
- Rhabdomyosarcoma
What is the presentation, morphology and histology of Osteoma
Osteoma:
- Present as hard exophytic (gorwing outward, not inward) mass on the bone surface. Usually in middle-age and eldery.
- Very often on the bones of the face, head, and neck, including the bones of the nasal sinuses where they can cause obstruction, their only real problem.
- Totally benign and do not invade locally.
- Typically found as incidentalomas
- Form normal cortical bone structure with a mixture of woven and lamellar bone.
- If there are multiple, they are usually part of Gardner syndrome.
What is the presentation, mophology, histology of
Osteoid Osteomas and Osteoblastomas
Similar tumors, distinguished by their usualy locations, size, and presentation.
Both types:
- appear in teenagers with a 2:1 male preference
- benign
- rarely may have malignant transformation,
- treatment with radiation causes a strong increase in the risk for malignant transformation
Osteoid Osteoma:
- form beneath the periostem in the cortex
- form in the femur and tibia, or lower spinal vertebrae
- are by definition less than 2 cm diameter
- Cause localized pain that is relieved by aspirin
- Composed of osteoblasts and loose vascular connective tissue, with variable amounts of giant cells.
- Surrounded by a thick layer of reactive woven bone. (but tumor itself is smaller than osteoblastoma)
- Bony mass with radiolucent core on X-ray
Ostoeblastoma:
- Larger
- Form in vertebral column
- Cause pain that is not affected by aspirin
- Same morphology as osteoid osteoma but with less of a reactive bone rim.
Presentation and epidemiology of osteosarcoma
What mutations are associated with osteosarcoma?
- A bone-producing malignant tumor of mesenchyme.
- 3rd most common primary bone tumor, (myeloma, lymphoma, osteosarcoma)
- 1st most common bone tumor that is not of the hematopoeitic/lymphoid system.
Occurs in all age groups, with two peaks:
- the majority, 75% occuring in children and teenagers
- the second peak occurs in old age and is associated with specific conditions:
- Paget’s disease,
- bone infarcts
- previous irradiation
- familial retinoblastoma
- more common in men, ~1.5:1
Occurs in any bone, but has preferences for certain sites
- knee 60%
- hip 15%
- shoulder 10%
- jaw 8%
Mutations:
60-70% of spontaneous cases have mutated RB
It occurs at 1000 times more frequency in familial retinoblastoma.
What are the subtypes of osteosarcoma and its histology?
Subtypes are based on several categories:
- Location within the bone: medullary or cortical
- Degree of differentiation
- Number of sites
- Presence of previous/underlying/associated disease: Paget’s, irradiation
- Histologic features
Most common type: Primary, solitary, intramedullary, poorly differentiated, producing bony-matrix.
Histology:
- Pleomorphic cells size and shape,
- Typically very anaplastic with strange mitotic figures and nuclei.
- Always produces osteoid with may or may not be mineralized. This is a requirement for osteosarcoma diagnosis.
- Cells stain for vimentin - as do many other sarcomas, vimentin is a mesenchymal marker.
- The bone formed is typically amorphous and randomly shaped, but can be formed in sheets.
- Chondrocyte and Fibroblast differentiation occurs at varying levels.
- If there are significant malignant cartilaginous cells, it is called a Chondroblastic Osteosarcoma.
- Frequent vascular invasion
- Spontaneous tumor necrosis is also common.
- Invades through epiphyseal plate, into medulla or epiphysis, through the cortex, and forms masses of soft tissue/bony matrix on the surface of the bone.
Clinical presentation and prognosis of osteosarcoma
Presents as a bone pain and enlarging mass or bone fracture.
X-ray shows a mixed lytic and blastic mass with infiltrative, indistinct margins.
Tumors ofte invade through the cortex, lifting up the periosteum and causing reactive periosteal bone formatio, forming a structure called a Codman triangle, also described as having a ‘sunburst’ appearance.
They spread hematogenously, and 10-20% have visible lung metastases at time of diagnosis, and even more have microscopic metastases.
Despite this rapid spread, standard chemotherapy and removal of the tumor (limb salvage) has long-term survival of 60-70% for primary osteosarcomas
Secondary osteosarcomas arising after Paget’s or irradiation do not respond** to chemo and are **usually fatal.
Morphology, histology of
Osteochondroma
Somewhat common, benign, cartilage-capped tumor extending off a bony stalk to an underlying bone like a pedunculated polyp.
They form from long bones, arising from the metaphysis, near the growth plate. Often around the knee. Sometimes theyarise from the pelvis, scapula, or ribs and have a sessile structure. Very rarely they arise in the tubular bones of the hands and feed.
They occur in childhood and adolescence, and ten to stop growing when normal skeletal growth stops.
Are 1-20cm, with a cartilage cap that is less than 2cm thick. The cartilage has the histology of a disorganized growth plate with endochondral ossification occuring on the inside surface, causing it to grow.
Presentation, pathogenesis of
Osteochondroma
They appear in childhood, as they typically only grow during the years of normal bone growth.
Slow growing
Cause pain if the compress a nerve.
Have the possibility to fracture, also causing pain.
They are often incidental findings.
Solitary osteochondromas have the rare potential to transform to chondrosarcoma or other sarcomas.
Multiple osteochondromas occur as part of a hereditary syndrome and have a higher frequency of malignant transformation.
Chondroma morphology, histology
Benign neoplasm of hyaline cartilage
In the medulla: endochondromas these are more common, usually in the hands and feet.
On the surface of bone: juxtacortical chondromas
Form small, <5cm nodules that are grey-blue. Well circumscribed.
Cytologically benign chondrocytes and hyaline cartilage.
Endochondral ossification occurs at the periphery, and the center usually dies and then becomes calcified.
In the syndrome hereditary multiple chondromatosis, there is more cells and more atypia, making them resemble chondrosarcoma.
What are the syndromes that involve multiple chondroma formation?
Ollier disease:
- multiple condromas form preferentially on one side of the body.
Maffucci syndrome:
- multiple chondromas associated with benign soft tissue angiomas
- increased risk for ovarian cancers and brain gliomas
Both syndromes involve point mutations in isocitrate dehydrogenase 1 or 2 The mutations are not inactivating but ‘create new enzyme function’ probably allowing it to interact with a new substrate.
They are acquired syndromes, not inherited, but the mutations are seen at low frequency in some but not all other somatic tissue of the patients, suggesting a mutation early in development, and demonstrating a mosaic pattern.
What is the presentation and prognosis of Chondromas
- They develop between age 20 and 50.
- They are benign and typically incidental findings.
- Can be painful or cause fractures.
- Produce well circumscribed, non-minerlized cartilage radiolucent lesions surrounded by very thin rims of radiodense bone, O-ring sign.
- Can occur in multiple as part of the two syndromes.
- They grow for a limited period of time then stabilize.
- Can re-occur if incompletely removed.
- Solitary chondromas rarely transform, endochondromas have a higher risk than juxtacortical ones.
Chondrosarcomas, histology
Malignant tumor that secretes cartilage matrix.
Subclassified like osteosarcoma by: site (intramedullary, juxtacortical) and histological variants.
- Conventional chondrosarcoma: Intramedullary, producing both hyaline and myxoid cartilage.
- Myxoid chondrosarcoma: Produce viscous gelatinous cartilage that will ooze off a cut surface.
- Clear cell chondrosarcoma
- Mesenchymal chondrosarcoma
All types:
- Cause erosion and/or reactive thickening of adjacent bone cortex.
- Tumor grade is determined by the cytology, atypia, cell density, and mitotic figures.
- Low grade osteosarcomas can resemble endochondroma.
- High grade lesions are pleomorphic with lots of mitotic figures.
- 10% of low grade chondrosarcomas have within them a second high-grade component called de-differentiated chondrosarcoma with foci of fibrosarcoma or osteosarcoma
Chondrosarcoma, gross morphology, presentation, prognosis
Occur in patients usually over 40 years. 2:1 male preference
Form large, irregular masses, which invade through bone into surrounding tissue.
Chondrosarcomas typcially arise in the pelvix, shoulder, and ribs of the central skeleton. The more peripheral a cartilaginous mass is, the more likely it is a benign chondroma.
Present as a painful, growing mass.
- Low grade tumors are slow and cause reactive thickening of the bone cortex.
- High grade tumors erode and destroy the cortex and invade surrounding tissue.
- Thus the more transparent the tumor is on X-ray, the more likely it is to be high grade.
- Most chondrosarcomas are low grade, rarely metastasize, and have 5yrS of 80-90%.
- High grade tumors metastasize in about 2/3rds of cases and have a 40% 5yrS
- Tumors larger than 10cm are more aggressive and have significantly worse prognosis.
- They metastasize hematogenously to the lungs and other bones.
Treatment:
Conventional chondrosarcoma: Wide surgical excision
De-differentiated variants: Surgery and chemotherapy
