Bone Pathology II Flashcards
Osteogenesis imperfecta is also known as what?
Brittle Bone disease
What is the etiology of OI?
Defect in type I collagen –> inability to form triple helix
What happens to the bone in OI?
They brake so many times –> accordion- like collapse on themselves/shortening of limbs
Describe the teeth and eyes of someone with OI
Eyes- blue sclera
Teeth- small and misshapen
What is the most common form of dwarfism?
Achondroplasia
What is the etiology of achondroplasia?
Gain of function mutation in FGFR3 (signal transduction system in the growth plate)
What is the normal role of FGFR3?
Inhibition of cartilage proliferation
Describe the FGFR3 mutation
Activating mutation –> inhibition of chondrocyte differentiation and proliferation at the growth plate –> retards growth plate development
What is the inheritance pattern of achondroplasia?
AD
Why is the head enlarged in someone with achondroplasia?
Skull bone forms by intramembranous bone growth- only bones that form by endochondral calcification are affected
What is the prognosis of thanatophoric dwarfism?
Perinatal death. Underdeveloped thorax –> respiratory deficiency and death
What causes bone death?
Ischemia
What bone in the body is particularly susceptible to osteonecrosis?
The mandible/jaw- particularly in the presence of high-dose bisphosphonates
What are the three phases of Paget’s disease?
1) Osteoclast over activity
2) Osteoblast activity
3) Sclerosis
How common are primary bone neoplasms?
Uncommon, children > adults
Most primary bone tumors form from which cell type?
Hematopoietic
They form in the medullary sinus from hematopoietic cells
What is an osteoid osteoma?
Benign “nidus” of osseous tissue surrounded by a halo of reactive bone formation
Reactive bone is not tumor- it is in response to the tumor
How do osteoid osteomas present?
In men with PAIN (usually at night) and it is relieved by aspirin
These tumors produce prostaglandin E2
What is an osteosarcoma?
Most common Malignant Primary tumor of bone-
Presents in the medullary cavity in the metaphysis and they favor the long bones
What is codman’s triangle?
Triangular shadow between cortex and raised ends of periosteum-
The tumor has broken through and lifted the periosteum which leads to reactive bone formation
What are the characteristic genetic mutations associated with osteosarcomas?
Rb
p53 (Li-Fraumeni syndrome)
What the prognosis of an osteosarcoma?
They are aggressive with hematologic mets to the lungs
5 year survival is up to 70% with no mets, and 20% if there are overt metastasis or it is a sequelae of Paget’s disease
What is an osteochondroma?
Benign bone tumor characterized by a stalk of well-differentiated hyaline cartilage
What is another name for osteochondroma?
Exostosis
What are the gene mutations associated with Multiple Hereditary Exostosis Syndrome?
LOF mutations in EXT1 and EXT2
Where do chondrosarcomas most often form?
Central portion of skeleton- pelvis, ribs, shoulder
Name two tumors where “Grade” is very important for prognosis (as opposed to stage of tumor)
Gleason’s tumor- prostate cancer
Condrosarcoma
Name 4 primary tumors that readily metastasize to the bone
Prostate, breast, lung, kidney
Name three adolescent tumors that regularly metastasize to the bone
Neuroblastoma, Wilm’s, rhabdomyosarcoma
Why do some mets to the bone appear lytic?
The tumors produce PTH-like hormones that activate osteoclast resorption of bone
What protein stimulates osteoblastic bone formation?
WNT protein –> blastic bone appearance and a sclerotic response to metastasis to the bone
Which metastasis to the bone cause lytic bone mets?
BLTKM- (Bacon, lettuce, tomato with ketchup and mustard)
Breast, lung, thyroid, kidney and multiple myeloma
Which bone met appears as blastic metastasis
Prostate
What is another name for neuroectodermal tumor (PNETS)
Ewing Sarcoma
What is the chromosomal abnormality associated with Ewing sarcoma?
t(11;22)(q24;q12)
Results in a gene fusion of EWS/FLI-1 –> protein that functions as a transcription factor
