Flashcards in Histopathology Skeletal pathology Deck (31):
Systemic or generalised disorders
Infections – osteomyelitis
Skeletal effects of hyperparathyoirism
Pagets disease of bone
Bone forming tumours
Tumours of uncertain histogenesis
1. Bone consists of an outer, dense, cortex composed of compact bone and the inner medulla which is composed of a sponge like tissue of trabecular or cancellous bone.
2. Cancellous medullary bone composed of sponge like trabecular bone.
→ (In fibrous connective tissue) growth, which occurs in the growth of flat bones such as the skull bones and the ribs and also in appositional growth (growth in thickness) of the long bones.
Endochondral (in cartilage) →
growth, which occurs at the epiphyseal growth plates at the ends of long bones and which results in lengthening of the bone. The growth plates are active throughout childhood and disappear (fuse) at around sixteen years.
1. Shortened limbs
2. Trident hands – abnormal alignment of metacarpels
3. Normal trunk length
4. Contracted base of skull
5. Abnormal endochondral ossification
6. Cane be some compression @ transverse process
7. Jaw abnormality
Thorax and skull are of normal proportion while the limbs are restricted in length as a result of restriction of growth in the length of the long bones of the limbs.
• Commonest of the short limb pattern of dwarfism
• 1/30,000 of cases are sporadic (new mutations)
• 25% inherited as an autosomal dominant trait
Point mutation of FGFR3
Achondroplasia Defect in
1. Restriction of the growth in the length of the longbones (humerus, radius, ulna, femur, tibia and femur)
2. Pronounced architectural disturbance of the growth plates at the ends of these bones.
Achondroplasia Physiologicl endochonrl growth
Normal growth plate consists of
• Well-ordered columns of chondrocytes
• Which enlarge as they approach the growing end of the bone]Where they undergo calcification → subsequent ossification
Achondroplasia Achondroplasia: endochondral growth
• Disrupted chondrocytes columns
• Chondrocytes failing to hypertrophy as they approach the zone of bone formation
• Defective calcification
Osteogenesis Imperfecta →Definition
AKA brittle bones:
1. Group of disorders in which there is abnormality in the synthesis of type 1 collagen (about 90% of the organic matrix of bone).
2. Numerous point mutations in the collagen 1 genes have been described and these affect the functionality of the collagen molecules to different degrees
3. As a results the clinical phenotype may be mild, moderate or severe depending on the specific amino acid substitution in the type 1 collagen molecule
Osteogenesis Imperfecta → Severely affected patients
Osteogenesis Imperfecta → Adulthood severe and survive
Extreme fragility of the skeleton as a result of the defective organic matrix of the bone which leads to defective mineralisation
Osteogenesis Imperfecta → Mildly affected phenotype
Little clinical manifestations apart from early onset osteoporosis.
Defect in osteoclastic arm of the ‘bone forming unit’ a physiologically active system of osteoblasts, which make new bone, and osteoclasts which reabsorb mineralized bone (not clear at which point the defect occurs).
Increased amount but not organised lamellar bone.
Osteopetrosis:Children with defective osteoclastic function cannot
Resorb bone but continue to make new bone with the result that the bone becomes increasingly dense leading to disappearance of the marrow cavity and compromised haemopoiesis
Osteopetrosis: Children present with and why
Pancytopenia. New bone enters medullary cavity preventing intramedullary haemopoieis. Increased infection rates.
Leads to extramedullary haemopoiesis via spleen.
Acute osteomyelitis is a disease of the growing skeleton and it’s more or less confined to the ages between 18 months and 18 years.
• Due to nature of blood supply to the long bones.
• Only during skeletal growth because of the presence of the growth plate, is there a vascular condition which seems to allow the development of acute infection in the metaphysis of long bones.
Osteosarcoma → Epi
• Bone tumours are rare and represent less than 1% of all tumours diagnosed
• In the UK this means that there are around 1000 new cases each year
• About 155 of bone tumours are osteosarcoma giving approx. 150 new cases each year.
Osteosarcoma → Most common in
Children and young adults (12-25)
Osteosarcoma → Relative incidence of the different types
High grade intramedullary 80% - peak age 15
Periosteal 2% - mid 20’s
Parosteal 5% - broad age range
The different patterns of osteosarcoma have peak incidence at different ages.
Osteosarcoma →Incidence site
Osteosarcomas tend to occur at particular sites in the skeleton:
• >90% occurring in the metaphyseal part of the bone
High grade intramedullary osteosarcomas is particularly common around the knee:
>50% of the tumours arising in the distal femurs or the proximal tibia
Osteosarcoma is distinctly uncommon in sites such as rib, vertebral column, and in the peripheral parts of the limbs.
Osteosarcoma →Xry findgins
• Mixed lysis and sclerosis
• Sub-periosteal new bone: New bone formation is most easily seen outside the cortex and beneath the elevated periosteum.
• Codman’s triangle: the point where the periosteum becomes detached from the cortex there is often the appearance of an acute angled triangle.
⇒ Irregular islands of non-structura; tumour bone.
Osteosarcoma →Histological features
• The Tumour is composed of disorganised sheets of malignant osteoblasts, which show pleimorphism (variation in size and shape) and nuclear hyperchromatism (intense haematoxyphilia)
• The presence of tumour osteoid or bone is crucial to the diagnosis of osteosarcoma. Tumour osteoid/bone is structurally disorganised in comparison with normal bone.
⇒ Sheets of disorganised malignant osteoblasts fill the space between the bony component
⇒ Irregular islands of non-structura; tumour bone.