Musculoskeletal PathologyPart I

Bones

Bone diseases

Metabolic bone diseasesOsteoporosisOsteomalacia and ricketsFibrous osteodystrophyPaget’s disease

Fractures

InflammationsOsteomyelitisTuberculous osteomyelitis

TumoursPrimarySecondary (metastatic)

Osteoporosis

absolute decline in the bone mass (bone atrophy)

Pathogenesisexcessive amount of osteoclastic resorption or impairment of osteoblast-mediated bone formation, or both

Primary osteoporosis:

type I osteoporosis (postmenopausal): ↓oestrogen → ↑bone resorption (↑number and activity of osteoclasts)

type II osteoporosis (senile): individuals older than 70 yearsimpairment of bone formation (failure to replace resorbed bone)

Secondary osteoporosisCushing’s syndromehyperthyreoidismhypogonadism (early oophorectomy)malnutritionsubtotal gastrectomyimmobilisation, hemiplegia, paraplegiatreatment with glucocorticoids or certain anticonvulsants

Clinical features:fractures as a result of minimal trauma

hip fracturescompressive fractures of the vertebral bodies – kyphosis (“dowager’s hump“)fractures of the distal radius (Colles’ fracture)

Morphology:thinning of individual trabeculaloss of normal trabecular networkmineralisation is normal

Osteomalacia and Rickets (rachitis)

defective mineralisation of osteoid matrix

Lack of vitamin D:low dietary intakelack of sunlightsmall gut malapsorptionchronic liver and/or renal diseases (impaired hydroxylation of vitamin D precursors)

Hypophosphataemia (much less common, resistance to treatment with vitamin D):hereditary (abnormality of phosphate transport by the renal tubular epithelium)tumour-associated (effect of certain mesenchymal neoplasms)

Osteomalacia

adults with closed epiphysesnormal bone mass, but increase in amount of osteoid (more than 20% of the trabecular surface)deformities (kyphoscoliosis, contracted pelvis, limb curvature), fractures

Rickets

children (epiphyses still open and active)failure of matrix mineralisationdisturbance of endochondral ossification: very poor formation of zone of provisional calcification, marked enlargement of zone of hypertrophic cartilagedeformities: craniotabes rhachitica, caput quadratum (frontal and parietal bossing), bulging of the costochondral junctions („rickety rosary“)

Fibrous osteodystrophysevere hyperparathyreoidism (especially primary)excessive osteoclastic resorption of boneoutline of bony trabeculae shows deep indentations filled with numerous osteoclasts and connective tissue

In severe cases occur so-called brown tumors (a misnomer): areas in which trabecular bone has been completely eroded away and replaced by vascular fibrous tissue with many osteoclasts and hemosiderin depositions (brown color) – should not to be confused with true giant cell tumor uf bone

Clinical features: bone pain, pathological fractures occasionally, hypercalcaemia

Paget’s disease of bone (osteitis deformans)

chronic condition, enlargement and deformities of affected bones individuals over the age of 45 years, frequency increases with advancing ageonly one bone or many bones (polyostotic form)Sites: skull, pelvis, spineAetiology unknown, some osteoclasts contain intranuclear inclusions resembling the nucleocapsid structure of paramyxoviruses → viral infection suggested, but attempts to isolate virus failed

Macroscopic features: bones enlarged and thickened (thick calvarium) and softer (deformities – bowing of lower limbs), narrowing of the foramina of cranial nerves (neuropathies, deafness)

Microscopic features: repeated episodes of intense bone resorption and subsequent reparationOsteolytic phaseMixed or osteoblastic phaseOsteosclerotic or burned-out phase (mosaic-like appearance due to numerous cement lines)

Greater risk of developing osteosarcoma

Fracturesbreaks in the continuity of boneInfraction = incomplete fracturePathological fracture: bone altered by some previous lesion (osteoporosis, cysts, tumours), only minor trauma or spontaneously

Fracture healing:haematoma between severed ends of bone + necrosis of bone marroworganization of haematoma with granulation tissueconnection of bone ends by fibrous tissue (fibrous callus)woven bone and cartilage in fibrous tissue (provisional callus)gradual remodelling to mature lamellar bone (definite callus)

Impaired fracture healing (infection, poor immobilization, metabolic bone diseases): exuberant callus with excessive cartilage formation, sometimes non-union of bone ends (pseudo-arthrosis)

Osteomyelitisinfection-mediated inflammation of bonepus-forming organisms (staphylococci, streptococci...)

infection may penetrate bone:directly (compound fractures, operations)via the bloodstream from distant primary focus (haematogeneous osteomyelitis)

Morphologyacute pyogenic inflammation of bone marrow – rise in interstitial pressure compromises the local blood supply – ischaemic necrosis of cancellous bone

spread of inflammation to the subperiosteal space (subperiosteal abscess) – periosteal blood vessels shear off - ischaemic necrosis of cortical bone

perforation of the periosteum – spread through soft tissues and skin forming a sinus track, portions of dead bone can be discharged onto the skin

Complicationssepsis, amyloidosis, pyogenic arthritis, squamous carcinoma of the skin (after many years)

Tuberculous osteomyelitis

children, blood-borne infectionlong bones, vertebrae

bone destruction associated with granulomatous lesion with caseation

Tuberculosis of the spine (Pott’s disease): sharp anterior angulation of the spine (kyphosis), caseation may spread to the paravertebral soft tissues and track down along the psoas muscle to form an inguinal subcutaneous mass

Bone metastases

much more common than the primary bone tumoursusually multiple

Osteolytic (bone destruction)Osteoblastic (reactive bone formation)

Tumors commonly producing bone metastases: prostatic carcinoma, breast carcinoma, renal cell carcinoma, carcinoma of stomach, thyroid carcinoma

Primary bone tumoursLess common, usually solitaryFeatures of considerable diagnostic value: age of the patient, site of the lesion

Classification (simplified):Bone-forming tumoursOsteomaOsteoid osteomaOsteoblastomaOsteosarcomaCartilage-forming tumoursOsteochondromaChondromaChondrosarcomaOther tumoursGiant cell tumor of boneEwing’s sarcomaTumour-like lesionsFibrous dysplasiaBone cysts

Osteoma

benign lesiondense mature lamellar boneskull, facial bones, paranasal sinuses, orbit

Macrousually small bony outgrowth

Micromature lamellar bone

may be a component of Gardner’s colonic polyposis syndrome

Osteoid osteoma

benign osteoblastic lesionyoung people (5-24 years), male predominance

Clinical features: quite severe painlong bones (femur, tibia), ends of the shafts

Morphologysharply outlined osteolytic defect (nidus) less than 1 cm in diameter, surrounded by rim of sclerotic bonenidus composed of haphazardly oriented trabeculae of woven bone and highly vacularized fibrous stromatrabeculae lined by plump osteoblasts and rare osteoklasts

Osteoblastoma

rare, closely related to osteoid osteoma, but larger than 1cm (“giant osteoid osteoma“), and generally lacking the reactive rim of dense sclerotic bone

age similar to that of osteoid osteomaspine, small bones of the hands and feet

Microscopical appearancevery similar to osteoid osteoma (trabeculae of woven bone lined by plump osteoblasts and osteoclasts, vascularized fibrous stroma)

benign, but examples showing atypical osteoblast and a poorly demarcated edge tend to recur, although not metastasise (aggressive osteoblastoma)

Osteosarcoma

most common primary malignant neoplasm of bone

peak incidence between 10-25 years, in middle-aged and elderly people associated with Paget’s disease, predominance of males

metaphyseal region of the long bones (lower end of femur, upper end of tibia, upper end of humerus)

arises from within medullary cavity and invades the cortical bone, elevates the periosteum (Codman’s triangle) and penetrates into soft tissues

Microscopic features:bone or osteoid formation by the tumour cells (irregular „lace-like“ osteoid trabeculae surrounded by atypical malignant osteoblasts), areas of malignant cartilage and sarcomatous spindle cell stroma

highly malignant neoplasm with poor prognosis, metastases to lungs

Parosteal osteosarcoma

variant of osteosarcoma in slightly older people

juxtacortical position of metaphyseal region

large lobulated mass tending to encircle the shaft

very slow growth

well-formed bone and osteoid set in spindle cell stroma with only scanty cytological signs of malignancy

very good prognosis with adequate resection

Osteochondroma (exostosis)

very common, hamartomas rather than true neoplasms

young people, male predominance

long bones (femur, tibia, humerus), metaphyses

pedunculated or sessile lesions consisting of bone covered by a cap of cartilageordered columnar arrangement of chondrocytes and zone of endochondral ossification

Osteochondromatosis: multiple osteochondromas, some risk of malignant transformation (secondary chondrosarcoma)

Chondroma

benign tumour consisting of mature hyaline cartilage

children, adolescents and young adults, incidence equal in both sexes

medullary cavity of the small bones of the hands and feet (enchondroma)radiolucent lesion expanding and thinning cortical bone

lobules of mature hyaline cartilage, some irregularity and atypia of chondrocytes without any adverse prognostic significance

Ollier’s disease (multiple chondromas)

Chondrosarcoma

malignant cartilaginous tumour, primary (arising de novo) or secondary (malignant transformation of benign cartilaginous tumours)

middle aged and elderly (primary chondrosarcoma), younger age group (secondary chondrosarcoma), M/F ratio 3:2

central skeleton (ribs, pelvis, proximal end of femur and humerus)

aggressive growth (destruction of cortical bone, extension into the soft tissues)

high cellularity, cytologic atypia of chondrocytes, binucleated cells, mitotic activity, necrosis

Giant cell tumor of bone

third decade

long bone epiphyses

lytic and radiolucent lesion

brown with grey and red areas (fibrosis and haemorrhage)

mononuclear cells (the only neoplastic element) and multinuclear giant cells resembling osteoclasts (reactive)

locally aggressive, may recur

metastases to the lungs in about 4% of cases

Ewing’s sarcoma

primitive neuroectodermal tumour (PNET)

5-20 years, male preponderance

almost any bone, most often long bones and pelvis

lytic destruction of the bone, widening of the medullary cavity, cortical infiltration and elevation of the periosteum – “onion-skin“ or “sun-ray“ periosteal reactiongrayish white, focal necrosis and haemorrhage

sheets of small uniform round cells, droplets of glycogen in the cytoplasm of the tumor cells (PAS positive material)

very aggressive tumour with poor prognosis, metastatic spread to lungs and other bones

Fibrous dysplasia

non-neoplastic condition

children and adolescents

ribs, femur, tibia, maxilla, mandibula, humerus

monostotic and polyostotic form

well-demarcated localized area of bone replaced by the fibrous tissue containing spicules of woven bone with peculiar sickle or fish-hook shape

McCune-Albright syndrome: polyostotic FD + patchy skin pigmentation + precocious puberty

Bone cysts

Solitary bone cystunicameral cavity lined by smooth fibrous membrane

Aneurysmal bone cystmultiple spaces filled with red blood cells separated by thin fibrous septa with numerous osteoclasts