Cartilage
Strong, flexible type of connective tissue.- Supports and connects body parts (eg, costal cartilage that connects ribs to sternum)- Provides cushioning in joints Layers:Perichondrum: Layer of connective tissue that surrounds cartilage:- Outer layer of fibrous connective tissues and blood vessels - Inner layers with chondroblasts that make extracellular matrix (gell out of water and proteoglycan aggregates). Get trapped in the matrix and form lacunae → turn into chondrocytes that maintain and repair extracellular matrix. Growth:1. Appositional growth: Chrondroblasts create new matrix on perichondrium → cartilage expands & widens2. Interstitial growth: Chrondrocytes create new matrix within the cartilage → grows in length- Metaphysis contains the epiphyseal plate (growth plate) that has chondrocytes that produce cartilage - Osteoblasts ossify cartilage by depositing minerals Types:1. Elastic cartilage: Rarest, softest and most flexible cartilage, type II collagen. Found in pinnae, epiglottis.2. Hyaline cartilage: Most common, stronger but less flexible, type II collagen. Found in the nose, walls of the larynx, tracheal cartilages, articular cartilages in joints, costal cartilages, growth plates. 3. Fibrocartilage: Greatest tensile strength, secrete type I collagen. Found in meniscus, intervertebral discs.
Bone
Surface of bone is covered by periosteum.- Outer fibrous layer: Protects bones, provides attachment for tendons and ligaments.- Inner cellular layer: Progenitor stem cells that develop into osteoblasts and chondroblasts. Diaphysis:- Cortical bone contains osteons. → Each osteon is made of many lamellae (concentric layers made of collagen and hydroxyapatite)→ In the center of each Osteon is a Haversian canal (blood supply & innervation).- Medullary canal (inner bone)→ Hollow space lined by spongy/cancellous bone. → Contains bone marrow. Epiphysis:- Made of spongy bone out of crosslinking roads called trabeculae (resistant to mechanical stress).- Spaces in the spongy bone occupied by bone marrow.
Bone remodeling
Continuous process where bones are resorbed by osteoclasts and remade by osteoblasts. RANKL → initiates remodelingOsteoprotegerin → Turn off remodeling Repairs tiny cracks due to normal activities.Help bones heal after a fracture. Bone degradation:→ Osteoclasts sense microcracks and produce RANKL (receptor activator of nuclear factor κ ligand) → binds to RANK receptors on monocytes.→ Monocytes fuse to osteoclast cells.→ Osteoclasts secrete collagenase → digest collagen → drill pits known as Howship's lacunae→ Osteoclasts produce HCl which dissolves hydroxyapatite → Calcium and phosphate released in bloodstream Bone resorption:- Osteoblasts secrete osteoprotegerin, which binds to RANKL and prevents it from activating RANK receptors → slows actiation of osteoclasts- Undergo apoptosis- Secrete osteoid seam to fill in lacunae → calcium and phosphate deposit on seam and form hydroxyapatite- Some osteoblasts become trapped in lacunae and turn into osteocytes PTH promotes bone resorption.Calcitonin inhibits bone resorption.Mechanical stress causes high rate remodelling.Vitamin D decreases calcitonin → increased bone resorption.
Fibrous, cartilage, and synovial joints
206 bones connected by 360 joints. 1. Fibrous joints (fixed)- Bones are connected by ligaments.- Sutures: Completely fixed in adults; allows molding during childbirth- Syndesmosis: Joing between radius and ulna in forearm (interosseous membrane)- Gomphosis: Joint between roots of a tooth and its socket (peridontal ligaments) 2. Cartilaginous joints- Surrounded by hyaline cartilage- Synchondrosis: Costochondral joint - Between diaphysis and epiphysis and undergoes ossification- Symphysis: Pelvic bone 3. Synovial joints - Most common- Allow flexion & extension, abduction & adduction, rotation - Joint capsel (outer fibrous capsule and inner synovial membrane), synovial fluid: lubricates
Frakturkallus
1. Fraktur mit angrenzend devitalisierter Knochen mit leeren Osteozytenhöhlen 2. Periostaler und intramedullärer Kallus: Regelrecht gebildete, teilweise mineralisierte Knochensubstanz in Form von Arkaden (periostal) und Trabekel (intramedullär), besäumt von Osteoblasten 3. Markraumfibrose mit Granulationsgewebe 4. Frakturspalt mit Fibrinablagerungen 5. Einsprossende Gefässe
Osteoporose
1. Verschmälerte Kortikalis 2. Reduzierte Zahl und Breite der spongiösen Knochenbälkchen 3. Verminderung des Spongiosagerüsts im Zentrum stärker ausgeprägt als in der Peripherie 4. Keine Resorptionslakunen oder angelagerte Osteoblasten bzw. Osteoklasten 5. Ausgeweiteter Markraum gefüllt mit Fettgewebe
Osteoporosis
Skeletal condition in which the loss of bone mineral density leads to decreased bone strength and an increased susceptibility to fractures. Etiology:1. Primary Osteoporosis- Type I (postmenopausal osteoporosis): Estrogen stimulates osteoblasts and inhibits osteoclasts. The decreased estrogen levels following menopause lead to increased bone resorption.- Type II (senile osteoporosis): gradual loss of bone mass as patients age (especially > 70 years)2. Secondary osteoporosis- Drug-induced/iatrogenic: Corticosteroids (e.g., in patients with autoimmune disease), long-term therapy with proton-pump inhibitors, anti-epileptic drugs, aromatase inhibitors- Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, renal disease- Immobilization- Alcohol abuse Risk factors: Cigarette smoking, family history of osteoporosis, malnutrition, malabsorption, low body weight Localization: vertebral (most common) > femoral neck > distal radius (Colles) fracture, fractures of the long bones Diagnosis:- DXA (dual-energy X-ray absorptiometry): T-score ≤ -2.5 SD Pathology:- Thin, disconnected trabecular structures- Attenuated, pitted cortical bone- Increased osteoclast number and activity Treatment:- Lifestyle: Diet (sufficient intake in calcium and vitamin D), weight-baring exercise- Bisphosphonates- Teriparatide- Raloxifen- Densosumab
Paget disease of bone
Common, localized disorder of bone remodeling caused by ↑ osteoclastic activity followed by ↑ osteoblastic activity that forms poor-quality bone.- Leads to deformities and potential fractures.- Second most prevalent skeletal disease after osteoporosis- Age of onset: >55 years Localization: Skull, lumbar vertebrae, pelvis, femur 3 phases:1. Lytic phase: Osteoclasts aggressively demineralize the bone (20x more than normal)2. Mixed phase: Lytic + blastic phase.3. Sclerotic phase: New bone formation exceeds resorption → structurally disorganized and weaker bone4. Dormant state: "burned-out state" Clinical features:- Approximately 70-90% of cases are asymptomatic. - Bone pain, which may be associated with erythema and elevated skin temperature over the affected bones- Bony deformities; e.g., bowing of legs (saber shin)- Skull involvement (in ∼ 40% of cases)→ Skull enlargement (increasing hat size)→ Cranial nerve deficits→ Impaired hearing→ Headache- Pathological fractures- May lead to osteosarcoma (= Paget sarcoma) Diagnosis:- Normal calcium, phosphate, and parathyroid hormone (PTH) levels- ↑↑ Alkaline phosphatase- X-ray may shown lytic lesions (during lytic phase), thickened bone cortices (advanced)- Bone biopsy: Exclude malignancies Treatment: Bisphosphonates
Morbus Paget
1. Spongiosabälkchen sind auffallend verdickt, vermehrt und unregelmässig geformt. 2. Prominente Zementlinien sind mosaikartig angeordnet. 3. Riesenosteoklasten mit über 20 Kernen. 4. Lockere Markfibrose.
Renale Osteodystrophie
1. Stark erhöhter Spongiosaumbau 2. Fibroosteoklasie: Lakunen mit osteoklastäre Knochenresorption mit Begleitfibrose 3. Osteoidose: Osteoblasten- und Osteoidsaum
Osteoarthritis
Joint disease characterized by a degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. Synovium:- Consists of connective tissue, blood vessels, lymphatic vessels- Type A cells: clear cellular debris- Type B cells: produce synovial fluid Risk factors: Age, joint injury, mechanical stress, obesity, genetic factors Aritcular cartilage starts to flake off into synovial space (= Joint mice). When type A cells try to remove cellular debris, immune cells are recruited → inflammation of synovium (= Synovitis) → Joint space narrowing→ Sclerotic bone→ Subchondral bone cysts→ Osteophytes Symptoms: morning stiffness (<1 hour), worse at end of day, sharp ache/burning, worsens with activitiy, no swelling.- Heberden's nodes: DIP- Bouchard's nodes: PIP- Rhizarthosis: first carpometacarpal joint (between the trapezoid and the metacarpal bone) Treatment:- Nonpharmacological: Losing weight, exercise, physical therapy- NSAIDs, hyaluronic acid injections, joint replacement
Synovialitis bei chronischer Osteoarthritis
1. Synoviale Zottenhyperplasie 2. Verbreiterung der Deckzellschicht 3. Lymphofollikuläre Entzündungsinfiltrate im Stroma. 4. Einschlüsse von Knorpel- und Knochenfragmenten (Detritussynovialitis) 3. Fokale Fibrinauflagerungen
Rheumatoid arthritis
Systemic inflammatory autoimmune disorder characterized by joint pain, swelling, and synovial destruction. Risk factors: Genetics (HLA-DR1, HLA-DR4) and environmental trigger (smoking, infection) Citrullation of type II collagen and vimentin causes production of autoantibodies (anti-CCP).T cells secrete IFN-γ and IL-17, macrophages secrete TNFα, IL-1, IL-6 → synovial cell proliferation → pannusImmune complexes of anti-CCP and anti-RF form immune complexes that activate the complement system. Symptoms:- Usually ≥5 joints, symmetrical; commonly small joints (MCP PIP, MTP)- Morning stiffness >1h- Flares: Swollen, warm, red painful→ Ulnar deviation, Boutonniere deformity, swan neck deformity, Baker cyst- Fever (IL-1 and IL-6), malaise, muscle weakenss- Rheumatoid nodules in the skin around pressure points (eg, elbow)- ↑ risk of atherosclerosis- ↑ Hepcidin caused ↓ iron absorption → anemia- Interstitial lung disease, pleural effusion Felty syndrome: Rheumatoid arthritis + Splenomegaly + Granulocytopenia Diagnosis:- Rheumatoid factor, anti-citrullinated peptide antibody- X-Ray: ↓ bone density, soft tissue swelling, narrowing of joint space, erosions Treatment:- Disease-modifying anti-rheumatic medications (DMARDs): Methotrexate, hydroxychloroquine, sulfasalazine- Biologicals: Abatacept, rituximab, adalimumab/etanercept/infliximab, anakinra (blocks IL-1)- Acute flairs: NSAIDs, glucocorticoids
Osteoarthrose
1. Gelenkknorpel: Zerstörung unterschiedlichen Grades, von oberflächlicher Aufblätterung (Fibrillation) über vertikale Substanzrisse und Zerklüftung bis zur (sub-)totalen Abschleifung. 2. Mikrofrakturen und Einbruchzonen mit Ausbildung von Pseudozysten 3. Reaktive Veränderungen des subchondralen Knochengerüstes: Sklerose, gesteigerte Knochenumbauaktivität, Markfibrose und zelluläre Abbauaktivität (Makrophagen, evtl. FK-Riesenzellen) 3. Geringes entzündliches Infiltrat 4. Tela synovialis: Chronische Reizsynovialitis
Chondrosarcoma
Malignant tumor arising from mesenchymal cells that produce cartilage.- Age: usually > 50 years- M > F Symptoms:- Deep, dull pain (worsens at night, insidious progression over months to years)- Local swelling Location: Medulla of pelvis and central skeleton Diagnostics:- X-ray or CT → Osteolysis with moth-eaten appearance→ Calcifications (rings and arcs calcification, popcorn calcification)→ Endosteal scalloping and cortical breach with infiltration of soft tissue- MRI: rim-like contrast enhancement- Biopsy: Lobulated appearance (hyaline cartilage nodules with peripheral calcification ) Treatment:- Surgery (definitive resection) + chemotherapy and radiation therapy
Chondrosarkom
1. Zerstörung der Spongiosa und Kortikalis durch Tumorausläufer 2. Nodule/Läppchen aus hyalinem Knorpel, evlt. periphere Kalzifizierung 3. Leichte bis mässige Zell- und Kernpolymorphie; gelegentlich doppelkernige Zellen- Grad 1: Chondrozyten mit kleinen dichten Kernen, wenig multinukleäre Zellen. Überwiegend chondroide Matrix. Keine erhöhte Zellularität. Keine Mitosen.- Grad 2: erhöhte Zellularität, weniger und oft myxoide Matrix, selten Mitosen, Nekrosen.- Grad 3: Noch höhere Zellularität und Zellpleomorphismus, wenig oder keine chondroide Matrix, Zellanordnung in Bändern und Haufen, ausgeprägte Atypien, Kerne deutlich vergrössert, fast immer Mitosen und Nekrosen.
Osteosarcoma
Malignant, osteoid and bone-forming tumor arising from osteoblasts located in the periosteum.- Most common primary bone malignancy - Bimodal distribution→ Primary osteosarcoma: puberty/adolescence→ Secondary osteosarcoma: advanced age- Males > females Symptoms:- Pain (progressive, worsens at night and with activity)- Swelling after trauma to the bone - Limping and decreased range of motion- B symptoms Localization: metaphyses of long bones (particularly distal femur and proximal tibia) Diagnostics:- X-ray: → Signs of osteolysis adjacent to osteosclerosis (moth eaten appearance)→ Sunburst appearance of lytic bone lesions and/or codman triangles- MRI: assesses involvement of soft tissue, evaluation in cases of unclear radiographic findings- Biopsy: Osteosarcomas always feature woven bone matrix → distinction from chondrosarcomas and fibrosarcomas- Laboratory: ↑ alkaline phosphatase, ↑ LDH, ↑ ESR Treatment:- Definitive resection + neoadjuvant and adjuvant polychemotherapy (e.g., combination of methotrexate, doxorubicin, cisplatin, and ifosfamide)
Osteosarkom
1. Malignitätszeichen: Zell- und Kernpolymorphie, atypische Mitosen 2. Bildung von Osteoid (für die Diagnose eines Osteosarkoms ausschlaggebend; nicht anwesend beim Chondrosarkom)
Ewing sarcoma
Malignant bone tumor arising from neuroectodermal cells.- Associated with translocation t(11;22) (fusion protein EWS-FLI1) - Most common in Caucasians- Generally boys < 15 years old Symptoms:- Localized pain (progressive, worsens at night), hyperthermia, and swelling after trauma to the bone - B symptoms Localiization: Often diaphyses of long bones (particularly femur, tibia, fibula, and humerus) and bones of the pelvis Diagnostics- X-ray: lytic bone lesions, onion skin appearance of the periosteum- Laboratory findings: ↑ ESR, ↑ LDH, leukocytosis- Biopsy: Anaplastic small-blue-round-cell malignancy; chromosomal translocation t(11;22), CD99 Treatment: Definitive resection plus neoadjuvant and adjuvant polychemotherapy
Small blue round cell tumor - Differenzialdiagnose
- Ewing Sarkom - Lymphom - Embryonales Rhabdosarkom - Neuroblatom
Ewing-Sarkom
1. Blauer, klein- und rundzelliger Tumor 2. Uniforme Zellen mit schmalem, kaum abgrenzbarem Zytoplasmasaum und unscharfen Zellgrenzen 3. Lobuläre Architektur: Durch Bindegewebssepten abgegrenzte Knoten 4. Quetschartefakte (gequetschte Zellen sind dunkler und haben verkleinerte abgeflachte Zellkerne)
Giant-cell tumor of bone (osteoclastoma)
Locally aggressive tumor composed of giant cells that arise from the bone marrow. Peak incidence: 20-40 years Localization: Epiphyseal/metaphyseal region of the long bones (predominantly bones close to the knee) Symptoms:- Local pain and swelling- Limited range of motion- Pathological fractures Diagnostics:- X-ray: multicystic osteolytic lesions ("soap bubble appearance")- Histopathology: multinucleated giant cells Treatment: curettage and bone grafting, or en bloc resection to minimize reccurence rate
Riesenzelltumor
1. Mehrkernige Riesenzellen 2. Mittelgrosse, polygonale bis plump spindelige, einkernige Zellen 3. Nebst fokaler Kollagenisierung (Vernarbung, oft mit Hämosiderin) keine Matrixbildung, d.h. keine Knochen- oder Knorpelbildung durch die Tumorzellen.
Muskelfaser-Typen
Typ 1:- rot- langsam- ständige Aktivierung- viele oxidative Enzyme- Aerob (Oxidation)- viele Mitochondrien- viel Speicherfett- ATPase pH 9.4 hell Typ 2:- weiss- schnell- plötzliche Aktivierung- wenige oxidative Enzyme- Anaerob (Glykolyse)- wenige Mitochondrien- wenig Speicherfett- ATPase pH 9.4 dunkel
Entzündliche Myopathien
Polymyositis:- Lymphozytäre Invasion nichtnekrotischer Muskelfasern- Entzündliche Zellinfiltrate (CD8)- Muskelfasernekrosen und regenerierende Muskelfasern- MHC-I generalisiert überexprimiert- Endomysiale Fibrose Dermatomyositis:- Kapillardegeneration- spezifische ultrastrukturelle Endotheleinschlüsse- Komplementablagerungen, weniger lymphozytäre Infiltrate, mehr B-Zellen- Perifaszikuläre Atrophie (Ischämie-bedingt) Einschlusskörpermyositis (IBM; „inclusion body myopathy“):- ähnlich Polymyositis- zusätzlich Vakuolen in den Muskelfasern („rimmed vacuoles“)- typische Kerneinschlüsse
Inclusion-body myositis (IBM)
Inflammatory myopathy that progresses slowly over years. Symptoms:- Selective and asymmetric muscle involvement of both proximal and distal muscle groups- Quadriceps muscle weakness: knees lack support → frequent falling- Finger flexors: difficulties gripping, eg, shopping bags or a briefcase Pathology:- Vacuoles within the muscle fiber Diagnosis:- ↑ Muscle enzymes, eg CK- Electromyography- Muscle biopsy: Inflammation and vacuoles Treatment: Exercise, physical therapy
Achondroplasia
Etiology:- Activating mutation in fibroblast growth factor receptor 3 gene (FGFR3) → inhibited chondrocyte proliferation → reduced endochondral ossification- New mutations in ∼80% of cases; autosomal dominant inheritance in ∼20% of cases (homozygosity is lethal) Epidemiology:- Most common type of skeletal dysplasia and disproportionate short stature - The probability of new mutations increases with the father's age at the time of conception. Clinical features:- Short stature: average standing height of 131 cm in males or 124 cm in females- Average-sized torso; short, plump extremities- Macrocephaly, prominent brow, midface retrusion, flattening of the nose- Normal intelligence Diagnostics: X-ray- Lateral skull: midface hypoplasia, frontal prominence- Spine: abnormally narrow interpedicular distance → spinal canal stenosis; scoliosis- Extremities: bones are short and broad; short fingers Therapy:- Early administration of growth hormone (1-6 years)- Surgical corrections: spinal stenosis, secondary scoliosis, genu varum, foramen magnum decompression
Osteogenesis imperfecta (“brittle bone disease”)
Etiology: Autosomal dominant mutation in COL1A1 or COL1A2 genes; decreased formation of hydrogen and disulfide bonds between type 1 preprocollagen molecules → decreased triple helix formation → defective type I collagen synthesis → impaired bone matrix formation (osteogenesis) Clinical features:- Growth retardation- Skeletal deformities, brittle bones, and recurrent fractures from minimal trauma- Blue sclerae- Progressive hearing loss- Brittle, opalescent teeth- Type II: most severe form; lethal perinatally or within the first year Therapy- No cure available- IV bisphosphonates to increase cortical thickness- Surgery for functional improvement
Osteomalacia
Bone softening caused by impaired mineralization. Pathophysiology: Vitamin D deficiency and defective vitamin D metabolism- Hypocalcemia → defective bone matrix mineralization - Renal disease → ↓ production of vitamin D and metabolic acidosis → impaired calcification Clinical features:- Occurs in adults - Bone pain and tenderness- Pathologic fractures- Waddling gait and difficulty walking- Myopathy: muscle weakness, spasms, and/or cramps- Symptoms of hypocalcemia Diagnostics: - Lab: Calcium ↓, phosphate ↓, alkaline phosphatase ↑, parathyroid hormone ↑- X-ray: Low bone mineral density, thin cortices, looser zones (pseudofractures): transverse bands of radiolucency indicating defective calcification of osteoid Treatment:- Administration of vitamin D- Adequate daily intake of calcium
Rickets
Bone softening caused by impaired mineralization. Pathophysiology: Vitamin D deficiency and defective vitamin D metabolism- Hypocalcemia → defective growth plate mineralization- Renal disease → ↓ production of vitamin D and metabolic acidosis → impaired calcification Clinical features:- Occurs in children - Bone deformities→ Bending of primarily the long bones→ Rachitic rosary: distention of the bone-cartilage junctions in the ribs→ Marfan's sign: distention of the bone-cartilage junctions in the joints→ Craniotabes: softening of the occipital bones→ Varum/valgus deformities of the knee- Harrison's groove: depression of the thoracic outlet due to muscle pulling along the costal insertion of the diaphragm- Late closing of fontanelles- Impaired growth- Symptoms of hypocalcemia Diagnostics: - Lab: Calcium ↓, phosphate ↓, alkaline phosphatase ↑, parathyroid hormone ↑- X-ray: Low bone mineral density, thin cortices, growth plates in the metaphysis of the long bones are less defined and show cupping, stippling, and fraying, wide epiphysis, evidence of bone deformities Treatment:- Administration of vitamin D- Adequate daily intake of calcium
Osteopetrosis
Inherited, diffuse bone disease that results in increased sclerotic appearance of the skeleton on radiological examination (from Latin: "petrosus" = stony). Etiology:- Type I osteopetrosis (malignant osteopetrosis)→ Age of onset: infancy→ Clinical course: severe- Type II osteopetrosis (benign osteopetrosis, Albers-Schonberg disease)→ Age of onset: early adulthood→ Clinical course: mild Pathophysiology: impaired osteoclastic resorption of bone with preserved osteoblastic function Clinical features:- Pathological fractures- Cranial nerve disorders- Pancytopenia- Hepatosplenomegaly Diagnostics:- X-ray: homogenous, marbled thickening of both cortical and trabecular bone- Laboratory findings: Hypocalcemia, ↑ tartrate-resistant acid phosphatase (TRAP) Therapy: Bone marrow transplantation may be curative as osteoclasts are derived from monocytes.
Osteomyelitis
Osteitis: general term for inflammation of the boneOsteomyelitis: infection of the bone marrow Etiology:- Hematogenous osteomyelitis- Exogenous osteomyelitis: usually due to multiple pathogens→ Posttraumatic: infection following deep injury (penetrating injury, open fractures, severe soft tissue injury)→ Contiguous: spread of infection from adjacent tissue (foot ulcer, postoperative infection of a prosthetic joint implant) Pathogens:- Staphylococcus aureus: Children and adults- Staphylococcus epidermidis: Diabetic patients with foot ulcers and pressure ulcers, patients with prosthetics- Pseudomonas aeruginosa: IV drug users, plantar puncture wounds - Salmonella: Sickle cell anemia patients- Klebsiella: Patients with UTIs or a history of UT instrumentation Clinical features:- Onset: usually gradual, over several days- Chief complaint: pain at the site of infection, possibly related to movement- Possible localized findings: point tenderness, swelling, redness, warmth- Possible systemic findings: malaise, fever, chills- Common localization of hematogenous osteomyelitis:→ Infants: long bone metaphysis, joints→ Children: long bone metaphysis, joint infection very rare→ Adults: vertebral involvement is most common Diagnostics:- Initial work-up includes blood cultures, inflammatory markers, and x-ray imaging.- MRI: the most sensitive diagnostic study- Bone biopsy: confirmatory test
Benign bone tumors
Osteochondroma- Most common benign bone tumor.- Males < 25 years old.- Metaphysis of long bones.- Lateral bony projection of growth plate (continuous with marrow space) covered by cartilaginous cap. Osteoma- Middle age.- Surface of facial bones.- Associated with Gardner syndrome. Osteoblastoma- Vertebrae.- Similar histology to osteoid osteoma. - Larger size (> 2 cm), pain unresponsive to NSAIDs. Chondroma- Medulla of small bones of hand and feet.- Benign tumor of cartilage. Giant cell tumor- 20-40 years old.- Epiphysis of long bones (often in knee region).- Locally aggressive benign tumor. - Neoplastic mononuclear cells that express RANKL and reactive multinucleated giant (osteoclast-like) cells.- “Soap bubble” appearance on x-ray.
Malignant bone tumors
Osteosarcoma- Accounts for 20% of 1° bone cancers.- Peak incidence of 1° tumor in males < 20 years.- Less common in elderly- Usually 2° to predisposing factors, such as Paget disease of bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome.- Metaphysis of long bones (often in knee region).- Pleomorphic osteoid-producing cells (malignant osteoblasts).- Presents as painful enlarging mass or pathologic fractures.- Codman triangle (from elevation of periosteum) or sunburst pattern on x-ray. - Aggressive. 1° usually responsive to treatment (surgery, chemotherapy), poor prognosis for 2°. Chondrosarcoma- Medulla of pelvis and central skeleton.- Tumor of malignant chondrocytes. Ewing sarcoma- Most common in Caucasians. Generally boys < 15 years old.- Diaphysis of long bones (especially femur), pelvic flat bones.- Anaplastic small blue cells of neuroectodermal origin (resemble lymphocytes).- Differentiate from conditions with similar morphology (eg, lymphoma, chronic osteomyelitis) by testing for t(11;22) (fusion protein EWS-FLI1).- “Onion skin” periosteal reaction in bone.- Aggressive with early metastases, but responsive to chemotherapy.
Bone metastases
Bone metastasis >> 1° bone tumors (eg, multiple myeloma, lytic). - Breast (mixed)- Prostate (blastic)- Lung (lytic)- Thyroid (lytic)- Kidney (lytic) Predilection for axial skeleton.
