Chapter 14: Bone pathology Flashcards
Osteogenesis imperfecta
-‐ COL1A1 or COL1A2 gene mutation (impairment of collagen type 1 maturation)
-‐ Most common type of inherited bone disease
-‐ Bone fragility, blue sclera, opalescent teeth, hearing loss and joint hyperextensibility
-‐ Opalescent teeth: blue to brown translucency, may have shell teeth-‐ thin dentin, normal enamel
-‐ Wormian bones: 10+ sutural bones arranged in mosaic pattern
-‐ May mimic florid COD on panoramic xray
-‐ Types 1-‐4 (1-‐most common/mildest, blue sclera; 2-‐most severe/stillborn, 3-‐most severe perinatal; no blue sclera; 4-‐moderate adults, no blue sclera)
Osteopetrosis (Albers-‐Schonber disease, marble bone disease)
-‐ Marked increase in bone density due to failure of osteoclasts
-‐ Infantile (malignant osteopetrosis): marrow failure, bone fractures, cranial nerve compression
-‐ Broad face, snub nose, frontal bossing, deafness, blindness, facial paralysis and osteomyelitis
-‐ Xray: diffuse sclerosis of bone
-‐ Intermediate osteopetrosis: less severe infantile osteopetrosis. Marrow failure rare
-‐ Transient osteopetrosis: diffuse sclerosis and marrow failure, resolves w/o therapy
-‐ Adult (benign osteopetrosis): 1-‐nerve compression common, fractures rare; 2-‐ opposite
-‐ DDX: AD osteosclerosis (endosteal hyperostosis), sclerosteosis and Van Buchen disease
-‐ Histo: bone deposition in marrow space; absence of Howship’s lacunae
Cleidocranial dysplasia (cleidocranial dysostosis)
-‐ CBFA1 (RUNX2) gene mutation on chr 6 (guides osteoblasts/bone formation)
-‐ Clavicle malformation (absence, hypoplasia, leads to drooping shoulders);
-‐ Short stature; frontal/parietal bossing; long, “swan” neck; hypertelorism; depressed nasal bridge
-‐ Skull radiograph: sutures exhibit delayed closure.
-‐ Oral: supernumerary teeth (60+), unerupted teeth, cleft palate, high-‐arched palate, narrow rami with nearly parallel anterior and posterior borders; Slender, pointed coronoid processes with distal curvature
Focal osteoporotic bone marrow defect
-‐ Increased marrow causing RL defect (most post MD, women)
-‐ Causes: aberrante bone regeneration after extraction, persistence of fetal marrow, hyperplasia due to increased demand for erythrocytes
Idiopathic osteosclerosis (enostosis, focal periapical osteopetrosis, dense bone island, bone whorl, bone scar, bone eburnation)
-‐ Increased area of radiopacity with unknown cause (90% MD, post area, usually root apex)
-‐ If tooth is non-‐vital: condensing osteitis or focal sclerosing chronic osteomyelitis
-‐ If multiple: R/O Gardner syndrome
-‐ DDx compact osteoma: but no cortical expansion and failutre to grow
Massive osteolysis (Gorham disease, Gorham-‐Stout syndrome, phantom bone disease)
-‐ Spontaneous and progressive destruction of bone
-‐ Destryoed bone replaced with vessels then dense fibrous tissue
-‐ Cause: hyperactivity of bone; angiomatosis (multicentric prolif of blood or lymphatic vessels)
Paget’s disease of bone (osteitis deforman)
-‐ Abnormal and anarchic resportion and deposition of bone, causing distortion and weakening
-‐ Famila and sporadic cases show SQSTM1 (aka p62) mutation (NFKB pathway)
-‐ Valosin-‐containing protein (VCP) gene mutation (NFKB pathway): seen in rare syndrome of Paget’s, inclusion body myopathy and frontotemporal dementia
-‐ Most cases polyostotic. Bone pain is a common complaint, as well as limited mobility.
-‐ Most common affected bones: lumbar vertebrae, pelvis, skull and femur
-‐ Siminan (monkey-‐like) stance: due to bowing deformity of weight-‐bearing bones
-‐ MX enlargement may cause spacing of teeth (dentate) or denture may no longer fit (edentulous)
-‐ Leontiasis ossea (lion-‐like face): enlargement of middle 1/3 face
-‐ Osteoporosis circumscripta: large RL in the skull of Paget’s (early phase)
-‐ Cotton wool: patchy sclerotic areas (osteblastic phase). Teeth show hypercementosis.
-‐ Lincoln’s sign (black beard): increased MD uptake (condyle to condyle) in bone scintigraphy
-‐ DDx: COD (think Paget’s if patient has clinical expansion)
-‐ Histo: reversal lines with jigsaw or mosaic appearnce of bone, highly vascular stroma
-‐ serum alkaline phosphatase. Normal Ca+2 and phosphorus. Increased hydroxyproline in urine
-‐ Newer markers: N-‐telopeptides, C-‐telopeptides and pyridinoline cross-‐link assays
-‐ Complications: hypercementosis (difficult extraction), hemorrhage (active diseae), osteomyelitis (late disease), osteosarcoma (suspect if worsening pain, new mass or sudden fracture) and giant cell tumors
Central giant cell granuloma (Giant cell lesion, giant cell tumor)
-‐ Females < 30 yo anterior MD (crossing midline); non-‐aggressive and aggressive
-‐ Nonaggressive (most cases; no symptoms, slow growth) and aggressive (pain, rapid growth)
-‐ CGCG-‐areas can be seen in ABC and central odontogenic fibroma
-‐ Brown tumor: when seen in hyperparathyroidism
-‐ If multifocal: R/O cherubism (children) and hyperparathyroidism
-‐ Histo: spindle cells and giant cells.
-‐ Recurrence: 15-‐20%/ More cellular lesions and better distributed GC more aggressive.
-‐ Tx of aggressive lesions: corticoids, calcitonin and interferon α2a
Giant cell tumor
-‐ Most common in epiphyses of long tubular bones; locally aggressive
-‐ Histologically ~ to CGCG
-‐ Higher recurrence than jaw lesions and show malignant transformation in 10% of cases
Cherubism
-‐ AD, 50-‐70% penetrance F, 100% penetrance M, SH3BP2 mutation (4p16)
-‐ Bilateral involvement of MD (produces chubby cheeks)
-‐ “Eye upturned to heaven” (wide exposed sclera below iris): due to orbital involvement
-‐ May have eosinophilic cuffing around blood vessels (like a pulse granuloma or schwannoma) (helpful to differentiate from CGCG of hyperparathyroidism)
-‐ Multiple GC lesions: Ramon, Jaffe-‐Campanacci and Noonan-‐like syndromes
-‐ Ramon: cherubism + gingival fibromatosis
Simple bone cyst (traumatic bone cyst, solitary bone cyst, idiopathic bone cavity)
-‐ Empty or fluid-‐containing cavity that is devoid of epithelium
-‐ Trauma-‐hemorrhage theory: trauma w/o fracture-‐>hematoma-‐>liquefies-‐> cystic defect
-‐ Most in long bones. Jaw cases in pts 10-‐20y
-‐ Jaws: usually unilateral, post MD, RL scalloping between roots. May associate with florid COD
Aneurysmal bone cyst
-‐ 17;16 translocation.
-‐ Predilection for teenagers
-‐ Theory: disruption (trauma, neoplasm) of normal bone hemodynamics, causing hemorrhage
-‐ Ballooning or blow-‐out distortion of bone contour
-‐ Sx: blood-‐soaked sponge
-‐ Histo: spaces filled with blood, cellular fibroblastic stroma and lacelike calcifications
-‐ In 20% of cases, associated with FOL or CGCG
-‐ Primary or secondary to GCT/CGCG, FD, OF or other bone lesions
– Primary lesions exhibit recurrent translocations and consequent transcriptional upregulation of the ubiquitin-specific prostease 6 (USP6) (also known as Tre-2 or TRE17) oncogene on chromosome 7p13
Fibro-‐osseous lesions of the jaws
Fibrous dysplasia
-‐ GNAS1 mutation. Replacement of bone by connective tissue.
-‐ Monostotic: single bone. 80% cases. If in maxilla, named craniofacial FD. Ground glass on xray
-‐ Increased density of the occiput, sphenoid, roof of orbit anf fronta bones is the most characteristic features of FD od the skull
-‐ Polyostotic: 2+ bones
-‐ Polyostotic FD + café-‐au-‐lait: Jaffe-‐Lichtenstein
-‐ Polyostotic FD + café-‐au-‐lait + endocrine abnormalities (sexual precocity, pituitary adenoma, hyperparathyroidism): McCune-‐Albright
-‐ Polyostotic FD + intramuscular myxomas: Mazabraud syndrome (increased risk of ostesarc)
-‐ Hockey stick deformity: leg length discrepancy due to involvement of upper femur
-‐ Hypophosphatemia: due to renal phosphate wasting (bone produces FGF23)
-‐ Café-‐au-‐lait have irregular margins (map of Maine); NF regular margins (map of CA)
-‐ Histo: Chinese characters. Monotonous pattern of bone trabeculae.
Fibro-‐osseous lesions of the jaws
Cemento-‐osseous dysplasias
-‐ Most common FOL.
-‐ Focal (white F, post MD), periapical (ant MD), florid (multifocal + ant MD)
-‐ SBC may be seen within COD: due to obstruction to drainage by COD. Do not heal as quickly and abnormal xray pattern may persist.
-‐ FCOD vs OF: OF separate easily from surrounding bone, FCOD does not. On histo, OF has more delicate trabeculae, often with osteoblasts. Cementum-‐like particles in FCOD has retraction artefact, in OF more ovoid and brush borders. COD hemorrhage throughout lesion, OF on periphery
-‐ In final stages, lesions are prone to necrosis (avoid biopsy and extractions) and osteomyelitis
Fibro-‐osseous lesions of the jaws
Familial gigantiform cementoma
-‐ AD, ~ to FCOD. Ultimately leads to massive sclerotic masses of disorganized mineralized material
-‐ Usually in whites. First decade. May affect all four quadrants
-‐ Increased serum alkaline phosphatase (declines after surgical removal)
-‐ Anemia reported in females. GYN exam recommended (polypoid adenomas may develop)
-‐ Non-‐familial cases: spontaneous mutations. Named multiple or bilateral OF
-‐ Histo: equal to COD.
Fibro-‐osseous lesions of the jaws
Ossifying fibroma
-‐ HRPT2 (parafibromin) mutation
-‐ Downward bowing of MD cortex
-‐ Hyperparathyroidism-‐jaw tumor syndrome: HRPT2 mutation. Parathyroid tumors, OF jaws, renal cysts and Wilm’s tumor
-‐ Hard tissue may be osteoid, bone or cementum-‐like (FD is more uniform)
Juvenile active ossifying fibroma
Juvenile active ossifying fibroma
-‐ Differences from OF: age of patient, site of involvement and clinical behavior
-‐ Trabecular: younger pts
-‐ Psammomatoid: 4x more common; 70% outside jaws (orbit, frontal bone and paranasal sinuses)
-‐ x;2 translocation in psammomatoid form
-‐ Males, MX, rapid growth
-‐ ABC may develop in psammomatoid variant
-‐ Myxomatous foci, pseudocysts, hemorrhage, giant cells
Osteoma
-‐ Periosteal (peripheral, exophytic) or endosteal (central)
-‐ Osteoma cutis: located in the muscle or dermis of skin
-‐ Post MD (lingual surface PM) or condyle. Also coronoid process, ramus and angle MD
-‐ Condylar osteoma: causes shift of the chin (ddx: condylar hyperplasia, hemifacial hyperplasia).
Osteoma is lobulated; if hyperplasia, condyle maintains its form
-‐ Paranasal sinus lesions are more common than gnathic (usually frontal sinus)
-‐ Xray: periosteal-‐ sclerotic mass; endosteal-‐ similar to idiopathic osteosclerosis
-‐ Histo: compact-‐ dense bone with minimal marrow; cancellous-‐ bone trabeculae and marrow
Gardner syndrome
-‐ APC (adenomatous polyposis coli) gene mutation.
-‐ Colonic polyps -‐> 100% transform into adenoca (also in small intestine and stomach)
-‐ Osteomas: 3-‐6, skull, paranasal sinuses and mandible (angle). Precede bowel lesions.
-‐ Dental: odontomas, supernumerary teeth and impacted teeth
-‐ Also: epidermoid cysts, thryroid CA, desmoids tumor and pigmentation of ocular fundus (90%), Lipomas, fibromas, neurofibromas, and leiomyomas
Osteoblastoma and osteoid osteoma
-‐ Osteoblastoma: > 2cm, post MD, <30y
-‐ Osteoid osteoma: < 2 cm, produce PG, nocturnal pain alleviated by aspirin, rare jaws
-‐ Periosteal osteoblastoma: no evidence of central involvement
-‐ Aggressive osteoblastoma: atypical histo and aggressive behavior (>4 cm, >30y, pain)
-‐ If attached to rooth of a tooth: cementoblastoma
-‐ OB: RL or mixed, usually no rim; OO: RL with RP nidus (target-‐like), usually has rim
-‐ Hsto: reversal lines, “blue bone”, bland looking, plump, active osteoblasts
-‐ Aggressive (epitheliod) osteoblastoma: histo very similar to WD osteosarcoma
Cementoblastoma
-‐ 75% in MD (90% post). 50% 1st molar. 75% < 30y; 66% pain and swelling
-‐ RP attached to root with RL rim
-‐ Histo same as osteblastoma
Chondroma
– Benign tumor of mature hyaline cartilage
– Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene
-‐ Most in short bone of hands and feet.
-‐ Gnathic: from cartilaginous rests (ant MX, condyle symphysis and coronoid process)
-‐ Ollier disease: multiple chondromas, usually unilateral
-‐ Maffucci’s syndrome: multiple chondromas and hemangiomas; phleboliths; skin macules
Chondromyxoid fibroma
-‐ Chr 6 abnormality. Rare in jaws (usually long bones)
-‐ Usually <30y, MD, pain and swelling
-‐ Histo: lobules of spindle or stellate cells with abundant myxoid or chondroid intercellular substance. Lobules separated by cellular tissue with spindle or round cells and giant cells
-‐ DDx: myxoid chrondrossarcoma
Synovial chondromatosis (chondrometaplasia)
-‐ Metaplastic nodules of cartilage in synovial membrane (usually large joints)
-‐ Sometimes secondary to other joint conditions (eg trauma, joint overuse)
-‐ Primary synovial chondromatosis: no identifiable etiologic factor
-‐ Stages: 1-‐foci arise in synovial lining; 2-‐foci increased and detach, material found in synovial membrane and joint; 3-‐cartilage found only in joint
-‐ May rarely affect TMJ (symptoms non-‐specific)
-‐ Loose bodies: round, irregular radiopacities in joint region (but no specific) on radiograph
-‐ Histo: nodules of cartilage within the synovium and loose in joint space (may ossify)
Desmoplastic fibroma
-‐ Bone counterpart of fibromatosis. Few cases assoc with tuberous sclerosis
-‐ Post MD (molar and angle-‐ascending area)
-‐ Histo: small fibroblasts and abundant collagen
Osteosarcoma
-‐ Excluding hematopoietic, most common malignancy of bone
-‐ Bimodal: 10-‐20 yo (period of bone growth) then 50+ (paget’s, previous RT)
-‐ Jaw osteosarcoma 33y vs 23y long bones. MX (inferior region) = MD (post).
-‐ Spiking of roots, sunburst, symmetrical widening of PDL (tumor infiltration)
-‐ Codman’s triangle: triangular elevation of the periosteum
-‐ Secondary osteosarcoma: irradiated bone, fibrous dysplasia, Paget’s disease and bone infarct
-‐ Long bones: male predilection; most before 20 y; spread is via bloodstream
Peripheral (juxtacortical) osteosarcoma
-‐ Parosteal: pedunculated, no elev of periosteum, spindle cells+bone, low grade
-‐ Periosteal: sessile, elev periosteum, primitive sarcoma with chondroid and osteoid, mid grade
Postirradiation sarcoma
-‐ Average 14y after RT, >7000 cGy
-‐ 50% ostesarcomas, 40% fibrosarcomas
Chondrosarcoma
-‐ Half as common as osteosarcoma and twice as Ewing sarcoma
-‐ Rare in jaws. MX, painless (vs ostesarc painful). > 50y (osteosarcs also younger)
-‐ 30% HN extra-‐osseous (larynx or soft tissue)
-‐ Often shows lobular pattern (periphery of lobules more immature)
-‐ Grades: 1-‐similar chondroma (look for binucleated chondrocytes); 2-‐ increased cellularity, matrix is myxoid; 3-‐highly cellular with spindle cells
-‐ 6 types: WD, myxoid, mesenchymal, clear cell, periosteal and dedifferentiated (WD chondros + fibrosarcoma-‐like)
Mesenchymal chondrosarcoma
-‐ Biphasic pattern (about 10% of all chondrosarcomas)
-‐ Most common in jaws, younger patients. 30% ST.
-‐ Histo: Spindle/round undifferentiated cells with HPC-‐like areas with stag-‐horn vessels
-‐ Cartilagenous component variable, usually low-‐grade and well-‐demarcated.
-‐ May show 11;22 translocation.
-‐ Cells are CD99+, cartilagenous component S100+
Chordoma
-‐ Malignant tumor that recapitulates notochord (arises from remnants of notochord)
-‐ 3 categories: spheno-‐occipital, sacrococcygeal (most common) and vertebral
-‐ Cranial area: clivus and paraselar most common location, usually in midline
-‐ Symptoms: headache and diplopia (6th nerve palsy)
-‐ Histo: lobular configuration with fibrous septa. Lobules consist of solid masses of tumor cells or pools of mucin with tumor cell.
-‐ Physaliferous cells: large cells with central nuclei and vacuolated and reticulated cytoplasm
-‐ Chondroid chordoma: contains hyaline-‐type cartilaginous tissue with tumor cells in lacunae
-‐ IHC: CK, EMA, S100 and NSE+
