Bread and Butter Bone Pathology
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1 Bread and Butter Bone Pathology NICOLE D. RIDDLE, MD RUFFOLO, HOOPER, AND ASSOC. / UNIVERSITY OF SOUTH FLORIDA Goals: Fundamentals of neoplastic bone pathology Bone Producing Cartilage Producing Miscellaneous Essential features of bone tumor imaging Importance to recognize one s diagnostic limitations Bone Tumors Are rare Pathologist may not accumulate enough experience Surgeons may not have specialized training Improper excisions Unfamiliarity with terminology Ignorance about the role of molecular studies 1
2 Bone Tumors cont Oncologists may not be familiar with clinical protocols and trials Radiologists may not be familiar with neoplastic bone radiology Initial biopsy is often very small Communication between surgeon and pathologist is key If in doubt.. SEND IT OUT! Clinical presentation: Age Symptoms Radiologic information: Size Bone Pattern Periosteal Reaction Location 2
3 Age Distribution Age group Most Common Benign Most Common Malignant 0-10 Simple bone cyst Ewingʼs sarcoma Leukemia Age Distribution Age group Most Common Benign Most Common Malignant Non-ossifying fibroma Osteosarcoma Simple bone cyst Ewingʼs sarcoma Aneurysmal bone cyst Adamantinoma Osteochondroma Osteoid osteoma Age Distribution Age Group Most Common Benign Most Common Malignant Enchondroma Chondrosarcoma Giant cell tumor Metastatic Tumors 3
4 Age Distribution Age Group Most Common Benign Most Common Malignant 40 and above Osteoma Metastatic tumors Enchondroma Myeloma Chondrosarcoma Osteosarcoma (Paget's ) Chordoma CENTRAL Simple Bone Cyst Enchondroma Fibrous Dysplasia ECCENTRIC Giant Cell Tumor Fibrous Cortical Defect Aneurismal Bone Cyst Chondromyxofibroma Osteoma BENIGN Narrow zone Transition Solid Periosteal Reaction Geographic Bone Destruction MALIGNANT Broken Periosteal Reaction Permative Bone Destruction Soft Tissue Mass Wide Zone Transition 4
5 Grade I Grade II Grade III IA IB IIA IIB IIIA IIIB IIIC Geographic With Sclerosis Geographic No Sclerosis Geographic Wide Zone Transition Changing Margin Moth Eaton Permeative Invisible 5
6 BONE FORMING TUMORS OSTEOID OSTEOMA OSTEOBLASTOMA OSTEOSARCOMA OSTEOID OSTEOMA Benign bone-forming tumor of limited growth potential that elicits a prominent reaction on adjacent bone Any age - 75% < 25; average : 19; rare >30 Male : Female = 2.2 : 1 Dull, progressive pain, worse at night, relieved by salicylates (70%) - nerve fibers, prostaglandin E2, prostacyclin PGI2 Pain may precede radiographic manifestations and may be referred to adjacent joints or bones 5%, painless (typically in the fingers) OSTEOID OSTEOMA Long bones, typically cortical Metaphysis and diaphysis - rarely epiphyseal Proximal femur > 50% (neck, inter-trochanteric), tibia Hand: Proximal and distal phalanges Foot: Metatarsal bones and calcaneus Very rare multicentricity Rarely intra-articular 10% in vertebrae: neural arc (scoliosis) 6
7 OSTEOID OSTEOMA Small, oval, cortical radio-lucency with variable mineralization Sclerosis and cortical reaction Nidus at the center 25% not evident on plain radiography CT ideal for diagnosis and surgical planning OSTEOID OSTEOMA Nidus Hemorrhage around the nidus Reactive sclerosis around the nidus OSTEOID OSTEOMA Round, oval, red, haphazardly arranged, trabeculated osteoid with variable mineralization (greatest at the center) in a background of fibrovascular tissue with occasional giant cells and surrounded by sclerosis that disappears when the nidus is removed NIDUS 7
8 OSTEOID OSTEOMA Woven bone Variable mineralization OSTEOBLASTOMA Benign bone-forming tumor similar to osteoid osteoma with potential for progressive growth (giant osteoid osteoma) M:F = 2:1 80% in first three decades (average: 20) Long bones: 38% (75% in diaphysis) Predilection for posterior vertebral column (65% purely dorsal) 43% in spine and sacrum scoliosis More than 2 cm: Osteoblastoma Less than 1 cm: Osteoid osteoma Between 1 and 2 cm: Indistinguishable OSTEOBLASTOMA Intense nocturnal pain is uncommon Neurological complaints in vertebral tumors Appendicular skeleton Lucent with variable ossification Well defined, sclerotic margins (50% of cases) Central nidus rarely seen In 20%, cortical destruction (confused with malignancy) Vertebrae Margin well defined (in 50%, sclerosis) In 15% malignancy is considered 8
9 OSTEOBLASTOMA Unlimited growth potential (2-12 cm) Soft tissue extension often with a calcified periosteal shell It frequently lacks the halo of osteoid osteoma Confused with giant cell tumor or sarcoma Some stop growing or even regress Aggressive destruction by secondary ABC (10%) OSTEOBLASTOMA OSTEOBLASTOMA 9
10 OSTEOBLASTOMA OSTEOBLASTOMA Osteoblastic rimming Mineralized trabeculae Lace-like osteoid Cartilaginous differentiation OSTEOSARCOMA Malignant tumor in which bone or osteoid are directly produced by tumor cells 35% of all sarcomas - second to myeloma Males: 58% - Females: 42% 80% in metaphysis of long bones most common, distal femur 46% in second decade - most between 15 and 25 Secondary to Paget s disease (older patients) or radiation therapy Pain may be intermittent, sometimes nocturnal, for weeks to months Swelling and pathologic fracture 10
11 OSTEOSARCOMA MEDULLARY CORTICAL SURFACE Parosteal Periosteal High Grade OSTEOSARCOMA MEDULLARY HIGH GRADE Osteogenic (osteoblastic, bone-rich) - 50% Chondroblastic (cartilage-rich) - 25% Fibroblastic (spindle cell-rich) 10% MFH-like Telangiectatic (ABC-like) Small-cell Epithelioid MEDULLARY LOW-GRADE Fibrous Dysplasia-like NOF-like CMF-like Chondroblastoma-like OSTEOSARCOMA Lytic, blastic or mixed (10%) Geographic, poorly demarcated Periosteal new bone formation (spiculation, cummulus cloud, Codman s triangle) Cortex erosion and soft tissue extension Variable mineralization on X-rays 11
12 OSTEOSARCOMA Codman s angle Spiculated, hair-on-end, mineralization OSTEOSARCOMA Cortex destruction Epiphyseal plate invasion Bone marrow spread (skip areas in 25% of cases) Frozen section of marrow margins: avoid Codman s triangle (non-neoplastic) Variable appearance: Soft, fleshy to firm, fibrous tumor with irregular ossification and various amounts of chondroid material and sclerosis OSTEOSARCOMA Anaplasia + Osteoid = Osteosarcoma 12
13 OSTEOSARCOMA OSTEOSARCOMA Invasion of Skeletal Muscle Necrosis Cortex Invasion Osteoid SURFACE OSTEOSARCOMA MEDULLARY CORTICAL SURFACE Parosteal Periosteal High Grade 13
14 PAROSTEAL OSTEOSARCOMA Well differentiated OS that arises on the bone surface and appears as a heavily mineralized mass Usually low grade Long duration Males 30%; Females 70% 80% between years (a decade older than conventional OS) Pain rare PAROSTEAL OSTEOSARCOMA Usually low grade, Long duration, Pain rare M 30%; F 70% String sign 80% trs (decade older than conv) 80% occur in posterior aspect of distal femur Inability to bend the knee Lobulated, densely mineralized: pasted on Broad attachment to intact, thickened cortex Intramedullary extension in 20% (CT, MRI) Large tumors may encircle the bone Dedifferentiation to HGS in 15% Intact cortex PAROSTEAL OSTEOSARCOMA 14
15 PAROSTEAL OSTEOSARCOMA Periosteal expansion WD Osteosarcoma Osteoid formation Chondroblastic component Cortex invasion Fibrosarcoma like component PAROSTEAL OSTEOSARCOMA Hypocellular fibroblastic stroma with no bone marrow Trabeculae parallel to each other Minimal atypia - Rare mitoses Cartilage at the surface may resemble osteochondroma (chondrocytes are mildly atypical and they are not arranged in columns) PERIOSTEAL OSTEOSARCOMA Moderately differentiated, predominantly chondroblastic surface OS with no medullary involvement M 55%; F 45% 85% around the knee Pain and swelling Symptoms for up to 24 months High grade osteosarcoma Diaphyseal saucer Codman s triangle common No intramedullary involvement Adjacent cortex is thickened 15
16 PERIOSTEAL OSTEOSARCOMA PERIOSTEAL OSTEOSARCOMA Abundant chondroid matrix with spicules of osteoid Spindle cells at the periphery (fine lacelike osteoid) Mild atypia in chondrocytes and spindle cells No intramedullary involvement HIGH GRADE SURFACE OSTEOSARCOMA M 78%; F 22% Warm, painful, erythema Most common in the femur Cortical destruction Periosteal new bone formation None or minimal intramedullary involvement Often chondroid matrix 16
17 HIGH GRADE SURFACE OSTEOSARCOMA CARTILAGE-FORMING TUMORS OSTEOCHONDROMA CHONDROBLASTOMA CHONDROMYXOID FIBROMA ENCHONDROMA PERIOSTEAL CHONDROMA MULTIPLE CHONDROMATA CHONDROSARCOMA OSTEOCHONDROMA Common (second to NOF) Pedunculated or sessile Metaphysis of long bones (limbs) 40% about the knee (lower femur, upper tibia, upper humerus) 1-2 % malignant transformation Corticomedullary continuity Metaphyseal based Growth points away from joint 17
18 OSTEOCHONDROMA OSTEOCHONDROMA Cartilaginous cap Bone marrow inside the tumor Cortex of the bone in continutiy with the cortex of the osteochondroma Broadening of bone OSTEOCHONDROMA The cap resembles endochondral ossification Cancellous bone underlies the cap Chondrocytes in cap are relatively normal 18
19 CHONDROBLASTOMA Almost always benign - Rarely, non-progressive lung mets M 59% - F 41% 60-70% in 2nd decade 95% < 25 years Epiphyseal, all bones 30% around the knee Lobulated and sharply demarcated 95% chondroid differentiation Ossification rare Secondary ABC in 1/3 CHONDROBLASTOMA Chondroblasts Giant cell CHONDROBLASTOMA Lace-like calcification between degenerated cells in 1/3 of tumors Chicken wire 19
20 CHONDROBLASTOMA Giant cells Moderate Atypia Hemosiderin ABC-like CHONDROBLASTOMA CHONDROMYXOID FIBROMA M 62%; F 38% Metaphysis of long bones It rarely involves the epiphysis 2/3 in long tubular bones - 1/3 in the tibia 20
21 CHONDROMYXOID FIBROMA CHONDROMYXOID FIBROMA Nodules of spindle/stellate cells in myxoid or chondroid stroma containing giant cells Well demarcated by either bone or connective tissue Small amount of fibrous tissue as narrow septa CHONDROMYXOID FIBROMA Hyaline cartilage is rare Mitoses are rare In 1/3 of cases, bizarre nuclei 10% necrosis 21
22 CHONDROMYXOID FIBROMA ENCHONDROMA Intramedullary neoplasm of mature hyaline cartilage Males 48%; Females 52% 55% in 2 nd to 4 th decades Bone cortex uninvolved Bone entrapment should not occur - No permeation Chondrocytes in lacunae with small, round regular nucleus in a bluish matrix Binucleation possible but rarely several cells in lacunae Even mineralization Histology depends on location: In the sternum, likely CHS In small bones, atypia is allowed ENCHONDROMA 22
23 ENCHONDROMA ENCHONDROMA LOBULARITY MILD ATYPIA ENCHONDROMA BENIGN OSSIFICATION Enchondral ossification: pop-corn; arcs and rings 23
24 ENCHONDROMA Pop-corn calcification ENCHONDROMA Confluent semitranslucent lobular masses of hyaline cartilage, rimmed by fibrous tissue or bone ENCHONDROMA Slightly more atypia allowed in small bones 24
25 CHONDROSARCOMA CHONDROSARCOMA M 60%; F 40% 65% 4 th to 6 th decades 2/3 in the trunk and upper extremities Pelvis (30%) Proximal femur (20%) Benign Expansile lesions displacing bone Hypocellular Solid chondroid matrix Malignant Permeation entrapping bony trabeculae Soft tissue extension Myxoid change Atypia, binucleation CHONDROSARCOMA Grade 2 Scallop Cortical Breakage 25
26 CHONDROSARCOMA CHONDROSARCOMA Metaphyseal, diaphyseal Scalloped cortex Bone expansion Cortical breakthrough Soft tissue extension Punctate, flocculant popcorn mineralization CHONDROSARCOMA SCALLOPING ATYPIA BONE INVASION CELL DEATH 26
27 CHONDROSARCOMA BONE INVASION CHONDROSARCOMA Necrotic foci often calcify and form osseous masses Small bones of hand and feet affected in syndromes (Ollier s, Mafucci s) Rare mitoses Rare sheets of spindle cells Tendency to higher grade with recurrence CHONDROSARCOMA Grade 1: small nuclei (>8 micron), binucleation, chondroid matrix, rare myxoid areas Grade 2: less matrix (more cellular), rare mitoses, large vesicular or hyperchromatic nuclei, often more than one cell per lacuna, necrosis, myxoid stroma Grade 3: greater cellularity and nuclear pleomorphism, absent chondroid matrix and prominent myxoid matrix, chondrocyte cords with grotesque shape, extensive necrosis, vesicular nuclei 5-10 times larger than normal 27
28 CHONDROSARCOMA GRADE 1 GRADE 2 GRADE 3 DEDIFFERENTIATED CHONDROSARCOMA 12% of chondrosarcomas Large and aggressive Calcification in 50% Extraosseous mass in 55% DEDIFFERENTIATED CHONDROSARCOMA 28
29 MISCELLANEOUS TUMORS OF BONE First two decades of life M:F = 3:1 Children: proximal humerus (62%), proximal femur (27%) Adults: calcaneus, ilium Solitary, intramedullary 30% proximal humerus 17% femur 11% proximal tibia Typically unilocular SIMPLE BONE CYST SIMPLE BONE CYST Bone protuberance with thin periosteal covering Thin cyst wall with few giant cells 10% cementum-like calcospherites (Liesegang s phenomenon) Prior fracture/hemorrhage with fibro-osseous repair (exuberant fibroblasts, osteoid, woven bone, hemosiderin, lymphocytes, cholesterol clefts) Fallen leaf sign 29
30 ANEURYSMAL BONE CYST Benign lesion with cyst-like walls Up to 50% are secondary to other lesions Fibrous dysplasia GCT Chondroblastoma Osteosarcoma Short duration, pain, swelling Slight female predominance Any bone ; Knee most common Metaphysis of long bones / Vertebrae (posterior, multiple in 50% of cases) ANEURYSMAL BONE CYST 85% < 20 years Long bones (53%), spine (15%) 85% with swelling +/- pain 20% with pathologic fracture Scoliosis or kyphosis (10% of spine cases) ANEURYSMAL BONE CYST Blood-filled spaces separated by septa with giant cells and osteoid Solid areas with spindle cells (prominent in the solid variant) Bony trabeculae with prominent osteoblasticrimming 30
31 SOLID ABC It lacks blood-filled spaces and cyst walls Blowout" evident on x-ray Exuberant spindle cell component Osteoid +/- woven bone; lacy chondroid Maturational areas Osteoclast-like giant cells METAPHYSEAL FIBROUS DEFECT Spindle cell proliferation that involves the cortex, or both the cortex and the medullary cavity, in the metaphysis of long bones of children. It tends to resolve spontaneously Explanation of terms: If only cortex is involved: Fibrous Cortical Defect If both cortex and medulla are involved: Non-Ossifying FIbroma Abundant xanthomatous cells: Fibroxanthoma Similar histology (adults) may be seen in Benign Fibrous Histiocytoma and GCT METAPHYSEAL FIBROUS DEFECT Clinical features First two decades Asymptomatic 30-40% of all children Imaging Metaphyseal, eccentric Soap bubble appearance 31
32 METAPHYSEAL FIBROUS DEFECT 80% between 20 and 50 y of age (98% after physeal closure) M:F = 1:1.3 Solitary, meta-epiphyseal 55% around the knee; 10% in distal radius, Vertebral body involvement (anterior) Elevated alkaline phosphatase Normal serum Ca ++ and PO = 4 2% metastasize GIANT CELL TUMOR Malignancy very rare Anaplastic transformation True malignant: < 6 m survival Epiphyseal, metaepiphyseal Intramedullary, eccentric Geographic destruction No host bone sclerosis GIANT CELL TUMOR Lack of ominous periosteal reaction Cortical erosion - A soft tissue mass may be present 32
33 GIANT CELL TUMOR GIANT CELL TUMOR Syncytial fusion of mononuclear cells into a giant cell GIANT CELL TUMOR More Spindly Foamy Histiocytes Bone Formation ABC Changes 33
34 GIANT CELL TUMOR FIBROUS DYSPLASIA Benign fibro-osseous proliferation Monostotic 6 times more common than polyostotic Clinical features: 70 % present with pain / limp Pathologic fracture Deformity shepherds crook Fracture McCune-Albright Syndrome Triad: Multifocal FD Café au lait spots coast of maine Precious puberty Endocrine abnormalities 2x malignant transformation risk Metaphyseal or diaphyseal Ground glass X-ray Cortical expansion, Scalloping Sclerotic, well defined margins Very hot on bone scan FIBROUS DYSPLASIA 34
35 FIBROUS DYSPLASIA FIBROUS DYSPLASIA No (Minimal) Osteoblastic Rimming Foamy Histiocytes Paucicellular Fibrous Areas Benign Cartilage OSTEOFIBROUS DYSPLASIA Middle third of tibia 2/3 below age 5 Pain uncommon Intracortical, lytic, eccentric Anterior bowing Histology similar to FD, but PROMINENT osteoblastic rimming 35
36 OSTEOFIBROUS DYSPLASIA Hopefully: Fundamentals of neoplastic bone pathology Bone Producing Cartilage Producing Miscellaneous Essential features of bone tumor imaging Importance to recognize one s diagnostic limitations Thank you Credit to Drs. Carlos Muro-Cacho and Douglas Letson for many of these images 36
37 Additional Material CHONDROBLASTIC OSTEOSARCOMA Bone production among chondroblastic areas, atypia, necrosis FIBROBLASTIC OSTEOSARCOMA Prominent fibrous component with focal osteoid 37
38 GIANT CELL OSTEOSARCOMA Prominent giant cell component malignant osteoid production SMALL CELL OSTEOSARCOMA Males 88% - Females 12% Pain in 2/3 of cases Swelling in 15% Symptoms: days to years Neurologic deficit if vertebra involved Metaphysis with epiphyseal involvement in 1/3 of cases Purely diaphyseal 15% Soft tissue mass in 60% of cases (25% mineralized) EPITHELIOID OS Epithelioid appearance Signet-ring, plasma cells 38
39 CHONDROBLASTOMA-LIKE OS Invasion of fat (bone marrow permeation) Coarse pattern of matrix calcification LOW-GRADE INTRAOSSEOUS OS M/F : 50/50 No specific signs (no swelling) Pain common Medullary extension to the end of the bone Trabeculated or sclerotic Periosteal new bone formation Soft tissue extension LOW-GRADE INTRAOSSEOUS OS 39
40 TELANGIECTATIC OS 3.5% of osteosarcomas Males: 66% - Females 34% Tender mass - often fracture Large, metaphyseal Lytic, poorly marginated Prominent medullary and cortical destruction Periosteal new bone formation common TELANGIECTATIC OS TELANGIECTATIC OS Spaces and septa like ABC Cells lining septa malignant Benign giant cells present Minimal osteoid 40
41 JAWBONES OS 6% of Osteosarcomas Young adults 50% Chondroblastic Peripheral spindle cells Central, poorly formed trabeculae PERIOSTEAL CHONDROMA 75% in second-third decades M:F = 2:1 Local swelling, Pain of long duration Appendicular skeleton 2/3 metaphysis and the remainder diaphysis PERIOSTEAL CHONDROMA Eccentric cortical lucent lesion Reactive periosteal bone Calcification Medulla uninvolved 41
42 PERIOSTEAL CHONDROMA Lobules of mature hyaline cartilage embedded under periosteum CLEAR CELL CHONDROSARCOMA M 70%; F 30% Third and fourth decades End of bones, extending to articular cartilage Lobulated growth pattern, capillary proliferation Slow-growing CLEAR CELL CHONDROSARCOMA Well-defined cellular borders Vesicular nucleus Prominent nucleoli Clear cytoplasm (glycogen) Difficult to be recognized as cartilaginous 42
43 CLEAR CELL CHONDROSARCOMA ADAMANTINOMA Low-grade malignancy with epithelial islands of unknown origin 50-75% in second and third decades 90% involved the tibia (diaphysis) Synchronous lesions in tibia and fibula Central to eccentric, elongated Well circumscribed Honeycomb Soft tissue mass possible ADAMANTINOMA 43
44 ADAMANTINOMA Bland nuclei with minimal or no atypia Mitoses from absent to 10/10 HPF Four histologic patterns: Spindle: Fibrosarcoa-like (spindle lesion in tibial cortex = adamantinoma; metastatic lesions to the tibia are uncommon) Basaloid: Basal-like cells palisading around stellate stroma Tubular Squamoid Oosteofibrous dyslasia-like Ewing sarcoma-like IHC - Strong positivity for pancytokeratin ADAMANTINOMA 44
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