Bone Tumor Pathology
Bone Tumor Pathology
Bone Tumor Pathology
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<strong>Bone</strong> <strong>Tumor</strong> <strong>Pathology</strong><br />
Carrie Y. Inwards, MD<br />
MMayo Cli Clinic i<br />
Rochester Rochester, MN
<strong>Bone</strong> <strong>Tumor</strong>s<br />
• Benign Benign, malignant, malignant or non-<br />
neoplastic<br />
• Primary, secondary, or<br />
metastatic<br />
CP1059536-1
<strong>Bone</strong> <strong>Tumor</strong>s<br />
Classification<br />
• Cl Classified ifi d according di tto cytology t l or<br />
products of the lesional cells<br />
• Chondroid or osteoid: Chondrosarcoma,<br />
osteosarcoma, etc<br />
• Fibrogenic: MFD, fibrosarcoma, etc<br />
• Notochord: Chordoma<br />
CP1059536-3
Cartilage <strong>Tumor</strong>s<br />
• Benign<br />
• Osteochondroma<br />
• Enchondroma<br />
• Ch Chondroblastoma<br />
d bl t<br />
• Chondromyxoid fibroma<br />
• Malignant<br />
• Chondrosarcoma
Osteochondroma<br />
• Benign outgrowth of cortical and<br />
medullary bone (“exostosis”)<br />
• 33% of benign bone tumors<br />
• 10% of all bone tumors<br />
• Majority ajo ty are a e solitary so ta y lesions es o s (spo (sporadic) ad c)<br />
• Multiple hereditary exostosis<br />
( (autosomal t l ddominant i t di disorder)<br />
d )<br />
CP1059536-4
Osteochondroma<br />
• 60% of patients p proximal humerus ><br />
proximal i l tibi tibia<br />
• Solitary y lesions uncommon in small<br />
bones<br />
CP1059536-6
Osteochondroma<br />
Radiographic Features<br />
• Cortex and medullary cavity continuous<br />
with the underlying bone<br />
• Often arise at the site of tendon<br />
insertions ( (direction of f growth along line<br />
of tendon)
Osteochondroma<br />
Gross <strong>Pathology</strong><br />
• Sessile or pedunculated<br />
• Thin, regular, blue/grey cap (usually < 2<br />
cm)<br />
• Underlying cancellous bone<br />
• May be associated with a bursa<br />
CP1059536-8
CP1059536-5
CP1059536-9
CP1059536-10
Osteochondroma<br />
Histologic Findings<br />
• Cartilage cap<br />
• Chondrocytes in lacunae arranged in<br />
clusters peripherally and in columns<br />
near base of cap cap, simulating normal<br />
epiphyseal plate<br />
• Stalk<br />
• Cancellous bone surrounded by fat<br />
and dbbone<br />
marrow
Stalk<br />
Cartilage Cap<br />
Osteochondroma<br />
CP1059536-11
Chondrocytes arranged in<br />
columns at base of<br />
cartilage cap<br />
Osteochondroma
Osteochondroma<br />
Differential Diagnosis<br />
• Parosteal osteosarcoma<br />
• Chondrosarcoma arising in<br />
osteochondroma<br />
• Bizzare parosteal osteochondromatous<br />
proliferation (Nora’s lesion)<br />
• HHeterotopic t t i ossification ifi ti<br />
• Subungual exostosis
Osteochondroma<br />
Treatment<br />
• Surgical excision if lesion is<br />
symptomatic<br />
y p
Enchondroma<br />
• Benign, g , intramedullary, y, hyaline y cartilage g<br />
tumor<br />
• 16% of benign bone tumors<br />
• 60% of pts are between 15 and 40 yr of age<br />
• 50% located in the small bones (hands, feet)<br />
• MMost t commonly l a solitary lit ttumor<br />
CP1059536-12
Multiple Enchondromas<br />
• Ollier disease<br />
• Multiple enchondromas involving the entire<br />
skeleton, half of the body, or one limb<br />
• Non-hereditary disorder<br />
• May show increased cellularity<br />
• Maffucci’s syndrome:<br />
• MMultiple lti l enchondromas h d with ith soft ft ti tissue<br />
hemangiomas<br />
Increased risk of de eloping<br />
• Increased risk of developing<br />
chondrosarcoma (~ 35%)
Enchondroma<br />
Radiographic Features<br />
• Intramedullary area of rarifaction<br />
• Variable mineralization<br />
• Long bones:<br />
• Usually no cortical erosion or destruction<br />
• Small bones:<br />
• Cortex may be thinned and expanded
CP1059536-14
CP1059536-16
Enchondroma<br />
Gross Features<br />
• Usually curetted lobulated fragments of<br />
grey/white g y tissue<br />
• No significant myxoid or mucoid quality
Enchondroma<br />
Histologic Features<br />
• Long and flat bones<br />
• Hypocellular; occasional moderately<br />
cellular areas<br />
• Bland cytologic y g features<br />
• Occasionally degenerative changes<br />
• Small bones<br />
• Moderately cellular, increase in nuclear<br />
size size, variable myxoid change<br />
• No invasion of medullary or cortical bone
Enchondroma abutting cortical bone – no evidence of invasion
Enchondroma – lobules of cartilage filling the marrow
Enchondroma in a long bone: hypocellular; no atypia
Enchondroma in a small bone: increased cellularity<br />
and nuclear enlargement
Enchondroma<br />
Differential Diagnosis<br />
• Chondrosarcoma<br />
• Overall increased cellularity &<br />
cytologic atypia<br />
• Frequent permeation of cortical bone bone,<br />
entrapment of host bone<br />
• MMore aggressive i radiographic di hi<br />
features
• Curettage/grafting<br />
Enchondroma<br />
Treatment
Chondroblastoma<br />
• 1.4% of primary bone tumors<br />
• 5% of benign bone tumors<br />
• 60% involve long tubular bones<br />
• Di Distal t l ffemur > proximal i l hhumerus<br />
><br />
proximal tibia<br />
• 60% in second decade of life
Chondroblastoma<br />
Radiographic Features<br />
• Benign radiographic<br />
appearance<br />
• Lucent defect at the end<br />
of the bone<br />
• 40% confined to the<br />
epiphysis<br />
• 60% in epiphysis and<br />
metaphysis<br />
• 50% have a sclerotic rim
Chondroblastoma<br />
Histologic Features<br />
• Mononuclear cells with well-defined<br />
cytoplasmic y p boundaries, , oval-to<br />
elongated nucleus, eosinophilic<br />
cytoplasm y p<br />
• 95% contain cartilage matrix (usually<br />
pink)<br />
• 35% contain lace-like (“chicken wire”)<br />
calcification<br />
• Multinucleated giant cells common
Chondroblastoma: lobules of pink chondroid matrix<br />
surrounded by mononuclear cells
Chondroblastoma: cells with oval nuclei, eosinophilic cytoplasm,<br />
well defined cytoplasmic boundaries
Chondroblastoma: lobule of pink – blue chondroid matrix and<br />
multinucleated giant cells
Chondroblastoma with chunky (left) and “chicken wire” (right)<br />
calcification
Chondroblastoma<br />
• Differential Diagnosis<br />
• Giant cell tumor<br />
• Chondromyxoid fibroma<br />
• OOsteosarcoma t<br />
• Treatment<br />
• Curettage and bone graft
Chondromyxoid Fibroma<br />
• 0.5% of bone tumors<br />
• 11.6% 6% of benign bone tumors<br />
• Peak incidence in second and third<br />
decades<br />
• 45% occur in the long bones<br />
• Proximal tibia > distal femur<br />
• Flat bones: ilium and ribs<br />
• 30% in hands and feet
Chondromyxoid Fibroma<br />
Radiographic Features<br />
• Benign appearance<br />
• Usually y<br />
metaphyseal<br />
• Eccentrically located<br />
• Circumscribed<br />
• Scalloped p<br />
appearance with<br />
sclerotic rim
Chondromyxoid Fibroma<br />
Histologic Features<br />
• Lobulated growth pattern<br />
• Macrolobules or microlobules<br />
• Cells with small oval to spindle<br />
shaped nuclei and pink cytoplasmic<br />
extensions<br />
• CCellular ll l proliferation lif ti of f oval l tto spindle i dl<br />
shaped cells and multinucleated giant<br />
cells ll surround d llobules b l
Chondromyxoid fibroma: macrolobular growth pattern
Chondromyxoid fibroma: Microlobular growth pattern
Chondromyxoid fibroma: microlobular growth pattern
Chondromyxoid fibroma: cells with small nuclei and cytoplasmic<br />
extensions
Chondromyxoid Fibroma<br />
• Differential diagnosis<br />
• Chondroblastoma<br />
• Chondrosarcoma<br />
• TTreatment t t<br />
• Curettage
Chondrosarcoma<br />
• Conventional chondrosarcoma<br />
• Dedifferentiated chondrosarcoma<br />
• Clear Cell chondrosarcoma<br />
• MMesenchymal h l chondrosarcoma<br />
h d
Chondrosarcoma<br />
• Males > females<br />
• 60% in 4th to 6th 60% in 4 to 6 decades of life<br />
• Two thirds located in pelvic and<br />
shoulder girdles and upper ends of the<br />
femur and humerus<br />
• < 3% distal di t l to t wrist i t and d ankle<br />
kl
Chondrosarcoma<br />
Radiographic Features<br />
• Usually large (ave. size 9.5 cm)<br />
• 75% are mineralized<br />
• Poorly marginated<br />
• 85% show h cortical ti l abnormalities<br />
b liti<br />
• Endosteal scalloping, cortical<br />
destruction, expansion of the bone<br />
• 40% with soft tissue mass
CP1059536-21
Chondrosarcoma arising secondary in enchondroma (Ollier<br />
Disease)
Chondrosarcoma<br />
Gross Features<br />
• Lobulated, pale<br />
blue/white<br />
• Solid or partially cystic<br />
• Myxoid change<br />
common<br />
• Degenerative change<br />
and necrosis<br />
• Permeative
CP1059536-23
CP1059536-25
Chondrosarcoma<br />
Histologic Features<br />
• Hypercellular, nuclear enlargement and<br />
hyperchromasia<br />
• Permeation of cortical and medullary<br />
bone<br />
• Liquifactive myxoid change in matrix<br />
• Small bones: permeation required<br />
• Grades 1, 2, & 3
Chondrosarcoma: malignant cartilage permeating between host<br />
bone<br />
CP1059536-29
Chondrosarcoma: hypercellular and nuclear atypia
Chondrosarcoma: permeative growth pattern
Chondrosarcoma: myxoid change in the matrix
Grade 1 Chondrosarcoma
Grade 2 Chondrosarcoma
Grade 3 Chondrosarcoma
Chondrosarcoma in a small bone permeating into<br />
soft tissue
Chondrosarcoma<br />
Treatment<br />
• Surgery: wide resection<br />
• Not responsive to chemotherapy and<br />
radiation
Chondrosarcoma of Long <strong>Bone</strong>s,<br />
Shoulder Girdle and Pelvis<br />
% with<br />
metastasis<br />
Survival Free of Metastasis<br />
100<br />
80<br />
60<br />
metastasis Grade Grade 2 + 3<br />
40<br />
20<br />
0<br />
Grade Grade 1<br />
0 2 4 6 8 10 12 14 16 18 20<br />
Years from Mayo diagnosis<br />
CP1059536-35
Dedifferentiated<br />
Chondrosarcoma<br />
• Occurs in 2 settings<br />
• De novo<br />
• In recurrent tumors<br />
• Old Older adults d lt ( (a ddecade d older ld th than<br />
conventional chondrosarcoma)<br />
• Pelvis and shoulder girdle most<br />
common sites
Dedifferentiated Chondrosarcoma<br />
Radiographic Features<br />
• Oftentimes suggests<br />
dedifferentiation<br />
• Central portion has<br />
features of a<br />
cartilage til ttumor<br />
• Cortical and soft<br />
ti tissue portions ti<br />
usually look more<br />
aggressive
Dedifferentiated Chondrosarcoma
Dedifferentiated Chondrosarcoma<br />
• Blue/grey cartilage<br />
tumor juxtaposed to<br />
a fleshy, tan/white<br />
sarcomatous tumor<br />
• VVariable i bl amounts t of f<br />
2 components<br />
• CCareful f l sampling!<br />
li !<br />
Gross Features
Dedifferentiated Chondrosarcoma<br />
Histologic Features<br />
• Bimorphic pattern<br />
• Low-grade Low grade chondrosarcoma<br />
juxtaposed to a high grade sarcoma<br />
• High grade sarcoma<br />
• Osteosarcoma, high grade spindle<br />
cell ll sarcoma, pleomorphic l hi<br />
undifferentiated sarcoma
Dedifferentiated Chondrosarcoma: low-grade malignant<br />
cartilage (left); high-grade osteosarcoma (right)
Dedifferentiated Chondrosacoma<br />
• Treatment<br />
• En bloc resection<br />
• +/- chemotherapy<br />
• PPrognosis i<br />
• Worse than conventional<br />
chondrosarcoma<br />
• 5 year y<br />
survival 10%
Clear Cell Chondrosarcoma<br />
• Extremely uncommon<br />
• Tends to involve the ends of the long<br />
bones (proximal femur and humerus)<br />
• Male predilection<br />
• 4th and 5th decades of life
Clear Cell Chondrosarcoma<br />
Radiographic Features<br />
• Lytic, extending to<br />
the end of the<br />
bone<br />
• Occasionally has<br />
a benign<br />
appearance<br />
•
Clear Cell Chondrosarcoma<br />
Histologic Features<br />
• Lobulated growth pattern<br />
• <strong>Tumor</strong> cells have distinct cytoplasmic<br />
boundaries, central nucleus with<br />
prominent nucleolus, nucleolus clear cytoplasm<br />
• Trabeculae of woven bone commonly<br />
present<br />
• 50% of tumors contain nodules of<br />
conventional ti l chondrosarcoma<br />
h d
Clear cell chondrosarcoma: clear cells and hyaline cartilage
Clear cell chondrosarcoma: cells with clear cytoplasm and<br />
multinucleated giant cells
Clear cell chondrosarcoma
Clear Cell Chondrosacoma<br />
Differential Diagnosis<br />
• Chondroblastoma<br />
• Osteoblastoma<br />
• Osteosarcoma
Mesenchymal Chondrosarcoma<br />
• 2/3 in bone; 1/3 in soft tissue<br />
• 50% in 2nd and 3rd 50% in 2 and 3 decades<br />
• Jaw bones common site<br />
• Ili Ilium, spine, i ribs<br />
ib
Mesenchymal Chondrosarcoma<br />
• Malignant radiographic appearance<br />
• Histologic features<br />
• Well differentiated hyaline cartilage<br />
merging or juxtaposed with highgrade<br />
small blue cell component
Malignant cartilage<br />
Small blue cells<br />
Mesenchymal Chondrosarcoma
<strong>Bone</strong>-Forming <strong>Tumor</strong>s<br />
• Benign<br />
• Osteoid osteoma<br />
• Osteoblastoma<br />
• MMalignant li t<br />
• Osteosarcoma
Osteoid Osteoma<br />
• Size < 1.5 cm<br />
• Most common in adolescents and<br />
young adults<br />
• Three fourths of patients are between<br />
5 and 24 yrs<br />
• PPainful; i f l relieved li d with ith NSAID’s NSAID’<br />
• Most common sites is the proximal<br />
femur
Osteoid Osteoma<br />
Radiographic Findings<br />
• Sclerosis and<br />
new bone<br />
surround the<br />
lesion<br />
• Small round nidus<br />
in cortex<br />
• CT helpful in<br />
identifying the<br />
nidus
• Well demarctated<br />
red/brown nidus<br />
• Surrounding<br />
sclerotic l ti or<br />
cortical bone<br />
Osteoid Osteoma<br />
Gross Features<br />
CP1059536-66
Osteoid Osteoma<br />
Histologic Features<br />
• Irregular trabeculae of woven bone<br />
surrounded by y loose fibrovascular<br />
stroma<br />
• Multinucleated giant cells common<br />
• Nidus sharply demarcated from<br />
surrounding bone
Nidus<br />
Osteoid osteoma: central nidus surrounded by trabeculae of bone
Osteoid osteoma: nidus with woven bone rimmed by osteoblasts
Osteoid Osteoma<br />
Treatment<br />
• Radiofrequency ablation<br />
• Surgical excision<br />
• Histologic confirmation of nidus
Osteoblastoma<br />
• Same histologic features as osteoid<br />
osteoma<br />
• > 2 cm<br />
• 75% of patients are under 25 yrs of age<br />
• Long bones > spine (body/dorsal<br />
elements) l t ) > jawbones<br />
j b
Osteoblastoma<br />
Radiographic Features<br />
• Variable and nonspecific<br />
p<br />
• 25% simulate<br />
malignancy
• Tan/red-brown,<br />
friable<br />
• Well demarcated<br />
Osteoblastoma<br />
Gross Features
Osteoblastoma: trabeculae of woven bone surrounded<br />
by fibrovascular tissue
Osteoblastoma: woven bone, osteoblasts, fibrovascular stroma
Osteoblastoma: solid areas of bone production
Osteoblastoma<br />
Differential Diagnosis<br />
• Osteosarcoma<br />
• Can be very difficult to make the<br />
distinction<br />
• Osteoid osteoma<br />
• ABC<br />
• Giant cell tumor
Osteosarcoma<br />
• Medullary<br />
• Conventional osteosarcoma<br />
• Surface<br />
• PParosteal t l osteosarcoma<br />
t<br />
• Periosteal osteosarcoma<br />
• High grade surface osteosarcoma
Osteosarcoma<br />
• Second most common malignant bone<br />
tumor<br />
• Mayo Clinic<br />
• 23% of primary bone tumors<br />
• 30% of primary p y malignant g<br />
tumors
Osteosarcoma<br />
• 85% before 30 years of age<br />
• Distal femur > proximal tibia > proximal<br />
humerus > proximal p femur<br />
• Metaphyseal region of the long bones
Osteosarcoma<br />
Radiographic Features<br />
• Aggressive,<br />
destructive features<br />
• “Codman’s triangle”<br />
• Lytic Lytic, sclerotic<br />
• MRI and CT aid in<br />
evaluating l ti extent t t of f<br />
tumor
CP1059536-43
CP1059536-48
CP1059536-55
Chondroblastic Osteosarcoma<br />
CP1059536-53
Osteosarcoma<br />
Histologic Subtypes<br />
• Osteoblastic, chondroblastic,<br />
fibroblastic fibroblastic, telangiectatic telangiectatic, low low-grade grade<br />
central, giant cell rich, small cell<br />
• 85% % are high grade
Osteoblastic Osteosarcoma: permeating between host trabeculae
Osteoblastic Osteosarcoma: malignant osteoid in a lace-like<br />
pattern surrounding anaplastic tumor cells<br />
CP1059536-50
Chondroblastic Osteosarcoma: malignant osteoid and cartilage
Fibroblastic Osteosarcoma: malignant spindle cell stroma<br />
and bone<br />
CP1059536-56
Telangiectatic Osteosarcoma: fragments of cyst wall<br />
containing pleomorphic tumor cells<br />
CP1059536-49
Osteosarcoma<br />
Treatment<br />
• Preoperative chemotherapy<br />
• Wide surgical resection<br />
• Postoperative chemotherapy
Fig 1. Event-free survival (EFS) and overall survival for<br />
patients newly diagnosed with osteosarcoma without<br />
clinically detectable metastatic disease<br />
Copyright Meyers, © American P. Society A. et of Clinical al. Oncology J Clin Oncol; 26:633-638 2008
OGS: Histologic % Necrosis s/p<br />
Neoadjuvant Chemotherapy<br />
• Important prognostic indicator<br />
• Huvos grading system<br />
• Grade 1: 90% necrosis: Good prognosis<br />
• < 90% necrosis: Poorer prognosis
Necrotic osteosarcoma following neoadjuvant chemotherapy
Low-Grade Osteosarcoma<br />
• Low-grade central (intramedullary)<br />
• Extremely rare<br />
• Radiographs show areas with<br />
aggressive features<br />
• Parosteal osteosarcoma
Parosteal Osteosarcoma<br />
• 4% of all osteosarcomas<br />
• Most common in young adults<br />
• Distal femur > proximal tibia > proximal<br />
humerus<br />
• posterior cortex of the distal femoral<br />
metaphysis t h i most t common site it<br />
• Treatment is wide resection without<br />
chemotherapy
Parosteal Osteosarcoma<br />
Radiographic Features<br />
• Heavily mineralized mass attached by a<br />
broad base to the underlying y g cortex<br />
• CT and MRI helpful in identifying<br />
whether there is medullary involvement
Parosteal Osteosarcoma<br />
Histologic Features<br />
• Well formed trabeculae of bone<br />
• Spindle cells with minimal atypia<br />
• Cartilaginous differentiation in about half<br />
of tumors; occasionally in a “cap” cap<br />
• 15% contain a high-grade sarcoma<br />
(d (dedifferentiated diff ti t d parosteal t l<br />
osteosarcoma)
Parosteal osteosarcoma: long trabeculae of bone (left)<br />
surrounded by spindle cell stroma with minimal atypia
Periosteal Osteosarcoma<br />
• Chondroblastic, moderately<br />
differentiated osteosarcoma on the<br />
surface of bone<br />
• 11.5% 5% of osteosarcomas<br />
• Children and adolescents<br />
• Di Diaphysis h i of f ffemur and d tibi tibia
Periosteal Osteosarcoma: histologically chondroblastic<br />
osteosarcoma (right)
Fibrogenic <strong>Tumor</strong>s<br />
• Fibrous dysplasia<br />
• Metaphyseal fibrous defect (non- (non<br />
ossifying fibroma)
Fibrous Dysplasia<br />
• Non-familial somatic mutation<br />
• Biology driven by activating oncogenic<br />
mutations of GNAS1 gene<br />
• Monostotic (80%) or polyostotic (20%)
Fibrous Dysplasia<br />
• McCune Albright Syndrome<br />
• 3% of patients<br />
• Polyostotic fibrous dysplasia<br />
• Endocrine abnormalities<br />
• Cutaneous pigmentation<br />
• Mazabraud’s Mazabraud s syndrome<br />
• Very rare<br />
• Fib Fibrous ddysplasia l i<br />
• Soft tissue myxoma
Fibrous Dysplasia<br />
• 75% diagnosed before 30 yrs of age<br />
• Femoral neck is the most common site<br />
• 1/3 in the craniofacial bones, 1/3 in the<br />
femur or tibia, and 20% in the ribs
Fibrous Dysplasia<br />
Radiographic Features<br />
• Well defined zone<br />
of rarefaction<br />
• Sclerotic rim<br />
• Mineralization:<br />
“ground glass”<br />
appearance
CP1059536-81
CP1059536-79
CP1059536-80
Fibrous Dysplasia<br />
Histologic Features<br />
• Irregular spicules of<br />
woven bone<br />
• Bland spindle cells<br />
• Occasionally foam<br />
cells, myxoid<br />
change change, fibrosis
Fibrous Dysplasia
Fibrous Dysplasia<br />
CP1059536-83
Fibrous Dysplasia<br />
Treatment<br />
• Observation if asymptomatic<br />
• Curettage and grafting<br />
• Resection in some cases<br />
• LLocal l recurrence iis possible ibl<br />
• Polyostotic may be progressive
Metaphyseal Fibrous Defect<br />
• Also known as non-ossifying fibroma<br />
• Cortex or cortex and medullary cavity<br />
• 80% in the distal femur, distal tibia, and<br />
proximal tibia<br />
• Seen in as many as 35% of children
Metaphyseal Fibrous Defect<br />
Radiographic Features<br />
• Metaphyseal,<br />
eccentric<br />
• Sclerotic margin margin,<br />
circumscribed<br />
• Often diagnosed<br />
by x-ray alone
CP1059536-92
Metaphyseal Fibrous Defect<br />
Histologic Features<br />
• Plump spindle cells in a loose storiform<br />
pattern p<br />
• Multinucleated giant cells, foam cells,<br />
chronic inflammation<br />
• Mitotic activity
Metaphyseal fibrous defect: hypercellular fibrogenic stroma,<br />
multinucleated giant cells
Metaphyseal Fibrous Defect<br />
CP1059536-93
Metaphyseal Fibrous Defect<br />
• Most are small and may regress<br />
spontaneously<br />
p y<br />
• Symptomatic, large, or atypical lesions<br />
are biopsied and treated surgically
Ewing Sarcoma<br />
• Fourth most common primary tumor of<br />
bone<br />
• Male predilection<br />
• 75% in the first 2 decades of life<br />
• 60% in pelvic girdle and lower<br />
extremities t iti<br />
• Femur > ilium > fibula
Ewing Sarcoma<br />
Radiographic Features<br />
• Permeative,<br />
destructive, poorly<br />
defined margins<br />
• Periosteal new bone<br />
fformation ti “onion “ i<br />
skin” appearance<br />
• Di Diaphysis h i &<br />
metaphysis
Ewing Sarcoma<br />
Histologic Features<br />
• Small, round cell malignancy<br />
• Sheet-like Sheet like growth pattern in bone<br />
marrow; lobular or fillagree in soft tissue<br />
• Oval or round nuclei surrounded by<br />
clear or indistinct eosinophilic cytoplasm
Ewing Sarcoma<br />
Histologic Subtypes<br />
• Classic / conventional / typical: ~ 70%<br />
• Pi Primitive iti neuroectodermal t d lttumor<br />
(PNET): ~ 15%<br />
• Atypical: ~ 15 – 20%
Ewing Sarcoma<br />
Histologic Subtypes<br />
• Morphologic variation<br />
• Identical immunohistochemical and<br />
genetic features
Conventional Ewing Sarcoma: small blue cells with scant cytoplasm
Atypical Ewing Sarcoma: more cytologic variability
PNET: rosette formation
Ewing Sarcoma<br />
Immunohistochemistry<br />
• CD99 is the most helpful marker<br />
• SSensitive; iti not t 100% specific ifi<br />
• CD99: 95%<br />
• Keratin: 32%<br />
• FLI-1: FLI 1: 94%
Ewing Sarcoma<br />
Genetics<br />
• Most common translocation and fusion<br />
genes g<br />
• t(11;22)(q24;q12) EWSR1-FLI1 (95%)<br />
• t(21;22)(q22;q12) EWSR1 EWSR1-ERG ERG (5%)<br />
• Others (
Ewing Sarcoma<br />
Differential Diagnosis<br />
• Primary consideration is lymphoma<br />
• Panel of immunostains is essential<br />
• T and B- cell markers: lymphoma<br />
• CD99 positive: iti EEwing i sarcoma and d<br />
lymphoblastic lymphoma
• Treatment<br />
Ewing Sarcoma<br />
• Neo-adjuvant chemotherapy<br />
• Wide resection<br />
• Adjuvant j chemotherapy py<br />
• +/- radiation<br />
• Histologic response to neo neo-adjuvant adjuvant<br />
chemotherapy<br />
• IImportant t t predictor di t of f survival<br />
i l
Ewing Sarcoma<br />
Prognosis<br />
• Grier et al NEJM; Feb 2003<br />
• 5 year event free survival: 70%<br />
• Overall survival: 72%<br />
• Child Children’s ’ oncology l group (COG): (COG)<br />
every-two week vs every-3-week<br />
chemotherapy h th cycles l show h an iimproved d<br />
(90%) overall survival
Ewing Sarcoma<br />
• Poor prognostic factors<br />
• Older age (>17 yrs)<br />
• Pelvic tumor<br />
• LLarge t tumor ( (>8 8 cm) )<br />
• Metastatic disease
Giant Cell <strong>Tumor</strong><br />
• BBenign, i llocally ll aggressive i<br />
• 20% of benign bone tumors<br />
• Majority are solitary; may be multiple<br />
• Most common in 3 to 5th decades<br />
• Female predilection
Giant Cell <strong>Tumor</strong><br />
• Most common in the end (epiphysis) of<br />
the long g bones<br />
• Distal femur > proximal tibia > distal<br />
radius > sacrum<br />
• Anterior elements more common when<br />
located in the mobile spine
Giant Cell <strong>Tumor</strong><br />
Radiographic Features<br />
• Eccentric, purely lytic,<br />
end of bone<br />
• Cortical destruction,<br />
soft tissue mass with<br />
shell of bone<br />
• One fourth look<br />
aggressive
CP1059536-123
CP1059536-127
Giant Cell <strong>Tumor</strong><br />
Histologic Findings<br />
• Numerous multinucleated giant cells<br />
scattered throughout g the tumor<br />
• Mononuclear cells with round to oval<br />
nuclei and eosinophilic cytoplasm<br />
• Mitotic activity<br />
• FFoam cells, ll reactive ti new bbone,<br />
occasional spindle cell areas,<br />
secondary d ABC
Giant Cell <strong>Tumor</strong>: numerous multinucleated giant cells
Giant cell tumor: stromal cells resemble cells in multinucleated<br />
giant cells
Giant cell tumor<br />
CP1059536-125
Giant cell tumor: spindle-shaped and oval-shaped stromal cells
Giant Cell <strong>Tumor</strong><br />
necrosis
Giant Cell <strong>Tumor</strong><br />
Treatment<br />
• Curettage if the joint surfaces can be<br />
saved<br />
• Resection/reconstruction if joint<br />
surfaces can not be saved<br />
• Occasionally chemical cautery or<br />
cryosurgery
Aneurysmal <strong>Bone</strong> Cyst<br />
• May arise primary or secondarily in<br />
other tumors (most ( commonly y benign g<br />
tumors)<br />
• Most common in first and second<br />
decades of life; 50% in second decade<br />
• Most common sites are distal femur and<br />
proximal tibia; usually in the metaphysis<br />
• IIn the th spine, i the th posterior t i elements l t are<br />
most commonly affected
Aneurysmal <strong>Bone</strong> Cyst<br />
Radiographic Findings<br />
• Lucency in the<br />
metaphysis of long<br />
bones<br />
• May be eccentric,<br />
central, t l cortical, ti l or<br />
surface of bone<br />
• CCortex t may be b<br />
destroyed<br />
• Fluid Fluid-fluid fluid levels<br />
common
• Red-brown<br />
Aneurysmal <strong>Bone</strong> Cyst<br />
• Solid or cystic<br />
Gross Features
Aneurysmal <strong>Bone</strong> Cyst<br />
Histologic Findings<br />
• Multiple cystic spaces separated by<br />
septa; p ; occasionally y “solid”<br />
• Fibrous septa composed of spindle cells<br />
without atypia, atypia mitotic activity activity,<br />
multinucleated giant cells; no<br />
endothelial lining<br />
• Osteoid and bony matrix (woven bone)<br />
may be present<br />
• Calcification frequently seen
ABC with cystic spaces surrounded by cellular septa
ABC: loose fibroblastic stroma of cyst wall, no cytologic<br />
atypia, multinucleated giant cells
Solid area of ABC with reactive bone and fibrous stroma
Anerurysmal <strong>Bone</strong> Cyst<br />
• Differential Diagnosis<br />
• Telangiectatic osteosarcoma<br />
• Giant cell tumor<br />
• TTreatment t t<br />
• Curettage<br />
• Occasionally resection for large<br />
lesions
Unicameral <strong>Bone</strong> Cyst<br />
• Also known as simple cyst<br />
• Majority of patients are in the first two<br />
decades of life<br />
• Pathologic fractures common<br />
• Proximal humerus and proximal femur<br />
are most t common sites<br />
it
Unicameral <strong>Bone</strong> Cyst<br />
Radiographic Findings<br />
• Located centrally in<br />
the medullary cavity<br />
abutting the<br />
epiphyseal plate<br />
• NNo wider id th than<br />
epiphyseal plate<br />
• Thi Thinned, d bbut t iintact t t<br />
cortex<br />
• Trabeculation
Unicameral <strong>Bone</strong> Cyst<br />
Histologic Findings<br />
• Cyst wall fragments with bland spindle<br />
cells admixed with fragments g of bone<br />
• Irregular masses of degenerating fibrin<br />
that occasionally become calcified
UBC: fragments of bland cyst wall and bone
UBC containing eosinophilic fibrin
Unicameral <strong>Bone</strong> Cyst<br />
Treatment<br />
• Most are aspirated and injected with<br />
methylprednisolone<br />
yp<br />
• Occasionally curetted
Chordoma<br />
• Malignant tumor arising from notochord<br />
remnants<br />
• 6 % of malignant bone tumors<br />
• Males > females (2:1)<br />
• Most patients in the 5th to 7th decades<br />
• Patients with base of skull lesions<br />
generally a decade younger
Chordoma<br />
• Anatomic location<br />
• Sacrum: 50%<br />
• Base of skull: 37%<br />
• MMobile bil spine: i 13%
Chordoma<br />
Radiographic Findings<br />
• Often difficult to see in plain radiographs<br />
• CT & MRI most helpful in delineating<br />
the tumor<br />
• Lytic Lytic, destructive destructive, frequent soft tissue<br />
mass
• Lobulated<br />
• Gray-tan Gray tan, red- red<br />
brown, glistening,<br />
translucent<br />
Chordoma<br />
Gross Findings
Chordoma<br />
Histologic Findings<br />
• Lobules separated by fibrous septa<br />
• Cords and nests of tumors cells in a<br />
pale blue myxoid background<br />
• Round nuclei with central nucleoli<br />
• Eosinophilic or clear cytoplasm with<br />
prominent i t iintracytoplasmic t t l i<br />
vacuolization (physaliphorous cell)<br />
• Chondroid chordoma
Chordoma<br />
Immunohistochemical Stains<br />
• Keratin positive<br />
• EMA positive iti<br />
• Brachyury positive
Chordoma: lobulated growth pattern
Chordoma: cells with round nuclei & vacuolated cytoplasm<br />
arranged in cords
Metastatic <strong>Bone</strong> <strong>Tumor</strong>s<br />
• More common than primary bone<br />
tumors; ; carcinoma most common type yp<br />
• Adults: 80% are from lung, kidney,<br />
breast breast, prostate<br />
• Children: neuroblastoma, Wilm’s, OGS,<br />
Ewing’s Ewing s, rhabdomyosarcoma<br />
• Spine, pelvis, ribs, skull, proximal long<br />
bones
Metastatic <strong>Bone</strong> <strong>Tumor</strong>s<br />
Radiographic Features<br />
• Lytic: kidney, GI,<br />
thyroid, y ,<br />
melanoma<br />
• Blastic: prostate<br />
• Both: breast, lung
CP1059536-114
CP1059536-113
Metastatic adenocarcinoma Metastatic squamous cell CP1059536-110 ca
Metastatic Breast Carcinoma<br />
CP1059536-116
Metastatic Renal Cell Carcinoma<br />
CP1059536-118
<strong>Bone</strong> <strong>Tumor</strong>s<br />
Conclusion<br />
• Care of the patient requires a<br />
multidisciplinary approach<br />
• Pathologist<br />
• RRadiologist di l i t<br />
• Orthopedic surgeon<br />
• Medical oncologist<br />
• Radiation oncologist
Question #1
Question #1<br />
• The most likely anatomic site for this tumor<br />
would be:<br />
• Sacrum<br />
• Epiphysis of the femur<br />
• Metaphysis of the femur<br />
• Posterior vertebrae<br />
• Ilium
Question #2
Question #2<br />
• All but one of the following are false<br />
about this tumor except: p<br />
• It is most commonly seen in young<br />
adults<br />
• It is responsive to chemotherapy<br />
• It commonly l involves i l th the small ll bbones<br />
• It is graded on a scale of 1 to 3
Question #3
Question #3<br />
• The most effective treatment of this<br />
tumor is:<br />
• Surgery alone<br />
• Curettage<br />
• Surgery and chemotherapy<br />
• Radiation and surgery
Question #4
Question #4<br />
• This tumor:<br />
• Most commonly occurs in the 5th to 6th Most commonly occurs in the 5 to 6<br />
decades of life<br />
• Rarely occurs in the small bones<br />
• Contains a macro or micro lobular<br />
growth th pattern tt<br />
• Is the most common benign tumor in<br />
children
Question Q<br />
#5
Question #5<br />
• A tumor this these histologic features:<br />
• Would be consistent with a periosteal<br />
osteosarcoma<br />
• Would be consistent with a parosteal<br />
osteosarcoma<br />
• IIs most t commonly l seen in i th the pelvic l i<br />
bones<br />
• Frequently contains a secondary<br />
aneurysmal bone cyst component
Question #6
Question #6<br />
• A common finding in this tumor is:<br />
• EWSR1-FLI1 EWSR1 FLI1 fusion gene<br />
• SYT-SSX fusion gene<br />
• t(X t(X;18)(p11;q11)<br />
18)( 11 11)<br />
• t(11;12)(q22;21)
Question #7
Question #7<br />
• The radiographic and histologic findings<br />
given for this lesion:<br />
• Fit well<br />
• Do not fit well since the tumor is most<br />
likely located in the metaphysis<br />
• Do not fit well since the tumor is<br />
uncommon iin the h di distal l radius di<br />
• Do not fit well since the tumor is not<br />
destroying the cortex
Question #8
Question #8<br />
• This tumor<br />
• Has histologic features that overlap<br />
with chondroblastoma<br />
• Is often associated with pain that is<br />
relieved with steroids<br />
• IIs oftentimes ft ti effectively ff ti l treated t t d with ith<br />
observation only<br />
• Is frequently located in the proximal<br />
femur
Question #9
Question #9<br />
• This tumor:<br />
• Is rarely seen in the ribs<br />
• Results from GNAS1 mutation<br />
• Sh Shows radiographic di hi ffeatures t similar i il<br />
to ground stones<br />
• Most commonly located at the end of<br />
a long bone
Question #10
Question #10<br />
• This lesion<br />
• Is also known as non-ossifying non ossifying fibroma<br />
• Is effectively treated with chemotherapy<br />
and surgery<br />
• Contains few mitotic figures<br />
• Only rarely presents with a pathologic<br />
fracture
Question #11
Question #11<br />
• This tumor is frequently:<br />
• Located in the metaphysis of the long<br />
bones<br />
• Located in the sacrum<br />
• Affects children<br />
• Cytokeratin negative
Question #12
• This lesion<br />
Question Q #12<br />
• Radiographically shows cortical and<br />
medullary continuity between the<br />
lesion and underlying bone<br />
• Commonly involves the small bones<br />
• Commonly evolves into secondary<br />
chondrosarcoma<br />
h d<br />
• Contains fibrous tissue diffusely<br />
surrounding bone within the stalk
Question #13
Question #13<br />
• Common histologic findings of this<br />
lesion include all but one of the<br />
following:<br />
• Mitotic activity<br />
• Reactive or woven bone<br />
• CCalcification l ifi ti<br />
• Cytologic atypia<br />
• Solid and cystic areas
Question Q<br />
#14
Question #14<br />
• This tumor<br />
• Frequently involves the small bones<br />
• Is commonly seen in children<br />
• Sh Shows radiographic di hi evidence id of f<br />
cortical thickening and scalloping<br />
• Commonly contains myxoid change<br />
within the matrix
Question #15
• This tumor<br />
Question Q #15<br />
• Is associated with a relatively good<br />
prognosis<br />
• Contains low-grade chondrosarcoma &<br />
high g ggrade sarcoma components p<br />
• Contains high-grade chondrosacoma &<br />
high grade sarcoma components<br />
• Contains two histologic components<br />
that merge imperceptively with one<br />
another
Question #16
Question #16<br />
• This tumor<br />
• Frequently involves the jaw bones<br />
• Frequently contains a high grade<br />
osteosarcoma component<br />
• Frequently contains a high grade<br />
cartilaginous til i component t<br />
• Is the most common malignant bone<br />
tumor of children