Cartilage tumors of bone

2007 UCSF Stanford Current Issues in Anatomic Pathology

Andrew Horvai M.D. Ph.D.

Outline• Principles: Definitions, radiology, treatment • Common intramedullary tumors

– Chondroblastoma– Enchondroma– Conventional chondrosarcoma– Dedifferentiated chondrosarcoma– Variants: clear cell & mesenchymal chondrosarcoma

• Current issues and controversies– Grading– Malignant transformation– Cartilage tumors of small bones of hands and feet

Principles: Definitions• Unifying characteristics

– Production of a matrix rich aggrecan, a proteoglycan (65% water)

– Chondroitin sulfate Keratan sulfate

Principles: Radiology• Opacity

– Lytic– Sclerotic– Mixed

• Border– Marginated– Circumscribed– Moth eaten– Permeative

• Periosteum– Solid: Thickened cortex– Elevated: Codman’s triangle– Spiculated: New bone at right angles to cortex– Onion skin: New bone parallel to cortex

Principles: Radiology

Principles: Radiology

Principles: Radiology

Ring-like calcifications

Principles: Treatment

Enchondroma ObservationCurettage

Grade I chondrosarcoma, chondroblastoma

Curettage and cement

Grade II-III chondrosarcoma

Wide local excision

Grade III chondrosarcoma AmputationChemotherapy

Principles: Syndromes

Syndrome MOI* Locus Gene Associated conditions

Malignanttransformation15-35%

15-50%

5-35%

Maffucci syndrome Sporadic Cavernous hemangiomas

Ollier disease(multiple enchondromatosis)

Sporadic 3p21-22 PTHR1(?)

Multiple osteochondromas

AD 8q24,11p11

EXT1, EXT2

Deformities of forearm, knee, short stature

*MOI: Mode of inheritance

Malignant transformation

• Chondroblastoma– Case reports (correct diagnosis?)– Benign metastasizing chondroblastoma

• Solitary Enchondroma– Case reports

• Sporadic Osteochondroma– 1-8%

Case 1

• 17 year old girl, injured her left knee playing soccer and has had persistent pain at the site prompting X-Rays

Clinical Radiology Histology Ddx

Age: 10-25Loc: Long bones

Recurrence: 15%, Higher in temporal bone.

Epiphysis +physisLytic, marginated,septae

•Fibrochondroid matrix•Chickenwire calcifications•Plasmacytoid, nuclear grooves

Moderate atypiaOsteoclast-giant cells

Giant cell tumorABC (30% association)

Chondroblastoma

Case 2

• 20 year old woman with history of “lesion”in right tibia.

• No pain, no palpable mass.

Clinical Radiology Histology Ddx

Age: AllLoc: Hands/feet, long tubular bones

MetaphysisLytic, lobularRing calcificationsIntact cortex

LobularPeripheral ossificationNo permeationLow cellularityNo atypia/mitoses

Grade I Chondrosarcoma

Enchondroma

Enchondroma

Case 3

• 53 year old woman with “hip” pain x 2 months

• Needle biopsy performed of hip mass

Enchondroma or Grade I chondrosarcoma?

• Enchondroma: “Multiple nodules of hyaline cartilage separated by normal marrow (and) plates of lamellar bone that conform to the irregular shapes of cartilage lobules.”

• Chondrosarcoma: “Single confluent mass of cartilage… trapping host lamellar bone or invasion into Haversian or Volkman systems.”

- J. Mirra (1985)

• Pitfalls– Small biopsy– Curettage– Small bones of hands and feet

Mirra JM et al. Clin Ortho Rel Res 1985 201:214-237

Permeation

Enchondroma or Grade I chondrosarcoma?

• “Diagnosis should be based on what the tumor is doing to the patient” - Dr. Kempson– Progression over time– Radiology

Case 3

Grade I Chondrosarcoma

Enchondroma or Grade I chondrosarcoma?• Radiographic features:

Most predictiveMost predictive Least predictiveLeast predictive

Pathologic fracture Axial skeleton Infiltratingmargin

Soft tissue mass Size > 5 cm Lobulated contour

Periosteal reaction

Cortical disruption or thickening

Murphey MD Flemming DJ Radiographics 1998; 18:1213-1237.Geirnaerdt et al A J roentgenol 1997;169:1097Brien EW Mirra JM Kerr Skeletal Rad 1997 Jun; 26(6) 325-53

• Genetic features:– Karyotype: (C.H.A.M.P. study)

• Enchondroma (n=14) and CHUMP (n=3): karyotypically normal• Grade I chondrosarcoma: Numerical and structural aberrations

(n=3).

– Comparative genomic hybridization:• Enchondroma: 13q21; 19, 22q• Chondrosarcoma: 2-11, 14, 15, 18, 21• Similar numbers aberrations

Enchondroma or Grade I chondrosarcoma?

Tallini, G., et al. J Pathol, 2002; 196(2):194Ozaki et al. Anticancer Res 2004; 1721

Conventional chondrosarcoma

Conventional chondrosarcomaClinical Radiology Histology Ddx

Age: 50+Loc:

Central: pelvis, meta-diaphysis long bones

Peripheral: osteochondroma

Large (> 5 cm)Cortical disruptionEndosteal scallopingSoft tissue extensionRing calcifications

Permeates viable, lamellar boneHypercellularMyxoid changeAtypia NecrosisMitoses

EnchondromaClear cell chondrosarcomaChondroblastic OGS

Chondrosarcoma: permeation

Chondrosarcoma: Myxoid change

Chondrosarcoma: GradingPROGNOSTIC FACTORS IN CHONDROSARCOMA

OF BONE A Clinicopathologic Analysis with Emphasis on Histologic Grading

HARRY L. EVANS, M.D.* ALBERTO G. AYALA, MD

AND MARVIN M. ROMSDAHL, MD, PHD

Cancer 40:818-831, 1977.

Histology 5 year survival

10 year survival

90

81

43

Grade I Hypercellular, uniform but hyperchromatic nuclei, nuclear detail not visible

83

Grade II Diffusely hypercellular, nuclei paler with visible intranuclear detail

64

Grade III Sheets of cells, larger nuclei, mitotic activity > 2mf/10 hpf

29

Chondrosarcoma: Grading• Subjective• No universally accepted scheme• High interobserver variability

• Despite limitations, grade does predict mortality, recurrence and metastasis

0

25

50

75

100

Mayo Rizzoli MD Anderson

Perc

ent o

f cas

es

I II III I II III I II III

1998 1981 1977

Grade I ChondrosarcomaGrade I Chondrosarcoma

Grade II ChondrosarcomaGrade II Chondrosarcoma

Grade III ChondrosarcomaGrade III Chondrosarcoma

Grade III ChondrosarcomaGrade III Chondrosarcoma

Chondrosarcoma of small bones of hands and feet

• Enchondromas of hands and feet– Clinical: Very common site (~30%), painful,

pathologic fracture common– Radiographs: Cortical erosion common– Histology: Hypercellular, myxoid change,

nuclear hyperchromasia, permeation within medulla

• Mayo Clinic: (n=163) 12/70 metastasized– Radiographs: Permeative pattern, cortical

destruction, soft tissue mass– Histology: Permeation through cortex into soft

tissue (“sweating”)• Baylor (n=15) 0/8 metastasized.• Leiden (phalanges only, n=35) 0/28

metastasized

Chondrosarcoma of small bones of hands and feet

• Meta analysis (Grades I-III)

Site Recurrence MetastasisPhalanges 29/115 (25%) 2/115 (<2%)

Metacarpals metatarsals,Carpals, tarsals

26/62 (42%) 16/62 (26%)

All other sites ~35% ~25%

Chondrosarcoma of small bones of hands and feet

• Metacarpals, metatarsals, wrist and ankle:– Diagnosis requires either grade III cytology if

equivocal radiology or evidence of soft tissue involvement

• Phalanges:– Probably does exist but with a metastatic rate

that is very low– Local resection is favored over amputation

whenever possible.

Summary: chondrosarcoma of small bones of hands and feet

Case 4

• 44 year old man• Thigh pain for 3 years

Dedifferentiated chondrosarcoma

Clinical Radiology Histology Ddx

Age: Adult >50Loc: Pelvis>Femur>Humerus5 year survival < 10%

MetaphysisBimorphic (especially on MRI)

Abrupt transition:1. Chondrosarcoma I2. OGS / MFH / FS

Chondroblastic osteosarcoma-Less abrupt transition-High grade chondroid component

Is it really “dedifferentiated”chondrosarcoma?

Take-home messages• Correlation of radiologic, clinical and histologic features

critical, especially in low-grade lesions• Permeation is the most sensitive histologic criterion

separating enchondroma from chondrosarcoma.• Chondrosarcoma of small bones of the hands and feet

should be diagnosed with caution. • Grade is most important prognostic indicator for

chondrosarcoma• Chondrosarcomas are predominantly locally aggressive,

but local disease can be fatal even in the absence of metastases

Case 6

• 18 year old man with painful mass in thigh

Mesenchymal chondrosarcomaClinical Radiology Histology Ddx

Age: 20-30Loc: Jaw, rib, pelvis, soft tissueMultifocal

10yr survival 25% Variable course

LyticRing calcificationsRarely circumscribed

1. Benign cartilage islands/perivascular2. Small round blue cell tumorHPC-ish vessels common

Ewing sarcoma (CD99)Dediff chondrosarc (abrupt)Small cell osteosarcoma

Case 4

• 28 year old man with shoulder discomfort

Clear cell chondrosarcomaClinical Radiology Histology Ddx

Age: 25-50 M>FLoc: Proximal femurSkull, rib, spineSlow growing~25% Metastasize~15% mortality

EpiphysisCircumscribedEarly: lytic, septaeLate: sclerotic

Permeates Osteogenic “No” hyaline cartilageClear cells, well defined membrane, macronucleoli (S100+)

Chondroblastic osteosarcomaOsteoblastoma

Chondroblastoma (radiology Ddx)