Cartilage Forming Tumours

Question 1

Tumour specific imaging patterns

Answer 1

• Diaphyseal tumour, Hair on end appearance –> Ewings Sarcoma
• Metaphyseal tumour, **Sunray **appearance, Codman’s triangle –> Osteosarcoma
• Marrow cavity must be continuous with bone of origin –> Osteochondroma
• **Soap bubble **appearance –> Giant cell tumour
• Popcorn calcification –> Chondrosarcoma

Lytic mets:
* Thyroid cancers
* Melanoma
* Multiple myeloma
* Renal cancers

Lytic/Blastic mets:
* Lung cancers
* Breast cancer

**Blastic mets: **
* Prostate cancer

Question 2

Osteochondroma

Answer 2

• Benign bone surface tumor composed of mature bone with a cartilage cap
• May be solitary or occur as multiple hereditary exostoses
• Exophytic lesion of bone surface composed of a stalk of mature bone with a cartilaginous cap
• The marrow space / cancellous bone of the stalk communicates with that of the underlying bone
• Most common in the metaphysis of long bones: femur > humerus > tibia
• Involvement of flat bones (ilium, scapula) may occur

Radiology:
* Pedunculated or sessile
* Mature bony stalk continuous with the cortex; cancellous bone of stalk communicates with that of underlying bone
* Thin, lobulated cartilaginous cap, which may contain calcifications
* Growth perpendicular to the long axis of the bone

Micro:
* Cap composed of mature hyaline cartilage with overlying fibrous perichondrium
* In young patients, transition between bone and cartilage cap resembles growth plate, showing endochondral ossification into mature bone; cartilage cap diminishes and may essentially be absent in older adults
* Marrow elements may be present within bony stalk; marrow space / cancellous bone contiguous with that of the native bone

Molecular:
* Loss of function mutations in EXT1 (8q24) and EXT2 (11p11) genes
* In solitary lesions, EXT gene inactivation is restricted to the cartilage cap and is somatic
* MHE shows autosomal dominant inheritance

Question 3

Enchondroma

Answer 3

• Enchondroma is a benign hyaline, cartilaginous tumor that arises within the medullary cavity of bone
• Enchondromatosis presents with multiple enchondromas; most common subtypes are Ollier disease and Maffucci syndrome.

Ollier disease:
* Multiple enchondromas in the appendicular skeleton in an asymmetric manner
* Typically in short and long bones of the limbs; epiphyseal tumors can prevent normal bone growth in young patients
* 20% malignant transformation to chondrosarcoma

Maffucci syndrome
* Multiple enchondromas in association with soft tissue and visceral hemangiomas and lymphangiomas
* BOSE - Brain gliomas, ovarian carcinomas, Soft tissue, Endochondromatosis
* Inevitable malignant transformation to chondrosarcoma

Radiology:
* well defined, solitary defects in the metaphyseal region of bones, especially in the long bones

Micro:
* Enchondromas are hypocellular, with an abundance of hyaline cartilage matrix
* Tumor cells are embedded within lacunar spaces and evenly dispersed
* Nuclei are small and round, with condensed chromatin (lymphocyte-like)
* Cytoplasm is eosinophilic
* Architecture can be multinodular or confluent
* Separate cartilaginous nodules can be surrounded by bone, which is referred to as encasement (a sign of slow growth)

Molecular:
* Hotspot mutations are exclusively found at the IDH1 p.Arg132 and the IDH2 p.Arg172 positions

Question 4

Periosteal chondroma

Answer 4

• Rare benign cartilaginous neoplasm that arises on the surface of cortical bone beneath periosteum
• Children and young adults
• Small bones of the hands and long bones of the skeleton, particularly proximal metaphyseal or diaphyseal regions of humerus and femur
• Well defined dome shaped lesion on the surface of the bone
• Composed of benign hyaline cartilage
• No connection with medullary cavity (radiologically)

Radiology:
* Contains popcorn or ring-like calcifications, characteristic of cartilaginous tumors
* Plain radiographs may show a discernible soft tissue mass with underlying cortical saucerization or scalloping, subjacent cortical sclerosis and overhanging margins

Micro:
* Well demarcated from the underlying sclerotic bone, which may be focally eroded but never permeated
* Lobular architecture
* Covered by a continuous layer of attenuated periosteum
* Cellularity is variable but generally low
* Chondrocytes do not show cytologic atypia

Molecular:
* IDH1 and IDH2 mutations have been identified in periosteal chondromas

Question 5

Chondroblastoma

Answer 5

• Benign neoplasm; rare (< 1% of primary bone neoplasms), arising in second to third decades of life, with slight male predilection
• Treatment with surgical curettage is generally curative; recurrence varies with location
• Common location includes epiphysis of long bones > metaphysis; may involve skull in older patients
• Pain in the affected area

Radiology:
* well defined lucent lesion
* thin sclerotic rim, with or without matrix calcifications
* commonly arising eccentrically within the epiphysis of long bones; extension to the metaphysis can be seen

Micro:
* Composed of round or polyhedral chondroblasts with abundant eosinophilic cytoplasm and well defined cell borders; spindle shaped cells may be focal
* Nuclei are oval, hyperlobulated with grooves
* Pericellular lace-like or chicken wire type calcification among degenerative chondroblasts
* Chondroid matrix almost always present (pink rather than blue matrix)
* May have marked cellularity, intracytoplasmic glycogen granules, mitotic figures, necrosis and osteoclast type giant cells
* No significant nuclear atypia as compared with malignant chondroblastoma
* Aneurysmal bone cyst-like change is common

Molecular:
* K36M mutations commonly identified within H3F3B and rarely in H3F3A

IHC:
* H3.3B (H3F3B) p.Lys36Met (K36M): diffuse nuclear staining may be helpful to distinguish from aneurysmal bone cyst
* S100
* DOG1

Question 6

Chondromyxoid fibroma

Answer 6

• Benign cartilaginous tumor of young adults, arising in proximal or distal parts of long bones, showing zonal architecture
• Local recurrence is common; malignant transformation is extremely rare
• Long tubular bones; most frequently distal femur and proximal tibia
• Long term history of pain
• Lobulated tumor mass with intact periosteum

Radiology:
* Lytic lesions are expansile, loculated and locally destructive

Micro:
* Lobulated architecture; lobules separated by mononuclear spindle cells and admixed multinucleated giant cells
* Lobules have hypocellular centers and hypercellular periphery
* Variably myxoid to chondroid stroma, representing various stages of cartilaginous development
* Marked nuclear pleomorphism with nucleoli may be seen in some cases
* Periphery of lobules show spindle shaped fibroblast-like cells and scattered multinucleated osteoclast-like giant cells
* Low mitotic rate
* Coarse calcifications may be seen in the stroma, particularly in tumors arising in older age group and unusual sites
* Hemosiderin deposition and lymphocytes may be seen

Molecular:
* GRM1 upregulation is highly specific for chondromyxoid fibroma

Question 7

Chondrosarcoma

Answer 7

• Locally aggressive or malignant group of tumors characterized by formation of cartilaginous matrix

Primary:
* arising without a benign precursor

Secondary:
* Central: arising in preexisting enchondroma
* Peripheral: arising in preexisting cartilaginous cap of an osteochondroma

Periosteal chondrosarcoma:
* occurs on the surface of the bone in association with the periosteum

• Second most common primary malignant bone tumor after osteosarcoma
• Most common sites are the pelvic bones, femur and humerus
• Other sites are the trunk, skull and facial bone

Radiology:
* popcorn-like calcifications (punctate and ring-like opacities)
* lytic lesions, endosteal scalloping, thickened cortex, cortical erosion or destruction, soft tissue involvement
* Cortical destruction and soft tissue extension of pre-existing enchondromas might be indicators of secondary central chondrosarcoma

Micro:
* Abundant cartilaginous matrix with chondrocytes embedded in lacunae
* Lobular or diffuse growth (depending on grade)
* Varying degrees of increased cellularity, nuclear atypia and mitotic activity

Grade I:
* minimally increased cellularity, nodular growth and occasional binucleate nuclei

Grade II:
* moderate cellularity and diffuse growth

Grade III:
* high cellularity, marked atypical cells, pleomorphic appearance and easily identifiable mitotic figures

• Myxoid changes, chondroid matrix liquefaction and necrosis can be seen

Molecular:
* DH1 and IDH2 mutations in approximately 50% of cases
* Aneuploidy is seen with increasing histologic grade
* TP53 mutations and affected active signaling pathways (RB1, CDKN2A, CDK) are identified particularly in high grade chondrosarcomas

IHC
* S100: uniformly strongly positive but in grade III it can be focally negative in less differentiated areas
* D2-40

Mesenchymal chondrosarcoma:
* high grade tumour
* Small round blue cells
* Islands of benign-appearing cartilage
* haemangiopericytomatous pattern of growth with ‘staghorn’ like vessels

Clear Cell chondrosarcoma:
* low-grade tumour
* Round cells with abundant clear cytoplasm
* Distinct cytoplasmic borders with background of cartilaginous matrix
* Multinucleated giant cells are usually apparent