Important bone tumours

Bone infarct

"smoke up the chimney"

medullary lesion of sheet-like central lucency surrounded by sclerosis with a serpiginous border

Ewing's sarcoma

Introduction

A malignant small round cell tumor found in young patients Age & location found in patients from 5-25 years of age ~50% are found in the diaphysis of long bones common locations include the femoral shaft, knee (distal femur and prox tibia), pelvis and proximal humerus Genetics 90% have t(11:22) translocation which leads to the formation of a fusion protein (EWS-FLI 1) Prognosis 60-70% long term survival with treatment only 40% long term survival with pelvis lesions only 15% long term survival if patient presents with metastasis to the lung

Symptoms

Presentation pain often accompanied by fever often mimics an infection Physical exam swelling and local tenderness

Imaging

Radiographs large destructive lesion in the diaphysis or metaphysis with a moth-eaten appearance  periosteal lifting may give "onion skin" or "sunburst" appearance Bone scan hot required as part of workup MRI often shows a large soft tissue component  CT chest is important to rule out mets to lungs (very common)

Labs

ESR is elevated WBC is elevated Anemia is common Bone marrow biopsy  required as part of workup for Ewing's to rule out metastasis to the marrow

Histology

Characteristic findings sheets of monotonous small cells  cells have scant cytoplasm  may have pseudo-rosettes (circle of cells with necrosis in center)  Immunostain CD99 reactivity

Treatment

Multimodality multistage chemotherapy and limb salvage resection preoperative chemotherapy given for 8-12 weeks followed by maintenance chemotherapy for 6-12 months after surgical resection  irradiation current trend towards surgical resection and away from irradiation due to high risk of irradiation-induced secondary malignancies situations where radiation can be used include  radiation alone for areas that cannot be resected (ie, large bulky pelvic tumors), in combination with local resection if surgical margins are close

Small-round-cell tumor differential

• if < 5 yrs. and there are small round cells think neuroblastoma or leukemia
• if approximately 10 years think eosinophilic granuloma
• if 10-30 yrs and there are small round cells think Ewing's
• if >30 yrs think lymphoma
• if > 50 yrs. and there are small round cells think myeloma

Giant cell tumour

Introduction

A benign but aggressive tumor of unknown origin that is usually found in the epiphysis of long bones  Age more common in females (unlike most bone tumors) ages 20-40 years (80% of giant cell tumors occur in patients older than age 20 years, with the peak incidence in the third decade of life) patient age/gender on previous OITE questions: 17F, 21M, 27F, 34F, 36F, 40M  Location 50% around knee (distal femur or proximal tibia), most common location  10% in sacrum and vertebrae (sacrum is most common site in axial skeleton)  distal radius is third most common location phalanges of the hand is also a very common location Malignant potential as primary malignant giant cell tumor metastasizes to lung in 2%  hand lesions have greater chance of metastasis secondary malignant giant cell tumor occurs following radiation or multiple resections of giant cell tumor Differential If multiple lesions (~1%) than rule out hyperparathyroidism

Symptoms

Presentation   pain referable to involved joint

Imaging

Radiographs lytic and destructive metaphyseal lesion that often extends into the epiphysis and often borders subchondral bone  may have cortical thinning with breakthrough Bone scan is very hot  MRI shows clear demarcation on T1 image between fatty marrow and tumor

Histology

Characteristic findings basic proliferating cell type is the mononucleur spindle-shaped stromal cell  hallmark Giant cells are numerous  nucleus of giant cell appears same as spindle-shaped stromal cells

Treatment

Operative extensive curettage with chemical cauterization (phenol), bone grafting and cementing  challenge of treatment is to remove lesion while preserving joint and providing buttress support to subchondral joint aggressive exterioration of overlying cortex is required  10-30% recurrence with curettage alone verses 3% with cementation hand lesion treatment is controversial if no cortical breakthrough treat with curettage and cementing if significant cortical breakthrough consider intercalary resection (with free fibular graft) vs. amputation radiation alone for inoperable lesions only leads to 15% malignant transformation

Chondrosarcoma

Introduction
Malignant chondrogenic lesions can occur in two forms primary chondrosarcoma which includes low-grade, high-grade, de-differenitated chondrosarcoma clear cell chondrosarcoma  mesenchymal chondrosarcoma  secondary chondrosarcoma arises from benign cartilage lesions including  osteochondroma (<1% risk of malignant transfomation) multiple hereditary exostosis (1-10% risk of malignant transfomation) enchondromas (1% risk of malignant transfomation) Ollier's disease (25-40% risk of malignant transfomation) Marfucci's (100% risk of malignant transfomation) Age & location typically, chondrosarcomas are found in older patients (40-75 yrs) there is a slight male predominance most common locations include the pelvis, proximal femur, scapula  tumor location is important for diagnosis as the same histology may be diagnosed as benign in the hand but malignant if located in the long bones Grade 85% of chondrosarcomas are grade 1 or 2 15% of chondrosarcomas are grade 3 or dedifferentiated chondrosarcoma  de-differentiated chondrosarcomas are high grade lesions which develop from low grade chondroid lesions and require more aggressive treatment including adjuvant chemotherapy Prognosis axial and proximal extemity lesions have a more aggressive course histologic grade correlates with survival Grade I: 90% survival Grade II: 60-70% survival Grade III: 30-50% survival De-differentiated chondrosarcoma: 10% survival increased telomerase activity in chondrosarcoma, as determined byreverse transcriptase-polymerase chain reaction (RT-PCR), has been shown to directly correlate with the rate of reccurence  Primary Chondrosarcoma sub-types Clear cell chondrosarcoma  malignant immature cartilaginous tumor accounting for <2% of all chondrosarcomas most common in 3rd and 4th decades of life commonly presents with insidious onset of pain  presents as an epiphyseal lesion and can be mistaken for low-grade chondroblastoma locally destructive with potential to metastasize  Mesenchymal chondrosarcoma chondrosarcoma variant which presents with a biphasic pattern of neoplastic cartilage with associated neoplastic small round blue cell component occurs in younger patients than typical chondrosarcomas may occur at several discontinuous sites at presentation and can occur in the soft tissues treatment includes neo-adjuvant chemotherapy followed by wide surgical resection

Symptoms

Presentation pain is the most common symptom may present with slowly growing mass or symptoms of bowel/bladder obstruction due to mass effect in the pelvis 50% of de-differentiated chondrosarcomas present with a pathologic fracture

Imaging

Radiographs lytic or blastic lesion with reactive thickening of the cortex  low-grade chondrosarcomas have a similiar appearance to enchondromas with additional cortical thickening/expansion and endosteal erosion   high-grade chondrosarcomas are less well defined on plain radiographs and frequently present with cortical destruction and a soft tissue mass intra-lesional "popcorn" mineralization  may be seen described as rings, arcs, and stipples of mineralization de-differentiated chondrosarcomas radiographically show a lower grade chondroid lesion with superimposed highly destructive area consistentwith the high grade transformed dedifferentiated chondrosarcoma  MRI or CT helpful to determine cortical destruction, marrow involvement, and the soft tissue involvement  Bone scan is usually very hot in all grades of chondrosarcoma

Histology

Chondrosarcoma needle biopsy is not indicated for cartilage tumors due to difficulties with diagnosis it is often difficult to determine malignancy based on histology alone chararcteristic histology low-grade chondrosarcomas show few mitotic figures with a bland histologic appearance and associated enlarged chondrocytes with plump multinucleated lacunae  high-grade chondrosarcomas have a hypercellular stroma consisting of characteristic "blue-balls" of a cartilage lesion which permeate the bone trabeculae  enchondromas of hand, Ollier's disease, Maffucci's disease, periosteal chondromas, and chondrosarcoma may all have similar histology De-differentiated chondrosarcomas characterized by a bimorphic histology low grade chondroid component high grade spindle cell component (similiar histology to osteosarcoma, fibrosarcoma, MFH)

Treatment

Operative intra-lesional curettage  indications Grade 1 lesions  treatment of grade 1 lesions located in the pelvis or axial skeleton is controversial many authors recommend wide excision of all chondrosarcomas (even grade 1) if located in the pelvis wide surgical excision  indications grade 2 or 3 lesions some say grade 1 lesions in pelvis historically, there is no significant role for radiation or chemotherapy in typical intramedullary chondrosarcoma  wide surgical excision combined with multi-agent chemotherapy  indications high-grade de-differentiated chondrosarcoma mesencymal chondrosarcoma

Telangiectatic osteosarcoma

Introduction

Occur in same location as ABC (look similar radiographically as well)

Symptoms

Presentation 25% present with pathologic fracture

Imaging

Radiographs lytic, destructive, and expansile lesion Bone scan hot

Histology

Characterized by few cellular components (those present have malignant characteristics) not as much osteoid as intramedullary osteosarcoma  lakes of blood mixed with malignant cells (not in ABC)

Treatment

Same as intramedullary osteosarcoma   multi-agent chemotherapy and limb salvage resection chemotherapy preoperative chemotherapy given for 8-12 weeks followed by maintenance chemotherapy for 6-12 months after surgical resection 98% necrosis with chemo is good prognostic sign expression of multi-drug resistence (MDR) gene portends very poor prognosis cells can pump chemo out of cell present in 25% of primary lesions and 50% of metastatic lesions surgical resection trend towards limb salvage whenever possible

Prognosis

More chemosensitive but same survival as intramedullary osteosarcoma

Parosteal Osteosarcoma

Introduction

A low grade osteosarcoma Age & location more common in females, age 30-40 previous exam question ages: 75, 74 yrs occurs on surface of metaphysis of long bones most common sites include posterior distal femur, proximal tibia, and proximal humerus marrow invasion in 25%

Symptoms

Presentation often presents as a painless mass can limit joint motion (knee)

Imaging

Radiographs heavily ossified, lobulated mass arising from cortex (appears as if sticking to cortex) Bone scan mandatory and always hot CT chest mandatory to rule out pulmonary mets MRI mandatory to determine soft tissue involvement and skip lesions

Histology

Characteristic histology regularly arranged normal osseous trabeculae  slightly atypical spindle cells within trabeculae cartilage is often present and may take the form of a cartilage cap Pathologist ocassionally mistakes for fibrous dysplasia

Treatment

Operative wide local surgical excision often curative chemotherapy not indicated unless there is a high grade component

Prognosis

95% long term survival when local control has been achieved dedifferentiation is a poor prognostic factor

Groups & Differentials

Fibrous dysplasia (similar on histology, but xrays are different) Myositis Ossificans Traumatica (juxtaposed to bone) Osteochondral exostosis (shares cortex with bone) Developmental defect at insertion of adductor magnus

Osteosarcoma

An osteosarcoma is a malignant bone forming tumour and is the second common primary bone tumour after multiple myeloma . They account for ~ 20 % of all primary bone tumours.

Epidemiology

Osteosarcomas can be either primary or secondary, and these have differing demographics. 

• primary osteosarcoma : typically occurs in young patients (10 - 20 years) with 75% occurring before the age of 20  . There is a slight male predominance
• secondary osteosarcoma : occurs in the elderly, usually secondary to malignant degeneration of Paget's disease, extensive bone infarcts or post radiotherapy for other conditions.

Clinical presentation

Patients usually present with bone pain, occasionally accompanied by a soft-tissue mass or swelling. At times, the first symptoms are related to pathologic fracture.

The distribution of primary and secondary osteosarcomas is also different. 

• primary tumours typically occur in the metaphyseal regions of long bones, and have a striking predilection for the knee, with up to 60% occurring there
• secondary tumours on the other hand, have a much wider distribution largely mirroring the combined incidence of their underlying condition, and thus much have a higher incidence in flat bones, especially the pelvis (a favourite site of Paget's disease)

Pathology

Osteosarcomas can be divided into a number of sub types according to degree of differentiation, location within the bone, and histological variants . 

These sub types vary in imaging findings, demographics and biological behaviour, and include :

• intramedullary ~ 80%
  • conventional high-grade : most common and discussed in this article
  • telangiectatic osteosarcoma
  • low-grade osteosarcoma
• surface ~ 10 - 15 %
  • intracortical osteosarcoma
  • parosteal osteosarcoma
  • periosteal osteosarcoma
• extra skeletal ~ 5 % 
  • extra skeletal osteosarcoma

Macroscopically osteosarcomas are bulky tumours where a heterogeneous cut surface demonstrates areas of haemorrhage, fibrosis and cystic degeneration. Their extension within the medullary cavity is often much more extensive than the bulky part of the tumour would suggest. Areas of bone formation are characteristic of osteosarcomas, with the degree of bone formation varying widely.

Microscopically poorly formed trabecular bone is seen with (in the typical high grade conventional sub type) cellular pleomorphism and mitoses. Variable amounts fibrocytic and chondroblastic appearing cells may also be encountered. 

Location

They typically occur at the metadiaphysis of tubular bones in the appendicular skeleton. Common sites include 

• femur : ~ 40% (especially distal femur)
• tibia : ~ 16% (especially proximal tibia)
• humerus : ~ 15% 

Other less common sites include

• fibula
• innominate bone
• mandible
• maxilla
• vertebrae  

Markers

Serum alkaline phosphatase (ALP) may be raised (particularly with advanced disease)

Radiographic features

Plain film

Conventional radiography continues to play an important role in diagnosis. Typical appearances of conventional high grade osteosarcoma include:

• medullary and cortical bone destruction
• wide zone of transition, permeative or moth-eaten appearance
• aggressive periosteal reaction
  • sunburst type
  • Codman triangle
  • lamellated (onionskin) reaction : less frequently seen
• soft-tissue mass
• tumour matrix ossification / calcification
• variable:  reflects a combination of the amount of tumour bone production, calcified matrix, and osteoid
• ill-defined "fluffy" or "cloud-like" c.f to the rings and arcs of chondroid lesions

Chondroblastoma

Introduction
A benign chondrogenic lesion  Age & location epiphyseal lesion in young patients (usually around 12 years of age)  common locations include distal femur, proximal tibia, proximal humerus, proximal femur, and apophysis or triradiate cartilage of the pelvis typically epiphyseal but may occasionally cross the physis Genetics may have genetic abnormalities on chromosome 5 and 8 Prognosis 2-5% of benign chondroblasts metastasize to the lungs (similar to giant cell tumor in this respect)

Symptoms

Presentation pain referred to involved joint Physical examination exam may show mechanical symptoms with limitations of motion

Imaging

Radiograph well-circumscribed epiphyseal lytic lesion with thin rim of sclerotic bone that is sharply demarcated from normal medullary cavity  lesions often cross physis into metaphysis mineralization within the lesion may or may not be present

Histology

Classic characteristics are chondroblasts arranged in "cobblestone" or "chickenwire" pattern may be present  occasional multinucleated giant cells may be present  loose myxoid tissue

Treatment

Operative extended intralesional curettage and bone grafting  may do local adjuvant treatment with phenol or cryotherapy

Enchondroma

Introduction

A benign chondrogenic lesion caused by an abnormality of chondroblast function in the physis chondroblasts escape the physis and proliferate in metaphysis  2nd most common benign cartilage lesion (osteochondroma is most common) Age & location age range is 10-60 years occurs in medullary cavity in diaphysis or metaphysis hand is most common location (60%) presentation as pathological fractures common other locations include the femur (20%) and proximal humerus (10%) Include solitary enchondroma 1% chance of malignant transformation (chondrosarcoma) Ollier's disease (multipe enchondromatosis)  no genetic predisposition has been identified multiple enchondromas in long bone diaphysis 10-30% chance of malignant transformation into chondrosarcoma however associated with high rate of both skeletal and non-skeletal malignancies involved bones are dysplastic Maffucci's syndrome no genetic predisposition has been identified multiple enchondromas and soft-tissue angiomas 100% chance of malignant transformation into chondrosarcoma  increased risk of visceral malignancies (astrocytoma, GI malignancy)

Symptoms

Presentation most are asymptomatic  often present as pathologic fx of the hand but asymptomatic in foot Physical exam enchondroma may disrupt the growth plate and lead to shortening and angular deformities

Imaging

Radiograph "pop-corn" mineralization (calcification), stippled ringsin diaphyseal or metaphyseal medullary cavity  occasionally may have purly lytic appearance (especially in hand)  Bone scan may be helpful and is usually minimally warm MRI may show steak of cartilage or "sled runner tracks"

Histology

Classic characteristics include hypocellular with bland hyaline cartilage (blue balls of cartilage)    lesions in hand are more hypercellular and even display some worrisome histologic characteristics small chondroid cells in lacunar spaces

Differential

Must differentiate from a bone infarct ("smoke-up-chimney" appearance)

Treatment

Nonoperative observation treatment for most enchondromas  watch with serial xrays for interval growth (obtain xrays at 3 months and 1 year from time of presentation) Operative curettage and bone grafting indications lesion that shows any change on serial xrays hand fractures after fracture has first been allowed to heal with imobilization Ollier's disease and Maffucci's treat deformity with diaphysectomy watch lesions carefully for malignant transformation