Osteosarcoma Left Femur

Case History: 18-year-old patient presents with complaints of swelling in left lower limb around and just above left knee. MRI was advised.

MRI showed a hyperintense heterogenous soft tissue mass on T2W and STIR images. Marrow signal changes were seen with cortical breakdown and periosteal elevation. The lesion is aggressive, extending across fascial planes, and encasement of neurovascular bundles is seen. Final diagnosis of osteosarcoma was given and confirmed by biopsy.

Figure 1. Stir image showing heterogenous mass originating from left femur with marrow edema. Figure 2. Images show heterogenous soft tissue mass originating from distal femur. Figure 3. T1W image shows a hypointense mass originating in distal femur with marrow replacement. Figure 4. T2W image shows encasement of neurovascular bundle and tumor crossing fascial planes.

Osteosarcoma
Osteosarcomas are malignant bone forming tumors and the second most common primary bone tumor after multiple myeloma. They account for ~ 20% of all primary bone tumors.

Epidemiology
Osteosarcomas can be either primary or secondary with differing demographics.
• Primary osteosarcoma: typically occurs in young patients (10-20 years) with 75% occurring before the age of 20; which is logical because the growth centers of the bone are more active during the puberty-to-adolescence time period. Therefore, the epidemiology can be easily understood. For less clear reasons, 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 tumors typically occur in the metaphyseal regions of long bones, and have a striking predilection for the knee, with up to 60% occurring there.
• Secondary tumors, on the other hand, have a much wider distribution, largely mirroring the combined incidence of their underlying condition, and thus have a much higher incidence in flat bones, especially the pelvis (a favorite site of Paget's disease).

Pathology
Osteosarcomas can be divided into a number of subtypes according to degree of differentiation, location within the bone, and histological variant . These subtypes vary in imaging findings, demographics, and biological behavior, and include: • Intramedullary ~ 80%

• Conventional high-grade: most common and discussed in this article
• Telangiectatic osteosarcoma
• Low-grade osteosarcoma

• Surface or juxtacortical ~ 10%-15%

Intracortical osteosarcoma
• Parosteal osteosarcoma
• Periosteal osteosarcoma

• Extraskeletal ~ 5%

• Extraskeletal osteosarcoma

Macroscopically, osteosarcomas are bulky tumors in which a heterogeneous cut surface demonstrates areas of hemorrhage, fibrosis, and cystic degeneration. Their extension within the medullary cavity is often much more extensive than the bulky part of the tumor 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 subtype) cellular pleomorphism and mitoses. Variable amounts of fibrocytic and chondroblastic appearing cells may also be observed.

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 (gnathic osteosarcoma)
• Maxilla
• Vertebrae
Associations
• Paget's disease of bone
• Irradiation
• Rothmund-Thomson syndrome

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
• Tumor matrix ossification/calcification

• Variable: reflects a combination of the amount of tumor bone production, calcified matrix, and osteoid
• Ill-defined "fluffy" or "cloud-like" c.f to the rings and arcs of chondroid lesions

CT
The role of CT is predominantly in assisting biopsy and staging, and adds little to plain radiography and MRI in direct assessment of the tumor. The exception to this rule is predominantly lytic lesions in which small amounts of mineralized material may be inapparent on both plain film and MRI.

MRI
MRI is proving essential in accurate local staging and assessment for limb sparing resection, particularly for evaluation of intraosseous tumor extension and soft-tissue involvement. Assessment of the growth plate is also essential as up to 75%-88% of metaphyseal tumors do cross the growth plate into the epiphysis.

• T1

• Soft tissue non-mineralized component: intermediate signal intensity
• Mineralized / ossified components: low signal intensity
• Peri-tumoral oedema: intermediate signal intensity
• Scattered regions of hemorrhage will have variable signal (see aging blood on MRI)
• Enhancement: solid components enhance

• T2
• Soft tissue non-mineralized component: high signal intensity
• Mineralized/ossified components: low signal intensity
• Peri-tumoral oedema: high signal intensity

Treatment and Prognosis
Work-up: local staging by MRI prior to biopsy and distant staging with bone scan and chest CT.

Cure, if achievable, requires aggressive surgical resection often with amputation followed by chemotherapy. If a limb-salvage procedure is feasible, a course of multi-drug chemotherapy precedes surgery to downstage the tumor, followed by wide resection of the bone and insertion of an endoprosthesis. Currently, the 5-year survival rate after adequate therapy is approximately 60%-80%. The most frequent complications of conventional osteosarcoma are pathologic fracture and the development of metastatic disease, particularly to bone, lung, and regional lymph nodes.

Differential Diagnosis
General differential considerations include:
• Osteomyelitis
• Other tumors

• Metastatic lesion to bone
• Ewing sarcoma
• Aneurysmal bone cyst

When the lesion is at the posteromedial distal femur consider
• Cortical desmoid

Bone Tumors
The differential diagnosis for bone tumors is dependent on the age of the patient, with a very different set of differentials for the pediatric patient.
• Bone tumors
   • Bone-forming tumors

• Osteoid osteoma
• Osteoblastoma
• Enostosis (bone island)
• Osteopoikilosis
• Osteoma
• Osteosarcoma

• Cartilage-forming tumors[+]
• Fibrous bone lesions[+]
• Bone marrow tumors[+]
• Bony metastases