Metastatic Bone Disease

Aiman Awad
Darlington Memorial Hospital

Pathophysiology
How tumour cells migrate to bone? How tumour cells grow in bone?

Diagnosis.
Primary or secondary. Solitary or multiple. If secondary, where is the primary? The local extension of the metastatic tumour. Differential diagnosis.

Pathophysiology
How

tumour cells migrate to bone?

By 3 main mechanisms:

(1) direct extension, (2) retrograde venous flow, and (3) seeding with tumour emboli via the blood circulation

Sources of Bone Metastases

Breast Prostate Kidny Lung Thyroid Bladder Gastrointestinal Tract.

Bone metastasis

the most common locations include the following:

Spine Pelvis Ribs Proximal limb girdles

Metastases distal to the knee and elbow are extremely uncommon, but approximately 50% of these acral metastases are secondary to primary lung tumors. Carcinomas, such as those of the breast and prostate, rarely exhibit such a distinct pattern.

How tumour cells grow in bone?

There are two forms of bone Metastasis

Osteolytic

bone disease. bone disease.

Osteoblastic

Osteolytic bone disease

(1)

(2)

(3)

(4)

Metastatic tumour cells release humoral factors that stimulate osteoclastic recruitment and differentiation. Osteoclasts begin to break down bone. Bone resorption results in the release of growth factors that stimulate tumour cell growth. As the tumour proliferates, it produces substances that increase osteoclast-mediated bone resorption.

Osteoblastic bone disease

1- Metastatic tumour cells release growth factors that stimulate the activity of osteoclasts. 2-Tumor cells also secrete growth factors that stimulate the activity of osteoblasts. 3-Excessive new bone formation occurs around tumour-cell deposits. 4-Osteoclastic activity releases growth factors that stimulate tumor cell growth. 5-Osteoblastic activation releases unidentified osteoblastic growth factors that also stimulate tumour cell growth.

Clinical Presentation

Pain initially related to activity then progressive day and night. Pathological fracture. Mass. Abnormal radiographic finding detected during the evaluation of an unrelated problem.

Diagnosis of bone Metastasis

History and Physical Examination Laboratory Investigation X Ray Bone Scan CT MRI Biopsy

METASTASES OF UNKNOWN ORIGIN

a patient over the age of 40 with a new, painful bone lesion, multiple myeloma and metastatic carcinoma are the most likely diagnoses Prostate cancer and breast cancer are the two most common primary sources for bone metastasis. If a patient has no known primary tumour, the most likely sources are lung cancer and renal cell carcinoma.

Biopsy should not be done until the evaluation is complete:

1.

2. 3.

4. 5. 6.

The lesion may be a primary sarcoma of bone that may require a biopsy technique that allows for future limb salvage surgery; Another more accessible lesion may be found If renal cell carcinoma is considered likely, the surgeon may wish to consider preoperative embolization to avoid excessive bleeding; If the diagnosis of multiple myeloma is made by laboratory studies, an unnecessary biopsy will be avoided; The pathological diagnosis will be more accurate if aided by appropriate imaging studies; and the pathologist and surgeon may be more assured of a diagnosis of metastasis made on frozen section analysis if supported by the preoperative evaluation. This is important if stabilization of an impending fracture is planned for the same procedure.

physical examination

The evaluation begins with a history focusing on any previous malignancies. Examination includes not only the involved extremity, but also the thyroid, lungs, abdomen, prostate in men, and a breast examination in women

Laboratory analysis

should include a FBC, ESR , electrolytes, liver enzymes, alkaline phosphatase, a serum protein electrophoresis, and possibly prostate-specific antigen. A FBC may be helpful to rule out infection and leukemia. The ESR usually is elevated in infection, metastatic carcinoma, and small "blue cell" tumors such as Ewing sarcoma, lymphoma, leukemia, and histiocytosis.

A serum protein electrophoresis should be ordered if multiple myeloma is part of the differential diagnosis. Hypercalcemia may be present with metastatic disease, multiple myeloma, and hyperparathyroidism. Alkaline phosphatase may be elevated in metabolic bone disease, metastatic disease, osteosarcoma, Ewing sarcoma, or lymphoma. Blood urea nitrogen and creatinine may be elevated with renal tumors, and a urinalysis may reveal hematuria in this setting.

A basic metabolic panel may be indicated to evaluate the overall health of a patient.

plain roentgenograms

provides useful diagnostic information for evaluation of bone lesions. Most vertebral lesions in adult patients are metastases, myelomas, or hemangiomas. The aggressiveness of the lesion, and whether it is likely to be benign or malignant, usually can be determined by careful evaluation of the plain films.

Technetium bone scans

With the exception of myeloma, all malignant neoplasms of bone demonstrate increased uptake on technetium bone scans A normal bone scan is therefore very reassuring; however, the converse statement is not true because most benign lesions of bone also demonstrate increased uptake.

Computed tomography (CT)

Helpful in assessing ossification and calcification and in evaluating the integrity of the cortex CT of the chest, abdomen, and pelvis should be obtained for Unknown Metastasis.

Axial CT scan shows 2 rounded, mixed osteolytic-sclerotic lesions in the thoracic vertebral body of a 44-yearold woman with lung carcinoma.

Magnetic resonance imaging (MRI)

the most accurate technique for determining the limits of disease both within and outside bone.

not very useful in differentiating benign from malignant lesions.

Biopsy

patient with a suspected primary musculoskeletal malignancy should be referred before biopsy to the institution where definitive treatment will take place A biopsy should be planned as carefully as the definitive procedure. Regardless of whether a needle biopsy or an open biopsy is done, the biopsy track should be considered contaminated with tumor cells The surgeon performing the biopsy should be familiar with incisions for limb salvage surgery