Bone carcinoma and the rheumatologist

Cause and effect are difficult to define clearly in many situations of musculoskeletal syndromes and malignancy. 

Certain rheumatic diseases have been associated with an increased risk of developing malignancy. One such example is the development of lymphoma in an individual with primary Sjögren’s syndrome. 

The converse also exits, in that certain rheumatic diseases are seen more frequently in the presence of an underlying malignancy, such as dermatomyositis. Other factors can contribute to the association of musculoskeletal syndromes and malignancy. 

Introduction

Many of the medications used to treat rheumatic diseases modulate the immune system and may be associated directly or indirectly with an increased risk of development of malignancy. In unusual circumstances, musculoskeletal involvement occurs as a paraneoplastic process, defined as a hormonal, neurological, haematological or biochemical disturbance associated with malignancy, but not directly related to invasion of the neoplasm or its metastases. 

This article specifically focuses on primary bone tumours and metastatic disease, and how they relate to rheumatology. The most common tumours will be discussed, and symptoms that may arise.

Bone tumours can show a wide range of nonspecific rheumatic manifestations. The presence of unexplained or atypical chronic bone pain, an enlarging bone mass, neurovascular compression syndromes or pathologic fractures should alert us to the possibility of a bone tumour causing these symptoms. 

These patients must undergo a complete physical examination, adequate imaging, and, if needed, a biopsy to confirm their diagnosis and offer them an opportune treatment. 

In addition, bone tumours and other malignancies can present remote clinical manifestations and unusual laboratory findings (eg. hypertrophic osteoarthropathy [HOA], hypophosphataemia, hyperphosphaturia and hypercalcaemia) that may be the first and early manifestation of an occult cancer. These findings should motivate a cancer screening according to age, sex and personal history. 

Primary musculoskeletal tumours

The primary tumours of bone can be either benign or malignant.

A primary malignant bone cancer is any neoplasm that develops from the tissues or cells found within bone that has the ability to metastasise. Neoplasms may develop or arise from any of the types of cells present within the bone, eg. osteoblasts, chondrocytes, adipose and fibrous tissue. A neoplasm developing from any of these tissues is called a sarcoma, which signifies that it is derived from mesenchymal tissue. The bone sarcomas are named for the predominant differential tissue type, such as osteosarcomas, chondrosarcomas and liposarcomas.

The most common manifestation of these tumours is the development of pain in the area of the lesion, which may be accompanied by a sympathetic effusion or stiffness in the surrounding joint. This discomfort does not seem to be activity-related and is often worse at night. These tumours can manifest, however, as painless masses or as pathological fractures. Systemic features, such as fatigue, malaise, weight loss, fevers and night sweats, are rare with all of these tumours except for Ewing’s sarcoma. 

Primary malignant bone tumours are uncommon, particularly compared with other types of carcinomas. They have their highest incidence in childhood and adolescence, and constitute 3.2% of childhood malignancies that occur before 15 years of age. These tumours commonly arise out of areas of rapid growth, with the most common site of primary bone sarcomas being the metaphysic near the growth plate.

Osteosarcomas are the most common type of primary malignant bone tumours. They generally occur in individuals in the second decade of life or in elderly individuals. Unfortunately they can occur secondary to radiation therapy delivered as treatment for other malignancies. 

Paget’s disease of bone can rarely (< 1% of cases) proceed to malignant transformation. Severe pain in the setting of Paget’s disease may signal transformation to osteogenic sarcomas. These tumours most frequently affect the femur, humerus, skull and pelvis and can result in pathological fractures. Survival is usually less than one year. Differentiating malignancy from Paget’s disease may require a biopsy.

Chondrosarcomas have been reported as the second most common of the malignant bone tumours. This tumour may occur as a primary tumour or as a malignant transformation in the setting of benign lesions, such as an enchondroma or osteochondroma. Fibrosarcomas are significantly less common than the previously mentioned tumours and accounts for less than 4% of primary malignant bone tumours.

In addition to the primary malignancies of bone, there are multiple malignant tumours that can arise from mesenchymal connective tissue; these are also known as sarcomas. They can result in the joint complaints, but more often result in soft tissue complaints. They are very rare.

Metastatic disease

When bone lesions are identified, primary tumours need to be considered, although most malignant lesions in bone are metastatic. Metastasis rarely affects muscles, joints or adjacent connective tissue. More commonly, it affects bone. The most common sites are the spine and pelvis. It is uncommon to find metastatic lesions distal to the elbow, and, although rare, metastasis to the foot is more common than to the hand. 

When distal metastasis is identified, it is often associated with lung carcinoma. Primary tumours generally associated with metastases to bone include tumours of the prostate gland, thyroid gland, breasts, lung and kidneys. 

Although most skeletal metastases do not produce pain, one of the most common causes of cancer pain is the infiltration of bone. The pain can be intense and stabbing or dull. It is often worse with weight-bearing and movement. Rheumatic or arthritic complaints often can occur before lesions are easily identified on radiographs. Arthritis associated with metastatic carcinoma is most commonly monoarticular and most commonly affects the knee. 

Metastases to the hip, ankle, wrist, hand and foot have been reported, but occur less frequently. Breast and lung carcinomas are present in most patients. 

Metastases to the extremities can simulate gout, osteomyelitis or tenosynovitis. The development of joint involvement can be related to direct synovial implantation or involvement of the juxta-articular or subchondral bone.

Post-chemotherapy rheumatism

Several rheumatic or musculoskeletal manifestations can develop in patients after administration of chemotherapy for the treatment of carcinomas. Post-chemotherapy rheumatism has been best described in patients treated for breast carcinoma, but also has been described in other malignancies, including ovarian carcinoma and non-Hodgkin lymphoma. 

The phenomenon has been described as a non-inflammatory, self-limited, migratory arthropathy. Typically, symptoms develop several weeks to several months after the completion of chemotherapy and often include myalgia, stiffness, arthralgia and arthritis involving the small joints of the hands, ankles, and knees. 

It can be mistaken for rheumatoid arthritis based on the symptoms; however, most patients have little or no evidence of synovitis and have no radiographic or serological evidence to suggest a diagnosis of RA. 

The pathogenesis of this process is unknown; however, it is self-limited, usually lasting less than one year, and is best treated in a conservative manner. Evaluation should be performed to exclude recurrent carcinoma or another inflammatory condition.