N Miscellaneous musculoskeletal problems in patients with neoplasia

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1. Bone and joint infections. Patients with malignancy, especially those receiving cytotoxic therapy, are predisposed to septic complications such as pyarthrosis and osteomyelitis. Organisms include both common and opportunistic pathogens. Pyogenic arthritis caused by Streptococcus bovis or enteric organisms may signal an occult colonic neoplasm.

2. Referred pain to the joints, neck, or back. Knee pain exacerbated by recumbency has been attributed to diffuse histiocytic lymphoma of the spinal cord.

Back pain and radiculitis may be secondary to leukemic meningeal involvement or be the initial manifestation of Hodgkin's disease. Shoulder pain with normal findings on shoulder examination may be referred pain caused by infradiaphragmatic, intraabdominal neoplasms. Alternatively, intrathoracic neoplasms (e.g., Pancoast tumor) may extend into the brachial plexus and cause pain in a shoulder with a normal range of motion but evidence of muscle atrophy and loss of deep tendon reflexes.

Mimics of vasculitis such as subacute bacterial endocarditis, cholesterol emboli, and anti-cardiolipin syndrome may occur in any patient with concomitant neoplasia.

II. Malignancies associated with an established rheumatic syndromeThe risk for certain types of cancer appears to be increased in some of the rheumatic syndromes. The increased incidence of malignancy does not appear to be related to antirheumatic therapy in the following instances:

A. Polymyositis is associated with all types of neoplasm. Although the increased risk for cancer after the diagnosis of polymyositis is consistent with cancer detection bias, clinical vigilance for associated neoplasia is indicated. Routine urinalysis, complete blood count, examination of stools for occult blood, sigmoidoscopy, mammography, prostate and testicular examinations, chest radiography, and Papanicolaou's smear are recommended screens. A more extensive search for occult malignancy may be indicated in patients at greatest risk, such as older men or patients with severe, refractory dermatomyositis.

B. RA, even in the absence of treatment with potentially oncogenic drugs, appears to be associated with an increased risk for hematologic malignancies, including lymphoma and myeloma. There is also an increased risk for leukemia in some cohorts of RA patients. In certain patients with Felty's syndrome, there is a twofold increase in total cancer incidence and a 12-fold increased risk for non-Hodgkin's lymphoma. There is also an increased risk for CD16+ large granular lymphocytes and leukemia. RA patients with secondary Sjogren's syndrome are at a 33-fold increased risk for non-Hodgkin's lymphoma. Paraproteins are an additional marker of increased risk for hematopoietic neoplasms.

The overall risk for malignancy is reduced in some RA cohort studies. Prospective, longitudinal cohort studies of RA patients have demonstrated a lower incidence of stomach and colon carcinomas, the latter possibly related to use of nonsteroidal antiinflammatory drugs.

C. Patients with Sjogren's syndrome are at increased risk for the development of non-Hodgkin lymphoma. Waldenstrom's macroglobulinemia also appears to be more frequent in these patients. The risk is increased in both primary and secondary Sjogren's syndrome in National Institutes of Health (NIH) cohorts. In Italian studies, women with primary Sjogren's syndrome are at greatest risk. Risk factors such as disappearance of rheumatoid factor were predictive of the evolution in the NIH cohort but not in a Vanderbilt cohort.

D. Systemic sclerosis patients with pulmonary fibrosis and "honeycomb" lung are at increased risk for bronchoalveolar cell carcinoma.

Discoid lupus erythematosus lesions may develop into epidermoid carcinoma. Patients with eosinophilic fasciitis are at increased risk for associated aplastic anemia and lymphoproliferative disease.

Immunodeficiency states. Patients with X-linked hypogammaglobulinemia, common variable immunodeficiency, ataxia-telangiectasia, and Wiskott-Aldrich syndrome are at increased risk for the development of lymphoreticular malignancy. Leukemia, medulloblastoma, and adenocarcinomas may also occur with increased frequency. Asymptomatic patients with isolated immunoglobulin A deficiency do not appear to have an increased risk for neoplasia.

Patients with systemic lupus erythematosus do not appear to be at increased risk for malignancy, except for neoplasia complicating cytotoxic therapy ( Table

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Table 50-3. Malignancies associated with established connective tissue disorders

G. Mixed cryoglobulinemia associated with vasculitis and hepatitis C was associated with non-Hodgkin's lymphoma in 14 of 200 patients. Monitoring for hepatocellular carcinoma should also be considered.

H. Paget's disease. Osteogenic sarcoma may complicate Paget's disease in 1% of patients and present with persistent, severe pain. Bone biopsy may be necessary for accurate diagnosis.

I. Multicentric reticulohistiocytosis may herald a subsequent malignancy.

J. Chronic osteomyelitis. Squamous cell carcinoma may occur in adjacent cutaneous tissue in up to 2% of cases.

III. Malignancy as a complication of antirheumatic therapy The influence of immunosuppressive drug therapy in altering the incidence of cancer in the rheumatic population is unclear, but an increased risk for neoplasia is apparent with some regimens.

A. Alkylating agents such as cyclophosphamide and chlorambucil can increase the risk for leukemia and myelodysplastic syndromes. Cytogenetic abnormalities of chromosome 5/7 are associated with therapy-related myelodysplastic syndromes seen in rheumatic disease. In addition, cyclophosphamide is associated with bladder and other genitourinary cancers. As the latter may occur 20 years after exposure, ongoing surveillance should be considered.

Sodium-2-mercaptoethane sulfate can bind the toxic metabolite acrolein and may diminish the incidence of bladder carcinoma.

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