Biopsy Dx

Overview: Tissue biopsy is often a useful means of establishing the diagnosis or degree of disease activity in selected rheumatic disorders (Table 4). Tissue samples may reveal histologic evidence of inflammation, vasculitis, fibrosis, atrophy, necrosis, or infection. For all sites, one must determine how the tissue must be processed before obtaining the sample. This should be communicated by the pathologist to the surgeon before the procedure. Specimens for culture, for example, cannot be put in fixative, and samples that are to undergo immunofluorescent analysis may require freezing rather than fixation. The most common and useful biopsy sites are skin, muscle, blood vessels, synovium, and nerves, as described below.

Skin: Histologic examination of skin using light or immunofluorescent microscopy may be helpful in the diagnosis of systemic lupus erythematosus (SLE), discoid lupus, dermatomyositis, scleroderma, cutaneous vasculitis, or panniculitis. The lupus band test uses skin biopsy to detect deposition of immunoglobulins at the dermal-epidermal junction of uninvolved skin. Although quite specific for the diagnosis of SLE, the lupus band test is not sensitive, seldom necessary and does not discriminate between those with cutaneous versus systemic features of lupus. Inflammation in the walls of small cutaneous blood vessels can be used to diagnose cutaneous vasculitis, usually of leukocytoclastic vasculitis.  Although many issues can be successfully addressed using a 4-mm punch biopsy specimen, a deeper, incision wedge biopsy specimen may be required to evaluate some problems such as eosinophilic fasciitis and panniculitis or to optain small to medium size vessels.  Tissue samples should be taken from fresh new lesions, with an edge of normal skin included. Both punch and wedge biopsies are usually performed by dermatologists as a simple outpatient procedure.

Muscle: Biopsy of involved muscle is often required to diagnose inflammatory myositis, metabolic myopathies, muscular dystrophies, or can even be used to diagnose small to medium sized vessel vasculitis. The biopsy site should be the most symptomatic area. End-stage, atrophic and areas of recent trauma should be avoided.  Also, muscles previously used for injection or electromyography should be avoided as they may yield false-positive results. Needle aspiration of muscle is useful for histologic evaluation, and the diagnostic yield may be improved by taking as many as four samples from the same cutaneous puncture site. Open surgical biopsies are usually required to obtain sufficient tissue to measure functional enzyme levels for evaluation of metabolic disorders. Contraction of the biopsied muscle should be avoided (as this causes artifact) by using a surgical muscle clamp. The biopsy specimen should be delivered to the pathologist immediately (within 30 minutes) after collection for proper specimen handling for histology by light microscopy, electron microscopy, and enzyme analysis.

Blood Vessels: Histologic analysis of the vasculature is routinely done whenever tissue biopsies are obtained. Blind tissue biopsies (i.e., muscle, skin, testes) are uncommonly useful in identifying significant vascular pathology. Hypersensitivity (also known as leukocytoclastic) vasculitis (inflammation of venules) is one of the most common vascular abnormalities seen on outpatient punch skin biopsies of “palpable purpura”. Unfortunately the differential diagnosis is inversely proportional to vessel size.  Hence the finding of leukocytoclastic vasculitis has a numerous causes including drugs, infections, malginancies and autoimmune disorders.  Conversely, identification of a large vessel vasculitis results in few diagnostic considerations.   Temporal artery biopsy is useful in establishing a diagnosis of giant cell arteritis. The diagnostic yield of the procedure is maximized by taking a large section of vessel (at least 3 cm in length) and examining at least 20 to 25 cross-sections. Multiple section analysis is required because “skip” vascular lesions may be missed. This procedure is usually done in the operating room under local anesthesia. The other large vessel vasculitic disorder, Takayasu’s arteritis, is best diagnosed by angiography.

Synovium: Because synovial fluid often reflects processes active within the synovium, synovial fluid analysis is often attempted before considering synovial biopsy. Although synovial histology was once used as a diagnostic criterion for RA, this diagnosis is easily and preferably made on clinical grounds without synovial biopsy. However, synovial tissue biopsy is essential for the diagnosis of synovial neoplasias or chronic joint infections such as those caused by mycobacteria or evaluation of chronic undiagnosed monarthritis.  Synovial biopsy may be necessary when synovial fluid is unrevealing or not accessible. Synovial tissue culture is more often positive for mycobacterial or fungal infection than synovial fluid culture. Blind needle or arthroscopically guided biopsies usually yield sufficient tissue for histologic analyses and cultures; open surgical biopsies are only rarely required. Tissue samples are usually fixed in formalin or in alcohol if gout is suspected.

Nerve: Biopsy of the sural nerve is useful for evaluating suspected vasculitis with a mononeuritis multiplex.  The yield of such a procedure is likely to be enhanced in the setting of a foot drop or lower extremity neuropathy. Thus, an abnormal nerve conduction study is likely to improve the diagnostic yield of a sural nerve biopsy. Usually, the biopsy is performed under local anesthesia, at the bedside, or in the clinic. There may be residual local hypesthesia present after the procedure.

Kidney: Renal biopsies are occasionally necessary to determine the underlying pathology in acute renal failure, progressive nephrotic syndrome, SLE, acute nephritic syndrome (hematuria, red cell casts, proteinuria, hypertension), and undiagnosed hematuria and to assess renal allograft and possible rejection. Kidney biopsy is not indicated in all patients with SLE with renal or urine abnormalities.  It is most helpful in determining whether current renal abnormalities are owing to coexistent conditions [e.g., diabetes, hypertension, non steroidal anti-inflammatory drug (NSAID) therapy] or if lupus renal lesions are reversible (high activity score) or irreversible (high chronicity score). Before the procedure, the patient’s complete blood count (CBC), prothrombin time, PTT, and bleeding time should be checked. Relative contraindications for biopsy may include active infection, uncontrolled hypertension, thrombocytopenia, bleeding diathesis, and pregnancy. Biopsy is usually percutaneous, with ultrasound guidance.  The most common complication, gross hematuria, occurs in 5% to 10% of patients and usually resolves in 2 to 3 days.

Cost: Depending on whether done as an outpatient or inpatient/operating room procedure; skin, $150; muscle, $250–350; kidney, $325–625 (plus hospital costs).

BIBLIOGRAPHY

Cardinali C, Caproni M, Fabbri P. The utility of the lupus band test on sun-protected non-lesional skin for the diagnosis of systemic lupus erythematosus. Clin Exp Rheumatol.1999;17:427-32. PMID: 10464552