Biopsy in the Diagnosis of Infection: Clinical Approach

Overview: Biopsy

The practice of clinical infectious disease management has undergone a revolution with the advent of newer technologies, such as organism-specific molecular or protein-based diagnostic tools and, more recently, high throughput sequencing technologies on microbial diagnosis and the management of infection. Coupled with a variety of newer antimicrobial therapies, such as those for fungal and viral infections, significant shifts have occurred in clinical care. Despite these advances, a specific and timely diagnosis is often not achieved to guide therapy. In some conditions in which the disease process is self-limited or the therapies are broadly active or relatively nontoxic, a specific diagnosis may not be essential. Thus in community-acquired pneumonia a specific diagnosis is made in fewer than half of cases, but common therapies (e.g., with an antimicrobial macrolide or fluoroquinolone agent) have an antimicrobial spectrum broad enough to “cover” the common pathogens or the patient gets better on his or her own (i.e., viral syndrome). By contrast, in rapidly progressive infection in an immunocompromised host or infections of uncertain etiology, early and specific diagnosis allows targeted antimicrobial therapy with the best opportunity for success and with minimization of toxic side effects of such interventions. Specimen management and the selection and performance of appropriate assays are also critical to the success of interventional diagnosis. Cytologic or histopathologic diagnosis is a valuable adjunct to culture-based techniques because these may allow the interpretation of the significance of microbial detection (e.g., for herpesviruses in respiratory specimens).

Assessing the Benefit of Invasive Testing

Whether or not to obtain a biopsy depends on the condition of the patient and the urgency for diagnosis. Many factors will affect the decision process. Common considerations include whether the patient will tolerate the procedure. Complex patients often have multiple coexisting processes that increase clinical risk. What is the likelihood of success—can we reach the affected site and obtain an adequate sample?

Added considerations in biopsy-driven diagnostic procedures include the following:

• Urgent diagnosis before the patient becomes “too sick” for invasive procedures or in the face of rapidly progressive disease

• In patients in whom various therapies carry significant or unacceptable toxicities

• Distinguishing between infectious and noninfectious etiologies (e.g., inflammatory or cancer), notably in patients with atypical presentations of disease

• Sampling of a likely infection for microbiologic analysis (i.e., culture and susceptibility testing)

• Detection of organisms for which microbiologic culture techniques may be imprecise or unavailable (parasitic infections)

• Microbiologic and histopathologic evaluation in the patient with a lesion failing to respond to “appropriate therapy” ( Fig. 3.1 ) or slow to respond

  

• To help to resolve infection (excisional biopsy)

In general, a biopsy is utilized in patients in whom a specific diagnosis is critical to optimal management. The timing of the biopsy procedure is important. Some patients will predictably become “sicker” or less able to tolerate complications of a biopsy (bleeding tendency, significant cardiac disease, pneumothorax, infection, bowel perforation) later in the course of their disease process. These include patients undergoing cancer chemotherapy, organ or stem cell transplantation, or planning travel to medically underserved regions. These conditions may mitigate towards early “definitive” diagnosis. Underlying clinical conditions will often define the biopsy approach used; transjugular liver biopsies are used in patients with bleeding tendencies (the patient may bleed but into the vasculature from which the biopsy was obtained). Transjugular biopsies tend to be adequate for diagnosis less often than percutaneous biopsies (87% vs 69%), but in a retrospective study the difference was not significant. Transjugular biopsies require cardiac monitoring for arrhythmias induced by the catheterization procedure. The samples obtained are often fragmented but generally adequate for histologic diagnosis. The yield of a biopsy often depends on sampling and the skill of the pathologist interpreting the specimen, notably in certain conditions such as in hepatitis C infection of liver allografts. It is essential that an adequate tissue sample be obtained if a biopsy procedure is performed. This may be limited by the patient's clinical condition and ability to tolerate complications (low platelet count, mechanical ventilation, and encephalitis). However, an inadequate sample may necessitate repeat biopsies. Thus the specific biopsy procedure selected depends on the urgency for diagnosis, the tissue being sampled, and the likely pathogens in a given host. Notably, in the immunocompromised host with a wide array of potential pathogens, the handling of the specimen must be determined in advance so as to ensure the best chance of microbial diagnosis.

An example of the decision-making process is in the evaluation of diffuse pulmonary infections. Such processes may reflect multiple lung injuries, including noninfectious (e.g., fibrosis, radiation injury, heart failure, hemorrhage) as well as infectious. In acquired immunodeficiency syndrome (AIDS) patients, bronchoalveolar lavage (BAL) often provides a diagnosis, whereas BAL with transbronchial biopsy may be preferred in the non-AIDS immunocompromised host. This reflects the higher organism burden and slower progression of common infectious processes in AIDS (pneumocystis pneumonia, mycobacterial infection) than in the immunosuppressed or neutropenic individual. Similarly, a small tissue sample from fine-needle aspiration (FNA) may be adequate for diagnosis of a focal process (abscess) or transjugular biopsy for a diffuse process or if molecular amplification techniques can be used (viral hepatitis). A larger sample (core biopsy) is needed for patchy processes (BK polyomavirus infection of the transplanted kidney). FNA and percutaneous biopsies may have the disadvantage of tracking of infection or cells along the biopsy path. Thus video-assisted thoracoscopic surgical (VATS) or open (thoracotomy) excision of lung lesions in immunocompromised hosts (e.g., for focal Aspergillus -species pneumonia) may be more likely to provide adequate tissue for microbial diagnosis and, with disease debulking, allow the initiation of otherwise potentially fatal chemotherapy. Advantages of VATS biopsy include larger sample size, better selection of the biopsy site, and direct visualization of the biopsy site, which allows better control of any bleeding encountered. Radiologic techniques are often used to guide the biopsy procedure directly (under ultrasound or computed tomography [CT] scan) or generally, as in patchy processes affecting the lungs.