Summary: Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.
Fungal infections are becoming more frequent because of expansion of at-risk populations and use of treatment modalities that permit longer survival of these patients (109 ). Some of the changes in endemic fungal infections can be attributed to climate changes, extension of human habitats, ease of travel, and shifting populations. At-risk populations for opportunistic fungal infections or disseminated endemic fungal infections include patients who have received transplants, those prescribed immunosuppressive and chemotherapeutic agents, HIV-infected patients, premature infants, the elderly, and patients undergoing major surgery. Thus, a shift in the mycoses encountered in the health care setting has occurred. Prior to the 21st century, bloodstream infections were more frequently caused by Candida spp. and agents of invasive pulmonary infections included primarily endemic mycoses and Aspergillus spp. Today, fungi previously considered nonpathogenic, including mucoraceous genera (formerly called zygomycetes) and a variety
of both hyaline and dematiaceous molds, are commonly seen in immunocompromised patients. In addition, diagnosis of infection versus colonization with these fungi is a frequent problem that has important treatment implications for these patients. Furthermore, advances in diagnostic radiology and in patient support (such as platelet transfusions, etc) have allowed greater ability to pursue specific diagnoses by collecting tissue biopsy specimens from body sites formerly not available for histopathologic examination.
The advantages of obtaining these specimens have created a series of diagnostic challenges because of the limited amount of tissue obtained and the architectural distortion produced by these new procedures. In addition, the therapeutic armamentarium now available and the presence of resistance of these fungi to different drugs have compounded the diagnostic challenges. Histopathology continues to be a rapid and cost-effective means of providing a presumptive or definitive diagnosis of an invasive fungal infection. However, the use of fungal silver impregnation stains (Grocott or Gomori methenamine silver [GMS]) cannot alone solve these challenges, and newer diagnostic techniques may be required. Microbiologists, pathologists, and clinicians need to be aware of the limitations of tissue diagnosis, the pitfalls of morphological diagnosis, and the tests that can be performed with tissue and other samples to make organism-specific diagnoses. In this review we present epidemiologic, clinical, and morphological findings and interpretation pitfalls regarding the most frequently encountered yeasts and molds, as well as alternative testing that can be performed with other samples. Table 1 summarizes the clinical presentations and host reactions produced by the mycoses discussed in this review, Fig. 1 to to3 3 summarize the morphologies of these fungi and the differential diagnoses for each, and Table 2 summarizes the alternate testing that can be performed with specimens that were not sent to the pathology laboratory. Additionally, we present methods that can be used for diagnosis of specific yeasts and molds in formalin-fixed, paraffin-embedded tissue submitted for histopathologic diagnosis, as well as a series of scenarios that should help guide the diagnosis and treatment of patients with mycoses.