Chronic Cavitary Pulmonary Histoplasmosis-Novel Concepts Regarding Pathogenesis

Abstract

Because the apices of the lungs are most commonly involved in chronic cavitary histoplasmosis (CCPH), it has been assumed by many to have a pathogenesis which is similar to post-primary tuberculosis. Fungi such as Aspergillus may colonize pulmonary bullae. Although less common, colonization by Histoplasma capsulatum in a heavily endemic area is possible or even probable. In chronic obstructive pulmonary disease (COPD), apical bullae are characteristic. Since COPD is common and CCPH is rare, the pathogenesis of CCPH remains incompletely understood. What is presently known about the pathogenesis of CCPH has not changed appreciably since 1976. A cellblock from a patient with CCPH was analyzed with histochemical stains for T cells, B cells, plasma cells, and macrophages to better understand the pathogenesis of CCPH. The pathogenesis of cavitary disease in histoplasmosis has been assumed to resemble that of tuberculosis. However, liquefaction of a caseous focus in lung apices which resulted from blood-borne tubercle bacilli is distinctly unlike CCPH, as caseation is unusual. Rather, repeated colonization of the apical and other bullae by propagules (microconidium, macroconidium, hyphal fragment) of H. capsulatum in patients with COPD who have resided in heavily endemic areas appears to be the primary event in CCPH. Immunohistochemical enumeration of specific cell types in a patient with CCPH has not been previously carried out to our knowledge, but is only a first step in understanding the disease. In future studies, identification of the varieties of macrophages and cytokines in CCPH may reveal whether the process is pro-inflammatory, anti-inflammatory, or both.

Keywords: cavitary; histoplasmosis; pathogenesis.

Figure 1

(A) Microscopic examination of the tissue section revealed pulmonary parenchyma with a mixed inflammatory infiltrate predominated by macrophages and neutrophils, with associated necrotic debris. Chronic inflammatory cells were also present, including several lymphocytes and a few plasma cells. (B) Grocott–Gömöri’s methenamine silver stain; Special staining revealed numerous yeasts, including budding forms. (C) Immunohistochemical analysis confirmed the presence of numerous macrophages with abundant cytoplasm (CD163 immunohistochemical stain. (D) Although T-cells predominated over B-cells, B-cells were present in a mostly perivascular pattern as noted by immunohistochemical analysis (CD20 immunohistochemical stain). Scale bar: 10 µm.

Figure 1

(A) Microscopic examination of the tissue section revealed pulmonary parenchyma with a mixed inflammatory infiltrate predominated by macrophages and neutrophils, with associated necrotic debris. Chronic inflammatory cells were also present, including several lymphocytes and a few plasma cells. (B) Grocott–Gömöri’s methenamine silver stain; Special staining revealed numerous yeasts, including budding forms. (C) Immunohistochemical analysis confirmed the presence of numerous macrophages with abundant cytoplasm (CD163 immunohistochemical stain. (D) Although T-cells predominated over B-cells, B-cells were present in a mostly perivascular pattern as noted by immunohistochemical analysis (CD20 immunohistochemical stain). Scale bar: 10 µm.

Figure 1

(A) Microscopic examination of the tissue section revealed pulmonary parenchyma with a mixed inflammatory infiltrate predominated by macrophages and neutrophils, with associated necrotic debris. Chronic inflammatory cells were also present, including several lymphocytes and a few plasma cells. (B) Grocott–Gömöri’s methenamine silver stain; Special staining revealed numerous yeasts, including budding forms. (C) Immunohistochemical analysis confirmed the presence of numerous macrophages with abundant cytoplasm (CD163 immunohistochemical stain. (D) Although T-cells predominated over B-cells, B-cells were present in a mostly perivascular pattern as noted by immunohistochemical analysis (CD20 immunohistochemical stain). Scale bar: 10 µm.