H. capsulatum: roundtooval,smallyeastformsmeasuring2to5µmindiameter(
Fig.13.39A
C. immitis: thick-walled,nonbuddingspherules,20to60µmindiameter,oftenfilledwithsmallendospores(see
Fig.13.39B
B. dermatitidis: roundtoovalandlargeryeastformsthanHistoplasma (5to25µmindiameter)thatreproducebycharacteristicbroad-basedbudding(see
Fig.13.39CandD
Clinical manifestations may take the form of (1) acute (primary) pulmonary infection, (2) chronic (granulomatous) pulmonary disease, or (3) disseminated miliary disease. The primary pulmonary nodules, composed of aggregates of macrophages filled with organisms, are associated with similar lesions in the regional lymph nodes. These lesions evolve into small granulomas complete with giant cells and may develop central necrosis and later fibrosis and calcification. The similarity to primary tuberculosis is striking, and differentiation requires identification of the yeast forms (best seen with silver stains). The clinical symptoms and signs resemble those of a “flulike” syndrome and are most often self-limited. In the vulnerable host, chronic cavitary pulmonary disease develops, with a predilection for the upper lobe, resembling the secondary form of tuberculosis. It is not uncommon for these fungi to give rise to perihilar mass lesions that resemble bronchogenic carcinoma radiologically. At this stage, manifestations may include cough, hemoptysis, and even dyspnea and chest pain.
In infants or immunocompromised adults, particularly those with HIV infection, disseminated disease (analogous to miliary tuberculosis) may develop. Under these circumstances, there are no well-formed granulomas. Instead, focal collections of phagocytes containing yeast forms are seen within the liver, spleen, lymph nodes, lymphoid tissue of the gastrointestinal tract, and bone marrow. The adrenal glands and meninges also may be involved, and in a minority of cases, ulcers form in the nose and mouth, on the tongue, or in the larynx. Disseminated disease produces a febrile illness marked by hepatosplenomegaly, anemia, leukopenia, and thrombocytopenia. Cutaneous infections with disseminated Blastomyces organisms frequently induce striking epithelial hyperplasia, which may be mistaken for squamous cell carcinoma.
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Fig. 13.39 (A)Histoplasma capsulatum yeastformsfillphagocytesinalymphnodeofapatientwithdisseminatedhistoplasmosis(silverstain).(B)Coccidioidomycosiswithintactspheruleswithinmultinucleatedgiantcells.(C)Blastomycosis,withroundedbuddingyeasts,largerthanneutrophils.Notethecharacteristicthickwallandnuclei(notseeninotherfungi).(D)Silverstainhighlightsthebroad-basedbuddingseeninBlastomyces immitis organisms.