JOHNS HOPKINS
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Department of Pathology
600 N. Wolfe Street / Baltimore MD 21287-7093
(410) 955-5077 / FAX (410) 614-8087
Division of Medical Microbiology
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER Vol. 26, No. 09
Tuesday, May 15, 2007
A. Provided by Emily Luckman, Division of Outbreak Investigation, Maryland Department
of Health and Mental Hygiene.
There is no information available at this time.
B. The Johns Hopkins Hospital, Department of Pathology, Information provided by,
Zarir E. Karanjawala, M.D., Ph. D
Case presentation:
The patient is a 64 year-old Caucasian female with a history of Hashimoto thyroiditis, rheumatoid arthritis
and a 150 pack-year history of smoking. She presented with increasing dyspnea over several weeks and
an 8-pound weight loss. A chest X-ray revealed a 2 cm posterior right upper lobe mass with spiculations.
A biopsy of the lung mass, from an outside hospital, revealed adenocarcinoma. Additionally, PETpositive hilar lymphadenopathy was detected. Pulmonary function tests revealed a FEV1 of 77% and a
DLCO of 46%. A staging mediastinoscopy procedure was planned prior to lung lobectomy. An
intraoperative frozen section of an enlarged mediastinal lymph node revealed necrotizing granulomatous
inflammation. Subsequent tissue studies, including a silver stain, revealed numerous fungal organisms
consistent with Histoplama capsulatum. On day 14, fungal cultures were positive for H. capsulatum.
Epidemiology:
H. capsulatum is an intracellular organism that resides within the macrophages of the reticuloendothelial
system. It is a dimorphic fungus that has been reported worldwide and is a common fungal disease in the
United States, as well as Central America. It is also reported to be a common fungal disease among the
HIV/AIDS population. Within North America, the most common areas of histoplasmosis include the St.
Lawrence, Ohio, Mississippi and Missouri River valleys. Many individuals residing in these regions are
skin-test positive, indicating past infection. The organism resides in warm, moist soil that is organically
rich, typically containing bird or bat excrement. The organism is most often present in bird roosts, chicken
housing or caves. Historically, there have been three major outbreaks of histoplasmosis, each occurring in
Indianapolis. In these instances, the outbreak was associated with major construction activity and land
excavation.
Mycology and identification:
Definitive diagnosis of H. capsulatum is achieved by isolating cultures from the infected tissue site.
Cultures should be incubated for up to six weeks, however growth is often noted within three weeks.
Success of recovering the organism is variable and often depends on the tissue source and concentration of
the organism within the tissue. In cases where there is a heavy concentration of organisms in the tissues,
growth has been reported as early as five days.
H. capsulatum exists in two discrete forms, the mold or a mycelial phase and a yeast phase. Mold colonies
are white with areas of beige developing when sporulation occurs. Microscopically, the presence of 10-20
m spherical macroconidia with an irregular, or “spiked”, surface is diagnostic.
Additionally, examination of early cultures may reveal smaller microconidia emanating from the
sides of hyphae similar to the microconidia of B. dermatitidis.. The microconidia are thought to be
highly infectious due to their smaller size and ability to reach the alveoli and terminal bronchioles.
The yeast colonies are glistening, smooth, and yellow-white and have a pasty consistency. Upon
microscopic examination, the yeast cells are small (2-4 m in diameter). In tissue sections, the yeast cells
appear in clusters, both extracellularly and intracellularly within macrophages. The clustered organisms
identified within macrophage are surrounded by a clear halo, thus lending to the name “capsulatum”. The
inflammatory response is typically necrotizing and granulomatous, and in some cases, may simulate
tuberculosis. It is important to note that the tissue inflammatory response in immunocompromised hosts
can be blunted. Additionally, the organisms are often difficult to appreciate on routine hematoxylin and
eosin stained tissue. Therefore, in cases where there is a high clinical suspicion of an infectious etiology,
tissue sections should be silver stained (Gomori methenamine silver, GMS) to highlight the organisms,
which appear as small, intracellular budding yeast.
In culture, the conversion from the mold to the yeast form can be difficult. Therefore, the final
identification should be confirmed with either a nucleic-acid probe test or an exoantigen test. These assays
may be completed within one day after initial growth and do not need developed conidia for probe testing.
Probe testing involves using a chemiluminescent, single-stranded DNA probe (acridinium ester labeled) that
hybridizes to the ribosomal RNA of H. capsulatum mold forms. Stockman et al. reported a sensitivity and
specificity of 100% utilizing probe testing of 86 strains of H. capsulatum and 154 other fungi. Additionally,
antigen detection assays (enzyme linked immunosorbent assay, ELISA) against a polysaccharide antigen
can be detected in urine, serum, CSF and other body fluids.
Clinical presentation:
Histoplasmosis typically involves an acute pulmonary illness that is characterized by fevers, headache,
cough and chest pain. The pulmonary symptoms are variable in severity. Underlying pneumonia and
mediastinal lymphadenopathy are often associated. In less than 1% of cases, a chronic pulmonary infection
may develop, which includes cough, low-grade fevers and hemoptysis. On plain films, cavitary lesions
known as “histoplasmomas” may be seen. Histoplasmosis is frequently seen in HIV/AIDS, where it is often
disseminated. Progressive disseminated histoplasmosis is characterized by fever, fatigue and weight loss.
Early diagnosis in the HIV/AIDS population is important, since dissemination can be rapidly progressive
and fatal. The CNS can be involved and may present as chronic meningitis, and in some cases, mass lesions
may be detected in the cerebrum or spinal cord. Disseminated histoplasmosis may involve the
gastrointestinal tract in 70-90% of cases, while isolated gastrointestinal involvement is uncommon. The
small bowel is typically involved, where the disease is characterized by ulceration or a mass. In some cases,
these lesions have a similar endoscopic appearance of malignancy. Other sites of involvement include the
skin, oropharynx and eye.
References:
1. Koneman et al. Color atlas and textbook of diagnostic microbiology. 6th edition,
Lippincott-Raven, Philadelphia, 2006.
2. Mandell et al., Principles and practice of infectious disease. 6th edition, ChurchillLivingstone.