PART TWO
Diagnostic Cytology
A 55-year-old woman with fever, cough, and bloody sputum
production was admitted to the hospital. Radiographs of the
chest revealed bilateral pulmonary infiltrates. Significant in
the history of the patient was the presence of diabetes mellitus
that had been difficult to control. Characteristic spherules of
coccidioides were present in a Papanicolaou-stained specimen
of sputum. Culture results were confirmatory.
Another characteristic case is that of a 45-year-old resident
from southern California who presented with a 2-cm nodule
in the periphery of the left lower lobe. FNA was obtained and
revealed the classic spherules of coccidioides. A confirmatory
thoracotomy was performed.
In a 1986 study, Freedman and associates demonstrated the
utility of FNA in the diagnosis of pulmonary coccidioidomycosis.
In a series of 112 FNAs performed on solitary pulmonary nod-
ules, eight cases were identified as coccidioidomycosis by the
presence of spherules in the aspirated material.209 Chen has
emphasized the pitfall of misinterpreting atypical bronchial
epithelial cells as carcinoma cells in patients with coccidioido-
mycosis.210
Pulmonary Histoplasmosis
The term
histoplasmosis
actually refers to two different and clini-
cally distinct entities. The more common use of the term is
applied to a systemic disease produced by the dimorphic fun-
gus
Histoplasma capsulatum
var.
capsulatum.
A second disease,
endemic to Africa and called African histoplasmosis, is pro-
duced by infection with
Histoplasma capsulatum
var.
duboisii.
Pulmonary involvement with this disease is much less common
than that with
H. capsulatum
var.
capsulatum.
The mycelial phase
of the latter organism is found in soil and other areas heavily
contaminated with bird droppings. Although it is worldwide in
distribution, some highly endemic areas include the Mississippi
and Ohio River valleys in the United States, Mexico, Guatemala,
Peru, and Venezuela. Respiratory infection occurs by inhalation
of the highly infectious conidia. Rapid systemic dissemination
through infected macrophages may occur. The majority of pul-
monary infections are asymptomatic and resolve spontaneously.
A minority of patients may develop acute pulmonary disease,
systemic disease, or chronic pulmonary disease. Disseminated
disease has also been reported as a complication of lymphopro-
liferative disease, anticancer chemotherapy, organ transplanta-
tion in association with immunosuppressive drugs, and AIDS.
Young children are more susceptible to disseminated disease.
Chronic pulmonary disease mimics tuberculosis with granulo-
matous inflammation, caseous necrosis, cavitation, and fibrosis.
A special form of the disease of particular interest to cytologists
is the peripheral coin lesion, also referred to as a histoplas-
moma. These lesions are always suspicious signs of carcinomas
and must be evaluated. FNA is an appropriate technique for
initial evaluation.
Histoplasma capsulatum
has been reported in sputum, bron-
chial washings, FNAs, and gastric washings from patients with
symptoms. The organism is small enough to make recognition
on Papanicolaou-stained specimens difficult. With special stain-
ing, particularly methenamine silver, it may be visualized as a
2- to 4-pm round-to-oval, single budding yeast-like organism
(Fig. 13.51). For diagnostic purposes, it should be intracellular
in macrophages or meutrophils.211,212 A number of small bud-
ding yeasts present as contaminants are remarkable in their
resemblance to
Histoplasma;
however, they are usually found
extracellularly.167
Fig. 13.51
Histoplasma capsulatum.
Tracheal aspirate (methenamine
silver x OI).
We have seen histoplasmosis in such diverse cytologic speci-
mens as touch preparations from mediastinal lymph nodes, tra-
cheal aspirates from an infant, and an FNA from a peripheral
subpleural nodule.
Pulmonary Candidiasis
Various species of the genus
Candida
but most frequently
Can-
dida albicans
are capable of producing superficial mucocuta-
neous and systemic fungal infections in humans. As noted by
Chandler and Watts, candidiasis is the most frequently encoun-
tered opportunistic fungal infection and accounts for approxi-
mately 50% of such infections among immunocompromised
patients.193 In healthy humans,
C. albicans
makes up part of the
flora of the oral cavity, upper respiratory tract, digestive tract,
and vagina.
Pulmonary candidiasis is almost exclusively a fungal infec-
tion that occurs in patients who have underlying disease or who
are immunocompromised. The symptoms and signs consist of
fever, cough, dyspnea, and pulmonary infiltrates on radiography.
Because of the frequent presence of
Candida
species in the absence
of disease, laboratory confirmation of pulmonary candidiasis is
difficult. Positive findings in cultures of sputum and bronchial
material may be ambiguous. Conclusive diagnosis of pulmonary
infection should be provided either by open biopsy in which
microscopic examination provides evidence of parenchymal inva-
sion by organisms or by transthoracic FNA in which organisms
are demonstrated and confirmed by cultural identification.
Species of
Candida
are the most frequently encountered fungi
in cytologic specimens. Because of this frequency, their clinical
significance may be discounted. All
Candida
species may appear
as small, oval, 2- to 4-pm budding yeasts. They may occasionally
elongate into pseudohyphal forms with additional budding at
the points of constriction (Fig. 13.52). Although their presence
in pulmonary material is not usually significant, it may reflect
overwhelming candidiasis in a compromised host.167 We have
experienced such a situation in an immunocompromised patient
in whom the finding of candidal pseudohyphae in a bronchial
brushing correlation with a blood culture positive for
C. albicans.
This patient died 2 days later. Ness and associates have recom-
mended testing BAL for
Candida
antigen to distinguish between
Candida
pneumonia and
Candida
colonization of the respiratory
tract or oral contamination.213
324
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