Fig. 13.7 Flattened and low cuboidal alveolar epithelium lining the
alveolar walls. Pulmonary resection (H&E x MP).
cells or pneumocytes are cuboidal and have prominent nucleoli.
They are characterized ultrastructurally by prominent microvilli
and osmophilic lamellated inclusion bodies. These cells are the
source of surfactant, the chemical substance that coats the lining
of the alveoli and prevents their collapse on expiration. They also
have been shown to be the chief cell types involved in repair of
the alveolar epithelium. Also of significance in cytologic evalua-
tions are the alveolar macrophages found both within the alveo-
lar air spaces and within the extracellular lining of the alveolar
surfaces. These macrophages are discussed in more detail later.
Cytology of Normal and Benign Components
The morphology of benign cellular components of respiratory
cellular material has been well described in the literature by
Farber and associates,69 Woolner and McDonald,70 Koss,17 and
Frost and associates.24 Electron microscopy of sputum has been
studied by Kory.71
The components of respiratory specimens (sputum, bron-
chial aspirates or brushings, BALs, and FNAs), in the absence
of neoplasm, may be divided into epithelial cells, macrophages,
leukocytes, intrinsic noncellular inanimate components, extrin-
sic noncellular inanimate components, and living organisms.
Cytology of Normal Epithelial Cells
squamous epithelial cells exfoliating from the oral cavity and
pharynx, columnar cells exfoliating most frequently from the tra-
cheobronchial tree and occasionally from the upper respiratory
tract, bronchiolar cells, and alveolar pneumocytes. Squamous
cells are present most commonly in sputum. Ciliated columnar
cells and goblet cells are most common in bronchial specimens
and BALs. Lesser numbers may be seen in FNAs. Bronchiolar
cells and alveolar pneumocytes probably will not be recognized,
unless they are hyperplastic or atypical.
Squamous cells, usually of oral origin, are commonly seen in
specimens of sputum and bronchial material. A mixture of inter-
mediate and superficial squamous cells is most frequent. The
intermediate cells are characterized by a round-to-oval vesicular
nucleus embedded in a uniformly thin, cyanophilic cytoplasm.
The superficial cells have pyknotic nuclei and orangeophilic
cytoplasm. Anucleate squames and parabasal cells may occa-
sionally also be present.
Ciliated Bronchial Columnar Cells
An individual bronchial cell is characterized in profile by a
columnar or prismatic shape-ending in a tail. The nucleus is ori-
ented toward this tail and shows a finely granular chromatin
pattern with one or more small nucleoli (see Fig. 13.2). In longi-
tudinal profile, the nucleus may appear to be wider in diameter
than the cell itself, but more careful examination reveals a thin
margin of cytoplasm between the nuclear membrane and the
cytoplasmic membrane. Cilia with a terminal plate are present.
Ciliated columnar cells are characteristically seen in bronchial
washings, aspirates, or brushings, and in BALs and FNAs. They
should not be present in large number in sputum, except in post-
bronchoscopy specimens or in cases in which extensive damage
to the respiratory epithelium has occurred. Scattered single cells
and small cell clusters of bronchial epithelium are commonly
found in BALs and FNAs.
A less commonly encountered epithelial cell present in the
bronchial epithelium lining is the mucus-producing bronchial
cell, or goblet cell. Such cells are readily recognized by the
presence of either single or multiple vacuoles filled with mucus.
These goblet cells are more common in patients with chronic
tracheobronchial disease, such as asthmatic bronchitis, chronic
bronchitis, and bronchiectasis. They are occasionally present
in bronchial brushings and FNAs in such great numbers that a
mucus-producing adenocarcinoma may be suggested.72 Exam-
ples of goblet cells are shown in Fig. 13.4.
Epithelial Cells from Bronchioles and Alveoli
Although the use of a number of modern laboratory techniques
has made it possible to differentiate various subtypes of termi-
nal bronchiolar and alveolar cells, conventional light micro-
scopic examination of cytologic specimens in the absence of
disease does not permit the observer to appreciate these various
cell types. Indeed, the terminal bronchiolar and alveolar cells
in their normal forms are probably not present in cytologic
material very often. These cells are relatively small and, when
present in cytologic material, appear as rounded single cells
with finely vacuolated cytoplasm and centrally placed nuclei
with one or two small nucleoli (see Fig. 13.6). Some may bear
cilia. With such morphology, they are usually interpreted as
alveolar macrophages. Among various specimen types, these
cells are likely to be most commonly encountered in BALs and
FNAs, and if they are reactive, they may be a diagnostic pitfall
in such specimens.
Cytology of Abnormal Epithelial Cells
Abnormal but benign squamous cells may be exfoliated in
the presence of a number of diseases of the mouth. Infection,
inflammation, and ulceration may release parabasal cells. These
may be confused with metaplasia. Chronic mucosal irritation
with leukoplakia may produce masses of anucleate squames.