Respiratory Tract
Fig. 13.31 Radiation changes. Compared with the adjacent bronchial
epithelium, the cells in the center of the field exhibit nuclear enlargement
with a concomitant increase in the amount of cytoplasm, prominent nucleoli,
and multinucleation. Bronchial brushing (Papanicolaou x OI).
Bronchopulmonary Dysplasia
In 1967, Northway and associates noted a special incidence of
atypical squamous metaplasia in neonates with respiratory dis-
tress syndrome, termed bronchopulmonary dysplasia.111
tional studies have been reported by D'Ablang and associated112
and by Kanbour, Doshi, and associates.113,114 In the early stages,
the cellular findings in tracheal aspirates include bronchial cells
and metaplastic cells. As the disease progresses, the metaplas-
tic cells become more atypical. Bronchopulmonary dysplasia is
a well-known complication in babies who have hyaline mem-
brane disease and who have received intensive care with oxygen
and respirators.
Epithelial Cellular Changes Following Radiation
Therapy, Chemotherapy, and Toxic Chemicals
Severe morphologic changes in benign cells of the lungs and
upper respiratory tract may occur at varying intervals after treat-
ment with ionizing radiation or with various drugs. These cells
may be so severely altered that they may be mistaken for cancer
cells. Knowledge of a history of prior therapy with such agents is
the best safeguard against an erroneous cancer diagnosis.
Cellular alterations in response to radiation therapy may
involve both squamous cells and columnar cells and are char-
acterized by cytomegaly with both cytoplasmic and nuclear
enlargement, multinucleation, macronucleoli, and cytoplas-
mic vacuolation (Fig. 13.31). An acute radiation response can
stimulate such cellular changes within the area irradiated or at a
remote site. For example, a patient who had received radiation
treatment to the neck could exhibit changes in bronchial epithe-
lium; a patient who had received radiation treatment to the left
lung could exhibit changes in the right lung. As the radiation
response in the lung becomes more chronic, a diffuse interstitial
fibrosis ensues. Epithelial abnormalities may persist and span
the gamut from focal areas of squamous metaplasia of the lin-
ing bronchial cells to severe squamous atypia. A false-positive
diagnosis of squamous cell carcinoma on specimens of sputum
and bronchial material is a potential dangerous pitfall in such
a patient.
A number of drugs used for anticancer chemotherapy may
be associated with the production of severe changes in the
Fig. 13.32 Chemotherapy changes in a patient being treated for
acute leukemia. The cells show nuclear enlargement, hyperchromasia, and
abnormal chromatin distribution, but the cytoplasm maintains a columnar or
boxcar shape. Bronchial brushing (Papanicolaou x OI).
lung parenchyma.115 These drugs include the alkylating agents
busulfan, cyclophosphamide, chlorambucil, melphalan, bleo-
mycin,116 bis-chlorethylnitrosourea (BCNU), and the antime-
tabolites methotrexate and azathioprine.117 The toxic injury to
the lungs is that of diffuse alveolar damage. The initial phase
of this damage consists of pulmonary edema and hemorrhage.
The striking feature of this phase that permits this type of alveo-
lar damage to be differentiated from that resulting from causes
other than these drugs is the presence of atypical epithelial cells
in great abundance. Bedrossian has shown that these atypical
cells are in fact abnormal type II pneumocytes that have under-
gone degranulation and loss of lamellar bodies.117 These atypical
pneumocytes may shed into sputum or be harvested in brush-
ings, BALs, or FNAs. These pneumocytes are most like to be seen,
however, in BALs.118 Bedrossian has emphasized the significance
of the presence of these cells in sputum and BALs. They may
herald the progression of drug-induced lung damage to diffuse
Cells resulting from chemotherapy are prone to occur singly
and to show cytomegaly, hyperchromasia, and macronucleoli
(Fig. 13.32). In addition to type II pneumocytes, cells of the tra-
cheobronchial epithelium and the terminal bronchiolar epithe-
lium may be involved. A major key to the correct recognition of
these cells lies in the tendency of many of them to be roughly
rectangular, to occur singly, to be sparse, and to exhibit nuclear
degeneration. Some may show remnants of cilia.
We have observed extremely atypical changes in the bronchial
epithelium of a farmer who inhaled the insecticide parathion.
Stein and associates have reported macrophage abnormalities in
patients on amiodarone, an antiarrhythmic drug.119
Other Cellular Components
Various cells of nonepithelial origin may appear in various types
of cytologic specimens from the lungs. The type and frequency of
these cells are dependent on the type of specimen and the disease
process in the patient. Perhaps the most frequent cell encoun-
tered is the pulmonary alveolar macrophage. Although it was
once believed that the macrophage originated from the alveolar
lining epithelium, it is now established that the pulmonary
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