PART TWO
Diagnostic Cytology
Fig. 13.72 Small-cell carcinoma. Pulmonary resection (H&E x MP).
than352-354 that of pure small-cell carcinoma. Because the thera-
peutic approach to small-cell carcinoma may differ significantly
from that of the non-small-cell carcinoma, accurate histologic
and cytologic distinction between these two groups is of para-
mount importance.
Lung cancer may come to clinical attention as a result of vari-
ous signs and symptoms, the most common of which are weight
loss, cough, dyspnea, weakness, chest pain, and hemoptysis.284,355
In other situations, an opacity on a chest radiograph may be the
first clue to the presence of a neoplasm. In one series of 955
cases, nearly half of all coin lesions observed by radiography
were malignant, and most of these (78%) were primary lung
cancers.356 Some patients may present with symptoms related to
ectopic hormone production. The syndrome of inappropriate
antidiuretic hormone production (SIADH) and Cushing's syn-
drome are most closely associated with small-cell carcinoma,
where hypercalcemia due to production of a parathyroid-like
hormone has been described with squamous cell carcinoma.296
Carcinoma of the lung tends to spread initially via lymphatics
to regional lymph nodes and hematogenously to distant organs,
most commonly the liver, adrenals, bone, and brain.313 By far
the most important factor for predicting prognosis of these
tumors is stage,357 as determined by tumor size, local extent,
lymph node involvement, and the presence or absence of dis-
tant metastases.358 Histologic features reported to be associated
with survival include cell type, as previously discussed, vascular
invasion,359 the presence or absence of a plasmacytic infiltrate,339
and the extent of tumor necrosis.340
Cytology of Lung Cancer
At present, most of the major medical institutions throughout
the world use some variety or combination of different cytologic
specimens in the diagnostic workup of a patient with suspected
lung cancer. Sputum continues to be the most frequently exam-
ined specimen, but bronchial washings and brushings, BALs,
and FNAs are gaining positions in the use of cytology. These
procedures used appropriately in concert have the capability of
both diagnosing and classifying correctly the vast majority of
the common lung neoplasms. Sputum examined as multiple
specimens detects the more central tumors, whereas bronchial
brushings and FNAs detect the remaining ones, usually occur-
ring as the more peripheral or even subpleural lesions. Recalling
the histogenesis of primary lung cancers is very persuasive as
an aid in comprehending exactly why it is that cytologic diag-
nosis of the respiratory tract has been so successful. It is mainly
because most primary lung cancers arise from the epithelium
lining the respiratory passages and have the potential of shed-
ding cancer cells into specimens of sputum or of having their
cells harvested for cytologic diagnosis by methods of fiberoptic
bronchoscopy, BAL, or FNA.
As an example of the distribution of lung tumors likely to
be encountered in a large laboratory of cytology and surgical
pathology, a summary of several large series including the expe-
rience of our laboratory is presented in Table 13.8. Our experi-
ence includes the major types of lung cancer and their relative
frequencies based on a combination of cytologic and histologic
diagnoses. The relative incidence of adenocarcinoma was noted
to increase, and the absolute incidence of lung cancer in women
also increased, corresponding to trends observed elsewhere.
Squamous Cell Carcinoma
Squamous Cell Carcinoma in Situ
Squamous cell carcinoma of the lung is the only malignant
tumor of the lung for which a preinvasive or in situ phase has
been well documented.360 Although our knowledge of the his-
togenesis of this tumor is still quite rudimentary, some basis
exists for the belief that squamous cell carcinoma of the lung
shares with its counterpart in the uterine cervix a demonstrable
preinvasive stage of development in which the epithelium of the
tracheobronchial tree undergo a series of alterations, which can
be morphologically classified as atypical metaplasia or dysplasia
and carcinoma in situ.
A number of reports in the literature have documented the
cytologic manifestations of these biologic events.361-363 Sac-
comanno and colleagues, in their cytologic studies of cigarette-
smoking uranium miners, have reported the progression of
dysplastic changes in metaplastic epithelium to carcinoma in
situ and invasive carcinoma.38,79,95,96 They divided the observed
cellular changes into the categories of regular metaplasia, mildly
atypical metaplasia, moderately atypical metaplasia, markedly
atypical metaplasia, carcinoma in situ, and invasive carcinoma.
Using similar criteria, Nasiell and associates have described
increasing degrees of aneuploidy that suggest progression toward
neoplasia.107 Unfortunately, few published data are available to
give information on progression and regression rates between
these atypias and invasive cancer.
The extent to which cytologic techniques are capable of
contributing to the detection of these preinvasive lesions was
evaluated most effectively in three major screening projects
for the early detection of lung cancer in high-risk populations.
Under the sponsorship of the National Cancer Institute, a Coop-
erative Early Lung Cancer Group (Memorial Sloan-Kettering,
Johns Hopkins, and Mayo Clinic) examined the usefulness of
prolonged surveillance of persons without clinical or radio-
graphic evidence of lung cancer but with increased risk for
developing the disease.364-367 For example, the participants
admitted to the Mayo Clinic Lung Project were enrolled from a
group of asymptomatic men 45 years of age or older at increased
risk of lung cancer because of their smoking histories. The
project design called for an initial chest radiograph and sputum
334
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