Diagnostic Cytology
Table 13.7 Histologic Classification of Malignant Neoplasms of the Lung
Squamous cell carcinoma
Clear cell
Small cell
Small-cell carcinoma
Combined small-cell carcinoma
Mixed subtype
Large-cell carcinoma
Clear cell
Rhabdoid phenotype
Adenosquamous carcinoma
Sarcomatoid carcinoma
Spindle cell
Giant cell
Pulmonary blastoma
Carcinoid tumor
Salivary gland carcinoma
Adenoid cystic
Lymphoproliferative tumors
Adapted from WHO Classification of Tumors of the Lung.
tal evidence implicates cigarette smoking in the etiology of
lung cancer.101,104,280-282 Approximately 80-85% of lung cancer
deaths are attributed to smoking.283 Although the association
is strongest for squamous cell carcinomas and small-cell carci-
nomas, even in the case of adenocarcinoma, most patients are
cigarette smokers.284 Other factors that have been implicated
in the development of lung cancer include asbestos exposure,
for which a synergistic effect with cigarette smoking has been
described,285 radon exposure,286,287 nickel,288 arsenic,289 cadmium
beryllium,290 and vinyl chloride.291
Fig. 13.60 Keratinizing squamous cell carcinoma. Pulmonary resection
(H&E x LP).
Although all major types of lung carcinoma are believed to
arise within the epithelium that lines the respiratory tract, the
in situ carcinomas that have been identified are largely those of
the squamous type.101,292-294 They are thought to arise in a pro-
gressive epithelial dysplasia occurring in metaplastic squamous
epithelium.101 Areas of atypical epithelial proliferation occurring
in association with adenocarcinomas have been observed,90 sug-
gesting that such areas may give rise to adenocarcinoma. Attempts
to identify an in situ lesion of small-cell carcinoma, however,
have been unsuccessful. The not uncommon occurrence of het-
erogeneity in lung cancer,152,295 as evidenced by the existence of
adenosquamous carcinomas and combined small-cell/large-cell
carcinomas, would lend support to the theory that lung carcino-
mas arise from precursor cells of endodermal origin, capable of
expressing one or more patterns of cellular differentiation.295,296
The previous claims of a separate neural crest origin297 for small-
cell carcinoma appear unfounded, in view of the occurrence of
mixed small-cell/large-cell carcinomas and in light of the obser-
vation that small-cell undifferentiated carcinomas may convert,
over a period of time, to large-cell carcinomas.298
Table 13.7 shows a classification modified from that of the
World Health Organization (WHO)299 and the Armed Forces
Institute of Pathology Fascicle300 on malignant epithelial tumors
of the lung. Squamous cell carcinomas are characterized by his-
tologic findings that mimic, to a greater or lesser degree, the fea-
tures of a normal squamous epithelium (Figs 13.60 and 13.61).
These include keratinization, which is manifested by the pres-
ence of either keratin pearls or individually keratinized cells, and
so-called intercellular bridges, which are spicules of cytoplasm
observed at the sites of desmosomal junctions. In well-differen-
tiated neoplasms, these features are identified without difficulty,
whereas in poorly differentiated tumors, they are much less
common, with the predominant histologic pattern consisting of
nests and sheets of undifferentiated cells (Fig. 13.62). Areas of
squamous dysplasia or carcinoma in situ may be observed in the
adjacent bronchial epithelium (Fig. 13.63). Electron microscopy
of these tumors reveals, in addition to desmosomes, variable
numbers of cytoplasmic tonofilament bundles.301
Although primary peripheral squamous cell carcinomas have
been described with increasing frequency,302 most reported cases
of squamous cell carcinoma have occurred centrally,284 arising in
the segmental, lobar, or main stem bronchi. These neoplasms
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