Respiratory Tract
Fig. 13.96 Bronchioloalveolar carcinoma. Single tumor cell.
Distinguishing between single tumor cells and macrophages may be very
difficult. Sputum (Papanicolaou x OI).
Overall, the mucinous (type I) tumors possess more abun-
dant cytoplasm and more innocuous nuclear features than do
the nonmucinous tumors, and therefore the former are more
likely to be overlooked during routine cytologic screening. How-
ever, so much overlap exists between the cytologic features of the
type I and type II tumors in exfoliated material that the inves-
tigators consider such specimens unreliable for distinguishing
between the two patterns.
The possible confusion of BAC with reactive alveolar epithe-
lium has been discussed. As mentioned, bronchial goblet cell
hyperplasia may occasionally be confused with this neoplasm.
Some metastatic adenocarcinomas with bland nuclear features,
particularly carcinoma of the breast, may closely resemble BAC
in cytologic preparations. Wang and Nieberg have reported a
case of so-called sclerosing hemangioma, a tumor of presumed
type II pneumocyte origin, which was erroneously diagnosed as
BAC by FNA.381 Several more recent reports in the literature also
describe this entity.382-385
A small percentage of BACs are poorly differentiated and
exhibit pronounced nuclear atypia, similar to that observed in
other poorly differentiated adenocarcinomas.31,380,386 In view of
this and the fact that pulmonary adenocarcinomas not infre-
quently exhibit mixed acinar and bronchioloalveolar patterns,
it is unreasonable to expect that cytologic preparations will
consistently permit the distinction of BACs from other adeno-
carcinomas, just as it is unreasonable to expect this from a
transbronchial biopsy specimen.387 Such a distinction, from a
practical standpoint, is far less important than is the recogni-
tion that cells exhibiting the bland features described here may
indeed be derived from a malignant neoplasm.
Large-cell Undifferentiated carcinoma (Synonym:
Large-cell carcinoma)
The cytologic characteristics of large-cell undifferentiated carci-
noma are listed in Table 13.13. These neoplasms exfoliate large
numbers of diagnostic cells that appear in respiratory specimens
both as single cells and as tissue fragments. The single cells are
large and possess multiple criteria for malignancy, including high
nucleocytoplasmic ratios, marked aberrations in the chromatin
patterns, abnormal nuclear contours, and multiple enlarged,
irregular nucleoli. Cytoplasm may be wispy or homogeneous,
Fig. 13.97 Papillary cell cluster from a patient with bronchioloalveolar
carcinoma. Sputum (Papanicolaou x OI).
with a tendency toward cyanophilia. No evidence of keratiniza-
tion is seen, and insufficient cytoplasmic differentiation is seen
to warrant a diagnosis of adenocarcinoma (Fig. 13.98). The
large tissue fragments that may be present lack any recognizable
architectural pattern such as squamous pearls, acini, or papillary
structures. Occasionally seen is the giant cell carcinoma variant
(sarcomatoid carcinoma) of large-cell undifferentiated carci-
noma, so named because of the presence of many multinucle-
ated tumor giant cells (Fig. 13.99).388-392 Differential diagnostic
considerations for large-cell undifferentiated carcinoma include
metastatic undifferentiated carcinomas, amelanotic malignant
melanomas, sarcomas, chemotherapy changes, and radiation
changes. Benign irradiated epithelial cells may possess very large
nuclei, but their equally abundant cytoplasm should help to dif-
ferentiate them from tumor cells. Previous irradiated neoplasms
may exhibit bizarre giant cells indistinguishable from those
observed in giant cell carcinoma.
All of the non-small-cell carcinomas of the lung may exfoli-
ate only large anaplastic malignant tumor cells into the cyto-
logic specimens, and thus the cytologic diagnosis of large-cell
undifferentiated carcinoma is made. Furthermore, sampling
methods such as bronchial brushings or FNA may reach only
undifferentiated portions of squamous cell carcinomas or
adenocarcinomas. FNAs obtained from poorly differentiated
adenocarcinomas have, in the experience of our laboratory, been
particularly difficult to classify correctly.
Key features of large cell undifferentiated carcinoma
• Mixture of large single cells and syncytial groupings;
• Nuclei round to lobulated with irregularly dispersed,
intensely hyperchromatic chromatin;
• Macronucleoli, sometimes multiple;
• Tumor giant cells; and
• Cytoplasmic outline frequently ill-defined.
Small-cell Undifferentiated carcinoma (Synonym:
Small-cell carcinoma)
As mentioned, small-cell undifferentiated carcinoma of the
lung may be subclassified into small-cell carcinoma, and a
combined cell type (small-cell carcinoma in combination with
squamous cell carcinoma, large-cell undifferentiated carcinoma,
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