Respiratory Tract
Fig. 13.88 Adenocarcinoma. This three-dimensional cell cluster is a true
acinus with a central lumen, visualized here by focusing the microscope at
the midpoint of the cell cluster. Sputum (Papanicolaou x OI).
crystadenocarcinoma.376 Expression of vacuoles in adenocarci-
noma is, in the experience of our laboratory, less common in
specimens prepared by the Saccomanno blender technique. In
well-differentiated neoplasms, the cells may assume a columnar
shape, whereas in other cases, many cells exhibit extremely high
nucleocytoplasmic ratios and are recognized only as undifferen-
tiated malignant tumor cells.
Cell groups in specimens of adenocarcinoma may consist
of ball-like clusters
papillary fragments
(see Fig. 13.87), loose clusters, or true acini with central lumina
(see Fig. 13.88).With decreasing differentiation of the neoplasm,
one sees increasing nuclear hyperchromasia, coarsening of
chromatin, more irregular nuclear contours, and greater cellular
pleomorphism, such that the cytomorphology begins to merge
with that of large-cell undifferentiated carcinoma.
Key features of acinar adenocarcinoma
• Mixture of cell clusters, tissue fragments, and single cells;
• Tissue fragments may show only cells arranged in syn-
cytial groupings or true acini, tubules, and papillary
• Nuclei vescicular, round, ovoid, or lobulated and
eccentrically placed;
• Macronucleoli centrally placed in nuclei; and
• Cytoplasm granular, finely vacuolated, or exhibiting
hyperdistended vacuoles.
Bronchioloalveolar Carcinoma
Histologic diagnosis of BAC is based on a predominant pattern of
growth of cuboidal or columnar cells along alveolar or fibrovascu-
lar septa. Although this pattern may sometimes be appreciated in
FNAs,377 one obviously does not have benefit of this architectural
feature in sputum or bronchial specimens. However, a number of
cytologic features seen (see Table 13.12) are typical of BAC and
may allow one to suggest this diagnosis in cytologic material. Like
other adenocarcinomas, BAC tends to exfoliate as both single cells
and cell groups. The nuclei are characteristically round to oval and
uniform in size, with finely granular or powdery chromatin and
small, inconspicuous nucleoli (Fig. 13.89).324,373,374,377 A minor-
ity of cases, however, show prominent nucleoli. Nuclear folds
are commonly present (Fig. 13.90), and in some cases nuclear
Fig. 13.89 Papillary cell cluster from a patient with bronchioloalveolar
carcinoma. Note the bland appearance of the nuclei. A nuclear
pseudoinclusion is present at one tip of the cluster. Sputum
(Papanicolaou x OI).
pseudoinclusions (invaginations of cytoplasm into the nucleus)
are observed (Fig. 13.91). The cytoplasm varies in amount from
modest to abundant and, like that of other adenocarcinomas,
may be homogeneous, granular, finely vacuolated, or distended
by single or multiple large vacuoles (Figs 13.92 and 13.93).
Smith and Frable,374 Elson and associates,324 and Silverman
and associates377 have emphasized the extreme depth of focus
in the three-dimensional cell clusters of BAC. The cell groups
frequently exhibit a radiating flower-petal or cartwheel pattern
13.94).324 Papillary-shaped fragments lacking fibrovas-
cular cores are also common (Fig. 13.95).27 In some cytologic
preparations, numerous nonpigmented macrophage-like cells
are present (Fig. 13.96). It may be extremely difficult or impos-
sible to determine in individual cases whether these cells rep-
resent tumor cells or macrophages. Their presence, however,
should prompt a search for three-dimensional, diagnostic clus-
ters of similar cells (Fig. 13.97). In a small number of cases,
psammoma bodies may be encountered,156,378 and exceptionally
they may be the only cytologic clue to the presence of carcinoma.
Some tumor cells with features of type II pneumocytes may pos-
sess numerous distended microvilli, which may be mistaken for
cilia in cytologic preparations.331,379
The cytologic appearance of BAC in FNAs is similar to that
described, except that sheets of tumor cells may be prominent
and, as mentioned, tissue fragments containing alveolar septa
may be present.
Key features of bronchioloal veolar carcinoma
• Ball-like cell clusters without intercellular
• Papillary fronds;
• Nuclei are round to oval with finely-granular
• Nucleoli are present but inconspicuous;
• Cells may or may not exhibit secretory vacuoles; and
• Cytoplasmic microvilli may mimic cilia.
Tao and coworkers have observed that diffuse and multifocal
BACs are far more likely to exfoliate tumor cells in sputum and
bronchial specimens than is the solitary nodular form of the
disease.380 For the latter, FNA is a much more effective means of
obtaining tumor cells.
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