Fig. 8.110 Nonkeratinizing squamous cell cancer. Syncytial aggregate
of tumor cells with indistinct cell borders. Moderate amount of cytoplasm
causing an intermediate nucleocytoplasmic ratio. Nuclei are round to oval
or irregularly shaped. Nuclear chromatin is moderately hyperchromatic,
coarsely granular, and irregularly distributed. Nucleoli are conspicuous
(Papanicolaou x OI).
epithelial cells are relatively frequent. The cells have a relatively
large body of cyanophilic cytoplasm and have large round-
to-oval nuclei (Fig. 8.112). The nuclear chromatin is hyperchro-
matic, irregularly distributed, and usually coarsely granular (Fig.
8.113). Nucleoli are frequently observed. Macronucleoli are
found in less-differentiated tumors and can be considered an
expression of the high proliferative activity of the tumor cells.
Particularly in cases of moderately to poorly differentiated non-
keratinizing squamous cell carcinomas, cytologic distinction
from a poorly differentiated adenocarcinoma may be difficult.
In adenocarcinomas, the cells are often aggregated as clusters
with overlapping nuclei. The nuclei are eccentrically located, and
nuclear chromatin is only slightly to moderately hyperchromatic
and very irregularly distributed, leaving intranuclear clear spaces
(Fig. 8.114). Nuclear chromatin is often sedimented against the
nuclear membrane, which then becomes sharply outlined.
Key features of nonkeratinizing squamous cell carcinoma
• Round-to-oval cells predominantly arranged in
• Cyanophilic cytoplasm with relative increase in
Fig. 8.111 Nonkeratinizing squamous cell cancer. Tumor cells are
relatively rich in cytoplasm. No evidence of keratinization. Nuclei vary greatly
in size. Nucleoli are conspicuous. Nests of tumor cells are surrounded by
layers of degenerated cells with hyperchromatic nuclei without nuclear
detail. In less adequately prepared cytologic smears, only this degenerated
material, cellular debris, and proteinaceous material is often present.
Compare the lack of cellular detail with the sharply outlined detail of the
underlying vital tumor cells (H&E x HP).
• Round-to-oval nuclei with considerable variation in
• N/C is lower than in carcinoma in situ due to larger
volume of cytoplasm;
• Unevenly distributed, coarsely granular hyperchro-
matic nuclear chromatin;
• Irregularly shaped micronucleoli are present, macro-
nucleoli are frequently found; and
• Possible association with unsatisfactory specimens due
to tissue necrosis and bleeding.
Keratinizing cancers are composed of irregular masses of cells
usually sharply demarcated against the surrounding stroma (Fig.
8.115). Characteristically, infiltrating nests are irregular in shape
and often elongated (Fig. 8.116). Blunt borders of infiltrating
masses are less frequently seen. Cytoplasmic keratinization of
individual cells and formation of epithelial pearls are character-
istic features. From a practical standpoint, a single well-formed
epithelial pearl includes a neoplasm in the category of a kerati-
Superficial hyperkeratosis and atypical parakeratosis may be
present. The surrounding stroma usually shows a mononuclear
infiltrate of moderate density. Typically, a small rim around the
infiltrating nests is free of inflammatory cells. Squamous cell dif-
ferentiation is conspicuous. Mitotic activity may be variable and
is low in those parts of the tumor with a relatively large number
of cells showing signs of cytoplasmic keratinization. Necrosis is
In cytologic specimens, tumor cells frequently appear singly.
Elongated, caudate, or bizarre cell forms are often present (Fig.
8.117). Admixture with cellular debris and blood cells in these
tumors, due to their often exophytic growth, is less frequently
seen than with large-cell nonkeratinizing cancers.