BREAST CYTOPATHOLOGY

Breast Ductal Lavage 161
two cell layers are found in half of the cases. These cells show
disorderly arrangement, moderate to marked nuclear enlargement,
with high nuclear to cytoplasm ratio, nuclear overlap
and anisonucleosis, irregular nuclear membrane, and coarse
chromatin. Multinucleated cells and mitoses can also be
present. Calcifications occur in about half of cases with
marked atypia, but necrotic debris is rare.
Neoplastic cells in DL specimens show the characteristic
features of malignancy. In our experience, the number of
malignant cells is also a determinant in rendering a definitive
diagnosis of malignancy.
Ljung and collaborators speculate that the diagnostic category
of “mild atypia” encompasses the spectrum of changes
of usual ductal hyperplasia and atypical ductal hyperplasia,
whereas “marked atypia” corresponds to a spectrum of
changes from atypical ductal hyperplasia to ductal carcinoma
in situ. However, information from clinical follow-up studies
is required and not yet available to support (or disprove) this
statement.
Reproducibility in diagnosis of DL samples in time and
among different observers is a requisite for clinical application
of the technique. High agreement (kappa >0.70) among
two reviewers from the same laboratory was reported for
characteristics of nuclear size, anisonucleosis, nucleoli,
mitoses, and necrosis. In another study, interobserver agreement
among three reviewers from different laboratories was
fair to good (kappas 0.6, 0.5, and 0.48), and mild atypia was
the least reproducible diagnosis. Johnson-Maddux and colleagues
have reported low reproducibility in the diagnosis of
mild atypia in DL samples obtained from the same patient
after a 6-month interval and have hypothesized that mild
atypia might not be a correlate of epithelial dysplasia, but
rather of hormonal status.
The findings in DL samples obtained from women undergoing
mastectomy for carcinoma have been correlated with
the histologic findings in the paired mastectomy specimen.
In one study, dye injection through the microcatheter was
used to identify the duct sampled by DL. Ducts involved by