PART TWO
Diagnostic Cytology
In marked cytologic atypia, the ductal cells are arranged in
large clusters of greater than two cell layers. Anisonucleolo-
sis with irregular nuclear membranes are noted in half of the
cases, with coarse granular chromatin and variable nucleoli.
Increased N/C ratios with multinucleation and occasional
mitotic figures are seen. Microcalcifications were present in
half of the cases, but necrotic debris is rarely noted. Markedly
atypical cells may be associated with ADH or low- to interme-
diate-grade DCIS.
Malignant cells demonstrated markedly enlarged cells with
high N/C ratios, large nuclei, and large variable nucleoli. Single
cells are also found, along with cells in monolayers and small
and large groups. Irregular arrangements and nuclear overlap-
ping are present. Conspicuous anisonucleosis is present, with
marked membrane irregularity and clumped, uneven chroma-
tin granularity. Multinucleation and necrotic debris are noted.
Foam cells, inflammatory cells, and red blood cells are noted in
the background. Ductal lavage lends itself not only to cytologic
evaluation but also to molecular studies.476,477
O'Shaughnessy et al. have published management recom-
mendations based on ductal lavage results.475 The interpreta-
tion of lavage cytology as "benign" is a basis for repeat lavage
in 1-3 years. Mildly atypical cytology may warrant repeat lav-
age within a year or raise consideration of prevention therapy.
Markedly atypical or "malignant" cytology would be the basis
of additional studies to confirm the results, such as ductoscopy,
ductogram, or tissue biopsy.482
Most of the questions concerning ductal lavage will, it is
hoped, be addressed by a large multicenter ductal lavage trial
termed the
Serial Evaluation of Ductal Epithelium Trial,
in which
our institution is participating. Ductal lavage samples will be
collected from women at 6-month intervals and assessed for
both cytologic features and novel markers. This trial will attempt
to answer several questions, such as the frequency that ductal
lavage should be performed in high-risk women, the negative
predictive value of ductal lavage cytology, the significance of
nipple aspiration fluid yielding versus nonyielding ducts, the
ability of cytology to stratify the risk of a high-risk woman, and
the utility of molecular markers as an adjunct to or replacement
for cytologic evaluation. This study is anticipated to end by
2011.483
Concluding Remarks
In conclusion, FNA biopsy still has a role in the workup of breast
lesions, since cytologic examination can quickly and accurately
separate benign from malignant lesions and often establish a
specific diagnosis. FNA cytology can also be useful in diagnos-
ing locally advanced or inoperable breast carcinoma and/or
metastatic breast carcinoma. However, especially in the United
States, there has been a decline in the utilization of FNA biopsy
due mainly to limitations of the procedure, including FNA's
inability to separate ADH from low-grade DCIS and high-grade
DCIS from invasive carcinoma. In this chapter, we present the
diagnostic criteria for a variety of benign and malignant breast
lesions, as well as discuss the advantages and limitations of the
procedure. In addition, the potential for false-positive diagnoses
in the aspiration of a number of benign reactive, inflamma-
tory, and metaplastic breast lesions and aspirates of lesions that
have a potential for a false-negative diagnosis of malignancy are
presented.
Fig. 25.81 Ductal lavage. (A) Honeycomb sheets of benign ductal cells
with abundant foam cells and proteinaceous material in the background
(Papanicolaou x LP). (B) Small clusters of ductal cells with cytologic atypia
and vacuolated cytoplasm. This was interpreted as mild cytologic atypia
(Papanicolaou x HP).
It is apparent that the role of FNA cytology in the core biopsy
era is changing. It appears that breast FNA is now more often
being used at many centers in the United States to complete the
triple test to confirm a negative diagnosis rather than in the past,
when it was used primarily to establish a diagnosis of malig-
nancy. Although still widely used as the initial procedure of
choice for the workup of breast lesions in many countries, the
future role of FNA of the breast at many centers is uncertain.
Finally, we also discuss the application of nipple aspiration and
especially ductal lavage of the breast for the evaluation of mam-
mary lesions. The future role of ductal lavage in the workup of
high-risk women also needs to be further evaluated.
References 1
2
3
4
1.
Martin HE, Ellis EB. Biopsy by needle puncture and aspiration.
Ann Surg
1930;92:169-181.
2.
Martin HE, Ellis EB. Aspiration biopsy.
Surg Gynecol Obstet
1934;59:578-589.
3.
Stewart FW. The diagnosis of tumors by aspiration.
Am J Pathol
1933;9:801-812.
4.
Adair FE. Surgical problems involved in breast cancer.
Ann R Coll
Surg Engl
1949;4:360-380.
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