Fig. 25.79 (A and B) Nipple discharge of intraductal papilloma:
a complex papillary group of benign ductal cells with fibrovascular cores
and mild cytologic atypia (Papanicolaou x HP).
Intraductal p ap illom a w ill show three-dim ensional clusters o f
cells in w hich considerable variation in cell size is evident
(Fig. 25.79). A ltho ug h nuclear atypicality m ay be present w ith in
the clusters, single atypical cells, a useful feature o f malignancy, are
n o t seen w ith any significant frequency. A m alig nant cytologic
diagnosis should n o t be rendered in a nipple discharge specimen
unless m any in d ivid u a lly scattered atypical cells are present
(Fig. 25.80). In addition, it is also recom m ended th a t i f a m alig-
n ant diagnosis is made, histologic c onfirm ation should be
obtained before d efinitive treatm ent.460 Evaluation fo r occult
b lood, m ucin staining, CEA, and other biom arkers have been tried
to increase the sensitivity o f nipple discharge to detect nonpalpa-
ble breast cancer.459,466
Ductal Lavage Cytology
C e llu la r atypia was fo u n d to be predictive o f an increased risk
o f developing breast carcinom a.468-470 W o m e n w h o have atypical
intrad uctal cellular p rolifera tion s have ap p roxim ately tw o fo ld
greater risk o f developing invasive breast cancer, independent o f
o th e r risk factors such as fa m ily history. W h e n com bined w ith
o th e r factors, th e y have a 1 2-fo ld greater ris k th an the general
Fig. 25.80 Nipple discharge showing loosely cohesive clusters and
individually scattered malignant cells. Resected specimen shows ductal
carcinoma. (Papanicolaou x HP).
p o p ulatio n. Som e investigators have proposed ran d o m peri-
areolar FN A to detect cellu la r atypia as a risk factor o f develop-
ing breast cancer.468
W rensch et al. showed th a t w o m e n w h o had ab norm al cells
in th e ir n ip p le asp iration flu id sam ple had an increased ris k o f
developing breast cancer.471 D uctal cells can be collected b y either
n ip p le asp iration o r ductal lavage. D o o le y et al. dem onstrated
th a t ductal lavage recovers fa r m ore cells th an n ip p le aspiration,
w ith a m edian n um b er o f 13 500 versus 120 cells in n ip p le aspi-
rate flu id per duct (range, 4 3 -4 9 2 0 0 0 ).472 In th e ir study, duc-
tal lavage was successful in 92% o f p articip ating w o m e n , 78%
o f w h o m contained adequate cells fo r diagnosis. D uctal lavage
seems to be a convenient m eth od to assess the presence o f aty-
pia in h ig h risk w o m e n .473-476
D uctal lavage, by detecting atypical breast e p ith elial cells, can
be used to im p rove risk stratific ation fo r w o m e n w h o already
are at an increased risk fo r developing breast carcinom a, such as
w o m e n w ith contralateral breast cancer o r w h o have genetic risks
such as BRCA1 o r BRCA2 m u ta tio n .473,476,477 T he se n sitivity and
specificity o f ductal lavage fo r diagnosis o f carcinom a are n o t
w e ll kno w n . In tw o studies, lavage cytology was unable to id en-
tify cancer in the m a jo rity o f patients undergoing m astectom y
fo r carcinom a.478 S im ila rly, Brogi et al. fo u n d th a t ductal lavage
had lo w se n sitivity to detect breast carcinom a.479 Furtherm ore,
the c orrelation o f various cytologic a b norm alities w ith specific
histo p atho lo g ic degrees o f p rolifera tive breast disease is very
poor.478 Therefore ductal lavage is n o t sensitive fo r breast cancer
detection and sho uld n o t be used as a screening o r sub stituting
o th e r diagnostic procedure and fo llo w -u p , inc lu d in g periodic
physical e xa m in ation and m am m ography.480,481
Ljung et al. evaluated 431 ductal lavage specimens fo r cells
features inc lu d in g cell arrangem ents, cell size and variatio n,
nuclear features, n uc le oli, and background find ing s.482 Benign
cases showed few o r large e p ith elial clusters o f ductal cells
arranged in one layer and associated w ith m yo ep ith elial cells in
a s lig h tly d iffe re n t plane o f focus ( Fig. 25.81).
In m ild cytologic atypia, the ductal cells are m oderately
enlarged, w ith cells occurring singly, in m onolayer arrangem ent
and sm all clusters. N uclear m em branes are regular and chrom atin
rem ains fin e ly granular. S m all nuc le oli are also noted. Increased
N /C ratios are noted in 4% o f specimens. M ild atypia m ay repre-
sent histolog ic lesions o f hyperplasia, A D H , o r low-grade DCIS.
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