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Eur Radiol (2003) 13:94–99

DOI 10.1007/s00330-002-1401-7 BREAST

M.A. Funovics Galactography: method of choice


M.O. Philipp
B. Lackner in pathologic nipple discharge?
M. Fuchsjaeger
P.T. Funovics
V. Metz

Received: 21 August 2001 Abstract Our objective was to as- gations occurred in 16 (12%) cases.
Revised: 17 January 2002 sess the role of galactography in the Cytology showed 69.2%/66.8%
Accepted: 4 February 2002 diagnostic work-up of patients with for papillomatous borderline or
Published online: 16 May 2002 pathological nipple discharge togeth- malignant cells; 53.8%/75.3% for
© Springer-Verlag 2002
er with exfoliative cytology, and in- borderline or malignant cells; and
vestigation of secretion colour. All 7.7%/100% for one case of malig-
galactographies performed in this nant cells. For the assessment of
center between 1993 and 1998 were pathological secretions, galactogra-
evaluated retrospectively. In 134 phy is a sensitive but unspecific
cases, outcomes, defined as either a method for the detection of papillo-
M.A. Funovics (✉) · B. Lackner postoperative histology or a negative mas or carcinomas. Filling defects,
M. Fuchsjaeger · V. Metz follow-up over 2 years after galac- ductectasia and ductal distortion car-
Department of Radiology,
University of Vienna Medical School, tography, were available. In 96 of ry the highest levels of suspicion for
Vienna General Hospital, these cases, exfoliative cytology was carcinoma. A normal galactogram is
Währinger Gürtel 18–20, performed, and in 65 cases the col- a specific yet moderately sensitive
1090 Vienna, Austria our of the secretion was determined. indicator of absence of localized dis-
e-mail: martin_funovics@yahoo.com Galactograms, cytological findings ease. Exfoliative cytology shows low
Tel.: +43-1-404007620
Fax: +43-1-404004898 and colour of the secretions were sensitivity but better specificity for
compared with the outcomes. At carcinomas when borderline or ma-
M.O. Philipp
Department of Biomedical Research, galactography, the radiographic lignant cells are found. In the present
University of Vienna Medical School, findings had the following individual series, the colour of the secretions
Vienna General Hospital, sensitivities/specificities in detecting does not add significant information
Währinger Gürtel 18–20, carcinomas: filling defect 55.6%/ about underlying pathology.
1090 Vienna, Austria 62.1%; ductectasia 22.2%/94%; and
P.T. Funovics filling stop 5.6%/77.6%. Normal Keywords Breast · Abnormalities ·
Department of Trauma Surgery, galactograms (n=33, 25%) had a Neoplasms · Diagnosis ·
University of Vienna Medical School,
Vienna General Hospital, sensitivity of 78% and a specificity Galactography · Ductography ·
Währinger Gürtel 18–20, of 93% in predicting absence of dis- Nipple secretion
1090 Vienna, Austria ease. Technically inadequate investi-

Introduction thus, pathological nipple discharge is usually regarded as


an indication for surgical removal of the diseased ductal
While the incidence of breast carcinoma in women who system.
undergo routine screening mammography ranges around To avoid incomplete or excessive tissue removal, pre-
0.5% [1], the incidence of carcinoma in women with uni- operative localisation of the diseased duct and identifica-
lateral, single-pore, spontaneous (i.e. pathological) nip- tion of intra- or periductal abnormalities is necessary.
ple discharge ranges from 4 to 31% [2], with the majori- Galactography has been advocated as the method of
ty of studies reporting a rate between 10 and 15% [3, 4]; choice for the evaluation of nipple discharge.
95

To date, studies have demonstrated the association be- water-soluble, non-ionic contrast material (Iopamidol) as far as the
tween abnormal galactograms and presence of intraduc- patient could tolerate, up to a maximum of 1 ml per duct. No pro-
cedure-related complications were observed, and the contrast ma-
tal pathologies in general, and even with distinct histo- terial was completely resorbed on subsequent investigations, in
pathological entities [3], but no attempt has been made contrast to previous experiences with Lipiodol [5]. After removal
to calculate the sensitivities and specificities of specific of the cannula, plain-film mammography was performed in the
radiographic patterns in predicting the presence of carci- craniocaudal and oblique planes on a Philips Mammovision unit
(Philips Medical Systems, Hamburg, Germany).
noma in subsequent excisional biopsy. Furthermore, the The radiographic findings on the galactograms were classified
negative predictive value of a normal galactogram is un- according to a modified scheme of Gregl [6] into the following
known. Traditionally, galactography is often performed groups:
together with exfoliative cytology of the secrete, al- 1. Technically inadequate investigation
though the value of this investigation remains controver- 2. Normal findings
sial. 3. Ductectasia (i.e. duct over 2 mm width)
In this study we present the results of a large series of 4. Filling defects
5. Filling stops
galactograms performed at our centre which have been 6. Distorted ducts
reevaluated for the presence of specific radiographic
findings with verification of the findings by either histol- In all cases of papilloma or carcinoma, plain-film mammography,
which was performed immediately before galactography, was
ogy or a negative follow-up over 2 years and including a evaluated for the presence of lesions suggestive for malignancy.
group of normal galactograms. In addition, the results of For 94 of the patients undergoing galactography (70.1%), exfo-
exfoliative cytology are compared with the histological liative cytology performed at the same time of galactography was
findings. available. The cytological findings were classified according to
previous studies into five groups [7, 8]:
Group 0: insufficient material
Group 1a: benign cytology without papillomatous formations
Materials and methods Group 1b: benign with papillomatous formations
Group 2: borderline
A retrospective study was performed in which the medical reports Group 3: malignant cytology
and files of all patients who underwent galactography at this cen-
ter were reviewed. Between 1993 and 1998, a total of 316 galac- The colour of the secretion could be determined in 65 of the pa-
tographies were performed in 285 patients who were referred to tients undergoing galactography (48.5%) and was differentiated
the radiology department because of nipple discharge. Patients en- into:
tered the study if they had unilateral, spontaneous secretion from 1. Haemorrhagic
one to four ducts and if either surgery was performed within 2. Clear
2 weeks of the galactography, or if a record of 2 years of negative 3. Yellow/green
follow-up of the secreting breast was available. 4. White/milky
Surgery performed after galactography included ductectomy or
segmentectomy under guidance of the galactography films, but For each group and combination of groups, the sensitivity, speci-
without placement of a hook wire or dye staining of the ducts. The ficity and significance in predicting presence of carcinoma were
negative follow-up over 2 years was defined as follows: determined.
Outcomes were classified as:
1. Negative gynecological screening investigation on a yearly ba-
sis including palpation of the breasts 1. Benign by follow-up
2. Negative mammography screening on a yearly basis for pa- 2. Benign by histology
tients who were over 50 years of age 3. Papilloma
3. No subjective complaints such as masses, abnormal pain, in- 4. Carcinoma
flammation or ongoing secretions
These groups were correlated with the radiographic findings as
For those patients who were not followed-up at this centre, the well as with the exfoliative cytology results and the colour of the
above criteria were verified by telephone interview. secretions using crosstables. Sensitivity and specificity for each
A total of 134 galactographies entered the study. All patients radiographic abnormality in the detection of carcinoma were cal-
reported spontaneous secretion over at least 6 weeks. In 125 cases culated. The correlation of the radiographic finding, filling defect
a single duct was secreting, in 9 cases two to four ducts. or filling stop, with the histological finding, papilloma or carcino-
In 33 cases a negative follow-up was available, and in 101 ma, was tested using the χ2 test. A receiver-operating characteris-
cases surgery was performed. In 96 of the 134 cases, exfoliative tics (ROC) curve was drawn for overall sensitivity versus specific-
cytology was performed additionally, and in 65 cases the colour of ity of galactography in the detection of carcinoma by means of
the secretions was available. Cytology and the colour of the secre- stepwise inclusion of the radiographic abnormalities in the order
tions were correlated with the outcomes in the same way as the ra- of their respective individual sensitivities (Fig. 1). The area under
diographic findings. the curve (Az) was calculated by triangulation and the significance
Galactography was performed with the patient in supine posi- by χ2 analysis using dedicated statistics software (SPSS, Chicago,
tion and the ipsilateral arm resting behind the head. By examining Ill.).
a small drop of secretion, the orifice of the secreting duct was lo-
calized. The ducts were cannulized by insertion of blunt sterile
steel cannula, measuring 25 mm in length and 0.6 mm in diameter
(42-G end-port sialography cannula). Once the tip entered the ori-
fice, the cannula easily descended into the duct. A 1-ml tuberculin
syringe was attached to the cannula and the duct was filled with
96

Results
Of the 134 galactographies available for study, Table 1
shows outcomes correlated with the radiographic find-
ings. The galactograms showed filling defects (Fig. 2) in
54 cases (40.3%), filling stops (Fig. 3) in 27 (20.1%),
duct distortion in 3 (2.2%) and ductectasias in 11 (8.2%)
cases. Sixteen cases (11.9%) did not show properly filled
ducts and were considered technically inadequate (col-
umn 1 in Table 1). In 6 of these cases the patient could
not tolerate cannulation of all secreting ducts. In 8 of the
cases the duct could not be cannulated properly, and in
the 2 remaining cases there was paravasation of contrast
material that did not allow for proper delineation of the
ducts.
Normal galactographic findings correlated in 18 cases
with a negative follow-up over 2 years; thus, normal
findings at galactography showed a sensitivity of 78.3%
in detecting absence of intraductal pathology, with a
specificity of 92.6% (p<0.001; χ2 test). The galacto-
graphic correlation of intraductal processes (i.e. filling
defects or filling stops) in 51 cases showed a sensitivity
Fig. 1 Receiver-operating characteristics curve for ductal patholo- of 86.4% and a specificity of 49.2% in predicting papil-
gies at galactography (filling defects, ductectasias, distorted ducts,
filling stops included in the order of their individual sensitivities) loma or carcinoma (p<0.001; χ2 test). The low specifici-
for the detection of carcinoma ty is largely due to a high rate of 22 false-positive find-
ings that were identified as periductal fibrocystic chang-
es on subsequent surgery. Seventy-three percent of all

Table 1 The radiographic find-


ings at galactography (col- Technically Normal Duct- Filling Filling Distor- Total
umns) vs the histological out- inadequate ectasia defect stop tion
come (rows) for 134 patients
with pathological secretion. Benign by follow-up 7 18 4 2 2 33
The last two rows represent the Benign by histology 2 3 3 16 10 35
sensitivities and specificities of Papilloma 6 1 26 14 1 48
the respective radiographic Carcinoma 1 1 4 10 1 1 18
findings in the detection of car- Total 16 23 11 54 27 3 134
cinomas
Sensitivity (%) 5.6 22.2 55.6 5.6 5.6
Specificity (%) 81.0 94.0 62.1 77.6 98.3

Table 2 Results of exfoliative


cytology (columns) vs the his- 0 1a 1b 2 3 Total
tological outcome (rows) for Insufficient Benign Papillomatous Borderline Malignant
96 patients with pathological material
secretions. The sensitivities and
specificities of cytology results Benign by follow-up 12 1 13
1b or higher, 2 or higher, and Benign by histology 16 3 9 28
3 in predicting carcinoma on Papilloma 9 17 3 11 40
subsequent surgery are given in Carcinoma 4 2 6 1 13
the lower rows Total 9 49 9 26 1 94
Sensitivity |.......................... 69.2% ...........................|
|............. 53.8% ............|
|... 7.7% ...|
Specificity |.......................... 66.6% ...........................|
|............. 75.3% ............|
|...100% ...|
97

Fig. 2 Galactogram in the cra-


niocaudal plane in a 62-year-
old patient with pathological
nipple discharge. In the ectatic
duct, there is a lobulated
mass. Histology after lumpec-
tomy showed an intraductal
papilloma

Fig. 3 Galactogram in the cra-


niocaudal plane in a 77-year-
old patient with secretions and
pain, negative mammography
and no palpable mass. There is
a filling stop of the ectatic duct
after 4 cm due to a convex
mass protruding into the lumen.
Histology after segmentectomy
showed an invasive ductal
carcinoma

false-positive findings could be attributed to fibrocystic individual sensitivities, an ROC curve is obtained which
changes, whereas the proportion of fibrocystic changes is shown in Fig. 1. The area under the curve (Az) is
among all histological groups other than papilloma or 0.652 (p=0.038).
carcinoma was only 39.7%. Table 2 shows the 94 cases in which cytology was ob-
There were 18 cases of carcinomas, corresponding to tained and correlated with the histological diagnosis. In
a percentage of 13.4% in the study population. Of these the 13 cases of carcinoma, normal benign cytology had
18 cases, 11 showed filling defects or filling stops at ga- been reported in 4 cases, benign cytology with papillo-
lactography. In 1 case galactography was technically in- matous formations in 2 cases, borderline cytology in
adequate, and of the remaining 6 cases, galactography 6 cases and malignant cytology in only 1 case. In 9 cases
was normal in only 1 case. In this case the carcinoma there was not enough material for diagnosis. All of these
was detected at mammography. This was the only case 9 cases were papillomas at histology. Sensitivity and
of carcinoma, where mammography, which was per- specificity for detection of carcinoma were 69.2 and
formed together with galactography in all patients, re- 66.6%, respectively, for types 1b, 2 or 3 cytology, 53.8
vealed a suspicious lesion. The last two lines of Table 1 and 75.3%, respectively, for types 2 or 3 cytology, and
show the respective sensitivities and specificities of each 7.7 and 100%, respectively, for 1 case of type-3 cytolo-
single radiographic abnormality in the detection of carci- gy.
noma. If the radiographic abnormalities are stepwise in- In 65 cases the colour of the secretions was noted.
cluded in the diagnosis of carcinoma in the order of their There was no significant correlation between any colour
98

group or any combination of groups and carcinoma or present a precanceromatous condition [16, 17]; however,
papilloma. Haemorrhagic secretion showed a sensitivity the frequency of carcinomas in patients with pathologi-
of 66.7% and a specificity of 43.4% (p=0.523), and clear cal nipple discharge is high enough to mandate excision-
secretion showed a sensitivity of 8.3% and a specificity al biopsy of the diseased region, typically performed af-
of 86.8% (p=0.643). The fact that most secretions for car- ter galactography to locate intraductal lesions. In addi-
cinomas and papillomas were of the haemorrhagic type is tion, nipple discharge together with a palpable mass, are
due to the high proportion (58%) of haemorrhagic secre- symptoms that are normally discovered and easily ob-
tions in the entire study group. The incidence of carcino- served by the patient herself. In such cases the indication
ma in patients with haemorrhagic secretions was 21.1%, for further diagnosis and biopsy/surgery is broader, be-
and in those with secretions of other colours, 14.8%. cause even if the symptom itself has a benign cause, an
eventual incidental carcinoma could occur, and in such a
case it would be difficult to justify a conservative work-
Discussion up.
Traditionally, haemorrhagic nipple discharge has been
Nipple discharge is relatively common and occurs in associated with carcinoma or with localized intraductal
3–8% of the patients who consult a doctor for a disease disease. The incidence of haemorrhagic secretion ranges
of the breast [9, 10]. Usually, the underlying cause is be- between 22 and 55% for all patients, and up to 51% for
nign. Approximately 50% of the secretions are physio- patients with carcinoma [12, 13, 18, 19]. Watery and se-
logical or secondary secretions with an underlying sys- rous secretion has been found in 2–33% of cases [20].
temic cause, and the other half are pathologic secretions Furthermore, up to 11% of the patients with physiologi-
caused by a lesion in the breast [11, 12]. cal secretions have been reported to produce haemor-
The results of this study suggest that in the assess- rhagic secretions [11, 19].
ment of pathologic nipple secretions, normal findings at In the present study the overall incidence of haemor-
galactography do carry a high specificity and a moderate rhagic secretion was 58%, and the haemorrhagic secre-
sensitivity in predicting the absence of intraductal dis- tions in the carcinoma group were 67%. There was no
ease, whereas filling defects and filling stops are a sensi- statistically significant correlation between the colour of
tive yet unspecific indicator for intraductal papilloma or the secretions and any histological diagnosis; however,
carcinoma. in this relatively small cohort of 65 cases, the absence of
In this study the most important limitation of galac- statistically significant differences between two groups
tography was the high number of false-positive results in has to be regarded very carefully and cannot be interpret-
predicting intraductal processes, with most misinterpre- ed as equality. With this number of cases, the beta error
tations in the fibrosis group (including mastopathy, peri- is still >0.2, i.e. a difference of over 20% between the
ductal fibrosis and sclerosing adenosis). At our centre groups in carcinoma incidence would go unnoticed.
surgical excision of diseased ducts is performed with Some previous studies also found a trend to higher inci-
guidance of the galactograms alone and usually without dence of carcinoma in patients with haemorrhagic secre-
the aid of placing a hook wire or dye staining of the tions [21], but these correlations have not been tested for
duct; thus, a certain proportion of intraductal pathology significance.
shown on the galactograms may have been missed at The results of exfoliative cytology showed only 1
surgery [13]. In addition, galactography alone cannot case of malignant cytology, whereas 4 of the 13 carcino-
distinguish between intrinsic and extrinsic obliteration of mas had benign cytology. These results correspond well
a duct, and some fibrotic processes in the breast have with several other studies where exfoliative cytology and
been shown to produce distortion, calibre irregularities galactography were correlated with histological diagno-
and extrinsic occlusions of ducts. This explains the over- sis [22]. One reason may be the proportion of well-dif-
lap between the fibrosis group and the group of intraduc- ferentiated ductal carcinomas, of which only 30–40%
tal pathologies. have been shown to be associated with malignant cytolo-
There were 14.5% of patients evaluated for pathologi- gy [10]. In a large series of exfoliative cytology investi-
cal nipple discharge who had in situ or invasive ductal gations comprising 225 cases, only 2 definitive malig-
carcinomas, a rate consistent with the literature [14, 15]. nant cytologies were found [13]. In contrast to galactog-
The most frequent cause for discharge (38.7%) was pap- raphy, borderline or malignant exfoliative cytology has a
illoma. Mammography which was performed together low sensitivity but high specificity in detecting carcino-
with galactography in all of these cases revealed in only mas, and therefore has the potential to increase the likeli-
1 case a suspicious mass. This low sensitivity may be hood of malignant disease if it occurs together with in-
due to the typically small size of the malignant lesions traductal pathologies at galactography.
that were detected at galactography.
Generally, solitary papillomas are regarded as benign
lesions, whereas papillomatosis has been found to re-
99

Conclusion intraductal pathology at galactography does not allow for


a reliable differentiation between benign and malignant
In conclusion, galactography should be the method of lesions by radiographic features. The role of galactogra-
choice in the work-up of pathological nipple secretions. phy is therefore a topographic one. For these cases initial
If galactograms are negative, a close follow-up with results with MR galactography have shown a high speci-
mammography and repetitive galactographies seems jus- ficity in exclusion of malignant disease and thus the po-
tified. In the case of pathological findings at galactogra- tential to reduce unnecessary surgery [23]; however, if
phy, especially filling defects or filling stops, one should MR galactography is not available, the high prevalence
be aware that these findings are an unspecific yet sensi- of carcinomas in patients with ductal pathologies justi-
tive indicator for the presence of papilloma or carcino- fies excisional biopsy, eventually after placement of a
ma, even if mammography is negative. The presence of hook wire or dye staining of the diseased ducts, since
borderline or malignant cytology for such cases further this has been shown to reduce the volume of the resec-
increases likelihood of malignant disease. Presence of tion necessary for reliable inclusion of the pathology [2].

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