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Alvarez et al.
Sonography
of Lymph
Node
Metastases

W O M E N S
IMAGING

Soledad Alvarez1
Enrique Aorbe2
Pilar Alcorta1
Fernando Lpez2
Ignacio Alonso1
Julia Corts1
Alvarez S, Aorbe E, Alcorta P, Lpez F, Alonso
I, Corts J

Keywords: breast cancer, lymph nodes, metastases,


sonography
DOI:10.2214/AJR.05.0936
Received June 2, 2005; accepted after revision
August 22, 2005.
1Department

of Nuclear Medicine, Hospital Santiago


Apstol, Olaguibel 29, 01004 Vitoria, Alava, Spain. Address
correspondence to S. Alvarez
(salvarez@hsan.osakidetza.net).

2Department

of Radiology, Hospital Santiago Apstol,


Olaguibel, 01004 Vitoria, Alava, Spain.

AJR 2006; 186:13421348


0361803X/06/18651342
American Roentgen Ray Society

1342

Role of Sonography in the


Diagnosis of Axillary Lymph Node
Metastases in Breast Cancer:
A Systematic Review
OBJECTIVE. The purpose of our study was to evaluate the accuracy of sonography and
sonographically guided biopsy in the preoperative diagnosis of metastatic invasion of the axilla
in patients with breast carcinoma.
MATERIALS AND METHODS. We performed a MEDLINE search (keywords, sonography OR ultrasound AND axillary) and a manual search of the references of relevant
studies and reviews of preoperative diagnosis on sonography of possible axillary metastases.
The gold standard required was axillary lymph node dissection; we accepted sentinel node biopsy as an alternative gold standard. Considering the sonographic findings and the results of
the sonographically guided biopsy, the sensitivity and specificity were calculated using metaanalysis. We also checked the existence of heterogeneity of the summary results.
RESULTS. Sixteen articles were selected. In sonography of axillae without palpable
nodes, and using lymph node size as the criterion for positivity, sensitivity varied between
48.8% (95% confidence interval, 39.658%) and 87.1% (76.194.3%) and specificity, between
55.6% (44.766.3%) and 97.3% (86.199.9%). When lymph node morphology was used as the
criterion for positivity, sensitivity ranged from 26.4% (15.340.3%) to 75.9% (56.489.7%)
and specificity, from 88.4% (82.193.1%) to 98.1% (90.199.9%). The results are different if
axillae with palpable nodes are included. The sonographically guided biopsy shows a sensitivity that varies between 30.6% (22.539.6%) and 62.9% (49.774.8%) and a specificity of 100%
(94.8100%). Many of the summary results obtained after meta-analysis show a heterogeneity
that disappears, on occasion, on excluding the studies that use a double gold standard.
CONCLUSION. Axillary sonography is moderately sensitive and fairly specific in the diagnosis of axillary metastatic involvement. Sonographically guided biopsy of the sonographically suspicious nodes somewhat increases the specificity, which reaches 100%. Negative
sonographic results do not exclude axillary lymph node metastases.
he presence of axillary lymph
node metastases in breast cancer
is an important factor in assessing
prognosis and determines management after surgery [1]. Axillary staging is
traditionally performed by means of axillary
lymph node dissection.
The traditional use of axillary lymph node
dissection has been justified by the need for
staging and the possibility of reducing the tumoral load by resecting the possibly affected
lymph nodes. Doubt has been cast on the latter aspect with the publication of contradictory results about the effect of lymph node
dissection on patient survival. A meta-analysis performed by Orr [2] and published in
1999 shows a slight improvement in the survival of women who have undergone axillary
lymph node dissection. On the other hand, a

randomized trial with a long follow-up period


performed by Fisher et al. [3] shows no survival advantage in patients undergoing lymph
node dissection. To this has been added the recent introduction of the sentinel node biopsy
in the decision to perform an axillary lymph
node dissection. One of the problems that
arises from the sentinel node biopsy is the existence of false-negative results, which leads
to axillary lymph node dissection not being
performed in patients with a negative sentinel
node biopsy but who in fact have axillary metastases. It has been found that 115% of patients with a negative sentinel node biopsy for
metastases have other affected lymph nodes
in the same region [4]. Most of these falsenegatives are due to massive lymph node metastases in the first drainage node [57]. Axillary sonography is not used systematically

AJR:186, May 2006

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Sonography of Lymph Node Metastases


in patients with breast cancer because of its
low sensitivity. However, the possibility of
detecting some of these metastases and reducing the number of false-negatives at sentinel
node biopsy has renewed interest in the use of
sonography before sentinel node biopsy [8].
Our aim was to learn, through a systematic
review, the accuracy of sonography in the diagnosis of axillary lymph node metastases in
patients with breast cancer, taking into account the different criteria for diagnosis and
the contribution of sonographically guided biopsy of suspicious nodes.
Materials and Methods
Literature Review
We performed a literature review starting with
an electronic bibliographic search (Ovid-MEDLINE, Ovid Technologies) January 1980 to March
12, 2004. The search was made using the text words
ultrasound OR sonography AND axillary, by
which we found 367 articles. The selection was
limited to articles written in English, Spanish,
French, and Italian. After reading the titles, we selected those abstracts that gave data about the diagnostic accuracy of axillary sonography in breast
cancer; 31 articles were selected. Then we performed a manual search in the reference lists of the
relevant articles previously selected and in the reference lists of the articles reviewed. For the final selection we chose those articles that fulfilled the following criteria for inclusion: patients were
diagnosed as having breast cancer and axillary
sonography was performed before axillary lymph
node dissection or sentinel node biopsy; sonography was performed using transducers of 7 MHz or
higher frequencies; sonographic criteria as to size
and morphology, or sonographically guided biopsy,
were used to classify a lymph node as positive or
negative for metastases; the histopathologic result
of total axillary lymph node dissection or results of
dissection of first (nodes outside the smaller pectoral muscle) and second (behind the smaller pectoral
muscle) levels was required as the gold standard,
and a sentinel node biopsy was accepted as an alternative gold standard in those studies that used
this technique; and results were expressed in terms
of sensitivity and specificity. For the inclusion of
the results in the meta-analysis, we required that in
each study it was possible to establish the number
of true-positives, true-negatives, false-positives,
and false-negatives.
We collected data from the selected studies
about the methodology used: type of design (prospective or retrospective), selection and number of
patients, blind interpretation of the diagnostic
tests, and any other data that might prove useful
for a later analysis.

AJR:186, May 2006

Accuracy Measures for Primary Studies


and Meta-Analysis
Statistical testing was performed using Meta-DiSc
[9]. For each study, the sensitivity, specificity, and exact 95% confidence intervals (CIs) were calculated.
Summary sensitivity and specificity were calculated as a weighted average in which the weight of
each study is its sample size. The 95% CIs of individual and pooled sensitivity and specificity were
calculated using the F distribution method to compute the exact confidence interval for the binomial
proportion. The degree of variability (homogeneity)
among study results of sensitivity and specificity was
tested using chi-square distribution with K 1 degrees of freedom (K being the number of studies).

Results
Sixteen studies fulfilled the criteria for inclusion and were considered valid in the final
selection [1025].
Methodology of the Studies
The methodologic characteristics of the
studies included, and the sonographic criteria
for positivity, are shown in Table 1. Fourteen
studies were prospective, although only eight
specified that the patients were selected consecutively. The gold standard used was total
or first- and second-level axillary lymph node
dissection in 11 studies, whereas the other
five used as a gold standard the results of the
sentinel node biopsy or the axillary lymph
node dissection in patients who rejected sentinel node biopsy.
One study always used axillary lymph
node dissection after the sentinel node detection technique, regardless of its result [19]. In
those studies that used axillary lymph node
dissection as the gold standard, only one
study specified the methodology used for the
histologic processing of the axillary lymph
nodes and their criteria for positivity [21], and
another [11] stated that serial sections were
not performed. The remaining studies did not
explain the method of processing material for
histologic studies. In all the studies in which
the sentinel node technique was applied, multiserial sections were made except in one that
omitted this information [23]. Only three
studies claimed to have performed a blind assessment of the gold standard (axillary lymph
node dissection) or the sonography results.
In three studies, the sonographic criterion to
establish whether an axillary lymph node was
metastatic was a node larger than 5 mm [10,
11, 13], whereas other studies considered any
node visible on sonography to be metastatic,
regardless of its size [12]. In the remaining

studies, various morphologic or structural criteria for the node were applied (a rounded
shape, hypoechogenicity, cortical thickening,
obliteration of the hilum, lobulation) or a combination of size and morphologic criteria. In
the last column of Table 1 we indicate the frequency of the transducer used, the stage
(TNM) or tumor size (T) of the patients, and
other data of interest. The detailed analysis of
some studies allowed us to deduce sensitivity
and specificity data, making use of sonographic criteria of size or morphology that had
not been analyzed directly by the authors.
In all the studies in which a sonographically guided biopsy was performed, smallcaliber needles were used (2022 gauge), except in one study [23] in which core-biopsy
(14 gauge) was performed, limiting the fineneedle biopsies to technically difficult cases.
In two studies [24, 25], biopsy aspiration with
a fine needle was performed although the authors did not give the needle caliber. The
sonographically guided biopsy criteria were
different, depending on the studies: in three
studies, any sonographically visible axillary
lymph node was biopsied [17, 19, 21], but in
the other five studies [20, 2225] needle biopsy was limited to indeterminate nodes or
those suspected of being malignant.
Accuracy of Axillary Sonography
To establish the parameters for accuracy of
sonography in the diagnosis of axillary lymph
node metastases, we divided the results into
three groups: studies that included axillae
with both palpable and nonpalpable nodes
(Table 2), studies that included only axillae
with nonpalpable nodes (Table 3), and studies
that included sonographically guided biopsy
of the axillary lymph nodes (Table 4).
Studies that included palpable and nonpalpable nodesIn these studies (Table 2), if the
size (> 5 mm) or visibility on sonography of
the node was used as the criterion for positivity,
sensitivity oscillated between 66.1% (95% CI,
52.677.9%) and 72.7% (49.889.3%), with
no heterogeneity found between the results,
both when we include only those studies that
used axillary lymph node dissection as the gold
standard and when we also include the studies
that used sentinel node biopsy. Specificity varies between 44.1% (34.354.3%) and 97.9%
(88.799.9%), with heterogeneity found between the results, even when we exclude studies with sentinel node biopsy.
If the morphology of the lymph node was
used as a criterion for sonographic positivity,
sensitivity oscillated between 54.7% (95%

1343

Alvarez et al.
TABLE 1: Methodology and Characteristics of the Studies Selected
Year

Design

Gold Standarda

Bruneton et al. [10]

1986

Prospective

Lymphadenectomy

NS

> 5 mm

57 MHz; stage, T1T4

Tate et al. [11]

1989

Prospective,
consecutive

Lymphadenectomy

Yes

> 5 mm

7.5 MHz, no serial sections,


stages IIII

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Study

Blindedb

Criteria for Positivity

Comments

Mustonen et al. [12]

1990

Prospective

Lymphadenectomy

Yes

Visible node

7.5 MHz; stage, TisT4

Vaidya et al. [13]

1996

Prospective,
consecutive

Lymphadenectomy

NS

> 5 mm

7.5 MHz; stage, T1T3

Lam et al. [14]

1996

Prospective, not Lymphadenectomy


consecutive

Yes

Round, hypoechoic node, obliteration of


hilum, with or without cortical
hypertrophy

1015 MHz; T stage, NS

Yang et al. [15]

1996

Prospective,
consecutive

Lymphadenectomy

NS

Round, hypoechoic node, with or without 10 MHz; stage, T1T4


eccentric cortical hypertrophy and
obliteration of hilum

Verbanck et al. [16]

1997

Prospective, not Lymphadenectomy


consecutive

NS

Round or oval node, hypoechoic, > 5 mm 7.5 MHz; T stage, NS; selection
of patients in radiology
department, probably biased

Bonnema et al. [17]

1997

Prospective,
consecutive

Lymphadenectomy

NS

> 5 mm, hypoechoic node,


heterogeneous

7.5 MHz; stage, T1T3

Yang et al. [18]

1998

Prospective

Lymphadenectomy

NS

Node with loss of hilum, eccentric


cortical hypertrophy

10 MHz; T stage, NS

de Kanter et al. [19]

1999

Prospective,
consecutive

Lymphadenectomy
after sentinel node
biopsy

NS

Homogeneous or not homogeneous


node

710 MHz; stage, T1T3; only


data from patients with
biopsied nodes

Krishnamurthy et al.
[20]

2002

Retrospective

Lymphadenectomy

NS

Hypoechoic node with cortical


thickening or eccentric lobulation

7.5 MHz; T stage, NS; selected


only patients with needlebiopsied nodes

Kuenen-Boumeester
et al. [21]

2003

Prospective

Lymphadenectomy
and sentinel node
biopsy

NS

All visible nodes independently of


pattern

7.5 MHz; stage, T1T3; includes


only patients with needlebiopsied nodes

Sapino et al. [22]

2003

Prospective,
consecutive

Lymphadenectomy
and sentinel node
biopsy

NS

Round, hypoechoic node, eccentrically


thickening

10 MHz; T stage, NS

Damera et al. [23]

2003

Prospective,
consecutive

Lymphadenectomy
sample and/or
sentinel node biopsy

NS

Round or oval node with cortical


thickening

814 MHz; stage, NS; variable


gold standard

Deurloo et al. [24]

2003

Prospective,
consecutive

Lymphadenectomy
and sentinel node
biopsy

NS

> 5 mm or atypical cortex

13 MHz; stage, T1T4

Bedrosian et al. [25]

2003

Retrospective,
archive

Lymphadenectomy,
sentinel node biopsy

NS

Round, oval, or hypoechoic node, or with 7.512 MHz; stage, TisT4


eccentric cortical lobulation

NoteNS = not specified, T = tumor stage.


a Lymphadenectomy = axillary lymphadenectomy.
b For assessment of results.

CI, 41.767.2%) and 92.3% (74.999.1%)


and specificity, between 80.4% 73.986.2%)
and 97.1% (9099.6%). Heterogeneity does
not exist for either parameter when studies
with sentinel node biopsy are excluded.
Studies that included only nonpalpable
nodesIn these studies (Table 3), if the size
on sonography of the node (> 5 mm) or its
visibility was used as a criterion for positivity,
sensitivity varies from 48.8% (95% CI,
39.658%) to 87.1% (76.194.3%) and specificity, from 55.6% (44.766.3%) to 97.3%
(86.199.9%). The chi-square test shows het-

1344

erogeneity in both, even when studies with


sentinel node biopsy are excluded.
If the morphology of the node was used as
the criterion for positivity, sensitivity varies
from 26.4% (95% CI, 15.340.3%) to 75.9%
(56.489.7%) and specificity, from 88.4%
(82.193.1%) to 98.1% (90.199.9%). The
results are heterogeneous in all groups except
specificity when studies with sentinel node
biopsy are excluded.
Sonographically guided biopsyAlthough
studies using sonographically guided biopsy
are included in Table 4, studies with retro-

spective selection of patients were excluded


from the meta-analysis.
Counting only those patients in whom it was
possible to perform a sonographically guided
biopsy and obtain material for histologic analysis of axillary lymph nodes, the sensitivity of
sonography varies between 43.5% (95% CI,
3354.7%) and 94.9% (88.598.3%) and specificity, between 96.9% (91.399.4%) and
100% (96.2100%). Logically, heterogeneity
is shown only in the sensitivity results.
When all patients are included just as they
were initially selected (considering as false-

AJR:186, May 2006

Sonography of Lymph Node Metastases


TABLE 2: Diagnostic Accuracy of Axillary Sonography in Patients with Breast Carcinoma
(Studies That Include Axillae with Both Palpable and Nonpalpable Nodes)
Study

Date

TP

TN

Bruneton et al. [10]

1986

16

37

Tate et al. [11]

1989

39

61

FP

FN

Sensitivity (%)

Specificity (%)

72.7 (49.889.3)

97.4 (86.299.9)

20

20

66.1 (52.677.9)

75.3 (64.584.2)

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Size criteriona

Mustonen et al. [12]

1990

12

46

66.7 (40.986.6)

97.9 (88.799.9)

Vaidya et al. [13]

1996

78

78

35

69.0 (59.677.4)

89.7 (81.395.2)

Damera et al. [23]

2003

46

45

57

18

71.8 (59.282.4)

44.1 (34.354.3)

68.4 (61.774.6)

87.7 (83.191.5)

Summaryb
Heterogeneityb,c

0.38

Summary

0.94

69.2 (63.474.6)

Heterogeneityc

0.67

20.86

0.000

75.2 (70.479.6)
0.95

90.27

0.000

Morphologic criteriond
Lam et al. [14]

1996

19

72.7 (39.094.0)

95.0 (75.199.8)

Yang et al. [15]

1996

35

68

79.5 (64.790.2)

97.1 (90.099.6)

Verbanck et al. [16]

1997

24

20

92.3 (74.999.1)

95.2 (76.299.9)

Yang et al. [18]

1998

31

40

79.5 (63.590.7)

95.2 (83.899.4)

Sapino et al. [22]

2003

60

144

35

28

68.2 (57.477.7)

80.4 (73.986.2)

Damera et al. [23]

2003

35

83

19

29

54.7 (41.767.2)

81.4 (72.488.4)

Summaryb
Heterogeneityb,c

81.7 (73.688.1)
3.18

Summarye

71.0 (65.276.3)

Heterogeneityc,e

18.38

96.1 (91.798.5)
0.36

0.4

0.94

86.2 (82.689.3)
0.003

23.53

0.000

NoteNumbers in parentheses are 95% confidence intervals. TP = true-positive, TN = true-negative. FP = false-positive, FN = false-negative.
a Studies in which criterion for classifying axillary node as positive was size.
b Includes only studies in which gold standard was axillary lymph node dissection.
c Using chi-square test.
d Studies in which criterion for classifying axillary node as positive was morphologic or structural.
e Includes studies in which gold standard was axillary lymph node dissection or sentinel node biopsy.

negatives those women in whom sonography


did not find nodes, and those in whom nodes
were not suspicious or processable material
was not obtained on needle biopsy and metastatic invasion was later shown), sensitivity
descends with respect to the previous group
and varies from 30.6% (95% CI, 22.539.6%)
to 62.9% (49.774.8%) and specificity is always 100% (94.8100%). The average sensitivity result excluding studies with sentinel
node biopsy is from a sole study and therefore
does not show heterogeneity.
Discussion
The studies selected had different degrees
of methodologic quality. We have included
only the prospective studies, and many of
them were consecutive. There is no explicit
reference to the manner of selecting patients,
and in most studies there does not seem to
have been a blind interpretation of the results
(gold standard and sonography). The gold
standards used were two: in most studies the

AJR:186, May 2006

standard was axillary lymph node dissection,


whereas in others it was the combination of
biopsy of the sentinel node and, when this
was not accepted, axillary lymph node dissection. In the case of axillary lymph node dissection, neither the positivity criterion nor the
method of processing the nodes was specified. These aspects have a decisive influence
because the use of more exhaustive histology
sections permits a greater percentage of metastases to be discovered [26, 27].
Our review shows that axillary sonography
is moderately sensitive and quite specific in
the diagnosis of axillary metastatic involvement in patients with breast cancer. The different studies show variable results
(Tables 24). With the aim of reducing this
variability, we performed analyses according
to whether the axillary nodes were palpable.
The existence of palpable axillary nodes is often used to decide whether to perform a sentinel node biopsy or an axillary lymph node
dissection, although axillary palpation has

low sensitivity and specificity [28]. Within


these groups we subdivided the studies according to the two sonographic criteria used
to diagnose a node as positive: size (> 5 mm)
and morphology (round, hypoechoic, with
loss of central hilum, eccentric cortical hypertrophy). Even so, the results continued to be
variable in each group by the heterogeneity
tests performed in the meta-analysis.
To lessen as much as possible the sources of
variability, we performed a second meta-analysis, excluding the studies that used sentinel
node biopsy as a gold standard. With this procedure the heterogeneity disappeared in most
but not in all cases. Sentinel node biopsy may
give false-negative results, which may lead to
verification bias. Other factors may determine
residual heterogeneity. One of these could be
the type of patients selected (e.g., different
staging) or the way in which they were selected
(sometimes consecutively and sometimes not),
and independently of this, the place in which
the selection was performed: in almost all

1345

Alvarez et al.
TABLE 3: Diagnostic Accuracy of Axillary Sonography in Patients with Breast Carcinoma
(Studies That Include Axillae with Nonpalpable Nodes Only)
Study

Date

TP

TN

FP

FN

Sensitivity (%)

Specificity (%)

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Size criteriona
Bruneton et al. [10]

1986

36

58.3 (27.684.8)

97.3 (86.199.9)

Vaidya et al. [13]

1996

28

64

20

58.3 (43.272.4)

95.5 (87.599)

Bonnema et al. [17]

1997

54

49

39

Deurloo et al. [24]

2003

59

113

34

62

87.1 (76.194.3)

55.6 (44.766.3)

48.8 (39.658)

76.9 (69.283.4)

Summaryb

73.0 (64.280.6)

Heterogeneityb,c

13.25

Summaryd

60.9 (54.567.1)

Heterogeneityc,d

28.36

77.6 (71.083.3)
0.001

49.69

0.000

77.3 (72.581.6)
0.000

49.72

0.000

Morphologic criterione
Yang et al. [15]

1996

22

53

75.9 (56.489.7)

98.1 (90.199.9)

Bonnema et al. [17]

1997

22

Deurloo et al. [24]

2003

48

84

130

17

40

35.0 (23.748.7)

95.5 (88.798.7)

72

40.5 (31.749.8)

Bedrosian et al. [25]f

2003

14

141

14

88.4 (82.193.1)

39

26.4 (15.340.3)

91.0 (85.395.0)

Summaryb

48.4 (37.150.8)

96.5 (92.098.8)

Heterogeneityb,c

13.35

Summaryd

43.9 (65.276.3)

Heterogeneityc,d

14.65

0.000

0.78

0.37

92.4 (88.795.2)
0.001

7.8

0.02

NoteNumbers in parentheses are 95% confidence intervals. TP = true-positive, TN = true-negative. FP = false-positive, FN = false-negative.
a Studies in which criterion for classifying axillary node as positive was size.
b Includes only studies in which gold standard was axillary lymph node dissection.
c Using chi-square test.
d Includes studies in which gold standard was axillary lymph node dissection or sentinel node biopsy.
e Studies in which criterion for classifying axillary node as positive was morphologic or structural.
f Retrospective, so excluded from meta-analyses.

cases, selection of patients took place in the


surgery department, but in a few cases selection took place in the radiology department
[16] and in other studies the place of selection
was not recorded. The different equipment
used may also have an influence (with greater
resolution resulting with the use of more up-todate apparatus); different transducer frequencies were also used. Also, small variations existed in the criteria applied by different authors
to determine on sonography whether the node
was benign or malignant.
On occasion, our results are contradictory.
Sensitivity should be greater when palpable
and nonpalpable nodes are included than
when considering only nonpalpable nodes,
because the palpable ones, being larger,
should be detected better on sonography.
However, if we compare the sensitivities in
Tables 2 and 3, we observe the opposite tendency. Equally, sensitivity should be greater
when size criteria are used as compared with
morphologic criteria, because the latter require the node to be seen and to have certain
sonographic characteristics. This hypothesis

1346

is borne out in those articles that used data


based on both size and morphologic criteria:
thus Bonnema et al. [17], Damera et al. [23],
and Deurloo et al. [24] found greater sensitivity for sonography when they used size as a
positivity criterion than when they used morphologic criteria. This same finding, although
with heterogeneity, is observed in the average
results of the series that include only nonpalpable nodes (Table 3) but not in the average
results considering all the nodes, both palpable and nonpalpable (Table 2).
On the contrary, although it shows heterogeneity in some groups, specificity is more
uniform in tendency, being greater when
morphologic criteria are used than when
only size is considered.
In an attempt to improve the results of
sonography, sonographically guided biopsy
of the axillary nodes has been introduced.
The criteria applied as indications for needle
biopsy are different in the various studies because in some cases only those nodes suspected of being malignant on sonography are
biopsied [20, 2225], and in other cases all

the nodes are biopsied independently of their


appearance on sonography or their size [17,
19, 21]. The use of sonographically guided
biopsy notably increases specificity, which
reaches as high as 100%, although sensitivity is reduced because it is necessary to have
visualized the node previously (in cases in
which all nodes were biopsied) or to fulfill
the sonographic criteria for malignancy (in
those cases in which only nodes suspected of
being malignant on sonography are biopsied), and a needle biopsy must be technically possible. Therefore, sensitivity decreases if we consider all the axillae studied
on sonography and not only those cases in
which it was possible to perform the biopsy.
Those axillae should be considered negative
if lymph nodes were not visualized, they
were not deemed suspicious, or needle biopsy was not technically possible. True-negatives were those that were found to be free
of metastasis according to the gold standard,
and false-negatives were those found to be
metastases. The specificity of the sonographically guided biopsy is greater (100%)

AJR:186, May 2006

Sonography of Lymph Node Metastases


TABLE 4: Diagnostic Accuracy of Sonographically Guided Needle Biopsy of Axillary Nodes in Patients with Breast Carcinoma
(Studies That Include Only Needle-Biopsied Cases and Total of Axillae Studied)
Study

Date

TP

Bonnema et al. [17]

1997

de Kanter et al. [19]

1999

TN

FP

FN

Sensitivity (%)

Specificity (%)

39

32

10

79.5 (65.689.7)

100 (86.5100)

93

119

94.9 (88.598.3)

100 (96.2100)

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Only needle biopsya

Krisnamurthy et al.

[20]b

Kuenen-Boumeester et al. [21]

2002

67

24

12

84.8 (75.291.9)

100 (85.7100)

2003

37

95

48

43.5 (33.054.7)

96.9 (91.399.4)

Sapino et al. [22]

2003

49

35

11

81.6 (69.690.5)

100 (87.6100)

Damera et al. [23]

2003

27

19

77.1 (59.989.6)

100 (78.4100)

Deurloo et al. [24]

2003

37

17

12

75.5 (61.186.7)

100 (80.5100)

Bedrosian et al. [25]b

2003

10

25.0 (5.557.2)

100 (69.2100)

Summaryc

89.8 (83.794.2)

Heterogeneityc,d

7.8

99.3 (96.4100)
0.005

Summarye

75.0 (70.379.3)

Heterogeneitye

68.03

0.4

0.53

98.3 (96.299.4)
0.000

2.78

0.73

All axillae studiedf


Bonnema et al. [17]

1997

39

88

23

62.9 (49.774.8)

100 (94.8100)

Sapino et al. [22]

2003

49

179

39

55.6 (44.766.3)

100 (97.4100)

Damera et al. [23]

2003

27

102

37

42.2 (30.055.2)

100 (95.5100)

Deurloo et al. [24]

2003

37

147

84

30.6 (22.539.6)

100 (96.9100)

Bedrosian et al. [25]b

2003

155

50

5.7 (1.215.7)

100 (97.6100)

Summaryc
Heterogeneityc,d

62.9 (49.774.8)
3.18

100 (94.8100)
0.36

Summarye

45.4 (40.050.9)

Heterogeneityd,e

22.76

0.4

0.94

99.6 (98.6100)
0.000

0.16

0.98

NoteNumbers in parentheses are 95% confidence intervals. TP = true-positive, TN = true-negative. FP = false-positive, FN = false-negative.
a Includes only patients in whom processable material was obtained at fine-needle aspiration biopsy.
b Retrospective, so excluded from the meta-analyses.
c Includes studies in which gold standard was axillary lymph node dissection.
d Using chi-square test.
e Includes studies in which gold standard was axillary lymph node dissection or sentinel node biopsy.
f Includes all patients who were selected initially regardless of whether fine-needle aspiration biopsy was performed.

than that of sonography alone (96.5% using


morphologic criteria).
However, the number of women who benefit from the results obtained with biopsy is
small because there are ultimately few patients in whom a biopsy is performed. In the
series of Bonnema et al. [17], sonographically
guided biopsy was performed in only 81
women of the initial 150, and in the series of
Sapino et al. [22], in only 95 of 267.
Furthermore, we cannot consider all the
sonographically guided biopsy results to be
equally useful. Only those with positive findings have a high predictive value (100%).
Negative results are not reliable because of
the high proportion of false-negatives. That is
to say, a negative sonographically guided biopsy does not exclude lymph node metastasis.
This is reflected in Table 4, which shows an

AJR:186, May 2006

average sensitivity of sonographically guided


biopsy of 89.8%. This figure indicates that
10.2% of patients with a negative biopsy result (false-negative) had axillary metastases
(none of the articles mentions whether the
metastases were micro- or macrometastases).
If, instead of considering only those cases in
which it was possible to perform a biopsy, we
take into account the total number of axillae
initially studied with sonography, we obtain
an average sensitivity of 62.9% and, therefore, 37.1% false-negatives (among these are
included patients with invisible or not sonographically suspected lymph nodes and in
whom no biopsy was performed but who were
found to have metastases).
The results of our review have some limitations as to their applicability, such as the inconsistency of the sensitivity results and the

methodologic flaws in some studies that reduce their internal validity. The methodologic
flaws and the presence of bias is a common
feature affecting publications about diagnostic tests, as was shown in a study that reviewed the quality of research on diagnostic
testing [29].
In conclusion, our review shows that axillary sonography cannot be used in isolation as
a method for deciding whether to perform axillary lymph node dissection. If it is decided to
use axillary sonography before a sentinel node
biopsy, once axillae with palpable nodes have
been excluded, we recommend using morphologic sonographic criteria for malignancy.
When suspected metastatic axillary nodes are
visualized, a sonographically guided biopsy
can be performed. This procedure adds some
specificity compared with the use of sonogra-

1347

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Alvarez et al.
phy alone (100% vs 96.5%), but it entails a certain degree of aggression and extra resources.
In fact, with the use of sonography alone, applying morphologic criteria to establish malignancy, approximately half of the axillae with
metastases would be detected (48.4% sensitivity) with a high specificity (96.5%). The results
of sonography would allow patients with sonographically positive axillae to be directed to
axillary lymph node dissection. The remaining
patients with sonographically negative axillae
would be candidates for sentinel node biopsy,
improving the negative predictive value of the
sentinel node biopsy because of the lower
prevalence of metastases and thereby increasing the certainty of this technique.

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