© Turkish Society of Radiology 2012
small and oval with a lucent center due to hilar fat (Fig. 1). Abnormal
lymph nodes are characterized by high density, absence of hilar fat, and
a round, irregular, ill-defined shape with or without intra-nodal calcifi-
cations on the MLO view (2, 3). The spectrum of calcifications within
lymph nodes comprises microcalcifications, punctate or amorphous
calcificatons, and coarse calcifications. An abnormal density can some-
times be partially seen on the MLO view, and to better view the lesion, a
tangential axillary view is taken. This helps to enlarge the axillary region
and to see abnormal densities that are not clearly demonstrated on the
MLO view. Ultrasonography (US) of the axillary region is another avail-
able imaging method that can be used when an abnormal lymph node is
detected on a negative mammogram. On US, a normal lymph node has
a thin hypoechogenic cortex in the periphery and an echogenic hilum
(Fig. 1). Abnormal nodes tend to become more rounded. Eccentric en-
largement with focal thickening of the cortex is a strong indicator of
malignant transformation. Indentation of the hilum, and especially ob-
literation of the hilum, is highly suggestive of malignancy (4).
Peripheral flow and transcapsular vessels seen on color Doppler favor
malignancy compared with central flow in normal axillary lymph nodes
(Fig. 1). For an accurate diagnosis, needle aspiration or biopsy should be
performed under US guidance. Enlargement of lymph nodes can be due
to a variety of benign and malignant causes. The most common malig-
nant cause of abnormal axillary lymph nodes is breast cancer; however,
when lymph nodes enlarge because of metastatic breast cancer, the pri-
mary tumor within the breast is usually visualized mammographically.
Conversely, occult breast cancer presenting as axillary metastasis is un-
common, accounting for less than 1% of all patients with primary breast
cancer at diagnosis (5, 6).
In addition to metastatic breast cancer, another malignant cause of
lymph node enlargement with a negative mammogram is metastases
from other primary tumors (e.g., lymphoma, malignant melanoma, or
lung, stomach, or ovarian carcinomas) (6, 7). Benign causes of abnormal
axillary lymph nodes occuring with negative mammography include
systemic inflammatory processes (sarcoidosis), infectious diseases (bac-
terial lymphadenitis, tuberculosis), collagen vascular diseases, and sev-
eral miscellaneous causes (silicon implants, tattooing).
Here, we discuss the common causes of abnormal lymph nodes excluding
breast cancer on negative mammograms and provide the imaging findings
from our retrospective review of adult cases including patients with lym-
phoma, human immunodeficiency virus (HIV), silicone implants, histiocy-
tosis, sarcoidosis, bacterial lymphadenitis (abscess formation), and tattoos.
ormal and abnormal axillary lymph nodes are commonly seen
on mediolateral oblique (MLO) mammograms (1). Normal ax-
illary lymph nodes are frequently identified and are typically
Abnormal axillary lymph nodes on negative mammograms: causes
other than breast cancer
Süreyya Burcu Görkem, Avice M. O’Connell
From the Department of Radiology (S.B.G. drburcugorkem@
gmail.com), Erciyes University School of Medicine, Kayseri,
Turkey; the Department of Radiology (A.M.O.), University of
Rochester Medical Center, Rochester, New York, USA.
Received 17 December 2011; revision requested 21 December 2011;
revision received 6 February 2012; accepted 7 February 2012.
Published online 13 March 2012
Enlargement of lymph nodes can be due to a variety of benign
and malignant causes. The most common malignant cause
is invasive ductal carcinoma, which is usually visualized with
mammography. Excluding breast cancer, other causes of ab-
normal lymph nodes that produce a negative mammogram
include lymphoma, metastases from other malignancies, and
benign etiologies such as inflammatory processes, infectious
diseases, collagen vascular diseases, and miscellaneous causes.
In this essay, we described common causes of abnormal axil-
lary lymph nodes on negative mammograms excluding breast
Key words: • mammography • lymph nodes • ultrasonography
Diagn Interv Radiol 2012; 18:473–479
Görkem and O’Connell
474 • September–October 2012 • Diagnostic and Interventional Radiology
the diagnostic checklist of abnormal
axillary lymph nodes with a negative
mammogram and unknown primary
tumor after occult breast cancer (5).
Non-Hodgkins lymphoma is the most
common type of breast lymphoma.
There are two types of Non-Hodgkins
lymphoma. Primary lymphoma of the
breast, which is an extra-nodal lym-
phoma arising from periductal and
perilobular lymphoid tissue, or in-
tramammary lymph nodes, represents
0.04% to 0.5% of all primary malig-
nant breast tumors. Secondary lym-
phomatous (systemic lymphoma) in-
volvement of the breast, which is more
commonly encountered in breast im-
aging, usually presents with unilateral
or bilateral abnormal axillary lymph
nodes of variable sizes (Fig. 2).
Malignancies other than breast cancer
Systemic lymphoid dissemination of
a malignancy may result in multiple
abnormal lymph nodes. The clinical
history of a patient with a known pri-
mary malignancy provides important
information. It is therefore important
to consider metastases when abnor-
mal lymph nodes are observed in any
body region. Lymphoma is the first on
Figure 1. a, b. Mediolateral
oblique (MLO) view of a
mammogram (a) shows slightly
enlarged lymph nodes with a
lucent center due to the fatty
hilum (arrows). On US normal
lymph-node is seen with its
echogenic fatty hilum, and
central flow is noted on Color
Doppler US (b).
Figure 2. a, b. A 52-year-old
patient with a history of non-
Hodgkin lymphoma presented
with a left axillary lump. MLO
view (a) shows dense, round left
axillary lymph nodes (arrows).
Transverse US of a palpable area
shows a round, hypoechoic lymph
node with an eccentric hilum, and
color Doppler US shows increased
peripheral flow (b).
Abnormal axillary lymph nodes on negative mammograms • 475
Volume 18 • Issue 5
Figure 3. a, b. MLO views (a) of bilateral breasts show multiple round, dense, enlarged lymph nodes in a patient with history of stomach
cancer who presented with bilateral lumps in the axillary regions (arrows). A round hypoechoic lymph node with a diffusely enlarged cortex is
seen on US, and color Doppler US shows increased central flow (b).
Figure 4. An 84-year-old woman with Langerhans cell histiocytosis. There are enlarged axillary lymph nodes in the right axillary region on the right
MLO view (arrow). US of the right axillary region shows a plump node with an enlarged, somewhat lobular, and hypoechoic cortex. However, the
fatty hilum is preserved.
Other metastases from primary tu-
mors, such as malignant melanoma,
lung carcinoma, or stomach or ovar-
ian carcinoma, are also on the list of
causes of abnormal lymph nodes de-
tected on mammograms (Fig. 3). As a
rare multisystemic disease, Langerhans
cell histiocytosis (LCH) can involve
many different anatomical sites in-
cluding the bone, skin, neurohypo-
physis, oral cavity, anogenital region,
lungs, liver, spleen, kidney, and lymph
nodes (8). The occurrence of LCH
in lymph nodes, either as a primary
isolated manifestation of the disease or
as part of a systemic disease, has been
previously described in the literature.
There is no specific imaging finding to
diagnose lymphadenopathy caused by
LCH (Fig. 4).
Görkem and O’Connell
476 • September–October 2012 • Diagnostic and Interventional Radiology
Benign diseases: infections and
Inflammation of lymph nodes by
bacterial or granulamotous infections
such as tuberculosis is known as lym-
phadenitis. The most common causes
of axillary lymphadenitis are bacterial
agents that are located in the normal
flora of the skin. Focal lymphadenitis is
prominent in streptococcal infection,
tuberculosis, nontuberculous myco-
bacterial infection, tularemia, plague,
and cat-scratch disease. Multifocal
lymphadenitis is common in infec-
tious mononucleosis, cytomegalovirus
infection, toxoplasmosis, brucellosis,
secondary syphilis, and disseminated
histoplasmosis (3, 4). Tuberculous
lymphadenitis (or tuberculous adeni-
tis) is a chronic specific granulomatous
inflammation with caseation necro-
sis of the lymph nodes. On physical
swelling, fluctuation, or abscess forma-
tion are detected as a result of bacte-
rial lymphadenitis, while tuberculosis
lymphadenitis may result in cold ab-
scesses, which develop so slowly that
there are no signs of inflammation un-
less it becomes complicated (Fig. 5).
HIV infection is associated with a
range of lymphoid alterations, from
generalized lymphadenopathy to ab-
normal lymphoid proliferations and
malignant lymphomas. Multiple bi-
lateral, enlarged, dense axillary lymph
nodes may be seen on screening mam-
mograms in female patients infected
with HIV (Fig. 6).
Sarcoidosis is an idiopathic sys-
temic inflammatory granulomatous
disorder. It usually invades the lungs
with fibrosis and may also involve
lymph nodes, skin, liver, spleen, eyes,
phalangeal bones, and parotid glands.
Pathologically, the most characteris-
tic feature of sarcoidosis is the pres-
ence of noncaseating granulomas in
a lymphatic or perilymphatic distri-
bution. The list of differential diag-
noses should also include other gran-
ulomatous infections due to specific
organisms such as tuberculosis and
histoplasmosis. Enlarged, dense axil-
lary lymph nodes can be detected on
mammograms. Coarse calcifications
within lymph nodes are seen in other
specific granulomatous diseases, such
as histoplasmosis and tuberculosis. US
shows hypoechoic, round, abnormal
lymph nodes of variable sizes (Fig. 7).
Collagen vascular diseases
Collagen vascular diseases are diseas-
es of connective tissue and are caused
by immune disorders. Because this is a
group of diseases, no unique symptoms
exist. The symptoms generally include
anemia, fever, joint inflammation, and
persistent fatigue. The list of collagen
vascular diseases comprises rheumatoid
arthritis, systemic lupus erythematosus,
systemic sclerosis, dermatomyositis,
and polyarteritis nodosa. It is possible
to observe enlarged lymph nodes sec-
ondary to a spectrum of diseases, and
punctate or amorphous densities mim-
icking calcifications in enlarged lymph
Figure 5. A 53-year-old female patient with a tender left axillary lump. On the spot tangential view of the left axilla (BB marker is over palpable
lesion), there is a dense, ill-defined mass, and surrounding enlarged axillary lymph nodes are easily seen (arrow). The sagittal US image shows
a complex mass with adjacent hypoechoic nodules that have the appearance of enlarged lymph nodes lacking a normal fatty hilum. Color
Doppler US demonstrates no flow within it. The diagnosis was abscess formation secondary to bacterial lymphadenitis.
Abnormal axillary lymph nodes on negative mammograms • 477
Volume 18 • Issue 5
nodes can be detected on MLO views
after gold injections for treatment of
rheumatoid arthritis (3, 4).
Calcifications within lymph nodes
Three types of calcifications in en-
larged axillary lymph nodes may be
seen on mammograms: 1) microcalcifi-
cations; e.g., metastatic breast carcino-
ma with secondary calcifications that
are similar to the primary tumor; 2)
punctate or amorphous densities mim-
icking calcifications; e.g., secondary to
gold injections for treatment of rheu-
matoid arthritis or rarely secondary to
tattoo injections; and 3) benign, coarse
calcifications; e.g., secondary to granu-
lomatous diseases such as tuberculosis
and sarcoidosis (Fig. 8). Calcifications
can be identified as echogenic foci with
posterior acoustic shadowing on US (9).
Silicone gel implants have been used
for breast augmentation and recon-
struction since 1963. In the USA, more
than one million women have under-
gone implant surgery. The silicone gel-
filled variety is the most common type
of implant used, although other types
are available, such as the saline-inflata-
ble implant and double-lumen implant
(combination of outer saline solution
and inner silicone compartments). A
silicone leak, which can be gross or
microscopic, is defined as free silicone
found anywhere outside the implant
envelope. This could be intra-capsu-
lar (contained by a capsule) or extra-
capsular (within the soft tissues of the
breast or axilla). Microscopic leakage of
gel, which is called gel bleed, through
an intact envelope occurs in all sili-
cone implants to some extent. This
represents a microscopic leak without
a rupture. Silicone gel particles can mi-
grate by the lymphatic system and be
deposited in the axillary nodes (10).
Enlarged, dense axillary lymph nodes
are seen on mammograms. A snow-
storm appearance (echogenicity in the
node with incoherent posterior shad-
owing) is typical for silicone from cur-
rent or prior rupture or a microscopic
leak (Fig. 9).
Tattooing is a popular cosmetic
practice, and the technique has been
adopted in breast reconstruction.
Intradermally injected pigment is
Figure 7. A 51-year-old woman presented after six-month follow-up of US-guided biopsy of the
left breast with findings of sarcoidosis. MLO mammography shows round-to-oval, dense axillary
lymph nodes (black arrows) and three biopsy clips (red arrows) in the left breast. Sagittal US
images of the left axilla reveal well-circumscribed, diffusely hypoechoic lymph nodes.
Figure 6. Multiple bilateral, enlarged, dense lymph nodes were detected on a screening
mammogram of a 48-year-old woman with HIV (arrows). Transverse and oblique US and Color
Doppler of the bilateral axillae show hypoechoic, round lymph nodes with central flow.
Görkem and O’Connell
478 • September–October 2012 • Diagnostic and Interventional Radiology
transported to lymph nodes, leading
to permanent pigmentation. Enlarged,
pigmented lymph nodes are seen in
both melanoma and tattoo pigmenta-
tion. The differential diagnosis between
tattoo and melanotic pigmentation of
lymph nodes is made microscopically.
Pigmentation of lymph nodes can also
occur by deposition of anthracosilico-
tic pigment, which appears similar to
high-density deposits simulating calci-
um from dental amalgam, aluminium,
gold, and titanium (Fig. 10) (9).
In addition to occult breast malig-
nancies, causes of non-breast malig-
nant as well as benign processes should
be included in the differential diagno-
sis of abnormal axillary lymph nodes
on negative mammograms. Although
the MLO view has been very useful
for detecting abnormal axillary lymph
nodes, the tangential axillary view, US,
and color Doppler US of the axillary re-
gion also give useful information about
Figure 9. MLO spot compression mammogram of a palpable axillary lump in a 56-year-old woman
shows enlarged lymph nodes of varying sizes (arrow). She had silicone implants without perceptible
changes or other symptoms of leakage. Longitudinal US of the palpable nodes shows well-defined,
echogenic, enlarged lymph nodes with a snowstorm appearance and incoherent posterior shadowing
and silicone within nodes. There is no flow in the lymph nodes on color Doppler US.
Figure 10. A 35-year-old woman with extensive tattooing on her arms and back. A
photograph of the patient’s right arm and posterior shoulder shows extensive tattooing
with black, blue, red, and yellow pigments. MLO mammogram of the right breast shows an
axillary lymph node (arrow) containing foci of calcification densities. A photomicrograph of a
fine-needle aspiration biopsy specimen from the lymph node reveals abundant black granular
tattoo pigment obscuring lymphocytes. Arrows indicate some of the pigment (Diff-Quick
[Dade-Behring, Deerfield, Illinois, USA], ×60). Reprinted with permission from ref. 9.
Figure 8. On the screening
mammogram of a 50-year-old female
patient, the MLO image of the left
breast shows a group of benign
calcifications in enlarged axillary
lymph nodes (arrow), which was
related to old granulomatous disease.
There was no history of rheumatoid
arthritis or gold injection.
Abnormal axillary lymph nodes on negative mammograms • 479 Download full-text
Volume 18 • Issue 5
abnormal lymph nodes and may help
to shorten the list of differential diag-
noses and aid the physician in making
an accurate diagnosis by needle aspira-
tion or biopsy.
Conflict of interest disclosure
The authors declared no conflicts of interest.
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