7O M E N S ) M A G I N G s 0E R S P E C T I VE

Hovanessian Larsen et al.

Granulomatous Lobular Mastitis

Women’s Imaging
Perspective
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Granulomatous Lobular Mastitis:

W O M E N ’S
IMAGING Imaging, Diagnosis, and Treatment
Linda J. Hovanessian Larsen1 OBJECTIVE. Granulomatous lobular mastitis is a rare chronic inflammatory disease that
Banafsheh Peyvandi1 has clinical and radiologic findings similar to those of breast cancer. We performed a retro-
Nancy Klipfel2 spective analysis of clinical, imaging, and treatment findings in 54 women diagnosed with
Edward Grant1 granulomatous lobular mastitis between January 2000 and April 2008.
Geeta Iyengar1 CONCLUSION. The imaging findings of granulomatous lobular mastitis overlap with
those of malignancy. The most common presentation is a focal asymmetric density on mam-
Hovanessian Larsen LJ, Peyvandi B, Klipfel N, mography and an irregular hypoechoic mass with tubular extensions on ultrasound. Core bi-
Grant E, Iyengar G opsy is typically diagnostic. Once the diagnosis is established by tissue sampling, corticoster-
oids are the first line of treatment.

Keywords: corticosteroid therapy, focal asymmetric
density, granulomatous lobular mastitis, hypoechoic
mass with tubular extensions, nonnecrotizing
granulomas
DOI:10.2214/AJR.08.1528
Received July 13, 2008; accepted after revision
January 27, 2009.
1
Department of Radiology, University of Southern
California Keck School of Medicine, USC/Norris
Comprehensive Cancer Center, 1441 Eastlake Ave., Ste.
2315, Los Angeles, CA 90033. Address correspondence
to L. J. Hovanessian Larsen (lhovanes@usc.edu).
2
Department of Pathology, University of Southern
California Keck School of Medicine, Los Angeles, CA.
CME
This article is available for CME credit.
See www.arrs.org for more information.
AJR 2009; 193:574–581
0361–803X/09/1932–574
© American Roentgen Ray Society
G
ranulomatous lobular mastitis is
a rare inflammatory disease of
the breast that was first described
by Kessler and Wolloch [1] in
1972. This disease usually affects women of
child-bearing age or those with a history of
oral contraceptive use [1]. It is characterized
pathologically by chronic granulomatous in-
flammation of the lobules without necrosis
[2]. Its cause is unclear, but an autoimmune
disease is favored. The clinical and radiologic
findings of granulomatous lobular mastitis
are similar to those of breast cancer, so it is
often initially misdiagnosed and proper treat-
ment is delayed (Fig. 1). Effective diagnostic
protocols and treatment plans for granuloma-
tous lobular mastitis have not yet been estab-
lished [1]. Before 1980, surgical excision of
the entire lesion was performed [3]. More re-
cently, treatment has included the use of cor-
ticosteroid therapy [4].
We report a series of 54 cases of granu-
lomatous lobular mastitis occurring in wom-
en between the ages of 22 and 44 years at our
center. The purpose of this study is to review
and describe the clinical, imaging, and patho-
logic features of granulomatous lobular mas-
titis and to discuss diagnostic protocols and
treatment plans to better diagnose and treat
this rare disease.
Materials and Methods
A retrospective review of records from our in-
stitution between January 2000 and April 2008
yielded 54 women between the ages of 22 and 44
years with the histologic diagnosis of granuloma-
tous lobular mastitis. These women represented
fewer than 1% of all women who underwent biop-
sy for breast diseases during that time. This study
was approved by our institutional review board
and was HIPAA-compliant.
All of the women underwent a clinical breast
examination to identify palpable lumps, skin
thickening, or axillary lymphadenopathy. Mam-
mography was the initial imaging evaluation in
women older than 30 years (45/54) and was not
performed in women younger than 30 years. Two
standard views (mediolateral oblique and cranio-
caudal) of each breast were performed. Addition-
al mammographic projections were performed as
needed.
An ultrasound examination of the affected
breast was performed in all 54 women using an
ultrasound scanner and a 10- to 12-MHz transduc-
er. Transverse and longitudinal planes of the pal-
pable lesion or the area of concern were obtained.
Each picture was labeled with the patient’s name,
left or right breast, lesion location, and transduc-
er orientation. Doppler sonography was used as
an adjunct.
Definitive diagnosis was obtained by fine-
needle aspiration (FNA) using an 18-gauge nee-
dle, percutaneous ultrasound-guided core biopsy
(14-gauge), or surgical excision. The slides were
analyzed with H and E stain, special stains (Kiny-
oun acid-fast bacilli [AFB], Gomori methenamine
silver [GMS], Gram), and cultures for bacteria and
AFB, immunohistochemistry, and polarization.

574 AJR:193, August 2009

 Granulomatous Lobular Mastitis
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A B
C D
Fig. 1—34-year-old woman with
invasive granulomatous mastitis
simulating cancer with palpable
mass and axillary adenopathy on
clinical examination.
A and B, Mammograms show
ill-defined mass (arrow, A) and ill-
defined mass with adenopathy and
nipple retraction (arrows, B).
C and D, Sonograms of axilla show
irregular mass and associated
hypoechoic abnormal lymph node.
E, Diagnosis was confirmed
on histology as shown on
photomicrograph: granulomatous
inflammation (epithelioid
histiocytes [long arrow] and
lymphocytes [arrowhead]) with
admixed neutrophils (short
arrows). (H and E, ×200)
E
AJR:193, August 2009
Results
Clinical Features
All affected women were of child-bearing
age (mean, 33.1 years; range, 22–44 years).
Most of the patients were taking antibiot-
ics. Nine of 54 patients had undergone in-
cision and drainage (I&D) before presenta-
tion. Symptoms persisted in spite of several
courses of various antibiotics and multiple
attempts at I&D in selected cases. The dura-
tion of symptoms ranged from 2 days to 12
months. The most common presenting symp-
toms were a mass in the breast (48/54, 89%)
and pain, erythema, and inflammation (6/54,
11%) (Fig. 2B). Draining sinus tracts were
seen in 10 women at initial presentation, and
axillary adenopathy was noted in 15 of 54
(28%) women (Fig. 2A). Associated nipple
discharge and ulceration were seen in five
and two patients, respectively. The mass was
hard on palpation in 50% of the women and
clinically measured 1.0–8.2 cm. None of the
women had any systemic disorder or history
of a specific infection.
Radiologic Evaluation
Twenty-five of 45 (56%) patients showed
a heterogeneously dense or extremely dense
parenchymal breast pattern on mammog-
raphy. Twenty women showed a large focal
asymmetric density (Fig. 3), and seven pre-
sented with an irregular or lobulated mass.
Three women had diffusely increased den-
sity of the affected breast. Associated skin
thickening or axillary adenopathy was seen
in 11 women (Fig. 3).
Ultrasound examination showed lesions in
all 54 women. A large irregular hypoecho-
ic mass with multiple tubular extensions was
identified in 32 women (59%). A lobulated or
irregular mass was seen in 18 women (33%).
All masses were heterogeneously hypoecho-
ic, with the mean diameter ranging from 0.8
to 6 cm. Parenchymal distortion with acous-
tic shadowing and no discrete mass was not-
ed in four women (7%). We observed skin
thickening in 28 women (52%) and axillary
adenopathy in 15 (28%) (Fig. 4). More than
half of the lesions were located at the pe-
riphery of the breast, and the remaining le-
sions were seen as diffuse involvement of the
breast or in the subareolar location. These
findings are summarized in Table 1.
Diagnostic Pathologic Evaluation
FNA was performed in 19 women but was
diagnostic in only four (21%). All women with
an inconclusive FNA underwent ultrasound-
575

Fig. 2—32-year-old woman with granulomatous
mastitis.
A and B, Photographs show unilateral breast
erythema (A) and breast inflammation with abscess
associated with mass and draining sinus (B) after
incision and drainage.
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guided core biopsy or surgery to obtain a defini-
tive diagnosis. Forty-eight women had an ultra-
sound-guided core biopsy, of which 46 (96%)
were diagnostic for granulomatous lobular
mastitis. The remaining four women underwent
surgical excision that subsequently confirmed
granulomatous lobular mastitis. In all patients,
granulomatous lobular mastitis was the final di-
agnosis and was characterized microscopically
by the presence of lobulocentric nonnecrotiz-
ing granulomas (clusters of epithelioid histio-
cytes) in which no microorganisms or features
of other pathologic entities (see Discussion sec-
tion) were identified. Additional microscopic
findings included lymphocytes, plasma cells,
neutrophils, and giant cells. The inflammation
often extended into adjacent perilobular and in-
terlobular tissue.
Fig. 3—Mammographic findings seen with granulomatous mastitis.
A, Mammogram shows palpable asymmetric density (arrows) with associated axillary adenopathy in 34-year-old woman.
B, Mammogram of 28-year-old woman with palpable mass shows irregular mass (arrows) in right breast.
576
(OVANESSIAN,ARSENETAL
A B
Treatment and Follow-Up
Concordance of core biopsy findings was
established before beginning treatment by
correlating the clinical, imaging, and patho-
logic findings [5]. In our study, nonsurgical
treatment included antibiotic therapy or cor-
ticosteroid therapy. Antibiotic treatment con-
sisted of dicloxacillin, cephalexin, or clin-
damycin for 10 days, but only two of 38 (5%)
women treated with antibiotic therapy im-
proved. Thirteen women were treated with
steroids, and 10 improved (77%). Three pa-
tients with mild disease improved with obser-
vation only. Surgical treatment with wide sur-
gical excision was performed for patients with
localized disease, patients with resectable dis-
ease who responded to steroids, and nonre-
sponsive patients with extensive disease.
A B
Six women treated with wide local exci-
sion improved; one patient who showed no
improvement underwent mastectomy. Post-
treatment response was monitored with
mammograms and ultrasound in 17 of 54
patients and with ultrasound only in 33 pa-
tients at 1- and 3-month intervals. Only four
of 54 patients were lost to follow-up. Vari-
able treatment response was seen and ranged
from 3 to 27 months.
$ISCUSSION
Granulomatous lobular mastitis is a rare
and benign inflammatory disease of the
breast that was first described in 1972 [1].
Granulomatous lobular mastitis is character-
ized histologically by nonnecrotizing gran-
ulomas confined to breast lobules, with no
AJR:193, August 2009

4!",% -AMMOGRAPHICAND5LTRASOUND&INDINGSOF'RANULOMATOUS
Lobular Mastitis
Findings
Mammography (n = 45 patients)
Large focal asymmetric density
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Lobulated or irregular mass
Diffusely increased density
Axillary adenopathy
Skin thickening
Ultrasound (n = 54 patients)
Large, irregular hypoechoic mass with multiple tubular extensions
Lobulated or irregular hypoechoic mass
Parenchymal distortion with acoustic shadowing and no discrete mass
Axillary adenopathy
Skin thickening
evidence of microorganisms [2]. It is not
associated with trauma, specific infection,
or foreign material. Granulomatous lobular
mastitis should be differentiated from other
causes of chronic inflammatory breast dis-
eases, such as plasma cell mastitis, Wegen-
er’s granulomatosis, ruptured cyst, sarcoi-
dosis, fat necrosis, tuberculosis, carcinoma,
duct ectasia, and fungal infection [3]. The
A B
C D
AJR:193, August 2009
Granulomatous Lobular Mastitis
this was reflected in our study (mean age of
our patients, 33.1 years). Women with gran-
ulomatous lobular mastitis typically present
No. %
with a breast mass that may be associated
with pain, skin thickening, sinus formation,
20 44 or axillary adenopathy [7]. Many women in
7 16 our study were initially thought to have car-
cinoma because most presented with a uni-
3 7
lateral mass (89%) and regional adenopathy
8 18 (28%) and did not have a history or clinical
3 7 findings suggestive of inflammation.
Imaging features of granulomatous lob-
ular mastitis have not been described fre-
32 59
quently in the literature and currently are
18 33 found only in reports of small series. Mam-
4 7 mographic findings are considered nonspe-
15 28 cific in granulomatous lobular mastitis. Han
et al. [8] described multiple small masses or
28 52
a large focal asymmetric density. Yilmaz et
al. [9] and Memis et al. [5] identified a fo-
cause is unclear, but an autoimmune reac- cal asymmetric density as the most frequent
tion, possibly to the protein secretions in the pattern. More recently, a study of 11 women
ducts, is favored [1, 3]. The response to ster- by Lee et al. [10] showed an irregular ill-de-
oids supports this autoimmune hypothesis fined mass to be the most common finding.
[4]. Other causes include undetected organ- Similar to the findings shown by Yilmaz et
isms, oral contraceptives, and a reaction to al. and Memis et al., our study showed that
childbirth [6]. the most common mammographic presenta-
Granulomatous lobular mastitis usual- tion in granulomatous lobular mastitis was
ly affects women of child-bearing age, and a focal asymmetric density with no distinct
Fig. 4—Sonographic findings seen with
granulomatous mastitis.
A and B, 32-year-old woman with 3-month history
of palpable mass. Sonograms show large irregular
hypoechoic mass with multiple tubular extensions
(arrows).
C, Sonogram shows solid irregular mass in 32-year-old
woman.
D, Sonogram shows heterogeneous hypoechoic mass
in 31-year-old woman.
E, 30-year-old woman with palpable mass in right
breast. Sonogram of mass shows parenchymal
distortion, acoustic shadowing, and no discrete mass.
E
577
 (OVANESSIAN,ARSENETAL
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Fig. 5—Photomicrograph of tissue specimen shows lobulocentric granulomatous Fig. 6—Photomicrograph of tissue specimen shows granulomatous inflammation
and lymphocytic inflammation as well as mild (short arrow) and severe (long (outlined) involving half of lobule. (H and E, ×100)
arrow) lobulocentric granulomatous and lymphocytic inflammation involving two
lobules (outlined). (H and E, ×40)

margins (20/45) and was most easily iden-
tified when compared with the contralateral
breast. Granulomatous lobular mastitis was
mainly unilateral and most often seen in the
periphery of the breast.
Less common mammographic findings
included a lobulated or irregular mass (7/45)
and diffusely increased density (3/45) in
the affected breast. Lesions were mammo-
graphically occult in 15 of 45 women, possi-
bly because of an overlying dense breast pat-
tern seen in most women (36/45). Abnormal
lymph nodes or skin thickening was identi-
fied in 20% of the women.
In our study, ultrasound identified a lesion
in all women. The ultrasound patterns of the
disease are varied. The most frequent finding
was an irregular hypoechoic mass associated
with multiple tubular hypoechoic structures
with fingerlike extensions (32/54 women).
These findings were similar to those previ-
ously reported by Han et al. [8], Yilmaz et
al. [9], and Lee et al. [10]. Other ultrasound
findings in our study included a lobulated or
irregular hypoechoic mass (18/54) and pa-
renchymal distortion with acoustic shadow-
ing but no discrete mass (4/54). In all cases,
the mass lesions were heterogeneously hy-
poechoic. Skin thickening, edema, or axil-
lary adenopathy was seen in more than half
of the women, and a sinus tract was seen in
15 women on ultrasound.
Because clinical and imaging studies of
granulomatous lobular mastitis are nonspe-
cific, definitive diagnosis is made by histopa-
thology [3]. FNA is still an option for tissue
sampling because it is more easily available
and provides faster results than core biopsy
[11]. FNA may be helpful in differentiating
malignancy from an inflammatory condition
even though it may not be as specific as core
biopsy. Because the findings in granuloma-
tous lobular mastitis may mimic an abscess,
FNA for fluid aspiration and culture can be
attempted. In our study, we found ultrasound-
guided core biopsy to be more accurate be-
cause it showed the tissue architecture. Core
biopsy was diagnostic in 96% of patients who

Fig. 7—Photomicrograph of tissue specimen shows granulomatous inflammation Fig. 8—Photomicrograph of tissue specimen from fine-needle aspiration shows
(epithelioid histiocytes [long arrow] and lymphocytes [arrowhead]) with admixed predominance of neutrophils (long arrows), with few giant cells (short arrows) and
neutrophils (short arrows). (H and E, ×200) histiocytes (arrowhead). (Papanicolaou stain, ×200)

578 AJR:193, August 2009

 Granulomatous Lobular Mastitis
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A B

C D E
Fig. 9—30-year-old woman with granulomatous mastitis.
A and B, Response after treatment with steroids. Color Doppler sonogram in August 2007 (A) and gray-scale sonogram in September 2008 (B) show complex mass with
adjacent vascularity (A) and response with small residual scar (arrow, B).
C and D, Minimal response after steroid therapy and treatment with wide local excision. Sonogram in April 2008 (C) shows 2.7-cm irregular mass with tubular extension.
Minimal response to treatment is also seen on sonogram in September 2008 (D).
E, Specimen radiograph shows spiculated mass with marking clip after wide local excision.

underwent ultrasound-guided biopsy, where-
as only four of 19 FNA procedures were di-
agnostic. Common causes for failure of FNA
include insufficient material and nonspecific
findings (e.g., fat necrosis, abscess).
Granulomatous lobular mastitis is charac-
terized histologically by the presence of non-
necrotizing granulomas, usually admixed
with neutrophils (Figs. 5–8) originating in the
breast lobules. This entity is a microscopic
diagnosis of exclusion; features overlap with
those of a variety of other diseases. The dif-
ferential diagnosis includes infectious organ-
isms, bacteria (culture), mycobacteria (Kiny-
oun AFB stain and necrotizing necrosis) and
fungus (GMS stain), sarcoidosis (“naked”
granulomas, i.e., lacking lymphocytic inflam-
mation), traumatic fat necrosis (foamy mac-
rophages and nonlobular), ruptured cyst (non-
lobular), duct ectasia (periductal fibrosis),
plasma cell mastitis (nongranulomatous), We-
gener’s granulomatosis (vasculitis), carcino-
ma (keratin immunohistochemistry), and for-
eign body reaction (polarizable material).
Few articles have described treatment pro-
tocols for granulomatous lobular mastitis [3,
12, 13], and the optimal treatment has not
yet been established. Before treatment, other
causes of granulomatous lesions in the breast,
such as tuberculosis, fungal infection, and
sarcoidosis, must be excluded. Most patients
in our study were already receiving antibiot-
ic therapy, and some of the patients had un-
dergone I&D before the diagnosis was estab-
lished. In our study, antibiotic therapy was not
beneficial; only 5% women showed improve-
ment. The most effective nonsurgical treat-
ment was corticosteroids, with 77% of patients
showing improvement (Fig. 9A). Patients with
mild symptoms were treated with observation
and close imaging surveillance.
Our study also indicates that wide surgical
excision is more beneficial than limited exci-
sion in patients with localized disease (Fig.
9B). The role of I&D is controversial because
it may lead to increased scarring and nonheal-
ing of incision tracks, which subsequently leads
to formation of sinus tracks. All of the wom-
en treated with surgical excision improved,
whereas only five of 12 women improved with
I&D. Those women who improved with I&D
were also given steroid treatment after the pro-
cedure. Our findings support current literature
that recommends the use of steroid treatment
after excision [7]. Methotrexate has been used
in patients who are resistant to steroid therapy
as well as for recurrence after surgical treat-
ment [14], although none of our patients re-
ceived it because it was not warranted.
On the basis of our study findings, we
have implemented the following treatment
plan at our institution for women diagnosed
with granulomatous lobular mastitis: We be-
gin a course of prednisone, 60 mg/day for 2
weeks; this course is tapered over weeks 3,
4, 5, and 6. If prednisone therapy fails, the

AJR:193, August 2009 579

 (OVANESSIAN,ARSENETAL

Radiologic Evaluation (mammography, ultrasound)

Fine-needle aspiration
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Fluid Solid

Aspirate, GM stain, and culture Core biopsy with cultures No GM Treat underlying cause

Culture positive: GM
Treat as abscess

Localized findings, Generalized findings,

Culture negative: mild symptoms severe symptoms
Symptoms resolve;
short-term follow-up

Observation Steroids Failure

Culture negative:
Symptoms persist
Steroids
or recur
Methotrexate

Excision

Partial or no response

Complete or partial response

Surgery
Observation

Fig. 10—Diagnostic and therapeutic algorithm for women of child-bearing age who present with abscess, mass, inflammation, or pain in whom granulomatous mastitis
(GM) is suspected.

second course of steroids is repeated as de-
scribed. If minimal or no improvement is
seen after the second steroid course, we con-
sider adding methotrexate, 10 mg/wk. Pa-
tients who are prone to recurrence may need
long-term low-dose steroids with or without
methotrexate and local excision.
Although we have seen satisfactory results
with high-dose steroids, close surveillance is
needed because of the potential side effects,
which include glucose intolerance and Cush-
ing’s syndrome. At our institution, patients
are examined by the breast surgeon at least
once each month until symptoms have re-
solved. In addition, ultrasound is performed
at 1- and 3-month intervals after the start of
treatment and earlier if there is no improve-
ment or if symptoms worsen. Once symp-
toms have resolved, 6-month follow-up ul-
trasound is performed. The patient returns to
annual screening when she is asymptomatic
and imaging is negative. At our institution,
we have developed a diagnostic and treat-
ment algorithm (Fig. 10).
#ONCLUSIONS
Granulomatous lobular mastitis has clin-
ical and imaging characteristics similar to
breast carcinoma. However, the mammo-
graphic finding of a focal asymmetric densi-
ty and appearance of an irregular hypoecho-
ic mass with multiple tubular extensions on
sonography suggest granulomatous lobular
mastitis. Final diagnosis relies on exclusion
of other causes of granulomatous mastitis
and specific pathologic findings on biopsy. In
our series, treatment with steroids before sur-
gical management appears to be beneficial.
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