Purpose: This study aimed to share our experience with anti-tuberculosis (TB) therapy for the management of Idiopathic
Granulomatous Mastitis (IGM).
Methods: A retrospective study was performed on 36 IGM cases treated with anti-TB therapy from Jan 2009 to Dec 2012
in our department. Clinical data, including on presentation, histopathology, and management, were analyzed by reviewing
Results: The diagnosis of IGM was based on histopathological evaluation. All patients had been excluded from tuberculosis
mastitis by lab examinations. Fifteen relapsed IGM patients were switched to anti-TB treatment after surgery or when prednisolone
failed. Another 21 patients accepted anti-TB drugs as their primary treatment. Among the 36 patients, 2 patients
stopped treatment because of the side effects of the anti-TB drugs. In a 29.6-month follow-up of 34 patients who completed
6-12 months of therapy, a satisfactory result was obtained for 33 patients.
Conclusions: Our study demonstrates that treatment with anti-TB drugs is a safe and effective therapy for IGM patients,
presenting a high cure rate for both initial and relapsed cases.
Keywords: Breast carcinoma; Inflammatory; Corticosteroid; Idiopathic granulomatous mastitis; Tuberculosis
Idiopathic Chronic Granulomatous Mastitis (IGM) is a
rare and benign inflammatory breast disease that was first
described by Kessler and Wolloch in 1972. Clinically,
IGM presents as an inflammatory process in the breast that
can mimic an inflammatory cancer or an abscess. A common
clinical finding is a palpable mass with erythematous
skin changes, pain, sterile abscesses, fistulae, and/or nipple
retraction. The mechanisms of IGM have been proposed
to be etiologic factors, including a chemical reaction associated
with oral contraceptive pills, autoimmune phenomena,
infection with yet-unidentified pathogens, and a localized
immune response to extravasated secretions from lobules.
The pathophysiology of the disease remains unknown. Certain reports claim a relationship between corynebacterial infection
and IGM[4,5]. To establish a diagnosis of IGM, other
causes of Granulomatous Mastitis (GM), such as Tuberculosis
(TB), sarcoidosis, foreign-body reaction, mycoticinfection,
ductal ectasia, Wegener’s granuloma, and histoplasmosis,
should be excluded.
Because the clinical findings of IGM are nonspecific, pathological
evaluation usually plays a crucial role in the diagnosis
of IGM. The treatment of IGM is still a challenge, as there
is little awareness of this disease. Although surgical excision
and steroid therapy are the most commonly used treatments,
the optimal treatment remains unclear. The surgical treatment
options vary widely, including drainage, wide excision,
and mastectomy[6,7]. Although the recurrence rate ranges
from 20% to 75% and although fistula formation has been
reported after excision[2,7], surgical excision is still the most
common treatment modality for IGM. Steroid use to treat
IGM was first proposed by Dehetrogh et al in 1980. Corticosteroid therapy has previously been shown to be efficacious
in IGM[8-10]. However, this treatment may not be appropriate
in the presence of complications such as abscess formation,
fistulae, and persistent wound infection. Akbulut’s study
demonstrated that methotrexate(MTX) was effective in the
treatment of 4 cases of IGM, especially in preventing complications,
resolving the inflammatory process, and limiting the
side effects of corticosteroids. Corynebacteria have been
identified in certain patients with IGM. Anti-TB drugs can be
used to treat corynebacterial infection. Thus, we began to use
anti-TB drugs to treat IGM in our clinical practice in 2009.
In this study, we share our experience with anti-TB drugs for
the treatment of IGM and describe the effectiveness of anti-TB
drugs in treating IGM.
We retrospectively reviewed the hospital records of 36 cases of
IGM that were pathologically diagnosed between Jan 2009 to
Dec 2012. We excluded 8 patients who were diagnosed with
TB Mastitis (TM) and another 21 patients who were cured by
surgery or prednisolone during the same time period. Clinical
information regarding the 36 patients, aged between 19 and
56 years, is presented in Table 1. An ultrasound was performed
on all patients. A mammogram was performed on 22 patients
older than 35 years. The diagnosis of IGM was based on a core
needle biopsy using a Bard®disposable 14-gauge needle or on
a surgical sample. All tissue samples were stained immunohistochemically
for pancytokeratin and epithelial cadherin. The
pus was sent for microscopy analysis, culture, ad antibiotic
sensitivity testing. All patients underwent chest radiography,
a tuberculin skin test, and a blood PCR test to exclude TB infection.
No microorganisms were found in the pus or tissuesample
culture. Stains for acid-fast bacilli and fungus were
negative in sections of cell and tissue blocks in all cases.
The prescriptions given to the patients were rifampicin (10mg/
kg/d) and isoniazid (5mg/kg/d) plusethambutol (15mg/kg/d)
or pyrazinamide (20mg/kg/d). The medical treatment lasted
for 6-12 months, based on the patient’s disease response. The
drugs were withdrawn when the patient achieved a finial complete
lesions relief by ultrasound.
This study describes 36 patients who presented a breast
lump and were diagnosed with IGM at Sun Yat-Sen Memorial
Hospital. The clinical characteristics of the patients were
as follows: 32 patients presented a breast lump ranging from
3-10cmin size (mean size, 4.2cm). The lesions were unilateral.
The right breast was affected in 19 patients, and the left breast
was affected in 17 patients. A total of 22 (61.1%) patients presented
painful swelling mimicking an inflammatory cancer.
Ten (27.8%) patients had ulcerative skin lesions, and 8 (22.2%)
patients formed a sinus (Figure 1 and Figure 2). Six (16.7%) of the
patients presented abscess, and 11 (30.6%) had nipple retraction
All patients presented a mass during the ultrasonography of
the breast, compared with only 3 (13.7%) patients showing an
ill-defined mass during the mammography (Table 2). The major ultrasonographic finding was a hypoechoic lobulated mass,
with dotted blood flow signals around the mass (Figure 3).
Mammography detected an asymmetric density or ill-defined
mass in the affected breast (Figure 4). There were fourteen
(38.9%) patients and six (27.2%) patients who were classified
as Breast Imaging Reporting and Data System (BI-RADS) category
4-5 by ultrasound and mammography, respectively.
The diagnosis of IGM was based on histopathological evaluation
by core needle biopsy or incisional biopsy of the affected
breast tissues. The major pathological change was found to be
a granulomatous inflammatory reaction centered on the lobules.
Granulomas composed of epithelioidhistiocytes, Langerhans
giant cells accompanied by lymphocytes, and plasma
cells were generally found within and around the dilated lobules
(Figure 5). In this study, 15 patients relapsed, including
11postoperative patients transferred from other hospital (4
cases of drainage and7 cases of drainage and wide excision)
and 4 patients for whom prednisolone treatment failed. Another
21 patients used anti-TB drugs as their primary treatment.
Among the 36 patients, two patients stopped the anti-
TB treatment two weeks or one month later because of the side
effects of the drugs and switched to prednisolone treatment.
There were 34 patients who finished 6-12 months of anti-TB
treatment. One patient exhibited recurrence after 22 months
of follow-up and then underwent mastectomy. During an average
follow-up of 29.6 months, 33 patients were cured. The
cure rate of anti-TB treatment for IGM was 91.7% (Table 3).
IGM is achronic inflammatory, benign clinical condition involving
the breast.IGM is an uncommon breast disease of
unknown etiology, generally affecting women of reproductive
age[13, 14]. This condition presents as a breast mass, with skin
thickening, nipple retraction, and regional lymphadenopathy,
and often mimics a breast carcinoma. Breast cancer is the
most important differential diagnosis for IGM. In our study,
approximately half of the patients with IGM had suspected
malignancy based on clinical and radiological signs. Because
radiology has limited value in the diagnosis of patients with
IGM, pathological diagnosis is crucial in the planning of
treatment for patients who have a similar presentation as in
breast carcinoma. Cytologic analysis by fine needle aspiration
biopsy is usually insufficient for definitive diagnosis and
may be misleading, so histopathological examination by core
needle biopsy has a significant role in obtaining a definitive
diagnosis[15, 16]. Another uncommon breast inflammatory
disease that should be differentiated from IGM is Tuberculosis
Mastitis (TM) of the breast. In the published literature, most
diagnoses of IGM are based on ruling out TB by histochemical
staining and clinical evaluation. There were 11 patients
in our hospital who were diagnosed with TM in the same period.
All of these patients had received anti-TB treatment for
more than 9 months. However, anti-TB treatment alone may
not be adequate to treat TM patients. 90% patients with TM
may ultimately need surgical intervention coupled with anti-
TB medication to eliminate draining sinuses, breast masses, or
non-healing ulcers [18, 19].
The exact causes of IGM are still unknown, although an autoimmune reaction to protein secretions from the mammary
ducts is one supposed causation. There is a higher rate of
IGM in women from developing countries than from developed
countries because the largest series report came from
developing countries. This may suggest that some kinds
of unidentified pathogens associated with environmental pollution
may be related to IGM. Many studies have tried to find
an infectious species in samples or tissues from IGM patients.
Certain case reports claim a relationship between corynebacterial
infection or mycobacterium and IGM[4, 22]. Although a
lot of queries about whether these organisms are contaminants
or pathogens exist, several lines of evidence suggest these bacteria
are true pathogens. Contaminative bacteria are detected
early in the disease process, while the consistent finding of C.
kroppenstedtii, a rare and unusual species, suggests pathogenicity[
The management of choice for IGM has still not been established.
The available treatment options include close followup;
anti-biotherapy; limited or wide surgical excision; steroid
and immunosuppressive drugs, such as MTX and azathioprine[
24-26].Surgical approaches varied from drainage to
wide excision to mastectomy. And the most commonly used
approach was wide excision. The reoperation rate ranged
from 21-75% either for completion of excision after surgical
drainage or for recurrence[15, 27]. The high incidence of recurrence
necessitates extensive resection to obtain disease-free
margins, but wide local excision or repeated incisions often
make the cosmetic outcome unacceptable. Additionally, mastectomy
for benign disease is a challenging decision for both
surgeons and patients. Mastectomy and breast reconstruction techniques may be the last option for patients with a long history
of recurrences. In our study, 11 (31.4%) patients had
recurrent disease after surgical treatment. All of these patients
were cured after receiving anti-TB medication. Several studies
have showed that systemic therapy is a safe and effective treatment
for IGM, including steroids and MTX, used either alone
or in combination. The full recovery rate with steroid treatment
is42-93.5%; the partial recovery rate, 6.4-58%; and non
response, 6.5%[7, 16, 28]. Treating those IGM patients who
have had no response to steroids or who have had recurrent
disease when steroid treatment was stopped is still a challenge.
Akbulut thought that MTX treatment should be considered in
IGM patients who have no response to steroids to resolve the
inflammatory process and to limit the side effects of corticosteroids[
12]. Although these studies showed a good response of
IGM to steroid treatment, most of the reports were based on a
small number of cases. Long-term steroid therapy may induce
severe side effects, including glucose intolerance and Cushingoid
features. If a patient fails to respond to systemic corticosteroid
therapy, chronic pathogenic bacteria infections such
as corynebacteria should be considered. Because anti-TB
medications can be used to treat corynebacteria infection according
to the drug description, we tried to use anti-TB drugs
to treat IGM patients beginning in 2009. Based on our observations,
treatment with anti-TB drugs produced excellent responses
and achieved a high cure rate for this type of disease.
The IGM patients presented good adherence to anti-TB treatment
and were satisfied with the therapeutic results. Among
the 34 patients who completed 6-12 months of treatment, 33 patients were cured, without additional surgical intervention.
This is the first report demonstrating that anti-TB medication
is another safe and effective systemic therapy for IGM patients,
especially in those patients for whom steroid or surgical treatment
has failed. Our study shows that anti-TB therapy may act
as a compensatory treatment for IGM in addition to immunosuppressive
therapy and surgical therapy.