Granulomatous Mastitis: A Clinical and Diagnostic Dilemma
Emel Ebru PALA1, Sumeyye EKMEKCI1, Melis KILIC1, Ayberk DURSUN2, Gul COLAKOGLU3, Cem KARAALI2, Mumin EMIROGLU1, Mustafa EMIROGLU2
1Department of Pathology, Tepecik Education and Research Hospital, University of Health Sciences, IZMIR, TURKEY
2Department of General Surgery, Tepecik Education and Research Hospital, University of Health Sciences, IZMIR, TURKEY
3Department of Radiology, Tepecik Education and Research Hospital, University of Health Sciences, IZMIR, TURKEY
Keywords: Breast, Granulomatous mastitis, Idiopathic
Granulomatous mastitis (GM) is a challenging inflammatory disorder of the breast. In this study we aimed to present the detailed
clinical and morphological features of GM cases, diagnostic clues for specific and idiopathic etiologies, the difficulties in evaluating trucut
biopsies, and the results of different therapeutic approaches.
Material and Method: We retrospectively analysed the clinical, radiological and morphological features of 114 GM cases diagnosed with fine
needle aspiration, and trucut, incisional, and excisional biopsy.
Results: The mean age was 35.8. Only eight cases were older than 45 years. Bilateral involvement was observed in 4 (3.5%) cases. The most common
clinical symptoms were breast mass/abscesses, tenderness, and skin changes. Microbiological culture was positive in 4 cases for gram-positive
bacteria. Only 3 cases showed a positive tuberculin/PCR test for tuberculosis. The major USG finding was a hypoechoic well-defined or ill-defined
mass/abscess; MRI finding was heterogeneous non-mass contrast enhancement. Cases diagnosed with cytology (35 cases) did not have breast
malignancy either in their history or clinical follow up period. Fine needle aspiration cytology materials revealed epitheloid granulomas mixed
with neutrophils, lymphocytes accompanied by giant cells, and suppurative necrosis. Histopathological reevaluation of 65 trucut/incisional/
excisional biopsies revealed granuloma formation in 65 (100%), Langhans type giant cells in 59 (90.7%), microabscess formation in 41 (63%),
caseous necrosis in 1 (1.5%), neutrophilic cysts in 30 (46.1%), eosinophilic infiltration in 48 (73.8%), interlobular inflammation in 14 (21.5%),
fat necrosis in 5 (7.6%), ductal ectasia in 6 (9.2%), and lactational changes in 4 (6.1%) cases. Granulomas were lobulocentric in 58 cases, foreign
body type/fat necrosis-related in 6 case, and periductular in 1 case. Cystic neutrophilic granulomatous mastitis was observed in one case. We also
evaluated the histochemical stains of these 65 biopsies. Only one sample was positive for acido-resistant bacilli (ARB) by the EZN method and
one sample was positive for gram-positive bacilli by gram stain.
Conclusion: Small, superficial trucut biopsies may cause difficulties in determining the etiology and differential diagnosis of granulomatous
mastitis. For optimal management and timing the appropriate therapy, the ideal biopsy procedure, special stains, and a multidisciplinary team
consisting of the surgeon, pathologist, and radiologist are the most important issues.
Granulomatous mastitis (GM) was described as a benign
inflammatory disorder in 1972 1
. It is characterized by
lobulocentric destructive granulomatous inflammation
relatively sparing interlobular stroma 2
. GM may present
with nipple discharge, orange peel sign and irregular masses
mimicking breast carcinoma clinically and radiologically
. Women with GM are usually parous and within 5 years
of pregnancy 3
. GM can be divided into two groups;
idiopathic and specific. Gestation, oral contraceptive
therapy, diabetes mellitus, smoking, autoimmunity are
considered as the major etiological factors of idiopathic
. Specific GM is due to the foreign body
reaction, sarcoidosis, vasculitis, infectious causes such as
tuberculosis, cat scratch disease, fungal inflammation, and corynebacteria infection 4
. The definitive diagnosis can
be made by histopathological examination.
The idiopathic form of GM is problematic for clinicians
and surgeons in terms of the diagnosis and treatment
strategy. The appropriate treatment modality depends on
the etiology, extent of the lesion, and skin changes with
In this study we aimed to present the detailed clinical and
morphological features, diagnostic clues for specific and
idiopathic GM, difficulties in trucut biopsies, and the
results of different therapeutic approaches.
We retrospectively analysed the clinical, radiological and
morphological features of 114 cases diagnosed as GM with fine needle aspiration (n=35) or trucut/incisional/
excisional biopsy (n=79). None of the cases had breast
malignancy in their history or during the clinical follow up
period. The clinical data included age, clinical presentation,
medical treatment history, and microbiological culture
results. Radiological features were collected from the
archived ultrasonographic, mamographic and MRI images.
We obtained the hematoxylin & eosin stained slides and
histochemical special stains of 65 cases. We reevaluated
the histopathological features including the existence
of granuloma formation, Langhans type giant cells,
microabscess formation, caseous necrosis, neutrophilic
cysts, eosinophilic infiltration, interlobular inflammation,
fat necrosis, periductal inflammation, and ductal ectasia in
65 cases. Periodic acid schiff (PAS), Ehrlich-Ziehl-Neelsen
(EZN), and Methanamine silver (MS) stained histochemical
slides were also reviewed.
The study was approved by the Local Ethics Committee
The mean age was 35.8 (min:19-max:76) years. Most of
the patients were at the reproductive and childbearing age.
Only eight cases were older than 45 years and three cases
had a pregnancy/breastfeeding history.
Bilateral involvement was observed in 4 (3.5%) cases and
the lesional breast was the left side in 63 (55.2%) cases. The
most common clinical symptoms were breast mass/abscess
(n=86), tenderness (n=34), skin changes (erythema,
peau d’orange, ulcerated areas, sinus tracts) (n=15), and
axillary mass (n=26) (Table I). Microbiological culture was
examined in 37 cases and 4 of them were positive for grampositive
bacteria. Only 3 cases showed a positive tuberculin/
PCR test for tuberculosis.
All patients were examined with ultrasonography (USG).
USG revealed a hypoechoic well-defined or ill-defined
mass/abscess (n=85), parenchymal heterogeneity/edema (n=12), parenchymal distortion (n=12), or dilated ductus
(n=5). Mammography or MRI was added in 35 cases,
because of suspected malignancy, bilaterality, or suspicious
lymphadenopathy. The major MRI findings were nonmass
forming heterogeneous contrast enhancement,
microabscess, and edema.
Cases diagnosed with cytology (n=35) did not have breast
malignancy either in their history or the clinical follow up
period. All of them were diagnosed between 2000 and 2004,
before the widespread use of trucut biopsy. Clinical and
radiological features were concordant with granulomatous
mastitis. Fine needle aspiration cytology materials
revealed epitheloid granulomas mixed with neutrophils,
lymphocytes accompanied by giant cells, and suppurative
Histopathological reevaluation of 65 cases revealed
granuloma formation in 65 (100%), Langhans type giant
cells in 59 (90.7%), microabscess formation in 41 (63%),
caseous necrosis in 1 (1.5%), neutrophilic cysts in 30
(46.1%), eosinophilic infiltration in 48 (73.8%), interlobular
inflammation in 14 (21.5%), fat necrosis in 5 (7.6%), ductal
ectasia in 6 (9.2%), lactational changes in 4 (6.1%) (Table
II). Granulomas were lobulocentric in 58 cases (Figure
1), foreign body type/fat necrosis-related in 6 cases, and
periductular in 1 case. Cystic neutrophilic granulomatous
mastitis was observed in one case (Figure 2). We also
evaluated the histochemical stains of these 65 cases for PAS,
EZN and MS. One sample was positive for acido-resistant
bacilli (ARB) with EZN, and one sample was positive for
gram-positive bacilli with gram stain (Figure 3).
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|Figure 1: Lobulocentric granuloma formation with giant cells
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|Figure 2: Central round cystic spaces rimmed by neutrophils and
cuff of epithelioid histiocytes. (HE, x100).
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|Figure 3: Some of the lipid vacuoles contain rod-shaped, grampositive
bacilli (Gram, x400).
Treatment options were medical therapy (steroid,
antibiotics, antituberculous therapy), abscess drainage,
and excision. Medical therapy was the first choice in large,
complicated lesions; and surgery in localized lesions.
Patients were given oral antibiotics during the biopsy
procedure, and then started steroid therapy. Steroid therapy
was gradually reduced and then discontinued. None of the
cases were treated with immunosuppressives. The cases
with ulceration, fistula formation, and affecting the skin
area had undergone excision.
Initial treatment option was medical therapy in 65,
abscess drainage+medical therapy in 15, affected skin excision+medical therapy in 4, and lumpectomy in 30
cases. Recurrence was observed in 15 (13.1%) cases, and 10
of them were from the medical therapy group. Recurrent
excisions were performed in 6 cases.
The etiology of GM is elusive in most cases and it presents
as a diagnostic and therapeutic dilemma. Mycobacterial,
fungal, parasitic disease, sarcoidosis, IgG4-related sclerosing
disease, and autoimmune diseases can involve the breast
and show a granulomatous inflammation pattern 7
foreign body reaction, fat necrosis, duct ectasia, epidermal
cysts of the nipple skin, squamous metaplasia of lactiferous
ducts (SMOLD), and cystic neutrophilic granulomatous
mastitis should be considered in the differential diagnosis
and ruled out with clinical, radiological and pathological
. In granulomatous lobular mastitis (GLM),
granulomas centered in the lobules are deeply located in
breast parenchyma. Fine needle aspiration biopsies (FNAB)
and small, superficial trucut biopsies may lead to difficulties
in identifying lobulocentric granulomas, the etiology of the
granulomas, and the differential diagnosis. FNAB is a quick,
noninvasive method with low sensitivity 8
. It may be
useful for excluding malignancy and obtaining a sample for
microbiological analysis but is usually ineffective to find out
the underlying cause. Core needle biopsies are more useful
for a definitive diagnosis 9
. However, granulomas may not
be identified on core biopsy in up to 15% of the cases 4,
especially the ones with intense microabscess formation
masking the granuloma. Incisional and excisional biopsies
are helpful to identify the localization of the granuloma,
and for architectural evaluation.
In the differential diagnosis, the clinical features are also
helpful. SMOLD is associated with smoking although GLM
is not 10. Unlike GLM, duct ectasia and related granulomas
occur in older woman 11. Etiopathogenesis of duct ectasia
is obscure, but weakened duct walls is probably the primary
process leading to rupture and release of duct secretions
into the stroma. Periductal chronic inflammatory reaction
and foreign body reaction occurs against the secretions.
Ruptured epidermal cysts in the superficial dermis of the
nipple skin may also cause foreign body type reaction and
granulomas. In cases of extensive foreign body giant cell
reaction, the classic features may not be visualized. Keratin
flakes may lead to the diagnosis in superficial biopsies.
In fat necrosis, the clinical history, lipid-laden foamy
histiocytes, and multinucleated foreign body type giant
cells are diagnostic. Our cohort also included granulomas
due to ruptured epidermal cyst in one case, ductal ectasia
in one case, and fat necrosis in five cases. However, the
etiology of granulomas was overlooked in these seven cases
at primary evaluation.
Cystic neutrophilic granulomatous mastitis (CNGM)
is characterized by lobulocentric mixed inflammatory
infiltrate composed of lymphocytes, neutrophils and
multinucleated giant cells; central round cystic spaces (lipid
vacuoles) rimmed by neutrophils and a cuff of epithelioid
histiocytes. Some of the lipid vacuoles may contain rodshaped,
gram-positive Corynebacterium bacilli 12.
One should be aware of the difficulties in detecting
corynebacterium by Gram stain or microbiological culture.
Targeted microbiological techniques may be necessary
for the detection 13. Central lipid spaces surrounded
by neutrophils are not specific for CNGM, and should be
investigated for fungal, mycobacterial and other bacterial
organisms 13. We observed these vacuoles in nearly half
of the cases and especially those including granulomas with
microabscess formation. We concluded that cystic lipid
vacuoles are also common in idiopathic granulomatous
mastitis (IGM). The choice of antibiotic therapy and
the optimal treatment duration still require further
investigation. Only one CNGM case existed in our cohort,
and showed resistance to prolonged antibiotic and steroid
treatment. The case underwent surgical excision due to
fistula and sinus formation (Figure 4).
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|Figure 4: Excision material of cystic neutrophilic granulomatous
mastitis case due to fistula and sinus formation.
Tuberculosis mastitis affects ducts rather than lobules and
is composed of necrotizing or nonnecrotizing granulomas.
EZN staining, culture or polymerase chain reaction can be
used for establishing the diagnosis 11,14. In our cohort,
three cases were positive for tuberculosis serologically,
but only one of them showed caseous necrosis and acidoresistant bacilli with EZN. The granulomas were associated
with both lobules and ducts. Lacambra et al. reported that
tuberculosis mastitis tends to show more eosinophils and
necrosis, but IGM is associated with more plasma cells 11.
We did not notice such a difference in our study group. The
features of the granulomas and giant cells were not useful
for distinguishing IGM and tuberculosis. Cases were given
anti-tuberculosis therapy for six months and there has been
no recurrence during follow-up period.
Eosinophils are rare in the mammary gland in breast
carcinoma as well. They are more commonly seen in
inflammatory conditions of the breast 15. Eosinophilic
mastitis is an extremely rare condition characterized by
heavy eosinophilic infiltrates around the ducts and lobules.
Few cases of eosinophilic mastitis have been reported
in the literature. Most of them were accompanied with
hypereosinophilic syndromes 16. The pathogenesis is
unknown, but localized allergic reaction to intraluminal
substances is accused 16. We noticed significant numbers
of eosinophils in the mixed inflammatory component of
granulomatous inflammation in the majority of GM cases
(Figure 5). This infiltration may be related to the efflux of
protein secretions into the intralobular stroma.
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|Figure 5: Eosinophils in mixed inflammatory component of
granulomatous inflammation (HE, x200).
When the patients had complaints of inflammatory breast
disease, short-term antibiotic therapy was started. At
the same time, baseline imaging was performed. Due to conflicting clinical and radiological features, core biopsy
confirmation was preferred. If the biopsy findings revealed
granulomatous mastitis, specific etiological factors were
investigated. Oral corticostreoid therapy was started if
all specific causes were excluded. The optimal treatment
strategy is controversial in IGM. Nearly half of the cases
develop a chronic course. Surgical complications may
lead to lesions that are worse than the primary lesion 17.
Recent approaches are biopsy, abscesses drainage, and
complex fistula excision rather than complete excision.
However, surgery is still also acceptable in selected cases.
Nearly half of the cases with small lesions and mild
clinical symptoms resolve spontaneously within 1-2 years
18. This group may be suitable for close observation.
Surgical excision should be performed in localized and
uncomplicated lesions with clear margins 19. Cases with
large, diffuse, complicated lesions are not suitable for surgery.
Medical therapy should be preferred in large, diffuse lesions
to reduce the size of the lesion and prepare the case for
surgery. Steroids should be the first choice in complicated
and recurrent cases. Methotrexate is appropriate for cases
resistant to maximal dose of corticosteroids.
Lei et al. have reported low recurrence rates (4%–6.8%)
with surgical managements with or without oral steroids
20. Recent studies recommend a conservative approach.
Shin et al. reported higher recurrence rates (25%) in the
excision group than the steroid and drainage group (7.1%).
Additional steroid therapy seems like a better choice in
recurrent cases because wider excisions lead to scarring
with deformation 21.
Close clinical observation was not the choice in the cohort.
Medical therapy was the first choice in 65 cases of which 10
showed recurrence. Recurrence after medical therapy was
higher than with surgery. Affected skin excision/drainage
combined with medical therapy was performed in 19 cases
and seemed to be an effective modality.
The first step of the diagnostic algorithm is excluding the
breast malignancy. Trucut biopsy should be preferred as the
first choice but open biopsies may be required. The ideal
biopsy procedure, special stains for the diagnosis, and the
etiology of the granulomas are the most important issues for
optimal management and timing the appropriate therapy.
CONFLICT of INTEREST
The authors have no financial or personal relationships
with other people or organizations to disclose that could
have appeared to influence the work reported in this paper.
Concept: EEP, SE, Design: EEP, SE, Data collection or
processing: MK, AD, GÇ, ME, Analysis or Interpretation:
EEP, SE, CK, ME, Literature search: EEP, Writing: EEP, SE,
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