Are all Granulomatous Mastitis Cases Tuberculous?: A Study on the Role of Cytology in Evaluation of Granulomatous Mastitis
Charu AGARWAL, Kanika SINGH, Mukta PUJANI, Sujata RAYCHAUDHURI, Nimisha SHARMA, Varsha CHAUHAN
Department of Pathology, ESIC Medical College and Hospital, NIT 3, FARIDABAD, INDIA
Keywords: Granulomatous mastitis, Tuberculous, Cytology, ZN stain, PCR, Breast
Granulomatous mastitis is a rare inflammatory condition of the breast clinically mimicking breast carcinoma and pyogenic abscess,
thereby creating a diagnostic dilemma. Tuberculous mastitis is a rare clinical entity accounting for approximately 3% of all mammary lesions. All
cases of granulomatous mastitis diagnosed cytologically over a period of 3 years were evaluated to ascertain the cases with tuberculous etiology.
Material and Method: Fine needle aspiration cytology of the breast lump was performed and all the cytological parameters were evaluated.
Wherever histopathology was available, the diagnosis was confirmed on Hematoxylin & Eosin stained sections and the Ziehl Neelsen (ZN) stain
Results: A total of 10 cases of granulomatous mastitis were diagnosed on cytology during the 3-year period. On cytological smears, four cases
showed presence of ill-formed granulomas and one case had scattered epithelioid histiocytes; however, the rest of the cases had well-formed
granulomas. Finally, four out of ten cases were labeled as tuberculous mastitis based on the ZN stain/Tuberculosis-Polymerase chain reaction
(TB-PCR) and the other six cases were granulomatous mastitis.
Conclusion: Cytology plays a significant role in the diagnosis of granulomatous mastitis. This study re-emphasizes the role of the cytopathologist
in the accurate and early diagnosis of these lesions so that unnecessary surgery can be avoided, and also highlights the fact that all granulomatous
mastitis cases are not tuberculous.
Granulomatous mastitis (GM) is a rare inflammatory
condition of the breast which can clinically mimic breast
carcinoma and pyogenic abscess, thereby creating a
diagnostic dilemma 1
. It was first described by Kessler
and Woolloch in 1972 2
. GM has an unclear etiology and
variable treatment options and has a tendency to persist or
. In Asian countries, the etiology of most cases
is tuberculosis but other rare causes of granulomatous
conditions include fungal diseases, sarcoidosis and
Wegeners granulomatosis. Idiopathic Granulomatous
Mastitis (IGM) is therefore a diagnosis of exclusion.
GM is a benign condition but it is crucial to arrive at a
correct diagnosis at an early stage so that an unnecessary
surgery can be avoided due to its resemblance to carcinoma
both clinically and radiologically.
Tuberculous mastitis is a rare clinical entity accounting
for approximately 3% of all mammary lesions mainly affecting Indian and African females and is often clinically
misdiagnosed as other benign or malignant lesions of the
breast 5. It may occur as a part of systemic tuberculosis or
as an isolated lesion.
Although histopathology remains the gold standard for
establishing the correct diagnosis, FNAC plays a pivotal
role in the early diagnosis of GM as a minimally invasive,
simple and cost effective outpatient technique. Thereby, a
correct etiological diagnosis of granulomatous lesions is
mandatory so as to administer appropriate therapy.
Here we are presenting a series of 10 cases of granulomatous
mastitis diagnosed cytologically over a period of 3 years.
Through this study, we wish to re-emphasize that all
granulomatous mastitis cases are not tuberculous, even in
the endemic countries like India as documented by several
other authors 6,7. Moreover, it highlights the role of
cytopathologist in the accurate and early diagnosis of these
lesions so that unnecessary surgery can be avoided.
The current study was performed at the Department of
Pathology, ESIC Medical College and Hospital, Faridabad
over a period of 3 years (April 2015 to April 2018). The
cases were retrieved from the archives of the cytopathology
and histopathology laboratories. All cases reported as
granulomatous mastitis on cytology were included in the
The patients presented to surgical outpatient department
with a breast lump and were referred to the cytopathology
laboratory. Fine needle aspiration cytology (FNAC) of the
lump was performed and smears were evaluated. In all the
cases, cytological parameters were evaluated including
the presence of epithelioid cell granulomas, histiocytes,
multinucleated giant cells, necrosis and neutrophils. The
Ziehl Neelsen (ZN) stain for acid fast bacilli (AFB) and
Periodic acid Schiff (PAS) stain for fungi were performed
on all cytological cases. The clinical details including
gender, age, history of trauma, family history of TB along
with radiological findings (if available) of all the patients
were recorded. Routine hematological findings with the
Erythrocyte sedimentation rate (ESR) and Mantoux test
along with the Tuberculosis-Polymerase chain reaction
(TB-PCR) were correlated. Wherever histopathology was
available, the diagnosis was confirmed on Hematoxylin
and eosin stained sections and the ZN stain was applied.
A total of 10 cases of granulomatous mastitis were
diagnosed on cytology during the 3-year period. All the
patients were female with a mean age of 36 years (range, 29-51). In six out of ten cases, the lesion was in the right
breast and four were on the left side, while the size of the
lump varied from 1 to 5 cm in diameter. The duration of
the lump ranged from 1 month to two years. All the cases
had varied clinical presentations with few showing an
irregular hard lump and were given provisional clinical
diagnosis of abscess, fibroadenoma and malignancy. One
case had a past history of being operated for abscess but few
months later she again developed a lump that turned out to
be granulomatous mastitis.
Ultrasonography was done in 7 cases and was reported
variably as abscess, irregular hypoechoic mass, increased
vascularity and lobulated mass, thereby creating a dilemma.
The clinico-pathological details of all the cases are shown
in Table I.
On fine needle aspiration, blood mixed aspirate was
obtained in all cases barring two where pus was aspirated.
On cytological smears (Figure 1,2), four cases showed the
presence of ill-formed granulomas, one case had scattered
epithelioid histiocytes and the rest of the cases had wellformed
granulomas. Four cases showed absence of necrosis
with one case showing patchy necrosis and the other five
cases showing abundant caseous necrosis. Multinucleated
giant cells, containing nuclei ranging from 5 to 18, were
present in six cases. These six cases also had predominance
of neutrophils among other inflammatory cells forming
micro abscesses. Three cases showed the presence of benign
ductal cells of the breast (Figure 1). The cytological features
of all the cases are depicted in Table II. On application of
ZN stain, three cases showed presence of AFB (Figure 2A,B) thereby confirming the diagnosis of TB mastitis, which was further reaffirmed on histopathology. The PAS stain for
fungus was negative in all the cases. TB-PCR was sent for
all cases that turned out to be granulomatous mastitis on
cytology (as depicted in Table II) and four were positive.
Three out of these four cases (TB-PCR positive) underwent
surgical excision. So finally four out of ten cases were
labeled as tuberculous mastitis. On reviewing the histories
of patients with GM, none of the patients had any evidence
of Crohns, sarcoidosis, etc.
Click Here to Zoom
|Figure 1: Giemsa stained smears showing well-formed granuloma
with patchy necrosis (Giemsa; x400) (Inset - showing benign
ductal cells cluster) (Case 5).
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|Figure 2: Giemsa stained smears showing well-formed granuloma
in a background of degenerated inflammatory cells (Giemsa;
x400). Inset: A) Giant cell (Giemsa;x200). B) AFB bacilli (ZN
stain; x1000) (Case 9).
Six cases underwent surgery and tissue was sent for
histopathological examination. On histopathology (Figure
3A,B), four cases showed the presence of well-formed epithelioid cell granulomas but the remaining two cases
had an ill-formed granulomas. There were multinucleated
giant cells and necrosis in four cases. The surrounding
breast showed features of adenosis. Three cases were
diagnosed histologically as TB mastitis and the other three
cases showed features suggestive of granulomatous mastitis
since they were negative on ZN staining (Table I).
Click Here to Zoom
|Figure 3: A) Photomicrograph showing an ill-formed granuloma (H&E; x400) (Case 10). B) Photomicrograph showing an well-formed
granuloma (H&E; x100) (Case 1).
Granulomatous mastitis (GM) is an uncommon breast
lesion that was first described in 1972 and representing
approximately 0.025-3% of all surgically treated breast
The etiology of GM is diverse, ranging from infectious
causes including bacterial (TB, Leprosy, Cat-scratch
disease), fungal (histoplasmosis, cryptococcosis), protozoal
(schistosomiasis) to autoimmune causes including Crohns,
sarcoidosis, vasculitis as well as a reaction to foreign bodies/
implants (silicon, beryllium) 9,10. Therefore, idiopathic
GM is a diagnosis of exclusion.
The disease usually occurs in women of reproductive age,
and may be associated with lactation or the postpartum
period. Affected women are nearly always parous and
usually present in their early thirties with the progressive
onset of a breast lump 11. All patients in the present study
were in the reproductive age group, not associated with
lactation or lymph node involvement.
The most common clinical presentation is a firm, unilateral,
discrete breast mass, often associated with inflammation of
the overlying skin. The disease course is characterized by
slow resolution, occasionally with intermittent episodes of
abscess or discharging sinus formation, particularly after
large core needle biopsies3,12 as in one of the cases in the
present study. It is well known for its worrisome clinical
presentation as a hard breast lump with or without nipple
retraction particularly in young women, thereby acting
as a mimic of carcinoma clinically as documented by
several authors 2,7,10,12,13. Regional lymphadenopathy
may be present in up to 15% of cases 14. It often
masquerades as other common conditions such as breast abscess, fibroadenoma, etc. Similarly, our three cases were
misdiagnosed clinically as carcinoma.
The breast and skin are considered to be the rarest sites of
extrapulmonary tuberculosis constituting only approx. 0.1-
0.5% of all TB cases 8. Tuberculosis (TB) of the breast is
an uncommon disease that is often difficult to differentiate
from cancer of the breast when it presents as a lump, as
mistakenly done in one of our cases.
FNAC is the primary investigation for breast lesions so
awareness about GM is a must among cytopathologists.
The common cytological features that have been evaluated
include necrosis, giant cells, epithelioid histiocytes,
granulomas, and neutrophils present in the background.
FNAC may not always differentiate between IGM and
other granulomatous diseases of the breast, and a confident
diagnosis may require histological samples, negative
microbiological investigations and clinical correlation. Its
histopathological features are characterized by chronic,
necrotizing granulomatous lobulitis. As IGM is essentially
a diagnosis of exclusion, and all causes of granulomatous
inflammation must be actively excluded by applying
special tests like AFB (TB bacilli), PAS (fungus), Gram
stain (bacterial), PCR (TB or atypical mycobacterium), etc.
The cases in the present study were all properly worked up
clinically and cytologically with histopathological work up
in six out of ten cases.
During our extensive search of the literature on GM,
we came across several studies across the globe. Seo et
al. in 2012 retrospectively reviewed the records of 68
patients with GM. FNAC was performed in 30 cases with
histopathology in all 68 patients, out of which 10 cases
were TBM (tuberculous mastitis) while IGM was the final
diagnosis in the rest of them 15. Helal et al. studied 65
cases of IGM over a period of 6 years. They have explained
cytomorphological and histomorphological features of
IGM 16. They emphasized the efficacy of cytology in
the diagnosis of such lesions. Ail et al. obtained 21 cases of
granulomatous mastitis diagnosed on cytology over eight
years, out of which 16 cases were of non specific GM and
five were TBM 6. They found that 25% of non specific
GM and 60% of TBM cases had a clinical suspicion of
malignancy and about 30% had a radiological suspicion of
malignancy. In the present study, we evaluated 10 cases of
GM over a period of 3 years. Cytological parameters were
evaluated in all the cases with applications of special tests
like the ZN and PAS stain. Histopathological correlation
was done wherever possible. Four out of ten cases were
labelled as tuberculous mastitis based on the ZN stain/
Tuberculosis-Polymerase chain reaction (TB-PCR) and the
remaining six cases were IGM. The comparative analysis of various studies (pubmed literature search) based on
cytopathological evaluation of GM is depicted in Table III.
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|Table III: Comparative analysis of various studies (pubmed literature search) based on cytopathological evaluation.
In a review by Benson and Dumitru 9, they favoured a
multidisciplinary approach for the treatment of IGM as
there is no consensus on the optimal treatment strategy.
Before adopting a surgical approach, the pros and cons
should be carefully weighed for individual cases so as to
avoid the worrisome complications arising out of surgery
9. Treating tuberculosis with steroids would aggravate
the infection, whereas giving unnecessary anti-tuberculosis
drugs in cases of idiopathic granulomatous mastitis may
cause numerous side effects. Therefore it is mandatory to
differentiate these two lesions before commencement of
In conclusion, cytology plays a significant role in the
diagnosis of GM. All granulomatous mastitis cases are
not tuberculous and the etiological diagnosis of GM
must be based on a multidisciplinary approach. The
definitive diagnosis of GM relies on correlation with histopathological
and microbiological investigations. This study
re-emphasizes the role of the cytopathologist in the accurate
and early diagnosis of these lesions so that unnecessary
surgery can be avoided.
CONFLICT of INTEREST
The authors declare no conflict of interest.
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