|Idiopathic granulomatous mastitis; Breast cancer
|The misery of affecting by Breast cancer, leads to one of the
most common cause of surgical clinic referrals by women. All other
differentials capture great attention till being excluded by clinical,
radiological and pathological documents.
|Idiopathic Granulomatous Mastitis; Despite its low incidence, is in
high interest due to masquerading as carcinoma of the breast though
finalizing an appropriate management is crucial. It is a rare, nonneoplastic
chronic inflammatory disease of the breast . This selflimiting,
non-case eating benign disorder also known as Idiopathic
Granulomatous Lobular Mastitis, a breast disease of unknown etiology
that was first described by Kessler and Wolloch in 1972 [2,3].
|It is reported to occur predominantly in parous young woman and
is usually unilateral, mainly affects women between the ages of 25 to 55.
The time interval between the last childbirth and presentation of the
first symptoms ranges from 1to 15 years [4,5].
|The lesions are usually unilateral, presenting as a single, firm,
palpable, painful mass varying in size from 0.5 to 10 cm mostly in sub
and peri areolar region. It may occur in any of the four quadrants and
be accompanied by regional lymphadenopathy [3,5].
|Patients are almost always afebrile and might present with multiple
areas of simultaneous peripheral infection with abscesses and or
inflammation of the skin overlying the region and ulceration or sinus
formation. These findings can be accompanied by peaud`orange like
changes, nipple inversion, nipple retraction and sinus formation skin
|Since the clinical and imaging findings of the IGM have high
resemblance to those in breast cancer, it can be mistaken and moreover
the management might be planned based on this misdiagnosis [7,8].
|In many cases, it hasn`t been possible to differentiate between
an inflammatory process and malignancy and the disease mimicking
Breast carcinoma worsens the scenario [4,9].
|In confirmed IGM case series, it’s been reported that more than
50% of patients were initially misdiagnosed as affecting by carcinoma
of the Breast .
|Due to this masquerade as Breast carcinoma and its resemblance to
infection; primarily exclusion of infectious causes of breast disease and
malignancy is mandatory [2,11-16].
|The imaging details of Idiopathic Granulomatous Mastitis are
not well-documented and multiple small masses or a large focal
asymmetrical density seen suggests malignancy. Ultrasound usually reveals a, large homogenous hypoechogenicity with interstitial tubular
lesions, central necrosis and abscess formation maybe also included
|Doppler examination reveals increased vascularity of lesions and
surrounding tissue, unfortunately not helping in the differentiation
from malignancy and infection.
|Patients often present with a distinct firm mass with or without
skin changes, preceding findings can be accompanied by axillary
lymphadenopathy, each one with the high probability of being confused
with an ongoing infectious granulomatous process or an underlying
malignant lesion, the ultimate method for differentiating, is tissue
diagnosis by core-needle biopsy.
|Sarcoidosis or tuberculosis of the breast can also induce
a granulomatous reaction in the breasts with almost cheating
feature. Histopathologically in IGM, the tissue is predominantly
composed of inflammatory cells, mostly lymphocytes associated with
epitheloidhistocytosis mixed with langhans giant cells. The typical
Histopathologic feature of IGM and characteristic for it is the presence
of multinucleated giant cells and epitheloidhistocytes around lobules.
As a non-caseating granulomatous feature of the disease, often minor
ductal and periductal inflammation is evident.
|Although etiology of Granulomatous Lobular Mastitis is not well
determined yet, several theories regarding its pathogenesis have been
postulated including infectious, autoimmune process while some have
attributed that to a local reaction to chemical secretions or foreign
bodies, also probable association with recent pregnancy and breast
feeding has been noted.
|The disease might be evaluated as breast cancer and its management
might be planned based on this incorrect evaluation, thereby increasing
the amount of unnecessary excisional biopsies and even mastectomies
adding to the load on health care system.
|Understanding IGM, is important in guiding clinical decision
making while dealing with breast lumps can save both the patient and
the physician from unnecessary diagnostic and treatment procedures.
|Complications seem to be related to both the disease process as
well as the surgical procedures including skin ulceration, abscess and
sinus formation, fistulae, wound infection, recurrent of disease post
treatment and chronic mastitis followed by excisional biopsies. In some
cases there are systemic signs and symptoms such as arthralgia, skeletal
pain, multiple lyphadenopathies, even in mediastinum.
|As far as the treatment of IGM is concerned, no single best
intervention; neither surgical nor pharmacological has been
proposed. The different managements used varying from conservative
pharmacological therapy with antibiotics, glucocorticoids and
methotrexate administration; excisional biopsies and even mastectomies
haven`t been promising enough to become the treatment of choice and
it remains a clinical challenge.
|Keeping in mind the self-limiting nature of the disease without
subsequent increase in risk of the breast cancer in patients with IGM, it
seems both logical and cost-effective to primarily confirm the diagnosis
by histopathological examination often exclusion of other more
important and dangerous differentials and then use a non-invasive
pharmacological treatment accompanied by close regular surveillance
based on the strategy of expectant management.
|Herein we are introducing a non-surgical management of IGM with
frequently aspiration of the masses accompanied by using bacteriostatics; such as Ciprofluxacin or trimetoprime-sulfamethoxazole known as
cotrimoxazole and close regular surveillance.
|Material and Method
|This was a before and after clinical trial looking at the effects of
repeated aspirations coupled with antibiotic treatment on the natural
course of IGM. Overall 55 patients met the inclusion criteria.
|A couple of patients who had presented with systemic constitutional
symptoms of malaise, arthralgia and myalgia were excluded from the
study and were referred to rheumatologists for further evaluations.
After initial evaluation with mammography and ultrasonography in
patients complaining of breast mass, those in whom imaging studies
revealed heterogeneous unilateral densities were referred to the Cancer
Research Center at Shohaday-e-Tajrish hospital. IGM was suspected
in patients presenting with the conglomerate of signs and symptoms
which include breast mass, breast inflammation, pain and no evidence
of febrile disease. These patients underwent clinical and imaging study
as well as Core Needle Biopsy (CNB) of the lesion with a 14-16 Gauge
needle. Any aspirated fluid was cultured, gram stained, and checked
for antibiotic susceptibility. At this time the patients were all put on
Ciprofloxacin 500 mg, or Trimethoprin-Sulfamethoxazol 400+80 mg
(Cotrimoxazole) every 12 hours.
|Cases with a positive culture result were treated as breast abscess
and being excluded from the study. Cases with a negative culture which
experienced improved symptoms were followed up, while those with
persistent symptoms or recurrent disease were aspirated again and
evaluated with fungal, aerobic and anaerobic cultures. The latter also
underwent CNB for evidence of IGM if any doubts persist for definite
|The criterion for pathologic confirmation of the diagnosis was the
presence of non-caseous non-vascular granules, giant cells, epithelioid
cells, leukocytes, and microabscess. If the diagnosis was still uncertain
Complete Blood Count, Chest X-ray, Purified Protein Derivative,
Erythrocyte Sedimentation Rate, Angiotensin Converting Enzyme
were checked in order to rule out other causes of granulomatous
disease. Patients with pathologic evidence suggesting IGM and no
other diagnosis were included in the study.
|A questionnaire including patient’s demographic information, past
medical, surgical, and obstetric history, presenting illness, symptoms at
presentation, physical examination findings, and a detailed description
of the condition was filled by a trained researcher. In cases with a past
history of treatment for IGM, the type, length and success of past
treatment was also documented. Pain was measured using the simple
method of evaluating the patients based on Visual Analogue Scale.
|Confirmed cases of IGM were treated with antibiotic therapy
(Ciprofloxacin 500 mg, or Trimethoprin-Sulfamethoxazol 400+80 mg
every 12 hours) until either the relief of symptoms or a maximum of
3 weeks. One or two Weeks follow up visits were conducted in the
first three months, monthly visits in the first six months, and then no
matter when the last visit was done, it was recorded. In each visit if
a mass or accumulation of inflammatory products was palpated; the
aspiration was done. On each follow up visit the patients were assessed
for edema, erythema, mass lesions, pain, sinus formation, and personal
satisfaction. Any further intervention at the time of the visit was also
|During the course of follow up, known confounding factors that
might influence the success of treatment including corticosteroid use
for other indications was also documented and excluded from the study.
|Signs and symptoms of disease before and after the treatment were
compared in order to reveal the treatment success. Also the relationship
between different demographic variables and the success of treatment
was analyzed. Statistical analysis was performed using the SPSS
|55 patients met the inclusion criteria and enrolled the study.
|Patients presenting sign and symptoms were categorized into
six variable ones, including Six following variables were evaluated;
inflammation, erythema, mass ,pain and sinus formation, also patient
satisfaction was evaluated in a predicted manner of 30-50% for mild
satisfaction, 60-80% for moderate satisfaction while those who declared
the percentage of 90-100% ,were recorded as excellent satisfaction.
|Patients were followed up in a regular manner of a single visit
during first to third weeks after first visit, followed by 1-3 months, 4-6
months and final visit which varied from 12 to 90 months.
|44 patients (80% of cases), elucidated signs of inflammation,
whereas solely 18 patients (32% of cases) were presented with inflamed
breasts at final visit. The inflammation rate at first and final visit were
80% (44 out of 55) and 32% (18 patients) respectively (P value=0.03).
|Among those who fulfill the inclusion criteria, 45 patients (81%
of cases) presenting symptom was erythema, ultimately there were 14
cases (25%) in whom erythema persists (p value=0.03).
|More specifically in a couple of patients (3.6%), decrease in the
surface involved by erythema was noted.
|Mass presence was the dominant sign being discovered in 45
(72%) of enrolled cases at the time of first visit. The reported results
has experienced a decline curve, finally 10 cases (18%) has remained
symptomatic with a mass (P value=0.02).
|Furthermore pain was elucidated in more than half of those who
entered the study, 25 cases (56%). Likewise the couple of previous
noted symptoms, number of patients experiencing pain at final visit
demonstrated significant decline. pain has affected small number of
patients at the final visit.
|Sinus formation has complicated 14.5% (8 cases) of the patients,
interestingly followed by a minimal rise at second visit during 1-3
weeks, the number of affected patients was consistently reported as 7
patients(12% of patients) during the further visits.
|Satisfaction rate was recorded in a manner of mild (30-50%),
moderate (60-80%) and excellent (90-100%). Following results were
obtained, there were solely 3 patients (5.6%) in whom satisfaction rate
varied from 30-50%.
|The mainstay of performed study, intervention by recurrent
aspiration and antibiotics administration was recorded as following,19
patients (34% of cases) undergone aspiration of less than 2 cc in
comparison with 48 patients (87% of cases) at final visit (p value=0.04).
|The aspiration of significant amount of more than 6 cc was reported
in 15 patients (27% of cases) at second visit followed by 4 patients (7%
of cases) at final visit.
|Antibiotics were administered for a duration of 2 weeks in the
second visit of follow up for all the participants except 5 (90% of cases),
and final visit were reported in 50 patients and 4 patients (7% of cases)
respectively (p value=0.01).
|Combinations of antibiotics were administered for duration of
3 weeks in 1 patient (1.8% cases) versus 18 patients (32% of cases) at
second and final visits respectively.
|Idiopathic Granulomatous Mastitis is a rare clinical situation of
breast affecting young women during reproductive period, which
mimics breast cancer in clinical evaluations, imaging studies and even
in pathological features.
|Neither understood etiologically nor the best management is
established, results in a great challenge.
|The appropriate diagnostic procedure is core needle biopsy and
pathological tissue evaluation.
|After confirmation of pathological diagnosis, the management
of cases are vested from excisional biopsy, lumpectomy and even
mastectomy also the non-surgical management varied from different
antibiotics, corticosteroids and anticellular agents such as methotrexate.
|The most acceptable management for such cases in recent
documents are combination of surgical interventions such as
lumpectomy, open biopsy and using pharmaceutical agents such as
antibiotics and corticosteroids.
|Because of the nature of the disease which is an inflammatory
reaction, any form of surgical intervention will be an unsuitable
procedure and may become a disaster for both patient and the physician.
|On the other hand using corticosteroid with long standing
complications is not an acceptable and well tolerated prescription;
therefore we recommend the procedure of recurrent and or multiple
drainage with a 10 cc syringe, 22-23 gauge needles.
|Rate of aspiration varied from a single to four time drainage.
Patient’s satisfaction was moderate to excellent in 94% at final visit and
no more intervention was required.
|Using some bacteriostatic antibiotics is based on the nature of the
disease which is not a purulent disease but there is a clinical feature of
|In our cases there was neither drug reaction with ciprofloxacin
nor with cotrimoxazole. Furthermore no systemic complication
was seen, but regarding the natural history of the disease, Antibiotic
administration may not be necessary and should be in consideration
in further studies.
|The current study elucidated that patients affected by Idiopathic
Granulomatous Mastitis, suffer from the accumulation of the
inflammatory products of mastitis.
|As a result, the procedure of recurrent drainage may resolve
the symptoms of pain, erythema and possibly the sinus formation,
ultimately the mass will be resolved; therefore the recurrent drainage
is highly recommended. On the other hand as the effectiveness of
antibiotic administration is not absolutely documented, we have used a
range of bacteriostatic antibiotics with cellular effects which may not be
administered necessarily in the further studies.
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