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\begin{document}

\title{Idiopathic granulomatous mastitis: a case report and literature review}



\author[1]{Shiva Shabani}%
\author[1]{Bahman  Sadeghi}%
\author[1]{Nader  Zarinfar}%
\author[1]{Roham  Sarmadian }%
\affil[1]{Arak University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 13, 2024}


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\textbf{Introduction}

Idiopathic granulomatous mastitis (IGM) or granulomatous lobular
mastitis is a rare chronic inflammatory disease of the breast in women
(1). This disease commonly occurs shortly after a women's last pregnancy
with a history of childbirth and breastfeeding that increases,
especially in developing countries (2, 3). Despite the reports of this
disease, which show an increase in its prevalence in recent years, the
cause of its etiopathogenesis remains little known and diversified (3).
An autoimmune or hypersensitivity reaction is the most common hypothesis
regarding the etiology of the disease. However, trauma to the epithelium
of the mammary ducts and extravasation of milk or duct secretions to the
connective tissue, hyperprolactinemia, oral contraceptives, or bacterial
origin have been considered (3, 4).

IGM usually presents with a unilateral or bilateral progressive painful
breast lump. Patients with chronic IGM can develop fistulae, sterile
abscesses, and nipple inversion (5). Bilateral IGMs have a higher
relapse rate and more excellent resistance to medical therapies than
unilateral IGMs (6). Histological evaluation applies to definite
diagnosis while imaging methods differential diagnosis for breast cancer
(3) because abscesses can lead to being mistaken for breast cancer (7).
Therefore, after causes must be considered, including breast cancer,
autoimmune breast disease, and infection, the final diagnosis of IGM is
often made (4, 7).

Although the most appropriate treatment protocol has not yet been
identified, some studies recommend surgical removal, while others
suggest medical treatment such as antibiotics, corticosteroids,
immunosuppressants, and anti-inflammatory drugs (3). The results of our
literature review about information and case report IGM are summarized
and exhibited in Table 1.

This study describes a patient who presented with a breast lesion
diagnosed as IGM, and two months after treatment with prednisolone, she
was infected by Brucella.

\textbf{Case history / examination}

A 38-year-old woman was presented with a 3-week history of a painful
right retro-areolar mass unresponsive to a course of antibiotics. She
had no significant past medical history. She was not on any chronic
medication and had not used the oral contraceptive pill. She had no
history of breast trauma and a family history of breast cancer. Our case
had two pregnancies in 14 and 2 last years. Also, she has a history of
breastfed for her second child for 12 months in the previous year.
Clinically, a unilateral firm right retro-areolar breast mass was tender
to palpation. The overlying skin was thickened and slightly warm. There
was no associated nipple discharge or skin sinus.

\textbf{Differential diagnosis, investigations and treatment}

In continuation, our investigation by mammography for breast mass
revealed bilateral moderately dense fibroglandular breast parenchyma in
the right retro-areolar region was a poorly defined area of increased
density. Ultrasound revealed an irregularly outlined hypoechoic mass
measuring 19 mm x 17 mm x 20 mm. Ultrasound-guided core biopsy of the
mass was performed. The biopsy demonstrated features of chronic
granulomatous mastitis that was negative for malignant cells (Fig.1).
Stains, in order to detect bacterial (Gram), fungal elements (PAS,
Grocott's), and acid-fast bacilli (Ziehl-Neelsen), were negative. In
continuation, negative results were obtained for the brucellosis
serologic and autoimmune disease tests. The patient was treated
conservatively with steroids and showed good resolution of her symptoms
within one month, but after 2months, the patient presented with symptoms
of joint pain and headache. She was tested for brucellosis and other
tests because she lived in a Brucella endemic area and used local dairy
products. The Brucella agglutination tests showed positive results with
tetration Wright: 1/160,2ME: 1/80, Coombs Wright: 1/160. Therefore, she
was treated with doxycycline and rifampin for six weeks, and
prednisolone was continued as prescribed. The symptoms and signs of the
recent illness (Brucella) improved. Moreover, prednisolone was tapered
out and stopped within five months of its initiation.

\textbf{Outcome and follow-up}

During the one-year follow-up, her symptoms and signs of IGM did not
return, and she was magnificent.

\textbf{Discussion}

IGM is a chronic benign breast disease observed in women of childbearing
age, occurring within five years of the last delivery (2). Veyssiere et
al. 1967 described IGM for the first time (Veyssiere 1967, as cited in
Oze,2022) (2). The literature described that the prevalence of IGM is
associated with race and region (8). Its etiopathogenesis remains
unsolved, that diagnostic and therapeutic are challenging.

Non-mass-like lesions with restricted diffusion were observed in IGM.
Despite, these lesions being pathology, they may show clustered
ring-like enhancement same as malignant lesions (9). They are of
variable size, usually firm, tender, ill-defined, and unilateral (5). In
our patient, lesion was retroaleolar unilateral, ill-defined, tender and
warm in touch, and erythemato in appearance.

Often IGM is challenging to differentiate clinically and radiologically
from infectious etiologies such as tuberculosis and fungal infections,
and also from malignancy, thus posing a diagnostic dilemma (10). Our
patient had received a course of antibiotic treatment due to a make a
mistaken diagnosis of the infection. Also, she denied any previous
disease and recent breast trauma. Finally, checking the breast for
cancer and negative results for infectious tests led to the IGM
diagnosis.

There is no consensus about the optimal treatment for IGM (11). Several
treatment modalities exist for patients with IGM that, to resolve its
lesions completely, require more than one (12). A meta-analysis
illustrated that combining steroids and surgery in treating patients
with IGM is better than only steroids. It even may lead to a lower rate
of recurrence and side effects in these patients (13). In the last
years, surgery has been avoided in most cases, introducing a more
conservative medical approach(14). While some studies declare surgical
in IGM patients with wide excision provides the best long-term outcome
(15, 16).

In our case, the medical team did not recommend surgery, and
corticosteroids were used to treat IGM. Unfortunately, after taking
prednisolone for 2 months, she got Brucella disease. There is systemic
immune dysregulation in patients with IGM, so alterations in T cells,
NK, and NKT cells were reported (17). Moreover\textbf{,} prednisolone
can weaken the immune system and make it easier to get infections. The
literature demonstrates that corticosteroids increase the risk of severe
conditions and some opportunistic infections (18).

IGM is a challenging chronic inflammatory disease of the breast with
unknown etiology and unusual manifestations. Although the most
appropriate treatment protocol has not yet been identified, prednisolone
was used in our patient as an effective and practical choice in the
treatment of IGM.

\textbf{Author Contributions}

Shiva Shabani: Conceptualization; diagnosis and treatment of the case;
writing -- original draft.

Bahman Sadeghi: Literature review; writing -- original draft.

Nader Zarinfar: Contributing to the diagnosis and treatment of the case.

Roham Sarmadian: Contributing to the diagnosis and treatment of the
case.

All authors read and approved the final manuscript.

\textbf{Acknowledgements}

Not applicable.

\textbf{Conflict of Interest Statement}

All authors declare that they have no conflict of interest.

\textbf{Ethics Approval Statement}

The study protocol was approved by the Arak University of Medical
Sciences Research Ethics Committee (IR.ARAKMU.REC.1401.227). All
procedures performed in this study were in accordance with the 1964
Helsinki Declaration and its later amendments.

\textbf{Consent Statement}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.

\textbf{Data availability statement}

The data that support the findings of this study are available on
request from the corresponding author.

\textbf{Key Clinical Message}

IGM is a challenging chronic inflammatory disease of the breast with
unknown etiology and unusual manifestations. Although the most
appropriate treatment protocol has not yet been identified, prednisolone
was used in our patient as an effective and practical choice in the
treatment of IGM. Moreover, our patient may have contracted Brucella
infection due to changes in the immune system.

\textbf{References}

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2. Oze KR, Yehouenou Tessi RT, Mendes P, Allali N, Chat L, El Haddad S.
Granulomatous mastitis: A case report. SAGE Open Medical Case Reports.
2022;10:2050313X221146671.

3. Sari F, Raei N, Najafi S, Haghighat S, Moghadam S, Olfatbakhsh A.
Idiopathic Granulomatous Mastitis: An institutional Experience from a
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\textbf{Table1}: Findings from literature review for IGM\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\textbf{Age}\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
-Most women of childbearing age, several months to years after
breastfeeding. -Rare cases were reported in 11 and 80 years-old\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(5, 19)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\textbf{Mentioned etiopathogenesis}\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
-The etiopathogenesis is still unknown -Inflammation as a result of
reaction to trauma, autoimmunity, and an infection such as
Corynebacterium spp, and Corynebacterium kroppenstedtii -Metabolic or
abnormal hormonal processes such as hyperprolactinemia, -Lactation
disorders\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(4, 8, 17, 20-22)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\textbf{Pathology}\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
- Noncaseating granulomas of a lobule-centric pattern (multi-nucleated
giant cells, and epithelioid histiocytic located in the center of the
lobules as well as neutrophils, lymphocytes, plasma cells, and a small
number of eosinophils in the surrounding tissue) -lesions can be
multifocal and form micro abscesses and vary in size\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(4, 8, 21)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\textbf{Differential diagnosis}\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
-Idiopathic granulomatous lobular mastitis, -Periductal mastitis
-Fibrocystic changes, and -Sclerosing lymphocytic lobulitis or diabetic
mastopathy, -Tuberculosis, fungal infections -Malignancy\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(10)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\textbf{Imaging}\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
-Ultrasonographic findings: hypo-echoic or heterogeneous mass with or
without tubular extensions -Magnetic resonance imaging (MRI) findings:
focal or diffuse asymmetrical signal intensity changes without
significant mass effect -On dynamic contrast-enhanced MRI findings: IGM
patients with mass-like or non-mass-like contrast enhancement, some of
them with abscess positive -Mammographic presence of multiple contiguous
iso-dense masses, the reniform contour of axillary lymph nodes with the
preserved fatty hilum -Contrast-enhanced cone-beam breast-CT (CBBCT)
findings: IGM mainly manifests as a non-mass enhancement on CBBCT, with
persistently enhancing or plateau TDC\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(9, 23-27)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\textbf{Treatment}\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
-Surgical, -Immunosuppressants, steroids, methotrexate, leflunomide, and
antibiotics drugs -Prolactin-lowering medications .\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(11, 12, 14-16, 28-31)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Figure Legends:}

\textbf{Figure 1.} \textbf{Pathological result for our patient with
Idiopathic granulomatous mastitis (IGM)} . Evaluating pathology
indicated a number of ductal cells (1-2 hpf), Red cells (15-20 hpf), and
frequent PMNs with macrophages and epithelioid granuloma without exist
of malignant cell.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\selectlanguage{english}
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