International Journal of Academic Medicine

LETTER TO EDITOR
Year
: 2017  |  Volume : 3  |  Issue : 2  |  Page : 336--339

Idiopathic granulomatous mastitis: A diagnostic and therapeutic challenge


Samuel Schadt1, Mark E Schadt1, Thomas R Wojda2, Franz S Yanagawa3, Stanislaw P Stawicki1,  
1 Department of Surgery, St. Luke's University Health Network, Bethlehem, PA, United States of America
2 Family Practice, Warren Hospital, St. Luke's University Health Network, NJ, United States of America
3 Surgery, Warren Hospital, St. Luke's University Health Network, NJ, United States of America

Correspondence Address:
Dr. Franz S Yanagawa
Department of Surgery, Warren Hospital, St. Luke's University Health Network, 185 Roseberry Street, Phillipsburg, 08865 NJ
United States of America




How to cite this article:
Schadt S, Schadt ME, Wojda TR, Yanagawa FS, Stawicki SP. Idiopathic granulomatous mastitis: A diagnostic and therapeutic challenge.Int J Acad Med 2017;3:336-339


How to cite this URL:
Schadt S, Schadt ME, Wojda TR, Yanagawa FS, Stawicki SP. Idiopathic granulomatous mastitis: A diagnostic and therapeutic challenge. Int J Acad Med [serial online] 2017 [cited 2021 Jan 19 ];3:336-339
Available from: https://www.ijam-web.org/text.asp?2017/3/2/336/222483


Full Text



To the Editor,

Idiopathic granulomatous mastitis (IGM) is a rare, benign, inflammatory disorder of the breast that can imitate a broad range of conditions, from abscess to carcinoma [Figure 1].[1],[2] IGM is most likely to affect women in the third decade of life, often in the presence of associated history of pregnancy, lactation, and oral contraceptive use.[3],[4] Clinical presentation typically involves the appearance of a tender, firm breast mass.[1],[5] IGM is clinically and radiographically difficult to diagnose,[6],[7] resulting in high incidence of misdiagnosis. Because of this, histopathologic confirmation is required [Figure 2]. Corticosteroid therapy and other forms of immunosuppression have shown promise in the treatment of this cryptic disease.[8],[9],[10],[11] Although surgical management can be effective in severe cases, it should not be considered first-line therapy due to the associated risks of recurrence, poor wound healing, and scar formation. Here, we describe a patient that presented with clinical signs consistent with a breast abscess, followed by the development of prominent rheumatological symptoms. On further workup, the diagnosis of IGM was confirmed. Despite attempts at intensive medical therapy, the patient continued to have severe pain and eventually opted to undergo bilateral simple mastectomy. A discussion of clinical presentation, diagnosis, pathology, and treatment of IGM is also provided, including a brief literature review on the topic.{Figure 1}{Figure 2}

 Case Report



A 39-year-old, Gravida 3 – Para 3, African American female presented to the outpatient office complaining of severe pain and swelling in her right breast. She reported an uneventful pregnancy within the past 4 years, including last breastfeeding approximately 18 months before the current presentation. Subjectively, she noticed that over the course of the preceding 6 months her breasts have become more firm and tender. Her medical history was otherwise unremarkable. She denied previous oral contraceptive use or recent breast trauma. Her family history was, however, significant for “aggressive breast cancer” in both her mother and her aunt.

Physical exam revealed firmness and tenderness localized to an indurated 11 cm × 11 cm mass in the central, upper right breast, as well as the presence of firmness in the upper outer quadrant. No sinuses, nipple discharge, or axillary adenopathy was noted. Ultrasound demonstrated ductal dilatation and a fluid collection resembling an abscess. Incision and drainage were performed, demonstrating several thick, white loculations deep within the upper and central breast. Wound and blood cultures revealed no growth. She patient was discharged with local wound care and a 1-week regimen of cephalexin.

The patient returned 1 month later with recurrent right breast mass, erythema, and worsening pain. A regimen of metronidazole and vancomycin was started, but her symptoms progressed to diffuse myalgias, arthralgias, chest pressure, and fevers. Concurrently, she began experiencing wrist, ankle, and knee swelling, with associated weakness in both upper and lower extremities, primarily attributable to pain. Subsequent brain, thoracic, and lumbar spine magnetic resonance imaging (MRI) found no evidence of disc disease or demyelinating disorder. Echocardiogram and ultrasound of the kidneys were unremarkable. Erythrocyte sedimentation rate was 69, and a battery of viral (human immunodeficiency virus), bacterial (blood/urine cultures, tuberculosis), and rheumatologic (anti-nuclear antibody, double-stranded DNA, rheumatoid factor, Sjogren's antibody, angiotensin-converting enzyme level, prolactin, C3/C4 levels, creatine phosphokinase, antineutrophil cytoplasmic antibodies, and human leukocyte antigen B27) tests showed no abnormalities. Of note, the patient's hemoglobin decreased in the interim from 10.9 g/dL to 7.5 g/dL, prompting bone marrow biopsy to rule out a paraneoplastic process.

To further characterize the primary complaint of mastalgia, mammography was performed and revealed dense breast tissue, contributing to limited clinical sensitivity. Ultrasound demonstrated heterogeneous hypoechoic lesions throughout the right breast, highly suspicious for multiloculated abscess recurrence. Finally, MRI was indeterminate with diffuse, non-specific breast changes. An excisional biopsy of the right breast revealed thick, loculated, white fluid with multiple deep extensions in the central and lateral directions. Intraoperatively, breast tissue was found to be firm and edematous. Pathology evaluation demonstrated acute and chronic inflammation with multinucleated giant cells [Figure 2]. Cytochemical stains were negative for tuberculosis, fungus, and amyloidosis. Culture results showed limited growth of Corynebacterium diptheria. Concurrent skin biopsy was negative for inflammatory breast cancer. Based on all available clinical data, including detailed consultation with an expert pathologist, the treatment for presumed IGM was initiated with glucocorticoids and doxycycline. There was a gradual improvement in the patient's breast pain and rheumatologic complaints.

The patient was discharged to home, with outpatient wound care regimen and medical management consisting of doxycycline, amoxicillin-clavulanic acid, plus prednisone 60 mg daily. At the 4-month follow-up appointment, she reported an estimated 50% reduction in right breast discomfort and 80% clearance of arthritic complaints. Erythema and inflammatory breast changes were noted to be significantly better [Figure 3]. Given this clinical improvement, prednisone was tapered from the initial 60 mg to a target dose of 10 mg over a 4-week period. Because of persistent mastalgia, methotrexate (10 mg/week) was started approximately 4 weeks later (e.g., 6 months postoperatively). However, this was associated with new onset, severe menorrhagia requiring transfusion and surgical dilatation/curettage, mandating the discontinuation of methotrexate. Given the persistent, significant bilateral mastalgia at 7 months, the patient requested to undergo bilateral mastectomy because of the pain, concerns regarding strong family history of breast cancer, and the presence of equivocal breast imaging.{Figure 3}

 Discussion



IGM is an uncommon, benign inflammatory breast disorder.[1],[2] The usual age of clinical presentation for IGM is between 25 and 50 years.[9] Although its exact prevalence is unknown, IGM is generally considered to be very rare. It has been suggested that the incidence may vary across geographic distributions and populations.[4],[11],[12] Unilateral breast mass often interpreted clinically as a breast abscess or malignancy is a common presentation.[13],[14] Associated findings may include galactorrhea, cellulitis/erythema, cutaneous fistulization, mastalgia, nipple inversion, peau d'orange appearance, and less commonly axillary adenopathy.[4],[14],[15]

The etiology and pathophysiologic mechanisms responsible for IGM are not well understood.[16] Currently, this condition is thought to involve autoimmune reaction or localized immune response,[4],[16] but the presence of infection suggests an inciting event that subsequently and gradually evolves into IGM.[9] Reports of favorable response to corticosteroids and similarities to granulomatous thyroiditis or orchitis support the immune etiology.[4] Despite substantial research involving a variety of suspected pathophysiologic mechanisms, no decisive progress has been made thus far.[4],[11],[12],[17]

Hormonal influences, including recent pregnancy, lactation, and the use of pharmacologic contraception may all play a role in IGM pathogenesis.[10] There may also be associations with blunt trauma, hyperprolactinemia, alpha-1-antitrypsin deficiency, and erythema nodosum.[11],[15] In addition, infection with Corynebacterium has been reported to play a role,[4],[16] including the finding of C. diptheria in the current report. It remains unclear how each of the above factors, alone or in combination, contributes to the emergence of IGM as a syndromic entity.

The nonspecific clinical and radiographic appearance of IGM usually results in a comprehensive breast evaluation before the diagnosis is made. The use of mammography, Doppler ultrasound, and MRI has been described, but regardless of the modality being employed, imaging fails to reliably differentiate IGM from abscess or carcinoma. Frequent findings include asymmetric diffuse densities of fibro-glandular tissue, hypoechoic mass lesions, and nodular structures. MRI may show enhancing masses with indistinct borders and associated breast tissue distortion.[10],[15]

As previously mentioned, definitive diagnosis of IGM requires histological examination of breast tissue. Characteristic histopathology features include granulomatous inflammation with giant cells and the concurrent presence of macrophages, polymorphonuclear leukocytes, eosinophils, and epithelioid histiocytes.[3],[14],[18] Distribution of findings is lobular in nature.[3],[13],[14] Noncaseating granulomas, microabscesses, and fat necrosis may be present.[3],[4],[10],[13],[15] Typical tissue changes associated with IGM are shown in [Figure 2].

Clinical management of IGM is challenging, mainly because of its ability to imitate other breast conditions, up to and including malignancy. Having said that, uncomplicated IGM cases have been described, with spontaneous resolution reported in approximately one-half of patients.[4],[10] There is no definitive, or universally agreed-upon, treatment for IGM. Majority of patients undergo a combination of medical and surgical approaches. Confirmatory breast biopsy followed by the administration of systemic steroids is the most common clinical management pattern.[8],[19] Recognition of IGM as a chronic inflammatory disease prompted the incorporation of corticosteroids and other types of immunosuppression into the overall therapeutic armamentarium. The use of prednisone [11] and methotrexate [10] has been described in difficult cases. As early as 1980, a case was made for corticosteroids to be administered before surgical resection.[20] During the past 3 decades, management of IGM has evolved to include a combination of surgery, corticosteroid tapering, and disease-modifying antirheumatic drugs such as methotrexate [21] and azathioprine.[15] Surgical excision produces mixed outcomes, with limited resections resulting in 5%–50% recurrence rate and partial mastectomy and mastectomy resulting in 79%–100% response.[11] However, the performance of routine surgery for IGM has been questioned, with some authors suggesting that careful diagnostic and risk-benefit assessment should be performed before embarking on increasingly invasive management approaches.[3]

 Conclusions



Being a diagnosis of exclusion, IGM continues to be a diagnostic and therapeutic challenge. Prompt and correct diagnosis is critical to avoiding unnecessary surgical intervention(s), with approximately half of IGM cases responding to medical therapy alone.[15] Immediate clinical improvement following the administration of corticosteroids may be seen. Patients with recurrent “sterile abscesses” of the breast should have IGM included in the differential diagnosis. Because IGM lesions can mimic malignancy,[4],[11],[12] a thorough and appropriate workup and risk-benefit determination must be performed to avoid overly aggressive surgical approaches. The current case demonstrates the clinical complexity associated with diagnosis and treatment of IGM and highlights the critical need for interdisciplinary approach to patient management.

Acknowledgment

Authors would like to thank Dr. Santo Longo and the Department of Pathology at St. Luke's University Hospital (Bethlehem, Pennsylvania) for their assistance in obtaining pathology slides/images.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

The authors attest that this scholarly work was conducted in accordance with the recommendations of The International Committee of Medical Journal Editors. Patient consent was obtained prior to the submission of this manuscript for publication in the International Journal of Academic Medicine.

References

1Kamra HT, Munde SL, Rana P, Kaur S, Singh K, Duhan A. Cytological features of granulomatous mastitis – A study of ten cases. Indian J Pathol Oncol 2016;3:129-32.
2Guray M, Sahin AA. Benign breast diseases: Classification, diagnosis, and management. Oncologist 2006;11:435-49.
3Bani-Hani KE, Yaghan RJ, Matalka II, Shatnawi NJ. Idiopathic granulomatous mastitis: Time to avoid unnecessary mastectomies. Breast J 2004;10:318-22.
4Patel RA, Strickland P, Sankara IR, Pinkston G, Many W Jr., Rodriguez M, et al. Idiopathic granulomatous mastitis: Case reports and review of literature. J Gen Intern Med 2010;25:270-3.
5Aldaqal SM. Idiopathic granulomatous mastitis. Clinical presentation, radiological features and treatment. Saudi Med J 2004;25:1884-7.
6Al-Khaffaf B, Knox F, Bundred NJ. Idiopathic granulomatous mastitis: A 25-year experience. J Am Coll Surg 2008;206:269-73.
7Baslaim MM, Khayat HA, Al-Amoudi SA. Idiopathic granulomatous mastitis: A heterogeneous disease with variable clinical presentation. World J Surg 2007;31:1677-81.
8Erozgen F, Ersoy YE, Akaydin M, Memmi N, Celik AS, Celebi F, et al. Corticosteroid treatment and timing of surgery in idiopathic granulomatous mastitis confusing with breast carcinoma. Breast Cancer Res Treat 2010;123:447-52.
9Gurleyik G, Aktekin A, Aker F, Karagulle H, Saglamc A. Medical and surgical treatment of idiopathic granulomatous lobular mastitis: A benign inflammatory disease mimicking invasive carcinoma. J Breast Cancer 2012;15:119-23.
10Akbulut S, Arikanoglu Z, Senol A, Sogutcu N, Basbug M, Yeniaras E, et al. Is methotrexate an acceptable treatment in the management of idiopathic granulomatous mastitis? Arch Gynecol Obstet 2011;284:1189-95.
11Kim J, Tymms KE, Buckingham JM. Methotrexate in the management of granulomatous mastitis. ANZ J Surg 2003;73:247-9.
12Sheybani F, Sarvghad M, Naderi HR, Gharib M. Treatment for and clinical characteristics of granulomatous mastitis. Obstet Gynecol 2015;125:801-7.
13Kessler E, Wolloch Y. Granulomatous mastitis: A lesion clinically simulating carcinoma. Am J Clin Pathol 1972;58:642-6.
14Diesing D, Axt-Fliedner R, Hornung D, Weiss JM, Diedrich K, Friedrich M, et al. Granulomatous mastitis. Arch Gynecol Obstet 2004;269:233-6.
15Naraynsingh V, Hariharan S, Dan D, Harnarayan P, Teelucksingh S. Conservative management for idiopathic granulomatous mastitis mimicking carcinoma: Case reports and literature review. Breast Dis 2010;31:57-60.
16Stary CM, Lee YS, Balfour J. Idiopathic granulomatous mastitis associated with Corynebacterium sp. Infection. Hawaii Med J 2011;70:99-101.
17Asoglu O, Ozmen V, Karanlik H, Tunaci M, Cabioglu N, Igci A, et al. Feasibility of surgical management in patients with granulomatous mastitis. Breast J 2005;11:108-14.
18Fletcher A, Magrath IM, Riddell RH, Talbot IC. Granulomatous mastitis: A report of seven cases. J Clin Pathol 1982;35:941-5.
19Lai EC, Chan WC, Ma TK, Tang AP, Poon CS, Leong HT, et al. The role of conservative treatment in idiopathic granulomatous mastitis. Breast J 2005;11:454-6.
20DeHertogh DA, Rossof AH, Harris AA, Economou SG. Prednisone management of granulomatous mastitis. N Engl J Med 1980;303:799-800.
21Hovanessian Larsen LJ, Peyvandi B, Klipfel N, Grant E, Iyengar G. Granulomatous lobular mastitis: Imaging, diagnosis, and treatment. AJR Am J Roentgenol 2009;193:574-81.