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Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment
G Model JIPH-1187; No. of Pages 3
ARTICLE IN PRESS Journal of Infection and Public Health xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph
Short Report
Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment Cennet Sahin, Burcin Agridag Ucpinar ∗ Radiology Department, SUAM Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, 34373, Turkey
a r t i c l e
i n f o
Article history: Received 26 January 2019 Received in revised form 29 April 2019 Accepted 16 September 2019 Keywords: Biopsy Imaging Idiopathic granulomatous mastitis Male breast cancer
a b s t r a c t Idiopathic granulomatous mastitis (IGM) is a benign chronic inflammatory disorder of the breast tissue, with unknown etiology. IGM is extremely rare among male gender. In this case report, we present a male patient with superficial high grade bladder cancer, who was complaining of a palpable mass in his right breast for two weeks following intravesical Bacillus Calmette–Guerin (BCG) treatment. There was an assymetrical, mass-like density without distinct contours in retroareolar area of the right breast. US guided core-needle biopsy was performed. Histopathology confirmed the diagnosis of IGM. To our knowledge, this is the first case of IGM following intravesical BCG administration. © 2019 Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Introduction
Case history
Idiopathic granulomatous mastitis is a rarely encountered benign chronic inflammatory disorder of the breast tissue, with unknown etiology. It was first described by Kessler and Wolloch et al. in 1972 [1]. Since the etiology is unknown, diagnosis is made by exclusion. The disease mostly affects parous women and patients mostly present with a palpable breast mass, which can mimic breast cancer clinically [2]. Possible underlying causes include; autoimmunity, oral contraceptives, hyperprolactinemia, breastfeeding, smoking, diabetes mellitus, alpha-1 antitrypsin deficiency and lactation. Diagnosis is achieved by histological examination and exclusion of other possible causes [2,3]. IGM is extremely rare among male gender and there are only 3 reported male cases in the literature [4–6]. In this case presentation, we present a case of idiopathic granulomatous mastitis in a male patient with superficial high grade bladder cancer, following intravesical Bacillus Calmette Guerin (BCG) treatment. To our knowledge, this is the first case of IGM following intravesical BCG administration.
A 49 year old male patient was admitted to the general surgery outpatient clinic, complaining of a palpable mass in his right breast for two weeks. He had no history of specific infection such as tuberculosis (TB) and he denied any systemic symptoms. His previous vaccination history for TB was unknown.The patient’s past medical history was unremarkable. He had a smoking history of 20 pack year. He was diagnosed with high grade non-muscle invasive (T1) bladder cancer 6 months prior to his current admission. He underwent transurethral resection (TUR) for a 3 cm bladder mass and a re-TUR was performed 4 weeks later and pathology results revealed no evidence of residual tumor. Thereby, intravesical BCG treatment was initiated and patient completed 6 cycles of induction and 3 cycles of maintenance intravesical BCG instillations. Routine cystoscopic examinations revealed no recurrent mass in the bladder. He had his final BCG treatment 10 days prior to his admission. On physical examination, a mass was palpated in the right breast without any accompanying skin change by inspection.Mammography revealed a nodular opacity in the retroareolar area, which was confirmed by ultrasonography as a 13 × 13 × 6 mm in diameter, hypoechoic mass with irregular borders (Figs. 1 and 2). Tru-cut biopsy was performed by an interventional radiologist and pathology results revealed non-caseating and non-necrotizing chronic granulomatous mastitis (Fig. 3). The Ziehl–Neelsen and auromain–rodamin stain for acid-fast bacteria were negative and ‘Polymerase Chain Reaction’ (PCR) of the obtained sample was negative for either Mycobacterium tuberculosis or Mycobacterium bovis.
∗ Corresponding author. E-mail addresses: [email protected] (C. Sahin), [email protected] (B. Agridag Ucpinar).
https://doi.org/10.1016/j.jiph.2019.09.006 1876-0341/© 2019 Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Sahin C, Agridag Ucpinar B. Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.09.006
G Model JIPH-1187; No. of Pages 3 2
ARTICLE IN PRESS C. Sahin, B. Agridag Ucpinar / Journal of Infection and Public Health xxx (2019) xxx–xxx
Fig. 1. Mammographic imaging. Asymmetrical, mass-like density without distinct contours in the retroareolar area of the right breast (arrows) on CC and MLO projections.
Discussion
Fig. 2. Ultrasonographic examination. Hypoechoic mass with irregular borders is shown in the retroareolar area of the right breast.
Fig. 3. Granulomatous mastitis: hematoxylin and eosin stain (H&E); ×100 magnification demonstrating periductal inflammation and granuloma formation in the backround of diffuse lympho-histiocytic infiltration (long arrow) with giant cells (short arrow) (inset 200×).
All blood cultures (Mycobacterial culture was performed) and urine cultures were negative either. Since the focal symptoms were mild without abscess formation and skin involvement and there were no systemic symptoms like fever or fatigue, follow-up without any medication or surgical management was decided for the patient. The patient was advised to come to the outpatient clinic if his symptoms got worse. On the next follow up 6 months later, patient had no complaint with his breast. On ultrasonographic examination, the mass was 4 × 6 × 6 mm in diameter and barely smaller in size than before. There was no accompanying skin erythema and abscess or fistula formation.
Intravesical ‘Bacillus Calmette Guerin’ therapy was first used effectively in the treatment of superficial transitional bladder carcinoma by Morales at al. in 1976 [7]. BCG is a viable strain of virulent M. bovis. The mechanism of action of BCG has been projected that BCG firstly was internalized by malignant epithelial cells followed by class II major histocompatibility complex overexpression by inflammated cells. BCG and other tumour specific antigens are presented to killer T-cells and T-cell mediated cytotoxicity to malignant cells are provoked. The underlying mechanism of complications after BCG instillations is unclear but both the inflammatory and infectious processes are thought to be responsible [8]. In our case, triggered systematic immune response was thought to induce IGM, since no evidence of Mycobacterium species was identified in tissue and blood samples. Intravesical BCG instillations have a broad range of complications presented as either focal complications in the genitourinary tract such as granulomatous prostatitis, chemical or bacterial cystitis, persistent hematuria or focal complications outside the genitourinary tract such as arthritis and mycotic aneurysm, or systemic complications like persistent high grade fever, pneumonitis with or without hepatitis and sepsis [8]. Risk factors of BCG associated complications include traumatized catheterization, instillation of repeated dose in patients with persistent local side effects and BCG instillation within the 14 days after TUR [8]. In our case, BCG instillation was performed approximately 1 month after TUR. Patients with IGM generally admits with a unilateral firm breast lump. Local pain, skin ulcerations, nipple retraction, abscess and fistula formation may accompany and these findings may mimic breast cancer, clinically [4]. Four possible underlying mechanisms were described by Bani-Hani et al. including; a chemical reaction due to oral contraceptives, autoimmune process, infectious etiology that can’t be detected and immune response to extravasated secretions which damages the ductal epithelium [9]. Mammographic and sonographic findings of IGM are described previously. Main mammographic finding is an asymmetrically increased density, without distinct contours. Additionally, mass lesion with distinct margins and small, multiple masses without microcalcifications have been reported. Mammography may also be totally normal in case of dense breast tissue [4,10]. The histopathologic diagnosis of IGM was made when smears prepared show noncaseating non-vasculitic granulomatous reaction with epithelioid cells, lymphocytes, giant cells that involve mainly the breast lobules. The absence of necrosis and mostly neutrophilic infiltrate suggests a diagnosis of granulomatous mastitis [3]. Treatment of IGM should be initiated after exclusion of infective causes. It involves non-surgical management including surveillance, corticosteroids and other immunosuppressive
Please cite this article in press as: Sahin C, Agridag Ucpinar B. Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.09.006
G Model JIPH-1187; No. of Pages 3
ARTICLE IN PRESS C. Sahin, B. Agridag Ucpinar / Journal of Infection and Public Health xxx (2019) xxx–xxx
agents including methotrexate or azathioprine, in case of refractory disease. If no regression is observed during surveillance or disease becomes symptomatic, corticosteroids should be initiated, by tapering the dose gradually. In case of recurrent disease besides all non-surgical management options, surgical excision can be considered as an option, as well. Although complete response can be achieved after appropriate application of treatment strategies, recurrence is common and patients should be closely followed [2]. In conclusion, IGM is an extremely rare disease among male population, that there are 3 reported cases in the medical literature. When there is a palpable mass in the male breast, inflammatory breast conditions like IGM should be kept in mind as a differential diagnosis in patients with a history of intravesical BCG instillations in the treatment of bladder cancer. Funding No funding sources. Competing interests None declared. Ethical approval Not required.
3
Acknowledgement We would like to extend thanks to Canan Tanık for her valuable contributions in sharing microphotographies of pathology specimens. References [1] Kessler E, Wolloch Y. Granulomatous mastitis: a lesion clinically simulating carcinoma. Am J Clin Pathol 1972;58(December (6)):642–6. [2] Altintoprak F, Kivilcim T, Ozkan OV. Aetiology of idiopathic granulomatous mastitis. World J Clin Cases 2014;2(December (12)):852–8. [3] Kamra Hemlata T, Munde Santosh L, Rana Parveen, Kaur Swarn, Singh Kulwant, Duhan Amrita. Cytological features of granulomatous mastitis—a study of ten cases. Indian J Pathol Oncol 2016;3(January–March (1)):129–32. [4] Leehi J, Soo Hyun Y, Sun Young K. Idiopathic granulomatous lobular mastitis in a male breast: a case report. Iran J Radiol 2018;15(July (3)):e55996. [5] Al Manasra ARA, Al-Hurani MF. Granulomatous mastitis: a rare cause of male breast lump. Case Rep Oncol 2016;9:516–9. [6] Marcus Reddy K, Meyer Carl ER, Amir N, Sunita S. Idiopathic granulomatous mastitis in the male breast. Breast J 2005;11(January–February (1)):73. [7] Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976;116(August (2)):180–3. [8] Bilsen MP, van Meijgaarden KE, de Jong HK, Joosten SA, Prins C, Kroft LJM, et al. A novel view on the pathogenesis of complications after intravesical BCG for bladder cancer. Int J Infect Dis 2018;72(July):63–8. [9] Bani-Hani KE, Yaghan RJ, Matalka II, Shatnawi NJ. Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies. Breast J 2004;10(July–August (4)):318–22. [10] Ozturk M, Mavili E, Kahriman G, Akcan AC, Ozturk F. Granulomatous mastitis: radiological findings. Acta Radiol 2007;48(March (2)):150–5.
Please cite this article in press as: Sahin C, Agridag Ucpinar B. Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.09.006
ARTICLE IN PRESS Journal of Infection and Public Health xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph
Short Report
Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment Cennet Sahin, Burcin Agridag Ucpinar ∗ Radiology Department, SUAM Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, 34373, Turkey
a r t i c l e
i n f o
Article history: Received 26 January 2019 Received in revised form 29 April 2019 Accepted 16 September 2019 Keywords: Biopsy Imaging Idiopathic granulomatous mastitis Male breast cancer
a b s t r a c t Idiopathic granulomatous mastitis (IGM) is a benign chronic inflammatory disorder of the breast tissue, with unknown etiology. IGM is extremely rare among male gender. In this case report, we present a male patient with superficial high grade bladder cancer, who was complaining of a palpable mass in his right breast for two weeks following intravesical Bacillus Calmette–Guerin (BCG) treatment. There was an assymetrical, mass-like density without distinct contours in retroareolar area of the right breast. US guided core-needle biopsy was performed. Histopathology confirmed the diagnosis of IGM. To our knowledge, this is the first case of IGM following intravesical BCG administration. © 2019 Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Introduction
Case history
Idiopathic granulomatous mastitis is a rarely encountered benign chronic inflammatory disorder of the breast tissue, with unknown etiology. It was first described by Kessler and Wolloch et al. in 1972 [1]. Since the etiology is unknown, diagnosis is made by exclusion. The disease mostly affects parous women and patients mostly present with a palpable breast mass, which can mimic breast cancer clinically [2]. Possible underlying causes include; autoimmunity, oral contraceptives, hyperprolactinemia, breastfeeding, smoking, diabetes mellitus, alpha-1 antitrypsin deficiency and lactation. Diagnosis is achieved by histological examination and exclusion of other possible causes [2,3]. IGM is extremely rare among male gender and there are only 3 reported male cases in the literature [4–6]. In this case presentation, we present a case of idiopathic granulomatous mastitis in a male patient with superficial high grade bladder cancer, following intravesical Bacillus Calmette Guerin (BCG) treatment. To our knowledge, this is the first case of IGM following intravesical BCG administration.
A 49 year old male patient was admitted to the general surgery outpatient clinic, complaining of a palpable mass in his right breast for two weeks. He had no history of specific infection such as tuberculosis (TB) and he denied any systemic symptoms. His previous vaccination history for TB was unknown.The patient’s past medical history was unremarkable. He had a smoking history of 20 pack year. He was diagnosed with high grade non-muscle invasive (T1) bladder cancer 6 months prior to his current admission. He underwent transurethral resection (TUR) for a 3 cm bladder mass and a re-TUR was performed 4 weeks later and pathology results revealed no evidence of residual tumor. Thereby, intravesical BCG treatment was initiated and patient completed 6 cycles of induction and 3 cycles of maintenance intravesical BCG instillations. Routine cystoscopic examinations revealed no recurrent mass in the bladder. He had his final BCG treatment 10 days prior to his admission. On physical examination, a mass was palpated in the right breast without any accompanying skin change by inspection.Mammography revealed a nodular opacity in the retroareolar area, which was confirmed by ultrasonography as a 13 × 13 × 6 mm in diameter, hypoechoic mass with irregular borders (Figs. 1 and 2). Tru-cut biopsy was performed by an interventional radiologist and pathology results revealed non-caseating and non-necrotizing chronic granulomatous mastitis (Fig. 3). The Ziehl–Neelsen and auromain–rodamin stain for acid-fast bacteria were negative and ‘Polymerase Chain Reaction’ (PCR) of the obtained sample was negative for either Mycobacterium tuberculosis or Mycobacterium bovis.
∗ Corresponding author. E-mail addresses: [email protected] (C. Sahin), [email protected] (B. Agridag Ucpinar).
https://doi.org/10.1016/j.jiph.2019.09.006 1876-0341/© 2019 Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Sahin C, Agridag Ucpinar B. Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.09.006
G Model JIPH-1187; No. of Pages 3 2
ARTICLE IN PRESS C. Sahin, B. Agridag Ucpinar / Journal of Infection and Public Health xxx (2019) xxx–xxx
Fig. 1. Mammographic imaging. Asymmetrical, mass-like density without distinct contours in the retroareolar area of the right breast (arrows) on CC and MLO projections.
Discussion
Fig. 2. Ultrasonographic examination. Hypoechoic mass with irregular borders is shown in the retroareolar area of the right breast.
Fig. 3. Granulomatous mastitis: hematoxylin and eosin stain (H&E); ×100 magnification demonstrating periductal inflammation and granuloma formation in the backround of diffuse lympho-histiocytic infiltration (long arrow) with giant cells (short arrow) (inset 200×).
All blood cultures (Mycobacterial culture was performed) and urine cultures were negative either. Since the focal symptoms were mild without abscess formation and skin involvement and there were no systemic symptoms like fever or fatigue, follow-up without any medication or surgical management was decided for the patient. The patient was advised to come to the outpatient clinic if his symptoms got worse. On the next follow up 6 months later, patient had no complaint with his breast. On ultrasonographic examination, the mass was 4 × 6 × 6 mm in diameter and barely smaller in size than before. There was no accompanying skin erythema and abscess or fistula formation.
Intravesical ‘Bacillus Calmette Guerin’ therapy was first used effectively in the treatment of superficial transitional bladder carcinoma by Morales at al. in 1976 [7]. BCG is a viable strain of virulent M. bovis. The mechanism of action of BCG has been projected that BCG firstly was internalized by malignant epithelial cells followed by class II major histocompatibility complex overexpression by inflammated cells. BCG and other tumour specific antigens are presented to killer T-cells and T-cell mediated cytotoxicity to malignant cells are provoked. The underlying mechanism of complications after BCG instillations is unclear but both the inflammatory and infectious processes are thought to be responsible [8]. In our case, triggered systematic immune response was thought to induce IGM, since no evidence of Mycobacterium species was identified in tissue and blood samples. Intravesical BCG instillations have a broad range of complications presented as either focal complications in the genitourinary tract such as granulomatous prostatitis, chemical or bacterial cystitis, persistent hematuria or focal complications outside the genitourinary tract such as arthritis and mycotic aneurysm, or systemic complications like persistent high grade fever, pneumonitis with or without hepatitis and sepsis [8]. Risk factors of BCG associated complications include traumatized catheterization, instillation of repeated dose in patients with persistent local side effects and BCG instillation within the 14 days after TUR [8]. In our case, BCG instillation was performed approximately 1 month after TUR. Patients with IGM generally admits with a unilateral firm breast lump. Local pain, skin ulcerations, nipple retraction, abscess and fistula formation may accompany and these findings may mimic breast cancer, clinically [4]. Four possible underlying mechanisms were described by Bani-Hani et al. including; a chemical reaction due to oral contraceptives, autoimmune process, infectious etiology that can’t be detected and immune response to extravasated secretions which damages the ductal epithelium [9]. Mammographic and sonographic findings of IGM are described previously. Main mammographic finding is an asymmetrically increased density, without distinct contours. Additionally, mass lesion with distinct margins and small, multiple masses without microcalcifications have been reported. Mammography may also be totally normal in case of dense breast tissue [4,10]. The histopathologic diagnosis of IGM was made when smears prepared show noncaseating non-vasculitic granulomatous reaction with epithelioid cells, lymphocytes, giant cells that involve mainly the breast lobules. The absence of necrosis and mostly neutrophilic infiltrate suggests a diagnosis of granulomatous mastitis [3]. Treatment of IGM should be initiated after exclusion of infective causes. It involves non-surgical management including surveillance, corticosteroids and other immunosuppressive
Please cite this article in press as: Sahin C, Agridag Ucpinar B. Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.09.006
G Model JIPH-1187; No. of Pages 3
ARTICLE IN PRESS C. Sahin, B. Agridag Ucpinar / Journal of Infection and Public Health xxx (2019) xxx–xxx
agents including methotrexate or azathioprine, in case of refractory disease. If no regression is observed during surveillance or disease becomes symptomatic, corticosteroids should be initiated, by tapering the dose gradually. In case of recurrent disease besides all non-surgical management options, surgical excision can be considered as an option, as well. Although complete response can be achieved after appropriate application of treatment strategies, recurrence is common and patients should be closely followed [2]. In conclusion, IGM is an extremely rare disease among male population, that there are 3 reported cases in the medical literature. When there is a palpable mass in the male breast, inflammatory breast conditions like IGM should be kept in mind as a differential diagnosis in patients with a history of intravesical BCG instillations in the treatment of bladder cancer. Funding No funding sources. Competing interests None declared. Ethical approval Not required.
3
Acknowledgement We would like to extend thanks to Canan Tanık for her valuable contributions in sharing microphotographies of pathology specimens. References [1] Kessler E, Wolloch Y. Granulomatous mastitis: a lesion clinically simulating carcinoma. Am J Clin Pathol 1972;58(December (6)):642–6. [2] Altintoprak F, Kivilcim T, Ozkan OV. Aetiology of idiopathic granulomatous mastitis. World J Clin Cases 2014;2(December (12)):852–8. [3] Kamra Hemlata T, Munde Santosh L, Rana Parveen, Kaur Swarn, Singh Kulwant, Duhan Amrita. Cytological features of granulomatous mastitis—a study of ten cases. Indian J Pathol Oncol 2016;3(January–March (1)):129–32. [4] Leehi J, Soo Hyun Y, Sun Young K. Idiopathic granulomatous lobular mastitis in a male breast: a case report. Iran J Radiol 2018;15(July (3)):e55996. [5] Al Manasra ARA, Al-Hurani MF. Granulomatous mastitis: a rare cause of male breast lump. Case Rep Oncol 2016;9:516–9. [6] Marcus Reddy K, Meyer Carl ER, Amir N, Sunita S. Idiopathic granulomatous mastitis in the male breast. Breast J 2005;11(January–February (1)):73. [7] Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976;116(August (2)):180–3. [8] Bilsen MP, van Meijgaarden KE, de Jong HK, Joosten SA, Prins C, Kroft LJM, et al. A novel view on the pathogenesis of complications after intravesical BCG for bladder cancer. Int J Infect Dis 2018;72(July):63–8. [9] Bani-Hani KE, Yaghan RJ, Matalka II, Shatnawi NJ. Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies. Breast J 2004;10(July–August (4)):318–22. [10] Ozturk M, Mavili E, Kahriman G, Akcan AC, Ozturk F. Granulomatous mastitis: radiological findings. Acta Radiol 2007;48(March (2)):150–5.
Please cite this article in press as: Sahin C, Agridag Ucpinar B. Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette–Guerin treatment. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.09.006