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Journal of Autoimmunity and Research

Breast Sarcoidosis: 3 Cases and Literature Review

Case Series | Open Access Volume 5 | Issue 1 |

  • 1. Department of Internal Medicine and Clinical Immunology, Groupe Hospitalier PitiéSalpêtrière, France
  • 2. Department of Inflammation-Immunopathology-Biotherapy, Sorbonne Universités, France
  • 3. Department of Neurology, France
  • 4. Departement of Gynecology, Hôpital Antoine Béclère, France
  • 5. INSERM, France
  • 6. CNRS, France
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Corresponding Authors
Abstract

Breast involvement in sarcoidosis is rare, reported in less than 1% of cases. We report 3 new cases of breast sarcoidosis and analyzed the 22 previously published cases. Breast involvement was the only manifestation of sarcoidosis in only three cases while breast sarcoidosis was the site of sarcoidosis at presentation in 12 cases. Sarcoidosis was multi-systemic in 45% of the 25 cases. Except in one case, physical examination revealed multiple breast masses without skin/nipple changes or lymphadenopathy. X-ray, ultrasound of the breasts showed multiple irregular and/or spiculated hypoechoic masses without micro calcifications. MRI showed mass with gadolinium enhancement. Treatments, rarely given for BS rather than sarcoidosis, included steroids and immunosuppressant therapy, usually showed a good efficacy in these series.

Citation

Chapelon-Abric C, Desbois AC, Dehais C, Barthier S, de Gennes C, et al. (2018) Breast Sarcoidosis: 3 Cases and Literature Review. J Autoimmun Res 5(1): 1031.

Keywords

•    Breast sarcoidosis; Breast malignancy; Sarcoidosis, 
FDG-PET-scan

INTRODUCTION

Sarcoidosis is a systemic granulomatous disease of unknown etiology which can affect any tissue in the body. Sarcoidosis mostly occurs in young adults, especially between 20 and 40 years [1]. This inflammatory disease is caused by alteration of cellular immune response after multiple factors i.e. environmental, occupational, and genetic and/or infections [2].The most frequent organs involved are lungs, lymph nodes, skin, eyes and liver. Sarcoidosis breast involvement is reported in less than 1%of cases although it is probably under-estimation due to non-systematic performance of mammography [3.4]. Malignancy must always be considered [5-7]. Breast sarcoidosis can be diagnosed during the follow up of carcinoma [3,6] or both diseases can be diagnosed concomitantly [8,9]. We here in report 3 new cases of breast sarcoidosis and review in depth 22 cases previously published in literature with English abstract) [4- 7; 10- 26].

CASE REPORT

Case 1

A 44-year-old Caribbean female with a multisystemic sarcoidosis (peripheral, thoracic and abdominal lymphadenopathy; pulmonary involvement; myelopathy and intracranial involvement was successfully treated by both prednisone (0.5 mg/kg/d) and subcutaneous methotrexate (0.3 mg/kg/week). Immunosuppressive therapy was progressively reduced to obtain in 2010 a maintenance dose regimen) prednisone 5 mg/d; hydroxychloroquine 400 mg/d). In June 2015, CT scan showed stable pulmonary changes. FDG PET scan demonstrated hypermetabolic activity of mediastinal (SUV max 3.7) and axillary (SUV max 3.7) lymphadenopathy and bilateral pulmonary condensation (SUV max 7.4). Of note, there was no breast hypermetabolism. A systematic mammography revealed cystic lesions of inferior quadrants of the left breast. Breast ultrasound showed bilateral ectasia of mammary duct associated with a left dense nodular lesion which was suggestive of bilateral breast cancer (ACR4 classification) .Pathology results of bilateral core biopsy showed a bilateral granulomatous inflammation consistent with sarcoidosis, without associated malignancy. The persistent pulmonary sarcoidosis activity was treated by prednisone (5 mg/d) and methotrexate (0.2 mg/week). In 2017, a clinical and morphologic relapse of sarcoidosis (central nervous system, pulmonary) was noted. FDG-PET-scan showed persisting bilateral breast hyper activity and abnormal pictures one chography (left hypoechoic lesion)/mammography (ill-defined mass with irregular contour) (right: ACR2; left ACR4) and MRI) breast hamartoma) (right: ACR2; left ACR3). She received for six months pulses of cyclophosphamide with no response. Then, she was treated by infliximab until March, 2018 (5mg/kg) when sarcoidosis remained quiescent with neither neurological nor pulmonary signs.

Case 2

In 1997, a 42-year-old Caribbean female presented a severe multi-systemic sarcoidosis with erythema nodosum, uveitis, severe lung infiltration, lymphadenopathy and liver involvement. Compliance to treatment revealed very poor for more than 5 years.

In 2005, she started a combination with prednisone (0.5 mg/ kg/d), mycophenolate mofetil (3gr/d), and monthly intravenous pulses of cyclophosphamide. A partial pulmonary and hepatic response was observed. After stopping cyclophosphamide, she was treated by infliximab (5mg/kg/8 weeks). Six months later, infliximab was withdrawn because of a paradoxical reaction (sarcoid lesions, biological inflammatory process, more severe hepatic disorders) and the patient status worsened. FDG-PETscan showed diffuse, severe, hypermetabolic activity on thoracic, abdominal and pelvic nodes (SUX max 5.5 to 15.8), liver (SUV max 6), lymphoid facial structure (SUV max 10.5), bones (SUV max 8.1) and left breast (SUV max 5.5). Mammography was normal. Due to the discovery of that breast hypermetabolism along a multi systemic and severe sarcoidosis relapse, without any mammographic abnormality, we did not consider adequate to request a breast biopsy and supposed that the breast hyper metabolism corresponded to BS. She was treated successfully by cyclophosphamide pulses with prednisone. Three years later, FDG-PET-scan showed a good persistent response on nodes, bones, and nasal localization; there was no more breast hypermetabolic activity.

A 57-year-old Maghrebian female was admitted for multisystemic sarcoidosis with skin (sarcoid lesion), nasal (nasal obstruction), salivary gland, joints (arthralgia), cervical nodes, stage II thoracic involvement and neurological signs migraines. Cerebral MRI revealed meningeal gadolinium enhancement. Physical exam revealed a non-inflammatory tumefaction in the upper outer quadrant of the left breast, without skin change. The echography/mammography revealed a lesion with irregular borders. Breast MRI showed a T2 enhancement with T1 hyposignal, associated with enhancement on gadolinium images. Breast biopsy showed non-caseating giant cell granulomas without element of breast cancer. She received prednisone (0.5 mg/kg/d) associated with methotrexate) 0.2 mg/kg/week). After 10 years-follow-up period, she presented a neurological relapse of the sarcoidosis; however, there was no relapse of breast granuloma and no appearance of breast cancer.

Literature review and discussion

Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology) [1]. Breast sarcoid involvement is rarely reported and always in women) [4-7, 10-26]. In our sarcoidosis’ series including 382 females, we observed 7 breast cancers (1.8%) and 3 breast sarcoidosis (0.8%), rates similar to those of the Lower’s series [3]. Main characteristics of our three cases and twenty-two cases found in the literature are detailed in Tables 1 and 2 [4-7, 10-26]. For the present study, we excluded cases with history of breast carcinoma and/or incidental finding of regional sarcoidosis-like reaction to the cancer in a breast removed for carcinoma as well as all differential diagnoses (Table 3). Of note, the comparative analysis revealed difficult to perform as cases were analyzed through either a pathological or radiological approach rather than clinical.

After review (Table 1) [4-7,10-26] (case 1-2-3), BS appears exceptional under 30 years, mean age at BS diagnosis is 47.84years (29-67) and in 59% (10/17) in black women [5,6,11,12,16,22,23,26](case 1 and 2). Breast involvement was the sole manifestation of sarcoidosis in only three cases [9,17,18], and BS revealed sarcoidosis in 50% of cases [4,17,23]. The most frequent sarcoidosis localizations associated with BS in 22 cases were thoracic in 81% of cases [stage I:6 cases; stage II: 8 cases; stage III: 4 cases) [5- 7, 10, 12, 13, 17- 21, 23-26] (case 1, 2 and 3), skin (23%) [11,14,18,22] (Case 2) and eyes (18%] [6,20] (case 2 and 3). Sarcoidosis was multi-systemic (≥ to 2 organs and/or hypercalcemia] in 45% of cases. Nodules, masses, and discomfort of breast revealed BS in 60% of cases with normal skin appearance [4-7,10-13,15,16-22,25] (case 3). Usually, physical examination revealed multiple unilateral or bilateral breast masses without skin/nipple changes or lymphadenopathy. Only 1 patient had extensive skin lesion with palpable in duration of left breast [25].

BS could also be discovered on systematic echo/ mammography (6 cases) [14.21,23,24,26] (case 1), or FDG-pet scan (case 2). The echographic lesion appears as an irregular hypoechoic mass (8/9 cases) [13,18-21,25,26] (case 3),or shows ectasia of mammary duct and dense nodular lesion [26] (case 1). Bilateral mammography performed in 17 cases was normal in 2 cases [12], (case 2), or demonstrate abnormal pictures in 10 cases such as unique [13,15,17-20,22-25] or multiple irregular and/or speculated masses [14,21]. Of note, micro calcifications are exceptional [23] as well as dilated duct [26]. MRI was rarely reported but it was always abnormal (4/4), showing irregular mass with gadolinium enhancement [13,18,19,25] (case 3). FDG-PET-scan can showed hyper metabolic breast lesion (as in our case 2), sometimes associated to sarcoidosis typical butterfly distribution pattern of hypermetabolic mediastinal and hilar lymphadenopathy [27] (case 2). As all imaging suggest malignancy, breast biopsies are mandatory to eliminate all differential diagnoses including carcinoma [Table 3]. In our case 2, once having eliminated differential diagnosis, we estimated appropriate to evoke a breast localization of sarcoidosis as breast hyper metabolism appeared simultaneously to a severe multi systemic flare up of the disease. Regression of hyper metabolism following immunosuppressive treatment confirmed our diagnosis.

In 2 cases, fine needle aspiration cytology demonstrates lymphocytes, epithelioid-like cells, aggregate histiocytes or/and reticulocytes without necrosis (17.24) and/ or core biopsy (10/10 cases) [14,15,19,21,22,24,25] (case 1 and 3), and/or excision (16/16 cases) [4-7,10,13,15-18,20,23,24]. In order to eliminate sarcoid-like reaction, clinical, laboratory and morphological investigations (Chest X ray, CT scan, FDG PET scan) must be consistent with a diagnosis of sarcoidosis. Typical histological pattern of sarcoidosis was noted in other organs than breast in 12 cases [5,6,7,11,13,14,24] (case 1, 2 and 3) or Kweim test alone [10,11]. Based on 14 cases with sufficient details, the mean follow up was 39.42 months (12 to 120). Among the 7 published cases who received steroids for their sarcoidosis, none relapsed from BS. However, in our 3 cases, despite immunosuppressive therapy, we did not observe regression of mammography abnormalities in two cases while we found a normalization of FDG-PET-scan in one case. In other published cases, BS was asymptomatic, with an indolent course and no therapy was required except excision. Breast localization of sarcoidosis was not an indication to immunosuppressive treatment. The latter was indicated for extra-breast severe localization of sarcoidosis which might compromise vital or functional prognosis. In those cases, corticosteroids were usually able to induce clinical and imaging improvement of BS [5,12,13,20,23-25] (case 1, 2 and 3). When BS is diagnosed, it is necessary to have regular follow up due to the possibility of coexisting BS and breast malignancy [3,5,10,30- 32]. Nevertheless, previous reports did not demonstrated any association between sarcoidosis and breast cancer [9,30].

Our three cases report and 22 previously published cases emphasize the possibility to observed BS, independently of breast carcinoma. Breast sarcoidosis remains a rare localization of sarcoidosis with diverse and nonspecific characteristics. Imaging features frequently mimic a breast cancer. Core biopsies are mandatory to confirm sarcoidosis and eliminate other diagnoses. In cases with localized BS, breast mass excision seems to be sufficient with no relapse of BS. Nevertheless, a prolonged breast follow-up is necessary in all cases.

Table 1: Main characteristics of patients with breast sarcoidosis.

  Ethnicity Age SS* (years) Age BS* (years) Manifestations of systemic sarcoidosis Positive biopsies for sarcoidosis ACE at BS* Treatment for sarcoidosis Follow up of BS (months)
Ridgen B (2) 1978 White 22 29 Unilateral linear shadowing, negative tuberculin test Breast ND 0 48
Ross MJ (3) 1983 Black 25 29 Stage I thoracic Kweim test ND Prednisone 48
Gansler TS (4) 1984, Case 1 Black 31 31 Stage II, lymph nodes, ocular Lymph node Pulmonary Breast ND ND ND
Fitzgibbons PL (5) 1985, Case 1 White 70 65 Stage I thoracic Lymph node ND 0 120
Fitzgibbons PL (5) 1985, Case 2 White 49 49 None Breast ND 0 ND
Banik S (8) 1986 White 28 29 Stage I thoracic, negative tuberculin test Kweim test high ND ND
McPherson (9) 1993 Black 54 64 Cutaneous, superior vena cava syndrome Kweim test, Cutaneous, Lymph node, Breast ND 0 60
Donaldson BA (10) 1995 Caribbean 44 44 Stage II thoracic, hypercalcemia Kweim test high Steroids ND
Kenzel PP (11) 1997 ND 55 61 Stage III thoracic, negative tuberculin test Bronchial normal prednisone 24
Gisvold JJ (12) 2000 ND 57 67 Cutaneous, cardiac Cutaneous ND ND ND
Harris KP (13) 2000 ND 53 53 None Breast normal 0 12
Ojeda H (14) 2000 Black 43 43 None Breast ND ND ND
Takahashi R (14) 2001 Japanese 48 48 Stage I thoracic Breast high ND 25
Ishimaru K (16) 2002 ND 26 31 Stage I thoracic, cutaneous, negative tuberculin test Breast normal 0 0
El Khoury M (17) 2005 ND 50 50 Stage III thoracic Breast ND 0 0
Fiorucci F (18) 2006 White 50 51 Stage II thoracic, uveitis Breast high Prednisone 0.5 mg/kg/d 20
Nicholson BT (19) 2007 ND ? 58 Stage III thoracic, pituitary Breast ND ND ND
Hermann G (20) 2008 Black 31 41 Cutaneous Breast ND 0 ND
Rishi MA (21) 2009 Black 31 39 Stage I thoracic Liver Breast ND Prednisone 12
Panzacchi R (22) 2010 ND 57 57 Stage II thoracic Trans bronchial biopsy high Steroids 15
ZujicPV (23) 2015 ND 54 54 Stage II thoracic High calcium level Breast high Prednisone 24
Mason C (24) 2017 Black 37 37 Stage II thoracic Breast ND 0 ND
Case 1 Caribbean 44 51 Stage II thoracic, central nervous system, salivary glands, diffuse lymphadenopathy Bronchial Lymphadenopathy Salivary glands, Nervous system High Prednisone: 5 mg/d + MTX 0.2 mg/ kg/wk; cyclophosphamide; infliximab 24
Case 2 Caribbean 42 58 Stage III thoracic, liver, ocular, cutaneous, nasal diffuse lymphadenopathy, poor general condition Bronchial, liver, Osteo-medullar Lymph node High Cyclophosphamide, Prednisone: 15 mg/d 12
*SS: systemic sarcoidosis; BS: breast sarcoidosis; ACE: angiotensin converting enzyme; MTX: methotrexate; ND, not determined

Table 2: Main characteristics of breast sarcoidosis.

  Age at BS* (years) BS detection Echography Mammography CT-scan/MRI Fine needle aspiration cytology Core biopsy/ excision
Ridgen B (2) 1978 29 Right breast nodule ND ND ND ND ND/+
Ross MJ (3) 1983 29 Two irregular non tender breast masses ND ND ND ND ND/+
Gansler TS (4) 1984, Case 1 31 Palpable nodule ND ND ND ND ND/+
Fitzgibbons PL (5) 1985, Case 1 65 Palpable nodule ND ND ND ND ND/+
Fitzgibbons PL (5) 1985, Case 2 49 Mass ND ND ND ND ND/+
Banik S (8) 1986 29 Smooth mobile lesion Normal Normal ND ND ND/+
McPherson (9) 1993 64 Firm breast left mass ND ND ND ND ND/+
Donaldson BA (10) 1995 44 Painless left breast masses, soft, non tender, movable ND ND ND ND ND/+
Kenzel PP (11) 1997 61 Mass Hypoechoic lesion, sharply outlined contours Ill-defined mass Hyper intense, inhomogeneous tissue, irregular contours early washout phase ND ND/+
Gisvold JJ (12) 2000 67 Systematic mammography ND Multiple non calcified spiculated bilateral nodules ND ND +/ND
Harris KP (13) 2000 53 Breast discomfort Localized nodule Normal Pronounced nodularity and architectural distortion ND ND +/+
Ojeda H (14) 2000 43 Mass ND ND ND - ND/+
Takahashi R (15) 2001 48 Painless right breast mass, soft movable mass ND Ill-defined mass without ND + ND/+
Ishimaru K (16) 2002 31 Mass Small, irregular hypoechoic lesion surrounded by echogenic rim Spiculated mass without calcifications Hyper intense with irregular border after gadolinium ND ND/+
El Khoury M (17) 2005 50 Palpable painless mass Hypoechoic lesion Mass with speculated margins. Intensely enhancing speculated mass ND +/ND
Fiorucci F (18) 2006 51 Palpable nodule Hypoechoic lesion Speculated left lesion ND ND ND/+
Nicholson BT (19) 2007 58 Mammography Multiple bilateral round ill-defined hypoechoic mass with hyperechoic rims Bilateral, round, ill defined equal density ND ND +/ND
Hermann G (20) 2008 41 Chest discomfort ND Asymmetric left breast density ND ND +/ND
Rishi M (21) 2009 39 Mammography ND Left breast microcalcifications ND ND ND/+
Panzacchi R (22) 2010 57 Mammography ND Suspicious left breast nodule ND + +/+
ZujicPV (23) 2015 54 Extensive skin lesion of left breast; palpable induration; pigmentation; axillary lymphadenopathy Hypoechoic lesion with thickened skin Parenchymal blurring fused within the pectoral muscle Extensive inflammatory changes of left breast;? infiltration of pectoral muscle; enlarged left axillary lymph ND +/ND
Mason C (24) 2017 37 Mammography Ill-defined hypoechoic lesion Single dilated duct of right breast ND ND +/ND
Case 1 51 Echography Bilateral ectasia of mammary ducts and dense nodular lesion Cystic lesions ND ND +/ND
Case 2 58 FDG- PET scan: intense hypermetabolic activity (SUV 10.5) ND Normal ND ND ND/ND
Case 3 57 Non inflammatory palpable tumefaction Hypoechoic lesion Nodular lesion T2 enhancement, Hyposignal T1, gadoliniumenhancement ND +/ND
*BS, breast sarcoidosis; MRI, magnetic resonance imaging; ND, not determined;

Table 3: Breast mass in sarcoidosis patients: differential diagnosis.

• Tuberculosis
• Leprosy
• Brucellosis
• Typhoid
• Blastomycosis
• Coccidioidomycosis
• Sporothrichosis
• Histoplasmosis
• Hydatid disease
• Cysticercosis
• Filariasis or oxyuris infestation
• Granulomatous mastitis
• Foreign-body
• Reaction from surgical procedures or substances introduced for cosmetic reasons

 

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Chapelon-Abric C, Desbois AC, Dehais C, Barthier S, de Gennes C, et al. (2018) Breast Sarcoidosis: 3 Cases and Literature Review. J Autoimmun Res 5(1): 1031.

Received : 16 Apr 2018
Accepted : 29 Jun 2018
Published : 30 Jun 2018
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ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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