Abstract
This case series reports the clinical presentation and course of treatment for 32 women with biopsy-proven idiopathic granulomatous mastitis.
Idiopathic (chronic) granulomatous mastitis (IGM) is a rare breast condition that may mimic bacterial abscesses, malignant neoplasms, and several other breast diseases. A thorough evaluation must be performed in suspected cases to exclude other causes, and heightened suspicion is necessary in diagnosing this often underrecognized condition.1,2 In this descriptive case series, we sought to better characterize the clinical presentation and to identify potentially successful therapies for IGM.
Methods
We consecutively enrolled women referred to our dermatology clinic for evaluation of biopsy-proven IGM from May 1, 2015, to April 30, 2019. No exclusion criteria were applied. This study was approved by the institutional review boards of NYU Langone Medical Center and Bellevue Hospital, both in New York, New York. Written informed consent was obtained from all patients before study inclusion.
Patient data were extracted on demographics, disease presentation, treatments, and clinical response. All patients underwent a comprehensive assessment, including a thorough review of systems and medical history, laboratory workup (including a blood test for tuberculosis [QuantiFERON-TB Gold; QIAGEN], prolactin levels, and angiotensin-converting enzyme levels), chest radiograph, mammogram, and breast ultrasonography with core biopsy (except for 1 patient who did not undergo biopsy because of pregnancy). Bacterial, fungal, and mycobacterial tissue cultures were obtained in all but 4 patients.
Diagnosis of IGM relied on exclusion of other causes through laboratory workup as well as characteristic clinical examination and histopathologic findings of cystic neutrophilic granulomatous mastitis. Clinical improvement was assessed through continued in-clinic evaluations by one or two of us (M.K.P. and A.N.F. [the senior authors]), review of medical records, and clinical photography. Treatment response was defined as partial response (improvement in all clinically significant symptoms, including pain, swelling, erythema, and induration) or complete response (complete resolution of the aforementioned symptoms). Treatment response was assessed at the initial visit (14 days after commencing therapy), 2 months into treatment, and approximately every 3 months afterward.
Results
Thirty-two women met the inclusion criteria (Table 1), and the mean (SD) age of these participants was 35.6 (5.5) years. Of these women, 26 (81%) were Hispanic, most of whom were from Mexico (15 [47%]).2 All cultures tested (n = 28) were negative for microorganisms (bacteria, fungi, or mycobacteria). Pain was present in all 32 patients and scarring in 22 (70%).
Table 1. Demographic and Clinical Characteristics.
| Characteristic | No. (%)a |
|---|---|
| All patients | 32 (100) |
| Age, mean (SD) [range], y | 35.6 (5.5) [25-48] |
| Race/ethnicity | |
| White | 0 |
| African American | 0 |
| Hispanic | 26 (81) |
| Asian | 5 (16) |
| Bangladeshi | 2 (6) |
| Chinese | 1 (3) |
| Malaysian | 1 (3) |
| Tibetan | 1 (3) |
| Other | 1 (3) |
| Ukranian | 1 (3) |
| Laboratory findings | |
| Elevated ESR | 12 (38) |
| Mean (SD), mm/h | 38 (13.5) |
| Elevated CRP level | 9 (28) |
| Mean (SD), mg/dL | 43.7 (31.5) |
| Elevated prolactin level | 3 (9) |
| With known prolactinoma | 1 (3) |
| Positive TB test result | 8 (25)b |
| Received TB treatment in childhood for 6-9 mo | 2 (6) |
| Received treatment for latent TB | 4 (13) |
| Tissue culture negative for mycobacterial infectionc | 7 (22) |
| Elevated ACE level or history of sarcoidosis | 0 |
| Microbiology findings | |
| Tissue culture negative for bacteria, fungi, or mycobacteria | 32 (100) |
| No. of patients | 28 (88) |
| Unobtained | 4 (13) |
| Became asymptomatic before tissue culture | 2 (6) |
| Lost to follow-up | 3 (9) |
| Was pregnant then breastfeeding | 1 (3) |
| Imaging findings | |
| Chest radiograph: normal | 32 (100) |
| Breast ultrasonography: ill-defined masslike areas, phlegmonous changes, increased density, and fluid collection | 32 (100) |
| Mammogram: focal asymmetry, skin thickening, scattered densities, masses, and abscesses | 32 (100) |
| Menstrual history | |
| Age at menarche | |
| Median (range), y | 13 (10-15) |
| Mean (SD), y | 12 (1.46) |
| Menstrual irregularities | 11 (34) |
| Current oral contraceptive use | 2 (6) |
| Current intrauterine device use | 1 (3) |
| Past oral contraceptive use | 9 (28) |
| Past intrauterine device use | 5 (1) |
| Breast trauma | 8 (25) |
| Time since most recent delivery | |
| ≤5 y | 20 (63) |
| >5 y | 7 (22) |
| Nulliparous | 3 (9) |
| Pregnant | 2 (6) |
| Time since most recent breastfeeding | |
| ≤5 y | 20 (63) |
| >5 y | 7 (22) |
| Nulliparous | 3 (9) |
| Never | 2 (6) |
| Total time breastfeeding | |
| Mean (SD), y | 2 (24) |
| Median (range), mo | 18 (0-120) |
| Pattern of disease | |
| Bilateral | 4 (13) |
| Unilateral | 21 (66) |
| Unilateral to bilateral | 7 (22) |
| Clinical presentation | |
| Pain | 32 (100) |
| Erythema | 22 (69) |
| Hyperpigmentation | 3 (9) |
| Induration | 18 (56) |
| Nodules | 20 (63) |
| Abscess | 4 (13) |
| Sinus tracts and/or drainage | 8 (25) |
| Ulceration | 6 (19) |
| Nipple inversion | 14 (44) |
Abbreviation: ACE, angiotensin-converting enzyme; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; TB, tuberculosis.
SI conversion factors: To convert CRP level to nanomoles per liter, multiply by 9.524; prolactin to picomoles per liter, multiply by 43.478.
Percentages do not sum to 100 because of rounding.
In addition, 1 patient was not treated, as it was deemed unnecessary per pulmonary/infectious disease, and 1 was lost to follow-up.
Tissue culture was not obtained on first biopsy, and patient did not undergo a second biopsy because she was asymptomatic.
Treatment and outcome information for all patients are shown in Table 2. The mean (SD) follow-up time was 14 (12.3) months. Three patients (9%) were lost to follow-up. Among the 29 remaining patients, 23 (79%) were treated with doxycycline, 100 mg twice daily; treatment failed for 6 (26%) of these patients, who required treatment with methotrexate sodium, usually starting at a test dose of 7.5 mg per week and escalating as needed. Among the 16 patients who responded to doxycycline therapy, 8 (50%) experienced complete response and 8 (50%) partial response. Of the 6 patients treated with methotrexate, 3 (50%) had a complete response and 3 (50%) a partial response. No patient received prednisone monotherapy.
Table 2. Patient Treatment and Outcome Information.
| Patient No.a | Treatment and Total Duration | Response | Corticosteroid Course | |||
|---|---|---|---|---|---|---|
| Initial | 6 mo | 12 mo | Final | |||
| 1 | Prednisone 5 mo | PR; prednisone and doxycycline | PR; methotrexate | PR; methotrexate D/C owing to liver enzyme elevation; receiving doxycycline | CR; no Rx | 2 Courses with flares |
| Doxycycline, 9 mo | ||||||
| Methotrexate sodium, 8 mo | ||||||
| 3 | Prednisone, 4 mo | None; prednisone and doxycycline | None; methotrexate | Not seenb | CR; no Rx | 1 Course |
| Doxycycline, 55 mo | ||||||
| Methotrexate 15 mo | ||||||
| 4 | Prednisone, 14 mo | None; prednisone | PR; prednisone, methotrexate, and doxycycline | PR; prednisone and methotrexate | CR; no Rx | 1 Course |
| Doxycycline, 2 mo | ||||||
| Methotrexate, 16 mo | ||||||
| 5 | Doxycycline, 3 mo | Not seenb | Not seenb | Not seenb | PR; no Rx | NA |
| 6 | Prednisone, 15 mo | None; prednisone and doxycycline | PR; methotrexate and prednisone | PR; methotrexate and prednisone | PR; methotrexate | 1 Course |
| Doxycycline, 3 mo | ||||||
| Methotrexate, 28 mo | ||||||
| 7 | Prednisone, 2 mo | PR; doxycycline | PR; methotrexate, colchicine, and prednisone | PR; no Rx | CR; no Rx | 1 Course |
| Doxycycline, 7 mo | ||||||
| Methotrexate, 7 mo | ||||||
| Augmentin, 14 d | ||||||
| Colchicine, 6 mo | ||||||
| 8 | Prednisone, 8 mo | PR; prednisone and doxycycline | PR; prednisone and ibuprofen | PR; doxycycline and ibuprofen | PR; doxycycline and ibuprofen | 3 Courses with flares |
| Doxycycline, 11 mo | NA | NA | NA | NA | ||
| Ibuprofen, 13 mo | NA | NA | NA | NA | ||
| 9 | Prednisone, 2 mo | None; prednisone and doxycycline | Not seenb | Not seenb | PR; no Rx | 1 Course |
| Doxycycline, 3 mo | ||||||
| 10 | None (disease quiescent) | Not seenb | Not seenb | Not seenb | CR; no Rx | NA |
| 11 | Prednisone, 3 wk | PR; doxycycline | PR; methotrexate | PR; methotrexate (+ prednisone for 3 wk before) | PR; methotrexate | 1 Course |
| Doxycycline, 3 mo | NA | NA | NA | NA | ||
| Methotrexate, 12 mo | NA | NA | NA | NA | ||
| 12 | Doxycycline, 4 mo | PR; doxycycline | CR; No Rx | Not seenb | CR; no Rx | NA |
| 13 | Doxycycline, 6 mo | None; indomethasin | PR; doxycycline and indomethasin | PR; no Rx | CR; no Rx | NA |
| Indomethacin sodium, 7 mo | ||||||
| Rifampin, 4 wk (for latent TB) | ||||||
| 14 | Prednisone, 1 mo | PR; prednisone and doxycycline | PR; no Rx | Not seenb | PR; no Rx | 1 Course |
| Doxycycline, 4 mo | ||||||
| Rifampin, 4 wk (for latent TB) | ||||||
| 15 | Doxycycline, 12 mo | Not seenb | Not seenb | CR; Doxycycline | CR; no Rx | NA |
| 16 | Prednisone, 3 mo | None; prednisone | PR; prednisone and methotrexate | CR; prednisone, methotrexate, and doxycycline | CR; no Rx | 3 Courses with flares |
| Doxycycline, 3 mo | ||||||
| Methotrexate, 5 mo | ||||||
| 17 | Ibuprofen, 5 mo | None; ampicillin | PR; ibuprofen | CR; no Rx | CR; no Rx | NA |
| Ampicillin, sodium 1 mo | ||||||
| 18 | Doxycycline, 7 mo | Not seenb | PR; doxycycline | CR; no Rx | CR; no Rx | NA |
| 19 | Minocycline hydrochloride, 9 mo | Not seenb | PR; minocycline | CR; no Rx | CR; no Rx | NA |
| 20 | Doxycycline, 3 mo | PR; doxycycline | Not seenb | Not seenb | PR; no Rx; | NA |
| 21 | None | Not seenb | CR; No Rx | CR; no Rx | CR; no Rx | NA |
| 22 | Ibuprofen, 3 mo | Not seenb | None; (ibuprofen in interim for 3 mo) | Not seenb | None | NA |
| 23 | Prednisone, 3 wk | None; amoxicillin | PR; doxycycline (prednisone and ibuprofen in interim) | Not seenb | PR; no Rx | 1 Course |
| Doxycycline, 2 mo | ||||||
| Ibuprofen, 4 mo | ||||||
| Amoxicillin, 2 wk | ||||||
| 24 | Doxycycline, 4 mo | PR; ibuprofen | PR; ibuprofen and doxycycline | CR; ibuprofen and doxycycline | CR; ibuprofen and doxycycline | NA |
| Ibuprofen, 12 mo | ||||||
| 25 | Doxycycline, 2 mo | Not seenb | None; ibuprofen | Not seenb | PR; doxycycline | NA |
| Ibuprofen, 4 mo | ||||||
| 26 | Doxycycline, 6 mo | PR; ibuprofen and doxycycline | PR; ibuprofen and doxycycline (intermittent adherence) | PR; ibuprofen and doxycycline; (intermittent adherence) | PR; doxycycline | NA |
| Ibuprofen, 6 mo | ||||||
| 27 | Doxycycline, 3 mo | Not seenb | CR; no Rx; (doxycycline in interim) | Not seenb | CR; no Rx | NA |
| 28 | Prednisone, 6 mo | PR; prednisone | PR; colchicine and methylprednisolone | PR; colchicine, solumedrol, and ibuprofen | PR; colchicine and ibuprofen | Continuous corticosteroids because patient was pregnant |
| Methylprednisolone, 4 mo | ||||||
| Solumedrol, 3 mo | ||||||
| Colchicine, 4 mo | ||||||
| Ibuprofen, 3 mo | ||||||
| 29 | Doxycycline, 6 mo | Not seenb | PR; doxycycline | CR; no rx | CR; no Rx | NA |
| 31 | Doxycycline, 3 mo | Not seenb | CR; No Rx (doxycycline in interim) | Not seenb | CR; no Rx | NA |
| Response totals | ||||||
| No response | 7 (24.1) | 3 (10.3) | 0 | 1 (3.4) | ||
| Partial response | 11 (37.9) | 17 (58.6) | 9 (31) | 12 (41.4) | ||
| Complete response | NA | 4 (13.8) | 7 (24.1) | 17 (58.6)c | ||
| Not seenb | 11 (37.9) | 5 (17.2) | 13 (44.8) | NA | ||
Abbreviations: CR, complete response; D/C, discontinued; NA, not applicable; No Rx, no prescription/treatment; PR, partial response; TB, tuberculosis.
Data available for 29 patients; 3 patients lost to follow-up.
Not seen: no appointment within stated time frame.
Two patients with complete response self-resolved.
The mean (SD) lengths of treatment were 4.6 (2.7) months for patients receiving doxycycline, 12.5 (8.4) months for those receiving methotrexate, and 4.8 (4.4) months for those receiving prednisone. Among the 12 women treated with prednisone, most required only 1 course and 3 (25%) required multiple courses.
Discussion
This case series of patients with IGM, uniquely conducted within a dermatology clinic, involved a relatively large sample compared with the 5 other studies on granulomatous mastitis conducted within the United States.2,3,4,5 Consistent with findings in the existing literature, IGM occurred predominantly in Hispanic women of childbearing age, although conclusions regarding the demographic distribution of IGM could not be reached in this single-center study. The present study supports the concern that IGM has major implications for quality of life, with a high prevalence of pain and scarring. We found that treatment with doxycycline, 100 mg twice daily, was successful as a first-line therapy, with complete response in 50% of patients in the present study.6 Corticosteroid courses in this study were short compared with those in previous studies, which have noted frequent 6- to 12-month courses.2 Methotrexate appeared to be a successful second-line therapy in patients with disease that was refractory to doxycycline (complete response in 50%). Although surgical therapy for IGM has been suggested in the literature, no patient in this study required a surgical procedure, suggesting that adequate medical management may alleviate the need for surgical intervention.
This study highlighted the advantage of dermatologic care for this rare condition. Limitations of this study included its single-institution observational design, lack of a validated outcome measure for IGM, and a relatively small sample size; however, to our knowledge, among the US studies on IGM, this sample was the largest. Furthermore, all patients were evaluated and treated by the same clinicians, who directed a standardized diagnostic workup and treatment algorithm. Further study of IGM is warranted.
References
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