In the past few decades, a histologically and microbiologically distinct form of mastitis has been identified and named “cystic neutrophilic granulomatous mastitis” (CNGM) [2, 6]. It is recognized based on its microscopic features and strong association with Corynebacteria species. CNGM is an uncommon condition that typically occurs in parous, reproductive-aged women, often presenting with breast mass lesion or breast pain. The clinical and imaging features can simulate malignancy.  Previously, many histologically proven cases of granulomatous lobular mastitis have been termed “idiopathic,”  and treated empirically with a variety of modalities, from surgery to antimicrobials, steroids, and combinations.  Studies have shown a good clinical response to antibiotic therapy tailored to Corynebacteria species, such as long courses of tetracycline or doxycycline. [4, 5] Recent studies showed CNGM cases were more prevalent in women of childbearing age, Hispanic women and those with a birthplace outside of the United States. This suggests a common genetic, environmental, immunologic, or infectious etiology. [7-9]
In CNGM, biopsies are typically done to rule out breast cancer. Once malignancy is ruled out, the main differential diagnoses are other types of infectious mastitis such as tuberculosis (TB) mastitis. Specimens showing granulomatous mastitis should be carefully analyzed for fungal, mycobacterial and bacterial organisms, especially microcystic spaces on Gram stain.  Microscopic identification of Corynebacteria in patients with CNGM can be challenging, as the number of identifiable organisms is usually very low and limited to the cystic vacuoles. In addition, microorganisms may be obscured by inflammatory debris. Culture can be diagnostically helpful, but Corynebacteria rods can be difficult to isolate as some species require special cultural media. [2, 6]. The most common isolates were identified as Corynebacterium kroppenstedtii. Sequencing of tissue can also be helpful when available. Recognizing the distinct histologic pattern is the key to the diagnosis and management of this disease. CNGM is characterized by lobulocentric granulomatous inflammation. The cystic spaces are stained positive for oil red O which is consistent with dissolved lip vacuoles. Corynbacterium tend to be identified in the cystic empty space due to its lipophilic feature. Subareolar breast abscesses can mimic CNGM due to their similar the clinical presentation and histology. Subareolar abscesses are considered a consequence of lactiferous duct obstruction by keratin debris and are strongly associated with cigarette smoking. Foreign body giant cell reactions to keratin may be seen in subareolar abscesses but there are no suppurative lipogranulomas as those in CNGM.
1. D'Alfonso, T.M., et al., Cystic Neutrophilic Granulomatous Mastitis: Further Characterization of a Distinctive Histopathologic Entity Not Always Demonstrably Attributable to Corynebacterium Infection. Am J Surg Pathol, 2015. 39(10): p. 1440-7.
2. Gautham, I., et al., Cystic neutrophilic granulomatous mastitis: The Cleveland Clinic experience with diagnosis and management. Breast J, 2019. 25(1): p. 80-85.
3. Troxell, M.L., et al., Cystic Neutrophilic Granulomatous Mastitis: Association With Gram-Positive Bacilli and Corynebacterium. Am J Clin Pathol, 2016. 145(5): p. 635-45.
4. Renshaw, A.A., R.P. Derhagopian, and E.W. Gould, Cystic neutrophilic granulomatous mastitis: an underappreciated pattern strongly associated with gram-positive bacilli. Am J Clin Pathol, 2011. 136(3): p. 424-7.
5. Taylor, G.B., et al., A clinicopathological review of 34 cases of inflammatory breast disease showing an association between corynebacteria infection and granulomatous mastitis. Pathology, 2003. 35(2): p. 109-19.
6. Wang, Y., et al., Cystic neutrophilic granulomatous mastitis with corynebacterium and staphylococcus mimicking breast carcinoma. Clin Case Rep, 2018. 6(11): p. 2208-2210.
7. Brem, R.F., Breast density, supplemental screening, and a streamlined approach to discussion between a patient and her doctor--a novel, efficient approach. Breast J, 2014. 20(3): p. 227-8.
8. Centers for Disease, C. and Prevention, Idiopathic granulomatous mastitis in Hispanic women - Indiana, 2006-2008. MMWR Morb Mortal Wkly Rep, 2009. 58(47): p. 1317-21.
9. Joseph, K.A., X. Luu, and A. Mor, Granulomatous mastitis: a New York public hospital experience. Ann Surg Oncol, 2014. 21(13): p. 4159-63.