1. 25. September
18.00
Granulomatous Mastitis
18.30
Low grade intraductal proliferations ADH vs DCIS
19.00
Special types of breast cancer: clinical & molecular correlates
19.40
Breast pathology post neoadjuvant chemotherapy
20.20
Predictive marker update & multiparameter molecular markers

2. Granulomatous Mastitis
September 25, 2018
Megan L. Troxell MD/PhD

3. Granulomatous mastitis
Differential diagnosis:
Infectious (TB, fungal, cat scratch, bacterial)
Bug stains (AFB/Fite, GMS and Gram)
Idiopathic
Diagnosis of exclusion
Autoimmune
Sarcoid
Rheumatoid nodules/RA
GPA/vasculitis
Rule out carcinoma
Infarct
SMOLD (Squamous Metaplasia of
Lactiferous Ducts)
IgG4 related disease??
(Biopsy site/foreign body)
Renshaw. AJCP :

4. ‘Idiopathic’ granulomatous mastitis
Young women, esp. post lactation
Mass lesions, painful, treatment refractory
Surgery
Immunosuppression (steroid, methotrexate)
Antibiotics (non-targeted)
May heal in 6-12 months without treatment
Histology: lobulocentric granulomatous inflammation
Also during pregnancy; different than lactation associated acute mastitis; Idiopathic ”lobular”

5. Granulomatous & necrotizing mastitis
AJCP. 2011; 136:
Granulomatous & necrotizing mastitis
Distinctive cystic spaces lined by polys
Spaces larger than adipocyte
Gram + organisms (corynebacterium)
Bugs are IN THE SPACES
Lipophilic, requires Tween to grow
Rx with tetracycline, doxycycline (2+ weeks)
Taylor. Pathology 2003:35:
NZ study with culture data
Small # bugs, over reactive immune reaction

6. 33 year old with breast mass
The mammogram just shows density in the upper outer quadrant, no discrete mass.
The ultrasound shows an irregular hypoechoic mass with suggestion of finger-like projections extending into the surrounding tissue.
Mammogram: no discrete mass
Ultrasound: irregular hypoechoic, finger like projections into surround

7. CNGM

8. Polys can be few around space, or more numerous

9. CNGM

10. Guatemala case (not shown, one with H&E bugs but no Gram stain from 2015; more acute & granulomatous, abscessy)

11. CNGM histologic pattern lipophilic bacteria
Granulomatous mastitis
Pattern
Age (range)
Child bearing
Gram+ bugs?
D’Alfonso AJSP
CNGM
34 (25-49) nd
5/12
Troxell AJCP
33 (19-47)
4.75 y ago
16/19
Other GM
47 (29-71)
14 y ago
0/16
CNGM: More polys (neutrophils)
CNGM with eosinophils
Hispanic ethnicity in OR; can also be fewer polys!
66% Hispanic GNGM vs 14% other GM
D’alfonso most or all cores
Acute and granulomatous/histiocytic

12. Microbiology perspective
Taylor & Paviour
“..granulomatous mastitis can be associated with Corynebacteria infection, particularly infection by C. kroppenstedtii.”
34 breast specimens with Corynebacteria spp.
13 C. kroppenstedtii.
Described lobular GM with suppurative lipogranulomas
79% Maori or Islander (NZ)
C. kroppenstedtii 1998
Difficult to grow
Lipophilic; requires Tween
Lacks mycolic acid at cell membrane
Long incubation (72+ hr)
Difficult to determine Abx susceptibility
May be disregarded as skin flora/contaminant
Tauch. Int J.ID 2016;48:33-9
37/42 (88%) C. Kropp from breast isolates
Taylor: Controls similar histology, but no bacterial isolates (probably same disease)
Many are pure isolates; Described cystic space
Johnstone and UNC have similar studies (starting with micro then looking at tissue)
Ten were identified as Corynebacterium kroppenstedtii, two as Corynebacterium tuberculostearicum, two as Corynebacterium amycolatum, one as Corynebacterium CDC group G2, one as Corynebacterium accolens and one as Corynebacterium minutissium. The C. amycolatum isolates and the C. minutissium isolate were the only non-lipophilic corynebacteria
identified. The seven isolates speciated biochemically were classified as C. kroppenstedtii (4), Corynebacterium CDC Group D2 (1), Corynebacterium CDC Group G2 (1) and C. minutissium (1).
C. kroppenstedtii was identified from 13 different women.

13. Granulomatous: Non-CNGM
Granuloma & eosinophilic
Post XRT for cancer
TB (T-cell lymphoma)
Hispanic ethnicity in OR
Troxell et al. AJCP.2016;145:
Stromal ‘idiopathic’ bilateral

14. Several groups have suggested granulomatous mastitis= IgG4 sclerosing disease of breast

15. No, not all IgG4+ is IgG4 RSD
Several groups have suggested granulomatous mastitis= IgG4 sclerosing disease of breast
No, not all IgG4+ is IgG4 RSD

16. Lymphoplasmacytic infiltrate, mass-forming
AJSP 2009;33:
Lymphoplasmacytic infiltrate, mass-forming
Stromal sclerosis and loss of breast lobules
NO GRANULOMAS!!
3 of 4 with multiple masses, elevated serum IgG or IgG4
IgG4+ also in some lymphomas

17. IgG4 ?granulomatous mastitis
IgG4+ plasma cells not specific for IgG4-RSD in other organs
Granulomas unusual in IgG4-RSD in other organs
Granulomatous mastitis is NOT IgG4-RSD (in my opinion)
Cheuk et al
IgG4+/hpf
IgG4-R mastitis
Lymphocytic mastopathy
0-5
Granulomatous mastitis
5-398
Our study
CNGM
6-58
Other GM
0-22
Our study
Cheuk Chan had lymphocytic mastopathy and granulomatous mastitis as controls
Our CNGM 2/9 with >30/hpf

18. GM literature problematic
IgG4+ plasma cells not specific for IgG4-RSD in other organs
Allen, Kleer. Breast J. 2016;22:501-9
What about cystic neutrophilic pattern?
Polys? Bugs? Clinical?
17/43 IgG4 seems high
Egypt & morocco
17 IgG4/8 GM/18 indet.

19. Core biopsy: granulomas

20. Same case: epithelioid histiocytes?

21. Same case: epithelioid histiocytes?
Keratin stain:
ILC with granulomas

22. Conclusions Recognize CNGM pattern
Do Gram (bacterial) stain along with AFB, fungal stain
Look in the ‘microcysts’ for bacterial organisms
Stain multiple blocks
Antibiotics for Corynebacterium
“lipophilic antibiotics with a high volume of distribution …..doxycycline and trimethoprim-sulfamethoxazole; clarithromycin and rifampicin”
Johnstone Pathology. 2017;49:405–12.
CNGM is major subset of ‘idiopathic’ or ‘lobular’ GM
Speculation: immune response out of proportion to indolent chronic bacteria?
I raise possibility even if bugs not ID’ed; put in ddx in right clinicopath context
Working on projects to compare immune infiltrates

23. Your experience?
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