1830 Low grade intraductal proliferations ADH vs DCIS 1900 Special types of breast cancer clinical amp molecular correlates 1940 Breast pathology post neoadjuvant chemotherapy 2020 Predictive marker update amp multiparameter molecular markers ID: 919542
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Slide1
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
Slide2Granulomatous Mastitis
September 25, 2018
Megan L. Troxell MD/PhD
Slide3Granulomatous mastitis
Differential diagnosis:
Infectious
(TB, fungal, cat scratch,
bacterial
)
Bug stains (AFB/
Fite
, GMS and
Gram)Idiopathic Diagnosis of exclusion AutoimmuneSarcoidRheumatoid nodules/RAGPA/vasculitisRule out carcinomaInfarctSMOLD (Squamous Metaplasia of Lactiferous Ducts)IgG4 related disease??(Biopsy site/foreign body)
Renshaw
. AJCP 2011. 136:424-427
Slide4‘Idiopathic’ granulomatous mastitisYoung 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
Slide5Granulomatous & 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 2003:35:109-19. NZ study with culture data
AJCP. 2011; 136:424-427
Slide633 year old with breast mass
Mammogram: no discrete mass
Ultrasound: irregular hypoechoic, finger like projections into surround
Slide7CNGM
Slide8Slide9CNGM
Slide10Slide11Granulomatous mastitis
Pattern
Age (range)
Child bearing
Gram+ bugs?
D’Alfonso AJSP
CNGM
34 (25-49)
nd
5/12
Troxell AJCP
CNGM
33 (19-47)
4.75 y ago
16/19
Troxell
AJCP
Other
GM
47 (29-71)
14 y ago
0/16
CNGM histologic pattern
lipophilic bacteria
CNGM: More polys (neutrophils)
CNGM with eosinophils
Slide12Microbiology perspective
Taylor &
Paviour
1993-2002“..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 lipogranulomas79% Maori or Islander (NZ)
C. kroppenstedtii 1998Difficult to growLipophilic; requires TweenLacks mycolic acid at cell membraneLong incubation (72+ hr)Difficult to determine Abx
susceptibility
May be disregarded as skin flora/contaminant
Tauch. Int J.ID 2016;48:33-937/42 (88%) C. Kropp from breast isolates
Slide13TB (T-cell lymphoma)
Stromal ‘idiopathic’ bilateral
Post XRT for cancer
Granulomatous: Non-CNGM
Granuloma &
eosinophilic
Troxell et al. AJCP.2016;145:635-645
Slide14Several groups have suggested granulomatous mastitis= IgG4 sclerosing
disease of breast
Slide15Several groups have suggested granulomatous mastitis= IgG4 sclerosing
disease of breast
No, not all IgG4+ is IgG4 RSD
Slide16Lymphoplasmacytic
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
AJSP 2009;33:1058-64
Slide17IgG4 ?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)
Our study
Cheuk
et al
IgG4+/
hpf
IgG4-R mastitis
272-495
Lymphocytic
mastopathy
0-5
Granulomatous mastitis
5-398
Our study
IgG4+/
hpf
CNGM
6-58
Other GM
0-22
Slide18GM literature problematic
IgG4+ plasma cells not specific for IgG4-RSD in other organs
Allen,
Kleer
. Breast J. 2016;22:501-9
17 IgG4/8 GM/18
indet
.
What about cystic
neutrophilic pattern?Polys? Bugs? Clinical?
Slide19Core biopsy: granulomas
Slide20Same case:
epithelioid
histiocytes
?
Slide21Same case:
epithelioid
histiocytes
?
Keratin stain:
ILC with granulomas
Slide22Conclusions
Recognize CNGM pattern
Do Gram (bacterial) stain along with AFB, fungal stain
Look in the ‘microcysts’ for bacterial organisms
Stain multiple blocksAntibiotics 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’ GMSpeculation: immune response out of proportion to indolent chronic bacteria?
Slide23Your experience?