GRANULOMATOUS MASTITIS:

AN AUTOIMMUNE PROCESS OR
IDIOPATHIC?
A CASE SERIES STUDY
AMINA LODHI, PGY 3
MICHAEL GRISANTI, MD
JOSEPH GRISANTI, MD
BUFFALO RHEUMATOLOGY

GRANULOMA
The term granuloma refers to a nodular organized
aggregation of mononuclear inflammatory cells or
collection of modified macrophages referred to as
epithelioid cells, usually surrounded by a rim of
lymphocytes and often containing multinucleated giant
cells. Some granulomas may also contain eosinophils and
plasma cells.

ETIOLOGY OF GRANULOMATOUS
INFLAMMATION
INFECTIOUS
CAUSES
1.BACTERIAL
TUBERCULOSIS
LEPROSY
CAT SCRATCH
DISEASE

2. FUNGAL
HISTOPLASMOSIS
CRYPROCOCCOSI
S

3.PROTOZOAL
SHISTOSOMIASIS

INERT
AUTOIMMUNE
AUTOIMMUNE CAUSES MATERIALS
CAUSES
1.CROHNS DISEASE
2.SARCOIDOSIS
3.VASCULITIS
GRANULOMATOSIS
WITH POLYANGIITIS
(WEGNERS
GRANULOMATOSIS
)
GIANT CELL
ARTERITIS
TAKAYASUS
ATERITIS
CHURG-STRAUSS
SYNDROME

1. SILICON
2. BERYLLIUM

IDIOPATHIC

PATHOGENESIS OF
GRANULOMA
FORMATION
Events that give rise to
the formation of
granuloma and role of
cytokines in the
pathogenesis of
granuloma (courtesy
Robins Pathologic Basis
of Disease, Chapter 5Diseases of the
immune system)

GRANULOMATOUS MASTITIS
Granulomatous mastitis also called granulomatous
lobular mastitisis is a benign chronic inflammatory
condition of breast which is diagnosed histologically
by the presence of granulomas.
Its clinical presentation is very vague, mimicking
breast abscesses, breast mass and inflammatory
carcinoma of breast.
It has chronic course with frequent recurrences.

GRANULOMATOUS MASTITIS
ETIOLOGY:

Lactation
Trauma
Largely been considered idiopathic

TREATMENT
SURGERY : As primary treatment modality.
Wide local excision as well as radical
mastectomy
Outcomes of surgery_ recurrence, Failure to
induce full remission, local scarring

MEDICAL TREATMENT: Prednisone and

GRANULOMATOUS MASTITIS
LITERATURE REVIEW
Most of the studies are either individual case
reports or a series of case reports
Most of them come from Surgery, Dermatology,
Radiology or Pathology
It has not been studied enough by the nonsurgical subspecialties
The countries in which it is studied mostly include
Italy, Turkey, India , Pakistan

 Largest that has been done so far

Granulomatous Lobular Mastitis: Imaging, Diagnosis
andTreatment
Linda J. Hovanessian Larsen, Banafsheh Peyvandi,
Nancy Klipfel Edward Grant and Geeta Iyengar
American Journal of Roentgenology2009193:2 574581 Department of Radiology, University of
Southern California Keck School of Medicine,
USC/Norris Comprehensive Cancer Center, 1441
Eastlake Ave., Ste. 2315, Los Angeles, CA 90033

METHODS

PATIENTS
To investigate the association between granulomatous
mastitis and autoimmunity we conducted a case series
study of seven patients with histologically proven
granulomatous mastitis who were being treated at Buffalo
Rheumatology between 2010 and 2013.

METHODS
OBSERVED PARAMETERS:
We measured different parameters in the patients history; age,
race, history of rheumatic autoimmune disease and history of
non-rheumatic autoimmune disease, personal or family history of
breast cancer, history ofpregnacy and lactation and history of
smoking.
Then we focused on the clinical presentation of the disease and
looked if the disease was unilateral or bilateral, the presence or
absence of nipple discharge, other nipple changes, ulcers,
palpable masses , draining sinuses, lymphadenopathy, presence
or absence of constitutional symptoms, associated articular
manifestations, extra-articular manifestations.

METHODS
OBSERVED PARAMETERS:
Also reviewed were the investigations to reach
diagnosis including inflammatory and autoimmune
markers, angiotensin converting enzyme levels as
sarcoidosis is an important differential diagnosis to
consider, ultrasound and mammographic description of
the lesions and the histologic appearance of the lesions.
Attention was also paid to the workup that was done to
exclude infectious causes of granulomatous mastitis
including gram stain, AFB stain, fungal and bacterial
cultures.

METHODS
OBSERVED PARAMETERS:
Finally we evaluated the treatment outcomes in these
patients.
We evaluated their response to
1. Immunosuppressive therapy which was measured as
complete remission, near complete remission and partial
remission
2. The role of antibiotics,
3. The surgical treatments

RESULTS

PARAMETERS OBSERVED IN HISTORY

Mean age at presentation

42.83 years

Race
History of Autoimmune
disease

Caucasian

Asian

5/7(71.42 %)

2/7(28.4%)
5/7 ((71.42 %).

Rheumatic Autoimmune disease

Non Rheumatic Autoimmune

disease

3/5 (60%)

3/5 (42.8%)

Sjogrens
Syndrome

Rheumatoid
Arthritis

Vasculitis

Hypothyrioidism

Psoriasis without joint

involvement

Personal history of breast

cancer

1/7( 14.3%)

Family history of Breast

Cancer

1/7 (14.3%)

History of Breast Implant

1/7 (14.3%)

Smoking history

2/7 (28.6 %)

Pregnancy within the last

two years

2/7 (28.6 %)

Breast feeding within the

last two years

1/7 (14.3 %)

STATISTICAL ANALYSIS OF THE AGE OF

PATIENTS
Mean
46.42857143
Median
42
Variance
206.6190476
Standard
14.37424946
Deviation

PARAMETERS OBSERVED ON PHYSICAL EXAMINATION

Constitutional symptoms

Fatigue (most common 83%), Fever, Night sweats,

Weakness

Articular manifestations

Arthritis
Arthralgia
3/7

Extra-articular
manifestations
laterality

Chronic Neck
and Back pain

1/7

1/7

(in association with

Rheumatoid arthritis)

3/7
Erythema Nodosum
1

Dry mouth and dry

eyes
1

Unilateral

Psoriatic skin rash

1

Bilateral

5/7 (71.4%)
Right

Left

1/7 (14.3
%)

4/7(57.1%)

1/7 (14.3%)

Nipple discharge

1/7 (14.3%)

Draining sinuses

4/7 (57.1%)

Abscesses and Ulcers

7/7 (100%)

Lymph nodes palpable or

Palpable as well as on

On imaging alone

Articular manifestations
With Articular manifestations

Without Articular manifestations

29%

71%

Articular Manifestations:Detailed Analysis

Arthritis

arthralgia

chronic neck and back pain

Extra-articular manifestations:Detailed Analysis

Erythema nodosum

Dy mouth and dry eyes

20%
33%

20%

34%

60%

33%

Psoriatic skin rash

IMAGING STUDIES AND HISTOPATHOLOGY

Ultrasound

dilated ducts to complex cystic structures

consistent with abscesses, dense parenchymal
lobules, increased thickness of skin and
subcutaneous nodules.

Mammogram

Mammographic changes reported were

nodularity with internal echoes, hyper dense
parenchymal changes, changes consistent with
abscesses and enlarged lymph nodes.

Histopathology

All seven patients had histologically proven

granulomatous mastitis. Other findings
reported on histopathology included foreign
body giant cells, acute mastitis, abscesses, and
fat necrosis and duct ectasias.
Most interesting association was with
lymphocytic infiltration within in smooth
muscles of walls of blood vessels of breast
in one patient consistent with lymphocytic
vasculitis of the breast

Granulomatous inflammation with foreign body giant cells, ductal

ectasia with eosinophillic cellular material, focal areas of fat
necrosis

Multiple vaguely nodular areas of neutrophils, mature lymphocytes,

macrophages and plasma cells consistent with granulomas with necrosis,
areas of fat necrosis

Acute purulent mastitis with areas of fibrin-o-purulent material consisting of

neutrophils and areas of granulomatous lobular mastitis

Acute mastitis with abscess formation and granulomatous lobular mastitis

with areas necrosis and multinucleated giant cells surrounding ducts.
Diffuse fibrin-o-purulent material.

Abscess formation with areas of granulomatous inflammation with foreign body giant
cells and granulation tissue, Areas of fat necrosis.

Areas of fat necrosis, blood vessels with lymphocytes within the

smooth muscle walls-lymphocytic vasculitis of breast with areas
of granulomatous inflammation

INFECTIOUS DISEASE WORKUP AND ANGIOTENSIN

CONVERTING ENZYME
Gram stain

Negative

AFB

Negative

Bacterial Cultures

Negative

Fungal Cultures

Negative

Angiotensin Converting Enzyme

Negative

MARKERS OF AUTOIMMUNITY
Patient 1
Patient 2

Negative
ANA 1:132, speckled pattern

Patient 3

Elevated ESR,CRP,
Positive Anti SSB, reduced C3

Patient 4

Negative

Patient 5

Elevated ESR,
IgE level very high

Patient 6

Anti CCP Positive

Patient 7

ANA positive, pANCA Positive

TREATMENTS AND OUTCOMES OF TREATMENT

Patient

Incision
and
Drainage

Yes

Yes

Yes

Yes

Yes

yes

yes

Excision

No

No

No

No

Yes, local
excision

no

no

Antibiotics

Multiple
Courses

Multiple
Course

Multiple
Courses

Multiple
Courses

Multiple
Courses

Multiple
Courses

Multiple
Courses

Prednison
e

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Methotrex
ate

yes

Yes

Yes

Yes

Yes

Yes

Yes

Treatment
outcomes

Full
Remission

Full
remission

Full
Remission

Full
Remission

Partial
remission

Near
Complete
remission

Near
complete
remission

 The presence of history of autoimmune diseases

and the markers of autoimmunity in 71% of patients
that immunomodulation
with________
prednisone
and
and
__ ________
__ _______ __ __________
___ ___
methotrexate
was able
remission
shows
_______
__ ____________
__ to induce
__ ________
___ ____
that it there is role
autoimmunity
in it.
________________
____of
__________
___ ____________
___
____
29 %__patients
had no autoimmune
markers
______ _________
_____ ____ __ _____
__ ____ __
positive, no __
history
of any autoimmune disorder
____________
__
demands
follow_______
up prospectively
see
which
________
___ __close
__________
________ __ to
_______
if they
develop signs
and_____
symptoms
any______ __
__
___ __________
________
_______ of
_____
autoimmune __
disorder
or seroconvert
negative
_____________
___ __ ____
_______ _____from
___ ________
__
___
__________ markers
________ __
____ ________
autoimmune
to ___________
positive autoimmune
__________
markers . _______ __ ________ __________ _______
It_ can
___ __
________
__ _or
_________
________
__
be_ a_______
primary
disorder
a secondary
disorder
___________
____with
_____
__________
________diseases.
in association
other
autoimmune

CONCLUSION

CONCLUSION
Granulomatous mastitis is a medically manageable disease
with the mainstay of treatment being immunosupressive
therapy
Failure to induce remission and recurrence is not
uncommon with primary immunomodulating agents
Considering important role of TNF in the pathogenesis of
formation as well as maintenance of granuloma, there can
be a potential role of anti TNF therapy in such patients who
fail to respond to first line immunosuppressive agents.
Role of surgery is only limited to the incision and drainage
in case of signs and symptoms of concurrent infection,
biopsy and excision for the purpose of diagnosis

CONCLUSION
More studies are needed to be done, retrospectively as well
as prospectively
1.To find the association between granulomatous mastitis
and autoimmune disorders and different autoimmune
markers.
2.To find if there are any markers which are unknown to us at
this time which are either specifically associated with
granulomatous mastitis or are common between
granulomatous mastitis and other autoimmune disorders
3.To identify the environmental, clinical as well as
biological factors that play a role in the pathogenesis
of granulomatous mastitis
4.To formulate reasonable treatment algoriths to treat it with
success

CONCLUSION
There is a need to spread awareness of this
disease among the PCP as well as specialists ,
so that these patients who present with
recurrent breast abscesses with failure to
respond to antibiotics and multiple incision and
drainage with little or no success can be
identified , worked up for this diagnosis and
managed appropriately.