MANAGEMENT OF IDIOPATHIC MANAGEMENT OF IDIOPATHIC GRANULOMATOUS MASTITISGRANULOMATOUS MASTITIS

Canon CHANCanon CHANDepartment of Surgery, North District Hospital. Department of Surgery, North District Hospital.

Hong Kong SARHong Kong SAR

Idiopathic Granulomatous Idiopathic Granulomatous Mastitis (IGM)Mastitis (IGM)

►Kessler and Wolloch 1972Kessler and Wolloch 1972►Cohen 1977Cohen 1977

Chronic granulomatous lobulitis Chronic granulomatous lobulitis Absence of an obvious etiologyAbsence of an obvious etiology

Kessler E, Wolloch Y. Am J Clin Pathol, 1972

Cohen C. S Afr Med J 1977

IntroductionIntroduction

►Rare inflammatory breast diseaseRare inflammatory breast disease►Unknown etiologyUnknown etiology►Women of childbearing ageWomen of childbearing age►Simulate breast cancer Simulate breast cancer

Breast massBreast mass Nipple retractionNipple retraction

Sakurai et al. Breast Cancer 2002

Cakir et al. Breast J 2002

IntroductionIntroduction

►Diagnosis is one of exclusionDiagnosis is one of exclusion Infectious and noninfectious causesInfectious and noninfectious causes Carcinoma/ carcinomatous mastitisCarcinoma/ carcinomatous mastitis Wegener granulomaWegener granuloma SarcoidosisSarcoidosis TuberculosisTuberculosis Histoplasmosis Histoplasmosis

Erhan et al. Breast 2000

Topic of interestTopic of interest

►The pathogenesis is not clear►Etiology unknownEtiology unknown►Treatment strategy controversialTreatment strategy controversial

Current argumentsCurrent arguments

► An etiology for an idiopathic disease?An etiology for an idiopathic disease? Oral contraceptive pillsOral contraceptive pills Pregnancy and lactationPregnancy and lactation InfectiveInfective Autoimmune processAutoimmune process Immune response to extravasated secretions Immune response to extravasated secretions

from lobulesfrom lobules

Kessler et al. Am J Clin Pathol. 1972

Cohen et al. S Afr Med J. 1977

Brown et al. Am J Surg. 1979

Imoto et al. Jpn J clin Oncol. 1997

Cserni et al. Breast J. 1999

IGM - PresentationIGM - Presentation

► PainPain► Swelling/ massSwelling/ mass► Discharge/ galactorrhoeaDischarge/ galactorrhoea► Nipple retractionNipple retraction► Skin ulcersSkin ulcers

IGM – Physical examinationIGM – Physical examination

► Skin ulcerationSkin ulceration► MassMass► IndurationInduration► AbscessAbscess► FistulaFistula► Enlarged lymph Enlarged lymph

nodenode Up to 15% of casesUp to 15% of cases

Asoglu et. al The Breast Journal. 2005

IGM - InvestigationsIGM - Investigations

IGM - investigationsIGM - investigations

►Manage as a breast massManage as a breast massMammography (MMG)/ Ultrasound (USG)/ Mammography (MMG)/ Ultrasound (USG)/ Magnetic Resonance Imaging (MRI)Magnetic Resonance Imaging (MRI)Fine needle aspiration cytology (FNAC)Fine needle aspiration cytology (FNAC)Core biopsyCore biopsy

Mammography in IGMMammography in IGM

► Oblique view demonstrates a diffusely increase asymmetric density and enlarged axillary lymph nodes

Asoglu et. al The Breast Journal. 2005

Mammography and IGMMammography and IGM

► Small, multiple, ill-defined masses without microcalcification

► Most commonly reported finding of IGM is an asymmetrically increased density without a distinct margin or mass effect, though this is not specific

► Low sensitivity caused by dense breast tissue limits the value of MMG in this age group

► In patients having dense breast parenchyma, MMG may be negative

Memis A et al. Clin Radiol. 2002Han BK et al. AJR Am J Roentgenol.

1999

Ultrasound and IGMUltrasound and IGM

► Hypoechoic indistinctly bordered heterogeneous masses

► May be connected by a few tubular hypoechoic structures

Kocaoglu et al. J Comput Assist Tomogr. 2004

MRI and IGMMRI and IGM► Segmental heterogeneity

► Hypointense on precontrast T1-weighted images and hyperintense on T2-weighted sequences

► Postcontrast dynamic T1-weighted scans showed heterogeneously enhancing ring-like abscesses

► Abscess walls reveal a benign type time-signal intensity curve (gradual and progressive enhancement without washout)

Kocaoglu et al. J Comput Assist Tomogr. 2004

Imaging and IGMImaging and IGMNN USGUSG MMGMMG MRIMRI

Schelfout et al.2001

11 Asymmetric diffuse increaseddensity

Focal irregular homogeneouslyenhanced masses

Van Ongeval et al.

1997

11 Inhomogeneous hypoechoic lesion with posterior acoustic shadow

Bilateral diffuse increased density ofthe fibroglandular tissue

An irregular ring-shaped enhancedlesion

Cakir et al.2002

11 Inhomogeneous hypoechoic lesionwith posterior acoustic shadow

Unilateral diffuse increased density Heterogeneously enhanced irregularlesion and gradual and progressive

enhancement without washout

Sakurai et al.2002

11 Inhomogeneous hypoechoic lesionwith posterior acoustic shadow

Unilateral diffuse increased density Irregularly enhanced mass withoutcontrast washout

Memis et al.2002

1515 Irregular hypoechoic mass withtubular extensions

Asymmetric opacities

Kara et al.2003

11 Well-defined hypoechoic areas withtubular extensions

Asymmetric densities with skinthickening

Engin et al1999

1010 Heterogeneous hypoechoic masses,circumscribed opacities,

and abscess cavities with sinustracts

Circumscribed opacities asymmetric dense parenchyma,nodular opacities

parenchymal distortion ,and bilateral dense parenchyma

Yilmaz et al2001

1212 Heterogeneous hypoechoic areaswith/without tubular extensions, hypoechoic irregular mass, and

edematous breast withskin thickening

Focal asymmetric density withoutmass formation, irregular

masses, and negative

Han et al1999

99 Tubular hypoechoic lesionsand oval hypoechoic masses withhypoechoic tubular connections

Multiple small ill-defined masses and local asymmetric

density

Idiopathic granulomatous mastitis is rare; hence, the number of patients in these studies can not make generalizations

Biopsy still remains the golden method of definite diagnosis

IGM - FNACIGM - FNAC

► The cytological diagnosis is difficult and often does not deliver any diagnostic information ~30% can be diagnosed by FNAC only

► The absence of necrosis and a predominantly neutrophil infiltrate in the background favor the diagnosis these signs overlap with other etiologies:

Tuberculosis Azlina AF et al. World J Surg 2003Sakurai T et al. Breast Cancer. 2002Kumarasinghe MP Acta Cytol. 1997Imoto S et al. Jpn J Clin Oncol. 1997

IGM - BiopsyIGM - Biopsy

► Gold standard in diagnosis of IGMGold standard in diagnosis of IGM

► Histological featuresHistological features Granulomas (100%) Background of inflammatory infiltrate (88%) Foamy macrophages and multinucleated giant

cells (65%) Microabscesses The ducts appear normal without evidence of

malignancy or caseation Stains for fungi and acid-fast bacilli are negative

Ramachandram K et al. Pathology. 2004

Histological reviewHistological review

Multinulceate Giant cells and lymphocyts set in an area of stellate fibrosis

Epithelioid histiocyts and neutrophilic leukocytes

Low power view High power view

Courtesy of Dr. TY Yau

Department of Pathology, QEH HKSAR

IGM - TreatmentIGM - Treatment

Current ArgumentsCurrent Arguments

►Management optionsManagement options Surgical excisionSurgical excision

►Wide local excision +/- reconstructionWide local excision +/- reconstruction►Invasive procedure for a benign disease entityInvasive procedure for a benign disease entity

Systemic steroid/ immunosuppressantSystemic steroid/ immunosuppressant►Immune suppressionImmune suppression►Underlying infective cause renders its use a Underlying infective cause renders its use a

concernconcern

Surgical excisionSurgical excision

►Asoglu Asoglu et al.et al. The Breast J. 2005. The Breast J. 2005. 18 patients with IGM18 patients with IGM All underwent surgical excision with All underwent surgical excision with

negative marginsnegative margins Mean follow up 18 monthsMean follow up 18 months Recurrence rate 6%Recurrence rate 6%

Prednisolone managementPrednisolone management

► DeHertogh DeHertogh et al. et al. N. Eng. J. Med. 1980.N. Eng. J. Med. 1980. Short course high dose prednisoloneShort course high dose prednisolone Single patient case reportSingle patient case report Short follow up periodShort follow up period Recurrence was not reportedRecurrence was not reported

► Azlina Azlina et al.et al. World J Surg. 2003. World J Surg. 2003. 25 patients with mean follow up of 6.5 months25 patients with mean follow up of 6.5 months Recurrence up to 50% for steroid treatmentRecurrence up to 50% for steroid treatment Short follow up periodShort follow up period

Conservative ManagementConservative Management

►Lai Lai et al.et al. Breast Journal. 2005. Breast Journal. 2005. 9 women with mean followed up of 18.7 9 women with mean followed up of 18.7

monthsmonths 50% spontaneous complete resolution 50% spontaneous complete resolution

after 14.5 monthsafter 14.5 months

Small size reviewSmall size review

Conservative vs SurgeryConservative vs Surgery

►Al-Khaffaf et al. J Am Coll Surg. 2008

18 patients wth IGM 25 years retrospective review FU period not mentioned Steriod use/ antiobiotic/ surgical procedures compared

► Overall outcomes were not related to any combination of treatment options

► All patients spontaneously resolved regardless of treatment used, it may be best to let this condition “burn out.”

MANAGEMENT OF IDIOPATHIC GRANULOMATOUS MASTITIS

EXPERIENCE FROM A REGIONAL HOSPITAL

CANON CHAN, N. S. C HO, M. POON, M. T. CHEUNGDepartment of Surgery, Queen Elizabeth Hospital.

Hong Kong SAR

ObjectiveObjective

This study is aimed to This study is aimed to determine the best determine the best

treatment modality for treatment modality for IGMIGM

Queen Elizabeth HospitalQueen Elizabeth Hospital

MethodsMethods

► A retrospective review A retrospective review

► Twenty three women with histopathologic Twenty three women with histopathologic diagnosis of IGM between 1997 and 2006 diagnosis of IGM between 1997 and 2006 was performedwas performed

► The difference in presentation, recurrence The difference in presentation, recurrence and outcome between those treated by and outcome between those treated by surgical intervention and those managed surgical intervention and those managed conservatively were assessed conservatively were assessed

ResultsResults

► The women had a mean follow-up of 22.7 months The women had a mean follow-up of 22.7 months and a mean age of 40 years (range 22-55 years) and a mean age of 40 years (range 22-55 years)

► Clinically and radiologically, 13% of the women Clinically and radiologically, 13% of the women were suspected to have malignancy were suspected to have malignancy

► All patients had unilateral involvementsAll patients had unilateral involvements

► None of the patient were pregnant or lactatingNone of the patient were pregnant or lactating

► None of the patient were given systemic steroid None of the patient were given systemic steroid therapytherapy

ResultsResults

► PresentationPresentation

Mass(n=19)83%

Ulcer(n=1)4%

Abscess(n=3)13%

Risk FactorsRisk Factors

No. of casesNo. of cases PercentagePercentage

Psychiatric illnessPsychiatric illness

schizophrenicschizophrenic

66 2626

Drug/ Hormonal Drug/ Hormonal RxRx

contraceptivescontraceptives

antipsychoticsantipsychotics

99

33

66

3939

1313

2626

Diabetes MellitusDiabetes Mellitus 11 4.34.3

DrugDrug

No. of casesNo. of cases PercentagePercentage

AntipsychoticsAntipsychotics

FlupenthixolFlupenthixol

ThioridazineThioridazine

PromethazinePromethazine

SulperideSulperide

TrifluroperazineTrifluroperazine

66

11

11

11

22

11

2626

Hormonal RxHormonal Rx

PrimulutPrimulut

PremarinPremarin

33

11

22

1313

ResultsResults

► TreatmentTreatment

I&D17%

Lumpectomy35%

Expectant48%

Results – Expectant Results – Expectant managementmanagement

►91% of the patients had spontaneous 91% of the patients had spontaneous complete resolution of disease without complete resolution of disease without recurrencerecurrence

►Mean interval of 12 months. Mean interval of 12 months.

►Remaining patients had either Remaining patients had either recurrence (4.5%) or static disease recurrence (4.5%) or static disease (4.5%)(4.5%)

Results – Surgical treatmentResults – Surgical treatment

►85% of patients had resolution of 85% of patients had resolution of disease after either lumpectomy or disease after either lumpectomy or surgical drainage of abscesssurgical drainage of abscess

►Two patients (15%) had disease Two patients (15%) had disease recurred and one of them (7.5%) recurred and one of them (7.5%) eventually became static after eventually became static after followed up for 24 monthsfollowed up for 24 months

Patient CharacteristicsPatient CharacteristicsSurgerySurgery ExpectantExpectant P P value value **

(P< 0.05)(P< 0.05)

Age (mean)Age (mean) 40.42 (7.50)40.42 (7.50) 39.55 (11.10)39.55 (11.10) 0.9280.928

Duration of follow Duration of follow up (mean)up (mean)

28.80 (23.06)28.80 (23.06) 15.3 (12.95)15.3 (12.95) 0.1260.126

Recurrence (%)Recurrence (%) 1515 4.54.5 0.9760.976

Static diseaseStatic disease 7.5%7.5% 4.5%4.5% 0.9760.976

Brackets = Standard Brackets = Standard deviationdeviation

*Mann-Whitney U *Mann-Whitney U testtest

Recurrent/ static casesRecurrent/ static cases

PatientPatient

numbernumberAgeAge Drug Drug

historyhistoryPresentationPresentation Duration Duration

of follow of follow upup

TreatmentTreatment Final Final OutcomeOutcome

11 3030 Sterile Sterile abscessabscess

1515 Incision Incision and and drainagedrainage

RegresseRegressed d

22 3939 SulpiridSulpiridee

Sterile Sterile abscessabscess

6060 Incision Incision and and drainagedrainage

regresseregressedd

33 3535 Sterile Sterile abscessabscess

2424 Incision Incision and and drainagedrainage

Static Static

44 4747 PremariPremarinn

PromethPromethazineazine

MassMass 4848 ExpectantExpectant RegresseRegressedd

55 4444 MassMass 1212 Expectant Expectant staticstatic

ConclusionsConclusions

► It is important to exclude malignancy by It is important to exclude malignancy by histopathology in IGMhistopathology in IGM

► The presence of a breast mass in a woman The presence of a breast mass in a woman with history of hormonal therapy or with history of hormonal therapy or antipsychotic drug use should alert the antipsychotic drug use should alert the differential diagnosis of IGMdifferential diagnosis of IGM

► Our results suggest expectant management Our results suggest expectant management with close regular surveillance has an with close regular surveillance has an acceptable recurrence rate of 4.5% and it is acceptable recurrence rate of 4.5% and it is the treatment of choice for patients with IGM the treatment of choice for patients with IGM

Hyperprolactinaemia and Hyperprolactinaemia and IGM?IGM?

► Antipsychotics block D2 receptors on Antipsychotics block D2 receptors on lactotroph cells and remove inhibitory lactotroph cells and remove inhibitory influence on prolactin secretioninfluence on prolactin secretion

► Seen in 40-60% of antipsychotic usersSeen in 40-60% of antipsychotic users► Causes breast enlargement and Causes breast enlargement and

galactorrhoeagalactorrhoea► Baseline levels take up to 3 weeks to return Baseline levels take up to 3 weeks to return

to normalto normal

► No study has yet looked into the association No study has yet looked into the association between antipsychotic usage and IGMbetween antipsychotic usage and IGM

Wieck, A.et al. British Journal of Psychiatry. 2003.

Future studyFuture study

►Randomized controlled trialRandomized controlled trial Difficulty lies in the rarity of this disease Difficulty lies in the rarity of this disease

entityentity

►Relationship between antipsychotics Relationship between antipsychotics and IGMand IGM Elevated serum prolactin level?Elevated serum prolactin level?

Cserni G, Szajki K. Breast J., 1999

Rowe PM. Br. J. Clin. Pract. 1984

Thank youThank you

IGM in the male breastIGM in the male breast

Reddy et al. The Breast Journal. 2005