Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia.

0.55 MB·English

by  Lin, Chih-Hsun

Linetal.DiagnosticPathology2012,7:2
http://www.diagnosticpathology.org/content/7/1/2
CASE REPORT Open Access
Idiopathic granulomatous mastitis associated with
risperidone-induced hyperprolactinemia
Chih-Hsun Lin1, Chih-Wei Hsu2, Tang-Yi Tsao3 and Jason Chou4*
Abstract
Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease. The etiology and treatment options
of IGM remain controversial. Previous case reports have suggested that hyperprolactinemia may be associated with
IGM. In the present report, we describe the first case of IGM associated with risperidone-induced
hyperprolactinemia.
Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/
vs/8120093785928228
Background hyperprolactinemia, and this case could be another one
Idiopathic granulomatous mastitis (IGM) is a rare belonging to this etiologic group.
benign breast disease characterized by non-caseating
granulomas without any evidence of infection. This dis- Case Presentation
ease was first described by Kessler and Wolloch in 1972 The patient in this study was a 39-year-old Chinese
[1]. It usually affects young parous women with a his- woman who presented with a painful right breast lump
tory of breast-feeding. The clinical presentation is on April 5, 2008. She had a history of schizophrenia for
usually a tender, erythematous breast mass with an over 20 years and had been receiving risperidone (2 mg
abscess or chronic sinus drainage. However, the clinical bid) for more than 3 years. She had developed a lump
and radiological features of this benign entity are fre- in her right breast a month before her visit and had
quently mistaken for malignancy. Several etiologies of noted a progressive worsening tenderness with erythe-
IGM have been postulated, including immune reaction matous changes around the lesion. She had no systemic
to extravasated milk secretion, breast trauma, or infec- symptoms nor did she have any known previous fungus
tion [2,3]. Definitive diagnosis is based on histological or tuberculosis exposure. The patient had a gestational
examination. Other causes of mammary granulomatous history of G0P0 and had amenorrhea for approximately
formation must be excluded prior to diagnosis, and a year. She had no history of any other breast disease or
microbiological investigation is necessary. Because of an receiving any breast surgery, and her medical history
absence of a consensus for an appropriate treatment was otherwise unremarkable. She had never consumed
modality for patients diagnosed with IGM, surgery, ster- tobacco, alcohol, oral contraceptive pills nor did she
oids, immunosuppressants, and antibiotics have been have any family history of breast cancer. On physical
attempted with varying degrees of success. Recurrence is examination, a 9-cm × 6-cm breast lump with localized
common in the absence of surgical treatment, and a redness over the right breast lateral aspect with an ill-
long-term follow-up is generally essential. defined margin was noted with no palpable lymphade-
Here we represent a case of granulomatous mastitis nopathy at the axilla. There was no splenomegaly or
associated with risperidone-induced hyperprolactinemia. hepatomegaly. She did not have fever, joint pain, airway
There have been only few cases associated with or urinary tract bleeding. No other skin lesion was
found. The patient’s blood count was normal. Breast
ultrasound images revealed a large ill-defined area with
*Correspondence:[email protected] heterogeneous echoes in the right upper and lower
4ChengHsinGeneralHospital,DepartmentofAnatomicPathology,Taipei,
outer quadrants, associated with increased vascularity.
Taiwan
Fulllistofauthorinformationisavailableattheendofthearticle Micro-calcification and tissue edema were noted. No
©2012Linetal;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommons
AttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproductionin
anymedium,providedtheoriginalworkisproperlycited.
Linetal.DiagnosticPathology2012,7:2 Page2of6
http://www.diagnosticpathology.org/content/7/1/2
enlarged lymph node was noted in the right axilla, and Aspiration culture showed no evidence of bacterial or
there was no dilatation of the lactiferous duct. CXR mycobacterial growth. In order to rule out previously
didn’t show any lung lesions. Mammography showed missed diagnosis, another incision biopsy was performed
asymmetry with increasing radiodensity at the outer 1 week later, and the pathology showed chronic inflam-
upper quadrant of the right breast with nipple retrac- mation with focal fibrotic changes in the fat tissues. Due
tion. Mastitis with edema and micro-abscess in the right to persistent drainage with erythematous swelling and in
upper and lower quadrants was suspected. However, consideration of malignancy, the patient then was
inflammatory carcinoma could not be ruled out. All scheduled for simple mastectomy. Macroscopic appear-
other laboratory and other radiological studies including ance demonstrated a huge mass with an ill-defined mar-
C-reactive protein (0.8 mg/L) were normal except that gin of inflammatory tissue at the center with peripheral
the prolactin level was 84.5 ng/ml (normal, < 20 ng/ml); fatty necrosis and hematoma (Figure 1). Microscopic
FSH, 4.6 mIU/ml; and LH, 6.0 mIU/ml. Although malig- examination revealed chronic inflammation and macro-
nancy had not been excluded, the patient received a pre- phage, giant histiocyte, and epithelioid-like cellular infil-
sumptive diagnosis of infectious mastitis and was treated tration, with cytologic features suggestive of a
with a 14-day course of keflex (first-generation cepha- granulomatous process. The noncaseous granulomatous
losporin), but there was no improvement. Therefore, lesions were centered at the breast lobules. The lesions
core breast biopsy was performed, which revealed an were characteristic with an empty space in the center
adipose tissue with acute and chronic inflammation. and surrounded by microgranulomas and
Figure1Ahugesofttissuemass(9×6cm)withfibrosis,spottynecrosis,inflammation,andhemorrhage.Thevirtualslidesforthis
articlecanbefoundhere:http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=1320701553,http://diagnosticpathology.
slidepath.com/dih/webViewer.php?snapshotId=1320701637,http://diagnosticpathology.slidepath.com/dih/webViewer.php?
snapshotId=1320701673,http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=1320701702.
Linetal.DiagnosticPathology2012,7:2 Page3of6
http://www.diagnosticpathology.org/content/7/1/2
microabscesses. Some granulomatous lesions composed the breast lobules, is histologically evident. Sarcoidosis is
of confluent epithelioid cells and huge abscess were also a systemic granulomatous disease of unknown etiology
seen (Figure 2A, B). Based on the histological features, with high prevalence rate in European countries. It
the differential diagnosis included autoimmune usually involves lung and associated lymph nodes and is
response, undetected organisms, systemic granuloma- histologically characterized by well-formed tight granu-
tous disease with breast involvement, granulomatous lomas without necrosis, extensive inflammation, and
reaction in a carcinoma and foreign body reaction. abscesses. The breast is involved in less than 1% of
There was no evidence of carcinoma or specific organ- cases [8]. Wegener’s granulomatosis is a form of large-
ism can be found. All cultures, Ziehl-Neelsen staining, size vasculitis that usually affects upper airway, lung and
PAS staining and GMS staining yielded negative results. kidney. It is featured as an autoimmune attack by an
Considering the patient’s clinical history and all the abnormal type of circulating antibody termed ANCAs
laboratory findings, the diagnosis was interpreted as (antineutrophil cytoplasmic antibodies). The histological
IGM. In suspect of the dopaminergic effect of risperi- presentation is small and medium vessel vasculitis with
done to cause hyperprolactinemia and IGM, the pre- necrotizing granulomas. Breast involvement is rare and
scription was shifted to prolactin-sparing second line usually accompanied by systemic manifestations of the
agent (clozapine). The residual breast lesions resolved disease [9,10]. Polyarteritis nodosa and giant cell arteritis
completely 3 months later and no recurrence was noted are occasionally classified as vasculitis, but actually are a
since then. form of arteritis since they mainly involve the arteries.
Granulomatous response to carcinoma is unusual and
Discussion characterized by multinucleated giant cells restricted to
Idiopathic granulomatous mastitis is characterized by the carcinoma or osteoclastic giant cells (OGCs) at per-
the presence of chronic granulomatous lobulitis. It is a ipheral hypervascular stroma. These two types have
disease of unknown etiology and is diagnosed by exclu- been easily identified with intraductal or invasive carci-
sion. Clinically, patients with IGM present a unilateral noma [11,12]. Foreign body reaction may be due to sili-
hard lump in the absence of any systemic signs of infec- con leakage from breast implant. Although there are no
tion. These lumps mimic carcinoma and may lead to risks of systemic disease or carcinogenesis, the relation-
nipple retraction and sinus formation [1,2]. ship between silicon breast implant and primary ana-
Approximately 200 cases of IGM have been reported plastic large cell lymphoma (ALCL) of the breast has
in the literature during the past 3 decades, with most of been reported [13]. Culture specimens and special stain-
them being reported in developing countries. More than ing of specimens, including Ziehl-Neelsen staining, PAS
50% of the reported cases of IGM were initially mista- staining, GMS staining, and Warthin-Starry silver
ken for breast carcinoma, even with a combined diagno- impregnation, can rule out rare infectious granuloma-
sis by mammography and ultrasound. A definitive tous breast lesions.
diagnosis can be made only through histological evi- The presumptive causes of IGM, including alpha-1-
dence of granuloma formation with the absence of any antitrypsin deficiency, oral contraceptives usage, preg-
infection. A well-formed granuloma centered at the nancy, lactation, and hyperprolactinemia have been
terminal ducts and the lobules was noted, and this reported [2,6,14,15]. Interestingly, hyperprolactinemia
could occur anywhere in the breast. A mixed chronic whether primary or secondary, might play an important
inflammatory process composed of lymphocytes, plasma role in IGM. It has been postulated that IGM results
cells, epithelioid histiocytes, multinucleated giant cells, from a localized autoimmune response to the retained
and a less frequent neutrophil infiltration with micro- or extravasated fat- or protein-rich secretion in the
abscess formation can be found in the granuloma [3,4]. breast ducts during childbearing age due to a previous
Before diagnosing IGM, any known cause of granulo- hyperprolactinemia in women [16]. To the contrary, as
matous breast inflammation, such as duct ectasia, sar- the occurrence of IGM without a history of recent preg-
coidosis, Wegener’s granulomatosis, giant cell arteritis, nancy is uncommon, the serum prolactin level and the
polyarteritis nodosa, tuberculosis, syphilis, corynebacter- pathogenesis of IGM in non-pregnant women therefore
ial infection, cat-scratch disease in breast lymph node might help us understand the role of hyperprolactinemia
tissue, mycotic infection, granulomatous reaction in a in the disease. Especially, the role of hormone in mam-
carcinoma and foreign body reaction, whether infectious mary tumor growth is under investigated and with some
or non-infectious, should be ruled out [5-7]. Duct ecta- trigger agents, such as environmental contaminants, the
sia can mimic IGM as both possess similar clinical increase of hormone receptors can promote cell prolif-
symptoms, including nipple retraction, pain, and occa- eration [17]. To the best of our knowledge, IGM in
sional bloody discharge. The dilation of the large duct non-pregnant women associated with high serum pro-
with peripheral duct inflammation, and not centered at lactin level can has been rarely reported associated with
Linetal.DiagnosticPathology2012,7:2 Page4of6
http://www.diagnosticpathology.org/content/7/1/2
Figure 2 Microscopic findings of idiopathic granulomatous mastitis. 2A Empty spaces of varying sizessurrounded by granulomatous
inflammationandmicro-abscessformation(H&E,40×)2BEpithelioidgranulomaadmixedwithpolymorphonuclearcellsandmultinucleated
giantcells.(H&E,100×)Thevirtualslidesforthisarticlecanbefoundhere:http://diagnosticpathology.slidepath.com/dih/webViewer.php?
snapshotId=1320701730,http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=1320701765,http://diagnosticpathology.
slidepath.com/dih/webViewer.php?snapshotId=1320701787.
Linetal.DiagnosticPathology2012,7:2 Page5of6
http://www.diagnosticpathology.org/content/7/1/2
pituitary adenoma, phenothiazine-induced hyperprolacti- accompanying images. A copy of the written consent is
nemia, and metoclopramide-related galactorrhea with available for review by the Editor-in-Chief of this
blunt trauma [16,18-20]. Our case is the fourth one in a journal.
non-pregnant woman with hyperprolactinemia and is
the first case to be reported that the hyperprolactinemia
Authordetails
was induced by risperidone.
1AntaiMedicalCareCooperationAntaiTian-ShengMemorialHospital,
Many antipsychotic agents are known to increase pro- DepartmentofSurgery,DivisionofPlasticandReconstructiveSurgery,
lactin secretion because of their inhibitory effect of PingTungCounty,Taiwan.2Tungs’TaichungMetroHarborHospital,
DepartmentofSurgery,DivisionofBreastSurgery,Taichung,Taiwan.3Tungs’
dopamine. Risperidone is known to increase serum pro-
TaichungMetroHarborHospital,DepartmentofPathology,Taichung,Taiwan.
lactin level to a greater extent than other antipsychotics, 4ChengHsinGeneralHospital,DepartmentofAnatomicPathology,Taipei,
such as quetiapine. It is thought that once the prolactin Taiwan.
level is elevated due to risperidone, it causes non-can- Authors’contributions
cerous tumors in the pituitary gland. This has been CH-LconstructedthemajorityofthemanuscriptandCW-Hwasresponsible
demonstrated to recur even after the drug has been forthesurgicalconsultation.JCandTY-Tprovidedpathologicalassistance
andwereresponsibleforasignificantportionofthemanuscript.Allauthors
switched to a different class of antipsychotic agents
readandapprovedthefinalmanuscript.
[21,22]. Interestingly, over the past decades, several stu-
dies have specifically examined the relationship between Author’sinformation
1No.210,Sec.1,ZhongzhengRd.,DonggangTownship,PingtungCounty
prolactin levels and granulomatous diseases. These stu-
928,Taiwan.2,3No.699,Sec.1,ZhongqiRd.,WuqiDist.,TaichungCity435,
dies suggest that prolactin contributes to a wide variety Taiwan.4No.45,ChengHsinSt.,Pai-Tou,Taipei.
of both physiological and pathological granulomatous
Competinginterests
cutaneous lesions, especially those of immune response,
Theauthorsdeclarethattheyhavenocompetinginterests.
such as the non-caseating granulomas [23,24]. The clini-
cal presentation of IGM patients is similar, despite the Received:3September2011 Accepted:5January2012
Published:5January2012
varied causes behind the laboratory evidence of hyper-
prolactinemia or galactorrhea. Based on these findings,
References
hyperprolactinemia and/or galactorrhea along with other 1. KesslerE,WollochY:Granulomatousmastitis:alesionclinicallysimulating
superimposing causes, such as local trauma or irritation carcinoma.AmJClinPathol1972,58(6):642-646.
2. Bani-HaniKE,YaghanRJ,MatalkaII,etal:Idiopathicgranulomatous
may be the sequential features that result in IGM.
mastitis:timetoavoidunnecessarymastectomies.BreastJ2004,
There is no consensus regarding the ideal manage- 10(4):318-322.
ment of IGM. A conservative non-operative treatment is 3. AkcanA,AkyildizH,DenememMA,etal:Granulomatouslobularmastitis:
acomplexdiagnosticandtherapeuticproblem.WorldJSurg2006,
usually recommended for IGM patients with mild symp-
30(8):1403-1409.
toms [25]. Therapy is recommended for patients with 4. FletcherA,MagrathIM,RiddellRH,etal:Granulomatousmastitis;areport
drug-induced hyperprolactinemia, and these patients are ofsevencases.JClinPathol1982,35(9):941-945.
5. GoldbergJ,BauteL,StoreyL,ParkP:Granulomatousmastitisin
usually shifted to a prolactin-sparing agent. For patients
pregnancy.ObstetGynecol2000,96(5):813-815.
with more severe symptoms, oral prednisolone is admi- 6. ImotoS,KitayaT,KodamaT,etal:Idiopathicgranulomatousmastitis:case
nistered [26]. Immunosuppressants may be effective in reportandreviewoftheliterature.JpnJClinOncol1997,27(4):274-277.
7. TaylorGB,PaviourSD,MusaadS,etal:Aclinicopathologicalreviewof34
refractory cases of the above regimens [27,28]. Finally,
casesofinflammatorybreastdiseaseshowinganassociationbetween
in persistent or recurrent cases, wide surgical excision corynebacteriainfectionandgranulomatousmastitis.Pathology2003,
and/or mastectomy should be considered [2,29]. 35(2):109-119.
8. PanzacchiR,GalloC,FoisF,etal:Primarysarcoidosisofthebreast:case
descriptionandreviewoftheliterature.Pathologica2010,102(3):104-7.
Conclusions 9. NaraynsinghV,HariharanS,DanD,etal:Conservativemanagementfor
Idiopathic granulomatous mastitis is an uncommon idiopathicgranulomatousmastitismimickingcarcinoma:casereports
andliteraturereview.BreastDis2010,31(1):57-60.
benign entity of the breast with a diagnosis exclusive of 10. AllendeDS,BoothCN:Wegener’sgranulomatosisofthebreast:arare
malignancy and infectious etiology. In this study, we entitywithdailyclinicalrelevance.AnnDiagnPathol2009,113(5):351-357.
report a case with this mysterious entity in a non-preg- 11. ObermanHA:Invasivecarcinomaofthebreastwithgranulomatous
response.AmJClinPathol1987,88(6):718-721.
nant woman with a laboratory evidence of hyperprolac-
12. Shishido-Hara,etal:Twocasesofbreastcarcinomawithosteoclastic
tinemia due to risperidone usage. Investigating more giantcells:Aretheosteoclasticgiantcellsprotumouraldifferentiationof
number of case reports and further assessments are macrophages?DiagnPathol2010,5:55-62.
13. BisharaMR,RossC,SurM:Primaryanaplasticlargecelllymphomaofthe
necessary for understanding the relationship between
breastarisinginreconstructionmammoplastycapsuleofsalinefilled
hyperprolactinemia and IGM. breastimplantafterradicalmastectomyforbreastcancer:anunusual
casepresentation.DiagnPathol2009,4:11-17.
14. AzlinaAF,ArizaZ,ArniT,etal:Chronicgranulomatousmastitis:
Consent
diagnosticandtherapeuticconsiderations.WorldJSurg2003,
Written informed consent was obtained from the 27(5):515-518.
patient for publication of this Case Report and any
Linetal.DiagnosticPathology2012,7:2 Page6of6
http://www.diagnosticpathology.org/content/7/1/2
15. SalamIM,AlhomsiMF,DanielMF,etal:Diagnosisandtreatmentof
granulomatousmastitis.BrJSurg1995,82(2):214.
16. CserniG,SzajkiK:Granulomatouslobularmastitisfollowingdrug-induced
galactorrheaandblunttrauma.BreastJ1999,5(6):398-403.
17. Andrade,etal:Malignantmammarytumorinfemaledogs:
environmentalcontaminants.DiagnPathol2010,,5:45-50.
18. GoingJJ,AndersonTJ,WilkinsonS,etal:Granulomatouslobularmastitis.J
ClinPathol1987,40(5):535-540.
19. RoweP:Granulomatousmastitisassociatedwithapituitary
prolactinoma.BrJClinPract1984,38(1):32-34.
20. DicksonRA,DalbyJT,WilliamsR,etal:Risperidone-inducedprolactin
elevationsinpremenopausalwomenwithschizophrenia.American
JournalofPsychiatry1995,152(7):1102-1103.
21. MegensAA,AwoutersFH,SchotteA,etal:Surveyonthe
pharmacodynamicsofthenewantipsychoticrisperidone.
Psychopharmacology1994,114(1):9-23.
22. SzarfmanA,TonningJ,LevineJ,etal:Atypicalantipsychoticsandpituitary
tumors:apharmacovigilancestudy.Pharmacotherapy2006,26(6):748-758.
23. FoitzikK,LanganEA,PausR:Prolactinandtheskin:adermatological
perspectiveonanancientpleiotropicpeptidehormone.JInvestDermatol
2009,129(5):1071-1087.
24. LinChih-Hsun,MaHsu,ChungMing-Tung,etal:Granulomatous
CutaneousLesionsAssociatedWithRisperidone-Induced
HyperprolactinemiainanAmputatedUpperLimb.IntJDermatology
2011,DOI:10.1111/j.1365-4632.2011.04906.x.
25. LaiEC,ChanWC,MaTK,etal:Theroleofconservativetreatmentin
idiopathicgranulomatousmastitis.BreastJ2005,11(6):454-456.
26. ErhanY,VeralA,KaraE,etal:Aclinicopathologicstudyofarareclinical
entitymimickingbreastcarcinoma:idiopathicgranulomatousmastitis.
Breast2000,9(1):52-56.
27. KimJ,TymmsKE,BuckinghamJM:Methotrexateinthemanagementof
granulomatousmastitis.ANZJSurg2003,73(4):247-249.
28. AkbulutS,ArikanogluZ,SenolA,etal:Ismethotrexateanacceptable
treatmentinthemanagementofidiopathicgranulomatousmastitis?
ArchGynecolObstet2011.
29. AsogluO,OzmenV,GorgunE,etal:Feasibilityofsurgicalmanagementin
patientswithgranulomatousmastitis.BreastJ2005,11(2):108-114.
doi:10.1186/1746-1596-7-2
Citethisarticleas:Linetal.:Idiopathicgranulomatousmastitis
associatedwithrisperidone-inducedhyperprolactinemia.Diagnostic
Pathology20127:2.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at
www.biomedcentral.com/submit