J Clin Pathol 1982;35:941-945

Granulomatous mastitis: a report of seven cases

A FLETCHER,* IM MAGRATH,t RH RIDDELL,* IC TALBOT*

From the *Department ofPathology, Clinical Sciences Building, Leicester Royal Infirmary, POB65, LeicesterLE2 7LX, tthe Croydon Area Laboratory, Mayday Hospital, Mayday Road, Thornton Heath, Surrey,CR4 6YE, and the tDepartment ofPathology, University of Chicago, 950 East 95th Street, Chicago, Illinois,USA 60637

SUMMARY The clinical history and histological features of seven cases of granulomatous mastitisare presented. The lesion occurs in young parous women as a tender extra-areolar breast lump.Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, inthree cases, coalescence of the granulomas and microabscess formation. Pathogenesis of thechanges is discussed. It is thought that granulomatous mastitis is an entity morphologicallydistinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breastdiseases.

A granulomatous inflammatory response can be areaction to either a specific agent-for example,Mycobacterium tuberculosis or a characteristic of adisease-for example, sarcoidosis. Five patients withbreast nodules showing such a reaction, yet unre-lated to any specific infection, trauma or foreignmaterial, were reported by Kessler and Wollochl in1972. They found a discrete granulomatous lobulitisand because of the morphological resemblance togranulomatous thyroiditis and orchitis, suggestedthat it might be immunologically mediated. Sincetheir publication further reports have appeared;Cohen2 reported five cases, Koelmeyer and Mac-Cormick3 two cases and Brown and Tang4 twofurther cases. Descriptions have not appeared in theEuropean literature, recent editions of standard text-books of pathology and a more specialised treatisewith the exception of Azzopardi's recent book.5 Theolder literature contains many descriptions of thepathology of chronic mastitis, some emphasising theplasma-cell infiltrate,6 others the presence offoreign-body giant cells,' but none mention agranulomatous reaction in a lobular distribution. Wetherefore wish to present the clinical details and his-tology of seven further cases of this evidently poorlyrecognised condition, from our routine biopsypathology service.

Report of the cases

The individual patients' clinical details are summar-ised in Table 1. They were all young, parous and all

Accepted for publication 20 January 1982

Table 1 A summary ofthe main clinical details frompatents presenting with an extra-areolar, painftl swelling ofabout four weeks duration

Age Parity Time since Breast Lymph nodes(yr) last pregnancy

(months) Enlarged Painful

1 31 6 24 R - -2 32 2 2 L - +3 22 5 6 L - -4 25 2 12 R - -5 29 2 78 R - -6 42 4 12 R - -7 23 1 1 L - -

presented within six years of a pregnancy with apainful extra-areolar swelling. None had breast fedtheir most recent infant and there was no constanthistory of oral contraceptive use. There was no pre-diliction for any particular site within the breast andonly one patient had tender axillary lymph nodeswhich were not clinically enlarged. After surgicalexcision of the swelling three out of five patients forwhich follow-up information is available developedsuperficial wound infections in the subsequent 10months. All responded to antibiotics or drainage.One patient (case 7) developed a further breastmass requiring re-excision and an indurated areadeveloped in the opposite breast. Culture of tissuefailed to grow any pathogens or mycobacteria. Shewas treated with steroids and the lesion graduallyresolved.The main histological feature, present in all seven

cases, was a granulomatous inflammatory responseaffecting the breast lobules (Fig. 1). The granulomaswere composed of epithelioid histiocytes, with occa-

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Fig. 1 Breast tissue showinginflammation centred on a lobule,with discrete granulomas (containingLanghans-type multinucleate cells).Haematoxylin and eosin x400

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Fig. 2 Part ofa breast lobule,showing discrete granulomas withmultinucleate cells, and occasionalpolymorphs. Haematoxylin andeosin x600

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sional Langhans-type multinucleate giant cells,eosinophils and scanty collections of polymor-phonuclear leucocytes (Fig. 2). They were usuallysmall, well circumscribed and confined to thelobules, but in three of the cases there was oblitera-tion of the lobular architecture by sheets ofepithelioid cells and microabscesses were present

(Fig. 3). In two of the cases marked ductular damagewas present, with ulceration of the ductularepithelium and polymorphs in the lumen (Fig. 4).Outside the microabscesses, there were no areas ofnecrosis or caseation within any of the granulomas.No refractile material was found. Ziehl-Neelsen andperiodic-acid Schiff stains were done and in none of

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Granulomatous mastitis: a report of seven cases 943

Fig. 3 An area of confiuentgranulomas, with microabscessformation centred on breast lobules.Haematoxylin and eosin x400

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Fig. 4 A breast ductule showingdamaged epithelium with epithelialulceration and polymorphs in thelumen. The surrounding acini areundergoing atrophy. Haematoxylinand eosin x 700

the patients was there any clinical or histological Discussionevidence of tuberculous infection or sarcoidosis. There-excision specimen in case 7 showed a The clinical findings of a painful extra-areolargranulomatous lobulitis similar to the original nodule occurring in young, parous women, com-biopsy but with marked microabscess formation. posed histologically of granulomatous lobulitis

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Table 2 A summary ofthe clinical details and histological appearances ofall the reported cases ofgranulomatous mastitis

Authors No of Age Parity Pain Extra- Axillary lymph tnodes Histological appearance: No of cases in each reportcases range areolar

(yr) site Tender Enlarged Discrete Confluent Ductular changesgranulomas epithelioid

cellslmicro Inflammation Misc *abscesses

Kessler and 5 23-42 2-6 + + 0 1 5 3 - 2WollochCohen2 5 17-34 - - + - 0 5 2 4Brown and 2 32-35 2-4 + + 1 1 2 1Tang4Koelmeyer and 2 24-26 1-2 + + 0 1 2 - -MacCormick3Miller' 1 33 - - + 0 0 1 - 1Present report 7 22-42 1-6 + + 1 0 7 3 2 0

*Ductular dilatation, squamous metaplasia.

accords well with the features previously reported(Table 2). In the absence of clinical and histologicalevidence of an infective cause for the granulomatousreaction we think that this morphological appear-ance is sufficiently distinct as to be considered aseparate disease entity.The main distinguishing histological feature is an

inflammatory reaction composed of discretegranulomas confined to the lobules. This has beenseen in all the reported cases, with the occasionaloccurrence of microabscesses, particularly whensheets of epithelioid cells are present. Other changeshave been seen; ductular dilatation,'-' squamousmetaplasia.36 a foreign-body reaction around kera-tin flakes,6 and ductular inflammation.6 This lastappearance, seen in two of our cases, probably rep-resents an early stage in the progression of theinflammation and may provide a clue to thepathogenesis; damage to ductular epitheliumwhether by infection, trauma or a chemically-induced inflammation would allow luminal secretionto escape into the lobular connective tissue, therebystimulating a granulomatous response, with result-ing further damage to lobular structures.Although the lesion is confined to young parous

women, we have found no clinical relation withbreast feeding or hormonal contraceptive use. Noneof the patients breast fed but we do not know ifhormonal means of milk suppression were used.Follow-up details after excision of the mass havebeen presented in some of the case reports in theliterature34 and have suggested that wound infectionis a frequent problem. Our observations support this,three of five patients developing superficial infectiveproblems, and one developing a recurrence withinthe breast. Steroid therapy has been recommendedbefore surgical excision9 and steroids were used withsome effect after the second excision in case 7.There is very little evidence in the reported cases

to suggest a distinct aetiology for granulomatous

mastitis. Kessler and Wolloch,' because of the mor-phological resemblance to granulomatous orchitis,suggested an immune aetiology but DeHertoghet a19 found no immune dysfunction in their reportedcase. The morphological features seen in immune-mediated inflammation; a predominantly plasmacell infiltrate, lymphoid aggregates with germinalcentres and a vasculitis, were not present in any ofthe seven cases examined and in none of those pre-viously reported. Solitary lesions with microabscessformation and a high proportion of postoperativeinfective complications does suggest a purely infec-tive aetiology. Unfortunately, no confirmatory bac-teriology is available. Until further studies on theimmune status of the patients with granulomatousmastitis and microbiological studies on the excisedtissue are reported, any suggestions as to itsaetiology are speculative.Inflammatory breast lesions of this kind may be

clinically mistaken for malignancy'0 particularly ifreactive draining lymph nodes are enlarged. Onlyone of our patients had tender nodes but in none ofthe cases were they enlarged. Certainly, carcinomashould not be excluded on clinical grounds alone,but we feel that on subsequent histology the correctdiagnosis can be made. The differentiation ofgranulomatous mastitis from most of the otherchronic inflammatory lesions of the breast should bepossible on histological grounds; in particular thegranulomas lack the caseation seen in tuberculousinfection, the predominance of plasma cells inplasma cell mastitis and foreign or oily material inoleogranuloma, but sarcoidosis of the breast wouldgive much the same histological picture and in theabsence of systemic disease could easily be confusedwith granulomatous mastitis.Granulomatous mastitis as a distinct morphologi-

cal entity but of as yet unknown aetiology, deserveswider recognition by practising diagnostic patholog-ists.

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Granulomatous mastitis: a report of seven cases

We would like to thank Drs JAH Finbow and MEAPowell for allowing us to use two of their cases, DrPowell for advice and criticism, the secretarial helpof Mrs G Holmes, and Dr K Sidky for translatingfrom the German.

References

Kessler E, Wooloch Y. Granulomatous mastitis: a lesion clini-cally simulating carcinoma. Am J Clin Pathol 1972;58:642-6.

2 Cohen C. Granulomatous mastitis: a review of 5 cases. S Afr MedJ 1977;52:15-16.

3Koelmeyer TD, MacCormick Dem. Granulomatous mastitis.Aust NZ J Surg 1976;46:173-6.

Brown LK, Tang PHL. Post-lactational tumoral granulomatousmastitis: a localised immune phenomenon. Am J Surg1979;138:326-9.

5 Azzopardi JG. Problems in breast pathology. London: WB Saun-ders. 1978:400.

6 Adair FE. Plasma cell mastitis-a lesion simulating mammary

carcinoma. Arch Surg 1933;26:735-49.Schultz A. Handbuch der pathologischem Anatomie Vol II, part

2. Berlin: Julius Springer, 1933: 142-50.8Miller F, Seidman I, Smith CA. Granulomatous mastitis. NY

State J Med 1971;71:2194-5.9DeHertogh DA, Rossof AH, Harris AA, Economou SG. Pred-

nisone management of granulomatous mastitis. N EngI J Med1980;308:799-800.

'Milward TM, Gough MH. Granulomatous lesions in the breastpresenting as carcinoma. Surg Gynaecol Obstet1970;130:478-82.

Requests for reprints to: Dr A Fletcher, Department ofPathology, Clinical Sciences Building, Leicester RoyalInfirmary, PO Box 65, Leicester LE2 7LX, England.

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