Clin Pathol 1997;50:324-327

Ovarian granulomas: a report of 32 cases

W G McCluggage, D C Allen

AbstractAims-To determine the causes ofovariangranulomatous inflammation and to dis-cuss the differential diagnoses.Methods-The pathological features of allovarian granulomas identified by pathol-ogy SNOMED coding in Northern Irelandover a 13 year period were reviewed. Casenotes of patients were also reviewed.Results-The most common cause ofovarian granuloma was a foreign bodyreaction to suture material introduced ata previous operative procedure (15 cases).Other causes were Crohn's disease (fourcases), previous diathermy (two cases),tuberculosis (two cases), a necrotisingreaction following previous surgery (twocases), endometriosis (one case), and bac-terial tubo-ovarian abscess (one case). Infive cases, no cause was apparent for thegranulomatous inflammation. In these,varying numbers of small, well circum-scribed cortical granulomas were present.These cases correspond to so-called "idio-pathic" cortical granulomas.Conclusion-The study confirms the widerange of conditions which can give rise toovarian granulomatous inflammation.(7 Clin Pathol 1997;50:324-327)

Keywords: ovary; granulomatous inflammation; differ-ential diagnosis

Department ofPathology, RoyalGroup of HospitalsTrust, Belfast,Northern IrelandW G McCluggage

Department ofPathology, Belfast CityHospital Trust,Belfast, NorthernIrelandD C Allen

Correspondence to:Dr WG McCluggage,Department of Pathology,Royal Group of HospitalsTrust, Grosvenor Road,Belfast BT12 6BLNorthern Ireland.

Accepted for publication16 January 1997

The finding of ovarian granulomas in a surgicalpathology specimen is relatively uncommon.

Worldwide, the most common cause of ovariangranulomatous inflammation is tuberculosis,usually in association with tuberculous salpin-gitis. In developed countries, descriptions ofovarian granulomas are usually reports ofsingle or small numbers of cases. We describe32 cases of ovarian granulomas collected fromall the pathology departments in Northern Ire-land over a 13 year period. The case notes of allpatients were reviewed. We describe theclinicopathological features and discuss thedifferential diagnoses of ovarian granulomas.

Patients and methodsThe histopathology service for Northern Ire-land is provided by laboratories in fivehospitals: the Royal Group of Hospitals Trust,Belfast; the Belfast City Hospital Trust,Belfast; Altnagelvin Hospital, Londonderry;Antrim Area Hospital, Antrim; and CraigavonArea Hospital, Craigavon. Cases of ovariangranulomas which had been SNOMED codedwere identified from the records of the pathol-ogy departments of these hospitals over the 13

Table 1 Causes of ovarian granulomas in 32 patients

Cause Number of cases

Foreign body reaction tosuture 15

Crohn's disease 4Previous diathermy 2Tuberculosis 2Postoperative necrotising

reaction 2Endometriosis 1Tubo-ovarian abscess 1Idiopathic 5

Table 2 Clinical details and pathologicalfeatures offivepatients with idiopathic ovarian granuloma

MenopausalAge (years) status Associatedpathology

45 Perimenopausal Adenomyosis, Brennertumour, paratubal cyst

43 Premenopausal Uterine fibroids61 Postmenopausal Cystic hyperplasia

endometrium, endometriosis,uterine fibroids

64 Postmenopausal Endometrial adenocarcinoma78 Postmenopausal Uterine fibroids

year period 1984-96. Haematoxylin and eosinstained sections of all cases were reviewed andthe case notes of all patients were examined.

Cases of granulomatous reaction to keratinin ovarian teratomas and cases of histiocyticreactions in endometriosis were excluded.

ResultsOver the period of the study, 32 cases of ovar-ian granulomas were identified. Table 1 showsthe causes of ovarian granulomas determinedfrom the pathological features and case notes.Table 2 provides brief clinical details and asso-ciated pathological findings in the five cases ofidiopathic granulomas, all of which wereincidental findings in ovaries removed duringhysterectomy.

POSTOPERATIVE CASESThe most common cause of ovarian granulo-mas (15 cases) was a foreign body reaction tosuture material, introduced at a previousoperative procedure. All cases contained for-eign body giant cells in relation to doublyrefractile suture material (fig 1). In twoadditional cases, areas of fibrinoid necrosiswere surrounded by a palisaded histiocyticreaction which included several Langhans-typegiant cells (fig 2). Organisms were notidentified with special stains. There was ahistory of previous surgery in both cases andthese were presumed to be unusual postopera-tive reactions.

CROHN'S DISEASEThree of the four cases in Crohn's diseasepatients had similar features; two of these

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Ovarian granulomas

Figure 1 Granuloma containing foreign body type giant cells.

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Figure 2 Granuloma containing central area offibrinoid necrosis with surroundinghistiocytic reaction, including an occasional giant cell.

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ian parenchyma. The granulomas were

posed of epithelioid histiocytes, lymphc

plasma cells, and multinucleate giant

some of which were of foreign body type.

of the granulomas had central suppurationwith microabscess formation (fig 3). Fissureulcers, lined by inflammatory granulationtissue, extended from the ovarian surface deepinto the parenchyma, and fragments of vegeta-ble material were identified. In the fourth case,

V which involved the left ovary, several small, wellcircumscribed, non-necrotising granulomaswere present in the ovarian cortex.

PREVIOUS DIATHERMYTwo cases of florid granulomatous reaction to

, . previous ovarian diathermy were identified. Inthese cases, areas of coagulated tissue weresurrounded by a histiocytic and giant cell reac-tion (fig 4).

NV TUBERCULOSISThe two cases of tuberculosis exhibited bilat-eral involvement of ovaries and fallopian tubes.Numerous granulomas with central caseousnecrosis and containing Langhans-type giantcells were present. In one case, granulomaswere also identified within the endometriumand in the other case there was peritonealinvolvement. Special stains revealed acid fastbacilli in one case and in the other there wasculture proven mycobacterium tuberculosis.

IDIOPATHIC CASESIn five cases, no cause for the ovariangranoluma could be determined. The left ovarywas affected in three cases and the right ovaryin two. All exhibited similar histologicalfeatures. Granulomas were confined to theovarian cortex and were generally few innumber, varying from one to several. Theywere small, well circumscribed, and composedof lymphocytes, histiocytes, and multinucleategiant cells, without central necrosis (fig 5). Inseveral cases, small collections of lymphocyteswere present in the ovarian cortex, separatefrom the granulomas. Organisms were notidentified with special stains.

"K-0j, OTHER CASESIn one case, well circumscribed granulomaswere present in an ovary with coexistentendometriosis. In another case, occasional wellcircumscribed granulomas were present in a

4 tubo-ovarian abscess. No acid fast bacilli or

other organisms were identified with specialstains. However, culture revealed a mixed bac-terial growth.

DiscussionIn developed countries, the female genital tractin general and the ovaries in particular arerarely the site of granulomatous inflammation

414; ..l and it is relatively uncommon to encountertration ovarian granulomas in a surgical pathology

specimen. Worldwide, the most common causeof ovarian granulomatous inflammation is

nd the tuberculosis. Both ovary and adjacent fallopianierous tube are usually affected and there is generallyovar- involvement of other parts of the female genitalcom- tract, especially the endometrium. We identi-

)cytes, fied two cases of ovarian involvement in tuber-cells, culosis in the present study. Other infectiousMany agents which may result in ovarian granulomas

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McCluggage, Allen

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Coagulated amorphous tissue with surrounding histiocytic and giant cell

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Figure 5 Small, compact idiopathic cortical granuloma of histiocytes and lymphocy,Collections of lymphocytes are present in the surrounding stroma.

include fungi, actinomyces, schistosomes, andEnterobious vermicularis. A granulomatous reac-

tion may occasionally occur as a non-specificresponse in a mixed bacterial tubo-ovarianabscess, as in one case in the present study.Demonstration of organisms may require theexamination of multiple histological sectionswith a panel of special stains.

In the present study, the most commoncause of ovarian granulomas was a reaction tosuture material introduced during a previousoperation. With the increasing emphasis on

conservative surgery with ovarianpreservation-for example, cystectomy andwedge resection, it is expected that suchgranulomas will be encountered more fre-quently. Talc and starch granulomas may alsooccur postoperatively. They are usually typicalforeign body type and, in starch granulomas,the pathognomonic Maltese cross pattern canbe demonstrated by examination under polar-ised light.

Postoperative necrobiotic granulomas in-volving the prostate and bladder have been welldocumented. Such lesions have occasionallybeen described within the ovary,' 2 as well as inother parts of the female genital tract.' 4 We

identified two cases in the present study. Thesegranulomas, consisting of central fibrinoidnecrosis surrounded by palisaded histiocytesand giant cells, raise the possibility of rheuma-toid disease or tuberculosis. As far as we areaware, such a lesion has not been described inthe ovary of a patient with rheumatoid arthritis.Pathologists should be aware that necrotisingovarian granulomas may occur as a reaction toprevious surgery. Kernohan et ar described twocases of non-infectious palisading granulomaof the ovary with central fibrinoid necrosis,similar to postoperative necrotising granulo-mas. In neither case was there a history ofrheumatoid disease or previous ovarian sur-gery.The second most common identifiable cause

of ovarian granulomas in the present study wasCrohn's disease. This suggests that ovarianinvolvement in Crohn's disease may be morecommon than is generally realised. One ofthese cases has been the subject of a previousreport6 and several other cases of ovarianinvolvement in Crohn's disease have beendocumented.7'-" Three of the cases we identi-fied showed similar histological features. Fis-sure ulcers, lined by inflammatory granulationtissue, extended from the ovarian surface deepinto the parenchyma. Numerous granulomaswere present, many of which contained centralareas of suppuration. Occasional fragments ofvegetable material were identified which elic-ited a foreign body giant cell reaction. In thesecases, the ovaries were adherent to adjacentsegments of bowel and the histological featuressuggest that the granulomatous involvementwas due to direct extension of the inflamma-tory process from adjacent segments of intes-tine. This is similar to the pathogenesis of thefistulous tracts between segments of bowel andbetween cutaneous surfaces and bowel whichare commonly seen in Crohn's disease. Rightsided ovarian involvement is more common inCrohn's disease resulting from adjacent termi-nal ileitis. However, the left ovary may beaffected by extension from diseased sigmoidcolon. The fourth case of ovarian involvementin a patient with Crohn's disease showed a dif-ferent picture with several small, well circum-scribed granulomas near the cortical surface. Itmay be that these granulomas were not relatedto the Crohn's disease but were small idio-pathic cortical granulomas.Diathermy granulomas involving the ovary

may occur in patients who have had laparo-scopic cauterisation for conditions such asendometriosis." Amorphous coagulated tissueis surrounded by a granulomatous reactioncontaining foreign body giant cells. Similarlesions have been described in the fallopiantube following tubal diathermy.'2 In the twocases we describe, laparoscopic cauterisationhad been performed 18 and 12 monthspreviously. Pathologists should be aware of thiscondition as the history of previous ovariancauterisation may not always be provided.A histiocytic reaction in the ovary may occur

in association with endometriosis. Such reac-tions are not usually granulomatous but consistof histiocytes which may contain both haemo-

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siderin and lipofuschin pigment. Clement etal"3 described cases of ovarian and peritonealnecrotic pseudoxanthomatous nodules in pa-tients with endometriosis. In these cases, foci ofrecognisable endometriosis were sparse andwere only identified by examination of multiplesections. Cases such as these were excludedfrom our study as were cases of granulomatousreaction to leaked contents of cystic teratomas.However, we identified a single case in whichsmall, well circumscribed ovarian granulomascoexisted with endometriosis. Whether thisrepresents a reaction to the nearby endome-triosis is uncertain. Another granuloma-likeprocess which may occasionally affect the ovaryis malacoplakia.'"There were five cases of ovarian granulomas

for which no cause was apparent, even afterexamination of the case records. All occurredas an incidental finding in an ovary removedduring hysterectomy. The histological featuresin all cases were remarkably similar. Varyingnumbers of small, compact, well circumscribedand non-necrotising granulomas were confinedto the ovarian cortex. The granulomas werecomposed of lymphocytes, histiocytes, andmultinucleate giant cells. In several cases, scat-tered collections of small lymphocytes werealso present within the cortex, perhaps suggest-ing an early stage in the evolution of ovariangranulomas. Such idiopathic cortical granulo-mas were first described in postmenopausalovaries by Hertig in 1944's and elaboratedupon in a subsequent study.'6 Similar lesionswere described later by Hughesdon. 7 Theauthors of these studies considered that theywere modified stromal lesions, representing areaction to regressing hyperplastic stromalnodules and suggested they were confined topostmenopausal ovaries. However, in thepresent study we identified identical granulo-mas in the ovaries of premenopausal and peri-menopausal women. Herbold et all8 describedfour apparently idiopathic cases of ovariangranulomas in premenopausal women, none ofwhom had a history of systemic granulomatousdisease. However, in three patients there was ahistory of previous ovarian surgery and,although organisms were not identified, thehistological features in the fourth were sugges-tive of an infectious process.The fact that only five cases of idiopathic

cortical granulomas were identified is some-what surprising. Such granulomas are generallyaccepted to comprise the majority of cases ofovarian granulomas-40% of cases in womenover age 40 has been quoted in some standardtexts. These granulomas are usually few innumber and, since only one or two histologicalsections of a grossly normal ovary will generallybe examined, may be missed by standardpathological analysis. In addition, such granu-lomas may easily be overlooked by the patholo-gist or not be commented upon in surgical

reports. Even if identified they may not becoded, presumably accounting for their spar-sity in the present study, which essentially hasidentified ovarian granulomas that were clini-cally relevant.

Ovarian involvement has rarely been re-

ported in sarcoidosis'9 21 and the small idio-pathic cortical granulomas described mayresult from this condition. In all cases, followup, which ranged from a few months to fouryears, did not reveal evidence of systemicgranulomatous disease. As with apparently iso-lated granulomatous involvement of otherorgans, systemic diseases such as sarcoidosisshould be excluded before designating suchgranulomas as idiopathic. However, the histo-logical features are sufficiently distinctive thatthe term idiopathic cortical granulomas can beconfidently applied when such lesions areidentified by the surgical pathologist.

We thank Dr R Clarke (Craigavon Area Hospital), Dr D Hughes(Altnagelvin Hospital), and Dr B Kenny (Antrim Area Hospital)for their assistance in collecting material for this paper.

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