Br J VenerDis 1983;59:198-201

Primary endometrial and endocervical granulomainguinale (donovanosis)Case report

E M SCRIMGEOUR, S K SENGUPTA, AND I A McGOLDRICKFrom the Departments ofMedicine, Pathology, and Obstetrics and Gynaecology, Faculty of Medicine,University ofPapua New Guinea, Papua New Guinea

SUMMARY Primary endometrial and endocervical granuloma inguinale (donovanosis) was

diagnosed in an 18-year-old Melanesian woman in Papua New Guinea. Granulomatousinvolvement of the parametrium, salpinges, ovaries, and ureters was associated with uretericobstruction and bilateral hydronephrosis. Granuloma inguinale of the cervix, labia majora, andanus developed after diagnostic endometrial curettage. Treatment with tetracycline and laterchloramphenicol had to be stopped because of poor patient compliance. Hysterectomy was

performed, after which the patient made a good recovery. This appears to be the first case ofprimary endometrial and endocervical granuloma inguinale to be reported.

Introduction

Granuloma inguinale (donovanosis) is a mildlycontagious, chronic, painless, ulcerative disease ofthe skin and lymphatic systems of the externalgenitalia, perianal area, and inguinal regions, whichis usually transmitted by sexual intercourse. Thedisease is caused by the Gram-negative bacillusCalymmatobacterium granulomatis, which may bedetected in large clusters in cyst-like spaces in thecytoplasm of large mononuclear cells in scrapingsfrom lesions. In histopathology reports theorganisms are commonly referred to as Donovanbodies. Extracellular bacilli may be observed, and theorganism has been recovered from faeces. Cgranulomatis is best shown by the s'ilver impreg-nation method but satisfactory definition is obtainedwith Giesma, Wright's and Leishman's stains and toa lesser extent with haematoxylin and eosin. It growsreadily at 37°C in the yolk sac of the chick embryo.In most cases the clinical diagnosis is confirmed byhistopathology. In doubtful cases the complementfixation serological test may be of value,1 though thesensitivity and specificity of the test, which is notcomm-ercially available, is low.The lesions of granuloma inguinale may spread

from the external genitalia or perianal area to the

Address for reprints: Dr E M Scrimgeour, 738 Doncaster Road,Doncaster, Victoria 3108, Australia

Accepted for publication 16 December 1982

cervix.3 4 The uterus, fallopian tubes, and ovaries arerarely affected.3 Primary cervical granulomainguinale3 smay be associated with involvement ofthe endometrium7 and the uterus, fallopian tubes,and ovaries.6 Extragenital lesions may occur in manydifferent sites8 by autoinoculation or by spread fromgenital lesions.3 Haematogenous dissemination withmetastatic lesions in bone is a rare complication.9'1

In the present case cervical ulceration was notvisible but endocervical and endometrial granulomainguinale was present and affected parametrial andpelvic structures; it later spread to the cervix, thelabia majora, and the anus.

Cae report

An 18-year-old married Melanesian woman fromChimbu Province in the highlands of Papua NewGuinea was admitted to Port Moresby GeneralHospital on 1 June 1981. She had had backache for ayear, menorrhagia for several months, and a blood-stained vaginal discharge and polyuria for a month.She had had two uncomplicated pregnancies, the lastof which occurred three years before.

CLINICAL FEATURESOn admission she was pale and her temperature was37 2°C. Ankle oedema was present and a firm,painless suprapubic mass was palpable. The externalgenitalia and the vagina were normal but the anteriorlip of the cervix was slightly distorted and retracted;

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Primary endometrial and endocervical granuloma inguinale (donovanosis)

neither cervical erosion nor ulceration was visible.Serosanguinous fluid exuded from the cervical os.The uterus was the size of an 18-week pregnancy andwas non-tender and mobile. Because of parametrialinduration the adnexae were difficult to define. Theanus and perianal region were normal.

INVESTIGATIONSThe urine contained protein 1 5 g/l but no sugar.Microscopy of the centrifuged urine deposit showeda few white cells and white cell casts but bacteria werenot isolated in culture. The haemoglobinconcentration was 6-4 g/dl and the white bloodcount 8 7 x 109/1 with 86% neutrophils; the filmshowed hypochromic normocytic anaemia. Malarialparasites were not seen. Routine biochemical testresults including estimation of the serum creatinineand the fasting and postprandial blood sugarconcentrations were within normal limits. The resultsof the pregnancy test and the Venereal DiseaseResearch Laboratory test were negative as was thatof the Mantoux test. The stool contained hookwormand Trichuris trichura. Pathogenic microorganismswere not isolated in culture of vaginal material.X-ray examination of the chest showed noabnormality.

CLINICAL COURSE AND TREATMENTA diagnostic curettage was carried out on 18 June1981 after a blood transfusion, and endometrialbiopsy specimens were obtained. The curettingsconsisted of caseous material, and endometrialtuberculosis was provisionally diagnosed. Pendingthe results of histological examination simultaneoustreatment with isoniazid and thiacetazone was startedtogether with prednisone 40 mg daily. Ten days laterDonovan bodies were found in the endometrialbiopsy specimen. Granuloma inguinale wasdiagnosed and oral tetracycline 500 mg six hourly bymouth given, and the antituberculosis treatment andprednisone stopped. Unfortunately two days laterthe patient insisted on leaving hospital. She was givena two weeks' supply of tetracycline and was advisedto report back to the outpatient department, but shedid not do so.

READMISSIONOn 23 July 1981 she returned complaining ofincreased swelling of her ankles, an offensive vaginaldischarge, and sores on her vulva and anus. She hadfailed to complete the course of tetracycline. Examin-ation showed painless enlargement of the uterus andascites. On vaginal examination five indurated,painless, beefy-red granulomatous ulcers on the labiamajora and one each on the cervix and anus werenoted. Pelvic examination under anaesthesia showed

multiple indurated masses merging into the enlargeduterus. Biopsy specimens from each of the ulcerscontained Donovan bodies. An intravenouspyelogram showed bilateral ureteric obstruction andhydronephrosis. The serum creatinine concentrationwas 70 gamol/l. Initially chloramphenicol 500 mg bymouth every six hours was given. After 14 days'treatment there was no clinical improvement andlaparotomy was undertaken.

LAPAROTOMYAt operation the pelvis was found to be invadedextensively by inflammatory granulomatous masseswhich affected the parametrium, uterine tubes,ovaries, broad ligaments, and ureters. Granu-lomatous tissue merged with the enlarged uterus, andadhesions of the sigmoid colon, the caecum, andappendix were found. The adhesions were dividedand the granulomatous masses excised, after whichpanhysterectomy and salpingo-oophorectomy werecarried out. Postoperatively treatment withchloramphenicol was continued for three weeks, andher convalescence was uneventful. The ulcers on theexternal genitalia and the anus healed and thehydronephrosis resolved with no further polyuria.She remained well after discharge but failed to returnfor review at six weeks and could not be traced.

HISTOPATHOLOGYEndometrial biopsy specimens obtained on 18 June1981 and those of cervical, vulval, and anal ulcers on27 July 1981 showed a chronic granulomatousreaction with vacuolated macrophages containingbacilli, which when stained with haematoxylin andeosin were typical of Calymmatobacteriumgranulomatis. When examined on 10 August 1981 theuterus measured 10 x 4 cm and was coveredexternally with granulomatous adhesions and largenodules. The endometrium and endocervix appearednormal, but multiple sections stained withhaematoxylin and eosin showed a chronicinflammatory reaction and vacuolated macrophagescontaining Donovan bodies. These last were alsoevident in large foamy histiocytes throughout thegranulomatous nodules in which the salpinges andovaries were embedded.

Endometrial biopsy specimens were sent to thepathology department at the Royal BrisbaneHospital, Brisbane, Australia, where silver impreg-nation stains were carried out. This confirmed thepresence of C granulomatis within the endometrium(figure).

Discussion

Granuloma inguinale occurs in many tropical areasincluding northern Australia, India, and Guyana and

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EM Scrimgeour, S K Sengupta, and I A McGoldrick

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*. *: : F .: .6W:.FIGURE Endometrial biopsy specimen showing (a) the granulomatous reaction in the stroma with foamy macrophages,polymorphonuclear granulocytes, and plasma cells (H & E x 250); (b) large foamy histiocytes with eccentric nucleiand groups of rod-shaped intracellular Donovan bodies within the cytoplasm (Warthin Starry stain x 1000).

is also prevalent among Negro homosexuals in thesouth-eastern states of the United States ofAmerica.'2 The disease was probably introduced intoPapua New Guinea during the early colonialperiod.'3 Subsequently it became one of the mostprevalent venereal diseases, occurring especially inyoung immigrant men in Port Moresby." By 1975 ithad become the commonest cause of anogenitallesions in women in Port Moresby.'4

In most cases granuloma inguinale is limited to thevulval, inguinal, and perianal regions but may rarelyspread to the cervix3 4; it may then resemblecarcinoma,'5 as may primary cervical granulomainguinale itself.56 Even more unusual are cases inwhich the disease extends from the external genitaliaand cervix (or from a primary cervical lesion) to theuterus and pelvic structures; in these cases it maysimulate advanced pelvic cancer.67 14 16

In Jofre's case'6 there was extensive involvementof the external genitalia and perianal areas as well as

the cervix, uterus, parametrium, and adnexae, whichproduced a "frozen pelvis" and simulated pelviccancer. Total resolution occurred after treatment for10 weeks with tetracycline in an oral dose of 250 mgfour times a day. In the case of primary cervicalgranuloma inguinale described by Bhagwandeen etal' there was no visible improvement despite fiveweeks' treatment with streptomycin. As a coexistentcarcinoma may have been present hysterectomy wasperformed. Histopathology showed extensive endo-metrial granuloma inguinale. In the case reported byVacca et alP4 fungating cervical lesions suggestingcervical carcinoma were associated with bilateralparametrial induration extending to the side walls ofthe pelvis with ureteric obstruction and hydro-nephrosis. Complete resolution occurred aftertreatment with chloramphenicol (the duration oftreatment was not stated). In the case reported byPund and Gotcher'2 histopathological examinationconfirmed that granuloma inguinale had spread from

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Primary endometrial and endocervical granuloma inguinale (donovanosis)

the cervix to the uterus, tubes, and ovaries. As well assimulating carcinoma of the genitalia granulomainguinale may be associated with the subsequentdevelopment of neoplasia,'5 1718 though this has notbeen established.2

In the present case there were no cervical ulcers orerosions initially, and the infection probably beganeither in the endometrium, with subsequent spread tothe parametrium and endocervix or in the endocervixextending subsequently to the endometrium, theparametrium, and other pelvic structures. In view ofthe extensive endometrial and pelvic disease andminimal endocervical involvement a primary endo-metrial focus is probable in this case. The laterdevelopment of ulcers on the cervix, vulva, and anusmay have resulted from abrasion of these areas2during diagnostic curettage and contamination byinfected endometrial curettings. Depression ofimmunity by high doses of prednisone may havecontributed to their evolution. The incubation periodfor granuloma inguinale lesions may vary from a fewdays to several months.'8

This case indicates that even when there is novisible cervical ulceration endocervical andendometrial granuloma inguinale may be present.Especially in tropical countries where granulomainguinale is endemic this possibility should beconsidered in the differential diagnosis of apparentendometrial tuberculosis or advanced pelvic cancerwith or without osteolytic bone metastases.

We thank Dr R A Cooke, anatomical pathologist,pathology department, Royal Brisbane Hospital,Brisbane, Queensland, Australia, who performed thesilver staining of endometrial biopsy specimens andconfi'rmed the diagnosis of endometrial granulomainguinale.

Referemces

1. Goldberg J, Weaver RH, Packer H et al. Studies on granulomainguinale. II The complement fixation test in the diagnosis ofgranuloma inguinale. Am J Syph Gon Vener Dws 1953;37:17-76.

2. Kuberski T. Granuloma inguinale. Sex Transm Dis 1980;7:29-36

3. Rajam RV, Rangiah PH. Donovanosis (granuloma inguinale,granuloma venereum). WHO Monogr Ser No 24, Geneva:WHO, 1954.

4. Douglas CO. Lymphogranuloma venereum and granulomainguinale of the vulva. Journal of Obstetrics and GynaecologyOf the British Commonwealth 1962;69871-80

5. Pund ER, Greenblatt RB. Granuloma venereum of the cervixuteri (granuloma inguinale) simulating carcinoma. JAMA1937; li: 1401.

6. Pund ER, Gotcher VA. Granuloma venereum of uterus, tubesand ovaries. Surgery 1938;3:34-S.

7. Bhagwandeen SB, Mottiar YA. Granuloma venereum. J ClinPathol 1972;25:812-6.

8. Nair VG, Pandaiai NG. Granuloma genito-inguinale. IndianMed Gaz 1934;69 361-72.

9. Packer H, Turner HB, Dulaney AD. Granuloma inguinale ofthe vagina and cervix uteri with bone metastases. JAMA1948; 136:327-9.

10. Kalstone BM, Howell jun JA, Cline FX. Granuloma inguinalewith haematogenous dissemination to the spine. JAMA1961; 176:530-2.

11. Maddocks I, Anders EM, Dennis E. Donovanosis in PapuaNew Guinea. Br J Vener Dis 1976;52:190-6.

12. Davis CM. Granuloma inguinale. JAMA 1970;211:632-6.13. Maddocks I. Venereal diseases. In: Bell C, ed. The diseesand

health services of Papua New Guinea. Port Moresby:Department of Public Health, 1973;234-7.

14. Vacca A, McMillan LL. Anogenital lesions in women in PapuaNew Guinea. Papua New Guinea Med J 1980;23:70-3.

15. Stewart DB. The gynaecological lesions of lymphogranulonavenereum and granuloma inguinale. Med Clin North Am1964;48:773-86.

16. Jofre ME, Webling DD'A, James ST. Granulona inguinalesimulating advanced pelvic cancer. Med JAust 1976;2:869-73.

17. Stewart DB. Ulcerative and hypertropic lesions of the vulva.Proc R Soc Med 1968;61:363-5.

18. Alexander LJ, Shields TL. Squamous cell carcinoma of thevulva secondary to granuloma inguinale. Archives ofDermatology and Syphilis 1953;67:395.402.

19. Lal S, Nicholas C. Epidemiological and clinical features in 165cases of granuloma inguinale. Br J Vener Dis 1970;46:461-3.

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