Giant cell arteritis of the female genital tract: report of a case and review of the literature.

Abstract: A 65-year-old female presented with constitutional symptoms of fever and weight loss with bilateral adnexal masses on physical examination. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed and subsequently revealed giant cell arteritis involving numerous small arteries in the ovaries, fallopian tubes, paraovarian and paratubal soft tissues, myometrium, and cervix. After surgery, the patient continued to have constitutional symptoms. Corticosteroid therapy led to a significant improvement and eventual resolution of symptoms. Several similar cases of giant cell arteritis of the female genital tract have been described, both with and without concomitant temporal arteritis. Implications for diagnosis and treatment are discussed.

Key Words: female genital tract, giant cell arteritis, polymyalgia rheumatica, temporal arteritis, vasculitis

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Giant cell arteritis is a rare systemic arterial inflammatory disease, classically characterized by chronic inflammation of the medium and small-sized arteries, most commonly the temporal arteries and extracranial branches of the aorta. (1) Patients typically present with constitutional symptoms such as fever, fatigue, and weight loss, in addition to localizing symptoms such as headache, jaw claudication, and occasionally vascular occlusion leading to stroke or transient ischemic attack. Atypically, giant cell arteritis may be discovered in visceral organs such as the kidney. (2) In this case report, we describe a patient who was found to have giant cell arteritis of the female genital tract with no localizing evidence of temporal arteritis. The literature concerning this unusual condition is reviewed as well.

Case Report

A 65-year-old female presented with a 1-month history of fatigue, fever, and lower abdominal pain. She had lost approximately 15 lbs in the previous 3 months. She reported no headaches, visual changes, rash, jaw claudication, night sweats, or cough. She had no other significant medical history and was taking no medications at the time of presentation. Her physical examination revealed only palpable fullness and discomfort in the area of bilateral adnexa. Temporal arteries were normal to palpation. Laboratory studies included erythrocyte sedimentation rate of 80 mm/h; hemoglobin, 8.3 g/dL; hematocrit, 25.8%; and platelet count, 629,000 cells/[mm.sup.3].

A computed tomographic scan of the abdomen and pelvis was performed, revealing a 3.5-cm mass in the right adnexal region (Fig. 1). Serologic tumor markers for alpha fetoprotein, cancer antigen 125, carcino-embryonic antigen, and human chorionic gonadotropin were low or normal. The patient subsequently underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy.

Gross examination of the specimen revealed a 4.0 X 3.0 X 3.0-cm, firm, well-circumscribed right ovarian mass with a solid, white cut surface. The left ovary showed a similar-appearing 2.5 X 1.0 X 0.8-cm mass. The myometrium contained two 0.5-cm leiomyomas.

Microscopic examination of the ovaries demonstrated bilateral benign Brenner tumors, composed of ovoid, stellate, or elongated nests of transitional cells arranged in a fibrous stroma with multifocal calcifications. In addition, there was a widespread giant cell arteritis affecting numerous small arteries in the ovaries, fallopian tubes, paraovarian and paratubal soft tissues, myometrium, and cervix. Affected arteries showed a dense inflammatory infiltrate composed primarily of lymphocytes and epithelioid histiocytes, forming loose granulomas, with fewer plasma cells, eosinophils, and multinucleated giant cells (Figs. 2 and 3). The inflammatory infiltrate concentrically or eccentrically involved affected arteries, was often transmural, and was most prominent in the media with associated disruption of the internal elastic lamina. Many of the involved vessels showed intimal fibrosis with luminal narrowing. No acute inflammation, fibrinoid necrosis, or associated thrombi were seen. The inflammatory infiltrate was sharply limited to the involved vessels with only focal extension of a mild chronic inflammatory infiltrate into the surrounding tissue. Fite and Grocott stains were negative for acid-fast and fungal organisms, respectively.

After surgery, the patient continued to have weight loss and fatigue. Further workup yielded negative results for antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibody tests. Tuberculosis skin testing was negative. Given the pathology results, which were consistent with giant cell arteritis of the female genital tract, and the patient's continued constitutional symptoms, treatment with 60 mg/d prednisone was initiated. The patient had a significant response, with resolution of symptoms, correction of anemia, and return to her previous weight. Her prednisone was tapered to 10 mg/d over a period of 3 months and was then further tapered off by 9 months after surgery. At follow-up, 1 year after surgery, the patient had no complaints and a normal physical examination and laboratory findings, with erythrocyte sedimentation rate of 11 mm/min and C-reactive protein of less than 0.4.

Discussion

Since an early description of giant cell arteritis of the female genital tract by Polasky et al (3) in 1965, at least 28 unique cases have been described in the English literature. (3-6) The clinical presentation of giant cell arteritis of the female genital tract is variable. In only three cases, including ours, patients presented with localized symptoms that could be attributable to this arteritis, whereas the remaining case reports were all incidental findings on hysterectomy specimens obtained for other reasons. (6,7) All patients have been post-menopausal, with an age range of 46 to 82 years (average, 71 years).

The association of giant cell arteritis of the female genital tract with temporal arteritis and polymyalgia rheumatica is also variable. In one autopsy series of 57 women with temporal arteritis, only one had genital tract involvement. (8) Conversely, of the above 28 reported patients with giant cell arteritis of the female genital tract, 10 (36%) had associated temporal arteritis and 8 (29%) had polymyalgia rheumatica. (4-6) Nearly all of these associated diagnoses were made within 4 months of diagnosis of giant cell arteritis of the female genital tract. In 5 of the 10 patients with associated temporal arteritis, the patients had no localizing signs or symptoms of temporal arteritis, but underwent biopsy of the temporal artery after discovery of the genital tract involvement. (2,3,9-11) We cannot rule out the possibility of such occult temporal arteritis in our patient.

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Various other gynecologic lesions have been described in association with giant cell arteritis of the female genital tract, including serous adenomas, squamous cell carcinoma, and leiomyomas and cysts. (4) No other previous case report has described Brenner tumors in association with this vasculitis. All of these associated lesions are believed to be incidental and not directly related to the vasculitis.

Giant cell arteritis is a disease that is effectively treated with anti-inflammatory agents and which, if untreated, may have serious complications. In giant cell arteritis of the female genital tract, therapy with corticosteroids has been variable. In six asymptomatic patients diagnosed by hysterectomy performed for other reasons, no treatment was given, with follow-up ranging from 2 months to 17 years, with no significant complications noted except for a dissecting aneurysm in one patient after 8 years. (12,13) All 18 patients with associated temporal arteritis or polymyalgia rheumatica were given corticosteroid therapy, with significant improvement and no complications of vasculitis after therapy. (4-6) Given the spectrum of findings described in patients with this condition, we recommend that patients with documented genital tract involvement be examined for involvement in other sites and that a temporal artery biopsy be considered even in the absence of localizing symptoms. We elected not to perform such a biopsy in our patient, given the decision to initiate corticosteroid therapy regardless of the result. In patients with persistent constitutional symptoms, elevated laboratory markers of inflammation, or documented temporal artery involvement, we believe that corticosteroid treatment would be warranted, at similar doses for classic temporal arteritis. On the other hand, in patients who show no signs or symptoms of systemic disease after surgery, close clinical follow-up without corticosteroid treatment may be appropriate.

Conclusion

Giant cell arteritis of the female genital tract is a rarely described vasculitis, occurring in postmenopausal women, often in association with temporal arteritis or polymyalgia rheumatica. This condition is often incidentally discovered on hysterectomy performed for other reasons. The role of corticosteroids in the treatment of this condition is unclear, though some patients, such as ours, appear to have a clinical response with corticosteroid treatment.

Acknowledgment

The authors thank Dr. Kyle Molberg for critical review and suggestions on the manuscript.

Accepted April 5, 2004.

References

1. Schoen FJ, Cotran RS. Blood vessels, in Cotran RS, Kumar V, Collins T (eds): Robbins Pathologic Basis of Disease. 6th ed. Philadelphia, WB Saunders Co, 1999, pp 517-519.

2. Medvedev G, Al-Shamari AE, Copland MA, Magil AB. Isolated renal giant cell arteritis. Am J Kidney Dis 2002;40:658-661.

3. Polasky N, Polasky SH, Magenheim H, Abrams NR. Giant-cell arteritis: review and report of case. JAMA 1965;191:341-343.

4. Ormsby AH, Haskell R. Giant cell arteritis of the uterus: case report and review. Pathology 1997;29:227-230.

5. Orbo A, Steffensen A. Endometrial cancer, vasculitis of the genital tract and occult temporal arteritis. Histopathology 2001;38:178-179.

6. Paccalin M, Le Moal G, Roblot P. Giant-cell arteritis of the female genital tract. Ann Intern Med 2001;134:626-627.

7. Birch PJ, Buchanan R. A gynaecological complication of polymyalgia rheumatica/giant cell arteritis. Br J Obstet Gynaecol 1989;96:1356-1358.

8. Evans CE, Flight GH, Neufeld VR, Muckle TJ. Giant cell arteritis of uterus and adnexa. Paroi Arterielle 1980;6:27-33.

9. Inanc M, Gul A, Tuzlali S, et al. Female genital tract giant cell arteritis associated with occult temporal arteritis. J Rheumatol 1996;23:393-395.

10. Kohn NN. Giant cell arteritis of the female reproductive tract associated with temporal arteritis. J Rheumatol 1989;16:832-833.

11. Lhote F, Mainguene C, Griselle-Wiseler V, et al. Giant cell arteritis of the female genital tract with temporal arteritis. Ann Rheum Dis 1992;51:900-903.

12. Marrogi AJ, Gersell DJ, Kraus FT. Localized asymptomatic giant cell arteritis of the female genital tract. Int J Gynecol Pathol 1991;10:51-58.

13. Bell DA, Mondschein M, Scully RE. Giant cell arteritis of the female genital tract: a report of three cases. Am J Surg Pathol 1986;10:696-701.

RELATED ARTICLE: Key Points

* Giant cell arteritis of the female genital tract is a rare vasculitis affecting postmenopausal women, often discovered incidentally.

* Concomitant temporal arteritis or polymyalgia rheumatica is described in the majority of reported cases of giant cell arteritis of the female genital tract.

* Giant cell arteritis of the female genital tract may present in postmenopausal women with constitutional symptoms and genital tract lesions on imaging, as was the case in our patient.

Rahul K. Patel, MD, and Kelley Carrick, MD

From the UNT Health Science Center at Fort Worth, Fort Worth, TX, and the Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.

Reprint requests to Rahul K. Patel, MD, 855 Montgomery Street, PCC 4-467, Fort Worth, TX 76107. Email: [e-mail]