Int J Gynecol Cancer 1992, 2, 52-54

Regression of peritoneal leiomyomatosis after treatment with gonadotropin releasing hormone analogue

P.A. CLAVERO,* F.F. N O G A L E S , I. R U I Z - A V I L A , J. L I N A R E S

& A. C O N C H A

*Departments of Pathology and Obstetrics and Gynecology, University of Granada Medical School, Spain

Abstract. Clavero PA, Nogales FF, Ruiz-Avila I, Linares J, Concha A. Regression of peritoneal leiomyomatosis after treatment with gonadotropin releasing hormone analogue. Int J Gynecol Cancer 1992; 2: 52-54.

A case of a 42-year-old woman with peritoneal leiomyomatosis (PL) un- related to pregnancy or any other obvious hormonal source is presented. After treatment with leuprolide acetate for six months, a second-look operation revealed that the majority of the nodules totally regressed. The few remaining ones were substantially reduced in size and exhibited histopathologic evidence of fibrotic change. This response to treatment is documented here for the first time. Since this case was not associated with initial abnormally raised hormonal levels, the regression was caused solely by the treatment and not by the removal of any hormonal stimulus. The usefulness of GnRH analogues in the treatment of PL is proposed.

KEYWORDS: disseminata, leiomyomatosis, leuprolide acetate, peritoneum, smooth muscle tumor.

Peritoneal leiomyomatosis (PL) is a rare, benign, hor- mone-dependent lesion characterized by the presence of widespread peritoneal nodules of smooth muscle. Since it is usually associated with conditions in which hormonal levels are significantly raised, suppressive treatments such as castration (1) and antiestrogens (2) are considered the treatments of choice. However, reports of success with gonadotropin-releasing hormone (GnRH) analogues in the treatment of leiomyoma (3), a condition histologically and pathogenetically similar to PL, led us to believe that GnRH could also be bene- ficial in cases of PL. We report a case of a 42-year-old, non-pregnant patient suffering from PL who was treated with leuprolide acetate and in whom there was regression of the disease together with a marked

Address for correspondence: F. Nogales, Department of Patho- logy, Universidad de Granada, Facultad de Medicina, 18012 Granada, Spain.

reduction of lesions, confirmed by a second-look operation.

C a s e h i s t o r y

A 42-year-old woman, gravida 3, para 3, last preg- nancy in 1976, with no history of hormonal treat- ment, presented with stress incontinence in March 1989. She also requested tubal sterilization. On examination she was found to have a urethrocele. Ab- dominal ultrasound revealed subserosal myomat- ous nodules in the uterus. Pre- and postoperative levels of gonadotropins, estrogens and progesterone were normal.

Initially, the patient did not consent to hysterec- tomy or oophorectomy. Laparotomy revealed previ- ously unsuspected widespread nodular tumors in the peritoneal surface involving the omentum, sigmoid colon, small intestine, uterine surface and left adnexal infundibulum which was anchored to the pelvis due to

Regression of peritoneal leiomyomatosis 53

the presence of nodules. The nodules ranged in size f rom 1 mm to 5 cm. PL was diagnosed, the o m e n t u m and tubes were r emoved and multiple biopsies of the nodules were taken. Postoperat ive t reatment con- sisted of daily subcutaneous injections with 500 ~g of leuprolide acetate for six months . Two months after complet ion of t reatment , the patient consented to a second-look operat ion which showed a smooth intest- inal serosa, all nodules having disappeared, a free and mobile left in fundibulum and, after a thorough search, only four small miliary nodules in the uter ine surface, the remainder of the o m e n t u m and the insert ion of the appendix. The pat ient was discharged with no fur ther t reatment . No ' r ebound ' effect in the growth of peri toneal tumors is evident six months after discon- t inuation of the rapy as demons t ra ted by u l t rasound and repeat CAT scans.

Pathology Nodules f rom the initial operat ion ranged from 1 m m

to 5 cm in diameter, were well-delineated from sur- round ing structures and often pediculated. Histolog- ically, there was a regular, fascicular smooth muscle proliferation wi thout atypia or mitoses (Fig. 1). In con- trast, the nodules from the second-look operat ion were much smaller with a max imum diameter of only 5 mm their smooth muscle cells were obliterated by a concomitant fibrocollagenous componen t (Fig. 2). In nei ther case was there any accompanying decidual metaplasia.

Electronmicroscopy showed typical smooth muscle cells, fibroblasts and myofibroblasts.

Discussion The histogenesis of PL is considered to be a meta- plastic smooth muscle change in the subperi toneal mesenchymal stem cel ls (2'4) which may show an abnor- mal response to high levels of circulating steroid hor- mones caused by pregnancy, oral contraceptives (2) or even funct ioning ovarian tumors (5). However , in very

Fig. 1. Leiomyomatous nodule from initial operation. There is marked cellularity. Subperitoneal fat and mesothelial surface can be seen on top. H&E x 100.

Fig. 2. Residual 0.5 cm nodule found in the second-look operation. Note marked fibrosis which involves preferentially the central portion. H&E x 100.

54 P.A. Clavero et al.

rare cases such as the one repor ted here, PL can occur w h e n the hormona l status is apparent ly normal and it would seem that there exists a selective sensit- ivity of the peri toneal s tem cells to p romote smooth muscle growth.

PL associated with p regnancy may regress follow- ing delivery (2'6) a l though persistence of the disease is possible (2). Since the growth of PL appears to be ho r mone dependen t , the t rea tment advocated in the literature for persis tent disease is castration (1) or ant iestrogens (2).

Uterine le iomyomata have been successfully t reated with GnRH analogues which are used as an adjunct or even as an alternative to surgery. Follow-up studies using magnetic resonance imaging show a marked reduct ion in tumor size (3). The reversible hypo- es t rogenism induced by therapy has an effect similar to castration a l though rarely it may have the opposi te effect and actually induce tumor growth (7).

Both le iomyomata (a) and PL (9) showed increased es- t rogen and proges terone receptors, unlike leiomyo- sarcoma which has complete lack of receptors (1°). This p h e n o m e n o n may explain w h y le iomyomata and PL respond to GnRH analogues whilst leiomyo- sarcoma does not.

The present case illustrates a striking positive re- sponse to GnRH analogue therapy with disappearance or marked reduct ion in size of nodules. An interesting histopathological f inding was the increase of the fibroblastic c omponen t following treatment , indicat- ive of regression. Since this case was not associated with initial abnormal hormonal levels, the regression was caused solely by the t rea tment and not due to removal of any hormona l source.

Once PL has been diagnosed histopathologically and le iomyosarcoma invading the per i toneum

excluded, GnRH analogues may be useful in the treat- ment of persis tent disease, as illustrated by the present case.

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Accepted for publication 14 June 1991