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Conservative treatment of diffuse uterine leiomyomatosis
FERTILITY AND STERILITY威 VOL. 82, NO. 2, AUGUST 2004
CASE REPORTS
Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Conservative treatment of diffuse uterine leiomyomatosis Luigi Fedele, M.D.,a Stefano Bianchi, M.D.,b Giovanni Zanconato, M.D.,c Silvestro Carinelli, M.D.,b and Nicola Berlanda, M.D.a Department of Obstetrics and Gynecology, University of Milan, Milan, and University of Verona, Verona, Italy
Objective: To describe the conservative treatment of diffuse uterine leiomyomatosis. Design: Descriptive study. Setting: Tertiary care centers. Patient(s): Three premenopausal women with diffuse uterine leiomyomatosis associated to persistent menorrhagia, two with desire of becoming pregnant and one with desire of preservation of the uterus. Intervention(s): Preoperative ultrasound showed symmetrically enlarged uteri with innumerable, poorly defined and small-sized (0.5–3 cm) myomas involving all the myometrium. An “extreme” myomectomy was performed in two cases, including the removal of a large portion of corporal myometrium. One patient was treated only medically with GnRH analogues (GnRH-a). Main Outcome Measure(s): Menstrual pattern and, when applicable, ability to conceive and pregnancy outcome. Result(s): Regular menses were restored in both patients who underwent surgery: one had no pregnancy desire and the other was not able to conceive after two IVF-ETs. The patient treated with GnRH-a conceived spontaneously as soon as medical treatment was discontinued; at 34 gestational weeks, an emergency cesarean section followed by hysterectomy was performed for vaginal bleeding and a healthy 2,400-g baby was born. Conclusion(s): Our experience supports the idea that a conservative approach to uterine leiomyomatosis may result in restoration of normal cycles and eventually in the birth of a viable fetus. (Fertil Steril威 2004;82: 450 –3. ©2004 by American Society for Reproductive Medicine.) Key Words: Diffuse uterine leiomyomatosis, uterine myomectomy, uterine bleeding, GnRH analogues Received August 15, 2003; revised and accepted January 7, 2004. Reprint requests: Luigi Fedele, M.D., Clinica Ostetrico-Ginecologica dell’Universita` di Milano, Ospedale San Paolo, Via Di Rudini n. 8, 20142 Milano, Italy (FAX: 39-0250323062; E-mail: luigi. [email protected]). a Clinica OstetricoGinecologica dell’Universita` di Milano, Ospedale San Paolo, Milano. b Istituto OstetricoGinecologica Luigi Mangiagalli, Milano. c Clinica OstetricoGinecologica dell’Universita` di Verona, Policlinico Borgoroma, Verona.
Diffuse leiomyomatosis of the uterus is a rare condition in which innumerable, ill-defined, small smooth-muscle nodules produce symmetrical enlargement of the uterus (1–3). The clinical course is typically characterized by menorrhagia and infertility. Up to now, hysterectomy has been the treatment of choice (4), as the diffuse nature of the lesion makes it difficult to perform a complete myomectomy with excision of all myomatous nodules. Nevertheless, the firm request of these unfortunate young women wishing to preserve uterine function and fertility caused us to look for a different conservative treatment, whose characteristics and results are described in this article.
0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2004. 01.029
Institutional Board approval was not requested for this descriptive study.
450
CASE REPORTS Case 1 A 34-year-old gravida 0, wishing to become pregnant, was first observed in October 1990 due to menorrhagia. Three years earlier she had undergone removal of 16 myomatous nodules of small size (0.5–3 cm) with a clinical and histological diagnosis of diffuse leiomyomatosis of the uterus. The size of the uterus was that of a 12-week pregnancy and the transabdominal ultrasound examination showed the presence of various nodules, the diameter of the largest being 3 cm (Fig. 1). Hemoglobin levels were 8 g/dL. The decision was taken to administer a 3-month course of a GnRH analogue (GnRH-a) (Buserelin at 900 g/day; Aventis, Strasbourg, France) followed by hysteroscopic resection of
FIGURE 1 Transabdominal ultrasound of case 1, showing multiple myometrial nodules, ranging in size from a few millimeters to 3 cm.
Menstrual periods have been normal since then but two subsequent IVF-ET attempts, in 1995 and 1996, have been unsuccessful. At the time of last clinical control (May 2003), uterine size was again as in a 9-week pregnancy and ultrasound scanning showed persistence of multiple small myomatous nodules.
Case 2
Fedele. Diffuse uterine leiomyomatosis. Fertil Steril 2004.
A 24-year-old gravida 0, first observed in 1991 due to menorrhagia persisting after a previous multiple myomectomy done at a different institution, was seen. An enlarged uterus, as in a 14-week pregnancy, was found at clinical examination and ultrasound imaging showed innumerable small-sized nodules within the myometrium, with normal ovaries. A myometrial biopsy performed during laparoscopy confirmed the diagnosis of diffuse leiomyomatosis of the uterus. In light of the woman’s wish for preservation of her fertility we treated her with Buserelin acetate (900 g/day), nasally, for 6 months, obtaining an approximately 50% reduction in total uterine size.
the larger intracavity fibroids (Fig. 2) at the end of the medical treatment. After 3 years of normal menses, menorrhagia started again. Meeting the patient’s desire that the uterus should be preserved, a large portion of the corporal myometrium and the largest nodules were removed by laparotomy (Fig. 3) and a small endometrial cavity reconstructed. Postoperative follow-up was uneventful.
After treatment and the first normal menstrual flow, the patient spontaneously conceived and went through a normal pregnancy, which reached 34 weeks. At this gestational age vaginal bleeding started requiring an immediate caesarean delivery followed by hysterectomy. The neonate, weighing 2,400 g with a good Apgar score, had agenesis of the third phalanx of the third finger in the left hand. During pregnancy we had observed a faster uterine growth during the initial 16
FIGURE 2 Hysteroscopic appearance in case 1. Multiple submucous nodules are shown, subverting completely the endometrial cavity.
Fedele. Diffuse uterine leiomyomatosis. Fertil Steril 2004.
FERTILITY & STERILITY威
451
FIGURE 3 Specimen at abdominal surgery of case 1. The myometrium is thickened and almost completely replaced by grayish-white, whorled, bulging nodules, often with ill-defined borders, ranging in size from 0.5–3 cm (original magnification).
Fedele. Diffuse uterine leiomyomatosis. Fertil Steril 2004.
weeks followed by a linear pattern of growth until the time of delivery. The patient has been in good health since then.
Case 3 A 39-year-old virgo with no pregnancy desire, was first observed in 1997 due to persistent menorrhagia. An enlarged uterus, as in a 20-week pregnancy, was found at clinical examination. Ultrasound imaging showed innumerable small-sized nodules, measuring ⬍3 cm in diameter, within the myometrium. Facing the patient’s firm request for a conservative treatment we chose to perform a myomectomy as the therapeutic solution. At laparotomy the uterus was symmetrically enlarged and the myometrium was almost entirely replaced by numerous small myomatous nodules, all having a diameter ranging from a few mm to 3 cm. Diffuse uterine leiomyomatosis was confirmed and, in spite of the diagnosis, the decision was taken to remove most of the myometrial thickness and the largest nodules until an almost normally sized uterus was obtained along with a small but regular endometrial cavity. The surgical procedure was carried out without complications. Histologic evaluation revealed a completely subverted myometrial structure with smooth-muscle nodules of various shape and size replacing the entire thickness, surrounded by thin muscular bundles. Since the time of operation the patient has had normal menses but has not, so far, attempted any pregnancy. The latest echographic evaluation (May 2003) showed an enlarged uterus of 8 weeks’ size and still identified innumerable small leiomyomatous nodules. 452
Fedele et al.
Diffuse uterine leiomyomatosis
DISCUSSION Our experience, although limited to three cases, supports the idea that diffuse uterine leiomyomatosis may be managed by combining medical treatment and a surgically conservative approach with encouraging results. Diffuse leiomyomatosis of the uterus is quite rare but its recognition is of utmost importance for the therapeutic decision-making process. On gross examination, the following are specific features: [1] innumerable, poorly defined and small-sized (0.5–3 cm) myomas; [2] total involvement of the myometrium; and [3] symmetrical enlargement of the uterus. Histologic examination reveals that all nodules consist of benign smooth muscle tissue with a mitotic index always less than 1 mitosis in 10 high power fields and no atypical mitotic figures. In a recent study, clonality analysis supports the independent origin of neoplastic clones for each single myomatous nodule and rejects the possibility of a single clonal origin of all tumor cells. The results of the molecular analysis suggest that diffuse leiomyomatosis of the uterus may be an exuberant example of diffuse and uniform involvement of the entire myometrium by multiple leiomyomata (5). At histological evaluation, the differential diagnosis of diffuse uterine leiomyomatosis includes multiple leiomyomas and intravenous leiomyomatosis. Low-grade endometrial stromal sarcoma only occasionally may resemble leiomyomatosis; however, the two lesions are different. On gross examination diffuse uterine leiomyomatosis, that is a type of myometrial hypertrophy, presents a thick and irregVol. 82, No. 2, August 2004
ular myometrium that may resemble adenomyosis, with numerous small myomas; tumor masses of endometrial stromal sarcoma are typically yellow, and vermiform projections are quite frequent. On microscopic examination, cells of diffuse uterine leiomyomatosis are typical, uniform, bland spindled smooth muscle cells grouped in small leiomyomas that are less circumscribed than typical leiomyomas. Cells of endometrial stromal sarcoma resemble early secretory endometrial stroma, including the presence of round to oval nuclei, and spiral arterioles; tumor masses are well circumscribed from the surrounding smooth muscle. Smooth muscle differentiation may occur, but in such cases the resemblance with diffuse uterine leiomyomatosis, if present, is focal. Diffuse uterine leiomyomatosis generally affects younger women, with menorrhagia and infertility as typical symptoms, often leading them to surgical treatment with the diagnosis of multiple myomas. In case of inadequate preoperative diagnostic work-up and in the absence of a clinical suspicion, the operating surgeon finds a symmetrically enlarged uterus diffusedly occupied by innumerable small nodules that preclude a conservative treatment. Until now, hysterectomy has been the treatment of choice for this condition because myomectomy carries the risk of symptom recurrence, as it does not allow complete removal of the lesions. Hysterectomy, however, represents a dramatic choice unlikely to be accepted by young women with desire of future fertility and should be discussed within an accurate preoperative counselling, which, on the contrary, takes place only occasionally. Our conservative approach has been different in each of the three cases reported, being surgical in two cases and medical in one case. In the two operated cases, we did not use preoperative GnRH agonist as we believe that this kind of treatment may make it impossible to identify smaller fibroids (6). The conservative surgical treatment consists in a rather “extreme” uterine myomectomy. All the innumerable largesize nodules are surrounded by a vascolarized pseudocapsule, without a specific vascular pedicle, and they shell out easily, as in conventional myomectomy. Small nodules, on the contrary, replace the structure of the myometrium and may be missed at visual inspection: therefore, a consistent part of the myometrium has to be removed. Caution has to be
FERTILITY & STERILITY威
taken to spare enough myometrial tissue for the reconstructive step of the procedure, which is the most challenging, aiming to obtain an almost normally sized uterus with a small but regular endometrial cavity. This approach, although incomplete with regard to the nodules left in place, has restored a normal menstrual function in both patients and has not been followed by a fast regrowth of the uterus nor by a new proliferation of other nodules. This last result seems to indicate that diffuse uterine leiomyomatosis is characterized by a low potential of new formation and growth of myomatous nodules. In case 2 a GnRH-a treatment was possible, the clinical and histological diagnosis being already available. Efficacy of GnRH-a in reducing the size of a myoma is well known but the observed reduction of the uterine size was quite unexpected as much as the pregnancy that followed. We believe that this therapeutic strategy may be adopted only when the patient has normal adnexa and a normally shaped uterine cavity. This represents the first case of a pregnancy obtained after medically treating such condition, although there are reports of pregnancies progressing to viable gestational ages in women affected by diffuse uterine leiomyomatosis (7, 8). In conclusion, our experience supports the idea of a new conservative approach, with medical and surgical measures, which may be considered when managing this rare disease and may result in restoration of normal cycles and eventually in the birth of a viable fetus. References 1. Fedele L, Zamberletti D, Carinelli S, Motta T, Candiani GB. Diffuse uterine leiomyomatosis. Acta Eur Fertil 1982;13:125–31. 2. Clement PB, Young RH. Diffuse leiomyomatosis of the uterus: a report of four cases. Int J Gynecol Pathol 1987;6:322–30. 3. Mulvany NJ, Ostor AG, Ross I. Diffuse leiomyomatosis of the uterus. Histopathology 1995;27:175–9. 4. Lapan B, Solomon L. Diffuse leiomyomatosis of the uterus precluding myomectomy. Obstet Gynecol 1979;53:82S–4S. 5. Baschinsky DY, Isa A, Niemann TH, Prior TW, Lucas JG, Frankel WL. Diffuse leiomyomatosis of the uterus: a case report with clonality analysis. Hum Pathol 2000;31:1429 –32. 6. Fedele L, Vercellini P, Bianchi S, Brioschi D, Dorta M. Treatment with GnRH agonists before myomectomy and the risk of short-term myoma recurrence. Br J Obstet Gynaecol 1990;97:393–6. 7. Grignon DJ, Carey MR, Kirk ME, Robinson ML. Diffuse uterine leiomyomatosis: a case study with pregnancy complicated by intrapartum hemorrhage. Obstet Gynecol 1987;69:477–80. 8. Domnitz SW, Roth JA, Corwin LJ. Diffuse leiomyomatosis of the uterus in pregnancy. A case report. J Reprod Med 1994;39:61–6.
453
CASE REPORTS
Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Conservative treatment of diffuse uterine leiomyomatosis Luigi Fedele, M.D.,a Stefano Bianchi, M.D.,b Giovanni Zanconato, M.D.,c Silvestro Carinelli, M.D.,b and Nicola Berlanda, M.D.a Department of Obstetrics and Gynecology, University of Milan, Milan, and University of Verona, Verona, Italy
Objective: To describe the conservative treatment of diffuse uterine leiomyomatosis. Design: Descriptive study. Setting: Tertiary care centers. Patient(s): Three premenopausal women with diffuse uterine leiomyomatosis associated to persistent menorrhagia, two with desire of becoming pregnant and one with desire of preservation of the uterus. Intervention(s): Preoperative ultrasound showed symmetrically enlarged uteri with innumerable, poorly defined and small-sized (0.5–3 cm) myomas involving all the myometrium. An “extreme” myomectomy was performed in two cases, including the removal of a large portion of corporal myometrium. One patient was treated only medically with GnRH analogues (GnRH-a). Main Outcome Measure(s): Menstrual pattern and, when applicable, ability to conceive and pregnancy outcome. Result(s): Regular menses were restored in both patients who underwent surgery: one had no pregnancy desire and the other was not able to conceive after two IVF-ETs. The patient treated with GnRH-a conceived spontaneously as soon as medical treatment was discontinued; at 34 gestational weeks, an emergency cesarean section followed by hysterectomy was performed for vaginal bleeding and a healthy 2,400-g baby was born. Conclusion(s): Our experience supports the idea that a conservative approach to uterine leiomyomatosis may result in restoration of normal cycles and eventually in the birth of a viable fetus. (Fertil Steril威 2004;82: 450 –3. ©2004 by American Society for Reproductive Medicine.) Key Words: Diffuse uterine leiomyomatosis, uterine myomectomy, uterine bleeding, GnRH analogues Received August 15, 2003; revised and accepted January 7, 2004. Reprint requests: Luigi Fedele, M.D., Clinica Ostetrico-Ginecologica dell’Universita` di Milano, Ospedale San Paolo, Via Di Rudini n. 8, 20142 Milano, Italy (FAX: 39-0250323062; E-mail: luigi. [email protected]). a Clinica OstetricoGinecologica dell’Universita` di Milano, Ospedale San Paolo, Milano. b Istituto OstetricoGinecologica Luigi Mangiagalli, Milano. c Clinica OstetricoGinecologica dell’Universita` di Verona, Policlinico Borgoroma, Verona.
Diffuse leiomyomatosis of the uterus is a rare condition in which innumerable, ill-defined, small smooth-muscle nodules produce symmetrical enlargement of the uterus (1–3). The clinical course is typically characterized by menorrhagia and infertility. Up to now, hysterectomy has been the treatment of choice (4), as the diffuse nature of the lesion makes it difficult to perform a complete myomectomy with excision of all myomatous nodules. Nevertheless, the firm request of these unfortunate young women wishing to preserve uterine function and fertility caused us to look for a different conservative treatment, whose characteristics and results are described in this article.
0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2004. 01.029
Institutional Board approval was not requested for this descriptive study.
450
CASE REPORTS Case 1 A 34-year-old gravida 0, wishing to become pregnant, was first observed in October 1990 due to menorrhagia. Three years earlier she had undergone removal of 16 myomatous nodules of small size (0.5–3 cm) with a clinical and histological diagnosis of diffuse leiomyomatosis of the uterus. The size of the uterus was that of a 12-week pregnancy and the transabdominal ultrasound examination showed the presence of various nodules, the diameter of the largest being 3 cm (Fig. 1). Hemoglobin levels were 8 g/dL. The decision was taken to administer a 3-month course of a GnRH analogue (GnRH-a) (Buserelin at 900 g/day; Aventis, Strasbourg, France) followed by hysteroscopic resection of
FIGURE 1 Transabdominal ultrasound of case 1, showing multiple myometrial nodules, ranging in size from a few millimeters to 3 cm.
Menstrual periods have been normal since then but two subsequent IVF-ET attempts, in 1995 and 1996, have been unsuccessful. At the time of last clinical control (May 2003), uterine size was again as in a 9-week pregnancy and ultrasound scanning showed persistence of multiple small myomatous nodules.
Case 2
Fedele. Diffuse uterine leiomyomatosis. Fertil Steril 2004.
A 24-year-old gravida 0, first observed in 1991 due to menorrhagia persisting after a previous multiple myomectomy done at a different institution, was seen. An enlarged uterus, as in a 14-week pregnancy, was found at clinical examination and ultrasound imaging showed innumerable small-sized nodules within the myometrium, with normal ovaries. A myometrial biopsy performed during laparoscopy confirmed the diagnosis of diffuse leiomyomatosis of the uterus. In light of the woman’s wish for preservation of her fertility we treated her with Buserelin acetate (900 g/day), nasally, for 6 months, obtaining an approximately 50% reduction in total uterine size.
the larger intracavity fibroids (Fig. 2) at the end of the medical treatment. After 3 years of normal menses, menorrhagia started again. Meeting the patient’s desire that the uterus should be preserved, a large portion of the corporal myometrium and the largest nodules were removed by laparotomy (Fig. 3) and a small endometrial cavity reconstructed. Postoperative follow-up was uneventful.
After treatment and the first normal menstrual flow, the patient spontaneously conceived and went through a normal pregnancy, which reached 34 weeks. At this gestational age vaginal bleeding started requiring an immediate caesarean delivery followed by hysterectomy. The neonate, weighing 2,400 g with a good Apgar score, had agenesis of the third phalanx of the third finger in the left hand. During pregnancy we had observed a faster uterine growth during the initial 16
FIGURE 2 Hysteroscopic appearance in case 1. Multiple submucous nodules are shown, subverting completely the endometrial cavity.
Fedele. Diffuse uterine leiomyomatosis. Fertil Steril 2004.
FERTILITY & STERILITY威
451
FIGURE 3 Specimen at abdominal surgery of case 1. The myometrium is thickened and almost completely replaced by grayish-white, whorled, bulging nodules, often with ill-defined borders, ranging in size from 0.5–3 cm (original magnification).
Fedele. Diffuse uterine leiomyomatosis. Fertil Steril 2004.
weeks followed by a linear pattern of growth until the time of delivery. The patient has been in good health since then.
Case 3 A 39-year-old virgo with no pregnancy desire, was first observed in 1997 due to persistent menorrhagia. An enlarged uterus, as in a 20-week pregnancy, was found at clinical examination. Ultrasound imaging showed innumerable small-sized nodules, measuring ⬍3 cm in diameter, within the myometrium. Facing the patient’s firm request for a conservative treatment we chose to perform a myomectomy as the therapeutic solution. At laparotomy the uterus was symmetrically enlarged and the myometrium was almost entirely replaced by numerous small myomatous nodules, all having a diameter ranging from a few mm to 3 cm. Diffuse uterine leiomyomatosis was confirmed and, in spite of the diagnosis, the decision was taken to remove most of the myometrial thickness and the largest nodules until an almost normally sized uterus was obtained along with a small but regular endometrial cavity. The surgical procedure was carried out without complications. Histologic evaluation revealed a completely subverted myometrial structure with smooth-muscle nodules of various shape and size replacing the entire thickness, surrounded by thin muscular bundles. Since the time of operation the patient has had normal menses but has not, so far, attempted any pregnancy. The latest echographic evaluation (May 2003) showed an enlarged uterus of 8 weeks’ size and still identified innumerable small leiomyomatous nodules. 452
Fedele et al.
Diffuse uterine leiomyomatosis
DISCUSSION Our experience, although limited to three cases, supports the idea that diffuse uterine leiomyomatosis may be managed by combining medical treatment and a surgically conservative approach with encouraging results. Diffuse leiomyomatosis of the uterus is quite rare but its recognition is of utmost importance for the therapeutic decision-making process. On gross examination, the following are specific features: [1] innumerable, poorly defined and small-sized (0.5–3 cm) myomas; [2] total involvement of the myometrium; and [3] symmetrical enlargement of the uterus. Histologic examination reveals that all nodules consist of benign smooth muscle tissue with a mitotic index always less than 1 mitosis in 10 high power fields and no atypical mitotic figures. In a recent study, clonality analysis supports the independent origin of neoplastic clones for each single myomatous nodule and rejects the possibility of a single clonal origin of all tumor cells. The results of the molecular analysis suggest that diffuse leiomyomatosis of the uterus may be an exuberant example of diffuse and uniform involvement of the entire myometrium by multiple leiomyomata (5). At histological evaluation, the differential diagnosis of diffuse uterine leiomyomatosis includes multiple leiomyomas and intravenous leiomyomatosis. Low-grade endometrial stromal sarcoma only occasionally may resemble leiomyomatosis; however, the two lesions are different. On gross examination diffuse uterine leiomyomatosis, that is a type of myometrial hypertrophy, presents a thick and irregVol. 82, No. 2, August 2004
ular myometrium that may resemble adenomyosis, with numerous small myomas; tumor masses of endometrial stromal sarcoma are typically yellow, and vermiform projections are quite frequent. On microscopic examination, cells of diffuse uterine leiomyomatosis are typical, uniform, bland spindled smooth muscle cells grouped in small leiomyomas that are less circumscribed than typical leiomyomas. Cells of endometrial stromal sarcoma resemble early secretory endometrial stroma, including the presence of round to oval nuclei, and spiral arterioles; tumor masses are well circumscribed from the surrounding smooth muscle. Smooth muscle differentiation may occur, but in such cases the resemblance with diffuse uterine leiomyomatosis, if present, is focal. Diffuse uterine leiomyomatosis generally affects younger women, with menorrhagia and infertility as typical symptoms, often leading them to surgical treatment with the diagnosis of multiple myomas. In case of inadequate preoperative diagnostic work-up and in the absence of a clinical suspicion, the operating surgeon finds a symmetrically enlarged uterus diffusedly occupied by innumerable small nodules that preclude a conservative treatment. Until now, hysterectomy has been the treatment of choice for this condition because myomectomy carries the risk of symptom recurrence, as it does not allow complete removal of the lesions. Hysterectomy, however, represents a dramatic choice unlikely to be accepted by young women with desire of future fertility and should be discussed within an accurate preoperative counselling, which, on the contrary, takes place only occasionally. Our conservative approach has been different in each of the three cases reported, being surgical in two cases and medical in one case. In the two operated cases, we did not use preoperative GnRH agonist as we believe that this kind of treatment may make it impossible to identify smaller fibroids (6). The conservative surgical treatment consists in a rather “extreme” uterine myomectomy. All the innumerable largesize nodules are surrounded by a vascolarized pseudocapsule, without a specific vascular pedicle, and they shell out easily, as in conventional myomectomy. Small nodules, on the contrary, replace the structure of the myometrium and may be missed at visual inspection: therefore, a consistent part of the myometrium has to be removed. Caution has to be
FERTILITY & STERILITY威
taken to spare enough myometrial tissue for the reconstructive step of the procedure, which is the most challenging, aiming to obtain an almost normally sized uterus with a small but regular endometrial cavity. This approach, although incomplete with regard to the nodules left in place, has restored a normal menstrual function in both patients and has not been followed by a fast regrowth of the uterus nor by a new proliferation of other nodules. This last result seems to indicate that diffuse uterine leiomyomatosis is characterized by a low potential of new formation and growth of myomatous nodules. In case 2 a GnRH-a treatment was possible, the clinical and histological diagnosis being already available. Efficacy of GnRH-a in reducing the size of a myoma is well known but the observed reduction of the uterine size was quite unexpected as much as the pregnancy that followed. We believe that this therapeutic strategy may be adopted only when the patient has normal adnexa and a normally shaped uterine cavity. This represents the first case of a pregnancy obtained after medically treating such condition, although there are reports of pregnancies progressing to viable gestational ages in women affected by diffuse uterine leiomyomatosis (7, 8). In conclusion, our experience supports the idea of a new conservative approach, with medical and surgical measures, which may be considered when managing this rare disease and may result in restoration of normal cycles and eventually in the birth of a viable fetus. References 1. Fedele L, Zamberletti D, Carinelli S, Motta T, Candiani GB. Diffuse uterine leiomyomatosis. Acta Eur Fertil 1982;13:125–31. 2. Clement PB, Young RH. Diffuse leiomyomatosis of the uterus: a report of four cases. Int J Gynecol Pathol 1987;6:322–30. 3. Mulvany NJ, Ostor AG, Ross I. Diffuse leiomyomatosis of the uterus. Histopathology 1995;27:175–9. 4. Lapan B, Solomon L. Diffuse leiomyomatosis of the uterus precluding myomectomy. Obstet Gynecol 1979;53:82S–4S. 5. Baschinsky DY, Isa A, Niemann TH, Prior TW, Lucas JG, Frankel WL. Diffuse leiomyomatosis of the uterus: a case report with clonality analysis. Hum Pathol 2000;31:1429 –32. 6. Fedele L, Vercellini P, Bianchi S, Brioschi D, Dorta M. Treatment with GnRH agonists before myomectomy and the risk of short-term myoma recurrence. Br J Obstet Gynaecol 1990;97:393–6. 7. Grignon DJ, Carey MR, Kirk ME, Robinson ML. Diffuse uterine leiomyomatosis: a case study with pregnancy complicated by intrapartum hemorrhage. Obstet Gynecol 1987;69:477–80. 8. Domnitz SW, Roth JA, Corwin LJ. Diffuse leiomyomatosis of the uterus in pregnancy. A case report. J Reprod Med 1994;39:61–6.
453