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Bilateral ovarian fibromas and endometrial adenocarcinoma in a postmenopausal patient with growing uterine myomas
Maturitas 39 (2001) 259– 264 www.elsevier.com/locate/maturitas
Bilateral ovarian fibromas and endometrial adenocarcinoma in a postmenopausal patient with growing uterine myomas Dolores Foth a,*, Frank Nawroth a, Torsten Schmidt a, M. Ortmann b, Thomas Ro¨mer a a
Department of Obstetrics and Gynecology, Uni6ersity of Cologne, Kerpener Str. 34, 50931 Ko¨ln, Germany b Institute of Pathology, Uni6ersity of Cologne, Kerpener Str. 34, 50931 Ko¨ln, Germany Received 31 October 2000; received in revised form 13 March 2001; accepted 30 March 2001
Abstract Bilateral ovarian fibromas are a rare condition. We report a case of bilateral ovarian fibromas with endometrial adenocarcinoma in a postmenopausal woman who clinically showed symptoms of an estrogen-producing tumour. Clinical and histopathological problems in the pre- and intraoperative diagnostics of fibromas are discussed. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Fibroma; Endometrial adenocarcinoma; Postmenopause
1. Introduction Ovarian fibromas are derived from the mesenchyme of the ovary. They account for approximately 5% of all primary ovarian tumours. Fibromas consist of fibrous connective tissue and fibroblasts, and occur mostly unilaterally in preand postmenopausal women. Ovarian sex cord tumours account for approximately 3% of all primary ovarian tumours (Deppe and Lawrence, 1988; Hoskins and Rubin, 1992). They are derived from sex cord elements and ovarian stroma elements and may consist of stromal cells, theca cells, granulosa cells, Sertoli cells and Leydig cells, * Corresponding author. Tel.: + 49-221-4783833; fax: + 49221-4786789. E-mail address: [email protected] (D. Foth).
either isolated or in various combinations. Many of these tumours are hormonally active; Granulosa- and theca cell tumours can secrete estrogens. We report a case of bilateral ovarian fibromas in a postmenopausal woman who showed clinically, but not histologically, symptoms of an estrogen-producing tumour. Diagnostic problems are discussed.
1.1. Case report A 61-year-old woman, gravida 4, para 3 was referred to our department with growing uterine myomas and deteriorating abdominal swelling over a one-year period. Urination and defecation were regular. Menopause had taken place 6 years earlier. The patient did not report any bleeding disorders or climacteric symptoms, and had never
0378-5122/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 7 8 - 5 1 2 2 ( 0 1 ) 0 0 2 0 9 - 2
D. Foth et al. / Maturitas 39 (2001) 259–264
260
received hormone replacement therapy. Previous medical history revealed two caesarean sections, but no other operations. The examinations confirmed the following results.
1.1.1. Gynaecological examination Vulvae and vagina with no abnormal findings, portio: transformation zone, cytology Papanicolaou II, Proliferation degree (Schmitt) 3–4; uterus hyperplastic and fixated, retroflexion, about 5 cm solid tumour in connection with the posterior part of the uterus, adnexa with no abnormalities. 1.1.2. Ultrasonic examination Hyperplastic uterus, intramurally a solid tumour at the right posterior part of the uterus 59 × 45× 43 mm, further small solid intramural tumours with less than B10 mm (leiomyomas); thickness of the endometrium 4,8 mm with a homogenous structure; ovaries with no abnormal findings and without ascites in the abdominal cavity. 1.1.3. Serum hormone measurements see Table 1 In agreement with the patient, an abdominal hysterectomy with bilateral salpingo-oophorectomy was carried out due to growing uterine myomas, lower abdominal pain and fixation of the hyperplastic uterus 1.1.4. Intraoperati6e situs Intraperitoneal adhesions; uterus myomatous with a typical leimyoma on the right posterior wall. Adnexa on both sides and the peritoneal surface presented no other macroscopic abnormalities.
Table 1 Serum hormone measurements (pre- and postoperative)
Estradiol in pg/ml FSH in mIU/ml LH in mIU/ml
preoperative
postoperative (day 7th)
55 31 20
B5 63 25
1.1.5. Microscopic findings 1. Uterus: diffuse myometrial hyperplasia, several typical leiomyomas without abnormalities; endometrium mostly thin and atrophic, but small focuses of an irregular glandular hyperplasia with parts of an intramucously growing, highly differentiated endometrial adenocarcinoma. The tumour was limited to the interior third of the myometrium: pT1b GI estrogen receptor 100% and progesterone receptor 70% positive cells (Fig. 1). 2. Adnexa right: 2×1× 0.5 cm in diameter atrophic ovary with a small typical initial fibroma, fallopian tube with no abnormal findings. 3. Adnexa left: 4×2× 2 cm in diameter atrophic ovary, centrally a solid tumour located, 2,3 cm in size. Microscopically, this tumour showed the appearance of a typical fibrom. The fallopian tube was also without abnormal findings (Fig. 2) The postoperative time period took a normal course without any complications. However, immediately after the operation, the patient developed climacteric symptoms. The histological diagnosis of a highly differentiated adenocarcinoma of the endometrium in the early stage (pT1b GI) and fibromas of both ovaries did not require more than the completed operative treatment.
2. Discussion We report a postmenopausal woman with bilateral fibromas and a highly differentiated endometrium adenocarcinoma in the early stage. Histologically, there was no evidence of a hormonally active ovarian tumour. However, clinically, we registered signs of estrogen production in this postmenopausal woman. Retrospectively, the lack of climacteric symptoms preoperatively and the new appearance of climacteric symptoms after surgical treatment, in combination with the results of serum hormone measurements, have to be assessed as a possible sign of an estrogen producing tumour. Furthermore, the post-
D. Foth et al. / Maturitas 39 (2001) 259–264
261
Fig. 1. Histology: intramucously growing, highly differentiated endometrial adenocarcinoma, limited to the interior third of the myometrium: pT1b GI (10 ×).
menopausal growth of myomas represents a possible sign of a hormone producing tumour. Exposure of the postmenopausal endometrium to estrogen can result in endometrial hyperplasia or even in carcinoma. In the reported case, a highly differentiated endometrium carcinoma was diagnosed. There was no sign of postmenopausal bleeding disorder. Vaginal bleeding is a late symptom of endometrial carcinomas and is often not reported in early stages. Pre- and intraoperatively, the patient was not suspected of having an endometrium carcinoma or ovarian tumour. In recent years, screening procedures have been proposed to detect ovarian and endometrial cancer. After reviewing recent literature, we recommend a sonographic control if the endometrium thickness is between 5 and 8 mm in postmenopausal women without bleeding and without hormone replacement therapy (Table 2; Ro¨ mer et al., in press). Endometrium thickness less than 4 mm is without consequences. Karlsson et al. 1995 describe the risk of finding endometrial pathologies when the endometrium is 54 mm with 5.5%. In general, a cut-off limit of 5 or 4 mm endometrial thickness (double layer) is used today. How-
ever, even if the sonographically measured endometrial thickness is below this limit, an endometrial carcinoma is possible. The development of de-novo carcinoma may happen in an atrophic endometrium. Not only the endometrial thickness is of importance, but also the echogenity and the endo-myometrial transition. Doppler sonography can improve diagnostic possibilities. Bourne et al. (1991) studied changes in uterine blood flow to detect endometrial cancer. Malignant tumours showed signs of altered vascularization and low pulsatility index (PI). But Sheth et al. (1995) could no show differences in mean PI and resistance index (RI) for benign and malignant endometrial lesions in postmenopausal women. In the reported case, no Doppler ultrasound was available. An ovarian tumour was not visualised. The diagnosis of fibromas was only histologically possible. According to macroscopic findings, the left ovary was double the size of the right ovary. Duda et al. (1990) describe significant differences in size between the postmenopausal right and left ovary as suspicious. As early as 1989, Campbell et al., recommended transabdominal ultrasound screening for early ovarian cancer (Campbell et al., 1989). Later Kur-
D. Foth et al. / Maturitas 39 (2001) 259–264
262
Fig. 2. Histology: fibroma of the left ovary (20 × ).
jak et al. (1992) describe the use of transvaginal colour and pulsed Doppler ultrasonography to detect ovarian carcinoma. Morphology alone has poor sensitivity, but when combined with Doppler indices, the sensitivity improves (Kurjak et al., 1992; Salem et al., 1994; Voigt, 1995). Spectral Doppler waveform characteristics (RI, PI) correlate well with malignancies but generally add little informatics to morphologic considerations (Jeong et al., 2000). Beside fibromas, fibrothecomas are hormonally active tumours derived from the gonadal mesenchyme. Thecomas occur primarily in postmenopausal women. Theca cell tumours are solid and of small size. Most of them occur unilaterally in otherwise normal ovaries (Barrenetxea et al., 1990; Aboud, 1997; Cronje´ et al., 1999). The natural history of theca cell tumours is generally one of slow
growth. True malignant thecomas are a rare condition (Novak et al., 1971; Waxman et al., 1979; Deppe and Lawrence, 1988). However, the clinical picture may be dominated by the results of the estrogen secretion. Even if a sex cord stromal tumour is benign, the resulting effects on the endometrium may become life threatening due to the potential production of estrogens over an extended period of time. From the pathological features, theca cell tumours are composed of monomorphic spindle cells, lipid vacuoles and fibromatous tissue. The differential diagnosis between fibroma and lipid containing Desmin-positive thecoma is sometimes difficult to make. However, again, in this case there was no histological evidence of a thecom. In a retrospective study by Barrenetxea et al. (1990), 29 cases of thecomas were reported with a mean age of 49 years. Nearly half of the patients
Table 2 Endometrial thickness (double layer) as measured by transvaginal ultrasonography for identifying endometrial abnormities: cut-off limits in postmenopausal women without bleeding disorders
Hyteroscopy+biopsy Control: (2–3 months) Without consequence
Sequential HRT* (mm)
Continuous-combined-HRT (mm)
No HRT (mm)
]13a 9–12 58
]9 5–8 54
]9 5–8 54
D. Foth et al. / Maturitas 39 (2001) 259–264
were postmenopausal. The main symptom in postmenopausal women was vaginal bleeding, which was present in 44.4% of cases. Postmenopausal bleedings and other bleeding disorders as well as abdominal swellings, especially in premenopausal women, are possible clinical symptoms (Barrenetxea et al., 1990; Aboud, 1997; Cronje´ et al., 1999). Cronje´ et al. (1999) reviewed 116 patients with thecomas. The great majority of these patients had abnormal bleedings and lower abdominal pain. However, 18.1% of the postmenopausal women did not show any bleeding disorders. This may be attributed to lower levels of estrogen secretion for an extended period. The reported incidences of patients with ovarian thecomas and associated endometrial hyperplasia of different degrees varies from 20%– 64%, while 4.5% –27% were found to have concomitant ade nocarcinoma (Hoskins and Rubin, 1992; Aboud, 1997; Cronje´ et al., 1999). The reported incidences of associated pathologies of the endometrium vary in the literature. True incidences of these associated pathologies are not clearly established. Many cases of thecomas did not have the required histological examinations of the endometrium available. Gonadal stromal tumours are often of such a small size that ovaries are not significantly enlarged. That is why in many cases, fibromas and thecomas are preoperatively not diagnosed. The indications for surgical treatment are often not limited to the adnexa. Ovarian tumours are the indication for operative intervention in only 58% of cases (Barrenetxea et al., 1990). Other indications for surgery are uterine myomas and bleeding disorders. Mostly the diagnosis is only a histological one. In this reported case of bilateral ovarian fibromas, the discrepancy between clinical signs of an estrogen producing tumour and histology still remains at present.
3. Conclusion From the clinical point of view, small fibromas are hard to diagnose. Possible symptoms of an estrogen-producing
263
tumour in postmenopausal women are: elevated estrogen serum levels growth of uterine myomas sonographically diagnosed endometrium hyperplasia other symptoms of estrogen production, for instance, hormonal effects on the vaginal epithelia [Proliferation degree (Schmitt)], mastalgia a.o. All the mentioned clinical symptoms are also possible without a hormone-producing tumour in postmenopausal women. There are estrogenic effects on the vaginal epithelium [Proliferation degree (Schmitt)] in 75% of postmenopausal women without hormone replacement therapy (Ro¨ mer and Foth, 1996). The absence of climacteric symptoms is also not a sure sign. As many as 25% of climacteric women do not report symptoms (Hauser, 1992). Still, all possible clinical symptoms should be evaluated accurately.
Acknowledgements We wish to acknowledge Margaret Priemer for her careful translation of this paper.
References Aboud E. A review of granulosa cell tumours and thecomas of the ovary. Arch Gynecol Obstet 1997;259:161 – 5. Barrenetxea G, Schneider J, Centeno MM, Martinez AJ, Fernandez de Larrino A, Gonzales del Tanago J, et al. Pure theca cell tumours. Eur J Gynaec Oncol 1990;11[6]:429 – 32. Bourne Th, Campbell S, Steer CV, Royston P, Whitehead MI, Collins WP. Detection of endometrial cancer by transvaginal ultrasonography with color flow imaging and blood flow analysis: a preliminary report. Gynecol Oncol 1991);40:253 – 9. Campbell S, Bhan V, Royston P, Whitehead MI, Collins WP. Transabdominal ultrasound screening for early ovarian cancer. Br J Med 1989;299:1363 – 7. Cronje´ HS, Niemand I, Bam RH, Woodruff D. Review of the granulosa-theca cell tumors from the Emil Novak Ovarian Tumor Registry. Am J Obstet Gynecol 1999;180:323 – 7. Deppe G, Lawrence WD. Cancer of the ovary. In: Gusberg SB, Shingleton HM, Deppe G, editors. Female Genital Cancer. New York: Churchell Livingstone, 1988.
264
D. Foth et al. / Maturitas 39 (2001) 259–264
Duda V, Rode G, Thein C, Schulz KD. Vaginalsonographie: Pilotstudie fu¨ r den Einsatz als Ovarial-Screening-Verfahren. Geburtshilfe Frauenheilkd 1990;50:388 –93. Hauser GA. Ha¨ ufigkeit klimakterischer Symptome-eine Literaturu¨ bersicht. In: Lauritzen C, editor. Menopause: Hormonsubstitution heute. Mu¨ nchen: Stabil-Verlag, 1992:18 – 21. Hoskins W, Rubin S. Malignant gonadal stromal tumours of the ovary: clinical features and mangement. In: Coppleson M, editor. Gynaecology Oncology. Edinburgh: Livingstone, 1992:961 –70. Jeong YY, Outwater EK, Kang HK. Imaging evaluation of ovarian masses. Radiographics 2000;20:1445 –70. Karlsson B, Granberg S, Wikland M, Ylostalo P, Torvid K, Marsal K, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding — a Nordic multicenter study. Am J Obstet Gynecol 1995;172:1488 – 94. Kurjak A, Schulman H, Sosic A, Zalud I, Shalan H. Transvaginal ultrasound, color flow, and Doppler waveform of the postmenopausal adnexal mass. Obstet Gynecol 1992;80:917 – 21. Novak ER, Kutchmeshgi J, Mupas RS. Feminizing gonaldal stromal tumors: Analysis of the granulosa-theca cell tu-
mours of the Ovarian Tumor Registry. Obstet Gynecol 1971;38:701 – 13. Ro¨ mer, Th., Foth, D., Duda, V., Rabe, Th., Empfehlung zur sonographischen Diagnostik bei asymptomatishcen postmenopausalen Patientinnen mit ohne ohne Hormonsubstitution. In press Ro¨ mer T, Foth D. Hormonelle vaginalzytologische und symptomatische U8 berwachung der Hormonsubstitution. J Menopause 1996;1:12 – 5. Salem S, White LM, Lai J. Doppler sonography of adnexal masses: the predictive value of the pulsatility index in benign and malignant disease. Am J Roentgenol 1994;163:1147 – 50. Sheth S, Hamper UM, McCollum ME, Caskey CI, Rosenshein NB, Kurman RJ. Endometrial blood flow analysis in postmenopausal women: can it help differentiate benign from malignant causes of endometrial thickening? Radiology 1995;195:661 – 5. Voigt HJ. Transvaginaler Doppler/Farbdoppler in der gyna¨ kologischen Diagnostik. Gyna¨ kologe 1995;28:254 – 61. Waxman M, Vuletin JC, Urcuyo R, Belling CG. Ovarian low-grade stromal sarcoma with thecoma features: a critical reappraisal of the so-called ‘malignant thecoma’. Cancer 1979;44:2206 – 17.
Bilateral ovarian fibromas and endometrial adenocarcinoma in a postmenopausal patient with growing uterine myomas Dolores Foth a,*, Frank Nawroth a, Torsten Schmidt a, M. Ortmann b, Thomas Ro¨mer a a
Department of Obstetrics and Gynecology, Uni6ersity of Cologne, Kerpener Str. 34, 50931 Ko¨ln, Germany b Institute of Pathology, Uni6ersity of Cologne, Kerpener Str. 34, 50931 Ko¨ln, Germany Received 31 October 2000; received in revised form 13 March 2001; accepted 30 March 2001
Abstract Bilateral ovarian fibromas are a rare condition. We report a case of bilateral ovarian fibromas with endometrial adenocarcinoma in a postmenopausal woman who clinically showed symptoms of an estrogen-producing tumour. Clinical and histopathological problems in the pre- and intraoperative diagnostics of fibromas are discussed. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Fibroma; Endometrial adenocarcinoma; Postmenopause
1. Introduction Ovarian fibromas are derived from the mesenchyme of the ovary. They account for approximately 5% of all primary ovarian tumours. Fibromas consist of fibrous connective tissue and fibroblasts, and occur mostly unilaterally in preand postmenopausal women. Ovarian sex cord tumours account for approximately 3% of all primary ovarian tumours (Deppe and Lawrence, 1988; Hoskins and Rubin, 1992). They are derived from sex cord elements and ovarian stroma elements and may consist of stromal cells, theca cells, granulosa cells, Sertoli cells and Leydig cells, * Corresponding author. Tel.: + 49-221-4783833; fax: + 49221-4786789. E-mail address: [email protected] (D. Foth).
either isolated or in various combinations. Many of these tumours are hormonally active; Granulosa- and theca cell tumours can secrete estrogens. We report a case of bilateral ovarian fibromas in a postmenopausal woman who showed clinically, but not histologically, symptoms of an estrogen-producing tumour. Diagnostic problems are discussed.
1.1. Case report A 61-year-old woman, gravida 4, para 3 was referred to our department with growing uterine myomas and deteriorating abdominal swelling over a one-year period. Urination and defecation were regular. Menopause had taken place 6 years earlier. The patient did not report any bleeding disorders or climacteric symptoms, and had never
0378-5122/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 7 8 - 5 1 2 2 ( 0 1 ) 0 0 2 0 9 - 2
D. Foth et al. / Maturitas 39 (2001) 259–264
260
received hormone replacement therapy. Previous medical history revealed two caesarean sections, but no other operations. The examinations confirmed the following results.
1.1.1. Gynaecological examination Vulvae and vagina with no abnormal findings, portio: transformation zone, cytology Papanicolaou II, Proliferation degree (Schmitt) 3–4; uterus hyperplastic and fixated, retroflexion, about 5 cm solid tumour in connection with the posterior part of the uterus, adnexa with no abnormalities. 1.1.2. Ultrasonic examination Hyperplastic uterus, intramurally a solid tumour at the right posterior part of the uterus 59 × 45× 43 mm, further small solid intramural tumours with less than B10 mm (leiomyomas); thickness of the endometrium 4,8 mm with a homogenous structure; ovaries with no abnormal findings and without ascites in the abdominal cavity. 1.1.3. Serum hormone measurements see Table 1 In agreement with the patient, an abdominal hysterectomy with bilateral salpingo-oophorectomy was carried out due to growing uterine myomas, lower abdominal pain and fixation of the hyperplastic uterus 1.1.4. Intraoperati6e situs Intraperitoneal adhesions; uterus myomatous with a typical leimyoma on the right posterior wall. Adnexa on both sides and the peritoneal surface presented no other macroscopic abnormalities.
Table 1 Serum hormone measurements (pre- and postoperative)
Estradiol in pg/ml FSH in mIU/ml LH in mIU/ml
preoperative
postoperative (day 7th)
55 31 20
B5 63 25
1.1.5. Microscopic findings 1. Uterus: diffuse myometrial hyperplasia, several typical leiomyomas without abnormalities; endometrium mostly thin and atrophic, but small focuses of an irregular glandular hyperplasia with parts of an intramucously growing, highly differentiated endometrial adenocarcinoma. The tumour was limited to the interior third of the myometrium: pT1b GI estrogen receptor 100% and progesterone receptor 70% positive cells (Fig. 1). 2. Adnexa right: 2×1× 0.5 cm in diameter atrophic ovary with a small typical initial fibroma, fallopian tube with no abnormal findings. 3. Adnexa left: 4×2× 2 cm in diameter atrophic ovary, centrally a solid tumour located, 2,3 cm in size. Microscopically, this tumour showed the appearance of a typical fibrom. The fallopian tube was also without abnormal findings (Fig. 2) The postoperative time period took a normal course without any complications. However, immediately after the operation, the patient developed climacteric symptoms. The histological diagnosis of a highly differentiated adenocarcinoma of the endometrium in the early stage (pT1b GI) and fibromas of both ovaries did not require more than the completed operative treatment.
2. Discussion We report a postmenopausal woman with bilateral fibromas and a highly differentiated endometrium adenocarcinoma in the early stage. Histologically, there was no evidence of a hormonally active ovarian tumour. However, clinically, we registered signs of estrogen production in this postmenopausal woman. Retrospectively, the lack of climacteric symptoms preoperatively and the new appearance of climacteric symptoms after surgical treatment, in combination with the results of serum hormone measurements, have to be assessed as a possible sign of an estrogen producing tumour. Furthermore, the post-
D. Foth et al. / Maturitas 39 (2001) 259–264
261
Fig. 1. Histology: intramucously growing, highly differentiated endometrial adenocarcinoma, limited to the interior third of the myometrium: pT1b GI (10 ×).
menopausal growth of myomas represents a possible sign of a hormone producing tumour. Exposure of the postmenopausal endometrium to estrogen can result in endometrial hyperplasia or even in carcinoma. In the reported case, a highly differentiated endometrium carcinoma was diagnosed. There was no sign of postmenopausal bleeding disorder. Vaginal bleeding is a late symptom of endometrial carcinomas and is often not reported in early stages. Pre- and intraoperatively, the patient was not suspected of having an endometrium carcinoma or ovarian tumour. In recent years, screening procedures have been proposed to detect ovarian and endometrial cancer. After reviewing recent literature, we recommend a sonographic control if the endometrium thickness is between 5 and 8 mm in postmenopausal women without bleeding and without hormone replacement therapy (Table 2; Ro¨ mer et al., in press). Endometrium thickness less than 4 mm is without consequences. Karlsson et al. 1995 describe the risk of finding endometrial pathologies when the endometrium is 54 mm with 5.5%. In general, a cut-off limit of 5 or 4 mm endometrial thickness (double layer) is used today. How-
ever, even if the sonographically measured endometrial thickness is below this limit, an endometrial carcinoma is possible. The development of de-novo carcinoma may happen in an atrophic endometrium. Not only the endometrial thickness is of importance, but also the echogenity and the endo-myometrial transition. Doppler sonography can improve diagnostic possibilities. Bourne et al. (1991) studied changes in uterine blood flow to detect endometrial cancer. Malignant tumours showed signs of altered vascularization and low pulsatility index (PI). But Sheth et al. (1995) could no show differences in mean PI and resistance index (RI) for benign and malignant endometrial lesions in postmenopausal women. In the reported case, no Doppler ultrasound was available. An ovarian tumour was not visualised. The diagnosis of fibromas was only histologically possible. According to macroscopic findings, the left ovary was double the size of the right ovary. Duda et al. (1990) describe significant differences in size between the postmenopausal right and left ovary as suspicious. As early as 1989, Campbell et al., recommended transabdominal ultrasound screening for early ovarian cancer (Campbell et al., 1989). Later Kur-
D. Foth et al. / Maturitas 39 (2001) 259–264
262
Fig. 2. Histology: fibroma of the left ovary (20 × ).
jak et al. (1992) describe the use of transvaginal colour and pulsed Doppler ultrasonography to detect ovarian carcinoma. Morphology alone has poor sensitivity, but when combined with Doppler indices, the sensitivity improves (Kurjak et al., 1992; Salem et al., 1994; Voigt, 1995). Spectral Doppler waveform characteristics (RI, PI) correlate well with malignancies but generally add little informatics to morphologic considerations (Jeong et al., 2000). Beside fibromas, fibrothecomas are hormonally active tumours derived from the gonadal mesenchyme. Thecomas occur primarily in postmenopausal women. Theca cell tumours are solid and of small size. Most of them occur unilaterally in otherwise normal ovaries (Barrenetxea et al., 1990; Aboud, 1997; Cronje´ et al., 1999). The natural history of theca cell tumours is generally one of slow
growth. True malignant thecomas are a rare condition (Novak et al., 1971; Waxman et al., 1979; Deppe and Lawrence, 1988). However, the clinical picture may be dominated by the results of the estrogen secretion. Even if a sex cord stromal tumour is benign, the resulting effects on the endometrium may become life threatening due to the potential production of estrogens over an extended period of time. From the pathological features, theca cell tumours are composed of monomorphic spindle cells, lipid vacuoles and fibromatous tissue. The differential diagnosis between fibroma and lipid containing Desmin-positive thecoma is sometimes difficult to make. However, again, in this case there was no histological evidence of a thecom. In a retrospective study by Barrenetxea et al. (1990), 29 cases of thecomas were reported with a mean age of 49 years. Nearly half of the patients
Table 2 Endometrial thickness (double layer) as measured by transvaginal ultrasonography for identifying endometrial abnormities: cut-off limits in postmenopausal women without bleeding disorders
Hyteroscopy+biopsy Control: (2–3 months) Without consequence
Sequential HRT* (mm)
Continuous-combined-HRT (mm)
No HRT (mm)
]13a 9–12 58
]9 5–8 54
]9 5–8 54
D. Foth et al. / Maturitas 39 (2001) 259–264
were postmenopausal. The main symptom in postmenopausal women was vaginal bleeding, which was present in 44.4% of cases. Postmenopausal bleedings and other bleeding disorders as well as abdominal swellings, especially in premenopausal women, are possible clinical symptoms (Barrenetxea et al., 1990; Aboud, 1997; Cronje´ et al., 1999). Cronje´ et al. (1999) reviewed 116 patients with thecomas. The great majority of these patients had abnormal bleedings and lower abdominal pain. However, 18.1% of the postmenopausal women did not show any bleeding disorders. This may be attributed to lower levels of estrogen secretion for an extended period. The reported incidences of patients with ovarian thecomas and associated endometrial hyperplasia of different degrees varies from 20%– 64%, while 4.5% –27% were found to have concomitant ade nocarcinoma (Hoskins and Rubin, 1992; Aboud, 1997; Cronje´ et al., 1999). The reported incidences of associated pathologies of the endometrium vary in the literature. True incidences of these associated pathologies are not clearly established. Many cases of thecomas did not have the required histological examinations of the endometrium available. Gonadal stromal tumours are often of such a small size that ovaries are not significantly enlarged. That is why in many cases, fibromas and thecomas are preoperatively not diagnosed. The indications for surgical treatment are often not limited to the adnexa. Ovarian tumours are the indication for operative intervention in only 58% of cases (Barrenetxea et al., 1990). Other indications for surgery are uterine myomas and bleeding disorders. Mostly the diagnosis is only a histological one. In this reported case of bilateral ovarian fibromas, the discrepancy between clinical signs of an estrogen producing tumour and histology still remains at present.
3. Conclusion From the clinical point of view, small fibromas are hard to diagnose. Possible symptoms of an estrogen-producing
263
tumour in postmenopausal women are: elevated estrogen serum levels growth of uterine myomas sonographically diagnosed endometrium hyperplasia other symptoms of estrogen production, for instance, hormonal effects on the vaginal epithelia [Proliferation degree (Schmitt)], mastalgia a.o. All the mentioned clinical symptoms are also possible without a hormone-producing tumour in postmenopausal women. There are estrogenic effects on the vaginal epithelium [Proliferation degree (Schmitt)] in 75% of postmenopausal women without hormone replacement therapy (Ro¨ mer and Foth, 1996). The absence of climacteric symptoms is also not a sure sign. As many as 25% of climacteric women do not report symptoms (Hauser, 1992). Still, all possible clinical symptoms should be evaluated accurately.
Acknowledgements We wish to acknowledge Margaret Priemer for her careful translation of this paper.
References Aboud E. A review of granulosa cell tumours and thecomas of the ovary. Arch Gynecol Obstet 1997;259:161 – 5. Barrenetxea G, Schneider J, Centeno MM, Martinez AJ, Fernandez de Larrino A, Gonzales del Tanago J, et al. Pure theca cell tumours. Eur J Gynaec Oncol 1990;11[6]:429 – 32. Bourne Th, Campbell S, Steer CV, Royston P, Whitehead MI, Collins WP. Detection of endometrial cancer by transvaginal ultrasonography with color flow imaging and blood flow analysis: a preliminary report. Gynecol Oncol 1991);40:253 – 9. Campbell S, Bhan V, Royston P, Whitehead MI, Collins WP. Transabdominal ultrasound screening for early ovarian cancer. Br J Med 1989;299:1363 – 7. Cronje´ HS, Niemand I, Bam RH, Woodruff D. Review of the granulosa-theca cell tumors from the Emil Novak Ovarian Tumor Registry. Am J Obstet Gynecol 1999;180:323 – 7. Deppe G, Lawrence WD. Cancer of the ovary. In: Gusberg SB, Shingleton HM, Deppe G, editors. Female Genital Cancer. New York: Churchell Livingstone, 1988.
264
D. Foth et al. / Maturitas 39 (2001) 259–264
Duda V, Rode G, Thein C, Schulz KD. Vaginalsonographie: Pilotstudie fu¨ r den Einsatz als Ovarial-Screening-Verfahren. Geburtshilfe Frauenheilkd 1990;50:388 –93. Hauser GA. Ha¨ ufigkeit klimakterischer Symptome-eine Literaturu¨ bersicht. In: Lauritzen C, editor. Menopause: Hormonsubstitution heute. Mu¨ nchen: Stabil-Verlag, 1992:18 – 21. Hoskins W, Rubin S. Malignant gonadal stromal tumours of the ovary: clinical features and mangement. In: Coppleson M, editor. Gynaecology Oncology. Edinburgh: Livingstone, 1992:961 –70. Jeong YY, Outwater EK, Kang HK. Imaging evaluation of ovarian masses. Radiographics 2000;20:1445 –70. Karlsson B, Granberg S, Wikland M, Ylostalo P, Torvid K, Marsal K, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding — a Nordic multicenter study. Am J Obstet Gynecol 1995;172:1488 – 94. Kurjak A, Schulman H, Sosic A, Zalud I, Shalan H. Transvaginal ultrasound, color flow, and Doppler waveform of the postmenopausal adnexal mass. Obstet Gynecol 1992;80:917 – 21. Novak ER, Kutchmeshgi J, Mupas RS. Feminizing gonaldal stromal tumors: Analysis of the granulosa-theca cell tu-
mours of the Ovarian Tumor Registry. Obstet Gynecol 1971;38:701 – 13. Ro¨ mer, Th., Foth, D., Duda, V., Rabe, Th., Empfehlung zur sonographischen Diagnostik bei asymptomatishcen postmenopausalen Patientinnen mit ohne ohne Hormonsubstitution. In press Ro¨ mer T, Foth D. Hormonelle vaginalzytologische und symptomatische U8 berwachung der Hormonsubstitution. J Menopause 1996;1:12 – 5. Salem S, White LM, Lai J. Doppler sonography of adnexal masses: the predictive value of the pulsatility index in benign and malignant disease. Am J Roentgenol 1994;163:1147 – 50. Sheth S, Hamper UM, McCollum ME, Caskey CI, Rosenshein NB, Kurman RJ. Endometrial blood flow analysis in postmenopausal women: can it help differentiate benign from malignant causes of endometrial thickening? Radiology 1995;195:661 – 5. Voigt HJ. Transvaginaler Doppler/Farbdoppler in der gyna¨ kologischen Diagnostik. Gyna¨ kologe 1995;28:254 – 61. Waxman M, Vuletin JC, Urcuyo R, Belling CG. Ovarian low-grade stromal sarcoma with thecoma features: a critical reappraisal of the so-called ‘malignant thecoma’. Cancer 1979;44:2206 – 17.