GYNECOLOGIC ONCOLOGY 15, 350-356 (1983)

Hysteroscopic Diagnosis of Malignant Mixed Miillerian Tumor of the Corpus Uteri

AKIRA SUZUKI, M.D.,’ HIDEYUKI TAHARA, AND HITOSHI OKAMURA, M.D.

Department of Obstetrics and Gynecology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan

Received February 8, 1982

Hysteroscopic findings of two cases with homologous type of malignant mixed mtillerian tumor of the corpus uteri are described. On hysteroscopic examination, not only were nodular or polypoid lesions with fairly smooth surfaces found but also lesions with rough uneven surfaces and dilated vessels resembling the figures of endometrial carcinoma were observed. The blood vessels of lesions with fairly smooth surfaces were not dilated. Under hysteroscopy, each lesion with a smooth surface seemed to be more closely related to a benign lesion, such as an endometrial polyp or submucous myoma. The lesions with smooth surfaces corresponded to the histologically sarcoma-dominant areas and the lesions with uneven surfaces and dilated vessels were equivalent to the sites where adenocarcinoma was noted. Thus, hysteroscopic findings of this tumor well reflected the histology near the surface of the endometrium.

INTRODUCTION

Recently, hysteroscopy has become a reliable procedure for diagnosis of the intrauterine lesions, such as endometrial polyp, submucous myoma, and endometrial carcinoma, accompanying the advance of illumination systems and methods of uterine distention [l-4]. Among the malignancy of the corpus uteri, Sugimoto [I] reported hysteroscopic diagnosis of the endometrial carcinoma in detail. He described how not only the extent of the tumor but also its histology could be predicted.

Malignant mixed mtillerian tumor of the uterus is a rare carcinomatous and sarcomatous disease which originates from totipotential mesenchymal cells located just beneath the surface epithelium [5]. This tumor is divided into heterologous and homologous types according to whether it has heterologous elements such as striated muscle, cartilage, and bone in the sarcomatous stroma or not [6]. This disease accounts for 2 to 5% of all uterine malignancies [7,8] and spreads mainly through the endometrium. Therefore, hysteroscopy seems to be valuable for the diagnosis of malignant mixed mtillerian tumor as well as endometrial carcinoma. Nevertheless, hysteroscopic findings of this type of tumor have not been reported until today probably due to the rarity of this disease.

’ To whom correspondence should be sent.

350

0090-8258/83 $1.50 Copyright 0 1983 by Academic Press, Inc. All rights of reproduction in any form reserved

HYSTEROSCOPY OF MIXED MtiLLERlAN TUMOR 351

From 1968, hysteroscopy has been routinely used for the diagnosis of intrauterine lesions of patients in Kyoto University Hospital. There were only two cases with the homologous type of malignant mixed mtillerian tumor until today. This paper is the first report of hysteroscopic findings of this disease.

INSTRUMENTS AND CLINICAL MATERIALS

Instruments

The instruments used were a Machida water-type hysteroscope with a multi- halogen cold light source (RM 300 type) and a Kowa SQ-type endoscope camera with Kodak Ektachrome ED 135 ASA 200 film for photographic recording. Sterile physiologic saline and Dextran T-70 solution were used as the distending medium. The examination was performed under anesthesia with intravenous injection of 15 mg pentazosine and 10 mg diazepam.

Case Reports

Case 1. A 61-year-old nulliparous woman was admitted to Kyoto University Hospital on March 7, 1980, with a l-month history of postmenopausal vaginal bleeding. Her family and past medical history were irrelevant except she had received injections of estradiol once a month since her uneventful menopause occurred at 45. Endometrial biopsy was performed two times at an outpatient clinic, but only necrotized tissue was obtained.

Physical examination revealed a well-nourished elderly woman. A ball-shaped soft tumor was palpable in the center of the lower abdomen, which extended to the level of 5 cm below the umbilicus. On pelvic examination, the cervix was smooth and epithelized; a small amount of dark blood emanated from the external OS. The uterus was enlarged to the size of a 12-week pregnancy. Both adnexa were not palpable. Vaginal cytology was class II. Hysteroscopy was performed on March 7 to clarify the cause of genital bleeding.

Case 2. A married woman, aged 52, gravida 5, para 3, entered the hospital March 25, 1981, complaining of continuous vaginal bleeding for the last 3 months. Her menstruation was regular until November 1980. Her last menstruation began on December 20, 1980 and then she complained of continuous vaginal bleeding. Nothing was noted on physical examination. Vaginal examination showed the cervix was slightly eroded: a small amount of dark blood emanated from the external OS. A specimen for histology taken from a 1 x l-cm polypoid mass protruding from the cervical OS was only necrotized tissue. The uterus was the size of an &week pregnancy. Both adnexa were not palpable. Vaginal cytology was class II. Hysteroscopy was performed on March 27, 1981.

HYSTEROSCOPIC FINDINGS AND MICROSCOPIC PATHOLOGY

Case 1

The length of the uterine cavity was 11 cm. Malignancy was suspected because many, large, nodular lesions filled the uterine cavity, but the majority of the nodular lesions had a fairly smooth surface and the gland ostia were not noted (Fig. 1). Blood vessels of these nodules with smooth surfaces were not dilated and the arrangement of the vessels was regular (Fig. 2). Many necrotic tissues

352 SUZUKI, TAHARA, AND OKAMURA

nodular lesion (smooth surface)

FIG. 1. Large nodular lesion with smooth surface of Case 1.

colored yellowish grey were also found. Microscopic sections of these nodular lesions were mainly occupied by sarcomatous stroma which possessed bizarre fusiform connective tissue cells including multinucleated giant cells with abnormal mitotic figures. Endometrial glands trapped in sarcomatous stroma were normal. The surface of the endometrium was smooth covered by a layer of lining epithelium. Besides these findings, there were some nodular lesions found on hysteroscopy which had rough uneven surfaces and engorged vessels (Fig. 3). Specimens from this part had both sarcomatous stroma and well-differentiated adenocarcinoma composed of striated hyperchromatic epithelial cells with frequent mitosis (Fig. 4). Heterologous elements such as striated muscle, cartilage, and bone were not seen in the stroma. The diagnosis was a homologous type of malignant mixed mtillerian tumor.

Case 2

The length of the uterine cavity was 8 cm. Numerous tentacle-like projections were noticed quivering in the rinsing water on the uterine fundus. Dilated vessels were noticed in the center of the tentacles (Fig. 5). These findings agreed with the characteristic of papillary endometrial carcinoma reported by Sugimoto [ 1,9]. The microscopic section from this area was mainly occupied by malignant epithelial cells. The stromal cells in this area did not show malignant change. The surface of the endometrium was eneven, showing papillary projection of adenocarcinoma.

blood vessel

nodular lesion (smooth surface)

FIG. 2. The blood vessels of the nodular lesion with smooth surface of Case I. The arrangement of the vessels is regular.

HYSTEROSCOPY OF MIXED MULLERIAN TUMOR

nodular lesson (uneven surface)

engorged vessels

nodular lesion (smooth sqrface)

FIG. 3. Nodular lesion with uneven surface and dilated vessels of Case I

353

FIG. 4. Photomicrograph of the nodular lesion with uneven surface of Case 2 which shows dominant sarcomatous stroma and well-differentiated adenocarcinoma.

FIG. 5. Tentacle-like projections which were seen on the uterine fundus of Case 2. Dilated vessels are noticed in the center of tentacles.

354 SUZUKI, TAHARA, AND OKAMURA

In addition to this carcinomatous finding, a polypoid mass arising from the left posterior wall of the uterine cavity was noted on hysteroscopy. This polypoid lesion looked flat and velvety on the whole. A necrotic area was found on the tip of this lesion. There were no dilated vessels on the surface of the polypoid mass (Fig. 6). In the microscopic section from this polypoid mass, there was malignant sarcomatous stroma made up of spindle and polyhedral-shaped cells. A part of endometrial glands was normal, but the other part showed the figures of moderately differentiated adenocarcinoma (Fig. 7). The surface was fairly smooth. The diagnosis was a homologous type of malignant mixed mtillerian tumor.

DISCUSSION

Hysteroscopy has the following advantages for diagnosis of the intrauterine lesions: (1) the location, extent, and quality of the lesion can be directly confirmed, (2) small and localized lesions which may be missed by curettage alone can be more correctly diagnosed by the biopsy under visual control. As to the malignant disease of the uterine corpus, the usefulness of hysteroscopy for diagnosis of endometrial carcinoma has been well documented recently [ 1,3,9]. Joelsson et al. [3] advocated the use of hysteroscopy to determine the extent of spread of the cancer and found it a useful aid to the more traditional fractional curettage. Moreover, Sugimoto [1,9] reported that not only the extent of the tumor but also its histology can be predicted by hysteroscopy.

Malignant mixed mtillerian tumor is the disease which spreads mainly through the endometrium and is diagnosed for 75% patients by curettage [8]. Therefore, it is postulated that hysteroscopy is a valuable aid for diagnosis of this disease. However, hysteroscopic findings of this tumor have not been reported until today probably due to the rarity of the disease. Both of our patients diseases were missed at biopsy by outpatient clinic examinations and first correctly diagnosed by curettage under hysteroscopy. From our experience, dilatation, hysteroscopy, and curettage proposed by Sugimoto [9] seems to be more safe and sure for diagnosis of such patients than traditional fractional curettages.

Hysteroscopic findings of our patients were both sufficiently suspicious of ma- lignancy. In comparison to microscopic pathology, both patients had lesions with uneven surface and dilated vessels resembling nodular type or papillary type of

FIG. 6. Polypoid mass pedunculating from the left posterior wall of the uterine cavity of Case 2. The surface is velvety on the whole.

HYSTEROSCOPY OF MIXED MtiLLERIAN TUMOR 355

FIG. 7. Photomicrograph of the polypoid lesion of Case 2 showing sarcomatous stroma and moderately differentiated adenocarcinoma.

endometrial carcinoma [9] where adenocarcinoma was noticed. On the other hand, both nodular lesions of Case 1 and polypoid lesions of Case 2, in which histologically sarcomatous elements were dominant, had fairly smooth surfaces. These findings were more closely related to benign lesions, than to that of the endometrial carcinoma. Thus, hysteroscopic findings of the patients with malignant mixed miillerian tumor were well reflecting the histology near the surface of endometrium. If the polypoid or nodular lesion is small and histologically sar- comatous elements are dominant, it is possible to mistake it for a benign endometrial polyp or a submucosal myoma macroscopically. Careful curettage under visual control must be done to obtain a correct diagnosis.

It is postulated that hysteroscopic findings will be different in compliance with the ratio of carcinomatous to sarcomatous elements. An accumulation of information about hysteroscopic findings of uterine sarcoma is desired.

In the case of malignant disease, distension of the uterine cavity with fluid for hysteroscopy has been criticized for the potential risk of tumor dissemination to the tubes, ovaries, and peritoneal cavity. However, of 91 cases with intrauterine malignancies including 89 endometrial carcinomas and the 2 cases in this report, we have never seen the spread of the tumor at laparotomy after hysteroscopy. The same experiences were also documented in the literature [ 1,3]. Other possible side effects of hysteroscopy are cervical laceration and uterine perforation, but these complications can be avoided completely by careful manipulation of the hysteroscope. Therefore, hysteroscopy seems to be not only a sure but also a safe method for diagnosis of intrauterine malignancy.

356 SUZUKI, TAHARA, AND OKAMURA

REFERENCES 1. Sugimoto, 0. Hysteroscopic diagnosis of endometrial carcinoma, Amer. J. Obsret. Gynecol. 121,

105-113 (1975). 2. Edstrom, K., and Fernstrom, I. The diagnostic possibilities of a modified hysteroscopic technique,

Acta Obstet. Gynecol. Stand. 49, 327-330 (1970). 3. Joelsson, I., Levine, R. U., and Moberger, G. Hysteroscopy as an adjunct in determining the

extent of carcinoma of the endometrium, Amer. J. Obstet. Gynecol. 111, 696-702 (1970). 4. Sciarra, J. J., and Valle, R. F. Hysteroscopy: A clinical experience with 320 patients, Amer. J.

Obsret. Gynecol. 127, 340-348 (1977). 5. Boram, L. H., Erlandoson, R. A., and Hadju, S. I. Mesodernal mixed tumor of the uterus: A

cytologic, histologic and electron microscopic correlation, Cancer 30, 1295-1306 (1972). 6. Ober, W. B. Uterine sarcoma, histogenesis and taxonomy, Ann. N. Y. Acad. Sci. 75, 568-585

(1959). 7. Falkinburg, L. W., Hoey, W. O., Savran, J., and Stuart, J. R. Mesodermal mixed tumor of the

corpus uteri. Review and report of six cases, one of which has survived fifteen years, Amer. J. Obstet. Gynecol. 90, 450-458 (1964).

8. Chaung, J. T., Van Velden, D. J. J., and Graham, J. B. Carcinosarcoma and mixed mesodermal tumor of the uterine corpus. Review of 49 cases, Obstet. Gynecol. 35, 769-780 (1970).

9. Sugimoto, 0. Endometrial carcinoma, in Diagnostic and therapeutic hysreroscopy, Igaku-Shoin Ltd., Tokyo/New York, pp. 67-86 (1978).