Hysteroscopic
diagnosis of endometrial carcinoma
A report of fifty-three
cases examined at the Women’s Clinic
of Kyoto University
Hospital
OSAMU
M.D.
SUGIMOTO,
Sakyoku,
Kyoto,
This presentation of endometrial by hysteroscopy, noma. It was
endometrial
Jafian
defines carcinoma. followed felt that carcinoma
cancerous lesions. diagnosis of curettage.
for
the instrumentation and technique of hysteroscopy for the diagnosis Fifty-three patients with abnormal uterine bleeding uere examined by curettage which confirmed the diagnosis of endometrial carcihysteroscopy not only could detect the existence and extent of but also might depict histologic structures near the surface of
Dilatation, endometrial
hysteroscopy, carcinoma,
and curettage should be an excellent method perhaps replacing conventional dilatation and
T H E D I A G N 0 s I s of endometrial cancer is usually more difficult than the detection of cervical malignancy, because, in general, the former is neither visible on speculum examination nor palpable by digital examination. Cell smears obtained by conventional cervical and vaginal fornix sampling do not always accurately reflect endometrial cancer. Diagnostic dilatation and curettage has been the most reliable method; however, it is a blind procedure and has the disadvantage that some lesions of the endometrium, particularly small early ones, may be missed. If hysteroscopy is used to confirm the presence, location, and extent of endometrial carcinoma and biopsy is done under visual control, then the correct diagnosis should be made more frequently and more accurately. Hysteroscopy is an old method first used by Pantaleoni (1869) to inspect the uterine cavity in a living human subject. Despite enthusiastic efforts to popularize the method, it has not been From the Department Gynecology, School Received
for
Revised
April
Accepted
May
of Obstetrics and of Medicine, Kyoto
publication 24, 10,
Nouember
generally accepted, because of the mechanical weak points of instrumentation and optical systems. During the past twenty years, little has been done in the use of hysteroscopy for the diagnosis of endometrial carcinoma,“, !I>I2 We have devised a reliable and useful hysteroscope for more accurate interpretation of intrauterine abnormalities. This paper reports 53 cases of endometrial carcinoma in a series of over 4,000 patients examined by hysteroscopy, with suspected intrauterine abnormalities, in the Women’s Clinic of Kyoto University Hospital. Material
and
methods
Instruments for hysteroscopy. Most rigid endoscopes are now equipped with a glass fiber bundle as the light-conveying system. The source of light is separated from the endoscope itself, and intense illumination is obtained through the light guide of glass fibers. The hysteroscope used in this study, manufactured by the Machida Company in Japan, is equipped with such an illumination system. The proximal light source is a xenon or multihalogen mercury bulb located in an air-cooled housing. This hysteroscope is attached to a rinsing compartment from which sterile saline or highly viscous dextran solution flows into the channel of the hysteroscope and out over the distal end of the hysteroscope to circulate through the uterine cavity. The outer
University.
15, 1973.
1974. 1974.
Reprint requests: Dr. Osamu Sugimoto, Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakucho Takatsuki, Osaka 569, Japan.
105
IO6
Sugimoto
(A
1
Pathologic
Classtflcatlon , Adenoma
Diffuse
( B )
ClassIf
Form
IcatIon
EndophytlcuUndifferentiatedLMedullary Form Type
on
Hysteroscopy
carclnOma
Form Exophytic
Circumscribed Form Dlffose
J
mallgnum
Form
EndophybcA Form
Fig. 1. Classification
Ulcerated
of endometrial
Type
cancer.
Fig. 2. Fiber optic hysteroscope (water type).
sleeve, a metallic pipe with an outer diameter of 8 mm., is an indispensable attachment of the hysteroscope to prevent injury of the endometrium and bleeding. Since one cannot obtain a clear vision if the hysteroscope is close to the object, the outer sleeve is made 2 mm. longer than the lens system of the hysteroscope. Technique of hysteroscopy. Preparation for hysteroscopic examination is similar to that for dilatation and curettage. The cervix is dilated to a No. 7 Hegar dilator, and then the outer sleeve with the obturator is inserted readily into the cervical canal just past the internal OS. In postmenopausal patients with narrow cervical canals, we recommend careful
insertion of the laminaria to prevent cervical lacerations the day before examination. The outer sleeve is removed, and the hysteroscope, connected with the water-intake-and-outflow apparatus, is introduced up to three fourths of the length of the outer sleeve. The uterine cavity is irrigated with saline from a container 50 cm. above the pelvis. Blood clots, mucus, and endometrial debris in the uterine cavity are carried away through an outflow tube. When the fluid becomes clear, the hysteroscope is inserted to the base of the sleeve and locked in position. The hysteroscopic examination should commence near the internal OS of the uterus, and then the
Volume Number
121 1
Hysteroscopic
diagnosis
of
Table I. Endometrial between hysteroscopic pattern
endometrial
carcinoma
107
carcinoma: relationship findings and histopathologic
I
Histopathologic
I
pattern
Differentiated (adenocarcinoma)
I
Hysteroscopic findings Polypoid Nodular Papillary Ulcerated Total
Fig. 3. .4 source of light holding
a xenon lamp.
hysteroscope is moved gradually toward the upper portion of the uterine cavity. It is absolutely necessary to dilate the uterine cavity adequately to obtain a clear view of the endometrial surface. In some cases, however, it is difficult to distend the uterine cavity with 50 cm. of water pressure. In these cases instillation of highly viscous dextran solution instead of saline at a pressure of 50 to 100 mm. Hg allows enough dilatation of the uterine cavity to visualize the whole endometrial surface without leakage through the Fallopian tube into the peritoneal cavity. Another advantage of the use of this medium is that there is little interference from hemorrhage during observation since no blood is mixed with the solution. It is easy to see the characteristic appearance of endometrial cancer on hysteroscopy, but the diagnosis is not confirmed until a microscopic examination of biopsy material obtained under visual control is completed. Materials. Since 1967, more than 4,000 hysteroscopic examinations have been performed at the Women’s Clinic of Kyoto University Hospital in Japan. All 1,824 patients noted to have abnormal uterine bleeding through the cervical canal on speculum examination were examined by hysteroscopy prior to conventional curettage. Of these, 53 cases were diagnosed as endometrial carcinoma by hysteroscopy followed by endometrial biopsy. The ages of these patients ranged from 38 to 81 years.
type type type type
3 4 1 8
1 7 4 12
1 23 5 29
4 4
Since many endometrial carcinomas have a typical external appearance, most are readily diagnosed by hysteroscopy alone. These characteristics depend upon the superficial components of cancer tissue, so hysteroscopic findings were correlated with the histopathology of superficial areas of lesions from endometrial biopsy or hysterectomy specimens. Results The histopathologic classification of endometrial cancer is shown in Fig. 1, A ; hysteroscopy also tells us whether the endometrial cancer is circumscribed or diffuse and whether the tumor growth is exophytic or endophytic, as noted in Fig. 1, B. Most of the endometrial cancers are of the circumscribed type which display exophytic growth with polypoid, nodular, or papillary processes in any part of the uterine cavity. Many of this type are histologically well differentiated. A polypoid appearance was noted in 4 of the 53 cases (Table I). This type usually consisted of several polyps with a gray-white, finely uneven surface and a characteristic venous dilatation in some areas (Fig. 2). Without this finding on hysteroscopy, the condition might sometimes be mistaken for benign adenomatous polyp. Most polypoid cancers proved histologically to be tubular adenocarcinoma (Fig. 3) (3 of 4 cases). The nodular type was seen in 12 of 53 cases (Table I). In this type the protrusion was larger, with a rough surface and marked subepithelial varicosities. The vessels, mostly veins, which were not all covered by the lining epithelium of the endometrium, rose tortuously from the surface of the tumor and were scattered over it (Figs. 4 and 5). Lesions of the nodular type were histologically well differentiated; adenomatous adenocarcinoma was
108
Sugimoto
Fig. 4. Hysteroscopic picture of the polypoid type of endometrial several polypoid tissues in a 56-year-old woman. The surface, on irregularly scattered, is rather smooth and gray-whitish in color.
Fig. 5. Microscopic metrium. Atrophic
pattern of Fig. endometrium
4. Well-differentiated (right lower) as
seen in 7 cases, and tubular adenocarcinoma was found in 4 (Fig. 6). One case of papillary adenocarcinoma did not show papillary projections on hysteroscopy. The papillary type had the highest incidence (23 of the 53 cases). This type showed apparently nodular protuberances on hysteroscopy, but with careful observation many tentacle-like projections of cancerous tissue could be seen quivering in the rinsing fluid. The surfaces of these tumors were rough, granular, or velvety because of papillary propagation of cancerous tissue. The arrangement of cancer cells in each tentacle was disorderly and rosette-like around atrophic stroma which contained a few
tubular contrasted
carcinoma composed which dilated vessels
adenocarcinoma to polypoid
of the carcinoma.
of are
endo-
blood vessels (Fig. 7). These tentacles, which gathered to form a dendritic structure, some long and others short, were light pink in color because of numerous cancer cells proliferating around the blood vessels (Fig. 8). Short tentacles looked like clusters of grapes (Fig. 9)) and long ones interlocking with each other looked like balls of yarn (Fig. 10). It is well known that the superficial parts of endometrial cancer can become ulcerated because of undernourishment at the end of cancerous tissues, since the blood supply cannot keep pace with the very rapid development of cancer cells. Many of the other types of cancer may also show ulceration, but the characteristic appearance of each type can
Volume Number
121 1
Hysteroscopic
Fig. 6. Hysteroscopic picture ing dilated, but interrupted,
Fig. 7. Hysteroscopic dilated blood vessels
of the nodular type of endometrial blood vessels on a rugged surface.
picture of nodular type of endometrial rising irregularly from the surface of the
diagnosis
carcinoma.
carcinoma. cancerous
of
endometrial
The
There tissue.
nodule
are
carcinoma
show-
numerous
Fig. 8. Microscopic pattern of adenomatous adenocarcinoma of the endometrium. The nodular type, as in Figs. 6 and 7, often shows this structure. A large shriveled blood vessel in this picture is observed as a more dilated one on hysteroscopy in the living uterus.
109
110
Sugimoto
Fig. 9. Cross-section composed of a few cancer cells (C).
Fig. 10. Longitudinal structure
be seen in the other
of tentacles
parts
of papillary blood vessels
adenocarcinoma (V) in atrophic
of the endometrium. stroma surrounded
section of papillary adenocarcinoma is observed also by the hysteroscope
of the lesion
on hysteros-
copy. The ulcerated type, in which the entire surface of the cancer is destroyed, was found in 14 cases (Table I). In 8 of these, the lesions were diffuse and showed purulent infection. The surface of the cancer in the cases of pyometria looked more ragged, and dull on hysteroscopy because of the fragile, coating of pus and debris. When these were washed away with saline, suppurating lesions showed a naked surface of numerous ragged protuberances and marked varicosities (Fig. 11). As mentioned formations on the surface of the endoabove, varix metrium were never seen in intrauterine lesions
with
Papillary tentacles are irregularly arranged
of the endometrium. as they are.
This
dendritic
other than endometrial cancer. In ulcerated cancers without pyometria, since the tissue of the ulcerated area had few specific features, it was often ver) difficult to determine the histologic pattern by hysteroscopy. The final histologic examination in 1-l cases of the ulcerated type of endometrial cancer revealed one tubular, 4 adenomatous, and 5 papillary adenocarcinomas and 4 undifferentiated cancers (Figs. 12 to 14). It seems that the less the differentiation, the more frequent the ulceration. Much of the noncancerous endometrium adjoining the cancer lesions was atrophic and smooth, though occasionally a hyperplastic pattern was evident even in postmenopausal women. In these cases,
Volume 121 vumber 1
Hysteroscopic
Fig. 11. papillary
Hysteroscopic projections
picture of papillary type of endometrial which resembles a cluster of grapes.
Fig. 12. Hysteroscopic pattern of the papillary type of endometrial tumor composed of long tentacles interlocking with one another yarn. Small vessels can be seen in the central axis of each tentacle.
Fig. 13. Hysteroscopic finding pus (P) and blood clots (B) is full of rugged protuberances.
of the ulcerated have been washed
type of endometrial away, the naked
diagnosis
carcinoma.
carcinoma. resembles
of
endometrial
A mass
carcinoma
of
short
A mass of the a ball of woolen
carcinoma. After overlying surface of cancer lesions (C)
112
Sugimoto
Fig. 14. Microscopic pattern of undifferentiated carcinoma of the endometrium. Infiltration of small round cells is marked. and a few vessels near the ragged surface are dilated and thrombosed. especially with the diffuse type of cancer, it may be very difficult to distinguish the cancer foci from the hyperplastic endometrium. In 2 of the 53 cases, hysteroscopy revealed that cancer tissue had invaded the cervix beyond the internal OS, and 50 patients were treated surgically. There were no complications of hysteroscopy, and no peritoneal implantation of cancer cells was noted at laparotomy. Comment Hysteroscopy in the past has been no more than a way to confirm the existence, location, and extent of intrauterine lesions, though experience accumulated in many cases of endometrial disorders has made it possible to deduce the pathology from the external appearance of the lesion seen by recent techniques of hysteroscopy. Furthermore, a biopsy of the suspected area under direct vision permits a more accurate diagnosis of intrauterine abnormalities than do conventional dilatation and curettage. With the procedures of dilatation, hysteroscopy, and curettage, dysfunctional endometrial disorders can be differentiated readily and accurately from organic lesions such as cancer, polyp, inflammation, etc. Diagnostic curettage before hysteroscopy leads to confusion in interpretation of the hysteroscopic findings of endometrial cancer because it destroys the structure of cancerous tissue and changes the original appearance of the tumor. In order to obtain a good view of the uterine
cavity on hysteroscopy, the uterus must be cleared of blood, mucus, and endometrial debris and then dilated. Methods of distending the uterine cavity for hysteroscopy have been insufflation with carbon dioxide”. I0 and irrigation with saline.“, ‘3 ‘I The latter has been used not only by Norment,a Englund and associates,’ Gribb,” and others but also by many investigators in Japan until quite recently. However, although it washes away obstacles in the uterine cavity, saline is inconvenient in that it mixes with blood so that the view on hysteroscopy may be obscured. Furthermore, it is feared that the saline may flow out through the Fallopian tubes into the peritoneal cavity even under relatively low pressure because of its low viscosity. The use of a viscous dextran solution, developed by Edstrom and Fernstrijml and manufactured by Pharmacia AB in Sweden, has overcome these disadvantages. This 32 per cent dextran solution is colorless, transparent. and very viscous, so that it does not mix with blood or enter the peritoneal cavity under a pressure of 100 mm. Hg or less. In this series of 53 endometrial cancers, almost all were clearly visible when this medium was used. Observations of endometrial cancer by hysteroscopy were attempted by Schroder,” Norment,” and Silander,l” although they were hesitant to diagnose endometrial cancer by this method. Our hysteroscopic examinations of over 4,000 cases, since 1967, have made it possible not only to differentiate endometrial cancer from other intrauterine abnor-
Volume Number
121 1
malities but also to speculate on its tissue structure. Most endometrial cancers tend to spread exophytically in the uterine cavity, and the histology shows a highly differentiated pattern of adenocarcinoma. Most of the tubular and some of the adenomatous adenocarcinomas are veiled with lining epithelium which usually shows a malignant transition stage. Consequently, on hysteroscopy, the tumor seems to be relatively smooth in external appearance and light gray in color and frequently shows varicose dilatations of the subepithelial vessels. Varix formations on the surface of the tumor are an important finding on hysteroscopy and a conclusive factor in the diagnosis of endometrial cancer. Papillary adenocarcinoma of the endometrium, the most frequently encountered endometrial cancer, usually forms a nodular mass near the fundus. With careful observation, however, the histopathologic appearance of the dendritic structure of the papillary projections can be determined at hysteroscopy. The dilated veins in the stroma of the tentacles are also visible. Thus, exophytic, usually circumscribed endometrial cancers can be identified by hysteroscopy more easily than might be expected. Diffuse, often poorly differentiated cancers have a more marked tendency to infiltrate broadly and endophytically. These diffusely extended tumors in the uterine cavity, when seen through the hysteroscope, sometimes show none of the features of a typical adenocarcinoma. Even when complicated by pyometria, the appearance remains still more indistinct because of the pus and debris overlying the tumor. In order to determine the best treatment for endo-
Hysteroscopic
diagnosis
of
endometrial
carcinoma
113
metrial cancer, it is important to confirm the extent and location of the tumor in the uterine cavity. Fractional curettage has been the most reliable method so far, though it is often difficult to determine whether or not the cancer has made it possible to interpret clearly the extent, location, and margins of the tumor.5’ I2 In this series of 53 cases, broad invasion of the cervix beyond the internal OS was seen in 2 cases, in which systematic extensive hysterectomy was performed. Some patients with endometrial cancer must be treated with radiotherapy or chemotherapy for reasons such as old age or poor health. Though the extensions of the tumor are not always confined within the uterus, at times hysteroscopy is most convenient for following transition of the tumor in the uterine cavity after conservative treatment. Three patients who had circumscribed endometrial cancer were treated with radiotherapy and large doses of progestins because of age or advanced heart disease. Follow-up hysteroscopy every 3 months revealed gradual resolution of the tumors. It is not too much to say that hysteroscopy is a safe and simple method for diagnosis of intrauterine abnormalities, and all the procedures may be done on an outpatient basis. The possible side effects of hysteroscopy are cervical laceration, uterine perforation, and intraperitoneal dissemination of cancer cells or infection. However, these side effects can be avoided completely by careful manipulation of the hysteroscope, and as a matter of fact, we have never encountered a side injury serious enough to force us to discontinue the examination.
REFERENCES
1. 2. 3. 4. 5. 6.
Edstrom, K., and Fernstrom, I.: Acta Obstet. Gynecol. Stand. 49: 327, 1970. Englund, S., Ingelman-Sundberg, A., and Westin, B.: Gynaecologia 143: 217, 1957. Gauss, C. J.: Arch. Gynaekol. 133: 18, 1928. Gribb, J. J.: Obstet. Gynecol. 15: 593, 1960. Jo&son, I., Levine, R. U., and Moberger, G.: AM. J. OBSTET. GYNECOL. 111: 696, 1971. Lindemann, H.-J.: Endoscopy 3: 194, 1971.
7. 8. 9. 10. 11. 12.
Mikuricz-Radecki, F., and Freund, A.: Z. Geburtshilfe Gynaekol. 9: 13, 1927. Norment, W. B.: Geriatrics 11: 13, 1956. Norment, W. B., and Greensboro, N. C.: AM. J. OBSTET. GYNECOL. 71: 426, 1956. Rubin, I. C.: AM. J. OBSTET. GYNECOL. 10: 313, 1925. Schroder, C.: Arch. Gynaekol. 156: 407, 1934. Silander, T.: Acta Obstet. Gynecol. Stand. 4: 284, 1963.
diagnosis of endometrial carcinoma
A report of fifty-three
cases examined at the Women’s Clinic
of Kyoto University
Hospital
OSAMU
M.D.
SUGIMOTO,
Sakyoku,
Kyoto,
This presentation of endometrial by hysteroscopy, noma. It was
endometrial
Jafian
defines carcinoma. followed felt that carcinoma
cancerous lesions. diagnosis of curettage.
for
the instrumentation and technique of hysteroscopy for the diagnosis Fifty-three patients with abnormal uterine bleeding uere examined by curettage which confirmed the diagnosis of endometrial carcihysteroscopy not only could detect the existence and extent of but also might depict histologic structures near the surface of
Dilatation, endometrial
hysteroscopy, carcinoma,
and curettage should be an excellent method perhaps replacing conventional dilatation and
T H E D I A G N 0 s I s of endometrial cancer is usually more difficult than the detection of cervical malignancy, because, in general, the former is neither visible on speculum examination nor palpable by digital examination. Cell smears obtained by conventional cervical and vaginal fornix sampling do not always accurately reflect endometrial cancer. Diagnostic dilatation and curettage has been the most reliable method; however, it is a blind procedure and has the disadvantage that some lesions of the endometrium, particularly small early ones, may be missed. If hysteroscopy is used to confirm the presence, location, and extent of endometrial carcinoma and biopsy is done under visual control, then the correct diagnosis should be made more frequently and more accurately. Hysteroscopy is an old method first used by Pantaleoni (1869) to inspect the uterine cavity in a living human subject. Despite enthusiastic efforts to popularize the method, it has not been From the Department Gynecology, School Received
for
Revised
April
Accepted
May
of Obstetrics and of Medicine, Kyoto
publication 24, 10,
Nouember
generally accepted, because of the mechanical weak points of instrumentation and optical systems. During the past twenty years, little has been done in the use of hysteroscopy for the diagnosis of endometrial carcinoma,“, !I>I2 We have devised a reliable and useful hysteroscope for more accurate interpretation of intrauterine abnormalities. This paper reports 53 cases of endometrial carcinoma in a series of over 4,000 patients examined by hysteroscopy, with suspected intrauterine abnormalities, in the Women’s Clinic of Kyoto University Hospital. Material
and
methods
Instruments for hysteroscopy. Most rigid endoscopes are now equipped with a glass fiber bundle as the light-conveying system. The source of light is separated from the endoscope itself, and intense illumination is obtained through the light guide of glass fibers. The hysteroscope used in this study, manufactured by the Machida Company in Japan, is equipped with such an illumination system. The proximal light source is a xenon or multihalogen mercury bulb located in an air-cooled housing. This hysteroscope is attached to a rinsing compartment from which sterile saline or highly viscous dextran solution flows into the channel of the hysteroscope and out over the distal end of the hysteroscope to circulate through the uterine cavity. The outer
University.
15, 1973.
1974. 1974.
Reprint requests: Dr. Osamu Sugimoto, Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakucho Takatsuki, Osaka 569, Japan.
105
IO6
Sugimoto
(A
1
Pathologic
Classtflcatlon , Adenoma
Diffuse
( B )
ClassIf
Form
IcatIon
EndophytlcuUndifferentiatedLMedullary Form Type
on
Hysteroscopy
carclnOma
Form Exophytic
Circumscribed Form Dlffose
J
mallgnum
Form
EndophybcA Form
Fig. 1. Classification
Ulcerated
of endometrial
Type
cancer.
Fig. 2. Fiber optic hysteroscope (water type).
sleeve, a metallic pipe with an outer diameter of 8 mm., is an indispensable attachment of the hysteroscope to prevent injury of the endometrium and bleeding. Since one cannot obtain a clear vision if the hysteroscope is close to the object, the outer sleeve is made 2 mm. longer than the lens system of the hysteroscope. Technique of hysteroscopy. Preparation for hysteroscopic examination is similar to that for dilatation and curettage. The cervix is dilated to a No. 7 Hegar dilator, and then the outer sleeve with the obturator is inserted readily into the cervical canal just past the internal OS. In postmenopausal patients with narrow cervical canals, we recommend careful
insertion of the laminaria to prevent cervical lacerations the day before examination. The outer sleeve is removed, and the hysteroscope, connected with the water-intake-and-outflow apparatus, is introduced up to three fourths of the length of the outer sleeve. The uterine cavity is irrigated with saline from a container 50 cm. above the pelvis. Blood clots, mucus, and endometrial debris in the uterine cavity are carried away through an outflow tube. When the fluid becomes clear, the hysteroscope is inserted to the base of the sleeve and locked in position. The hysteroscopic examination should commence near the internal OS of the uterus, and then the
Volume Number
121 1
Hysteroscopic
diagnosis
of
Table I. Endometrial between hysteroscopic pattern
endometrial
carcinoma
107
carcinoma: relationship findings and histopathologic
I
Histopathologic
I
pattern
Differentiated (adenocarcinoma)
I
Hysteroscopic findings Polypoid Nodular Papillary Ulcerated Total
Fig. 3. .4 source of light holding
a xenon lamp.
hysteroscope is moved gradually toward the upper portion of the uterine cavity. It is absolutely necessary to dilate the uterine cavity adequately to obtain a clear view of the endometrial surface. In some cases, however, it is difficult to distend the uterine cavity with 50 cm. of water pressure. In these cases instillation of highly viscous dextran solution instead of saline at a pressure of 50 to 100 mm. Hg allows enough dilatation of the uterine cavity to visualize the whole endometrial surface without leakage through the Fallopian tube into the peritoneal cavity. Another advantage of the use of this medium is that there is little interference from hemorrhage during observation since no blood is mixed with the solution. It is easy to see the characteristic appearance of endometrial cancer on hysteroscopy, but the diagnosis is not confirmed until a microscopic examination of biopsy material obtained under visual control is completed. Materials. Since 1967, more than 4,000 hysteroscopic examinations have been performed at the Women’s Clinic of Kyoto University Hospital in Japan. All 1,824 patients noted to have abnormal uterine bleeding through the cervical canal on speculum examination were examined by hysteroscopy prior to conventional curettage. Of these, 53 cases were diagnosed as endometrial carcinoma by hysteroscopy followed by endometrial biopsy. The ages of these patients ranged from 38 to 81 years.
type type type type
3 4 1 8
1 7 4 12
1 23 5 29
4 4
Since many endometrial carcinomas have a typical external appearance, most are readily diagnosed by hysteroscopy alone. These characteristics depend upon the superficial components of cancer tissue, so hysteroscopic findings were correlated with the histopathology of superficial areas of lesions from endometrial biopsy or hysterectomy specimens. Results The histopathologic classification of endometrial cancer is shown in Fig. 1, A ; hysteroscopy also tells us whether the endometrial cancer is circumscribed or diffuse and whether the tumor growth is exophytic or endophytic, as noted in Fig. 1, B. Most of the endometrial cancers are of the circumscribed type which display exophytic growth with polypoid, nodular, or papillary processes in any part of the uterine cavity. Many of this type are histologically well differentiated. A polypoid appearance was noted in 4 of the 53 cases (Table I). This type usually consisted of several polyps with a gray-white, finely uneven surface and a characteristic venous dilatation in some areas (Fig. 2). Without this finding on hysteroscopy, the condition might sometimes be mistaken for benign adenomatous polyp. Most polypoid cancers proved histologically to be tubular adenocarcinoma (Fig. 3) (3 of 4 cases). The nodular type was seen in 12 of 53 cases (Table I). In this type the protrusion was larger, with a rough surface and marked subepithelial varicosities. The vessels, mostly veins, which were not all covered by the lining epithelium of the endometrium, rose tortuously from the surface of the tumor and were scattered over it (Figs. 4 and 5). Lesions of the nodular type were histologically well differentiated; adenomatous adenocarcinoma was
108
Sugimoto
Fig. 4. Hysteroscopic picture of the polypoid type of endometrial several polypoid tissues in a 56-year-old woman. The surface, on irregularly scattered, is rather smooth and gray-whitish in color.
Fig. 5. Microscopic metrium. Atrophic
pattern of Fig. endometrium
4. Well-differentiated (right lower) as
seen in 7 cases, and tubular adenocarcinoma was found in 4 (Fig. 6). One case of papillary adenocarcinoma did not show papillary projections on hysteroscopy. The papillary type had the highest incidence (23 of the 53 cases). This type showed apparently nodular protuberances on hysteroscopy, but with careful observation many tentacle-like projections of cancerous tissue could be seen quivering in the rinsing fluid. The surfaces of these tumors were rough, granular, or velvety because of papillary propagation of cancerous tissue. The arrangement of cancer cells in each tentacle was disorderly and rosette-like around atrophic stroma which contained a few
tubular contrasted
carcinoma composed which dilated vessels
adenocarcinoma to polypoid
of the carcinoma.
of are
endo-
blood vessels (Fig. 7). These tentacles, which gathered to form a dendritic structure, some long and others short, were light pink in color because of numerous cancer cells proliferating around the blood vessels (Fig. 8). Short tentacles looked like clusters of grapes (Fig. 9)) and long ones interlocking with each other looked like balls of yarn (Fig. 10). It is well known that the superficial parts of endometrial cancer can become ulcerated because of undernourishment at the end of cancerous tissues, since the blood supply cannot keep pace with the very rapid development of cancer cells. Many of the other types of cancer may also show ulceration, but the characteristic appearance of each type can
Volume Number
121 1
Hysteroscopic
Fig. 6. Hysteroscopic picture ing dilated, but interrupted,
Fig. 7. Hysteroscopic dilated blood vessels
of the nodular type of endometrial blood vessels on a rugged surface.
picture of nodular type of endometrial rising irregularly from the surface of the
diagnosis
carcinoma.
carcinoma. cancerous
of
endometrial
The
There tissue.
nodule
are
carcinoma
show-
numerous
Fig. 8. Microscopic pattern of adenomatous adenocarcinoma of the endometrium. The nodular type, as in Figs. 6 and 7, often shows this structure. A large shriveled blood vessel in this picture is observed as a more dilated one on hysteroscopy in the living uterus.
109
110
Sugimoto
Fig. 9. Cross-section composed of a few cancer cells (C).
Fig. 10. Longitudinal structure
be seen in the other
of tentacles
parts
of papillary blood vessels
adenocarcinoma (V) in atrophic
of the endometrium. stroma surrounded
section of papillary adenocarcinoma is observed also by the hysteroscope
of the lesion
on hysteros-
copy. The ulcerated type, in which the entire surface of the cancer is destroyed, was found in 14 cases (Table I). In 8 of these, the lesions were diffuse and showed purulent infection. The surface of the cancer in the cases of pyometria looked more ragged, and dull on hysteroscopy because of the fragile, coating of pus and debris. When these were washed away with saline, suppurating lesions showed a naked surface of numerous ragged protuberances and marked varicosities (Fig. 11). As mentioned formations on the surface of the endoabove, varix metrium were never seen in intrauterine lesions
with
Papillary tentacles are irregularly arranged
of the endometrium. as they are.
This
dendritic
other than endometrial cancer. In ulcerated cancers without pyometria, since the tissue of the ulcerated area had few specific features, it was often ver) difficult to determine the histologic pattern by hysteroscopy. The final histologic examination in 1-l cases of the ulcerated type of endometrial cancer revealed one tubular, 4 adenomatous, and 5 papillary adenocarcinomas and 4 undifferentiated cancers (Figs. 12 to 14). It seems that the less the differentiation, the more frequent the ulceration. Much of the noncancerous endometrium adjoining the cancer lesions was atrophic and smooth, though occasionally a hyperplastic pattern was evident even in postmenopausal women. In these cases,
Volume 121 vumber 1
Hysteroscopic
Fig. 11. papillary
Hysteroscopic projections
picture of papillary type of endometrial which resembles a cluster of grapes.
Fig. 12. Hysteroscopic pattern of the papillary type of endometrial tumor composed of long tentacles interlocking with one another yarn. Small vessels can be seen in the central axis of each tentacle.
Fig. 13. Hysteroscopic finding pus (P) and blood clots (B) is full of rugged protuberances.
of the ulcerated have been washed
type of endometrial away, the naked
diagnosis
carcinoma.
carcinoma. resembles
of
endometrial
A mass
carcinoma
of
short
A mass of the a ball of woolen
carcinoma. After overlying surface of cancer lesions (C)
112
Sugimoto
Fig. 14. Microscopic pattern of undifferentiated carcinoma of the endometrium. Infiltration of small round cells is marked. and a few vessels near the ragged surface are dilated and thrombosed. especially with the diffuse type of cancer, it may be very difficult to distinguish the cancer foci from the hyperplastic endometrium. In 2 of the 53 cases, hysteroscopy revealed that cancer tissue had invaded the cervix beyond the internal OS, and 50 patients were treated surgically. There were no complications of hysteroscopy, and no peritoneal implantation of cancer cells was noted at laparotomy. Comment Hysteroscopy in the past has been no more than a way to confirm the existence, location, and extent of intrauterine lesions, though experience accumulated in many cases of endometrial disorders has made it possible to deduce the pathology from the external appearance of the lesion seen by recent techniques of hysteroscopy. Furthermore, a biopsy of the suspected area under direct vision permits a more accurate diagnosis of intrauterine abnormalities than do conventional dilatation and curettage. With the procedures of dilatation, hysteroscopy, and curettage, dysfunctional endometrial disorders can be differentiated readily and accurately from organic lesions such as cancer, polyp, inflammation, etc. Diagnostic curettage before hysteroscopy leads to confusion in interpretation of the hysteroscopic findings of endometrial cancer because it destroys the structure of cancerous tissue and changes the original appearance of the tumor. In order to obtain a good view of the uterine
cavity on hysteroscopy, the uterus must be cleared of blood, mucus, and endometrial debris and then dilated. Methods of distending the uterine cavity for hysteroscopy have been insufflation with carbon dioxide”. I0 and irrigation with saline.“, ‘3 ‘I The latter has been used not only by Norment,a Englund and associates,’ Gribb,” and others but also by many investigators in Japan until quite recently. However, although it washes away obstacles in the uterine cavity, saline is inconvenient in that it mixes with blood so that the view on hysteroscopy may be obscured. Furthermore, it is feared that the saline may flow out through the Fallopian tubes into the peritoneal cavity even under relatively low pressure because of its low viscosity. The use of a viscous dextran solution, developed by Edstrom and Fernstrijml and manufactured by Pharmacia AB in Sweden, has overcome these disadvantages. This 32 per cent dextran solution is colorless, transparent. and very viscous, so that it does not mix with blood or enter the peritoneal cavity under a pressure of 100 mm. Hg or less. In this series of 53 endometrial cancers, almost all were clearly visible when this medium was used. Observations of endometrial cancer by hysteroscopy were attempted by Schroder,” Norment,” and Silander,l” although they were hesitant to diagnose endometrial cancer by this method. Our hysteroscopic examinations of over 4,000 cases, since 1967, have made it possible not only to differentiate endometrial cancer from other intrauterine abnor-
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malities but also to speculate on its tissue structure. Most endometrial cancers tend to spread exophytically in the uterine cavity, and the histology shows a highly differentiated pattern of adenocarcinoma. Most of the tubular and some of the adenomatous adenocarcinomas are veiled with lining epithelium which usually shows a malignant transition stage. Consequently, on hysteroscopy, the tumor seems to be relatively smooth in external appearance and light gray in color and frequently shows varicose dilatations of the subepithelial vessels. Varix formations on the surface of the tumor are an important finding on hysteroscopy and a conclusive factor in the diagnosis of endometrial cancer. Papillary adenocarcinoma of the endometrium, the most frequently encountered endometrial cancer, usually forms a nodular mass near the fundus. With careful observation, however, the histopathologic appearance of the dendritic structure of the papillary projections can be determined at hysteroscopy. The dilated veins in the stroma of the tentacles are also visible. Thus, exophytic, usually circumscribed endometrial cancers can be identified by hysteroscopy more easily than might be expected. Diffuse, often poorly differentiated cancers have a more marked tendency to infiltrate broadly and endophytically. These diffusely extended tumors in the uterine cavity, when seen through the hysteroscope, sometimes show none of the features of a typical adenocarcinoma. Even when complicated by pyometria, the appearance remains still more indistinct because of the pus and debris overlying the tumor. In order to determine the best treatment for endo-
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metrial cancer, it is important to confirm the extent and location of the tumor in the uterine cavity. Fractional curettage has been the most reliable method so far, though it is often difficult to determine whether or not the cancer has made it possible to interpret clearly the extent, location, and margins of the tumor.5’ I2 In this series of 53 cases, broad invasion of the cervix beyond the internal OS was seen in 2 cases, in which systematic extensive hysterectomy was performed. Some patients with endometrial cancer must be treated with radiotherapy or chemotherapy for reasons such as old age or poor health. Though the extensions of the tumor are not always confined within the uterus, at times hysteroscopy is most convenient for following transition of the tumor in the uterine cavity after conservative treatment. Three patients who had circumscribed endometrial cancer were treated with radiotherapy and large doses of progestins because of age or advanced heart disease. Follow-up hysteroscopy every 3 months revealed gradual resolution of the tumors. It is not too much to say that hysteroscopy is a safe and simple method for diagnosis of intrauterine abnormalities, and all the procedures may be done on an outpatient basis. The possible side effects of hysteroscopy are cervical laceration, uterine perforation, and intraperitoneal dissemination of cancer cells or infection. However, these side effects can be avoided completely by careful manipulation of the hysteroscope, and as a matter of fact, we have never encountered a side injury serious enough to force us to discontinue the examination.
REFERENCES
1. 2. 3. 4. 5. 6.
Edstrom, K., and Fernstrom, I.: Acta Obstet. Gynecol. Stand. 49: 327, 1970. Englund, S., Ingelman-Sundberg, A., and Westin, B.: Gynaecologia 143: 217, 1957. Gauss, C. J.: Arch. Gynaekol. 133: 18, 1928. Gribb, J. J.: Obstet. Gynecol. 15: 593, 1960. Jo&son, I., Levine, R. U., and Moberger, G.: AM. J. OBSTET. GYNECOL. 111: 696, 1971. Lindemann, H.-J.: Endoscopy 3: 194, 1971.
7. 8. 9. 10. 11. 12.
Mikuricz-Radecki, F., and Freund, A.: Z. Geburtshilfe Gynaekol. 9: 13, 1927. Norment, W. B.: Geriatrics 11: 13, 1956. Norment, W. B., and Greensboro, N. C.: AM. J. OBSTET. GYNECOL. 71: 426, 1956. Rubin, I. C.: AM. J. OBSTET. GYNECOL. 10: 313, 1925. Schroder, C.: Arch. Gynaekol. 156: 407, 1934. Silander, T.: Acta Obstet. Gynecol. Stand. 4: 284, 1963.
