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Pseudomucinous cystadenocarcinoma associated with pregnancy
Pseudomucinous cystadenocarcinoma associated with pregnancy MACLYN E. WADE, M.D. NIKOLAS A. JANOVSKI, M.D. STANLEY M. BYSSHE, M.D. New York, New York
THE management of an ovarian cyst noted during pregnancy has been reviewed by such authors as Haas, 9 Gray, 6 Stech/ 5 Bryan/ Gustafson/ and Lespinasse. 12 Haas9 reports an incidence of 23 true ovarian cysts 5 em. or larger in 7,598 pregnancies (1:316). Stech15 reported 37 ovarian tumors in 28,442 deliveries ( 1: 768). In Stech's series of 37 tumors, 20 were benign cysts ( 15 serous, 2 papillary, 3 pseudomucinous), 13 were dermoid cysts, 1 was a struma ovarii, 1 was a teratoma embryonate, 1 was a fibroma, and 1 was a pseudomucinous cystadenocarcinoma. Lespinasse12 reported 3 cases out of 21,876 deliveries ( 1 : 1,000) . Gustafson8 reviewed 100,000 deliveries in eight different hospitals and found the incidence of associated ovarian tumors to vary from 1 in 1,000 to 1 in 8,000 depending upon the hospital. It is customary for obstetricians to follow carefully all pregnant patients with adnexal masses of 5 em. or less in size. During the first trimester of pregnancy these usually represent corpus luteum cysts6 which regress when the placenta becomes the chief source of estrogens and progesterones. Even if the adnexal mass is larger than 5 em., most clinicians prefer to wait until the second
trimester before performing the operation, unless signs and symptoms demand immediate laparotomy. Again, most obstetricians3• 4 • 10 are in agreement as to the necessity for surgical intervention when the presence of a 5 em. or larger adnexal mass is detected during the second trimester. With tumors noted during the third trimester, surgical intervention is usually deferred until the puerperium. The ratio of proved primary carcinoma of the ovary in pregnancy to the number of associated deliveries varies from 1 : 8,0005 to 1: 50,000 2 to 1: 100,000. 8 Amico1 states that ovarian malignancy is present in 2 to 3 per cent of all ovarian tumors removed during pregnancy and Stech15 considers the incidence to be 5 per cent. Although there is considerable agreement as to the therapy of ovarian carcinoma, there is little available literature to aid the obstetrician in the treatment of this neoplastic condition when it is associated with pregnancy. From 1951 to 1961 at the Sloane Hospital for Women, a total of 618 ovarian neoplastic cysts have been encountered in 18,391 laparotomies performed on the gynecologic service. Of these, 293 were papillary serous cystadenomas, 142 were pseudomucinous cystadenomas, 103 were serous cystadenocarcinomas, and 33 were pseudomucinous cystadenocarcinomas. In this same period there were 40,598 deliveries. During the antepartum course of these patients, there were 72 patients from whom ovarian tumors
From the Department of Obstetrics and Gynecology of the College of Physicians and Surgeons, Columbia University, and the Obstetrical and Gynecological Division of the Presbyterian Hospital in the City of New York (Sloane Hospital for Women), Columbia-Presbyterian Medical Center.
919
920
Wade, Janovski, and Bysshe \111
'q•J li L J~•l· ·. & C\ lWC
J ( iL-.r_,
Table I. Pseudomucinous cystadenocarcinoma associated with pregnancy
I
:
Authors
Year
Age of patient
Stuebler and Brandess 1 5
1933
As reported by Stech---no details given
Quehl"
1950
I Gravidity I
i
Parity
0
30
Week of
I gestation i
T2
Site of tumor
Treatment and fvtiow-up
Right ovary A. Cesarean section thirty-ninth week of gestation following onset of labor with delivery of a normal infant. B. Cesarean subtotal hysterectomy, bilateral salpingooophorectomy. Pathology--pseudomucinous cystadenocarcinoma of right ovary.
C. Spread to left ovary --none noted elsewhere. D. Patient received postoperative radiation therapy. No follow-up as to survival given.
Creene and Jones'
1959
26
0
I 0-12
Right ovary A. Right oophorectomy at !0 to 12 weeks' gestation. Pathology-pseudomucinous cystadenocarcinoma of right ovary-Grade I. B. Full-term normal spon-
taneous delivery,_ normal infant.
c.
Exploratory laparotomy H weeks post partum-- left cystectomy. Pathology-follicle cyst of left ovary.
D. No evidence of recurrence or spread at time of t'Xploratory laparotomy. E. No follow-up given.
Macdonald 13
1960
26
2
12
Left ovary
A. Prior to pregnancy · May. 1958, patient underwent a left salpingo-oophorectomy. Pathology-pseudomucinous cystadenocarcinoma. No signs of secondary sprc;Jd observed. B. :February, 1959, at !:! weeks' gestation a right sal pin gooophorectomy performed. Pathology-twisted pseudomucinous cyst-adem)carcinoma of right ovary.
C. Full-term normal spontaneous delivery, normal infant. D. Living and well 5 months following delivery. -----------~
..
"'
,.,._,,
Volume 85
Pseudomucinous cystadenocarcinoma
Number 7
921
Table I. Cont'd Authors
Stech Wade, Janovski, and Bysshe 15
Treatment and follow-up
1961 1961
given 1
0
12
Right ovary A. Right oophorectomy at 12 weeks' gestation. Pathology -pseudomucinous cystadenocarcinoma of right ovary. B. Full-term low forceps delivery, normal infant. C. November, 1961-total abdominal hysterectomy, bilateral salpingectomy and left oophorectomy. Pathology-theca lutein cyst and multiple follicle cysts of left ovary.
.,
D. No evidence of spread or recurrence. E. Living and well.
----------------------------------------5 em. or larger were surgically removed. Twenty-nine of these tumors ( 40.5 per cent) were found to be benign cystic teratomas, 3 ( 4.1 per cent) were pseudomucinous cystadenomas, 12 (16.7 per cent) were serous cystadenomas and 26 (36.1 per cent) were different types of nonneoplastic cysts (follicle cysts, corpus luteum cysts, paramesonephric cysts, and theca luteal cysts). Thus the percentage of benign ovarian cysts, neoplastic and nonneoplastic, found in antepartum patients, based on the total number of deliveries during this 10 year period, is 0.017 per cent. If the nonneoplastic cysts are eliminated, the percentage of benign neoplastic ovarian cyst becomes 0.009 per cent. Only one case of a pseudomucinous cystadenocarcinoma was encountered in a pregnant patient in this period. One serous cystadenocarcinoma was found associated with a tubal pregnancy. In this institution in this same period, the percentage of malignant ovarian tumors associated with pregnancy as compared to the total number of benign ovarian tumors associated with pregnancy is 4.34 per cent. In an extensive review of the literature, we have been able to find only 5 reported cases of primary pseudomucinous cystadenocar-
cinoma associated with pregnancy. These are summarized in Table I. We desire to report a sixth documented case of pseudomucinous cystadenocarcinoma associated with pregnancy and wish to discuss the management of the case. Case report A 21-year-old white, married, graduate nurse, gravida i, para 0, was admitted to the Sloane Hospital for Women on April 2, 1961, with a cystic pelvic mass. The patient experienced regular menses until Dec. 24, 1961. At her antepartum visit on Feb. 24, 1961, a grapefruit-sized, cystic, pelvic mass was noted and laparotomy was scheduled to be performed at the onset of the second trimester. The remainder of the review of systems and past history was unremarkable. Upon admission to the hospital for operation, pelvic examination revealed the external genitals to be normal. The vagina and cervix were nulliparous. The uterus was about 12 weeks' pregnancy size and in anterior position. A 12 by 5 em. cystic mass filled the posterior pelvis and could not be localized to either the right or left side. The pelvis was of a small gynecoid type and thought to be adequate for no more than an average sized baby. The remainder of the physical examination was within normal limits.
922
Wade, Janovski, and Bysshe
Laboratory data upon admission revealed: hemoglobin 10.9 Gm. per cent; white blood cells 12,400, with a normal differential count; urinalysis normal; blood group 0, Rh negative, with no antibodies; serologic test negative for syphilis; chest films normal. On April 3, 1961, at approximately 12 week> of pregnancy, the patient underwent laparotomy. The uterus was found to be of the expected size and lying well forward in the pelvis. The right ovary was replaced by a bilocular cystic tumor which had a smooth surface and dimensions of 13 by 9 em. The tumor was firmly wedged deep in the cul-de-sac and free of adhesions. One area of the cystic mass appeared butter-yellow, suggesting a teratoma. The left ovary was slightly enlarged to 4 by 2 em., and from gross inspection a corpus luteum was thought to be present in this ovary. There wa.' no free fluid in the peritoneal cavity. A right oophorectomy was performed. Pathologic diagnosis of pseudomucinous cystadenocarcinoma was established postoperatively. Because of the religious convictions of the patient, interruption of the pregnancy could not be considered. Decision was made to preserve the pregnancy and allow the patient to go to term. The postoperative course was uneventful and she was discharged from the hospital on the twelfth postoperative day. The patient was allowed to arrive at term, expected date of confinement being Sept. 30, 1961. The baby was considered to be small and the patient had developed no anti-Rh antibodies. She was admitted for the second time on Sept. 30, 1961, in active labor with the membranes ruptured. Early delivery could be anticipated
Fig. 1. The right ovary replaced by a biloculated cystic tumor.
\v~
,\m.
J.
Jl I, 1~Jb:l
Oh~·.L ,~ C.vJlf'l~.
and cesarran section was no longer t.hought to be necessary. Easy delivery was acu.mplishecl hy low forceps and episiotomv. Tlw i11 !ant "a' a viable female, weighing 2,810 grams. The patient's postpartum course was unevcut fu!. She was discharged on the sixth postpartum day along 11·irh a h.:althy infant. After d~li\·l'rv, the patient was completely appraised of the malignancy previously found in the right ovarv. Second laparotomy was planned with the purpose of rt:>moving the left ovary which could always he a potential danger to her .in the future. Certainly biopsy studies at a second ''])('ration could u.:v.:r completely rnle out an <~xisting microscopic malignancy or prevent th<' fut11re development of malignancy in an apparently innocuous ovary. The patient herself f:n·ored the seemingly radical advice of a castrati .. rr operation. She was readmitted to th•· hospital fur operation 5 weeks after delivery. Tlw ldt 0\·arv was found to be cystic and enlarged tu "pproximately 5 em. in diam~t.:r. There was no gross evidence of secondary peritoneal invoh cment ]JV carcinomatous spread. A total abdominal hysterectomy, bilateral salpingectomy, left oophorectomy, and prophylactic appendectomy w.:r<~ performed. One year following the sewnd laparotomy, tlw patient has been found to be in good condition. RPmarkably enough, .;he has had absolutely no m<:nopausal symptoms. The specimen received from the intrapartu!tl laparotomy consisted of the right
Volume 85 Number 7
Pseudomucinous cystadenocarcinoma
923
ovarian cortex was found to be normal in appearance. Several cystic structures were encountered. These were filled with approximately 10 c.c. of serous, straw-colored fluid. Of significance on microscopic examination were the myometrial interstitial hemorrhages. Fibrosed, dilated, and partly hyalinized vascular channels were noted and thought to be compatible with an involuting myometrium. The left tube revealed resting epithelium and a paramesonephric cyst. A theca lutein cyst and multiple follicular cysts were present in the left ovary. There was no evidence of malignancy. Fig. 2. Pliable papillary growth covering the inner surface of the smaller cyst.
.
ing approximately one fourth of its surface. On section, the cysts were found to contain 360 c.c. of fluid. The fluid in the larger cyst was clear and watery; that in the smaller cyst was thick, mucinous, and yellow. The inner wall of the larger cyst was smooth and contained no papillary projections. The inner wall of the smaller cyst contained a large, yellow, friable papillary growth which covered one quarter of the inner surface of the cyst. There was no gross evidence of hemorrhage or necrosis (Fig. 2). Microscopically, the larger cyst was lined by a single layer of columnar epithelium with basally placed nuclei. One area of the cyst wall showed a corpus luteum gravidarum. The tumor in the smaller cyst contained papillary projections lined by neoplastic multilayered epithelium with frequent mitoses. Mayer's mucicarmine stain and periodic acid-Schiff reaction revealed the presence of mucin within these cells. There was a moderate degree of invasion by the neoplastic cells of the capsular connective tissue stroma. Hyalinization, necrosis, and focal hemorrhage were occasionally seen (Figs. 3 and 4). On the basis of these findings, the following diagnoses were made: ( 1 ) pseudomucinous cystadenocarcinoma, moderately well-differentiated, right ovary, clinical stage I; (2) simple pseudomucinous cyst, right ovary, with corpus luteum gravidarum. The specimen received from the postpartum laparotomy consisted of the uterus, cervix, Fallopian tubes, left ovary, and appendix. The uterus and cervix weighed 150 grams. The myometrium measured 3 em. in thickness. The left ovary measured 4 em. in diameter and weighed 40 grams; it was soft and cystic (Fig. 5). The
Comment
The management of this patient's case presented an interesting problem. At the time of the first operation at the twelfth week of gestation, the tumor grossly appeared to involve the right ovary only. A decision based on biopsy at operation might have proved to be misleading, if the benign area of the ovary was alone examined. Subsequent histologic examination revealed the tumor to be a pseudomucinous cystadenocarcinoma, a tumor frequently unilateral in its early stages. 16 • 17 Because of the patient's desire to have a child, it was decided to allow the pregnancy to go to term. An immediate second laparotomy to biopsy the remaining ovary would be fruitful only if the . biopsy proved to be positive. Unless oophorectomy were performed, malignancy could never be completely ruled out. At the Sloane Hospital for Women series, there has been a 53.3 per cent 5 year survival rate (14.0) in patients with a pseudomucinous cystadenocarcinoma, irrespective of the clinical staging or the histologic grading. This is in marked contrast with our over-all 23.8 per cent survival rate 14 in patients with papillary serous cystadenocarcinoma. Since this tumor was moderately well-differentiated, it was felt that the possibility of the tumor appearing in the second ovary was sufficient to indicate additional surgical procedures. Cesarean hysterectomy, bilateral salpingectomy, and a left oophorectomy at term were considered. The patient, however, went into labor spontaneously and arrived at the hospital in advanced
924
Wade, Janovski, and Bysshe
.\p!ill, 196:! Am. ]. Ob,t. & Gynec.
Fig. 3. Tumor formed of papillary projections lined by neoplastic multilayered epithelial cells and massively producing m u c i n. (Hematoxylin and eosin. x25. i
Fig. 4. Cellular details of the tumor. (Hematoxylin and eosin. x250.)
labor. The second operation was postponed and finally performed 5 weeks post partum when proper evaluation of pelvic pathology could be made. A total hysterectomy, bilateral salpingectomy, and a left oophorectomy were performed. Fortunately, there was no evidence of carcinoma in the remaining left ovary or any gross metastases observed at the time of the second operation. Thus, her prognosis would appear to be excellent and no additional therapy seemed to be indicated. Despite accumulated knowledge of the
biology of ovarian carcinomas, there is no valid clinical or pathologicoanatomic prognostic criteria to predict malignant potentiality of the ovarian tumor. Accordingly, precise and definite therapy is impossible and only therapeutic measures, as applied to malignancy in general, are applicable. One wonders, if in this case a more conservative approach to the therapy might be warranted, irrespective of the histologic appearance of the tumor. The patient's ovarian tumor did not exhibit capsular excrescences
Volume 85 Number 7
Pseudomucinous cystadenocarcinoma
925
Summary
Fig. 5. Involuting uterus and multicystic left ovary removed 6 weeks post partum.
,.-
-r
or vegetation; there were no adhesions to surrounding pelvic and abdominal structures, and no evidence of peritoneal seeding. Clinically, it was classified as Grade I. Difficulty in deciding between the conservative therapeutic approach and radical one in a young women have been elaborated by Jamian and Lachowsky, 11 who treated 2 young patients with ovarian carcinomas associated with pregnancy. They concluded that management of such cases must be on an individual case-to-case basis because any systematization in such cases is impossible. No further or more definite suggestions for therapy in these cases could be offered.
REFERENCES
1. Amico, J. C.: AM. J. 0BsT. & GYNEC. 74: 920, 1957. 2. Betson, J. R., Jr., and Golden, M. L.: Obst. & Gynec. 12: 589, 1958. 3. Betson, J. R., Jr., and Golden, M. L. AM. J. 0BST. & GYNEC. 81: 718, 1961. 4. Bryan, W. M., Jr.: AM. J. 0BST. & GYNEC. 70: 1204, 1955. 5. Day, A. M. B., and Murray, D. J.: Canad. M. A. J. 78: 941, 1958. 6. Gray, L. A.: South. M. J. 54: 632, 1961. 7. Greene, W. L., and Jones, E. H.: Obst. & Gynec. 14: 349, 1959. 8. Gustafson, G. W., Gardiner, S. H., and Stout, F. E.: AM. J. 0BST. & GYNEC. 67: 1210, 1954. 9. Haas, R. L.: AM. J. 0BST. & GYNEC. 58: 283, 1949. 10. Hamilton, H. G., and Higgins, R. S.: Internat. Abst. Surg. 89: 525, 1942.
1. In the 10 year period from 1951 to 1961 a single case of pseudomucinous cystadenocarcinoma of the ovary associated with pregnancy was encountered in a total of 40,598 deliveries. 2. In this same period, 72 pregnant patients were operated upon for cystic ovarian tumors measuring 5 ern. or larger in diameter. 3. The total number of benign neoplastic and nonneoplastic ovarian cysts found in antepartum patients compared with the total number of deliveries was established at 0.017 per cent. The percentage of neoplastic cysts alone was 0.009 per cent. 4. The number of malignant ovarian tumors compared to the total number of benign cystic ovarian tumors in this same group of pregnant patients was found to be 4.34 per cent. 5. A review of the literature on this topic disclosed only 5 documented cases of pseudomucinous cystadenocarcinoma associated with pregnancy. We would like to add a sixth case to this series. 6. The management of ovarian carcinoma associated with pregnancy is discussed. The choice of conservative or radical operative treatment can be made only through individualization of each case.
11. J amain, B., and Lachowsky, M.: Gynec. et obst. 60: 585, 1961. 12. Lespinasse, F.: Rev. franc;. gynec. et obst. 57: 111, 1962. 13. Macdonald, R. R.: Scot. M. J. 5: 34 7, 1960. 14. Munnell, E. W., Jacox, H. W., and Taylor, H. C., Jr.: AM. J. 0BST. & GYNEC. 74: 1187, 1957. 15. Stech, von D.: Zentralbl. Gynak. 83: 49, 1961. 16. Taylor, H. C., Jr.: Treatment of Carcinoma of the Ovary-Surgical Aspects, Proceedings of the Third National Cancer Conference, The American Cancer Society, Inc., Philadelphia, 1957, J. B. Lippincott Company. 17. Taylor, H. C., Jr.: Clin. Obst. & Gynec. 1: 1078, 1958. 18. Quehl, E.: J. Obst. & Gynaec. Brit. Emp. 57: 253, 1950.
2400 Lakeview, Apt. 1106 Chicago 14, Illinois (Dr. Janovski)
THE management of an ovarian cyst noted during pregnancy has been reviewed by such authors as Haas, 9 Gray, 6 Stech/ 5 Bryan/ Gustafson/ and Lespinasse. 12 Haas9 reports an incidence of 23 true ovarian cysts 5 em. or larger in 7,598 pregnancies (1:316). Stech15 reported 37 ovarian tumors in 28,442 deliveries ( 1: 768). In Stech's series of 37 tumors, 20 were benign cysts ( 15 serous, 2 papillary, 3 pseudomucinous), 13 were dermoid cysts, 1 was a struma ovarii, 1 was a teratoma embryonate, 1 was a fibroma, and 1 was a pseudomucinous cystadenocarcinoma. Lespinasse12 reported 3 cases out of 21,876 deliveries ( 1 : 1,000) . Gustafson8 reviewed 100,000 deliveries in eight different hospitals and found the incidence of associated ovarian tumors to vary from 1 in 1,000 to 1 in 8,000 depending upon the hospital. It is customary for obstetricians to follow carefully all pregnant patients with adnexal masses of 5 em. or less in size. During the first trimester of pregnancy these usually represent corpus luteum cysts6 which regress when the placenta becomes the chief source of estrogens and progesterones. Even if the adnexal mass is larger than 5 em., most clinicians prefer to wait until the second
trimester before performing the operation, unless signs and symptoms demand immediate laparotomy. Again, most obstetricians3• 4 • 10 are in agreement as to the necessity for surgical intervention when the presence of a 5 em. or larger adnexal mass is detected during the second trimester. With tumors noted during the third trimester, surgical intervention is usually deferred until the puerperium. The ratio of proved primary carcinoma of the ovary in pregnancy to the number of associated deliveries varies from 1 : 8,0005 to 1: 50,000 2 to 1: 100,000. 8 Amico1 states that ovarian malignancy is present in 2 to 3 per cent of all ovarian tumors removed during pregnancy and Stech15 considers the incidence to be 5 per cent. Although there is considerable agreement as to the therapy of ovarian carcinoma, there is little available literature to aid the obstetrician in the treatment of this neoplastic condition when it is associated with pregnancy. From 1951 to 1961 at the Sloane Hospital for Women, a total of 618 ovarian neoplastic cysts have been encountered in 18,391 laparotomies performed on the gynecologic service. Of these, 293 were papillary serous cystadenomas, 142 were pseudomucinous cystadenomas, 103 were serous cystadenocarcinomas, and 33 were pseudomucinous cystadenocarcinomas. In this same period there were 40,598 deliveries. During the antepartum course of these patients, there were 72 patients from whom ovarian tumors
From the Department of Obstetrics and Gynecology of the College of Physicians and Surgeons, Columbia University, and the Obstetrical and Gynecological Division of the Presbyterian Hospital in the City of New York (Sloane Hospital for Women), Columbia-Presbyterian Medical Center.
919
920
Wade, Janovski, and Bysshe \111
'q•J li L J~•l· ·. & C\ lWC
J ( iL-.r_,
Table I. Pseudomucinous cystadenocarcinoma associated with pregnancy
I
:
Authors
Year
Age of patient
Stuebler and Brandess 1 5
1933
As reported by Stech---no details given
Quehl"
1950
I Gravidity I
i
Parity
0
30
Week of
I gestation i
T2
Site of tumor
Treatment and fvtiow-up
Right ovary A. Cesarean section thirty-ninth week of gestation following onset of labor with delivery of a normal infant. B. Cesarean subtotal hysterectomy, bilateral salpingooophorectomy. Pathology--pseudomucinous cystadenocarcinoma of right ovary.
C. Spread to left ovary --none noted elsewhere. D. Patient received postoperative radiation therapy. No follow-up as to survival given.
Creene and Jones'
1959
26
0
I 0-12
Right ovary A. Right oophorectomy at !0 to 12 weeks' gestation. Pathology-pseudomucinous cystadenocarcinoma of right ovary-Grade I. B. Full-term normal spon-
taneous delivery,_ normal infant.
c.
Exploratory laparotomy H weeks post partum-- left cystectomy. Pathology-follicle cyst of left ovary.
D. No evidence of recurrence or spread at time of t'Xploratory laparotomy. E. No follow-up given.
Macdonald 13
1960
26
2
12
Left ovary
A. Prior to pregnancy · May. 1958, patient underwent a left salpingo-oophorectomy. Pathology-pseudomucinous cystadenocarcinoma. No signs of secondary sprc;Jd observed. B. :February, 1959, at !:! weeks' gestation a right sal pin gooophorectomy performed. Pathology-twisted pseudomucinous cyst-adem)carcinoma of right ovary.
C. Full-term normal spontaneous delivery, normal infant. D. Living and well 5 months following delivery. -----------~
..
"'
,.,._,,
Volume 85
Pseudomucinous cystadenocarcinoma
Number 7
921
Table I. Cont'd Authors
Stech Wade, Janovski, and Bysshe 15
Treatment and follow-up
1961 1961
given 1
0
12
Right ovary A. Right oophorectomy at 12 weeks' gestation. Pathology -pseudomucinous cystadenocarcinoma of right ovary. B. Full-term low forceps delivery, normal infant. C. November, 1961-total abdominal hysterectomy, bilateral salpingectomy and left oophorectomy. Pathology-theca lutein cyst and multiple follicle cysts of left ovary.
.,
D. No evidence of spread or recurrence. E. Living and well.
----------------------------------------5 em. or larger were surgically removed. Twenty-nine of these tumors ( 40.5 per cent) were found to be benign cystic teratomas, 3 ( 4.1 per cent) were pseudomucinous cystadenomas, 12 (16.7 per cent) were serous cystadenomas and 26 (36.1 per cent) were different types of nonneoplastic cysts (follicle cysts, corpus luteum cysts, paramesonephric cysts, and theca luteal cysts). Thus the percentage of benign ovarian cysts, neoplastic and nonneoplastic, found in antepartum patients, based on the total number of deliveries during this 10 year period, is 0.017 per cent. If the nonneoplastic cysts are eliminated, the percentage of benign neoplastic ovarian cyst becomes 0.009 per cent. Only one case of a pseudomucinous cystadenocarcinoma was encountered in a pregnant patient in this period. One serous cystadenocarcinoma was found associated with a tubal pregnancy. In this institution in this same period, the percentage of malignant ovarian tumors associated with pregnancy as compared to the total number of benign ovarian tumors associated with pregnancy is 4.34 per cent. In an extensive review of the literature, we have been able to find only 5 reported cases of primary pseudomucinous cystadenocar-
cinoma associated with pregnancy. These are summarized in Table I. We desire to report a sixth documented case of pseudomucinous cystadenocarcinoma associated with pregnancy and wish to discuss the management of the case. Case report A 21-year-old white, married, graduate nurse, gravida i, para 0, was admitted to the Sloane Hospital for Women on April 2, 1961, with a cystic pelvic mass. The patient experienced regular menses until Dec. 24, 1961. At her antepartum visit on Feb. 24, 1961, a grapefruit-sized, cystic, pelvic mass was noted and laparotomy was scheduled to be performed at the onset of the second trimester. The remainder of the review of systems and past history was unremarkable. Upon admission to the hospital for operation, pelvic examination revealed the external genitals to be normal. The vagina and cervix were nulliparous. The uterus was about 12 weeks' pregnancy size and in anterior position. A 12 by 5 em. cystic mass filled the posterior pelvis and could not be localized to either the right or left side. The pelvis was of a small gynecoid type and thought to be adequate for no more than an average sized baby. The remainder of the physical examination was within normal limits.
922
Wade, Janovski, and Bysshe
Laboratory data upon admission revealed: hemoglobin 10.9 Gm. per cent; white blood cells 12,400, with a normal differential count; urinalysis normal; blood group 0, Rh negative, with no antibodies; serologic test negative for syphilis; chest films normal. On April 3, 1961, at approximately 12 week> of pregnancy, the patient underwent laparotomy. The uterus was found to be of the expected size and lying well forward in the pelvis. The right ovary was replaced by a bilocular cystic tumor which had a smooth surface and dimensions of 13 by 9 em. The tumor was firmly wedged deep in the cul-de-sac and free of adhesions. One area of the cystic mass appeared butter-yellow, suggesting a teratoma. The left ovary was slightly enlarged to 4 by 2 em., and from gross inspection a corpus luteum was thought to be present in this ovary. There wa.' no free fluid in the peritoneal cavity. A right oophorectomy was performed. Pathologic diagnosis of pseudomucinous cystadenocarcinoma was established postoperatively. Because of the religious convictions of the patient, interruption of the pregnancy could not be considered. Decision was made to preserve the pregnancy and allow the patient to go to term. The postoperative course was uneventful and she was discharged from the hospital on the twelfth postoperative day. The patient was allowed to arrive at term, expected date of confinement being Sept. 30, 1961. The baby was considered to be small and the patient had developed no anti-Rh antibodies. She was admitted for the second time on Sept. 30, 1961, in active labor with the membranes ruptured. Early delivery could be anticipated
Fig. 1. The right ovary replaced by a biloculated cystic tumor.
\v~
,\m.
J.
Jl I, 1~Jb:l
Oh~·.L ,~ C.vJlf'l~.
and cesarran section was no longer t.hought to be necessary. Easy delivery was acu.mplishecl hy low forceps and episiotomv. Tlw i11 !ant "a' a viable female, weighing 2,810 grams. The patient's postpartum course was unevcut fu!. She was discharged on the sixth postpartum day along 11·irh a h.:althy infant. After d~li\·l'rv, the patient was completely appraised of the malignancy previously found in the right ovarv. Second laparotomy was planned with the purpose of rt:>moving the left ovary which could always he a potential danger to her .in the future. Certainly biopsy studies at a second ''])('ration could u.:v.:r completely rnle out an <~xisting microscopic malignancy or prevent th<' fut11re development of malignancy in an apparently innocuous ovary. The patient herself f:n·ored the seemingly radical advice of a castrati .. rr operation. She was readmitted to th•· hospital fur operation 5 weeks after delivery. Tlw ldt 0\·arv was found to be cystic and enlarged tu "pproximately 5 em. in diam~t.:r. There was no gross evidence of secondary peritoneal invoh cment ]JV carcinomatous spread. A total abdominal hysterectomy, bilateral salpingectomy, left oophorectomy, and prophylactic appendectomy w.:r<~ performed. One year following the sewnd laparotomy, tlw patient has been found to be in good condition. RPmarkably enough, .;he has had absolutely no m<:nopausal symptoms. The specimen received from the intrapartu!tl laparotomy consisted of the right
Volume 85 Number 7
Pseudomucinous cystadenocarcinoma
923
ovarian cortex was found to be normal in appearance. Several cystic structures were encountered. These were filled with approximately 10 c.c. of serous, straw-colored fluid. Of significance on microscopic examination were the myometrial interstitial hemorrhages. Fibrosed, dilated, and partly hyalinized vascular channels were noted and thought to be compatible with an involuting myometrium. The left tube revealed resting epithelium and a paramesonephric cyst. A theca lutein cyst and multiple follicular cysts were present in the left ovary. There was no evidence of malignancy. Fig. 2. Pliable papillary growth covering the inner surface of the smaller cyst.
.
ing approximately one fourth of its surface. On section, the cysts were found to contain 360 c.c. of fluid. The fluid in the larger cyst was clear and watery; that in the smaller cyst was thick, mucinous, and yellow. The inner wall of the larger cyst was smooth and contained no papillary projections. The inner wall of the smaller cyst contained a large, yellow, friable papillary growth which covered one quarter of the inner surface of the cyst. There was no gross evidence of hemorrhage or necrosis (Fig. 2). Microscopically, the larger cyst was lined by a single layer of columnar epithelium with basally placed nuclei. One area of the cyst wall showed a corpus luteum gravidarum. The tumor in the smaller cyst contained papillary projections lined by neoplastic multilayered epithelium with frequent mitoses. Mayer's mucicarmine stain and periodic acid-Schiff reaction revealed the presence of mucin within these cells. There was a moderate degree of invasion by the neoplastic cells of the capsular connective tissue stroma. Hyalinization, necrosis, and focal hemorrhage were occasionally seen (Figs. 3 and 4). On the basis of these findings, the following diagnoses were made: ( 1 ) pseudomucinous cystadenocarcinoma, moderately well-differentiated, right ovary, clinical stage I; (2) simple pseudomucinous cyst, right ovary, with corpus luteum gravidarum. The specimen received from the postpartum laparotomy consisted of the uterus, cervix, Fallopian tubes, left ovary, and appendix. The uterus and cervix weighed 150 grams. The myometrium measured 3 em. in thickness. The left ovary measured 4 em. in diameter and weighed 40 grams; it was soft and cystic (Fig. 5). The
Comment
The management of this patient's case presented an interesting problem. At the time of the first operation at the twelfth week of gestation, the tumor grossly appeared to involve the right ovary only. A decision based on biopsy at operation might have proved to be misleading, if the benign area of the ovary was alone examined. Subsequent histologic examination revealed the tumor to be a pseudomucinous cystadenocarcinoma, a tumor frequently unilateral in its early stages. 16 • 17 Because of the patient's desire to have a child, it was decided to allow the pregnancy to go to term. An immediate second laparotomy to biopsy the remaining ovary would be fruitful only if the . biopsy proved to be positive. Unless oophorectomy were performed, malignancy could never be completely ruled out. At the Sloane Hospital for Women series, there has been a 53.3 per cent 5 year survival rate (14.0) in patients with a pseudomucinous cystadenocarcinoma, irrespective of the clinical staging or the histologic grading. This is in marked contrast with our over-all 23.8 per cent survival rate 14 in patients with papillary serous cystadenocarcinoma. Since this tumor was moderately well-differentiated, it was felt that the possibility of the tumor appearing in the second ovary was sufficient to indicate additional surgical procedures. Cesarean hysterectomy, bilateral salpingectomy, and a left oophorectomy at term were considered. The patient, however, went into labor spontaneously and arrived at the hospital in advanced
924
Wade, Janovski, and Bysshe
.\p!ill, 196:! Am. ]. Ob,t. & Gynec.
Fig. 3. Tumor formed of papillary projections lined by neoplastic multilayered epithelial cells and massively producing m u c i n. (Hematoxylin and eosin. x25. i
Fig. 4. Cellular details of the tumor. (Hematoxylin and eosin. x250.)
labor. The second operation was postponed and finally performed 5 weeks post partum when proper evaluation of pelvic pathology could be made. A total hysterectomy, bilateral salpingectomy, and a left oophorectomy were performed. Fortunately, there was no evidence of carcinoma in the remaining left ovary or any gross metastases observed at the time of the second operation. Thus, her prognosis would appear to be excellent and no additional therapy seemed to be indicated. Despite accumulated knowledge of the
biology of ovarian carcinomas, there is no valid clinical or pathologicoanatomic prognostic criteria to predict malignant potentiality of the ovarian tumor. Accordingly, precise and definite therapy is impossible and only therapeutic measures, as applied to malignancy in general, are applicable. One wonders, if in this case a more conservative approach to the therapy might be warranted, irrespective of the histologic appearance of the tumor. The patient's ovarian tumor did not exhibit capsular excrescences
Volume 85 Number 7
Pseudomucinous cystadenocarcinoma
925
Summary
Fig. 5. Involuting uterus and multicystic left ovary removed 6 weeks post partum.
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or vegetation; there were no adhesions to surrounding pelvic and abdominal structures, and no evidence of peritoneal seeding. Clinically, it was classified as Grade I. Difficulty in deciding between the conservative therapeutic approach and radical one in a young women have been elaborated by Jamian and Lachowsky, 11 who treated 2 young patients with ovarian carcinomas associated with pregnancy. They concluded that management of such cases must be on an individual case-to-case basis because any systematization in such cases is impossible. No further or more definite suggestions for therapy in these cases could be offered.
REFERENCES
1. Amico, J. C.: AM. J. 0BsT. & GYNEC. 74: 920, 1957. 2. Betson, J. R., Jr., and Golden, M. L.: Obst. & Gynec. 12: 589, 1958. 3. Betson, J. R., Jr., and Golden, M. L. AM. J. 0BST. & GYNEC. 81: 718, 1961. 4. Bryan, W. M., Jr.: AM. J. 0BST. & GYNEC. 70: 1204, 1955. 5. Day, A. M. B., and Murray, D. J.: Canad. M. A. J. 78: 941, 1958. 6. Gray, L. A.: South. M. J. 54: 632, 1961. 7. Greene, W. L., and Jones, E. H.: Obst. & Gynec. 14: 349, 1959. 8. Gustafson, G. W., Gardiner, S. H., and Stout, F. E.: AM. J. 0BST. & GYNEC. 67: 1210, 1954. 9. Haas, R. L.: AM. J. 0BST. & GYNEC. 58: 283, 1949. 10. Hamilton, H. G., and Higgins, R. S.: Internat. Abst. Surg. 89: 525, 1942.
1. In the 10 year period from 1951 to 1961 a single case of pseudomucinous cystadenocarcinoma of the ovary associated with pregnancy was encountered in a total of 40,598 deliveries. 2. In this same period, 72 pregnant patients were operated upon for cystic ovarian tumors measuring 5 ern. or larger in diameter. 3. The total number of benign neoplastic and nonneoplastic ovarian cysts found in antepartum patients compared with the total number of deliveries was established at 0.017 per cent. The percentage of neoplastic cysts alone was 0.009 per cent. 4. The number of malignant ovarian tumors compared to the total number of benign cystic ovarian tumors in this same group of pregnant patients was found to be 4.34 per cent. 5. A review of the literature on this topic disclosed only 5 documented cases of pseudomucinous cystadenocarcinoma associated with pregnancy. We would like to add a sixth case to this series. 6. The management of ovarian carcinoma associated with pregnancy is discussed. The choice of conservative or radical operative treatment can be made only through individualization of each case.
11. J amain, B., and Lachowsky, M.: Gynec. et obst. 60: 585, 1961. 12. Lespinasse, F.: Rev. franc;. gynec. et obst. 57: 111, 1962. 13. Macdonald, R. R.: Scot. M. J. 5: 34 7, 1960. 14. Munnell, E. W., Jacox, H. W., and Taylor, H. C., Jr.: AM. J. 0BST. & GYNEC. 74: 1187, 1957. 15. Stech, von D.: Zentralbl. Gynak. 83: 49, 1961. 16. Taylor, H. C., Jr.: Treatment of Carcinoma of the Ovary-Surgical Aspects, Proceedings of the Third National Cancer Conference, The American Cancer Society, Inc., Philadelphia, 1957, J. B. Lippincott Company. 17. Taylor, H. C., Jr.: Clin. Obst. & Gynec. 1: 1078, 1958. 18. Quehl, E.: J. Obst. & Gynaec. Brit. Emp. 57: 253, 1950.
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