Carcinoma of the fundus occurring in double uterus

CARCINOMA

OF THE FUNDUS Report

ORCENETH

OCCURRINf2

IN DOUBLE

UTElBUS

of Three Cases

A. FLY, JR., M.D., AND JOSEPH HYDE PRATT, M.D., ROCHESTER, MINN. (Born

the

Section

of

Surgery,

iKayo

Clinic

and

Yayo

Foondation*)

malformations of CONGENITAL failure of fusion or resorption

the female genitals occur as a result of the Miillerian duct system during early months of fetal life. These anomalies are most often observed in form of duplication, in some degree, of the uterus and cervix or vagina. coexistence of this type of abnormality with carcinoma of the body of uterus has been reported infrequently. TABLE

1.

REPORTED

CASES IN WITH

WHICH CARCINOMA OF THE UTERINE CONGENITAL UTERINE ABKORMALITIES

FuxDus

WAS

of the the Tht the

ASSWIATEII

-NO. *

REPORTED

YEAR REPORTED

BY*

&ASS OF ABNORMALITY

Hofmeier

1902

Uterus

Mintrop

1912

Uterus

hicornis

Unterberger

1913

Uterus

duplex

Uterus

bicornis

1923

Uterus

bicornis

1924

Uterus

bicornis

Illandes

1925

Uterus

duplex

Rrandes

1925

IJterus

bicornis

ron

1926

Uterus bicornis septus

Heck I’eterson Norris

9

and

Vogt

FranquE

TYPE OF MALICiNANCY

I

duplex

Adenocarcinoma Adenocarcinoma unicollis

B Adenoearcinoma

unicollis

Malignant

adenoma

Bdenocarcinoma Adenocarcinoma duplex

8quamous-cell carcinoma

sub

Adenocarcinoma

10

l’hiers~

1934

Uterus

bicornis

Adenocarcinoma

11

Mottas

1934

Titerus

bicornis

.\denocareinoma.

12

Danesir

1935

Uterus

didelphys

Chorionepithelioma

13

Case records of Massachusetts General Hospitals

1937

Uterus

wptus

Adenocarcinoma

14

Shelley6

1938

Uterus

biseptus

Adenocarcinoma

15

Corbetr

1949

Uterus

bicornis

Adenocarcinoma

8ieglers

1950

Uterus

didelphys

Adenocarcinoma

Uterus

duplex

Atlenocarcinoma ---

16

*The

versity

1953

Zippisg

li

flrst

nine

cases

*The Mayo Foundation, of Minnesota.

are

taken

Rochester,

from

van

.-

FranquB.'

Minn.,

is & part

669

of

the

Graduate

School

OC the

l’ni-

670

FLY

AND

Am. J. Obst. & Gynec.

PRATT

September, 1956

Von FranquB,l in reviewing the literature from 1777 to 1930, found reports of 9 cases in which malignant disease of the fundus occurred in a malformed uterus. In the ensuing twenty-four years, an additional 8 cases have been recorded.2-Q A complete list of these 17 cases is presented in Table 1. The following reports of 3 cases bring the total number reported to 20.

Report of Cases CASE 1.-A 49syear-old full-blooded Indian woman presented herself at the Mayo Clinic in 1949 complaining chiefly of a brownish-yellow vaginal discharge of six months’ duration. This had been treated elsewhere by the injection of estrogen compounds. The menses had been normal and regular prior to the onset of the condition at hand. This patient had been seen previously examinations. At the time of her first visit of the axillary glands had been made.

at in

the clinic on several occasions 1919, a surgical diagnosis of

TWO

surgical procedures had been performed elsewhere: bilateral in 1925, and cholecysteetomy for stones in 1948. Eight admission in 1949 she had been found to be diabetic, and the diabetes with difficulty by diet and the use of insulin.

salpingectomy and months prior to her was being controlled

appendectomy

She had

child

had been pregnant survived infancy,

three however.

times,

with

normal

delivery

in

for general tuberculosis

each

case.

Only

one

This patient was obese, weighing 200 pounds, but she apparently was in good health. The systolic blood pressure was 120 and diast.olic 80, in millimeters of mercury. The uterus was three times normal size and was freely movable. Fibroid tumors of the uterus had been reported in an examination in 1939. The adnexal areas were normal. The cervix was eroded, and a brownish-yellow discharge was seen. Otherwise, results of examination were negative. Glycosuria of Grade 4 was recorded. The value for fasting mg. per 100 C.C. of blood. The content of hemoglobin was 11.3 Gm. and the results of serologic tests were negative. Roentgenograms interpreted as showing nothing abnormal. A clinical diagnosis of fibromyoma of the observations, and total abdominal hysterectomy

uterus was was advised

made and

blood sugar was 327 per 100 C.C. of blood, of the thorax were

on the accepted.

Operation was performed. The uterus was found to be adherent abdominal wall, apparently as a result of a previous suspension. right part of the abdomen was unsatisfactory because of adhesions. tissues, the intestinal tract, and the liver were normal. The uterus Both ovaries contained cysts. The tubes had been removed previously. hysterectomy was performed without difficulty.

basis

of

the

pelvic

against the anterior Exploration of the The retroperitoneal was broad and soft. Total abdominal

Pathologic examination of a specimen of the tissues removed disclosed a polypoid, cavity of a uterus septus. Grade 4 adenocarcinoma, 8 by 5 by 2.5 cm., in the left The malignant process had penetrated the uterine wall to a depth of 5 mm. A single fibromyoma, 1 cm. in diameter, was present in the uterine wall. Examination of the cervix showed chronic cervicitis and marked squamous-cell metaplasia. The right ovary was cystic; a 2 cm. cyst of the corpus luteum was found on the left. The

postoperative course was uneventful, and the on the eleventh postoperative day. Roentgen irradiation was administered because of partial penetration of the uterine wall by the lesion.

patient

was

discharged

from

the

hospital the

This patient was last observed in July, 1952, time she was found to have metastatic processes portedly treated elsewhere by roentgen irradiation.

three in

the

high

years after the lungs.

grade

of

the

the operation, These lesions

lesion,

and

at which were re-

Volume72 Nunheri

CARCINOMA

OF

FUNDUS

IN

DOUBLE

UTERUS

671

CASE2.-A white woman, 36 years old, presented herself at the clinic in January, 194% for evaluation of a recently irradiated, Grade 1 papillary adenocarcinoma of the uterine fundus and severe factitial proctitis. Minimal vaginal spotting had developed during the first trimester of a pregnancy in Postpartum bleeding subsided 1945, and had subsided after the injection of hormones. spontaneously three weeks after a normal delivery in July, 1946, but recurred for a few days three weeks later. Menses were regular and normal until July, 1947, when vaginal spotting again recurred. Dilatation and curettage were performed, disclosing a Grade 1 papillary adenocarcinoma. The patient received intensive roentgen therapy and intrauterine radium irradiation, after which symptoms developed from irradiation proctitis. When this patient was examined in January, 1948, her weight had decreased from 145 to 116 pounds. The systolic blood pressure was 120 and diastolic, 76. The skin of the abdominal wall was thickened, indurated, inelastic, and deeply tanned as a result of roentgen irradiation. The vaginal walls were smooth and atrophic. There was a firm, white, elevated area on the posterior lip of the cervix which was diagnosed by biopsy as being an effect of irradiation. There was nothing to suggest recurrence of activity of the malignant process. Proctoscopic examination showed an irradiation slough extending from 8 to 16 em. above the dentate margin. The lumen in this area was cont,racted to 1 cm. The value for hemoglobin was 11.4 Gm. per 100 C.C. of blood, and the results of urinalysis were normal, as were those of serologic tests. Roentgenograms of the thorax disclosed nothing abnormal. A clinical diagnosis of postirradiation carcinoma of t,he uterine fundus and faetit,ial proctitis with rectal stenosis was made. Because of the marked reaction of the tissues to irradiation, it was felt wisest to defer surgical correction, and a medical regime was outlined. The condition of the patient was followed at frequent intervals. In February, 1948, a rectovaginal fistula developed. Vaginal and rectal bleeding occurred on four occasions between March 29 and April 22, 1948, and during the last episode 2,000 cc. of blood for replacement was required. Transverse loop colostomy was performed in May, 1948. During the ensuing three years there was gradual improvement in the general health of the patient, and in the condition of the tissues of the abdominal wall and pelvis. In May, 1951, the situation had become sufficiently stabilized for surgical correction to be advised for the rectovaginal fistula and the rectal stenosis. Operation was accepted. At laparotomy on June 2, 1951, the ileum, peritoneum, and sigmoid were found to he thickened. A rectovaginal fistula 1 cm. in diameter was situated just below the cervix. The uterus was atrophic and mobile. Total abdominal hysterectomy, low anterior rcbsection of the stenosed rectum, and resection of the fistnla were performed. Continuit,>of the colon was restored three months later. Pathologic. examination showed the uterus to be markedly atrophic, bicornate, aud containing no residual carcinoma. Chronic cervicitis and bilateral chronic salpingitin and oophoritis were noted. CASE3.-A white woman, 60 years old, presented herself at the clinic in April, 193Q, because of persistent postmenopausal bleeding of a year’s duration. There had been no pregnancies during twenty-one years of marriage. Menopause had occurred at the age of 54. Dilatation and curettage had been carried out elsewhere in November, 1935, which resulted in a diagnosis of chronic cerviritis and inflammatory polyps. The injection of hormones produced no benefit, and the bleeding continued to the time of the patient’s admission. Cholecystectomy for gallstones had been performed in lQ35, the surgeon reporting that there was no palpable pelvic abnormality. Physical examination at the time of the admission in 1939 revealed no abnormalities other than a pelvic mass the size of a grapefruit. The vagina was contracted about the cervix, which was difficult to visualize. Examination with the patient anesthetized rB-

672

FLY

AND

PRATT

Am. J. Obst. & Gynec. September, 1956

portedly revealed a normal pelvis. The cervix was buried because of the overlapping of the vaginal vault. Dilatation and curettage showed atrophic endometrium, with no evidence of malignancy. It was felt that the bleeding had been on the basis of senile vaginitis, and the use of estrone suppositories was advised. Re-examination was to be performed within six months, if the bleeding continued. The patient returned to the clinic in March, 1940, with a history of continued spotting. Hormone therapy had been continued at home, without benefit. During the two weeks prior to this admission, the patient had noted a tender mass in the lower part of the pelvis. The remainder of the history was not significant. The patient was apparently healthy, and weighed 147 pounds, without evidence of recent loss of weight. At vaginal examination, blood was seen on the vulva, but none was present in the vagina. There was a large, tender mass in the right part of the pelvic cavity. The value for hemoglobin was 11.6 Gm. per 100 C.C. of blood. Erythrocytes numbered 4.53 million per cubic millimeter of blood. Results of urinalysis, serologic tests, and roentgenologic examination of the thorax were recorded as negative. A clinical diagnosis of an ovarian malignant process with a secondary inflammatory process was entertained and exploration was advised and accepted. On March 16, 1940, preliminary dilatation and curettage were performed. A small opening was found in the vagina about 1 inch proximal to the urethral orifice. This opening led posteriorly for about 5 or 6 inches; when it was enlarged, it was found to be entirely lined with vaginal mucous membrane, representing complete reduplication of the vagina. A complete cervix was present in this cavity, separate from that in the normal vaginal cavity. Curettage through the second cervix produced tissue which was diagnosed as adenocarcinoma, Grade 2. Laparotomy was immediately performed. When the abdomen was opened, a ruptured, gangrenous, twisted cystadenocarcinoma of the right ovary was found which was collapsed, but which had been approximately the size of a small grapefruit. There W&S complete duplication of the uterus and cervix, the right one being atrophic and small, whereas the left was definitely enlarged and about twice the size of the right. There were only the usual tubes and ovaries. Total abdominal hysterectomy and bilateral salpingooophorectomy were performed. On further exploration, a nodule was found in the distal segment of the ileum. This nodule was removed; the pathologist’s report identified it as a carcinoid tumor. Pathologic examination of the removed specimen disclosed a Grade 2 adenoearcinoma which involved the dilated left horn of a completely double uterus, invading the muscle The right ovary contained a hemorrhagic, necrotic, multilocular to a depth of 5 mm. Grade 2 papillary intracystic cystadenocarcinoma approximately 15 cm. in diameter. The patient received intensive roentgenologic and radium therapy after this operation, and was reported as being well, with no evidence of recurrences, in 1951.

Comment During the five-year interval from 1950 to 1955, more than 4,500 hysterectomies were performed at the Mayo Clinic for causes other than malignancy. In some 4,000 of these cases, a pathologic diagnosis of fibromyomatosis uteri had been made, or the hysterectomy had been performed because of prolapse. In reviewing the records of this group of patients, we found 5 in whom some degree of reduplication of the uterus had been noted, an incidence of 1 in 800. This appears to confirm the opinion of Hoffman,l” Steinberg,ll and others that the incidence of 1 in 1,500, noted by SmithI among pregnant patients, is low, since many patients with these anomalies apparently have sterility problems. In the ten-year period, 1945 to 1955, hysterectomy was performed at the Mayo Clinic for 691 patients who had adenocarcinoma of the uterine fundus. A double uterus was present in 2 of these specimens, an incidence of 1 in 345.

\‘olume \m”ber

72 1

CARCINOMA

OF

FUNDUS

IN

DOUBLE

TJTERUS

673

During this same period, hysterectomy had been performed for 6X: patients who had carcinoma of the cervix, including carcinoma in situ. 1~ one of these, a congenital abnormality also was found. This case has been rf’ported in detail elsewhere.13 It may appear, on the basis of these statistics, that a malignant process is more likely to occur in a congenitally malformed uterus than in one which is normal in development, but because of the small number of cases included in the series, no such conclusion should be reached. The occurrence of a malignant process in a double uterus is probably coincidental. It is generally accepted that the incidence of sterility is greater among such patients as the ones in our 3 cases. Strassmann14 noted an incidence 01 t,errn deliveries of only 25 per cent among those becoming pregnant. It is of interest that 2 of our 3 patients had had normal pregnancies with a normal term delivery in each instance. Case 3 is of special significance, because of the simultaneous occurrence 01 three separate malignant processes, the difficulties in diagnosis which arise in uterine and vaginal duplication, and the extremely satisfactory survival period after therapy. The patient had had dilatation and curettage performed three times over a period of two years for the same symptoms, and the diagnosis of malignant involvement was made only on the last attempt, when the srconcl uterus was identified and was found to be the source of the bleeding.

Summary

and Conclusions

Three cases in which adenocarcinoma occurred in a double uterus have been presented. The observed incidence of congenital duplication of the uterus at the Mayo Clinic in hysterectomies carried out for malignant involvement is 1 in 300, and in hysterectomies for benign conditions is 1 in 800. The small number of patients with congenital duplication encountered prevents conclusions as to the real effect of the anomaly on the future development of uterine malignancy.

References 1. von 2. 3. 4. 5. 6.

7. 8. 9. IO. 11. 12. 13. 14.

Franque, Otto: Misbildung und Uteruscarcinom. In Stoeckel, W.: Handbneh der Gynlkologie, ed. 3, Miinchen, 1930, J. F. Bergmann, vol. 6, pp. 191-192. Thiers, M. E.: Bull. Sot. d’obst. et de gym%. 23: 53.5, 1934. Motta! G.: Clin. ostet. 36: 215, 1934. Danesl, Hugo: Semana med. 52: 368, 1935. Case Records of the Massachusetts General Hospital: Case 23382, New England ,T. Med. 217: 532, 1937. Shelley, H. J.: J. A. M. A. 110: 1913, 1938. Corbet, R. M.: Irish J. M. SC., series 6, p, 231, 1949. Siegler, S. L.: AM. J. OBST. & GYNEC. 59: 162,19X). Zippis, Nissen: Acta obst. et gynec. scandinav. 32: 345, 1953. Hoffman, E. S.: AM. J. OBST. & GYNEC. 51: 692,1946. Steinberg, Werner: AM. J. OBST. & GYNEC. 63: 827, 1952. Smith, F. R. : AM. J. OBST. & GYNEC. 22: 714, 1931. Fly, 0. A., Jr., Pratt, J. H., and Decker, D. G.: Proc. Staff Meet., Mayo Clin. 30: 391, 1955. Strassmann, E. 0.: AM. J. OBST. & GYNEC. 64: 25, 1952.