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Office aspiration curettage of the endometrium
Office aspiration curettage of the endometrium EARL
W.
HATHCOCK,
GEORGE SAM
A. M.
JR.,‘M.D.+
WILLIAMS,
M.D.
ENGELHARDT
ALDA
L.
Atlanta,
Georgia
MURPHY,
III,
M.D.
R.N.
A review of 1,784 aspiration curettages of the endometrium in the ofice is presented. Thirty-eight adenocarcinomas of the endometrium were found and either adenomatous hyperplasia or atypical adenomatous hyperplasia was discovered in 105 cases. A malignant or premalignant condition was found in 9.2 per cent and diagnostic accuracy, as judged by long-term follow-up, was very good. Insuficient material for diagnosis was only rarely encountered and did not present diagnostic difficulty. This procedure is highly recommended for ofice evaluation of the endometrium.
I N 1924 Kelley, in an address before a meeting of the Philadelphia Obstetrical Society, advocated “curettage without anesthesia on the office table” as a means of evaluation and treatment of certain endometrial prob1ems.l Novak2 and Randall3 in 1935 described instruments to facilitate the procedure and Israel and Mazer4 reported a series of 305 procedures in 1938. In spite of their discovery of five adenocarcinomas, the discussants of their paper were of the opinion that this was not an acceptable procedure. In 1947 Williams and Stewart5 reported their satisfactory experience with aspiration endometrial curettage in a cancer clinic and since then there have been numerous reports relating the results of office endometrial curettage and encouraging its use in the diagnosis and management of uterine disorders.+17 Monumental among these is the series of 17,666 biopsies over 18 years reported by Hofmeister and his colleagues.ls-zO
The purpose of this presentation is to report our experience with office endometrial aspiration curettage over an 11 year period and to discuss in detail our management of patients with adenomatous hyperplasia. Method Patients were selected on the basis of their symptoms, past history, or pelvic findings. Indications included menstrual disorders, such as perimenopausal bleeding, postmenopausal bleeding, menorrhagia, menometrorrhagia, pre- or postcoital bleeding, oligomenorrhea, and amenorrhea. It also was used in the evaluation of infertility, abnormal Pap smears, pelvic tumors, as a follow-up technique on patients who have previously demonstrated significant endometrial pathology, and recently as a preoperative screen for certain patients scheduled for pelvic surgery. Occasionally, it was used to complete an incomplete abortion. Aspiration curettage may be unsatisfactory when there is stenosis of the cervical OS or canal, marked distortion of the endometrial cavity (such as with leiomyomata) , when there is heavy uterine bleeding, or in a hyperesthetic patient. Frequently, polyps can be detected but cannot be removed with the aspiration curette. We feel strongly that a careful explana-
Presented as o$icial guest at the Thirty-sixth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Miami Beach, Florida, January 27-30, 1974. Reprint requests: Earl W. Hathcock, Jr., M.D., 710 Peachtree St., N.E., Atlanta, Georgia 30308. +Deceased.
205
206
Hathcock
Srptember 15. 1974 -Zm. J Obstet. Gynecol.
et al.
Table I. Age distribution Age (Yr.)
No. of patients
Percentage of total
45 173 160 146 194 304 337 239 91 43 20 33 1,784
2.5 9.7 9.0 8.2 10.9 17.0 18.9 13.3 5.1 2.4 1.1 1.8
15-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 61-65 66-70 70+ Total
Table II. Number
of patients
It is not unusual to remove several grams of tissue with this technique. According to the pathologist, usually as much tissue is obtained with this procedure as in a hospital curettage. The largest aspiration curettage specimen from our office weighed 27 Gm. Analgesia is provided by trichloroethylene,” administered by a Cyprane inhaler.+ Some of the patients receive propoxyphene, 65 mg.,$ and atropine sulfate, 0.6 mg.,§ prior to the procedure. Results
of biopsies
for patient
No.
of biopsies
) No.
of patients
1 Percentage
1,395 120 28 11 3 1 1,558
Total
89.6 7.7 1.7 0.7 0.2 0.1
tion of the procedure helps ensure the cooperation of the patient and is more likely to result in an acceptable procedure. After a careful bimanual examination, the cervix is exposed, cleansed with benzalkomium chloride [1:750],* and stabilized with a tenaculum. If cervical biopsies are indicated, multiple punches are taken as well as an endocervical scrape, which is submitted separately. The uterus is then sounded to confirm the depth and direction of the endometrial cavity. Following this, a Novak or Randall curette, which is attached to a standard 10 C.C. glass syringe, is gently inserted into the endometrial cavity. Almost never is cervical dilatation necessary. With the use of gentle motions, an attempt is made to aspirate the entire endometrial lining and to remove as much endometrium as possible. The aspirated material is immediately placed in 10 per cent formalin and then submitted to the pathologist. *Zephiran,
Winthrop
Laboratories,
New
York,
New
York.
During the almost 11 year period from January, 1963, through November, 1973, aspiration curettage was performed 1,784 times on 1,395 patients. This represents 298 months of physician experience. The ages of the patients are shown in Table I ; the youngest was 15 and the oldest 74. The number of biopsies per patient is recorded in Table II. Menstrual disorders served as the primary I indication for the number of procedures, accounting for 1,301 (73 per cent), Arbitrarily, bleeding in patients over age 40 and not preceded by 12 months of amenorrhea was classified as “perimenopausal.” The pathological findings are shown in Table III. The high percentage of secretory endometrium is an unexpIained finding in this group as well as throughout our study. Of interest is the fact that 61 (9 per cent) of these patients demonstrated a malignant or premalignant lesion. Evaluation of postmenopausal bleeding in 268 patients (15 per cent of the total) gave the results also listed in Table III. Nine per cent of these were found to have carcinoma of the endometrium and 12 per cent either adenomatous hyperplasia or atypical adenomatous hyperplasia. The results in patients with menorrhagia/ menometrorrhagia or oligomenorrhea/amen*Trilene, Ayerst Laboratories, Inc., New York, New York. tMfg. by Cyprane, Ltd., K&&Icy, England. $Darvon, Eli Lilly & Co., Inc., Indianapolis, Indiana. SAtropine sulfate, Eli Lilly & Co., Inc., Indianapolis, Indiana.
Volume Number
120
Office aspiration
2
Table III.
Pathology
reports
report
No.
bleeding
of procedures
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia
11 46 6 1 1 24 5
219 6
31 1
3
37 24 19
14 9 7 -
6 91 20
2 34 7
14 24 28
z 10 1 1
2 3 Gi
15
by indication
No. of procedures
Menometrorrhagia Percentage
No. of procedures
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps
54 5 -
Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
-
-
-
is
-3
-iz
Total
1 Percentage
-
35
Menorrhagia report
bleeding
of procedures
1
ET7
Pathology
No.
-
Total
reports
Postmenopausal
Percentage
71 290 38 4 4 150 31
Atypical adenomatousendometrium hyperplasia Adenocarcinoma Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
Table IV. Pathology
207
by indication Perimenopausal
Pathology
curettage
87 8 -
16 138 26 5 1
5
29 3 1
3
orrhea are given in Table IV. Again, we are unable to explain the high percentage of secretory endometrium. Pre- or postcoital bleeding (Table V) was the primary indication in only 31 patients but one of these was found to have carcinoma of the endometrium. The findings in the evaluation of 187 patients with infertility also are shown. The report of 89 per cent secretory endometrium is unusual but again unexplained. Table VI lists the reports in 45 patients in whom the procedure was used for evaluation of pelvic tumors (such as leiomyomas,
1 3
Oligoamenorrhea Percentage
No. of procedures
Percentage
7 62 12
12 43 9
13 48 10
2
I -
I
1 13 1 1 -1 1
20 2 1
G
3 -
-i -
ii
90
T
2 1
adnexal masses, etc.), and in 87 patients who underwent aspiration curettage as a preoperative screening procedure. Also shown are 34 procedures performed for follow-up assessment of patients who had previously been shown to have abnormal endometrial findings. Evaluation of an abnormal Pap smear was the primary indication for 103 aspiration curettages. Schiller’s staining of the upper vaginal vault and cervix, multiple punch biopsies of the cervix, and an endocervical scrape also were performed routinely on these patients. Twenty-two per cent were
208
Hathcock
et
al.
Table V. Pathology
reports
by indication -
Pathology
report
Pre-
or postcoital .No. of procedures
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
/ Percentage
‘) 2; 1
reports
report
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
3 6
-
1 1 -
2
s -
Percentage 2 89 4 1 -
8
4
-3 3
-
1
2
1
-
-
187
ro
by indication Pelvic
Pathology
4 166 7 1
-
G
Table VI. Pathology
Infertility No. of procedures
6 68 3 -
1 ‘)
Total
Total
bleeding
No. of procedures
tumor
Screen
Percentagr
7 18 2 4 9 2 1 6 1
4 40 4 -
-ii
-i
found to have carcinoma of the cervix, predominantly carcinoma in situ. Three per cent were found to have carcinoma of the endometrium and in two per cent adenomatous hyperplasia of the endometrium was reported. These results are shown in Table VII. Aspiration curettage was used therapeutically in 10 cases of known or suspected incomplete abortion (Table VII). As previously noted, products of conception were reported in four cases in which the primary indication for the procedure was perimeno-
y
2P 4 2 13
2
No. of proccdurss
Follow-up Percentage
8 37 .>
9 43 2
18 2 1 11 8
21 2 1
ii
-Y
No. of procedures 4 10 -
12 29 -
-
-ii 21 6 3 3 1” -
e
12
34
?
: 2 1 1 4
13
9
Percentage
pausal bleeding and in five cases in which the primary indication was menometrorrhagia. Additionally, one patient in whom the indication was the evaluation of an abnormal Pap smear was found to be pregnant. This patient, however, had returned to the office, as instructed, for this procedure on the first day of what appeared to be her normal menses. In all cases where the pathology report revealed products of conception, there had been recent vaginal bleeding. To our knowledge, no pregnancy was encountered which had not already ex-
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Office aspiration
120 2
Table VII.
Pathology
reports
report
Pap
*~;d.4es
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
also
produced
an
3
hibited some evidence of disturbance. We feel that the routine performance of this procedure at the time of the onset of menses has helped prevent the unexpected disruption of pregnancy and we recommend this policy in spite of the disadvantage of requiring an additional office visit and an occasional slight delay in diagnosis. Miscellaneous indications accounted for 19 procedures. TabIe VIII Iists by pathologica diagnoses the cummulative total of all of the procedures performed. Carcinoma of the cervix was found in 1.3 per cent, carcinoma of the endometrium in 2.1 per cent, and adenomatous hyperplasia of the endometrium in 5.8 per cent. Altogether, 9.2 per cent demonstrated a malignant or premalignant lesion. Most authorities recognize adenomatous hyperplasia and in particular atypical adenomatous hyperplasia of the endometrium as a potentially premalignant lesion, aithough some, notably led by Kistner and associates,21 have shown it to be reversible in some cases with the use of progestins. Cullen, in his book published in 1900, described the coexistence of atypical endometrium and endometrial adenocarcinoma; GusbergZ3 in 1947 named and defined adenomatous hyperplasia of the endometrium and in a later report Gusberg and Kaplan2i
-
5 63 11 5 -
2 1
(2;) -
which
r;;;re -
10 -
1 9
90 -
I
”
‘”
1
z
-
-
-
-
;;;
T
m
4 ii
diagnosis
1 ?$I;;;:
1 12
3
(239)* 4
endometrial
1 pi;I;ri;;ge
15 51 3 1 1 11 2
rl procedures
smear
1 Perge
15 52 3 1 1 11 2
Total ‘These
209
by indication Abnormal
Pathology
curettage
1
is listed
Table VIII. pathology
Number report
of procedures
No. Pnthology
report
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenamatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material Total *These procedures which is listed.
of
procedures 172 866 112 1 19 18 350 65 40
by
Percentage 9.6 48.3 6.3 0.1 1.1 1.0 19.6 3.6 2.2 2. 1
38
(@
(Y3, 0.2 1.6
28 1,784
also produced
an endometrial
diagnosis
reviewed the experience with this condition. In this series of patients with adenomatous hyperlasia, 12 per cent were found on adequate follow-up to have developed adenocarcinoma of the endometrium. They concluded that their data lend support to the concept of adenomatous hyperplasia as Stage 0 cancer of the endometrium and cited numerous references to the literature confirming this view. They projected a 30 per
210
Hathcock
Srptcrnber Am. J. Obstet.
et al.
Table IX. Indications and age distribution of patients with premalignant or malignant reports
Ade?lO??l&
tow
Atypical Ade-
Adenocarcinoma
noma-
tous
Of
hyperblasia
endometrium
31
21
9
20
14
24
hype+ blasia Indication:
P&menopausal bleeding Postmenopausal bleeding Menometrorrhagia Pre- or postcoital bleeding Oligoamenorrhea Abnormal Pap smear Follow-up Screen Pelvic tumor Miscellaneous Total Age: 26-30 31-35 36-40 40-45 46-50 51-55 56-60 61-65 66-70 70+
3
2 2 2 2 2
1 ss 1 1 4 5 23 20 7 3
ii-
1
-
-
1
-
1 1 1 1 1
40 1 1 1 5 12 12 z
1 3 40
3 1 38
1
: 12 9 5 2 1 38
cent cumulative risk of carcinoma of the corpus 10 years after a diagnosis of adenomatous hyperplasia. Our series includes 65 procedures in which the diagnosis was adenomatous hyperplasia, an additional 40 in which the diagnosis was atypical adenomatous hyperplasia, and 38 who were found to have carcinoma of the endometrium. The ages of these patients and the indications are shown in Table IX. The patients with a diagnosis of adenomatous hyperplasia were further evaluated by repeat aspiration curettage on 13 occasions, curettage on six occasions, and 46 have subsequently undergone hysterectomy. Only six were found to have more severe disease than originally reported. In three, atypical ade-
15, 19i4 Gynecol.
nomatous hyperplasia was found on the subsequent pathology report and an additional three cases were reported as adenocarcinoma of the endometrium. One of the three adenocarcmomas? however, was diagnosed by repeat aspiration curettage prior to hysterectomy. In four of the six cases there was a seven- to nine-month patient delay before the subsequent procedure. Twelve patients have not as yet undergone a follow-up endometrial study. Atypical adenomatous hyperplasia was found 40 times. Four have undergone an additional aspiration curettage and 33 a hysterectomy. Four of these were found to have adenocarcinoma of the endometrium, all at hysterectomy. Carcinoma of the endometrium has been diagnosed in 38 patients in our office by aspiration curettage. Years of follow-up of these patients are listed in Table X. Thirtysix patients are living and well. Two patients are deceased, one of cancer 29 months after diagnosis and one of an acute myocardial infarction one week after aspiration curettage and prior to definitive therapy. Ten additional patients were treated for adenocarcinoma of the endometrium who were originally diagnosed either by curettage or by another physician and referred to us for therapy. There has been one incidental finding of carcinoma of the endometrium. This patient, age 42, underwent vaginal hysterectomy and anterior and posterior colporrhaphy for pelvic relaxation. Her menstrual history was entirely normal and she has remained well for eight years since the operation. A review of the records of the 1,415 patients who did not have adenomatous hyperplasia, atypical adenomatous hyperplasia, or carcinoma of the endometrium on the original aspiration curettage revealed subsequent procedures of 366 aspiration curettages, 151 curettages, and 376 hysterectomies. Seventeen patients in whom the original diagnosis bad been simple hyperplasia had recurrent bleeding problems, usually one to two years later, and were found then to have edenomatous hyperplasia. One patient underwent
Volume Number
120 2
Office
curettage for recurrent postmenopausal bleeding three years after aspiration curettage and was found to have adenocarcinoma of the endometrium. One additional patient had endometrial polyps by aspiration curettage but curettage one month later revealed adenocarcinoma. A report of insufficient material for diagnosis was obtained 28 times. Nine procedures were done as a preoperative screen and no significant endometrial pathology was found subsequently. Two patients were being evaluated for postcoital spotting and this has not recurred on follow-up. Four procedures were done to evaluate abnormal Pap smears which were cervical in origin. Evaluation of the menstrual disorders accounted for nine curettages and follow-up of previous endometrial abnormalities accounted for four. These 28 patients have been followed for an average of 4.2 years; eight have subsequently undergone either curettage or hysterectomy. In none of the 28 has any serious endometrial problem been detected. Comment We believe office aspiration curettage is a satisfactory means of evaluating the endometrium for the indications listed. Its diagnostic accuracy is attested to by the fact that in only 29 instances was a more serious lesion subsequently found. Nineteen of these were diagnoses by repeat aspiration, usually with recurrent symptoms one to two years later. One was found at curettage three years later and in nine cases the lesion was found at hysterectomy. We are convinced that in no instance was the therapeutic outcome compromised. One point, however, must be made. If the operator does not feel that a satisfactory curettage has been carried out, or if symptoms persist or recur, then further evaluation is essential. In our series, obtain-
REFERENCES
1. Kelley, 9: 78, 2. Novak,
H. A.: AM. J. OBSTET. 1925. E.: J. A. M. A. 104: 1497,
curettage
Table X. Follow-up
of living patients of the endometrium
carcinoma Years
of follow-up <
1
No.
211
with
of patients
1 1 2 3 4 5 6 7 8 9 10
5 3 5 3 7 2 6 1 2 3 1
ing insufficient material for diagnosis has OCcurred in less than two per cent and in no instance was this found to affect the outcome. One patient, age 47, died of acute myocardial infarction approximately two hours after aspiration curettage. Autopsy revealed advanced coronary atherosclerosis with evidence of recent arterial occlusion as well as extensive myocardial fibrosis, thought representative of progressive subtle myomost likely occurring cardial infarctions, over a long period of time. With the exception of this patient, there have been no complications from this procedure. No perforations have occurred and no infections or other problems have become manifest. Office aspiration curettage is advantageous in that it shortens the delay to final diagnosis, is only transitorily disabling, does not require hospital facilities or a general anesthetic, and is much less costly than the conventional curettage. Additionally, it is more convenient for the patient and for the physician with regard to the amount of time involved. The procedure is painful but with proper patient presentation and mild analgesia it has been well accepted. We recommend this procedure for office evaluation of the endometrium as safe, accurate and advantageous.
3. GYNECOL.
4. 1935.
aspiration
Randall, L. M.: Proc. Staff Meet. 10: 143, 1935. Israel, S. L., and Mazer, C.: AM. GYNECOL. 36: 445, 1938.
Mayo
Clin.
J. OBSTET.
212
Hathcock
et al.
Srptt,mber Am. J. Obster
15, I974 Cynecol.
5. Williams, G. A., and Stewart, C. B.: .4br. J. OBSTET. GYNECOL. 54: 804, 1947. 6. Palmer, J. P., Kneer, W. J., and Eccleston, J. H.: AM. J. ORSTET. G~NECOL. 60: 671. 1950. 7. Wall. J, A., Fletcher, G. A., and MacDonald, E. J.: Am. J. Roentgenol. 71: 95, 1954. 8. Hecht, E. L.: AM. J. OBSTET. GYNECOL. 71: 819, 1956. 9. Burge, E. S., and Morley, B.: AM. J, OBSTET. GYNECOL. 80: 325, 1960. 10. McGuire, T. H.: Obstet. Gynecol. 19: 105. 1962. 11. Slaughter, C. R., and Schewe, E. J.: AM. J, OBSTET. GYNECOL. 83: 1302, 1962. 12. Nugent. F. B.: Obstet. Gynecol. 22: 168, 1963. 13. Parkhurst, G. F., Jameson, W. J., and Oran, J. F.: Surg. Gynecol. Obstet. 116: 631, 1963. 14. Wildhack, R. H., and Graham, J. B.: Obstet. Gynecol. 23: 446, 1964. 15. Abramson, D., and Driscoll, S. G.: Obstet. Gynecol. 27: 381, 1966.
16. Wall, J. A.. Collins. V. P., Kaplan, .4. I... and Hudgins. P. T.: AM. J. OBSTET. GYNECOL. 97: 787, 1967. 17. Kahler. V. L., Creasy, R. K., and Morris, J. A.: Obstet. Gynecol. 34: 91, 1969. 18. Hofmeister, F. J., and Barbo, D. M.: Obstet. Gynecol. 23: 386, 1964. 19. Hofmeister, F. J., Vondrak, B. F., and Barbo. D. M. : AM. J. OBSTET. GYNECOL. 95: 91. 1966. 20. Hofmeister, F. J.: J, Reprod. Med. 4: 33, 1970. 21. Kistner, R. W.? Gore, H., and Hertig, A. T. : AM. J. OBSTET. GYNECOL. 95: 1011, 1966. 22. Cullen, T. S.: Carcinoma of the Uterus, New York, 1900, D. Appleton & Company. 23. Gusberg, S. B.: AM. J. OBSTET. GYNECOL. 54: 905, 1947. 24. Gusberg, S. B., and Kaplan, A. L.: AM. J. OBSTET. GYNECOL. 87: 662, 1963.
Discussion T. VERNON FINCH, Sarasota, Florida. Dr. Hathcock’s report represents a considerable experience with a diagnostic procedure which is easily done in the office, with early available pathologic diagnosis, and with a considerable saving in hospital cost. For some 20 years I have employed aspiration endometrial biopsy for indications similar to the authors, and, more recently, I have used it in another category of so called “high-risk” individuals, who are hypertensive and obese, have a family history of diabetes, and have any suggestion of abnormal bleeding, present or past. Th e preoperative screening of patients suspected of pelvic neoplasm such as myomas and adnexal masses is especially comforting when definitive laparotomy is scheduled without an antecedent curettage. This screening will prevent almost all of the concern that surfaces when the electively removed uterus is reported as malignant. Concerning technique, there are two points to be made. In contradistinction to the authors, who frequently employ inhalation analgesia, I have found a paracervical block very useful in the anxious patient and also in individuals with a small cervical OS. A Hank dilator can then usually be used to dilate the cervix sufficiently to pass a uterine sound. One may find some advantage in using a plastic disposable 10 C.C. syringe because the plunger has a Aare on the proximal end which will allow for the use of a small wedge of wood some two inches in length
which can be used to hold the plunger back, to produce and hold a vacuum so that the operator can hold the curette lightly and with a greater sense of touch while performing the biopsy. The evaluation of these 1,784 procedures in 1,558 patients has involved a problem of abnormal uterine bleeding in 71 per cent. Some 60 per cent of the procedures have been in individuals 41 years of age and older. Several surprising findings are: ( 1) the high percentage (48) of secretory endometria reported, (2) the low percentage (2 per cent) of adenocarcinoma, and (3) the 25 per cent with hyperplasia of the endometrium, benign and atypical. The question which first occurs to me is to inquire of the authors if they have some idea as to how many of these patients were receiving exogenous estrogens, or estrogen-progestin products, which may have influenced the histologic picture of the tissues under study. The premalignant implications of adenomatous hyperplasia were discussed. The matter of reversibility with progestins was mentioned. However, it is worth mentioning also that there is a reversibility of adenomatous hyperplasia relating to the influence of estrogen, be it the endogenous estrogen of the premenopausal or the exogenous estrogen in the postmenopausal female. This matter of the reversibility of adenomatous hyperplasia in the postmenopausal female rez:iving estrogen replacement therapy by the simple withdrawal of this stimulus has been described by Dr. Donald Woodruff in personal communications. It would appear, then, that the adenoma-
DR.
Volume Number
120 2
tous hyperplasia developing in the untreated postmenopausal patient has a more malignant potential than in the estrogen-treated individual. Among the 65 cases with a diagnosis of adenomatous hyperplasia six cases were found to have a more severe process. In four of these six a delay of seven to nine months occurred. Three cases of adenocarcinoma occurred among the six. Twelve patients apparently have not undergone a follow-up study. Among the 40 cases of atypical adenomatous hyperplasia 33 patients underwent hysterectomy, four of whom already had adenocarcinoma at
Office
aspiration
curettage
213
the time of the hysterectomy. No mention was made of a curettage in any of the other seven individuals with this premalignant lesion. It would appear to this discussant that it has been shown by the authors that a positive diagnosis obtained at aspiration endometrial biopsy is useful in the early and efficient planning of therapy, e.g., hysterectomy with or without prior irradiation therapy. However, an essentially negative biopsy in a patient with symptoms, although highly accurate and in general relieving of anxiety, should require further investigation by a thorough curettage.
W.
HATHCOCK,
GEORGE SAM
A. M.
JR.,‘M.D.+
WILLIAMS,
M.D.
ENGELHARDT
ALDA
L.
Atlanta,
Georgia
MURPHY,
III,
M.D.
R.N.
A review of 1,784 aspiration curettages of the endometrium in the ofice is presented. Thirty-eight adenocarcinomas of the endometrium were found and either adenomatous hyperplasia or atypical adenomatous hyperplasia was discovered in 105 cases. A malignant or premalignant condition was found in 9.2 per cent and diagnostic accuracy, as judged by long-term follow-up, was very good. Insuficient material for diagnosis was only rarely encountered and did not present diagnostic difficulty. This procedure is highly recommended for ofice evaluation of the endometrium.
I N 1924 Kelley, in an address before a meeting of the Philadelphia Obstetrical Society, advocated “curettage without anesthesia on the office table” as a means of evaluation and treatment of certain endometrial prob1ems.l Novak2 and Randall3 in 1935 described instruments to facilitate the procedure and Israel and Mazer4 reported a series of 305 procedures in 1938. In spite of their discovery of five adenocarcinomas, the discussants of their paper were of the opinion that this was not an acceptable procedure. In 1947 Williams and Stewart5 reported their satisfactory experience with aspiration endometrial curettage in a cancer clinic and since then there have been numerous reports relating the results of office endometrial curettage and encouraging its use in the diagnosis and management of uterine disorders.+17 Monumental among these is the series of 17,666 biopsies over 18 years reported by Hofmeister and his colleagues.ls-zO
The purpose of this presentation is to report our experience with office endometrial aspiration curettage over an 11 year period and to discuss in detail our management of patients with adenomatous hyperplasia. Method Patients were selected on the basis of their symptoms, past history, or pelvic findings. Indications included menstrual disorders, such as perimenopausal bleeding, postmenopausal bleeding, menorrhagia, menometrorrhagia, pre- or postcoital bleeding, oligomenorrhea, and amenorrhea. It also was used in the evaluation of infertility, abnormal Pap smears, pelvic tumors, as a follow-up technique on patients who have previously demonstrated significant endometrial pathology, and recently as a preoperative screen for certain patients scheduled for pelvic surgery. Occasionally, it was used to complete an incomplete abortion. Aspiration curettage may be unsatisfactory when there is stenosis of the cervical OS or canal, marked distortion of the endometrial cavity (such as with leiomyomata) , when there is heavy uterine bleeding, or in a hyperesthetic patient. Frequently, polyps can be detected but cannot be removed with the aspiration curette. We feel strongly that a careful explana-
Presented as o$icial guest at the Thirty-sixth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Miami Beach, Florida, January 27-30, 1974. Reprint requests: Earl W. Hathcock, Jr., M.D., 710 Peachtree St., N.E., Atlanta, Georgia 30308. +Deceased.
205
206
Hathcock
Srptember 15. 1974 -Zm. J Obstet. Gynecol.
et al.
Table I. Age distribution Age (Yr.)
No. of patients
Percentage of total
45 173 160 146 194 304 337 239 91 43 20 33 1,784
2.5 9.7 9.0 8.2 10.9 17.0 18.9 13.3 5.1 2.4 1.1 1.8
15-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 61-65 66-70 70+ Total
Table II. Number
of patients
It is not unusual to remove several grams of tissue with this technique. According to the pathologist, usually as much tissue is obtained with this procedure as in a hospital curettage. The largest aspiration curettage specimen from our office weighed 27 Gm. Analgesia is provided by trichloroethylene,” administered by a Cyprane inhaler.+ Some of the patients receive propoxyphene, 65 mg.,$ and atropine sulfate, 0.6 mg.,§ prior to the procedure. Results
of biopsies
for patient
No.
of biopsies
) No.
of patients
1 Percentage
1,395 120 28 11 3 1 1,558
Total
89.6 7.7 1.7 0.7 0.2 0.1
tion of the procedure helps ensure the cooperation of the patient and is more likely to result in an acceptable procedure. After a careful bimanual examination, the cervix is exposed, cleansed with benzalkomium chloride [1:750],* and stabilized with a tenaculum. If cervical biopsies are indicated, multiple punches are taken as well as an endocervical scrape, which is submitted separately. The uterus is then sounded to confirm the depth and direction of the endometrial cavity. Following this, a Novak or Randall curette, which is attached to a standard 10 C.C. glass syringe, is gently inserted into the endometrial cavity. Almost never is cervical dilatation necessary. With the use of gentle motions, an attempt is made to aspirate the entire endometrial lining and to remove as much endometrium as possible. The aspirated material is immediately placed in 10 per cent formalin and then submitted to the pathologist. *Zephiran,
Winthrop
Laboratories,
New
York,
New
York.
During the almost 11 year period from January, 1963, through November, 1973, aspiration curettage was performed 1,784 times on 1,395 patients. This represents 298 months of physician experience. The ages of the patients are shown in Table I ; the youngest was 15 and the oldest 74. The number of biopsies per patient is recorded in Table II. Menstrual disorders served as the primary I indication for the number of procedures, accounting for 1,301 (73 per cent), Arbitrarily, bleeding in patients over age 40 and not preceded by 12 months of amenorrhea was classified as “perimenopausal.” The pathological findings are shown in Table III. The high percentage of secretory endometrium is an unexpIained finding in this group as well as throughout our study. Of interest is the fact that 61 (9 per cent) of these patients demonstrated a malignant or premalignant lesion. Evaluation of postmenopausal bleeding in 268 patients (15 per cent of the total) gave the results also listed in Table III. Nine per cent of these were found to have carcinoma of the endometrium and 12 per cent either adenomatous hyperplasia or atypical adenomatous hyperplasia. The results in patients with menorrhagia/ menometrorrhagia or oligomenorrhea/amen*Trilene, Ayerst Laboratories, Inc., New York, New York. tMfg. by Cyprane, Ltd., K&&Icy, England. $Darvon, Eli Lilly & Co., Inc., Indianapolis, Indiana. SAtropine sulfate, Eli Lilly & Co., Inc., Indianapolis, Indiana.
Volume Number
120
Office aspiration
2
Table III.
Pathology
reports
report
No.
bleeding
of procedures
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia
11 46 6 1 1 24 5
219 6
31 1
3
37 24 19
14 9 7 -
6 91 20
2 34 7
14 24 28
z 10 1 1
2 3 Gi
15
by indication
No. of procedures
Menometrorrhagia Percentage
No. of procedures
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps
54 5 -
Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
-
-
-
is
-3
-iz
Total
1 Percentage
-
35
Menorrhagia report
bleeding
of procedures
1
ET7
Pathology
No.
-
Total
reports
Postmenopausal
Percentage
71 290 38 4 4 150 31
Atypical adenomatousendometrium hyperplasia Adenocarcinoma Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
Table IV. Pathology
207
by indication Perimenopausal
Pathology
curettage
87 8 -
16 138 26 5 1
5
29 3 1
3
orrhea are given in Table IV. Again, we are unable to explain the high percentage of secretory endometrium. Pre- or postcoital bleeding (Table V) was the primary indication in only 31 patients but one of these was found to have carcinoma of the endometrium. The findings in the evaluation of 187 patients with infertility also are shown. The report of 89 per cent secretory endometrium is unusual but again unexplained. Table VI lists the reports in 45 patients in whom the procedure was used for evaluation of pelvic tumors (such as leiomyomas,
1 3
Oligoamenorrhea Percentage
No. of procedures
Percentage
7 62 12
12 43 9
13 48 10
2
I -
I
1 13 1 1 -1 1
20 2 1
G
3 -
-i -
ii
90
T
2 1
adnexal masses, etc.), and in 87 patients who underwent aspiration curettage as a preoperative screening procedure. Also shown are 34 procedures performed for follow-up assessment of patients who had previously been shown to have abnormal endometrial findings. Evaluation of an abnormal Pap smear was the primary indication for 103 aspiration curettages. Schiller’s staining of the upper vaginal vault and cervix, multiple punch biopsies of the cervix, and an endocervical scrape also were performed routinely on these patients. Twenty-two per cent were
208
Hathcock
et
al.
Table V. Pathology
reports
by indication -
Pathology
report
Pre-
or postcoital .No. of procedures
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
/ Percentage
‘) 2; 1
reports
report
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
3 6
-
1 1 -
2
s -
Percentage 2 89 4 1 -
8
4
-3 3
-
1
2
1
-
-
187
ro
by indication Pelvic
Pathology
4 166 7 1
-
G
Table VI. Pathology
Infertility No. of procedures
6 68 3 -
1 ‘)
Total
Total
bleeding
No. of procedures
tumor
Screen
Percentagr
7 18 2 4 9 2 1 6 1
4 40 4 -
-ii
-i
found to have carcinoma of the cervix, predominantly carcinoma in situ. Three per cent were found to have carcinoma of the endometrium and in two per cent adenomatous hyperplasia of the endometrium was reported. These results are shown in Table VII. Aspiration curettage was used therapeutically in 10 cases of known or suspected incomplete abortion (Table VII). As previously noted, products of conception were reported in four cases in which the primary indication for the procedure was perimeno-
y
2P 4 2 13
2
No. of proccdurss
Follow-up Percentage
8 37 .>
9 43 2
18 2 1 11 8
21 2 1
ii
-Y
No. of procedures 4 10 -
12 29 -
-
-ii 21 6 3 3 1” -
e
12
34
?
: 2 1 1 4
13
9
Percentage
pausal bleeding and in five cases in which the primary indication was menometrorrhagia. Additionally, one patient in whom the indication was the evaluation of an abnormal Pap smear was found to be pregnant. This patient, however, had returned to the office, as instructed, for this procedure on the first day of what appeared to be her normal menses. In all cases where the pathology report revealed products of conception, there had been recent vaginal bleeding. To our knowledge, no pregnancy was encountered which had not already ex-
Volume Number
Office aspiration
120 2
Table VII.
Pathology
reports
report
Pap
*~;d.4es
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenomatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material
also
produced
an
3
hibited some evidence of disturbance. We feel that the routine performance of this procedure at the time of the onset of menses has helped prevent the unexpected disruption of pregnancy and we recommend this policy in spite of the disadvantage of requiring an additional office visit and an occasional slight delay in diagnosis. Miscellaneous indications accounted for 19 procedures. TabIe VIII Iists by pathologica diagnoses the cummulative total of all of the procedures performed. Carcinoma of the cervix was found in 1.3 per cent, carcinoma of the endometrium in 2.1 per cent, and adenomatous hyperplasia of the endometrium in 5.8 per cent. Altogether, 9.2 per cent demonstrated a malignant or premalignant lesion. Most authorities recognize adenomatous hyperplasia and in particular atypical adenomatous hyperplasia of the endometrium as a potentially premalignant lesion, aithough some, notably led by Kistner and associates,21 have shown it to be reversible in some cases with the use of progestins. Cullen, in his book published in 1900, described the coexistence of atypical endometrium and endometrial adenocarcinoma; GusbergZ3 in 1947 named and defined adenomatous hyperplasia of the endometrium and in a later report Gusberg and Kaplan2i
-
5 63 11 5 -
2 1
(2;) -
which
r;;;re -
10 -
1 9
90 -
I
”
‘”
1
z
-
-
-
-
;;;
T
m
4 ii
diagnosis
1 ?$I;;;:
1 12
3
(239)* 4
endometrial
1 pi;I;ri;;ge
15 51 3 1 1 11 2
rl procedures
smear
1 Perge
15 52 3 1 1 11 2
Total ‘These
209
by indication Abnormal
Pathology
curettage
1
is listed
Table VIII. pathology
Number report
of procedures
No. Pnthology
report
Proliferative Secretory Hormonal imbalance Endometritis Products of conception Polyps Hyperplasia Adenamatous hyperplasia Atypical adenomatous hyperplasia Adenocarcinoma endometrium Atrophic/inactive Carcinoma cervix Miscellaneous Insufficient material Total *These procedures which is listed.
of
procedures 172 866 112 1 19 18 350 65 40
by
Percentage 9.6 48.3 6.3 0.1 1.1 1.0 19.6 3.6 2.2 2. 1
38
(@
(Y3, 0.2 1.6
28 1,784
also produced
an endometrial
diagnosis
reviewed the experience with this condition. In this series of patients with adenomatous hyperlasia, 12 per cent were found on adequate follow-up to have developed adenocarcinoma of the endometrium. They concluded that their data lend support to the concept of adenomatous hyperplasia as Stage 0 cancer of the endometrium and cited numerous references to the literature confirming this view. They projected a 30 per
210
Hathcock
Srptcrnber Am. J. Obstet.
et al.
Table IX. Indications and age distribution of patients with premalignant or malignant reports
Ade?lO??l&
tow
Atypical Ade-
Adenocarcinoma
noma-
tous
Of
hyperblasia
endometrium
31
21
9
20
14
24
hype+ blasia Indication:
P&menopausal bleeding Postmenopausal bleeding Menometrorrhagia Pre- or postcoital bleeding Oligoamenorrhea Abnormal Pap smear Follow-up Screen Pelvic tumor Miscellaneous Total Age: 26-30 31-35 36-40 40-45 46-50 51-55 56-60 61-65 66-70 70+
3
2 2 2 2 2
1 ss 1 1 4 5 23 20 7 3
ii-
1
-
-
1
-
1 1 1 1 1
40 1 1 1 5 12 12 z
1 3 40
3 1 38
1
: 12 9 5 2 1 38
cent cumulative risk of carcinoma of the corpus 10 years after a diagnosis of adenomatous hyperplasia. Our series includes 65 procedures in which the diagnosis was adenomatous hyperplasia, an additional 40 in which the diagnosis was atypical adenomatous hyperplasia, and 38 who were found to have carcinoma of the endometrium. The ages of these patients and the indications are shown in Table IX. The patients with a diagnosis of adenomatous hyperplasia were further evaluated by repeat aspiration curettage on 13 occasions, curettage on six occasions, and 46 have subsequently undergone hysterectomy. Only six were found to have more severe disease than originally reported. In three, atypical ade-
15, 19i4 Gynecol.
nomatous hyperplasia was found on the subsequent pathology report and an additional three cases were reported as adenocarcinoma of the endometrium. One of the three adenocarcmomas? however, was diagnosed by repeat aspiration curettage prior to hysterectomy. In four of the six cases there was a seven- to nine-month patient delay before the subsequent procedure. Twelve patients have not as yet undergone a follow-up endometrial study. Atypical adenomatous hyperplasia was found 40 times. Four have undergone an additional aspiration curettage and 33 a hysterectomy. Four of these were found to have adenocarcinoma of the endometrium, all at hysterectomy. Carcinoma of the endometrium has been diagnosed in 38 patients in our office by aspiration curettage. Years of follow-up of these patients are listed in Table X. Thirtysix patients are living and well. Two patients are deceased, one of cancer 29 months after diagnosis and one of an acute myocardial infarction one week after aspiration curettage and prior to definitive therapy. Ten additional patients were treated for adenocarcinoma of the endometrium who were originally diagnosed either by curettage or by another physician and referred to us for therapy. There has been one incidental finding of carcinoma of the endometrium. This patient, age 42, underwent vaginal hysterectomy and anterior and posterior colporrhaphy for pelvic relaxation. Her menstrual history was entirely normal and she has remained well for eight years since the operation. A review of the records of the 1,415 patients who did not have adenomatous hyperplasia, atypical adenomatous hyperplasia, or carcinoma of the endometrium on the original aspiration curettage revealed subsequent procedures of 366 aspiration curettages, 151 curettages, and 376 hysterectomies. Seventeen patients in whom the original diagnosis bad been simple hyperplasia had recurrent bleeding problems, usually one to two years later, and were found then to have edenomatous hyperplasia. One patient underwent
Volume Number
120 2
Office
curettage for recurrent postmenopausal bleeding three years after aspiration curettage and was found to have adenocarcinoma of the endometrium. One additional patient had endometrial polyps by aspiration curettage but curettage one month later revealed adenocarcinoma. A report of insufficient material for diagnosis was obtained 28 times. Nine procedures were done as a preoperative screen and no significant endometrial pathology was found subsequently. Two patients were being evaluated for postcoital spotting and this has not recurred on follow-up. Four procedures were done to evaluate abnormal Pap smears which were cervical in origin. Evaluation of the menstrual disorders accounted for nine curettages and follow-up of previous endometrial abnormalities accounted for four. These 28 patients have been followed for an average of 4.2 years; eight have subsequently undergone either curettage or hysterectomy. In none of the 28 has any serious endometrial problem been detected. Comment We believe office aspiration curettage is a satisfactory means of evaluating the endometrium for the indications listed. Its diagnostic accuracy is attested to by the fact that in only 29 instances was a more serious lesion subsequently found. Nineteen of these were diagnoses by repeat aspiration, usually with recurrent symptoms one to two years later. One was found at curettage three years later and in nine cases the lesion was found at hysterectomy. We are convinced that in no instance was the therapeutic outcome compromised. One point, however, must be made. If the operator does not feel that a satisfactory curettage has been carried out, or if symptoms persist or recur, then further evaluation is essential. In our series, obtain-
REFERENCES
1. Kelley, 9: 78, 2. Novak,
H. A.: AM. J. OBSTET. 1925. E.: J. A. M. A. 104: 1497,
curettage
Table X. Follow-up
of living patients of the endometrium
carcinoma Years
of follow-up <
1
No.
211
with
of patients
1 1 2 3 4 5 6 7 8 9 10
5 3 5 3 7 2 6 1 2 3 1
ing insufficient material for diagnosis has OCcurred in less than two per cent and in no instance was this found to affect the outcome. One patient, age 47, died of acute myocardial infarction approximately two hours after aspiration curettage. Autopsy revealed advanced coronary atherosclerosis with evidence of recent arterial occlusion as well as extensive myocardial fibrosis, thought representative of progressive subtle myomost likely occurring cardial infarctions, over a long period of time. With the exception of this patient, there have been no complications from this procedure. No perforations have occurred and no infections or other problems have become manifest. Office aspiration curettage is advantageous in that it shortens the delay to final diagnosis, is only transitorily disabling, does not require hospital facilities or a general anesthetic, and is much less costly than the conventional curettage. Additionally, it is more convenient for the patient and for the physician with regard to the amount of time involved. The procedure is painful but with proper patient presentation and mild analgesia it has been well accepted. We recommend this procedure for office evaluation of the endometrium as safe, accurate and advantageous.
3. GYNECOL.
4. 1935.
aspiration
Randall, L. M.: Proc. Staff Meet. 10: 143, 1935. Israel, S. L., and Mazer, C.: AM. GYNECOL. 36: 445, 1938.
Mayo
Clin.
J. OBSTET.
212
Hathcock
et al.
Srptt,mber Am. J. Obster
15, I974 Cynecol.
5. Williams, G. A., and Stewart, C. B.: .4br. J. OBSTET. GYNECOL. 54: 804, 1947. 6. Palmer, J. P., Kneer, W. J., and Eccleston, J. H.: AM. J. ORSTET. G~NECOL. 60: 671. 1950. 7. Wall. J, A., Fletcher, G. A., and MacDonald, E. J.: Am. J. Roentgenol. 71: 95, 1954. 8. Hecht, E. L.: AM. J. OBSTET. GYNECOL. 71: 819, 1956. 9. Burge, E. S., and Morley, B.: AM. J, OBSTET. GYNECOL. 80: 325, 1960. 10. McGuire, T. H.: Obstet. Gynecol. 19: 105. 1962. 11. Slaughter, C. R., and Schewe, E. J.: AM. J, OBSTET. GYNECOL. 83: 1302, 1962. 12. Nugent. F. B.: Obstet. Gynecol. 22: 168, 1963. 13. Parkhurst, G. F., Jameson, W. J., and Oran, J. F.: Surg. Gynecol. Obstet. 116: 631, 1963. 14. Wildhack, R. H., and Graham, J. B.: Obstet. Gynecol. 23: 446, 1964. 15. Abramson, D., and Driscoll, S. G.: Obstet. Gynecol. 27: 381, 1966.
16. Wall, J. A.. Collins. V. P., Kaplan, .4. I... and Hudgins. P. T.: AM. J. OBSTET. GYNECOL. 97: 787, 1967. 17. Kahler. V. L., Creasy, R. K., and Morris, J. A.: Obstet. Gynecol. 34: 91, 1969. 18. Hofmeister, F. J., and Barbo, D. M.: Obstet. Gynecol. 23: 386, 1964. 19. Hofmeister, F. J., Vondrak, B. F., and Barbo. D. M. : AM. J. OBSTET. GYNECOL. 95: 91. 1966. 20. Hofmeister, F. J.: J, Reprod. Med. 4: 33, 1970. 21. Kistner, R. W.? Gore, H., and Hertig, A. T. : AM. J. OBSTET. GYNECOL. 95: 1011, 1966. 22. Cullen, T. S.: Carcinoma of the Uterus, New York, 1900, D. Appleton & Company. 23. Gusberg, S. B.: AM. J. OBSTET. GYNECOL. 54: 905, 1947. 24. Gusberg, S. B., and Kaplan, A. L.: AM. J. OBSTET. GYNECOL. 87: 662, 1963.
Discussion T. VERNON FINCH, Sarasota, Florida. Dr. Hathcock’s report represents a considerable experience with a diagnostic procedure which is easily done in the office, with early available pathologic diagnosis, and with a considerable saving in hospital cost. For some 20 years I have employed aspiration endometrial biopsy for indications similar to the authors, and, more recently, I have used it in another category of so called “high-risk” individuals, who are hypertensive and obese, have a family history of diabetes, and have any suggestion of abnormal bleeding, present or past. Th e preoperative screening of patients suspected of pelvic neoplasm such as myomas and adnexal masses is especially comforting when definitive laparotomy is scheduled without an antecedent curettage. This screening will prevent almost all of the concern that surfaces when the electively removed uterus is reported as malignant. Concerning technique, there are two points to be made. In contradistinction to the authors, who frequently employ inhalation analgesia, I have found a paracervical block very useful in the anxious patient and also in individuals with a small cervical OS. A Hank dilator can then usually be used to dilate the cervix sufficiently to pass a uterine sound. One may find some advantage in using a plastic disposable 10 C.C. syringe because the plunger has a Aare on the proximal end which will allow for the use of a small wedge of wood some two inches in length
which can be used to hold the plunger back, to produce and hold a vacuum so that the operator can hold the curette lightly and with a greater sense of touch while performing the biopsy. The evaluation of these 1,784 procedures in 1,558 patients has involved a problem of abnormal uterine bleeding in 71 per cent. Some 60 per cent of the procedures have been in individuals 41 years of age and older. Several surprising findings are: ( 1) the high percentage (48) of secretory endometria reported, (2) the low percentage (2 per cent) of adenocarcinoma, and (3) the 25 per cent with hyperplasia of the endometrium, benign and atypical. The question which first occurs to me is to inquire of the authors if they have some idea as to how many of these patients were receiving exogenous estrogens, or estrogen-progestin products, which may have influenced the histologic picture of the tissues under study. The premalignant implications of adenomatous hyperplasia were discussed. The matter of reversibility with progestins was mentioned. However, it is worth mentioning also that there is a reversibility of adenomatous hyperplasia relating to the influence of estrogen, be it the endogenous estrogen of the premenopausal or the exogenous estrogen in the postmenopausal female. This matter of the reversibility of adenomatous hyperplasia in the postmenopausal female rez:iving estrogen replacement therapy by the simple withdrawal of this stimulus has been described by Dr. Donald Woodruff in personal communications. It would appear, then, that the adenoma-
DR.
Volume Number
120 2
tous hyperplasia developing in the untreated postmenopausal patient has a more malignant potential than in the estrogen-treated individual. Among the 65 cases with a diagnosis of adenomatous hyperplasia six cases were found to have a more severe process. In four of these six a delay of seven to nine months occurred. Three cases of adenocarcinoma occurred among the six. Twelve patients apparently have not undergone a follow-up study. Among the 40 cases of atypical adenomatous hyperplasia 33 patients underwent hysterectomy, four of whom already had adenocarcinoma at
Office
aspiration
curettage
213
the time of the hysterectomy. No mention was made of a curettage in any of the other seven individuals with this premalignant lesion. It would appear to this discussant that it has been shown by the authors that a positive diagnosis obtained at aspiration endometrial biopsy is useful in the early and efficient planning of therapy, e.g., hysterectomy with or without prior irradiation therapy. However, an essentially negative biopsy in a patient with symptoms, although highly accurate and in general relieving of anxiety, should require further investigation by a thorough curettage.