Intraepithelial carcinoma of the cervix in pregnancy

lntraepithelial carcinoma of the cervix in pregnancy JOHN G. BOUTSELIS, M.D. JOHN C. ULLERY, M.D. Columbus, Ohio

the epithelium of the cervix which simulate or ·mimic preinvasive squamous cell carcinoma and are indistinguishable from it. In a collective review of the literature and adding several series of their own, Greene and Peckham 17 have clearly demonstrated that this concept is incorrect and that the diagnosis of carcinoma in situ during pregnancy is a valid one. The purpose of this study is to report our experience with 69 cases of intraepithelial cervical carcinoma associated with pregnancy and attempt to correlate several interesting aspects of this intriguing neoplastic disease.

I N v A s 1 v E carcinoma of the cervix, the most common malignancy of the female reproductive tract, may be considered a preventable disease if we accept the concept that carcinoma in situ is the precursor to invasive cervical carcinoma. The progressive nature of this lesion is exemplified by the works of Smith and Pemberton, 35 Hertig and Young, 19 Galvin and TeLinde, 16 Pund and Auerbach, 3 ° Funk-Brentano,' 5 and Petersen. "8 Petersen 28 and Funk-Brentano15 observed 130 and 124 patients, respectively, without therapy and in each series approximately one third of the cases were invasive at the end of 9 and 10 years, respectively. Other writers have reported smaller but similar series concurring with these results. If we are to diagnose this lesion during it~ preinvasive stage, we must rely on cytologic means of detection, since approximately 75 per cent of intraepithelial carcinomas are associated with a clean-looking cervix and are asymptomatic.3·5 Suspicious or positive vaginal smears then necessitate a cold knife cervical conization to make a definitive diagnosis. It is still accepted today, by a minority group, 9 • 23 that pregnancy causes changes in

Incidence

Between the years 1940 and 1962 inclusive, there were 62,740 deliveries at University Hospital, Ohio State University College of Medicine of which 69 (0.11 per cent) had coexisting carcinoma in situ of the cervix and 59 ( 0.09 per cent) had invasive squamous cell carcinoma. During the same period of time, there were 35,466 gynecologic patients admitted of which 350 ( 1 per cent) had intraepithelial cervical carcinoma and 1,570 (4.1 per cent) had invasive carcinoma. As noted in Table I and graphically illustrated in Figs. 1 and 2, there has been a significant and striking decrease in the occurrence of invasive carcinoma and a corresponding increase in the diagnosis of carcinoma in situ as the years progressed from

From the Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine. Presented at the Eighty-seventh Annual Meeting of the American Gynecological Society, Hot Springs, Virginia, May 25-27, 1964.

593

594

Boutselis and Ullery

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November 1, 1964 J. Obst. & Gynec.

Table I. In situ and invasive cervical carcinoma in pregnant and nonpregnant patients ( 1940-1962) Not Invasive

I

D

<

In situ

I

I

'S ,..,.

In situ

lnvasil:e

%

Year

No.

%

No.

%

No.

1940 through 1951 1952 1953 1954 1955 1956 19.17 1958 1959 1960 1961

415

97.0

13

3.0

16

100

0

0

85 104 105 113 105 140 139 120 101 73 70

95.4 94.5 96.3 93.7 94.6 80.9

4 6 4 5 8 33

3

100

2

IOU

0 0

73

70.1 71.1 52.8 59.7

51 41 65 47

2 4 5 5 2 8 5 3

100 80 100 7L4 15.5 34.8 33.3 20.0 5.0

0 0 0 1 0

65.5

4.5 5.5 3.6 4.2 5.2 19 34.4 29.8 28.8 47.1 40.1

10 15 10 12 19

20 0 28.5 83.3 65.2 66.6 80.0 95.0

1,570

81.2

350

18.7

56

44.8

69

55.2

Total

%

I

No.

1940 to 1962. These changing incidences are undoubtedly attributed to the more frequent use of the Papanicolaou vaginal smear both in the obstetric and gynecologic patients. Complete cytologic screening of all patients seen in our clinics was rigidly enforced in 1957 which subsequently yielded gratifying results. As noted in Table I and Figs. 1 and 2, of the 89 cervical malignancies encountered in the gynecologic patients in 1952, only 4.5 per cent were preinvasive carcinomas while 95.4 per cent were invasive! A decade later the incidences of these lesions were 40.1 per cent and 59.7 per cent, respectively. Further analysis of the invasive lesions in 1962 revealed the majority to be clinical Stage I and Stage II. More striking are the corresponding data associated with the obstetrical patient which show a decrease in the invasive carcinoma from 100 per cent in 1952 to 5 per cent in 1962 and an increase in the diagnosis of carcinoma in situ from zero per cent in 1952 to 95 per cent in 1962. Once again these findings exemplify the value of a rigidly enforced program of complete cytologic screening of all patients regardless of age and lend support to the dictum that carcinoma in situ is a precursor to invasive carcinoma and the latter is a preventable disease.

I

2

I

0

Age distribution

The age distribution noted in Fig. 3 seems to be in accord with most reported series. It is interesting to note that the majority of patients were between the ages of 31 and 35 which corresponds closely to an age distribution among nonpregnant patients reported by Carter and associates, 5 Parker and coworkers,Z6 and Boyd and associates/ thus indicating that carcinoma in situ may be as prevalent in the pregnant woman when equal numbers and various related factors are considered. It is also interesting to note in the present series that 34.7 per cent of the patients were under the age of 26 years, again emphasizing the necessity of taking routine vaginal smears in this relatively younger age group of patients and not relying on the age factor as an indication for commencement of cytologic screening. Race, religion, parity, and marital status

Table II summarizes the race, religion, parity, and marital status of 69 obstetrical patients who were found to have carcinoma in situ of the cervix. The only unusual fact in this table is the rather disproportionately high incidence (60.8 per cent) of intraepithelial carcinoma associated with the Negro

lntraepithelial carcinoma of cervix m pregnancy

Volume 90 Num ber 5

100

100%

595

c::J PREGNANT -IN SITU Co c::J PREGNANT- INVASIVE Co c::::::l NON-PREG.- IN SITU Co NON-PREG -IN\IO.SIVE Co

75

.J

;!50

e

...0

;,t 25

----1962----

Fig. 1. In situ and invasive cervical carcinoma-Decade of progress in earlier diagnosis.

patient which is difficult to explain. One may speculate and explain it by the fact that the Negro patient may marry at an earlier age, practice sexual intercourse earlier in life, and, subsequently bear children at an earlier age. This, with the smegma factor may explain the higher predilection for the Negro patient. Other categories noted in Table II are in accord with the findings reported in other reports. 4 • 17 • 3 3 The majority of patients were of protestant denomination, married, and para i to iii. No Jewish patients were encountered with carcinoma in situ of the cervix, a finding which was anticipated. Chief complaint Noteworthy of emphasis is the paramount fact that 84 per cent of the patients in the present study had no complaints (Table III). These patients were seen either for routine prenatal or postpartum care at which time Papanicolaou vaginal smears were taken. Had it not been for a rigid cytologic screening program enforced in our prenatal and postpartum clinics and similarly practiced by our attending staff, the detection of intraepithelial carcinoma in a significant number of patients would have been delayed until symptoms appeared. Again, these findings are in accord with those carcinoma in situ studies reported by Carter and associates5 and Parker and co-workers. 26 Only 38.5

per cent of the in situ patients of Riva, Hefner, and Kawaski 33 were reported to be asymptomatic. Clinical impression of cervices Table IV gives the data on 69 obstetrical patients with intraepithelial carcinoma of the cervix, in whose protocols are recorded the clinical impression of the cervix on the initial examination. It is clear that cervices harboring carcinoma in situ have no characteristic general appearance and extremely important is the fact that in 73.9 per cent of our patients the examining physician assessed the cervix to be normal. These findings are in accord with other reports. 5 • 26 Visual cervical pathology was described as chronic cervicitis, cervical erosion, abnormal congestion, or as a nondescript lesion. These facts illustrate the obligation to screen all female patients by exfoliative cytologic techniques. All suspicious lesions should be biopsied in the office or in the clinic and, should invasive carcinoma be diagnosed by such a procedure, it would save the patient time, expense involved with hospitalization, and the risk of an anesthetic. Detection is used in the sense that this procedure is often the first indication that the patient may have a cervical malignancy. Our definition of a positive diagnosis means that certain procedures have enabled us to ascertain the diagnosis of carcinoma in situ

November 1, 1964

596 Boutselis and Ullery

Am. ]. Obst. & Gyn<'<:.

57'

59'

60'

61'

62'

PREGNANT -INVASIVE · - - · PREGNANT- IN SITU -

Fig. 2. In situ and invasive cervical carcinoma, 1940 through 1942.

35

30

...z

CJ)

2~

!!!

!i Q.

~

20

0

z ..J

I~

....0

10

"' ....b

~ ~

AGE RANGE OF PATIENTS

Fig. 3. Intraepithelial carcinoma of the cervix. The age distribution of 69 obstetrical patients.

of the cervix. It is noted in Table V that in 56 patients (81.1 per cent) vaginal smears were the first indication that an abnormal cervical epithelium may be present. In no instance, however, did we consider a suspicious or positive smear diagnostic of carcinoma in situ and administer definitive surgical therapy without tissue examination. In 8 patients a punch biopsy disclosed the presence of intraepithelial carcinoma. A cold

knife conization of the cervix supplemented the punch biopsy specimen for complete evaluation of the patient. In 2 instances, dilatation and uterine curettage obtained malignant cells strongly suggestive of carcinoma in situ of the cervix. A definitive diagnosis was made in one hysterectomy specimen, therefore, it was gratifying to note that in all other cases a positive diagnosis was made by cold knife cervical conization. It is our opinion that single or multiple punch biopsy procedures are considered inadequate to properly evaluate an abnormal cervical epithelium, an opinion not shared by some writersY• 12

Complications associated with diagnostic procedures during pregnancy A significant number of complications resulted from diagnostic procedures in 69 obstetrical patients (Table VI). Two patients who were in their first and second trimesters of pregnancy, respectively, had abortions within 3 days subsequent to cervical conization. Unsuspected pregnancies were aborted by diagnostic dilatation and curettage and cervical conization in 2 patients who had Class III vaginal smears necessitating tissue

Volume 90 Numher 5

lntraepithelial carcmoma of cervix

1n

pregnancy

597

Table II. Race, religion, parity, and marital

Table VI. Complications associated with

status

diagnostic procedures during pregnancy %

1?.ace

White ~egro

27 42

39.1 60.8

No.

%

h.l .... "'.:J: ........ U~~CU1115

4 2 2

5.7

60

86.9

2

2.9

10

14.5

5

0

0.0 7.2

2

2.9

Subsequent abortion Unsuspected abortion with dilatation and curettage Premature labor Total complications

Religion

Protestant Catholic Jewish Others

5.8

4

Parity ~ulliparous

to 3

35

50.7

60

86.9

4

5.8

Chief complaint

No.

%

Asymptomatic, prenatal examination Asymptomatic, postpartum examination Vaginal discharge Vaginal spotting-bleeding Incomplete abortion Ectopic pregnancy ~·topic and vaginal smear

39

i

Com plication Ah ..................... l

.ri.UUVlUH:U

+ to

25 7

6 7 to 8

36.2 10.1

Marital status

Married Singie Divorced

5

7.2

Table Ill. Chief complaint

56.5)

19

27.5

5

7.2 5.8 2.8 1.4 1.4

4

2

84

Appearance of cervix

No.

%

51

73.9 2.9 8.6 2.9 11.5

2

6 2 8

Table V. Methods of detection and diagnosis Detection Method

Vaginal smear Punch biopsy Cervical cone Dilatation and curettage of uterus Hysterectomy

I

No.

I

%

Dia{(nosis

I

No.

I

analysis. During the last trimester of pregnancy, premature labor was initiated by cervical conization in 2 instances. Both infants survived their prematurity and are doing well. Abnormal vaginal bleeding varying from 200 c.c. to 1,200 c.c. was experienced by 4 patients requiring additional hemostatic procedures. Therefore, the risks of surgical diagnostic procedures during pregnancy are evident but it is our definite opinion that risks greater than these are inherent in any policy that avoids intelligent and aggressive approach toward detection of cervical cancer during pregnancy. This opinion is shared by other writers 1 • :J. 11 who have reported similar experiences in obstetrical patients. Distribution of vaginal smears

Table IV. Clinical impression of cervices Clean or minimal cervicitis Chronic cervicitis Erosion Congestion Lesion, nondescript

~.9

2.9

%

56 8 3 2

81.1 11.5 4.3 2.9

00.0 00.0 68.0 00.0

00 00 99.0 0.0

0

0.0

1.0

1.4

Since there is a great variation in reporting vaginal smears, it is of paramount importance for a writer to clearly spell out the classification used. In the present study, the conventional Papanicolaou classification was used by the department of pathology which is interpreted as follows: Class !~negative; Class II~atypical cytology but no evidence of malignancy; Class III~cytology suggestive of malignancy; Class IV~cytology strongly suggestive of malignancy; Class V ~ cytology conclusive of malignancy. The distribution of vaginal smears in 69 obstetrical patients with intraepithelial carcinoma are noted in Table VII. It has been our experience that approximately 50 per cent of Class III smears are associated with cervical malignancy, hence, patients with Class III smears are admitted for diagnostic conization. In gynecologic patients, cervical conization is supplemented by a dilatation

598

Boutselis and Ullery

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Table VII. Distribution of vaginal smears Papanicolaou class II III IV

v

Not taken

No.

%

0

3 58 4 2

0.0 4.3 84.0 4.8 2.8

2

2.8

and curettage. A similar procedure is indicated in patients with a persistent Class II smear who have had sufficient time and treatment to clear up cervicovaginitis when present. It has also been our experience that invasive carcinoma in contradistinction to in situ carcinoma is rarely associated with a clean-looking cervix and a suspicious or positive smear. In the present study, of the 3 patients who had Class II smears, one had a persistent Class II smear, the second was associated with a nondescript cervical lesion, and the third, with an erosion. The second and third patients were reported to have in situ carcinoma from punch biopsy specimens. This illustrates the importance of not relying entirely on laboratory cytologic reports for total gynecologic evaluation of the patient. It is of interest to note that 84 per cent of our patients had Class III vaginal smears, an incidence significantly higher than those reported recently. Osband and Jones 25 reported 61 per cent, Parker and associates," 6 58.1 per cent, Riva, Hefner, and Kawaski/ 3 approximately 25 per cent, and Mussey and Soule, 24 23 per cent. Based on the strength of these reports, patients with Class III vaginal smears should be subjected to cervical conization in spite of the presence of a normal-appearing cervix. Residual tumor

It is generally accepted by most clinicians and pathologists that carcinoma in situ may progress to invasive carcinoma in the untreated patient in approximately 8 to 10 years. During this span of time the progres-

N o\'ember 1, 1964 J. Obst. & Gynec.

sive lesion must assume changing cellular characteristics involving variable degrees of surface and glandular involvement of the cervix. In a minority of patients/• 37 • 39 intraepithelial carcinoma may assume a retrogressive nature and disappear. However, antagonists of this theory postulate that the lesion in all probability was removed by a cervical biopsy procedure. 1,hat there are variable gradations of in situ carcinoma was emphasized by Hertig and Y oung19 more than a decade ago and recently reviewed and categorized by Frick and co-workers. 14 For more detailed cellular pathology, the reader is referred to the work of Regan and Hamonic. 31 Fifty-four patients were subjected to a total hysterectomy as a definitive form of therapy for carcinoma in situ of the cervix. Utilizing these patients, an attempt was made to see if any correlation existed between residual carcinoma in the postpartum cone or hysterectomy specimen and the histologic grade of the lesion. Based primarily on the anatomical extent of the tumor and secondarily on the cellular changes of the lesion, the three histologic grades are: Grade 1. The neoplastic changes have replaced a relatively small segment of the normal cervical epithelium in its full thickness and the underlying basement membrane is straight. There is a loss of polarity, the cells are pleomorphic, the nuclei are large, hyperchromatic, and irregular with frequent mitosis. Grade 2. The increased downward growth of the proliferating cells have caused the basement membrane to undulate and there is a more extensive surface growth with early extension into the endocervical glands. Abnormal mitoses are seen. There is a change in the cytoplasmic nuclear ratio. Grade 3. There is extensive surface growth and a marked degree of endocervical gland involvement but the basement membrane remains intact. Chronic inflammatory changes are noted beneath the basement membrane which at times gives it a hazy appearance. Microinvasion is excluded from this category.

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lntraepithelial carcinoma of cervtx

Table VIII. Residual tumor in second cone or hysterectomy specimens as related to histologic grade of tumor

tn

%

599

Table IX. Residual tumor in hysterectomy specimen following postpartum conization as related to histologic grade of tumor

tumor Histologic grade No. of patients

pregnancy

Histologic grade No. of patients

!Residual tumor No. %

r"'~~...:l ..... \J"l au~

10 lU

r-"- ... ..l ... \J"ld.UC:

10 lU

19 17

4 12 16

<)<) <) £..C.,,(..

Grade 2 Grade 3

63.1 94.7

Grade 2 Grade 3

19 17

5

29.4

Total

54

31

59.2

Total

54

10

18.5

As noted in Table VIII, residual tumor was present in 31 (59.2 per cent) patients with a significant variation in the three histologic grades. In those patients with histologic Grade 1 lesions, only 22.2 per cent exhibited residual tumor while those with Grade 3 lesions, residual tumor was present in 94.7 per cent of the patients. These findings should not be too surprising since a

higher per cent of residual tumor should be anticipated in those patients with extensive glandular involvement where in situ carcinoma may extend into the clefts and tunnels outside the perimeter of cervical conization. Conversely, smaller superficial lesions are accessible to cervical conization and are usually completely excised by adequate conization. Although other factors should be considered in this facet of the study, such as cervical configuration, depth and width of cervical conization, symmetry of excision, etc., histologic grading of intraepithelial carcinoma appears to be important in anticipating residual carcinoma after cervical conization has been performed. The incidence of 59.2 per cent residual tumor in the second cone or hysterectomy specimen concurs with 60 per cent reported by Osband and Jones" 5 and is at variance with other reported series. Greene and Peckham 17 report 78.4 per cent and Schulman and Ferguson 34 report 46 per cent. These '.vriters, however, do not include collectively the second cone and excised uterus. It should be noted that of 31 patients who had residual tumor in this study, 26 (89.6 per cent) were located in the endocervical glands. As noted in Table IX, similar correlative

2 3

11

1

ll.J

15.7

results are noted between histologic grading of the tumor and the excised uterus, the latter being preceded by an intrapartum diagnostic cone and a postpartum cone. Our residual tumor incidence of 18.5 per cent in the hysterectomy specimen is somewhat lower than most reported series: 31 per cent by Riva, Hefner, and Kawaski,3 3 30 per cent by Moore and co-workers, 22 38 per cent by Dilworth and Maxwe!I,B 27 per cent by Huey, Large, and Kemmelsteil/ 0 and 16 per cent by Peightal and associates. 2 ' Nevertheless, these represent a relatively high incidence of incomplete removal of cancerous tissue by cervical conizations. Thus, any treatment short of total hysterectomy should be reserved for the patient in the relatively rare and selected instance. This is usually a young woman who strongly desires more children and is willing to return for examination and cytologic evaluation every 3 to 4 months. Even then, after a waiting period of several years, definitive surgical treatment is usually indicated. During the successive months of pregnancy the changes in cervical growth and configuration and the various problems fac-

Table X. Residual tumor in postpartum cone as related to trimester of pregnancy Trimester of pregnancy

'!

I' No residual Residual tumor _ _t_u_,m,-o_r_ _

No.

\ %

No.

%

I II

III

3 6 13

30 66.6 72.2

5

27.7

Total

22

61.1

14

38.8

7 2

70 33.3

600

Boutselis and Ullery

ing the operating surgeon may influence the extent of cervical conization. Therefore, it was interesting to speculate if any correlation existed between residual tumor approximately 2 months post partum and the trimester of pregnancy in which cervical conization was performed. As noted in Table X, the incidence did vary with each trimester being 30 per cent in the first trimester and 72.2 per cent in the third trimester. Furthermore, in 61.1 per cent of the cases, residual tumor was encountered in the postpartum cone. Microinvasive carcinoma

In recent years this lesion has been given much attention in an attempt to categorize it properly and to detern1ine what constitutes adequate therapy."5 • 8 • 10 • 12 " 14 • ~"- 26 In spite of the numerous publications on the subject, sufficient differences of opinion regarding its therapy still exist. Conversely, there seems to be general agreement among pathologists and clinicians that microinvasive carcinoma is a distinct pathologic entity preceded by carcinoma in situ and followed by frank invasive carcinoma if permitted to exist without definitive therapy. Seven patients with microinvasive carcinoma were encountered in the present study, an incidence of I 0 per cent, concurring with a 10 per cent incidence reported by Young. "8 In all instances this lesion was associated with a histologic Grade 3 carcinoma in situ. In 4 patients the diagnosis was made from the postpartum cone, 3 of whom were treated by central cobalt 60 radiation and, subsequently, by a radical Wertheim procedure; the fourth patient was treated by a full complement of central and external radiation therapy. One case was diagnosed during the second trimester of pregnancy and was subjected to a hysterotomy and radical Wertheim hysterectomy. In 2 instances, the diagnosis was made from the hysterectomy specimen and no further therapy was administered. This facet of the study supports the belief which most clinicians have concerning the necessity of postpartum cervical conization in patients with

Am.

November 1, 1964 J. Obst. & Gynec.

carcinoma in situ before definitive surgical therapy is administered. Should this vital step be omitted, there is an appreciable risk of: ( 1) not detecting an ocult invasive cervical carcinoma until the uterus is excised, and ( 2) in exposing the patient to greater danger if she is a patient to be followed conservatively for reasons previously mentioned. On the other hand, the possible serious results of omitting a post partum cervical conization depends on the clinician's view of what constitutes adequate therapy for microinvasive carcinoma. This lesion is on rare occasions associated with lymph node metastases as reported in the literature. 6 Treatment

It is generally agreed that vaginal delivery should be permitted in all patients with intraepithelial carcinoma unless obstetrical indications indicate otherwise. In the present series, 60 patients were delivered vaginally and the remaining patients' pregnancies were terminated by cesarean section for placenta previa, for repeated sections, increased parity, salpingectomy for ectopic pregnancy, dilatation and curettage in unsuspected pregnancies, and hysterotomyradical Wertheim hysterectomy for microinvasive carcinoma. There is general agreement in recent reports5• 14 • 18 • 10 • 2 "· :l 3 and in most texts that the treatment of choice in the usual case of intraepithelial carcinoma is total hysterectomy, resection of 1 to 2 em. of upper vaginal cuff, and preservation of ovaries. Exceptions to this form of therapy would depend upon the patient's age, parity, desire for more children, general health, and psychological factors. The departmental policy at our institution concurs with this therapeutic regime and may be briefly summarized as follows: ( 1) the diagnosis is established by a cold knife cervical cone at any time during pregnancy and the procedure repeated 2 months post partum to rule out invasive carcinoma; ( 2) unless childbearing functions are to be preserved, total hysterectomy and resection of 1 to 2 em. of upper vaginal cuff are performed within 36 hours following

Volume 90 Number 5

601

lntraepithelial carcinoma of cervix m pregnancy

postpartum conization or it is postponed for at least 2 months after delivery. The type of hysterectomy to be performed depends on the concomitant presence of a cystocele and rectocele to be repaired when indicated. If an anterior posterior colpoperineorrhaphy is to be performed with a vaginal hysterectomy, it is best to defer these procedures for approximately 4 to 6 months after delivery; and ( 3) in gynecologic patients of menopausal or postmenopausal age, a bilateral salpingo-oophorectomy is performed in addition to total hysterectomy. As noted in Table XI, 54 patients were subjected to total hysterectomy, only one third of which were accomplished by the vaginal route. In a survey of the literature Carter" noted the vaginal hysterectomy to be more popular since it assures the resection of a more adequate vaginal cuff and preserves the cervical epithelium from being subjected to undue surgical trauma. Mussey and Soule 24 of the Mayo Clinic reported 4 77 vaginal hysterectomies and 193 abdominal hysterectomies in their review of 842 cases. Two of 7 microinvasive carcinomas in this series were treated by total hysterectomy as definitive therapy while 5 others were treated as early Stage I lesions. One patient who had received no definitive therapy died of causes unrelated to the cervical neoplasm. Of the 69 patients with intraepithelial carcinoma, 6 were between the ages of 15 and 23 who expressed strong desires for subsequent pregnancies. These patients, after having had a postpartum cervical conization, are being followed as described elsewhere in this report. Complications following definitive surgical treatment

It was surprising to note the high incidence of postoperative complications in patients subjected to definitive surgical therapy. As noted in Table XII these complications consisted generally of infection and poor hemostasis, particularly following abdominal hysterectomy. It is difficult to speculate \vhy such complications "vere pre-dominantly the sequelae of abdominal hys-

Table XI. Treatment Type of treatment

No.

%

Abdominal hysterectomy Vaginal hysterectomy Cesarean hysterectomy Cervical cone and follow Central CO,o and radical Wertheim Hysterectomy and radical Wertheim Central and external radiation Died, no therapy Currently pregnant

36 18 1 6 3

52.1 26.0 1.4 8.6 4.3

Total

69

1.4 1.4 1.4 2.8

2

Table XII. Complications follovving definitive surgical treatment Following vaginal hysterectomy Vaginal cuff hemorrhage Vaginal cuff hematoma Total Following abdominal hysterectomy Died of pulmonary embolism, third postoperative day Pelvic abscess Vaginal cuff hematoma with infection Cuff bleeding necessitating suturing Pelvic hematoma necessitating ligation hypogastric artery Ureteral obstruction Total

2

11.1'7<

I 3 3 2

11

26.9%

terectomy. It is reasonable to assume that more meticulous vaginal preparations for a sterile field were made prior to vaginal hysterectomy and better hemostasis of the vaginal cuff and pedicles were obtained under more direct visual exposure. More important is the well-established time relationship between cervical cone and hysterectomy. Unless hysterectomy is performed within 36 hours following cervical conization, it should be postponed for at least 6 weeks. During this time, postconization paracervical infection and friability subside. If hysterectomy is performed without considering this important cone hysterectomy time relationship, the operating surgeon will encounter friable, infected tissue in the cervical and paracervical areas and upper vaginal cuff which is

602

Boutsel is and Ullery

more apt to lead to the sequelae noted in Table XII. Comments

Intraepitheliai carcinoma of the cervix has a similar pathological pattern behavior both in the obstetric and gynecologic patient; therefore, any comments directed toward the pregnant patient are generally applicable to the nonpregnant patient. Since the advent of the Papanicolaou vaginal smear and particularly during the past 6 years, we have noticed a remarkable increase in the diagnostic frequency of carcinoma in situ and a corresponding decrease in invasive carcinoma. We believe this trend is found in all institutions actively engaged in cytologic screening programs. As borne out in the present series, the overwhelming majority of cases are asymptomatic and are associated with a clean looking cervix which in past years we considered normal. It is well worth re-emphasizing that visual inspection is a poor indicator for the presence or absence of malignancy in a normal- or abnormal-appearing cervix; therefore, we must rely heavily on cytological techniques to detect in situ carcinoma (Tables III through V). Other investigators 1 • 3 • 11 have pointed out the hazards associated with cervical conization during pregnancy and this has been borne out in our series (Table VI). In spite of these facts, it remains imperative that we utilize the diagnostic procedures necessary to evaluate properly the cervix before a patient is permitted to undergo labor and delivery through the vaginal route. It should be added that in the present series, one death was caused by a pulmonary embolus which occurred on the third postoperative day, following abdominal hysterectomy. The incidence of residual tumor in the postpartum cone and hysterectomy specimen is surprisingly high and emphasizes several facts. First, carcinoma in situ diagnosed during pregnancy is a valid diagnosis and it does not disappear in the puerperal period. Second, it points out the inadequacy of cervical conization for those who consider this

November I, 1964 Am . .). Obst. & Gyncc.

procedure both diagnostic and curative. Third, microinvasive carcinoma is being diagnosed with increased frequency during the past several years and a review of the literature by Fidler and Boyd 12 shows this incidence to vary between 5 to 63 per cent. Therefore, residual carcinoma may very well be microinvasive. Finally, it has been our experience that there is a correlation between residual tumor and histologic grading of the lesion or the trimester in which cervical conization was performed (Tables VII through X). That is, histologic Grade 3 lesions coned during the third trimester of pregnancy are more likely to be incompletely excised via diagnostic cervical cone biopsy. If we are to rninimize complications following hysterectomy for carcinoma in situ, then we must keep in mind the time factor relationship between diagnostic conization and hysterectomy. If hysterectomy is anticipated, it should be performed within 36 hours following cervical conization or be postponed for at least 6 weeks until infection, tissue friability, and necrosis resolve. As pointed out by Carter,5 the vaginal approach is the more popular method of performing hysterectomy in patients with carcinoma in situ of the cervix. More recently it has been our policy to postpone vaginal hysterectomy for at least 4 to 6 months after delivery if we anticipate a concomitant cystocele and rectocele repair. Definitive therapy for carcinoma in situ at our institution consists of total hysterectomy, resection of 1 to 2 em. of upper vaginal cuff and preservation of the ovaries during the childbearing years. Although most writers on the subject consider this to be the procedure of choice, there are some 2 • zo, 21 who feel that conservative management, such as wide cervical conization and close postoperative follow-up is sufficient therapy for this lesion. In a very interesting study of geographic distribution of intraepithelial carcinoma, Prybora and Plutowa 29 demonstrated that conservative management by such means as conization or amputation of the cervix can be curative in only 15 per

Volume 90 Number 5

lntraepithelial carcinoma of cerv1x in pregnancy

cent of these lesions. Richardson and Thiersch 32 who examined by serial block sections of the cervix removed following a variety of diagnostic procedures, especially conization and curettage, found residual in situ carcinoma in 31 of the 39 specimens (approximately 80 per cent). Other reports s, 11, 2o, zz, 21, 33 indicate that residual carcinema in the hysterectomy specimens vary between 16 per cent to 78 per cent. These findings indicate that conization and dilatation and curettage have failed to eradicate these protected endocervical foci of cancerous tissue which may be intrenched in the fibrous crypts and tunnels of a patulous and, sometimes, distorted endocervix. Another disadvantage to conservative management is the failure of the patient to cooperate in either regular follow-up examinations and smears or in refusal to accept further treatment if indicated. In the present series, we have encountered one such patient who had no definitive therapy and died 2 years later of some unrelated cause. Nevertheless, such a problem is realistic and should be anticipated in attempting to formulate a policy of therapy. Summary

1. Between the years 1940 and 1962, 69 obstetrical patients were encountered at University Hospital, Columbus, Ohio, with intraepithelial carcinoma, an incidence of 0.11 per cent. 2. Cytologic screening has resulted in a marked change in the diagnostic incidence of cervical carcinoma. In 1962, carcinoma in situ of the cervix in obstetrical patients

constituted 95 per cent of all cervical malignancies. 3. Thirty-five per cent of the patients in this series were under the age of 26 years and the necessity of cytologic screening in this age group has been emphasized. 4. Intraepithelial carcinoma was asymptomatic in 84 per cent of the patients and in 73.9 per cent the cervix was norma! to visual inspection. 5. Detection was accomplished by vaginal smears (predominantly Class III) in 81.1 per cent of the cases and by punch biopsy in 11.5 per cent. 6. The incidence of complications following diagnostic conization during pregnancy was 14.5 per cent, including one death. 7. Residual carcinoma was correlated with the histologic grade of the tumor and the trimester in which conization was performed. A correlation existed. 8. Seven microinvasive carcinomas ( 10 per cent) were encountered in this series and in 5 patients, planned therapy was carried out as in clinical Stage I lesions. 9. Unless childbearing functions were to be preserved, therapy consisted of total hysterectomy. Conservation of the ovaries depended on the age of the patient. 10. If complications following definitive therapy are to be minimized, the time relation factor between diagnostic postpartum conization and hysterectomy should be considered. 11. Two deaths in this series were not the direct result of the disease process itself. 12. Cytologic follow-up in this series indicates no vaginal recurrences to date.

REFERENCES

1. Beecham, C. T., and Andros, G. J.: Obst. & Gynec. 16: 521, 1960. 2. Bickenbach, W., and Soost, H. J.: Acta cytol. 6: 163, 1962. 3. Bottomy, R., and Boyd, R. A.: South. M. ]. 54: 584, 1961. . 4. Boyd, J. R, Royle, D., Fidler, H. K., and Boyes, D. A.: AM. ]. OasT. & GYNEC. 85: 322, 1963. 5. Carter, B., Cuyler, W. K., Kaufmann, L. A., Thomas, W. L., Creadick, R. N., Parker, R.

603

6. 7. 8. 9.

T., Peete, C. H., Jr., and Cherny, W. B.: AM. J. 0BST. & GYNEC. 71: 634, 1956. Decker, W. H.: AM. J. OasT. & GYNEC. 72: 1116, 1956. Diddle, A. W., Sholes, D. M., Jr., Hollingsworth, J., and Kinlaw, S.: AM. J. 0BST. & GYNEC. 78: 582, 1959. Dilworth, E. E., and Maxwell, G. E.: AM. J. OasT. & GYNEc. 84: 83, 1962. Epperson, J. W. W., Hellman, L. M., and Galvin, G. E.: AM. J. 0BST. & GYNEC. 61: 50, 1951.

604

November 1, 1964 Am.]. Obst. & Gynec.

Boutselis and Ullery

10. Fennell, R. H., Jr.: Cancer 8: 302, 1955. 11. Ferguson, J. H., and Brown, G. C.: Surg. Obst. & Gynec. 111: 603, 1960. 12. Fidler, H. K., and Boyd, J. R.: Cancer 13: 764, 1960. 13. Fricdell, G. H., Hertig, .A•• T., and Young, P. A.: A. M. A. Arch. Path. 66: 494, 1958. 14. Frick, H. C., Janovski, N. A., Gusberg, S. B., and Taylor, H. C., Jr.: AM. ]. 0BST. & GYNEC. 85: 926, 1963. 15. Funk-Brentano, Paul: Gym<:c. et obst. 59: I!!~

J.l,

1

n.cn

1::1UV.

16. Galvin, G. A., and TeLinde, R. W.: AM. ]. OasT. & GYNEC. 57: 15, 1949. 17. Greene, R. R., and Peckham, B. M.: AM. ]. OasT. & GYNEC. 75: 551, 1958. 18. Gusberg, S. B., and Marshall, D.: Obst. & Gynec. 19: 713, i962. 19. Hertig, A. T., and Young, P. A.: AM. ]. 0BST. & GYNEC. 64: 3, 1952. 20. Huey, L. W., Jr., Large, H. L., Jr., and Kemmelsteil, P.: AM. J. OasT. & GYNEC. 68: 761, 1954. 2i. Laird, T. K.: Am. Surg. 23: 222, i957. 22. Moore, J. G., Morton, D. G., Applegate, ]. W., and Hindle, W.: AM. J. 0BST. & GYNEC. 81:1175,1961. 23. Murphy, E. J., and Herbut, P. A.: AM. J. QllST. & GYNEC. 59: 384, 1950. 24. Mussey, E., and Soule, E. H.: AM. ]. OasT. & GYNF.C. 77: 957, 1959. 25. Osband, R., and Jones, W. N.: AM. ]. OasT. & GYNFC. 83: 599, 1962.

26. Parker, R. T., Cuyler, W. K., Kaufmann, L. A., Carter, B., Thomas, W. L., Creadick, R. N., Turner, V. H., Peete, C. H., Jr., and Cherny, W. B.: AM. J. 0BST. & GYNEC. 80: 693, 1960. 27. Peightal, T. C., Brandes, \A/. \A/., Crawford, D. B., Jr., and Dakin, E. S.: AM. ]. OasT. & GYNEC. 69: 547, 1955. 28. Petersen, Olaf: AM. J. OasT. & GYNEC. 72: 1063, 1956. 29. ~;rbo,r~~.L. A., and Plutowa, A.: Cancer 12: L;O.J,

!~JJ.

30. Pund, E. R., and Auerbach, S. H.: J. A.M. A. 131: 960, 1946. 31. Regan, J. W., and Hamonic, M. ].: Cancer 9: 385, 1956. 32. Richardson, H. L., and Thiersch, J. B.: Cancer 12: iO, 1959. 33. Riva, H. L., Hefner, J. D., and Kawaski, D. M.: Obst. & Gynec. 17: 525, 1961. 34. Schulman, H., and Ferguson, J. H.: AM. J. OasT. & GvNEC. 84: 1497, 1962. 35. Smith, G. V., and Pemberton, F. A.: Surg. Gynec. & Obst. 59: i, i954. 36. Thomson, ]. B., and Tosh, R. H.: AM. J. 0BST. & GYNEC. 84: 98, 1962. 37. Wespi, H.: New York, 1949, Grune & Stratton. 38. Young, P. A.: Am. J. Roentgenol. 79: 479, 1958. 39. Young, P. A., Hertig, A. T., and Armstrong, D.: AM. J. OBsT. & GYNEC. 58: 867, 1949.

Discussion DR. DANIEL G. MoRTON, Los Angeles, California. I was much impressed by the information contained in Table I in which a striking increase in the incidence of in situ cancers and a consequent decrease in the number of invasive growths were noted to have occurred in recent years. For the nonpregnant patients, the figures were GO per cent invasive versus 40 per cent in situ in 1962, as compared with 80 per cent and 20 per cent, respectively, as recently as 1957. For pregnant patients in 1962, 95 per cent were in situ lesions. A similar change has been occurring in our own clinic over the period of the last 9 years and in clinics throughout the world. This can only mean that the disease is being discovered at a much earlier and more easily curable stage than formerly and, as a result, there has, indeed, been a significant drop in the mortality from cervical cancer. The vaginal smear is largely responsible, both because it is a good method of detecting cervical cancer in

its early nonclinical stages, and also because it has made both doctors and patients aware of the possibilities of early detection. Dr. Ullery and his colleagues observe that the best method of making the definite diagnosis of intraepithelial cancer of the cervix is the cone biopsy, because it is the only way of obtaining adequate tissue for study short of hysterectomy. We certainly agree. However, we would like to have had some clarification of the size of the cone. There are small superficial cones and there are rather extensive cones, and there are many variations in size in between. Does he employ the same type of cone in pregnant as in nonpregnant patients, and, if so, how extensive is it? We have been afraid to employ a cone of the same extensiveness in both groups, since the apex of our cone biopsies in nonpregnant patients is almost at the internal os which might cause abortion in the pregnant woman. Therefore, we favor a more superficial cone

Volume 90 Number 5

lntraepithelial carcinoma of cervix in pregnancy

during pregnancy, even though we realize that a lesion high in the canal, which is rather rare, might be missed. Should there be such a case, we doubt if the lesion would be more than minimal in these asymptomatic subclinical cases and, thus, it would be of little significance. Judging from the fact that Dr. Ullery reports residual cancer after cone biopsy in 59 per cent of his cases, we feel that his cones must be srnall since rnost others report a much

lower incidence of residual cancer. But even the average figure of one third with residual cancer is not consistent with the good cure rate of those who treat patients by conization only. While I do not advocate conization as definitive treatment for in situ cancer except in special circumstances, Krieger's results have been excellent. In 22 cases at the UCLA Clinic, the cone biopsy resulted in rather severe hemorrhage in 3 patients, necessitating transfusions, but no pregnancies were interrupted. We agree that conization should be repeated post partum. Dr. Ullery does not mention some of the problems that we have encountered, such as nt>gative cones and smears post partum. In 8 of our 22 cases, no cancer was found post partum and smears have remained negative. All but one of these women has been followed and 2 have had subsequent pregnancies and delivt>ries. The question is, "Should a rigid attitude of treatment by hysterectomy, regardless of negative findings post partum, be maintained or not?'' We think not, hut a final decision in any one case might be influenced hy other factors also, surh as age and parity. Dr. Ullt>ry speaks of the importance of proceeding to hysterectomy after diagnosis by cone biopsy either immediately, that is within 36 hours, or waiting for 6 to 8 weeks in order to avoid the threat of serious infection. We agree heartily and subscribe to this modus operandi and think it deserves special emphasis. Another point of frequent discussion with respPct to treatment concerns the possible advisability of cesarean section followed by immediate hysterectomy, the section being per-

formed because of a previous one, because of development of a fortuitous obstetrical indication, or to avoid the massaging action of delivery through a cervix which might ~;till contain cancer; the hysterecton1y being performed because it would make a second operation unnecessary, would be convenient, and would provide the usual form of treatment anyway. I daresay that 9 out of 10 times such treatment would be very

605

satisfactory, but I doubt if it is wise policy as a rule, because one does run the risk of having overiooked an eariy invasive lesion, missed by the small cone and, on the other hand, one might often remove the uterus unnecessarily. We have treated only 2 patients in this manner. Finally, I believe that radical operation is unnecessary for microinvasive cancer of the cervix. We treat these patients as we do those v,rith purely in situ lesions. Thus far vve have had no reason to regret this policy, although it is possible that the simple hysterectomy and vaginal cuff should he accompanied by pelvic lymphadenectomy. DR. GERALD A. GALVIN, Baitimore, Maryiand. Three maxims evolve from Dr. Ullery's theses: ( 1) Invasive cancer is a preventable disease; ( 2) carcinoma in situ has the same significance in the pregnant as in the nonpregnant cervix; and ( 3) cytologic study of the pregnant cervix is an essential component of the prenatal examination. The reported incidence of carcinoma in situ associated with pregnancy of 0.1 per cent deserves further clarification. This incidence is computed on the basis of over 63,000 deliveries during a 23 year period, yet it has been only during the last 6 years of this study that routine cytologic screening of the pregnant cervix has been employed and, during this 6 year interval, 63 of the author's 69 cases were detected. Our experience at the Johns Hopkins Hospital parallels that of Dr. Ullery. In the 5 years preceding our adoption of the routine cytologic screening of the pregnant cervix in 1959, we had detected only 3 cases of carcinoma in situ, while in the period 1959 to 1963 we have encountered this lesion 37 times. This point is mentioned not to quibble with the essayist but rather to re-en1phasize the importance of routine prenatal cytologic study and to agree with Carter and his co-workers that the incidence of carcinoma in situ is the same in the pregnant and the nonpregnant cervix. Stressing this point, one finds it remarkable that our speaker is abie to report 68 cases of carcinoma in situ associated with pregnancy deiPcted on one obstetrical service in a 6-year period, when less than 10 years ago the largest individual series, 19, was that reported hy Peckham and Greene, and from the world literature these authors were able to collect only 122 cases.

Of the author's cases, 81 per cent have been detected by cytologic examination, 84 per cent of these being reported as Class III or suspicious of malignancy. In all of these cases the punch

606

Boutselis and Ullery

biopsy was bypassed and conization carried out immediately. To us, conization continues to be a respected procedure, one that, with its attrndant hospitalization and anesthesia is, to say the least, inconvenient to the patient and one that, particularly in pregnancy, is accompanied bv significant complication. It always has been our practice to subject the patient with a suspicious or positive smear initially to cervical biopsy and to reserve conization for those in whom the biopsy discloses d,~finite or suspected carcinoma in situ. In this manner we have spared from conization the patient with a false positive or suspicious smear, the patient who shows only a minor atypia, as well as the occasional case that shows invasion. In this connection one would be curious to know how many of the author's cases subjected to conization failed to reveal carcinoma in situ or marked atypia. The author is able to show a definite relationship between the histologic grade of the le~ion as well as the trimester of pregnancy in \vhich conization is carried out \Vith residual lesion following delivery. These, indeed, are factors. Ho"''ever, the most important factor is the pregnancy itself, as a cone carried out during pregnancy ran never be as extensive or as satisf) ing as that carried out during the nonpregnant state. All of our patients, unfortunately, were not coned during pregnancy. Initially, we relied completely upon our biopsy to exclude invasion, and delayed conization until the postpartum state. Of 28 patients coned during pregnancy, residual tumor was found in 18; whereas of the 12 that were coned only in the postpartum state, only 2 showed residual tumor, 64 per cent as compared to 16 per cent. The author reports that 5 cases of microinvasion were treated radically. While no one can question the adequacy of this treatment, our own experience prompts us to ask whether such extensive treatment is necessary or justified. In well over 500 cases of carcinoma in situ dating back to 1942, we have encountered microinvasion in 32 instances. We have treated these 32 cases with conservative hysterectomy and have had no reason to regret this therapy as \ve have had no recurrences in this group. It is our opinion that with mature clinical and histologic appraisal, the microinvasive lesion can and should be treated the same as carcinoma in situ. This excellent treatise and equally excellent presentation prompt one query: since 18 per cent of the cervices coned both before and after

Am.

:\f ovember I, 1964 J. Obst. & Gyncc.

delivery still showed residual tumor, how extensive is the conization carried out by Dr. Ullery:' DR. jASON H. CoLLINs, New Orleans, Louisiana. Drs. Ullery, Boutselis, and Vorys have presented to us the results of a 6 year program in a university hospital. The sharp transition noted in 195 7 is not surprising. Women under the age of 30 years constitute about one third of this and other series of cases of intraepithelial cancer (Table I). In addition, we are seeing more reports of intraepithelial carcinoma of the cervix in women less than 20 years of age. These observations are convincing that a vaginal smear should be made, regardless of age. A notation of "clean cervix" or ''suspicious" lesions are terms we should discard; "no lesion present" is preferable. Any lesion on the cervix, vagina, or vulva must be biopsied. To rely on visual appearance in deciding whether a given lesion should or should not be biopsied is hazardous, even if smears are made routinely. The admonition that diagnosis is established by tissue study and not by smear only is, of course, well taken. The relative incidence of cancer in Class III smears will vary in every institution. Suffice it to say that we have a decisive area where sufficient warning is given the clinician to continue studying the patient and, if necc'sary, intensify the program of search. Conization and biopsy of the cervix are not without danger to the mother or fetus. A respectable incidence of complications exists for everyone. We agree that with sufficient reason, whether clinical or by smears or biopsy, conization must be done. It must also be realized that conization of a pregnant woman's cervix will not, under average conditions, be as wide or as deep as conization done on the nonpregnant uterus. This is progressively truer the closer to term

Tabie i. Intraepithelial carcinoma of cervix in pregnancy age 30 II (No.) ~~ses II No.age 30% IIO~er No. %

Under

HosPitai

Charity in New Orleans ( 1955-63)

Baptist in

Ne,,v Orleans ( 1958-63)

Total

I

I

I

I

I

:l2

12

11

+

43

16

37.5

36.+

37

20

62.5

7

63.6

27

6.1

Volume 90 Number 5

lntraepithelial carcmoma of cervix

Table II. Intraepithelial carcinoma of cervix in pregnancy Management Cesarean section Abdomi- Vaginal hysterec- nal hys- hysterec... 1 u"""J-.~·~ VJ}'t.l.oUI>

~L

Charity Baptist Total

I

ton2'Y

ID't".D/"fn'YYlllo

1"~'"''-'"V""f

I

Total

f/1'»1<\! "OJ""'.f

3 1

2

23

3

18 2

4

5

20

29

---

6

Hysterectomy not done-more pregnancies desired Incidental in cesarean section or postpartum hysterectomy specimen

9 5 43

Total

Table III. Intraepithelial carcinoma of cervix in pregnancy Residual tumor in hysterectomy specimen Residual tumor Hospital

No.~-~

Charity Hospital New Orleans -No cone in pregnancy Charity Hospital New Orleans -Cone in pregnancy or 22 post partum Baptist Hospital New Orleans -Cone in pregnancy or 6 Total

29

0

0

8

36.3

3

50

11

36.7

the pregnancy has progressed. We are not surprised, therefore, at the incidence of residual tumor found in this series in postpartum conization specimens or in the hysterectomy specimen (Table II). We agree that intraepithelial carcinoma is a valid diagnosis in pregnancy; however, we have observed that some patients do not have residual tumor after delivery, and a sufficient number who have, for some reason or other, have delayed their return for follow-up visits and when reconed or operated upon for removal of the uterus, they did not have residual neoplasm. It is of interest to ask Dr. Ullery the incidence of residual tumor in the patients who waited 4 to 6 months for vaginal hysterectomy. Finally, we prefer to perform vaginal hysterectomy ( 80 per cent of our series), unless

In

pregnancy

607

contraindicated by obvious intrapelvic factors (Table III). We also prefer a cuff wider than 2 em. We also regard any type of invasion"micro," "superficial,"' or "minimal"-as invasive cancer, and we treat those patients the same as any other with invasive carcinoma. DR. RicHARD W. TELINDE, Baltimore, Maryland. I have often thought of the millions of words said about carcinoma in situ, and I have sometin1es thought that nothing could be added, and then I hear this stimulating paper by Dr. Ullery and realize that this is not true. This is a live subject, a subject on which we have not crystallized our ideas by any means. There have beeu differences of opinion rnentioned by the various discussants this morning. I am tempted to say a few words in regard to Dr. Ullery's findings and suggestions, most of which I agree with, as I believe most of us do. He said that 8i per cent of these patients had no symptoms, and I would say that no cases of carcinoma in situ have symptoms. If there are symptoms from carcinoma, the lesion is no longer situ, and if there are symptoms associated with intraepithelial carcinoma, they are from chronic cervicitis and not from carcinoma in situ because, by definition, the lesion is a nonulcerative one and strictly on the surface or in the glands. That may be a small point to make but it should be emphasized. I think we have gone a little bit overboard on the matter of conization. It is true we usually get more information from a wide cone than from biopsy, but just as there are cones and cones so there are biopsies and biopsies. I can take several biopsies which may be just as good as some cones, and sometimes I think it is better to do this. For example, I had a patient, a 72-year-old woman, with a positive smear and a very small senile cervix. I did a conization. I did not operate upon her within 48 hours, as is our custom, but did so 4 or 5 days later, performing a vaginal hysterectomy. There was so much reaction from the cone that, on dissecting the bladder free, we broke right into the cervical canal. We found carcinoma in situ in the cervical canal on microscopic examination. That woman would have been much better off with only biopsy for confirmation. In other words, a small postmenopausal cervix is not a good candidate for a conization. You can get as much information from a thorough series of biopsies usually as from a superficial cone. Why biopsy when we plan on a cone anyway in the usual case? There is one good reason: If

608

November 1. 1964 Am . .1. Obst. & Gynec

Boutselis and Ullery

you do a biopsy and find invasive carcinoma which puts this in Stage I, she should be treated with irradiation. Our irradiation complications after wide cone were greater than in the cases in v:hich no cone had been done. I would not proceed directly with a cone on a Class III smear. I would repeat the smear. If you proceed directly with a cone in such cases, you will do many unnecessary ones. I think this is particularly true in pregnant women in which the complication of hemorrhage from the cone is considerable, as well as the possibility of interference with the pregnancy. As for microinvasion, I agree with Dr. Morton. After all, there is microinvasion and microinvasion. If we have just a minimal microinvasion, we have treated the cases as we would in carcinoma in situ and the patients have remained well. If there is considerable microinvasion, we consider the case as stage I and irradiate. As for recurrences, we have had 8 in 400 cases. In the beginning we did not always use the Schiller test preceding surgery, but that should always be done to determine the extent of the lesion and guide one as to the amount of vagina to be removed. Of 400 cases of carcinoma in situ treated by hysterectomy, we have lost only 2 cases that we diagnosed as carcinoma in situ preoperatively. One patient with metastatic carcinoma died rather soon. The other woman had a recurrence the size of a golf ball beside the rectum. I opened the abdomen, but the condition was inoperable because it was part of the rectal wall. We have treated it with irradiation, but it is not responding. The lesion is growing and she will die. If further evidence of the relationship of preinvasive cervical cancer to the invasive disease is required, these 2 cases furnish such evidence. After all, that is the crux of the whole situation and, therefore, I cite these 2 cases of recurrence. DR. JoHN G. BouTSELis,* Columbus, Ohio. Dr. Eastman, Fellows, and Guests: During the next 3 minutes I would like to bring up-to-date the presentation made by Dr. Ullery on intraepithelial carcinoma of the cervix in pregnancy. As will be noted in the first slide, between 1940 and 1962, there were 69 patients with carcinoma in situ of the cervix associated with pregnancy. An additional 18 patients were encountered dur-

*By invitation.

Table I. Intraepithelial cervical carcinoma Patients 19401962 \ (No.)

I 1963j

1964 (No.)

1940-1964 No.

In pregnancy Invasive In situ

56 69

4 18

60 87

Not pregnant Invasive In situ

1,570 350

104

1,674 452

10~

% 40.8 59.1 73 23

ing the next 18 months, giVmg an up-to-date total of 87 cases (59.1 per cent). During similar periods of time, invasive carcinoma of the cervix in pregnancy was 56 + 4 = 60 ( 40.8 per cent). The per cent ratio in the nonpregnant patient is 73 per cent for invasive carcinoma and 23 per cent for carcinoma in situ (Table I). I am reasonably sure that the discrepancy in ratios between obstetric and gynecologic patients is best explained by the ages of the two groups. The statistical data noted in Table II at the top of the opposite page remain basically unchanged from that shown by Dr. Ullery and any additional remarks at this time would be repetitious. DR. ULLERY (Closing). Dr. Morton, we agree about the size of the cone. We cannot take the same size during pregnancy as post partum. During pregnancy, it is a more superficial cone. It is not completely satisfactory, but we have to be conservative and try to find out what we can. I believe that Dr. Morton also asked about the negative conizations in the postpartum period. In general, I might say that if the diagnosis of an in situ lesion is made during pregnancy, it is still in situ after that pregnancy is terminated. Of the 69 patients we saw showing a positive cone in the antepartum period, 54 had hysterectomy and of those, 10 who did not show any positive cones on postpartum examination showed residual tumor after the uterus was removed. This would make me think that we will not always find a second cone that is positive; however, once we make the diagnosis of in situ by microscopic examination, we adhere to it. I am sure there will be a difference of opinion on this subject. We used the year 1940 for the beginning of our series because this was the initiation of our obstetrical and gynecological clinics at Ohio State

Volume 90

lntraepithelial carcinoma of cerv1x

1n

pregnancy

609

~umlw1;;

Table II.* Intraepithelial cervical carcinoma in pregnancy Patients

1940-1962

1963-1964

(l\lo.)

(l\fo.)

I+

Clinical impression cervix-normal

58 51 58

+. Detection and diagnosis Detection by smear Diagnosis by conization 5. Post cone complications-intrapartum 6. Treatment by hysterectomy 7. Microinva~ivr carcinoma-7 cases

56 68 10 5+ 7

1. Chief complaint-asymptomatic •)

3. Distribution of Papanicolaou smear-Class III

- - - ---·--·· - - - *This tablt' is pan of the discussion of Boutsrlis.

University. Sixty-eight cases were seen in the later phases, and I can assure you the emphasis is on the latrr years when we have brcome sensitized to the Papanicolaou smear. The marked differencr in numbers is due to the fact that we had a cancer survey project in Columbus from 195li to 1959. E\ny patient in Franklin County and Columbus, Ohio, who could be induced to be •·xamined, rrceiwd a Papanicolaou smear as part of the cancer study project. I believe that is why we pick('d up a number of in situ lesions. Every single patient in our clinic had a Papanicolaou srnrar l'ach trimester, and we found some positives in the third trimester who were not positive at first. I agn'e with Dr. Morton and Dr. TeLinde that we do not have the ultimate answer to the

12 15 15 16 2 11 ()

1940-1964

1

--·-··--····-·-·-···--1 1

No. 72 63 7".1 71 8+ 12 65 7

I

~·~~

82.5 72.+ 83.9

81.6 98.7 1:1.7 7~.6

8.0

treatment of microinvasive lesions. We have follm,·pd a program that, if thf' lesion was invasive, it was invasive and we tr<'ated it a~ a Stage I lesion. Of coursf', that is opPn to arbitration, and certainly Dr. TeLinde's and Dr. Galvin's sf'rics would make me lean to the fact that their treatment is of great value. I cannot answer Dr. Collin's qurstion about the difference lwtwppn hystrrectorny in thf' second month and in the sixth month. vVe do not have statistirs on this. We did total abdominal hystrrrctorny abont 2 months after drlivery and vaginal hysterectomy 6 months after drliwry. However, that does not matter too much because, if it takes approximately 7 to 10 years for an in situ Je~ion to change to invasive, 4 months sho11ld not make much ditTrn~nce.