A ten-year retrospective study of cervical conization followed by hysterectomy for various grades of cervical intraepithelial neoplasia

CLAYTON T. SHAW, D 0 Omaha, Nebraska HEINZ 0. OSTERHOLZER, m D Philadelphia, Pennsylvania DAVID M. EVANS, m D Wiesbaden, West Germany

They are: (1) visualization of the entire lesion; (2) A ten-year retrospective study of expertise in colposcopy; (3) exclusion of invasive seventy-seven patients from January carcinoma by punch biopsy; (4) adequate cytologic 1971 to December 1980, at the Tripler and colposcopic follow-up; and (5) endocervical Army Medical Center, who curettage. underwent cold knife conization for Conization as a modality, however, is considered cervical intraepithelial neoplasia a definitive therapy for the removal of dysplastic (CIN) followed by hysterectomy, was tissue and is required if the colposcopic examina- performed to determine the tion is inadequate or the endocervical curettage is predictive value of cone clearance positive for CIN. Kolstad stated that conization is regarding residual CIN. Forty-four of the method of choice for carcinoma in situ. He the seventy-seven patients had found a 97 percent cure rate with 1 percent pro- clear cone margins but seven of these gressing to invasive carcinoma and 2 percent to re- forty-four had residual CIN at the current carcinoma in situ. Caglar 9 also studied the time of hysterectomy. This accuracy of the cervical cone. He performed coniza- represented a 15.9 percent tion in thirty-three patients and immediately fol- recurrence rate. Thirty-three patients lowed that procedure with a vaginal hysterectomy. had margins involved at the time of He found that in three patients (9 percent) of the conization, but only fourteen of these uteri specimens had the same diagnosis as the con- (42.4 percent) demonstrated residual ization. Jones" reported recurrence rates of 3.8 to CIN on hysterectomy specimen. 9.4 percent from a number of studies between 1970 Twenty-eight of the seventy-seven and 1976. An earlier report from Tripler Army were noted to have at least one Medical Center also demonstrated a similar cure concurrent gynecologic condition. rate." Ostergard," however, recently found that The efficacy of cold knife conization 16 percent of patients with clear cone margins and as a "cure" for CIN as generally 34 percent with involved margins had residual stated in the literature is not CIN. He concluded that a prediction cannot be supported by this paper. made as to recurrence based on cleared margin and that a failure rate is closer to 16 percent in skilled hands. The question then arises—Is coniza- tion as a definitive therapy really as good as ori- ginally perceived? The purpose of this study was to determine the Cervical intraepithelial neoplasia (CIN) is of ma- predictive value of cone clearance regarding resid- jor concern to the gynecologist because of its pre- ual CIN. It was the authors desire to determine cancerous nature. Since this disease is a contin- the following: (1) the cone pathology; (2) the num- uum and may well lead to invasive cancer, it is the ber of cone slides; (3) the cone margins; (4) hyster- obligation of the gynecologist to diagnose, treat, ectomy pathology for residual CIN; (5) the number and closely follow patients with CIN. Whether a of hysterectomy slides; and (6) concurrent gyneco- gynecologist utilizes cryosurgery, carbon dioxide logic pathology at the time of hysterectomy. laser therapy, or electrocoagulation diathermy, he can expect a cure rate of from 88 to 95 percent," Materials and methods provided that he follows the pretreatment evalua- A retrospective study of seventy-seven patients tion standards set down by Jordan and Chanen.7 who underwent conization for CIN from January

Ten-year retrospective study of cervical conization followed by hysterectomy for various grades of cervical intraepithelial neoplasia 994/65 TABLE 1. RELATIONSHIP OF AGE, CLEAR CONE MARGINS, INVOLVED terval of 12 weeks between conization and hyster- ENDOCERVICAL CONE MARGINS, INVOLVED ECTOCERVICAL CONE ectomy. MARGINS, AND SEVERITY OF CIN. The charts of the seventy-seven patients who Clear Involved Involved had a conization as well as hysterectomy were re- cone endocervical ectocervical trieved. These charts were examined for the afore- margin margin margin mentioned criteria to determine if conization for Age CIN I II III CIN I II III CIN I II III these patients supported the general literature or 25-29 7 7 1 Ostergards study. There were an average of 15 mi- 30-34 1 1 18 2 3 3 croscopic sections for conization specimens and an 35-39 2 7 1 1 5 2 average of 12 microscopic sections for the hysterec- 40-44 3 1 2 1 tomy specimens. All of the cone slides in the study 45+2– – — 1 1 5 _ _ Totals 6 2 36 2 4 21 1 5 were examined for margin clearance by the au- thors. The cone specimen was then matched with TABLE 2. RELATIONSHIP OF AGE, CLEAR CONE MARGIN WITH NO RE- SIDUAL CIN, AND CLEAR CONE MARGIN WITH RESIDUAL CIN AT THE its corresponding hysterectomy specimen to deter- TIME OF HYSTERECTOMY. mine the efficacy of conization in the treatment of Clear cone margin CIN. Residual CIN Clear cone margin ,------A----, Results Age No residual CIN CIN I II III Table 1 shows that forty-four of the seventy-seven 25-29 5 2 patients who had conization demonstrated clear 30-34 16 3 1 35-39 8 1 cone margins; thirty-six of these forty-four (81.8 40-44 6 percent) were diagnosed as having CIN III. There 45+ 2 — were twenty-seven patients with an involved en- 37 7 Totals docervical margin, twenty-one of whom (77.7 per-

TABLE 3. RELATIONSHIP OF AGE, INVOLVED CONE MARGINS WITH cent) had CIN III. Six patients had involved ecto- NO RESIDUAL CIN, AND INVOLVED CONE MARGINS WITH RESIDUAL cervical margins, five of whom (83.3 percent) had CIN AT THE TIME OF HYSTERECTOMY. CIN III. The total number of patients with in- Involved cone margin volved cervical cone margins was thirty-three Residual CIN Involved cone margin ,----"------, (42.8 percent) and of these thirty-three, CIN III Age No residual CIN CIN I II III was found in twenty-six patients (78.7 percent). 25-29 6 1 1 • Table 2 shows that in this population, seven of 30-34 6 2 the forty-four patients (15.9 percent) who had clear 35-39 3 1 5 cone margins had residual dysplasia at the time of 40-44 1 45+ 3 1 3 hysterectomy. When these seven were reviewed, it Totals 19 14 was determined that six of the seven had CIN III and one had CIN II diagnosed at the time of coniza- TABLE 4. COMPARISON OF AGE, HYSTERECTOMY SPECIMENS WITH tion. This residual rate is consistent with Oster- NO RESIDUAL CIN AND WITH RESIDUAL CIN. gards study which demonstrated a 16 percent re- Specimens with residual CIN sidual rate. Specimens without Table 3 shows that fourteen of the thirty-three Age residual CIN CIN I II III patients (42.4 percent) who had involved cone mar- 25-29 11 1 2 1 gins continued to have residual CIN at the time of 30-34 22 3 3 hysterectomy. When these fourteen were re- 35-39 11 1 6 40-44 7 viewed, it was determined that ten of the fourteen 45+ 5 1 3 had CIN III on both the cone and hysterectomy Totals 56 21 specimen, one had CIN III on the cone and CIN II at hysterectomy, one had CIN H on the cone and CIN III at hysterectomy, and one had CIN III at 1971 to December 1980 and followed with hyster- cone and CIN I at hysterectomy. This residual rate ectomy at, the Tripler Army Medical Center was for involved cone margins (42.4 percent) is higher performed. These seventy-seven represented the than Ostergards study which demonstrated a 34 population of patients who had a cold-knife coniza- percent residual rate. tion and were followed by hysterectomy, as deter- Table 4 shows that there were 56 hysterectomy mined by computer files at the center. specimens that had no residual CIN. These 56 in- Three patients had their hysterectomy immedi- cluded 37 specimens with prior clear margins as ately following conization and two had a hysterec- well as 19 specimens that were involved at the tomy nearly two years following their conization. time of conization. There were 21 hysterectomy The other seventy-two patients had an average in- specimens which contained residual CIN. These 21

295/66 Dec. 1983/Joumal of AOA/vol. 83/no. 4 included 14 specimens that had involved margins TABLE 5. CONCURRENT GYNECOLOGIC CONDITIONS FOUND IN 77 PA- at the time of conization which remained involved TIENTS WHO UNDERWENT HYSTERECTOMY FOR VARIOUS GRADES as well as 7 specimens that were clear at the time OF CIN. of conization but demonstrated CIN at the time of Number Condition hysterectomy. The total residual CIN rate was 10 Leiomyomata 27.3 percent (twenty-one of seventy-seven pa- 5 Adenomyosis and leiomyomata tients). There were 13 hysterectomy specimens 3 Adenomyosis 2 Endometriosis that demonstrated CIN III. This was 61.9 percent 1 Hydrosalpinx of those specimens with residual dysplasia. 1 Adenomyosis and acute salpingitis Table 5 shows that there were twenty-eight pa- 1 Adenomatous hyperplasia 1 Chronic pelvic inflammatory disease tients out of the seventy-seven in the study (36.4 1 Adenomatous change with atypia and percent) who demonstrated at least one concurrent leiomyomata gynecologic condition. Pure leiomyomata uteri or 1 Benign cystic teratoma 1 Endocervical polyp concurrent adenomyosis accounted for fifteen pa- 1 Stress urinary incontinence tients. There were a variety of other conditions ac- counting for the other thirteen patients. No carci- Ostergard, we feel that cone biopsy should not be nomas were encountered. considered the definitive therapy for CIN.

Discussion 1. Townsend, D.E.: Cryosurgery for CIN. Obstet Gynecol Sur y 34:828, Nov 79 Treatment of CIN can be accomplished by a num- 2. Ostergard, D.R.: Cryosurgical treatment of cervical intraepithelial ber of outpatient modalities. However, cold-knife neoplasia. Obstet Gynecol 56:231-3, Aug 80 conization has been considered a more definitive 3. Popkin, D.R., Scali, V., and Ahmed, M.B.: Cryosurgery for the treat- ment of cervical intraepithelial neoplasia. Am J Obstet Gynecol and acceptable method for treatment. One reason 130:551-4, Mar 78 is that the cure rates obtained were as high as 97 4. Kaufman, R.H., and Irwin. J.F.: The cryosurgical therapy of cervical intraepithelial neoplasia III continuing follow-up. Am J Obstet Gynecol percent. Ostergard 12 stated that an 84 percent 131:381-8, Jun 78 cure rate or 16 percent residual CIN rate was a 5. Sevin, B., et al.: Invasive cancer of the cervix after cryosurgery. Ob- more realistic figure when cone margins were stet Gynecol 53:465-71, Apr 79 6. Jordan, J.A.: Laser treatment of cervical intraepithelial neoplasia. clear. Further, he pointed out that if the cone mar- Obstet Gynecol Sury 34:831, Nov 79 gins were involved, these patients could expect a 7. Chanen, W.: Electrocoagulation diathermy treatment of cervical in- 34 percent residual CIN rate. traepithelial neoplasia. Obstet Gynecol Sury 34:829-30, Nov 79 8. Kolstad, P.: Conization treatment of cervical intraepithelial neopla- In reviewing the seventy-seven patients in this sia. Obstet Gynecol Sury 34:827, Nov 79 study, a 15.9 percent residual CIN rate for patients 9. Cagier, H., and Delgando, G.: Colposcopically directed cone biopsies with clear-cone margins, and a 42.4 percent resid- in the management of cervical intraepithelial neoplasia. Obstet Gynecol 5:634-5, May 78 ual CIN rate for patients with involved cone mar- 10. Jones, H.W., and Buller, R.E.: The treatment of cervical intraepi- gins were realized. This supports Ostergards thelial neoplasia by cone biopsy. Am J Obstet Gynecol 137:882-6, Aug statement that cold knife conization may not be as 80 11. Shaw, C.T., Miyazawa, K., and Osterholzer, H.: A retrospective definitive a therapy for CIN as generally accepted. study of exfoliative cytologic evaluation, colposcopy, and conization fol- In this population all grades of CIN were repre- lowed by hysterectomy for various stages of intraepithelial neoplasia of the cervix. JAOA 82:405-9, Feb 83 sented. The high number of patients, thirty-three 12. Ostergard, D.R.: Prediction of clearance of cervical intraepithelial (42.8 percent), with involved margins is disturb- neoplasia by conization. Obstet Gynecol 56:77-80, Jul 80 ing, especially the six patients with involved ecto- cervical margins. While no residual CIN was Accepted for publication in July 1983. Updating, as necessary, has been done by the authors. This paper was presented at the found at the time of hysterectomy in 19 of the 33 Twenty-first Annual Meeting of the Armed Forces Seminar on involved cones, the clinician cannot depend upon Obstetrics and Gynecology held in Portland, Oregon, October 3- necrosis from surgery to complete this task. When 8, 1982. Opinions expressed in this article are those of the authors just the twenty-one patients who had CIN III at and do not necessarily reflect those of the Department of the the time of hysterectomy are considered, ten had Army, Department of the Air Force, or Department of Defense. involved cones with CIN III, one with CIN II, and two had clear cones with CIN III. It appears that At the time this paper was written, Dr. Shaw was chief resident in the Department of Obstetrics and Gynecology at Tripler the grade of CIN severity on a cone specimen Army Medical Center, Honolulu, Hawaii. Marshall Matthews, should be of most concern to the gynecologist. The M.D., was chairman of the department. Dr. Shaw is currently chief of the Department of Obstetrics and Gynecology at the number of patients with a concurrent gynecologic Ehrling Bergquist Hospital, Offutt Air Force Base, Omaha, Ne- condition (twenty-eight) is interesting and stress- braska. Dr. Evans was chief resident in pathology at Tripler es that a patient being followed for CIN should al- Army Medical Center; he is now a staff pathologist at the USAF Hospital, Wiesbaden, West Germany. Dr. Osterholzer ways have a complete gynecologic examination. was chief of gynecologic surgery at Tripler Army Medical Cen- Because of the small number of patients in this ter; he is now a fellow in reproductive endocrinology in Phila- series, it is impossible to draw firm conclusions delphia. from this study; however, taken with the report of Dr. Shaw, 11805 Gow Circle, Omaha, Nebraska 68133.

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