Microinvasive carcinoma of the uterine cervix: A clinical-pathologic study ALEXANDER SANFORD

SALL,

YOSHI

M.D.

PARK,

CHARLES

M.D.

MANGAN,

HUGH

M.D.

M.D.

TSUKADA,

ROBERT

JOHN

SEDLIS,

M.D.

SHINGLETON, A.

BLESSING,

M.D. PH.D.

Nm York, Neur York Of 265 patients accessioned to a study of microinvasive cardnoma of the cervix by participating institutions in the Gynecologic Oncology Group, 132 were rejected after preliminary review because of no evidence of invasion (99 patients), invasion in excess of 5 mm. (18 patients), inadequate conization (nine patients), and protocol violations (six patients). The data available for the 133 evaluable patients included clinical patient information, operative reports, narrative pathology reports, and microscopic slides. Tumor penetration was less than 2 mm. in 90 patients (67.5 per cent) and greater than 3 mm. in 21 patients (18 per cent). Lateral tumor extension was less than 4 mm. in 76 patients (57 per cent) and wider than 8 mm. in 29 patients (22 per cent). Extensive lateral spread was observed more frequently than deep penetration. Positive correlation was noted between the depth of penetration and lateral extension. Capillary-like space invasion by tumor was noted in 31 cases (23 per cent) and increased with depth of penetration. Lack of tumor differentiation occurred in patients with less than 1 mm. penetration more frequently than in those with deep penetration. A confluent pattern of tumor was observed more frequently with advanced depth of penetration and greater lateral spread. There was a strong correlation with residual tumor on hysterectomy specimen and capillary-like (CL) space involvement with deep stromal penetration and extensive lateral spread. No positive lymph nodes were observed in the 74 patients treated by radical hysterectomy and recurrence was noted in two patients with extensive CL space involvement. Conization specimens with surgical margins involved with cancer are inadequate for diagnosis of microinvasion and constitute a clear indication for management as a frankly invasive lesion. Simple hysterectomy may be the mode of therapy in patients with questionable invasion, with invasion less than 2 mm. in depth and 4 mm. in width, and without evidence of CL space invasion. Such conservative treatment is unwarranted if the conization margin is inadequate, if the margins are not clear, if invasion is deeper than 2 mm., if lateral spread is greater than 4 mm., or if tumor is present in the CLspaces. (AM. J. OBSTET. GYNECOL. 133:64, 1979.)

From the Gynecologic

Oncolofl

Group.

Supported by the following grant awards by the National Cancer Instatute, Department of Health, Education, and Weyaw: 2 RIO CA 12483-07, 2 RIO CA 12535-06, 2 RIO CA 19189.03,5 RIO CA 15977-02, and 2 RIO CA 12484. Received Rev&d .4rcrptrd

for publication April April

October

19. 1977

IO, I978 12, 1978.

Reprint requests: Dr. Alexander Sedlis, Department of Obstetrics and Gynecology, Neu York Medical College, 1239 Ffth Ave., NPW York, New York 10029.

7‘HIS

PRELIMINARY

REPORT

t-epI?SeUtS

an

evdUa-

tion of 265 cases diagnosed as microinvasive squamous cell carcinoma of the uterine cervix in various centers throughout the United States, participating in the Gynecologic Oncology Group (G.O.G.). The study was prompted by contradictory published information on the prognosis and treatment of microinvasive carcinoma and the lack of precise diagnostic criteria.‘-r The data on the 265 cases in this study included clinical abstracts, pathology reports, and histologic slides of the conization and the hysterectomy specimens. These data 0002.9378/79/01006~+

11601.1010

0

1979

The

C. c’. Mosby

Co.

Volume

133

Number

1

were evaluated with the use of consistent and uniform criteria with regard to the diagnostic accuracy, the extent of invasion, the morphologic pattern of the tumor on microscopic examination, and the lymph node involvement. A correlation of various pathologic data with the clinical course was attempted with a view to establish diagnostic and prognostic criteria for microinvasive carcinoma.

Material and methods The only requirement for including the 265 cases into the study was the diagnosis of microinvasi,ve squamous cell carcinoma made by the contributing institution’s pathologist. The choice of therapy was according to institutional preference: conization, simple hysterectomy, radical hysterectomy, or radiation therapy. Pathology specimens were processed according to the protocol guidelines of the G.O.G. The conization specimens were opened in a fresh state, flattened out on a piece of cardboard, and cut into sections 2 mm. thick, with a total of 12 to 20 sections per specimen. The cervical specimens from hysterectomy material were processed in a similar way, 10 to 20 sections 2 mm. thick obtained by slicing the specimen in a radial fashion. Upon enrollment into the study, patient data were sent to the G.O.G. headquarters. The data available for the study included the clinical patient information, the operative reports, the narrative pathology report of the operative specimen, and microscopic slides. Follow-up information about the subsequent clinical status of the patients was forwarded to the G.O.G. headquarters at six-month intervals. Excluded from the study were patients who had previous conization of the cervix, previous carcinoma of the cervix, ana nrevious or concomitant malignancy in other organs. Histologic slides were reviewed by a panel of pathologists selected among the institutions that participated in the study. Each specimen was examined by two pathologists who rendered independent opinions. In cases of disagreement among the reviewing pathologists, the case was examined by the G.O.G. referee pathologist (Dr. Henry J. Norris). Cases were accepted into the study after the preliminary pathologic examination if they fulfilled the criteria agreed upon by the investigators: (1) invasion of the stroma of no more than 5 mm. from the surface epithelium and (2) incisional margins free of tumor if only a conization specimen was available or, if the cone margins were involved, invasion of no more than 5 mm. on the subsequent hysterectomy specimen. Presence of tumor in the capillary-like (CL) spaces or confluent pattern did not disqualify the patient from the studv.

Microinvasive

carcinoma

Table I. Results of preliminary of microinvasive carcinoma

of uterine

cervix

65

review of 265 cases No.

Accepted in the study from the studyfor; No evidence of invasion Invasion in excess of 5 mm. Inadequate specimen Protocol violation (second primary, additional therapy without recurrence) Total excluded Total initially entered

133

Excluded

99 18 9 6 132 265

Table II. Microinvasive carcinoma of cervix: Depth of invasion and frequency distribution in 133 cases Depth (mm.)

1>2 >2 > 3 >3 > 4 (4

Total

I

No. of cases 50 40 22 16 5 133

I

7C’ 37.5 30 16.5 12 4 100

Table III. Microinvasive carcinoma of cervix: Lateral Extent of tumor and frequency distribution in 133 cases Lateral extnlt (mm.) cc2 >2468

Total

No. of cases 53 23 18 10 29

133

R’ 40 17 13.5 7.5 22

100

In addition, for the purpose of this review, the pathology material was further examined by two of the authors (A. S. and Y. T.). After the preliminary screening, the morphologic features of this tumor were considered. Depth of invasion. This was measured with an ocular micrometer that had been previously calibrated with a stage micrometer. The depth was defined as the distance between the epithelial surface and the deepest point of invading tumor in those cases where penetration originated from the surface epithelium. The epithelial surface, rather than the epithelial stromal junction, was selected as a starting point because it was sometimes difficult to judge the location of the dividing line between the intraepithelial tumor and the area of invasion. Another reason for measuring from the surface was that on occasion the epithelium was absent, destroyed by either trauma or infection. In those cases

January

Sedlis et al.

66

1, 1979

Am. J. Obstet. Gvnrcol.

was found proximating

useful as the only available means of apthe peripheral extent of tumor.

Results

Fig.

1. Tumor

in CL spaces.

Microinvasive carcinoma of cervix: Correlation between the depth of invasion and the lateral extent Table

IV.

fl

Microinvasive carcinoma of the uterine cervix: a clinical-pathologic study.

Microinvasive carcinoma of the uterine cervix: A clinical-pathologic study ALEXANDER SANFORD SALL, YOSHI M.D. PARK, CHARLES M.D. MANGAN, HUGH...
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