Objective
The purpose of this study was to determine posthysterectomy pathologic findings in patients with a preoperative endometrial sampling diagnosis of International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrial adenocarcinoma with a background of complex atypical hyperplasia (CAH).
Study Design
We reviewed 1423 consecutive cases of endometrial cancer to identify cases with a preoperative endometrial biopsy that demonstrated FIGO grade 1 endometrial adenocarcinoma. Final uterine pathologic findings were grouped into low- and high-risk based on FIGO and Gynecologic Oncology Group criteria.
Results
We identified 123 cases with a background of CAH and 367 cases without a background of CAH. FIGO grade in the hysterectomy specimen was more than FIGO grade 1 in 11 of 123 cases (8.9%) with a background of CAH, compared with 60 of 359 cases (16.7%) without a background of CAH ( P = .04).
Conclusion
An endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma with a background of CAH is more likely to correlate with final posthysterectomy grade than a diagnosis not arising with a background of CAH.
Endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women overall in the United States, with an estimated 40,100 new cases diagnosed annually. This high incidence rate is also evident in many other countries, with an estimated 136,000 new cases diagnosed worldwide in 2002. The International Federation of Gynecology and Obstetrics (FIGO) replaced an inaccurate clinical staging system with a surgically staged system in 1988. The importance of surgical staging was supported by the findings from a large prospective surgical-pathologic study in patients with clinical stage I and II endometrial carcinoma that was conducted by the Gynecologic Oncology Group (GOG). Extrauterine disease, which included pelvic and paraaortic lymph node metastasis, was found relatively frequently in this study. The risk of nodal metastasis was associated with both final pathologic FIGO tumor grade and depth of myometrial invasion. Multiple extrauterine findings were also associated with outcome. These findings led to the change in the FIGO staging system. FIGO stage I was subdivided based on depth of myometrial invasion; nodal involvement was designated as FIGO stage IIIC.
Many surgeons have not embraced complete surgical staging with lymph node removal, despite the noted risk of nodal involvement in clinically apparent stage I disease, especially if the preoperative endometrial sampling revealed a FIGO grade 1 adenocarcinoma. This may be due to a variety of factors such as surgeon’s familiarity with lymph node dissection techniques, the perceived low incidence of nodal metastasis, and concern over complications that included prolonged operative times. It has been estimated that lymph node dissections are performed in only 30% of patients with endometrial carcinoma. Preoperative tumor grading with intraoperative assessment of depth of myometrial invasion and histologic subtype is used frequently to decide whether lymph node dissection is necessary at the time of hysterectomy. Surgeons base this approach on extrapolation of data from various reports that describe the rates of nodal metastasis and therapeutic benefits of lymphadenectomy. This is not an accurate method of nodal risk stratification because almost all of those reports are based on final pathologic assessments of grade and depth of myometrial invasion.
A higher FIGO grade on final hysterectomy pathologic assessment will be diagnosed in 24% of patients with preoperative FIGO grade 1, combining results from published series. Intraoperative assessment of myometrial invasion is also an inaccurate predictor of the actual depth of myometrial invasion. The combination of both preoperative grade and intraoperative assessments of myometrial invasion has a low predictive value for final pathologic findings in the hysterectomy specimen.
The American College of Obstetricians and Gynecologists (ACOG) states that surgical staging may not be necessary in young women with grade 1 endometrioid adenocarcinoma that is associated with atypical hyperplasia. The general clinical impression is that the presence of atypical hyperplasia in a preoperative biopsy sample may reflect a lower chance of higher or worse disease in the uterus. We previously reported a large series of 490 patients with a preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma. Our primary objective of this analysis, using the same cohort, was to determine whether the presence of atypical hyperplasia in a preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma was associated differentially with final posthysterectomy uterine pathologic finding.
Materials and Methods
After gaining approval from our Institutional Review Board, we reviewed 1423 consecutive cases of endometrial malignancies that had been treated at our institution between January 1, 1993, and May 31, 2006. All pathologic reports were reviewed to identify cases that had their preoperative endometrial biopsy (EMB) specimens reviewed at our institution. All patients had a hysterectomy with or without lymphadenectomy at our institution as primary treatment of their endometrial cancer. It is our institutional policy to confirm all outside diagnosis of cancer before operating on patients for uterine or other malignancies.
Cases were included if the pathologic review at our institution of a preoperative endometrial biopsy, by either curettage or office EMB, demonstrated an unequivocal diagnosis of FIGO grade 1 (well-differentiated) endometrial adenocarcinoma. Pathologic diagnoses from the referring institutions were not abstracted. All histologic findings were included, except for those with obvious serous or clear-cell adenocarcinoma whether alone or mixed with other subtype. Nonepithelial histologic findings were also not included. Cases with FIGO grade 1 adenocarcinoma that occurred with a background of complex atypical hyperplasia (CAH) were identified and compared with those cases in which an association with CAH was not reported. Cases were categorized as being with a background of CAH simply if the presence of CAH was reported. CAH and grade 1 adenocarcinoma were distinguished with the use of criteria that had been described by Longacre et al. Cases were excluded if the primary diagnosis was CAH alone or with any of the following qualifications: “bordering on adenocarcinoma” or “focal area suspicious for adenocarcinoma.” Cases were also excluded if the preoperative diagnosis was inconclusive or graded as FIGO grade 1-2. Cases with obvious extrauterine disease preoperatively or patients who received hormonal, cytotoxic, or radiation therapy before hysterectomy were also excluded.
Data were abstracted from the electronic medical record for the identified cases. Operative reports were reviewed to determine intraoperative findings and the exact nature of the procedure. Pathologic reports of the specimens that were removed from these procedures were reviewed, and the following data were abstracted: frozen section determinations of depth of myometrial invasion, if performed; FIGO grade; histologic subtypes; actual depth of myoinvasion (DOI); presence of extra-uterine metastases; peritoneal cytologic results, and presence of lymph-vascular space invasion. Nodal counts were abstracted, and nodal metastases were noted. Dates of last follow-up examinations and disease status at last follow-up were also abstracted.
Final pathologic findings of the hysterectomy specimens were then analyzed and dichotomized into low risk (LR) or high risk (HR) based on final FIGO grade and DOI ( Table 1 ). This was done with the use of both FIGO (LR- or HR-FIGO) and GOG 33 (LR-GOG or HR-GOG) groupings of DOI. LR-FIGO was defined as tumor limited to endometrium of any grade (FIGO stage IA, grades 1-3) or FIGO grade 1 with DOI <50% (FIGO stage IB, grade 1). LR-GOG was defined as tumor limited to endometrium of any grade or FIGO grade 1 with inner or middle third invasion. These risk groupings were based on the risk of nodal metastasis reported in previous series. Cases without any residual carcinoma in the hysterectomy specimen were considered to have tumor limited to the endometrium. Serous and clear cell histologic findings were considered as final FIGO grade 3.
| Depth of invasion | Grade 1 | Grade 2 | Grade 3 a |
|---|---|---|---|
| FIGO-based | |||
| Limited to endometrium | LR-FIGO | LR-FIGO | LR-FIGO |
| <50% | LR-FIGO | HR-FIGO | HR-FIGO |
| ≥50% | HR-FIGO | HR-FIGO | HR-FIGO |
| GOG-based | |||
| Limited to endometrium | LR-GOG | LR-GOG | LR-GOG |
| ≤33% | LR-GOG | HR-GOG | HR-GOG |
| >33% to <67% | LR-GOG | HR-GOG | HR-GOG |
| ≥67% | HR-GOG | HR-GOG | HR-GOG |
a Serous/clear cell (pure or mixed) was considered to be grade 3.
χ 2 and Fisher’s exact tests were used, as appropriate, to compare nominal variables. Median values were compared with the use of the Mann-Whitney U test. Data were not available for every subgroup analysis and account for some of the subgroup analyses not having all identified cases. All statistical analyses were performed with SPSS for Windows (version 15.0.1; SPSS Inc, Chicago, IL).
Results
We identified 490 cases with a preoperative endometrial sampling diagnosis of FIGO grade 1. The preoperative histologic finding was endometrioid in 477 cases and mucinous in the other 13 cases. One hundred twenty-three cases occurred with a background of CAH; 367 cases did not. The median age of each cohort and the method of endometrial sampling are described in Table 2 . The pathologic findings after hysterectomy are also described in Table 2 . The rate of ovarian metastasis or malignant cytologic finding was not different between the 2 cohorts. Overall, cases with a preoperative diagnosis of FIGO grade 1 endometrial adenocarcinoma that occurred with a background of CAH preoperatively were found less frequently to have a higher grade endometrioid or nonendometrioid histologic grade that was diagnosed in the hysterectomy specimen than those without a background of CAH (9% compared with 18%, respectively; P = .02; Table 3 ). No patients with FIGO grade 1 endometrial adenocarcinoma with a background of CAH was diagnosed with FIGO grade 3 or high-risk histologic finding (ie, serous or clear cell) in the final hysterectomy specimen. Cases that occurred with a background of CAH were also diagnosed less frequently with high-risk uterine disease based on FIGO or GOG criteria after hysterectomy ( P = .02; Table 3 ).
| Variable | CAH | No CAH | P value |
|---|---|---|---|
| n | 123 | 367 | |
| Age, y a | 57 (29–90) | 60 (32–90) | .03 |
| Endometrial sampling method, n (%) | < .001 | ||
| Curettage | 66 (54) | 121 (33) | |
| Office endometrial biopsy | 57 (46) | 241 (67) | |
| Not available | 0 | 5 | |
| Ovarian metastasis, n (%) | .42 | ||
| Yes | 3 (2.5) | 5 (1.4) | |
| No | 117 (97.5) | 352 (98.6) | |
| Malignant peritoneal cytologic findings, n (%) | .13 | ||
| Yes | 4 (3.5) | 18 (5.7) | |
| No | 111 (96.5) | 296 (94.3) | |
| Final FIGO grade, n (%) b | .42 | ||
| 1/no residual | 112 (91) | 299 (83.3) | |
| 2 | 11 (9) | 55 (15.3) | |
| 2-3 or 3 | 0 | 5 (1.4) | |
| Final histologic findings, n (%) c | .35 | ||
| Low risk | 123 (100) | 361 (98.4) | |
| High risk | 0 | 6 (1.6) |
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