ArticlePDF Available

Comparison of preoperative endometrial biopsy grade and final pathologic diagnosis in patients with endometrioid endometrial cancer

March 2012
Journal of the Turkish German Gynecology Association 13(2):106-10

DOI:10.5152/jtgga.2012.12

Source
PubMed

License
CC BY-NC-ND

Authors:

Behiye Pinar Cilesiz Goksedef

Haseki Training and Research Hospital

Ozgur Akbayır

Kanuni Sultan Süleyman Training and Research Hospital Istanbul

Hakan Guraslan

Bağcılar Training And Research Hospital

Show all 7 authorsHide

To compare preoperative grading in endometrioid endometrial cancer with the final pathologic assessment of the hysterectomy specimen. The second objective of the study was to determine a high risk group who will be upgraded in the postoperative evaluation. A total of 335 patients with endometrioid endometrial cancer were retrospectively reviewed between June 2000 and January 2011. All pathology results were pre- and postoperatively reviewed at two institutions, and all patients underwent surgical therapy. Sensitivity, specificity, positive and negative predictive values and accuracy rates were calculated for all grades in the preoperative assessment. The mean age of the patients was 56.2±9.6 and the vast majority of the patients were postmenopausal (n=239, 71.3%). FIGO grade was determined to be greater in 75 patients in the final hysterectomy specimen. Fifty-five (32.9%) of the patients with preoperative grade 1 were found to be grade 2 and 3.6% of them were upgraded to grade 3. Fourteen of the patients with grade 2 (11.4%) were found to be grade 3. The accuracy rates of the preoperative grade assessment with endometrial sampling were 75.5%, 66.2% and 88.3% for grades 1, 2 and 3, respectively. There were no statistically significant differences in the preoperative demographic characteristics between patients with or without upgraded tumors. A high percentage of preoperatively diagnosed grade 1 tumors were upgraded in the postoperative evaluation. The patients who would have been upgraded after hysterectomy could not have been predicted preoperatively using the characteristic features.

Content uploaded by Hakan Guraslan

Content may be subject to copyright.

Comparison of preoperative endometrial biopsy

grade and final pathologic diagnosis in patients with

endometrioid endometrial cancer

Endometrioid endometriyum kanserli olgularda preoperatif endometriyal biyopsi

grade ile postoperatif patolojik değerlendirmenin karşılaştırılması

Behiye Pınar Çilesiz Göksedef ¹, Özgür Akbayır ², Aytül Çorbacıoğlu², Hakan Güraslan², Fatmagül Şencan², Onur Erol³, Ahmet Çetin¹

¹Department of Gynecology and Obstetrics, Haseki Teaching and Research Hospital, İstanbul, Turkey

²Department of Gynecology and Obstetrics, İstanbul Kanuni Sultan Süleyman Research and Teacing Hospital, İstanbul, Turkey

³Department of Gynecology and Obstetrics, Antalya Teaching and Research Hospital, Antalya, Turkey

Address for Correspondence:

Behiye Pınar Çilesiz Göksedef, Department of Gynecology and Obstetrics, Haseki Teaching and Research Hospital, İstanbul, Turkey

Phone: +90 212 529 44 00 e.mail: bpgoksedef@yahoo.com

doi:10.5152/jtgga.2012.12

Objective: To compare preoperative grading in endometrioid endo-

metrial cancer with the final pathologic assessment of the hysterec-

tomy specimen. The second objective of the study was to determine a

high risk group who will be upgraded in the postoperative evaluation.

Material and Methods: A total of 335 patients with endometrioid en-

dometrial cancer were retrospectively reviewed between June 2000

and January 2011. All pathology results were pre- and postoperatively

reviewed at two institutions, and all patients underwent surgical therapy.

Sensitivity, specificity, positive and negative predictive values and accu-

racy rates were calculated for all grades in the preoperative assessment.

Results: The mean age of the patients was 56.2±9.6 and the vast

majority of the patients were postmenopausal (n=239, 71.3%). FIGO

grade was determined to be greater in 75 patients in the final hyster-

ectomy specimen. Fifty-five (32.9%) of the patients with preoperative

grade 1 were found to be grade 2 and 3.6% of them were upgraded to

grade 3. Fourteen of the patients with grade 2 (11.4%) were found to

be grade 3. The accuracy rates of the preoperative grade assessment

with endometrial sampling were 75.5%, 66.2% and 88.3% for grades 1,

2 and 3, respectively. There were no statistically significant differenc-

es in the preoperative demographic characteristics between patients

with or without upgraded tumors.

Conclusion: A high percentage of preoperatively diagnosed grade 1

tumors were upgraded in the postoperative evaluation. The patients

who would have been upgraded after hysterectomy could not have

been predicted preoperatively using the characteristic features.

(J Turkish-German Gynecol Assoc 2012; 13: 106-10)

Key words: Endometrial cancer, biopsy, grade, preoperative evalua-

tion, postoperative evaluation

Received: 15 January, 2012 Accepted: 22 March, 2012

Amaç: Endometrioid tip endometriyum kanserinde preoperatif ve

postoperatif histerektomi materyalindeki grade’in karşılaştırılmasıdır.

İkinci amaç ise postoperatif değerlendirmede upgrade olabilecek

yüksek riskli grubun tanımlanmasıdır.

Gereç ve Yöntemler: Haziran 2000 ve Ocak 2011 tarihleri arasında

endometrioid tip endometriyum kanserli 335 olgu retrospektif olarak

incelendi. Tüm patolojik sonuçlar pre ve postoperatif olarak aynı mer-

kezlerde değerlendirilerek, tüm olgulara cerrahi yapıldı. Preoperatif

grade için sensitivite, spesifisite, pozitif ve negatif prediktif değerler ve

doğruluk oranları hesaplandı.

Bulgular: Ortalama yaş 56.2±9.6 idi ve olguların çoğunluğu postme-

napozal idi (n=239, %71.3). Olguların 75’i histerektomi spesmeninde

daha yüksek grade’li olarak saptandı. Preoperatif grade 1 saptanan

55 olgu (%32.9) postoperatif olarak grade 2 saptanırken %3.6 olgu

grade 3 tespit edildi. Grade 2 saptanan 14 olgu (%11.4) postoperatif

olarak grade 3 saptandı. Endometriyal örnekleme ile preoperatif gra-

de değerlendirilmesinin tanısal doğruluk oranları grade 1, 2 ve 3 için

sırasıyla %75.5, %66.2 ve %88.3 idi. Upgrade olan ve olmayan olgular

arasında demografik karakteristikler açısından istatistiksel olarak an-

lamlı fark bulunmadı.

Sonuç: Preoperatif olarak grade 1 tanısı almış olgularda, yüksek oran-

da postoperatif olarak daha yüksek bir grade saptanmaktadır. Histe-

rektomi sonrası hangi olguların upgrade olabileceği preoperatif ka-

rakteristiklerle tahmin edilememektedir.

(J Turkish-German Gynecol Assoc 2012; 13: 106-10)

Anahtar kelimeler: Endometriyum kanseri, biyopsi, grade, preope-

ratif değerlendirme, postoperatif değerlendirme

Geliş Tarihi: 15 Ocak 2012 Kabul Tarihi: 22 Mart 2012

Introduction

The grade of a tumor is a well-known prognostic factor for

women with endometrial carcinoma and correlates with

the depth of myometrial invasion, lymph node involvement,

surgical stage and survival (1, 2). The staging for endome-

trial carcinoma has been suggested as a surgical-pathologic

system which includes peritoneal cytology, pelvic and para-

aortic lymphadenectomy (3). In 2005, the American College

of Obstetricians and Gynecologists (ACOG) recommended

surgical staging for women with endometrial cancer, except

for young or perimenopausal women with grade 1 endo-

Abstract Özet

Original Investigation

106

metrioid adenocarcinomas, as well as atypical endometrial

hyperplasia, and women at high risk of mortality secondary to

comorbidities (4). The role of lymphadenectomy has not been

clearly defined in the management of endometrial cancer,

especially in patients with grade 1 and 2 disease that is limited

in the uterus. Some authors advise performing a routine pelvic

and/or para-aortic lymphadenectomy in all women (5), where-

as others have questioned the clinical utility of this procedure

because of the complications of lymphadenectomy, especially

in patients at low risk of nodal involvement (grade 1 or 2 with

no or minimal myometrial invasion) (6, 7).

Approximately 52% of women with endometrial carcinoma

have a preoperative endometrial biopsy showing grade 1 (8).

The accuracy of preoperative grading is an extremely important

issue in young patients with well-differentiated endometrial

carcinoma who desire future fertility and uterine preservation.

In addition, preoperative endometrial biopsy is often the basis

of referral to centers and most of the well-differentiated tumors

are managed by general gynecologists and often without appro-

priate incision or surgical staging. Recently, two randomized

multicenter studies reported no evidence of benefits in terms

of overall or recurrence-free survival for pelvic lymphadenec-

tomy in women with preoperative International Federation of

Gynecology and Obstetrics (FIGO) stage I endometrial cancer

(9, 10).

Most of the studies which have investigated preoperative tumor

grading by various endometrial sampling methods have shown

that these methods are poorly correlated with the final patho-

logic grade (8, 11-13). A higher FIGO grade on final uterine

pathologic examination will be diagnosed in 24% of patients

with preoperative FIGO grade 1 and the vast majority of cases

will be upgraded to FIGO grade 2, but approximately 3% will be

upgraded to FIGO grade 3 or be diagnosed as a serous or clear

cell carcinoma on final pathologic assessment of the hysterec-

tomy specimen (7-12). However, there are some studies that

show nearly perfect agreement between preoperative and final

pathologic grades (14, 15).

The objective of this study was to compare preoperative grad-

ing with the final pathological assessment of the hysterectomy

specimen. The second objective of the study was to determine

the high risk group who will be upgraded in the postoperative

evaluation.

Materials and Methods

Between June 2000 and January 2011, a total of 335 patients

with endometrioid endometrial cancer were reviewed retro-

spectively. These cases were identified from a database after

approval was granted by the Institutional Review Board at the

Bakirkoy Women’s and Children’s Teaching and Research

Hospital and Haseki Teaching and Research Hospital. D&C was

used as the method of endometrial sampling in all cases. All

patients underwent hysterectomy and lymphadenectomy as

the primary treatment for their endometrial cancer. All of the

preoperative endometrial histological examinations were per-

formed and reviewed at these two institutions by specialized

gynecologic pathologists. Only the patients with preoperatively

diagnosed endometrioid endometrial carcinoma were evalu-

ated in this study. Cases of serous or clear cell adenocarcinoma,

whether alone or mixed with the other subtypes and non-

epithelial histology, were excluded.

Operative reports were reviewed to determine intraoperative

findings. The pathology reports of the specimens revealed the

FIGO grade, the depth of myometrial invasion, the FIGO stage

of disease, the presence of extra-uterine metastases, the perito-

neal cytologic results and the presence of lymphvascular space

invasion (LVSI). Patients were classified as upgraded if the post-

operative definitive grade was determined to be a greater then

the preoperative grade.

The sensitivity, specificity, positive predictive value (PPV), nega-

tive predictive value (NPV) and accuracy rates were calculated

for all preoperatively assessed grades. Chi-square and Fisher’s

exact tests were used, as appropriate, to compare nominal

variables. All statistical analyses were performed using SPSS for

Windows version 15.0.1 (Chicago, IL).

Results

A total of 335 patients with endometrioid type endometrial can-

cer were evaluated. The mean age of the patients was 56.2±9.6

and the vast majority of the patients were postmenopausal

(n=239, 71.3%). Table 1 summarizes the demographic and

clinic characteristics of the patients. Most of the patients had

grade 2 disease (n=152, 45.4%). 40.9% and 13.7% of them had

grade 1 and grade 3 disease at the final pathologic examination,

respectively.

Table 2 shows the distribution of the surgical outcomes accord-

ing to the preoperative grades of the patients. FIGO grade was

determined to be greater in 75 patients in the final hysterectomy

specimen. Fifty-five (32.9%) of the patients with preoperative

grade 1 were found to be grade 2 and 3.6% of them were

Table 1. Demographic and clinical characteristics of the

patients

n (%)

Age (mean±sd) 56.2±9.6

Gravida (median) 3.0

Parity (median) 3.0

Menopause 239 (46.0)

BMI ≥30 182 (35.0)

DM 88 (16.9)

HT 142 (27.3)

Operation

TAH-BSO-PLND 193 (55.7)

TAH-BSO-PPLND 142 (42.3)

BMI: body mass index, DM: diabetes mellitus, HT: hypertension, TAH-

BSO-PLND: total abdominal hysterectomy- bilateral salphingoopherec-

tomy-pelvic lymph node dissection, TAH-BSO-PPLND: total abdominal

hysterectomy- bilateral salphingoopherectomy-pelvic and para-aortic

lymph node dissection

J Turkish-German Gynecol Assoc 2012; 13: 106-10

Çilesiz Göksedef et al.

Comparison of pre and postoperative grade 107

upgraded to grade 3. Fourteen of the patients with grade 2

(11.4%) were found to be grade 3.

The vast majority of the patients with preoperative grade 1 had

stage I disease (80.2%), 6.0% of them had stage II, 9.0% and

4.8% of the patients had stage III and IV disease. Lymph node

involvement was detected in 11.4% and the depth of myome-

trial invasion (MI) was greater than 50% in 24.6% of the patients

who had grade 1 tumors preoperatively.

The overall accuracy rate of preoperative histologic grade eval-

uation was 64.1%. The sensitivity, specificity, PPV and NPV rates

of the preoperative grade prediction are summarized in Table 3.

Among the preoperatively assessed grades, grade 1 had higher

sensitivity (77.3%) and lower specificity rates (67.5%) compared

with grade 2 and grade 3. The accuracy rates of the preopera-

tive grade assessment with endometrial sampling were 75.5%,

66.2% and 88.3% for grades 1, 2 and 3, respectively.

If the patients with a preoperative diagnosis of grade 3 were

excluded, 25.8% of the patients were found to have a higher

grade in the final pathologic examination. A comparison of the

demographic and pathologic characteristics between patients

with or without upgraded cancer is summarized in Table 4.

Upgraded tumors were significantly related to a higher stage of

disease (p=0.003) and positive peritoneal cytology (p=0.04).

Discussion

The surgical approach for endometrial cancer varies from only

total hysterectomy with bilateral oophorectomy to hysterectomy

with full pelvic and para-aortic lymphadenectomy. Preoperative

tumor grading with pre- and/or intraoperative assessment of the

depth of myometrial invasion, as well as the histologic subtype,

is frequently used to decide whether lymph node dissection

is necessary at the time of hysterectomy. According to FIGO

guidelines, lymphadenectomy should be performed when

myometrial invasion is greater than 50% and/or when the tumor

is undifferentiated (16). Similarly, Mariani et al. (17) reported

that patients with FIGO grade 1 or 2 endometrial cancer with

macroscopically no or superficial myometrial invasion (<50%)

can be treated safely with only hysterectomy. However, pre- and

Table 2. Comparison of the surgical outcomes according to preoperative FIGO grade

Preoperative Grade

1 2 3

n (%) n (%) n (%)

Final Grade

1 (n) 106 (63.5) 28 (22.8) 3 (6.7)

2 (n) 55 (32.9) 81 (65.9) 16 (35.6)

3 (n) 6 (3.6) 14 (11.4) 26 (57.8)

Final FIGO stage

I 134 (80.2) 93 (75.6) 23 (51.1)

II 10 (6.0) 11 (8.9) 4 (8.9)

III 15 (9.0) 8 (6.5) 13 (28.9)

IV 8 (4.8) 11 (8.9) 5 (11.1)

Postoperative Histology

Endometrioid 166 (99.4) 120 (97.6) 44(97.8)

Non-Endometrioid 1 (0.6) 3 (2.4) 1(2.2)

LNI 19 (11.4) 16 (13.0) 15 (33.3)

Positive Cytology 15 (9.0) 14 (11.4) 11 (24.4)

LVSI 40 (24.0) 29 (23.6) 19 (42.2)

Depth of MI

<1/2 126 (75.4) 77 (62.6) 20 (44.4)

>1/2 41 (24.6) 46 (37.4) 25 (55.6)

LNI: lymph node invasion, LVSI: lymphovascular space invasion, MI: myometrial invasion

Table 3. Sensitivity, specificity, PPV and NPV for preopera-

tive grade prediction

Grade 1 Grade 2 Grade 3

Sensitivity 77.3% 53.2% 56.5%

Specificity 67.5% 77.0% 93.4%

PPV 63.4% 65.8% 57.7%

NPV 80.3% 66.5% 93.1%

Accuracy 75.5% 66.2% 88.3%

PPV: positive predictive value, NPV: negative predictive value

J Turkish-German Gynecol Assoc 2012; 13: 106-10

Çilesiz Göksedef et al.

Comparison of pre and postoperative grade

108

intraoperative assessment of the myometrium is an inaccurate

predictor of the actual depth of myometrial invasion (11). In a

series of 112 patients, Frumovitz et al. (11) reported that a frozen

section diagnosis of no myometrial invasion is not accurate in

72% of cases, and 26% of cases with a frozen section of myome-

trial invasion <50% will actually have deeper invasion, cervical

invasion and/or extra-uterine disease.

Preoperative tumor grade based on endometrial sampling is

also reported to be poorly correlated with the final pathologic

grade (8, 11-13, 18, 19) and a greater FIGO grade on final hyster-

ectomy pathological assessment will be diagnosed as high as in

30% of patients with preoperative FIGO grade 1 (12). In another

study, which compared histological grades between D&C and

the hysterectomy specimen in grade 1 tumors on the final hys-

terectomy pathological assessment showed an overall upgrade

rate of 50% and a concordance rate of 32.5% (20).

On the other hand, Kang et al. (14) recently evaluated a total of

122 patients with low-risk endometrial cancer for the necessity

of lymphadenectomy and showed nearly perfect agreement

between pre- and postoperative grades, even when Pipelle was

used for the preoperative diagnosis. Similarly, in a study with

a very large series of only preoperatively detected as grade 1

endometrial cancer, almost 15% of the pathology specimens

were upgraded in the final hysterectomy specimen (15).

In our study, nearly 35% of the patients with FIGO grade 1 endo-

metrial adenocarcinoma prior to hysterectomy were diagnosed

with a greater FIGO grade after hysterectomy. This finding may

be explained by the fact that FIGO grading is based on the per-

centage of solid growth within a specimen and will therefore

vary once the final specimen is obtained and a greater tissue

volume is examined. In addition to this, 13.8% of the patients

with preoperative grade 1 disease had advanced stage of dis-

ease (stage 3 and 4). Lymph node involvement was detected

in 11.4% of the patients with preoperative grade 1 and 9% of

them had positive peritoneal cytology. If the patients were

selected for surgical staging according to preoperative grading,

more than 10% of the patients with preoperative grade 1 would

have been subjected to inappropriate surgery in our cohort.

In an Italian multicenter study which evaluated the efficacy of

systemic lymphadenectomy in patients with preoperative and

intraoperative stage I disease, almost 25% of the total cohort

was upstaged (FIGO II, III, IV) after definitive surgery and

Table 4. Univariate analysis for the patients with or without upgraded tumors

Upgraded Not upgraded

n (%) n (%) p

Age (years)

<70 72 (96.0) 200 (93.0) 0.35

≥70 3 (4.0) 15 (7.0)

Menopause status 0.88

Premenopausal 22 (29.3) 65 (30.2)

Postmenopausal 53 (70.7) 150 (69.8)

BMI 0.19

<30 39 (52.0) 93 (43.3)

≥30 36 (48.0) 122 (56.7)

DM 15 (20.0) 58 (27.0) 0.23

HT 36 (48.0) 86 (40.0) 0.22

Final FIGO stage 0.003*

I 46 (61.3) 204 (78.4)

II 9 (12.0) 16 (6.2)

III 10 (13.3) 26 (10.0)

IV 10 (12.3) 14 (5.4)

LNI 59 (78.7) 226 (86.9) 0.07

Positive Cytology 14 (18.7) 26 (10.0) 0.04

LVSI 23 (30.7) 65 (27.0) 0.32

Depth of MI 0.59

<1/2 48 (64.0) 175 (67.3)

>1/2 27 (36.0) 85 (32.7)

BMI: body mass index, DM: diabetes mellitus, HT: hypertension, LNI: lymph node invasion, LVSI: lymphovascular space invasion, MI: myometrial invasion

*X2 test for trend

J Turkish-German Gynecol Assoc 2012; 13: 106-10

Çilesiz Göksedef et al.

Comparison of pre and postoperative grade 109

patients undergoing systemic lymphadenectomy had a higher

likelihood of being upstaged to FIGO IIIC disease compared the

no lymphadenectomy arm (13.3% vs. 3.2%) (10). Another ran-

domized trial (MRC ASTEC) also showed that 23% of patients

with a preoperatively diagnosed stage I tumor were upstaged

in both the standard surgery and lymphadenectomy arms (11).

Our second objective in conducting this study was to preopera-

tively determine the high risk group in which patients will be

upgraded in postoperative evaluation. However, there was no

statistically significant difference in the demographic and clini-

cal features between patients with or without upgraded tumors.

We found a significant relation only between the stage of dis-

ease, positive abdominal cytology and upgrading. However,

those were mostly detected after surgical staging. Thus, it is not

possible to predict the high risk group for upgrading preopera-

tive findings.

In conclusion, unpredictably, a high percentage of preopera-

tively diagnosed as grade 1 tumors were upgraded in the post-

operative evaluation. According to our study, it is not possible

to say that lymphadenectomy should be considered as com-

prehensive surgical staging in all patients with preoperatively

diagnosed endometrial cancer, but it should be mentioned

that patients with a preoperative diagnosis of grade 1 uterine

cancers have a risk of extra-uterine spread, and the informa-

tion achieved from an appropriate surgical staging procedure

affects the adjuvant treatment decision.

Conflict of interest

No conflict of interest was declared by the authors.

References

1. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE,

Heller PB. Surgical pathologic spread patterns of endometrial can-

cer. A gynecologic oncology group study. Cancer 1987; 60: 2035- 41.

[CrossRef]

2. Abeler VM, Kjorstad KE. Endometrial adenocarcinoma in Norway:

a study of a total population. Cancer 1991; 67: 3093-103. [CrossRef]

3. Announcement. FIGO stages: 1988 revisions. Gynecol Oncol 1989;

35: 125- 7. [CrossRef]

4. American College of Obstetricians and Gynecologists.ACOG prac-

tice bulletin, clinical management guidelines for obstetrician-gyne-

cologists, number 65, August 2005: management of endometrial

cancer.Obstet Gynecol 2005; 106: 413-25.

5. Barnes NM, Kilgore LC. Complete surgical staging of early endo-

metrial adenocarcinoma. Optimizing patients outcomes. Semin

Radiat Oncol 2000; 10: 3-7. [CrossRef]

6. Geisler JP, Wiemann MC, Zhou Z, Miller GA, Geisler HE. Using FIGO

histologic grade to determine when to perform lymphadenecto-

mies in endometrioid adenocarcinoma of the endometrium. Eur J

Gynaecol Oncol 1996; 17: 204-7.

7. Orr Jr JW, Roland PY, Leichter D, Orr PF. Endometrial cancer:

is surgical staging necessary? Curr Opin Oncol 2001; 13: 408-12.

[CrossRef]

8. Ben-Shachar I, Pavelka J, Cohn DE, Copeland LJ, Ramirez N,

Manolitsa T, et al. Surgical staging for patients presenting with

grade 1 endometrial carcinoma. Obstet Gynecol 2005; 105: 487-93.

[CrossRef]

9. ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C,

Parmar MK. Efficacy of systematic pelvic lymphadenectomy in

endometrial cancer (MRC ASTEC trial): a randomised study.

Lancet 2009; 373: 125-36. [CrossRef]

10. Benedetti Panici P, Basile S, Maneschi F, Alberto Lissoni A,

Signorelli M, Scambia G, et al. Systematic pelvic lymphadenectomy

vs. no lymphadenectomy in early-stage endometrial carcinoma:

randomized clinical trial. J Natl Cancer Inst 2008; 100: 1707-16.

[CrossRef]

11. Frumovitz M, Singh DK, Meyer L, Smith DH, Wetheim I, Resnik E, et

al. Predictors of final histology in patients with endometrial cancer.

Gynecol Oncol 2004; 95: 463-8. [CrossRef]

12. Eltabbakh GH, Shamonki J, Mount SL. Surgical stage, final grade,

and survival of women with endometrial carcinoma whose pre-

operative endometrial biopsy shows well-differentiated tumors.

Gynecol Oncol 2005; 99: 309-12. [CrossRef]

13. Case AS, Rocconi RP, Straugh Jr JM, Conner M, Novak L,WangW,

et al. A prospective blinded evaluation of the accuracy of frozen

section for the surgical management of endometrial cancer. Obstet

Gynecol 2006; 108: 1375-9. [CrossRef]

14. Kang WD, Kim CH, Cho MK, Kim JW, Kim YH, Choi HS, et al.

Lymphadenectomy for low-risk endometrial cancer based on pre-

operative and intraoperative assessments. Int J Gynecol Cancer.

2009; 19: 657-61. [CrossRef]

15. Leitao MM, Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et

al. Comparison of D&C and office endometrial biopsy accuracy in

patients with FIGO grade 1 endometrial adenocarcinoma Gynecol

Oncol 2009; 113: 105-8. [CrossRef]

16. Benedet JL, Bender H, Jones H 3rd, Ngan HY, Pecorelli S. FIGO

staging classifications and clinical practices guidelines in manage-

ment of gynecologic cancers. Int J Gyneacol Obstet 2000; 70: 209-

62. [CrossRef]

17. Mariani A, Webb MJ, Keeney GL, Haddock MG, Calori G, Podratz

KC. Low-risk corpus cancer: is lymphadenectomy or radiotherapy

necessary? Am J Obstet Gynecol. 2000; 182: 1506-19. [CrossRef]

18. Larson DM, Johnson KK, Broste SK, Krawisz BR, Kresl JJ.

Comparison of D&C and office endometrial biopsy in predicting

final histopathologic grade in endometrial cancer. Obstet Gynecol

1995; 86: 38-42. [CrossRef]

19. Obermair A, Geramou M, Gucer F, Denison U, Graf AH, Kapshammer

E, et al. Endometrial cancer: accuracy of the finding of a well dif-

ferentiated tumor at dilatation and curettage compared to the

findings at subsequent hysterectomy. Int J Gynecol Cancer 1999; 9:

383-6. [CrossRef]

20. Wang X, Zhang H, Di W, Li W. Clinical factors affecting the diagnos-

tic accuracy of assessing dilation and curretage vs frozen section

specimen for histologic grade and depth of myometrial invasion

in endometrial carcinoma. Am J Obstet Gynecol 2009; 201: 194.

e1-e10.

J Turkish-German Gynecol Assoc 2012; 13: 106-10

Çilesiz Göksedef et al.

Comparison of pre and postoperative grade

110

Concordance of preoperative and postoperative histological grades in endometrioid type endometrial cancer

Article

Full-text available

Apr 2020

To investigate concordance between grades determined by endometrial sampling and final pathology, and factors affecting this concordance, in endometrioid type endometrial cancer.

Complete blood count and selected clinical factors: are they related to the grade and stage ofendometrial cancer?

Article

Full-text available

Dec 2018

The amount of preoperative endometrial tissue surface in relation to final endometrial cancer classification

Article

Full-text available

Sep 2022
GYNECOL ONCOL

Objective To evaluate whether the amount of preoperative endometrial tissue surface is related to the degree of concordance with final low- and high-grade endometrial cancer (EC). In addition, to determine whether discordance is influenced by sampling method and impacts outcome. Methods A retrospective cohort study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC). Surface of preoperative endometrial tissue samples was digitally calculated using ImageJ. Tumor samples were classified into low-grade (grade 1–2 endometrioid EC (EEC)) and high-grade (grade 3 EEC + non-endometroid EC). Results The study cohort included 573 tumor samples. Overall concordance between pre- and postoperative diagnosis was 60.0%, and 88.8% when classified into low- and high-grade EC. Upgrading (preoperative low-grade, postoperative high-grade EC) was found in 7.8% and downgrading (preoperative high-grade, postoperative low-grade EC) in 26.7%. The median endometrial tissue surface was significantly lower in concordant diagnoses when compared to discordant diagnoses, respectively 18.7 mm² and 23.5 mm² (P = 0.022). Sampling method did not influence the concordance in tumor classification. Patients with preoperative high-grade and postoperative low-grade showed significant lower DSS compared to patients with concordant low-grade EC (P = 0.039). Conclusion The amount of preoperative endometrial tissue surface was inversely related to the degree of concordance with final tumor low- and high-grade. Obtaining higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade diagnosis in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome.

Histopathological pattern of endometrial biopsies in patients with abnormal uterine bleeding in a tertiary referral hospital in Jordan

Article

Full-text available

May 2022

BACKGROUND Abnormal uterine bleeding (AUB) is a symptom that deviates from the normal menstrual cycle. AUB is characterized by changes in the frequency, volume, and duration of the menstrual flow. The etiology of AUB, which varies with age, may be attributed to both structural and non-structural causes. OBJECTIVES Determine the histopathological pattern of endometrial biopsies in patients with AUB across different age and parity groups who have undergone dilation and curettage (D&C), along with the discrepancy between D&C and histopathological findings after hysterectomy. DESIGN Retrospective chart review SETTING Tertiary referral hospital PATIENTS AND METHODS We collected data on all patients diagnosed with AUB between January 2015 and December 2020. Histopathological findings of all D&C endometrial biopsy samples were examined after being categorized by age and parity groups. Sensitivity, specificity, positive predictive value, and NPV were calculated to evaluate the diagnostic accuracy of D&C. MAIN OUTCOME MEASURES Histopathological pattern of D&C endometrial biopsies by age and parity groups. SAMPLE SIZE 3233 patients. RESULTS Most patients were in the 18-39 year age group, with normal cyclical findings being the most common histopathological finding. Malignant lesions were observed in 42 patients with a majority being older than 50 years. In 13.3% (42/316) of patients, D&C failed to detect intrauterine disorder that was found on hysterectomy. The overall accuracy of D&C in determining the existence of normal versus pathological findings was 75.60%, the sensitivity was 72.90%, the specificity was 77.90%, the positive predictive value was 73.86% and the NPV was 77.05% in our patients. CONCLUSION Normal cyclic changes account for the highest proportion of histopathological findings. However, hyperplasia and malignancies are important causes of perimenopausal and postmenopausal bleeding. While the use of D&C as a sampling tool for AUB cases remains questionable, the use of D&C in diagnosing premalignant and malignant cases is highly effective. LIMITATIONS Single-center, retrospective design, incomplete medical records, and inter-rater reliability could not be determined. CONFLICT OF INTEREST None.

The Accuracy of Endometrial Sampling and Clinical Affecting Factors as a Predictor of Final Surgical Pathology in Endometrial Cancer

Article

Full-text available

Apr 2022
CLIN EXP OBSTET GYN

Background We conducted a retrospective study to evaluate the correlation between preoperative and final histologic diagnoses of endometrial cancer and to identify clinicopathologic factors associated with the concordance between initial and final hysterectomy specimens. Methods Patients who underwent primary surgical treatment for endometrial cancer at our institute from January 2016 through December 2020 were enrolled. The International Federation of Gynecology and Obstetrics (FIGO) grade and histologic subtype in the pathologic reports were recorded. The level of agreement of tumor grade and histologic type were analyzed. Results A total of 425 cases were recruited. The overall level of agreement between preoperative grading was moderate according to kappa statistics (κ = 0.469, 95% confidence interval [CI]: 0.385, 0.553). Furthermore, agreement related to the histologic subtype was substantial (κ = 0.778, 95% CI: 0.682, 0.874). The most frequently used endometrial sampling methods were the office endometrial sampling and endometrial curettage (49.2% and 32%, respectively). Among each diagnostic method, manual vacuum aspiration and endometrial curettage had high tumor grade correlation between the preoperative sampling and final pathology (κ = 0.743, 95% CI: 0.549, 0.937 and κ = 0.624, 95% CI: 0.512, 0.736, respectively). Negative peritoneal cytology was was the significant factor associated with concordance between preoperative endometrial sampling and final surgical pathology, with an adjusted odds ratio (OR) of 2.01 (95% CI: 1.03, 3.92; p = 0.040). Conclusions Regardless of the different diagnostic methods, preoperative endometrial biopsy has limitations in predicting tumor grade compared with final hysterectomy specimens in women with endometrial cancer.

Accuracy of preoperative sampling diagnosis for predicting final pathology in patients with endometrial carcinoma: a review

Article

Full-text available

Oct 2020

Endometrial cancer (EC) is the most common gynecologic cancer. The most frequent symptom of this disease is postmenopausal bleeding. Diagnosis of EC must be histologically confirmed, and there are several methods for endometrial sampling to obtain cells or endometrial tissue. The first step in diagnosis should be ultrasound measurement of endometrial thickness, followed by endometrial sampling, which can be performed by office endometrial biopsy, hysteroscopic biopsy, or dilatation and curettage (D&C). The review in this article was carried out to present previously published studies, comprehensively evaluate method performance (i.e., overall accuracy of preoperative sampling in patients with endometrial carcinoma, and overall agreement on grade and histological subtype between preoperative endometrial sampling and final diagnosis), and determine which sampling method is most accurate on the basis of the statistical data in the studies analyzed. From the literature analyzed and examined, it can be concluded that preoperative endometrial sampling is not always the best predictor of final histology in EC and has its limitations. In surgical decisions based only on preoperative sampling, a biopsy should be made with caution, and it is necessary to take other parameters into account. Inadequate grading leads to suboptimal clinical management, mainly in early-stage tumors. This review showed that, although hysteroscopic biopsy was mainly associated with the highest tumor grade agreement, and although D&C showed the highest overall accuracy in detecting endometrial carcinoma, the data do not therefore reliably indicate which method yields the most precise results. The results of this review indicate that further studies on larger samples and with greater statistical power are needed to accurately define the role and type of preoperative sampling methods.

Gaussian mixture model-based cluster analysis of apparent diffusion coefficient values: a novel approach to evaluate uterine endometrioid carcinoma grade

Article

Jul 2020

Objectives The purpose of our study was to perform Gaussian mixture model (GMM)-based cluster analysis of the apparent diffusion coefficient (ADC) data of patients with endometrioid carcinoma, and to evaluate the relationship between histological grade and the ratios of the different clusters in each patient.Methods This retrospective study enrolled 122 patients (training: n = 63; and validation: n = 59) imaged between May 2015 and February 2020. In the training cohort, manual segmentation was performed on the ADC maps to obtain the ADC data of each patient, and these ADC data were summated to obtain the “All-patient” ADC data. Cluster analysis (three clusters) was performed on this All-patient ADC data, and the ADC ranges of each cluster were defined as follows: cluster 1, 490–699 × 10−6 mm2/s; cluster 2, 700–932 × 10−6 mm2/s; and cluster 3, over 933 × 10−6 mm2/s. In the training and validation cohorts, the ADC data of each patient was classified into three clusters according to these ADC ranges. The cluster ratios of each patient were calculated and compared with histological grade.ResultsIn the training cohort, a significant positive correlation was found between the cluster 1 ratio and histological grade (ρ = 0.34, p = 0.0059). The cluster 1 ratios of high-grade lesions (grade 3) were significantly higher than those of low-grade lesions (grades 1 and 2) (p = 0.0084). A similar significant positive correlation was found between the cluster 1 ratio and histological grade in the validation cohort (ρ = 0.44, p = 0.0006).Conclusions The cluster 1 ratio containing voxels with low ADC was significantly correlated with the histological grade of endometrioid carcinoma.Key Points • We performed Gaussian mixture model (GMM)-based cluster analysis of the apparent diffusion coefficient (ADC) data of patients with endometrioid carcinoma. • The cluster 1 ratio, which included low ADC values, was significantly positive correlated with histological grade in the training and validation cohorts. • The GMM-based cluster analysis of voxel-based ADC data was effective for grading endometrioid carcinoma.

Prognostic value of serum HE4 level in the management of endometrial cancer: A pilot study

Article

Feb 2021
AUST NZ J OBSTET GYN

Background: Human epididymis protein 4 (HE4) has shown promising utility as a prognostic biomarker in endometrial cancer. Increased serum HE4 levels may be associated with deeper myometrial invasion, extrauterine disease and poorer prognosis. Aim: To evaluate the use of serum HE4 level, compared to and alongside other investigations, to accurately guide management in apparent early-stage endometrial cancer. Materials and methods: This is a single-site prospective study of 100 patients with histologically confirmed endometrial cancer. All patients underwent preoperative measurements of HE4 and CA125 levels and a preoperative magnetic resonance imaging (MRI) to assess the depth of invasion, nodal status and tumour size. Correlation was sought between serum HE4 level, CA125 level, MRI findings and intra-operative frozen section with tumour type, grade and stage. Results: While both median HE4 and CA125 levels were higher with worsening clinicopathological features, serum HE4 level showed a more consistent association with high-risk features. Patients with a low-grade biopsy preoperatively and a low HE4 level (<70 pmol/L) demonstrated an 86.8% likelihood of having low-risk disease on final histopathology. In comparison, preoperative MRI or intraoperative frozen section alongside a low-grade biopsy demonstrated a similar likelihood of 86.2 and 87.7%, respectively. Conclusions: When used in conjunction with an initial low-grade endometrial biopsy, serum HE4 level demonstrated a similar likelihood to both preoperative MRI and intraoperative frozen section in identifying low-risk disease on final histopathology. As a triaging tool this may be significant given that a preoperative, serum-based assay would likely be the least invasive, least resource-intensive and most cost-effective approach.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP)

Article

Jul 2020

Background High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. Methods A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. Results Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36–4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33–2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52–0.96). Conclusion GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

Differential Mueller matrix imaging of partially depolarizing optically anisotropic biological tissues

Article

Full-text available

Jun 2020
LASER MED SCI

Since recently, a number of innovative polarization-based optical imaging modalities have been introduced and extensively used in various biomedical applications, with an ultimate aim to attain the practical tool for the optical biopsy and functional characterization of biological tissues. The techniques utilize polarization properties of light and Mueller matrix mapping of microscopic images of histological sections of biological tissues or polycrystalline films of biological fluids. The main drawback of currently developed laser polarimetry approaches and Mueller matrix mapping techniques is poor reproducibility of experimental data. This is due to azimuthal dependence of polarization and ellipticity values of most matrix elements to sample orientation in respect to incidence light polarization. Current study aims to generalize the methods of laser polarimetry for diagnosis of partially depolarizing optically anisotropic biological tissues. A method of differential Mueller matrix mapping for reconstruction of linear and circular birefringence and dichroism parameter distributions of partially depolarizing layers of biological tissues of different morphological structure is introduced and practically implemented. The coordinate distributions of the value of the first-order differential matrix elements of histological sections of brain tissue with spatially structured, optically anisotropic fibrillar network, as well as of parenchymatous tissue of the rectum wall with an “islet” polycrystalline structure are determined. Within the statistical analysis of polarization reproduced distributions of the averaged parameters of phase and amplitude anisotropy, the significant sensitivity of the statistical moments of the third and fourth orders to changes in the polycrystalline structure of partially depolarizing layers of biological tissue is observed. The differentiation of female reproductive sphere connective tissue is realized with excellent accuracy. The differential Mueller matrix mapping method for reconstruction of distributions of linear and circular birefringence and dichroism parameters of partially depolarizing layers of biological tissues of different morphological structures is proposed and substantiated. Differential diagnostics of changes in the phase (good balanced accuracy) and amplitude (excellent balanced accuracy) of the anisotropy of the partially depolarizing layers of the vagina wall tissue with prolapse of the genitals is realized. The maximum diagnostic efficiency of the first-order differential matrix method was demonstrated in comparison with the traditional methods of polarization and Mueller matrix mapping of histological sections of light-scattering biological tissues.

Response: Re: Systematic Pelvic Lymphadenectomy vs No Lymphadenectomy in Early-Stage Endometrial Carcinoma: Randomized Clinical Trial

Article

Full-text available

Jun 2009

ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 76, October 2006: postpartum hemorrhage

Article

Oct 2006
OBSTET GYNECOL

American College of Obstetricians and Gynecologists

Severe bleeding is the single most significant cause of maternal death world-wide. More than half of all maternal deaths occur within 24 hours of delivery, most commonly from excessive bleeding. It is estimated that worldwide, 140,000 women die of postpartum hemorrhage each year-one every 4 minutes (1). In addition to death, serious morbidity may follow postpartum hemorrhage. Sequelae include adult respiratory distress syndrome, coagulopathy, shock, loss of fertility, and pituitary necrosis (Sheehan syndrome). Although many risk factors have been associated with postpartum hemorrhage, it often occurs without warning. All obstetric units and practitioners must have the facilities, personnel, and equipment in place to manage this emergency properly. Clinical drills to enhance the management of maternal hemorrhage have been recommended by the Joint Commission on Accreditation of Healthcare Organizations (2). The purpose of this bulletin is to review the etiology, evaluation, and management of postpartum hemorrhage.

Complete surgical staging of early endometrial adenocarcinoma: Optimizing patient outcomes

Article

Jan 2000
SEMIN RADIAT ONCOL

Endometrial adenocarcinoma is the most common gynecologic malignancy. Strategies for treatment of this disease should not only emphasize quality of care resulting in cure of disease, but also use health care resources in the most efficient manner possible. Based on available data, we recommend that all patients with the diagnosis of endometrial carcinoma undergo complete surgical staging with lymph node dissection. Radiation therapy is reserved only for patients with evidence of extrauterine disease. This approach maximizes the amount of information available for treatment planning and offers the potential therapeutic advantage of lymph node dissection. Additionally, in a cost analysis, this approach appears to be the most cost-effective.

A prospective blinded evaluation of the accuracy of frozen section for the surgical management of endometrial cancer [14]

Article

Mar 2007

Systematic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial

Article

Jan 2008

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): A randomised study

Article

Jan 2009

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

Article

Jan 2009
LANCET

The writing committee on behalf of the ASTEC study group

Background: Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. Methods: From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. Findings: After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). Interpretation: Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.

ACOG Practice Bulletin #65: Management of Endometrial Cancer

Article

Aug 2005
OBSTET GYNECOL

Endometrial cancer: Accuracy of the finding of a well differentiated tumor at dilatation and curettage compared to the findings at subsequent hysterectomy

Article

Dec 2001
INT J GYNECOL CANCER

Obermair A, Geramou M, Gücer F, Denison U, Graf AH, Kapshammer E, Medl M, Rosen A, Wierrani F, Neunteufel W, Frech I, Speiser P, Kainz C, Breitenecker G, Austrian Gynecologic Oncology Group. Endometrial cancer: accuracy of the finding of a well differentiated tumor at dilatation and curretage compared to the findings at subsequent hysterectomy.The objective of this study was to examine the accuracy of the finding of a histologically well differentiated endometrial carcinoma at dilatation and curettage (D & C) prior to hysterectomy. A retrospective multicentric chart review of 137 endometrial cancer patients was conducted, including all patients in whom a well differentiated endometrial carcinoma had been diagnosed by D & C. Histopathologic grading as determined by D & C was compared with the grading established at the final histologic examination after hysterectomy. Seventy-eight percent of all cases in which a well differentiated tumor was diagnosed with D & C were confirmed as well differentiated endometrial carcinomas, whereas 20.4% had to be upgraded as moderately differentiated tumors after evaluation of the hysterectomy specimen. In one case in which a uterine adenocarcinoma was diagnosed by D & C, a well differentiated adenocarcinoma was found to be combined with a carcinosarcoma in the hysterectomy specimen. In order to avoid false findings of a well differentiated tumor, the histologic grade should be confirmed by intraoperative frozen section examination. This is especially important in cases in which surgical staging was not planned initially.

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

Article