Annals of Diagnostic Pathology 19 (2015) 43–44
Contents lists available at ScienceDirect
Annals of Diagnostic Pathology
Original Contributions
Adequacy of cervical sampling in hysterectomy specimens for endometrial cancer☆,☆☆,★ Sheeba Syed, FRCPath a,⁎, Nick Reed, FRCP b, David Millan, FRCPath a a b
Department of Pathology Laboratory Medicine/FM Building, Southern General Hospital, Glasgow, UK Beatson Oncology Centre, Glasgow, UK
a r t i c l e
i n f o
Keywords: Endometrial cancer Cervical sampling Cervical stromal invasion
a b s t r a c t Aim: To determine whether sampling one section, which includes the anterior and posterior cervical lips in hysterectomy specimens, provides the best prospect for detecting stromal invasion in hysterectomy specimens for endometrial cancers. Methods: To assess the most likely section in which cervical stromal invasion was identified in 29 cases. Results: Cervical stromal invasion was detected in first section in 75.8% cases, whereas 24.1% detected in random sections other than first section. Conclusion: Cervical stromal invasion is most likely to be identified in one section taken in the midline, which includes anterior and posterior lips. However, in a significant number of cases, this one section missed invasion, which was detected in other random cervical sections. Therefore, sampling of one block (anterior and posterior) from the cervix is insufficient for detecting cervical stromal invasion for endometrial cancer. © 2015 Elsevier Inc. All rights reserved.
Introduction About 10% of endometrial carcinomas exhibit some form of spread to the cervix at the time of hysterectomy. The presence of cervical invasion has been considered important for decades in the prognostication and therapy of endometrial carcinoma. Most oncologists administer adjuvant brachytherapy with or without other adjuvant treatments depending on the other risk factors present, for patients with cervical stromal invasion [1]. Women with tumors involving the cervix have an overall worse prognosis than do those whose neoplasms are confined to the uterine corpus. Data from the International Federation of Gynecology and Obstetrics (FIGO) 2003 showed 5-year survival rates for patients with cervical involvement to be 75% compared with 88% for stage I neoplasms [2]. The 1988 FIGO staging divided stage II into those tumors that involved the surface or glandular (crypt) epithelium alone (stage IIA) and those that spread to the cervical stroma with or without surface or glandular involvement (stage IIB) [3]. The 2009 revision of FIGO staging includes only those tumors that have spread to the cervical stroma as stage II [4]. Although the prognostic significance in distinguishing tumors of cervical glandular involvement alone is not clear with some studies, suggesting that overall survival ☆ Conflict of interest: None. ☆☆ Disclosures: None. ★ Patient anonymity and informed consent: Not applicable. ⁎ Corresponding author. Department of Pathology Laboratory Medicine/FM Building, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TF, UK. Tel.: +44 7792124133. E-mail addresses: [email protected] (S. Syed), [email protected] (N. Reed), [email protected] (D. Millan). http://dx.doi.org/10.1016/j.anndiagpath.2015.02.003 1092-9134/© 2015 Elsevier Inc. All rights reserved.
rates are better and recurrence rates are lower in cases with cervical glandular involvement than in cases with stromal involvement and no different than in tumors without cervical involvement [5]. Other studies [6,7] suggest that there is no prognostic significance in distinguishing between cervical glandular and stromal involvement. In some institutions, there is no difference in management between tumors exhibiting cervical glandular involvement only and those exhibiting stromal involvement, whereas others thought that this should not be upstaged. For example, with a lowgrade endometrial adenocarcinoma confined to the inner half of the myometrium, involvement of the endocervical epithelium may result in no adjuvant therapy, whereas cervical stromal involvement will result in adjuvant therapy [5]. Guidelines of The Royal College of Pathologists recommend at least 2 blocks be taken from the cervix, one from the anterior and one from the posterior lip [8]. However, in our department, it has been standard practise for the last decade to section the entire cervical canal for hysterectomy specimens of endometrial carcinoma. Methods Cervical sections of 29 consecutive cases of hysterectomy specimens (between April 2012 and April 2014) with reported cervical stromal involvement were included in this study. One of the most problematic areas in the pathologic reporting of endometrial carcinomas in hysterectomy specimens is the evaluation of cervical involvement, and there are a few guidelines regarding this. In many cases, cervical involvement is not apparent clinically, radiologically, or on gross examination of the specimen and is only identified on microscopic assessment. Because of interobserver variation in
44
S. Syed et al. / Annals of Diagnostic Pathology 19 (2015) 43–44
assessment of cervical stromal involvement by endometrial cancers, all cases in this study were assessed by at least 2 pathologists with specialist interest in gynecologic pathology for cervical stromal invasion. The cervical stromal involvement was examined in all the cervical sections taken. In our department, 1 block (1 section) includes anterior and posterior lips; additionally, the entire endocervical canal is processed longitudinally as done for cervical loop specimens along with sections of lower uterine segment. Although routine processing of cervix in hysterectomy specimens of endometrial carcinoma involves only 1 block (anterior and posterior lips) in our department, there has always been a protocol to sample the entire cervical canal since the change in FIGO staging from 1998 to 2009. Results The histologic subtypes with cervical stromal involvement were mainly endometrioid (62%), followed by serous (17.2%), carcinosarcoma (17.2%), and undifferentiated (3.6%); 62.2% of the cases were grade 3, 27.5% were grade 2, and 10.3% were grade I. lymphovascular space invasion was detected in 82.75% of the cases, especially the grade I with cervical stromal invasion. Of these 29 cases, cervical stromal invasion was detected in the first section (which included anterior and posterior lips) in 22 cases (75.8%). In the remaining 7 cases (24.2%), cervical stromal invasion was detected in sections S2 to S9. On an average, 4.6 sections were taken. The staging of the 29 cases (FIGO 2009) is shown in Table. Of the 7 cases with cervical stromal invasion missed in the first section, 3 were stage II, 3 were IIIA, and 1 was stage IV. Discussion Accurate staging of endometrial carcinoma in hysterectomy specimens is essential to ensure optimum patient management. It is worth emphasizing that cervical involvement by endometrial carcinoma may be extremely focal. This raises questions to the method of sampling the cervix in hysterectomy specimens from patients with endometrial carcinoma [5]. Evidence exists about sampling of cervix in hysterectomy after a previous diagnosis of cervical intraepithelial neoplasia [9]. Kadar et al [10] in their study have found that in stage II disease, stromal involvement occurs in 87% cases (II B) and surface epithelial involvement in only 13% of cases (II A), suggesting that spread of endometrial carcinoma to the cervix occurs predominantly by deep tissue planes or lymph channels. However, they published their study prior to the FIGO 2009 classification, according to which only cervical stromal involvement is classified as stage II. Rubin et al [11] and Jordan and Al-Nafussi [12] support the traditional concept that endometrial carcinoma spreads by surface contiguity or by implantation more frequently than by deep tissue planes or via lymphatics, and they recommended pathologists to approach trimming the cervix of any case of endometrial malignancy in a similar manner to the technique used in the dissection of a cone biopsy or of a cervix from a Wertheim hysterectomy specimen. Based on this concept, in our department, it is a protocol to sample entire endocervical canal in hysterectomy specimens of endometrial carcinomas. Our study was relatively small but proved that there can be a significant number of cases that can be missed in terms of cervical stromal involvement if routinely only 1 section (which includes anterior and posterior lip) is taken. Nearly a quarter (24.2%) is a significant number of cases potentially under staged and risking mismanagement by under treatment and even if we consider that the stage after microscopic assessment 10 % cases will be under staged. The other significant aspect noted was that even from
Table Distribution of staging of the 29 cases Staging by FIGO 2009
No. of cases
Stage II Stage IIIA Stage IIIB Stage IIIC1 Stage IVA
17 8 2 1 1
the 75.8% of cases in which cervical stromal invasion was detected in section I, there were 4 cases that showed no cervical stromal invasion in additional sections or the tumor appeared in random sections in a skip pattern. Our results contradicts the study of Nayar et al [13] that showed that sampling or the entire cervix does not identify any more cases of cervical involvement compared with the routine sampling of 2 blocks and the guidelines by the Royal College of Pathologists 2014 [8]. We have modified our standard operative procedure accordingly to ensure the highest quality of pathological interpretation is offered to our patients, and furthermore, we have rolled this Standard Operative Procedure out to the other network pathologists in our regional practice.
Conclusions Our study has shown that sampling of one block from the cervix is insufficient for detecting cervical stromal invasion for endometrial cancer. We assessed small numbers, and the evidence of our study will be strengthened by a multicenter trial.
References [1] McCluggage WG, Colgan T, Duggan M, et al. Data set for reporting of endometrial carcinomas: recommendations from the International Collaboration on Cancer Reporting (ICCR) between United Kingdom, United States, Canada, and Australasia. Int J Gynecol Pathol 2013;32(1):45–65. [2] Creasman WT, Odicino F, Maisonneuve P, Beller U, Benedet JL, Heintz AP, et al. Carcinoma of the corpus uteri. Int J Gynaecol Obstet 2003;83(Suppl. 1):79–118. [3] Shepherd JH. Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol 1989;96:889–92. [4] Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2010;108(2):176. [5] McCluggage WG, Hirschowitz L, Wilson GE, Oliva E, Soslow RA, Zaino RJ. Significant variation in the assessment of cervical involvement in endometrial carcinoma: an interobserver variation study. Am J Surg Pathol 2011;35(2):289–94. [6] Ayhan A, Taskiran C, Celik C, et al. The long-term survival of women with surgical stage II endometrioid type endometrial cancer. Gynecol Oncol 2004;93:9–13. [7] Jobsen JJ, Schutter EM, Meerwaldt JH, et al. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma. Int J Gynecol Cancer 2001;11: 49–53. [8] Standards and datasets for reporting cancers: Dataset for histological reporting of endometrial cancer. http://www.rcpath.org/Resources/RCPath/Migrated %20Resources/ Documents/G/G090_EndometrialDataset_Feb14.pdf; 2014. [Accessed on 1st Jan 2015]. [9] Greene A, Heatley MK. The appropriateness of examining the entire cervix histologically in hysterectomy specimens from women with a previous history of cervical intraepithelial neoplasia or dyskaryosis. J Clin Pathol 2001;54(2):155–7. [10] Kadar NR, Kohorn EI, LiVolsi VA, et al. Histologic variants of cervical involvement by endometrial carcinoma. Obstet Gynecol 1982;59(1):85–92. [11] Rubin SC, Hoskins WJ, Saigo PE, et al. Management of endometrial adenocarcinoma with cervical involvement. Gynecol Oncol 1992;45(3):294–8. [12] Jordan LB, Al-Nafussi A. Clinicopathological study of the pattern and significance of cervical involvement in cases of endometrial adenocarcinoma. Int J Gynecol Cancer 2002;12(1):42–8. [13] Nayar AG, Cross PA, Bulmer JN, et al. Comparison of examination of the entire uterine cervix with routine cervical sampling in hysterectomy specimens from women with endometrial cancer. J Clin Pathol 2008;61(5):621–2.
Contents lists available at ScienceDirect
Annals of Diagnostic Pathology
Original Contributions
Adequacy of cervical sampling in hysterectomy specimens for endometrial cancer☆,☆☆,★ Sheeba Syed, FRCPath a,⁎, Nick Reed, FRCP b, David Millan, FRCPath a a b
Department of Pathology Laboratory Medicine/FM Building, Southern General Hospital, Glasgow, UK Beatson Oncology Centre, Glasgow, UK
a r t i c l e
i n f o
Keywords: Endometrial cancer Cervical sampling Cervical stromal invasion
a b s t r a c t Aim: To determine whether sampling one section, which includes the anterior and posterior cervical lips in hysterectomy specimens, provides the best prospect for detecting stromal invasion in hysterectomy specimens for endometrial cancers. Methods: To assess the most likely section in which cervical stromal invasion was identified in 29 cases. Results: Cervical stromal invasion was detected in first section in 75.8% cases, whereas 24.1% detected in random sections other than first section. Conclusion: Cervical stromal invasion is most likely to be identified in one section taken in the midline, which includes anterior and posterior lips. However, in a significant number of cases, this one section missed invasion, which was detected in other random cervical sections. Therefore, sampling of one block (anterior and posterior) from the cervix is insufficient for detecting cervical stromal invasion for endometrial cancer. © 2015 Elsevier Inc. All rights reserved.
Introduction About 10% of endometrial carcinomas exhibit some form of spread to the cervix at the time of hysterectomy. The presence of cervical invasion has been considered important for decades in the prognostication and therapy of endometrial carcinoma. Most oncologists administer adjuvant brachytherapy with or without other adjuvant treatments depending on the other risk factors present, for patients with cervical stromal invasion [1]. Women with tumors involving the cervix have an overall worse prognosis than do those whose neoplasms are confined to the uterine corpus. Data from the International Federation of Gynecology and Obstetrics (FIGO) 2003 showed 5-year survival rates for patients with cervical involvement to be 75% compared with 88% for stage I neoplasms [2]. The 1988 FIGO staging divided stage II into those tumors that involved the surface or glandular (crypt) epithelium alone (stage IIA) and those that spread to the cervical stroma with or without surface or glandular involvement (stage IIB) [3]. The 2009 revision of FIGO staging includes only those tumors that have spread to the cervical stroma as stage II [4]. Although the prognostic significance in distinguishing tumors of cervical glandular involvement alone is not clear with some studies, suggesting that overall survival ☆ Conflict of interest: None. ☆☆ Disclosures: None. ★ Patient anonymity and informed consent: Not applicable. ⁎ Corresponding author. Department of Pathology Laboratory Medicine/FM Building, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TF, UK. Tel.: +44 7792124133. E-mail addresses: [email protected] (S. Syed), [email protected] (N. Reed), [email protected] (D. Millan). http://dx.doi.org/10.1016/j.anndiagpath.2015.02.003 1092-9134/© 2015 Elsevier Inc. All rights reserved.
rates are better and recurrence rates are lower in cases with cervical glandular involvement than in cases with stromal involvement and no different than in tumors without cervical involvement [5]. Other studies [6,7] suggest that there is no prognostic significance in distinguishing between cervical glandular and stromal involvement. In some institutions, there is no difference in management between tumors exhibiting cervical glandular involvement only and those exhibiting stromal involvement, whereas others thought that this should not be upstaged. For example, with a lowgrade endometrial adenocarcinoma confined to the inner half of the myometrium, involvement of the endocervical epithelium may result in no adjuvant therapy, whereas cervical stromal involvement will result in adjuvant therapy [5]. Guidelines of The Royal College of Pathologists recommend at least 2 blocks be taken from the cervix, one from the anterior and one from the posterior lip [8]. However, in our department, it has been standard practise for the last decade to section the entire cervical canal for hysterectomy specimens of endometrial carcinoma. Methods Cervical sections of 29 consecutive cases of hysterectomy specimens (between April 2012 and April 2014) with reported cervical stromal involvement were included in this study. One of the most problematic areas in the pathologic reporting of endometrial carcinomas in hysterectomy specimens is the evaluation of cervical involvement, and there are a few guidelines regarding this. In many cases, cervical involvement is not apparent clinically, radiologically, or on gross examination of the specimen and is only identified on microscopic assessment. Because of interobserver variation in
44
S. Syed et al. / Annals of Diagnostic Pathology 19 (2015) 43–44
assessment of cervical stromal involvement by endometrial cancers, all cases in this study were assessed by at least 2 pathologists with specialist interest in gynecologic pathology for cervical stromal invasion. The cervical stromal involvement was examined in all the cervical sections taken. In our department, 1 block (1 section) includes anterior and posterior lips; additionally, the entire endocervical canal is processed longitudinally as done for cervical loop specimens along with sections of lower uterine segment. Although routine processing of cervix in hysterectomy specimens of endometrial carcinoma involves only 1 block (anterior and posterior lips) in our department, there has always been a protocol to sample the entire cervical canal since the change in FIGO staging from 1998 to 2009. Results The histologic subtypes with cervical stromal involvement were mainly endometrioid (62%), followed by serous (17.2%), carcinosarcoma (17.2%), and undifferentiated (3.6%); 62.2% of the cases were grade 3, 27.5% were grade 2, and 10.3% were grade I. lymphovascular space invasion was detected in 82.75% of the cases, especially the grade I with cervical stromal invasion. Of these 29 cases, cervical stromal invasion was detected in the first section (which included anterior and posterior lips) in 22 cases (75.8%). In the remaining 7 cases (24.2%), cervical stromal invasion was detected in sections S2 to S9. On an average, 4.6 sections were taken. The staging of the 29 cases (FIGO 2009) is shown in Table. Of the 7 cases with cervical stromal invasion missed in the first section, 3 were stage II, 3 were IIIA, and 1 was stage IV. Discussion Accurate staging of endometrial carcinoma in hysterectomy specimens is essential to ensure optimum patient management. It is worth emphasizing that cervical involvement by endometrial carcinoma may be extremely focal. This raises questions to the method of sampling the cervix in hysterectomy specimens from patients with endometrial carcinoma [5]. Evidence exists about sampling of cervix in hysterectomy after a previous diagnosis of cervical intraepithelial neoplasia [9]. Kadar et al [10] in their study have found that in stage II disease, stromal involvement occurs in 87% cases (II B) and surface epithelial involvement in only 13% of cases (II A), suggesting that spread of endometrial carcinoma to the cervix occurs predominantly by deep tissue planes or lymph channels. However, they published their study prior to the FIGO 2009 classification, according to which only cervical stromal involvement is classified as stage II. Rubin et al [11] and Jordan and Al-Nafussi [12] support the traditional concept that endometrial carcinoma spreads by surface contiguity or by implantation more frequently than by deep tissue planes or via lymphatics, and they recommended pathologists to approach trimming the cervix of any case of endometrial malignancy in a similar manner to the technique used in the dissection of a cone biopsy or of a cervix from a Wertheim hysterectomy specimen. Based on this concept, in our department, it is a protocol to sample entire endocervical canal in hysterectomy specimens of endometrial carcinomas. Our study was relatively small but proved that there can be a significant number of cases that can be missed in terms of cervical stromal involvement if routinely only 1 section (which includes anterior and posterior lip) is taken. Nearly a quarter (24.2%) is a significant number of cases potentially under staged and risking mismanagement by under treatment and even if we consider that the stage after microscopic assessment 10 % cases will be under staged. The other significant aspect noted was that even from
Table Distribution of staging of the 29 cases Staging by FIGO 2009
No. of cases
Stage II Stage IIIA Stage IIIB Stage IIIC1 Stage IVA
17 8 2 1 1
the 75.8% of cases in which cervical stromal invasion was detected in section I, there were 4 cases that showed no cervical stromal invasion in additional sections or the tumor appeared in random sections in a skip pattern. Our results contradicts the study of Nayar et al [13] that showed that sampling or the entire cervix does not identify any more cases of cervical involvement compared with the routine sampling of 2 blocks and the guidelines by the Royal College of Pathologists 2014 [8]. We have modified our standard operative procedure accordingly to ensure the highest quality of pathological interpretation is offered to our patients, and furthermore, we have rolled this Standard Operative Procedure out to the other network pathologists in our regional practice.
Conclusions Our study has shown that sampling of one block from the cervix is insufficient for detecting cervical stromal invasion for endometrial cancer. We assessed small numbers, and the evidence of our study will be strengthened by a multicenter trial.
References [1] McCluggage WG, Colgan T, Duggan M, et al. Data set for reporting of endometrial carcinomas: recommendations from the International Collaboration on Cancer Reporting (ICCR) between United Kingdom, United States, Canada, and Australasia. Int J Gynecol Pathol 2013;32(1):45–65. [2] Creasman WT, Odicino F, Maisonneuve P, Beller U, Benedet JL, Heintz AP, et al. Carcinoma of the corpus uteri. Int J Gynaecol Obstet 2003;83(Suppl. 1):79–118. [3] Shepherd JH. Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol 1989;96:889–92. [4] Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2010;108(2):176. [5] McCluggage WG, Hirschowitz L, Wilson GE, Oliva E, Soslow RA, Zaino RJ. Significant variation in the assessment of cervical involvement in endometrial carcinoma: an interobserver variation study. Am J Surg Pathol 2011;35(2):289–94. [6] Ayhan A, Taskiran C, Celik C, et al. The long-term survival of women with surgical stage II endometrioid type endometrial cancer. Gynecol Oncol 2004;93:9–13. [7] Jobsen JJ, Schutter EM, Meerwaldt JH, et al. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma. Int J Gynecol Cancer 2001;11: 49–53. [8] Standards and datasets for reporting cancers: Dataset for histological reporting of endometrial cancer. http://www.rcpath.org/Resources/RCPath/Migrated %20Resources/ Documents/G/G090_EndometrialDataset_Feb14.pdf; 2014. [Accessed on 1st Jan 2015]. [9] Greene A, Heatley MK. The appropriateness of examining the entire cervix histologically in hysterectomy specimens from women with a previous history of cervical intraepithelial neoplasia or dyskaryosis. J Clin Pathol 2001;54(2):155–7. [10] Kadar NR, Kohorn EI, LiVolsi VA, et al. Histologic variants of cervical involvement by endometrial carcinoma. Obstet Gynecol 1982;59(1):85–92. [11] Rubin SC, Hoskins WJ, Saigo PE, et al. Management of endometrial adenocarcinoma with cervical involvement. Gynecol Oncol 1992;45(3):294–8. [12] Jordan LB, Al-Nafussi A. Clinicopathological study of the pattern and significance of cervical involvement in cases of endometrial adenocarcinoma. Int J Gynecol Cancer 2002;12(1):42–8. [13] Nayar AG, Cross PA, Bulmer JN, et al. Comparison of examination of the entire uterine cervix with routine cervical sampling in hysterectomy specimens from women with endometrial cancer. J Clin Pathol 2008;61(5):621–2.
