Multicenter Study

. 2018 Sep;25(9):2756-2766.

doi: 10.1245/s10434-018-6547-x. Epub 2018 Jul 3.

Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma

Koji Matsuo¹, Yutaka Takazawa², Malcolm S Ross³, Esther Elishaev⁴, Mayu Yunokawa⁵, Todd B Sheridan⁶, Stephen H Bush⁷, Merieme M Klobocista⁸, Erin A Blake⁹, Tadao Takano¹⁰, Tsukasa Baba¹¹, Shinya Satoh¹², Masako Shida¹³, Yuji Ikeda¹⁴, Sosuke Adachi¹⁵, Takuhei Yokoyama¹⁶, Munetaka Takekuma¹⁷, Shiori Yanai¹⁸, Satoshi Takeuchi¹⁹, Masato Nishimura²⁰, Keita Iwasaki²¹, Marian S Johnson²², Masayuki Yoshida²³, Ardeshir Hakam²⁴, Hiroko Machida²⁵, Paulette Mhawech-Fauceglia²⁶, Yutaka Ueda²⁷, Kiyoshi Yoshino²⁷, Hiroshi Kajiwara²⁸, Kosei Hasegawa²⁹, Masanori Yasuda³⁰, Takahito M Miyake³¹, Takuya Moriya³², Yoshiaki Yuba³³, Terry Morgan³⁴, Tomoyuki Fukagawa³⁵, Tanja Pejovic³⁶, Tadayoshi Nagano³⁷, Takeshi Sasaki³⁸, Abby M Richmond³⁹, Miriam D Post³⁹, Mian M K Shahzad⁷, Dwight D Im⁴⁰, Hiroshi Yoshida²³, Takayuki Enomoto¹⁵, Kohei Omatsu⁴¹, Frederick R Ueland²², Joseph L Kelley³, Rouzan G Karabakhtsian^{42

43}, Lynda D Roman²⁵

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA. koji.matsuo@med.usc.edu.
² Department of Pathology, Cancer Institute Hospital, Tokyo, Japan.
³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, MaGee-Womens Hospital, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Department of Pathology, MaGee-Womens Hospital, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Department of Pathology, Mercy Medical Center, Baltimore, MD, USA.
⁷ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
⁸ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.
⁹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado, Boulder, CO, USA.
¹⁰ Department of Obstetrics and Gynecology, Tohoku University, Miyagi, Japan.
¹¹ Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Japan.
¹² Department of Obstetrics and Gynecology, Tottori University, Tottori, Japan.
¹³ Department of Obstetrics and Gynecology, Tokai University, Kanagawa, Japan.
¹⁴ Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
¹⁵ Department of Obstetrics and Gynecology, Niigata University, Niigata, Japan.
¹⁶ Department of Obstetrics and Gynecology, Osaka Rosai Hospital, Osaka, Japan.
¹⁷ Department of Gynecology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁸ Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan.
¹⁹ Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Japan.
²⁰ Department of Obstetrics and Gynecology, Tokushima University, Tokushima, Japan.
²¹ Department of Obstetrics and Gynecology, Aichi Medical University, Aichi, Japan.
²² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Kentucky Medical Center, Lexington, KY, USA.
²³ Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.
²⁴ Department of Pathology, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
²⁵ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
²⁶ Department of Pathology, University of Southern California, Los Angeles, CA, USA.
²⁷ Department of Obstetrics and Gynecology, Osaka University, Osaka, Japan.
²⁸ Department of Pathology, Tokai University, Kanagawa, Japan.
²⁹ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
³⁰ Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan.
³¹ Department of Obstetrics and Gynecology, Kawasaki Medical School, Okayama, Japan.
³² Department of Pathology, Kawasaki Medical School, Okayama, Japan.
³³ Department of Pathology, Kitano Hospital, Osaka, Japan.
³⁴ Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
³⁵ Department of Pathology, Iwate Medical University, Morioka, Japan.
³⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA.
³⁷ Department of Obstetrics and Gynecology, Kitano Hospital, Osaka, Japan.
³⁸ Department of Pathology, The University of Tokyo, Tokyo, Japan.
³⁹ Department of Pathology, University of Colorado, Boulder, CO, USA.
⁴⁰ Department of Gynecology, Mercy Medical Center, Baltimore, MD, USA.
⁴¹ Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan.
⁴² Department of Pathology, University of Kentucky Medical Center, Lexington, KY, USA.
⁴³ Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.

PMID: 29971677
PMCID: PMC7523233
DOI: 10.1245/s10434-018-6547-x

Multicenter Study

Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma

Koji Matsuo et al. Ann Surg Oncol. 2018 Sep.

. 2018 Sep;25(9):2756-2766.

doi: 10.1245/s10434-018-6547-x. Epub 2018 Jul 3.

Authors

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA. koji.matsuo@med.usc.edu.
² Department of Pathology, Cancer Institute Hospital, Tokyo, Japan.
³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, MaGee-Womens Hospital, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Department of Pathology, MaGee-Womens Hospital, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Department of Pathology, Mercy Medical Center, Baltimore, MD, USA.
⁷ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
⁸ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.
⁹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado, Boulder, CO, USA.
¹⁰ Department of Obstetrics and Gynecology, Tohoku University, Miyagi, Japan.
¹¹ Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Japan.
¹² Department of Obstetrics and Gynecology, Tottori University, Tottori, Japan.
¹³ Department of Obstetrics and Gynecology, Tokai University, Kanagawa, Japan.
¹⁴ Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
¹⁵ Department of Obstetrics and Gynecology, Niigata University, Niigata, Japan.
¹⁶ Department of Obstetrics and Gynecology, Osaka Rosai Hospital, Osaka, Japan.
¹⁷ Department of Gynecology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁸ Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan.
¹⁹ Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Japan.
²⁰ Department of Obstetrics and Gynecology, Tokushima University, Tokushima, Japan.
²¹ Department of Obstetrics and Gynecology, Aichi Medical University, Aichi, Japan.
²² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Kentucky Medical Center, Lexington, KY, USA.
²³ Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.
²⁴ Department of Pathology, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
²⁵ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
²⁶ Department of Pathology, University of Southern California, Los Angeles, CA, USA.
²⁷ Department of Obstetrics and Gynecology, Osaka University, Osaka, Japan.
²⁸ Department of Pathology, Tokai University, Kanagawa, Japan.
²⁹ Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
³⁰ Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan.
³¹ Department of Obstetrics and Gynecology, Kawasaki Medical School, Okayama, Japan.
³² Department of Pathology, Kawasaki Medical School, Okayama, Japan.
³³ Department of Pathology, Kitano Hospital, Osaka, Japan.
³⁴ Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
³⁵ Department of Pathology, Iwate Medical University, Morioka, Japan.
³⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA.
³⁷ Department of Obstetrics and Gynecology, Kitano Hospital, Osaka, Japan.
³⁸ Department of Pathology, The University of Tokyo, Tokyo, Japan.
³⁹ Department of Pathology, University of Colorado, Boulder, CO, USA.
⁴⁰ Department of Gynecology, Mercy Medical Center, Baltimore, MD, USA.
⁴¹ Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan.
⁴² Department of Pathology, University of Kentucky Medical Center, Lexington, KY, USA.
⁴³ Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.

PMID: 29971677
PMCID: PMC7523233
DOI: 10.1245/s10434-018-6547-x

Abstract

Objective: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS).

Methods: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome.

Results: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08).

Conclusion: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

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Conflict of interest statement

Disclosure All listed authors have no conflicts of interest to declare.

Figures

**FIG. 1**
Progression-free survival (a) and cause-specific survival (b) curves are shown based on LVSI type. Log-rank test for p values. LVSI-carcinoma: uterine tumor exhibiting LVSI with carcinomatous component only. LVSI-sarcoma: uterine tumor exhibiting LVSI with sarcomatous component with or without carcinomatous component. *LVSI* lymphovascular space invasion, *Car* carcinoma, *Sar* sarcoma

See this image and copyright information in PMC

References

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1. Matsuo K, Ross MS, Machida H, Blake EA, Roman LD. Trends of uterine carcinosarcoma in the United States. J Gynecol Oncol 2018;29:e22. - PMC - PubMed
1. Matsuo K, Takazawa Y, Ross MS, et al. Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma. Ann Oncol 2016;27:1257–1266. - PubMed
1. Morice P, Piovesan P, Rey A, et al. Prognostic value of lymphovascular space invasion determined with hematoxylin-eosin staining in early stage cervical carcinoma: results of a multivariate analysis. Ann Oncol 2003;14:1511–1517. - PubMed
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Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma

Affiliations

Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical