Objective: Liquid-based preparation (LBP) of the endometrial lesions is an important diagnostic tool for a variety of endometrial abnormalities because of its simplicity and high quali-quantitative diagnostic yield. We aimed to investigate the LBP method for endometrial cytology to evaluate both benign and abnormal endometrial lesions. Study Design: LBP is a semiautomated methodology that has recently become widely available and has gained popularity as a method of collecting and processing both gynecologic and nongynecologic cellular specimens. Results: Some peculiar endometrial cytoarchitectural features were described using LBPs. These were advantageous to screen as compared to conventional slides due to a smaller screening area and an excellent quality of cell preparations. Conclusions: LBP is a useful tool in the cellular diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBPs from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure.

1.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ: Cancer statistics, 2006. CA Cancer J Clin 2006;56:106-130.
2.
Oncology Committee: Annual report on cervical, endometrial, and ovarian cancer. Acta Obst Gynaec Jpn 2007;61:913-995.
3.
Nakagawa-Okamura C, Sato S, Tsuji I, Kuramoto H, Tsubono Y, Aoki D, Jobo T, Oomura M, Hisamichi S, Yajima A: Effectiveness of mass screening for endometrial cancer. Acta Cytol 2002;46:277-283.
4.
Geisinger KR, Stanley MW, Raab SS, Silverman JF, Abati A: Invasive glandular malignancies of the gynecologic tract; in Geisinger KR, Stanley MW, Raab SS, Silverman JF, Abati A (eds): Modern Cytopathology. Philadelphia, Churchill Livingstone, 2003, pp 147-197.
5.
Kobayashi H, Otsuki Y, Simizu S, Yamada M, Mukai R, Sawaki Y, Nakayama S, Torii Y: Cytological criteria of endometrial lesions with emphasis on stromal and epithelial cell clusters: result of 8 years of experience with intrauterine sampling. Cytopathology 2008;19:19-27.
6.
Norimatsu Y, Shimizu K, Kobayashi TK, Moriya T, Tsukayama C, Miyake Y, Ohno E: Cellular features of endometrial hyperplasia and well-differentiated adenocarcinoma using the Endocyte sampler: diagnositic criteria based on the cyto-architecture of tissue fragments. Cancer 2006;108:77-85.
7.
Nambu M, Matsumoto S, Takeshita M, Nabeshima K, Iwashita A: A multivariate statistical study to obtain effective criteria to detect well-differentiated adenocarcinoma in endometrial cytology. Diagn Cytopathol 2012;40:701-707.
8.
Norimatsu Y, Kouda H, Kobayashi TK, Moriya T, Yanoh K, Tsukayama C, Miyake Y, Ohno E: Utility of thin-layer preparations in the endometrial cytology: evaluation of benign endometrial lesions. Ann Diagn Pathol 2008;12:103-111.
9.
Norimatsu Y, Kouda H, Kobayashi TK, Shimizu K, Yanoh K, Tsukayama C, Miyake Y, Ohno E: Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma. Cytopathology 2009;20:395-402.
10.
Papaefthimiou M, Symiakaki H, Mentzelopoulou P, Giahnaki AE, Voulgaris Z, Diakomanolis E, Kyroudes A, Karakitsos P: The role of liquid-based cytology associated with curettage in the investigation of endometrial lesions from postmenopausal women. Cytopathology 2005;16:32-39.
11.
Papaefthimiou M, Symiakaki H, Mentzelopoulou P, Tsiveleka A, Kyroudes A, Voulgaris Z, Tzonou A, Karakitsos P: Study on the morphology and reproducibility of the diagnosis of endometrial lesions utilizing liquid-based cytology. Cancer 2005;105:56-64.
12.
Nishimura Y, Watanabe J, Jobo T, Hattori M, Arai T, Kuramoto H: Cytologic scoring of endometrioid adenocarcinoma of the endometrium. Cancer 2005;105:8-12.
13.
Hattori M, Kobayashi TK, Nishimura Y, Machida D, Toyonaga M, Tsunoda S, Ohbu M: Comparative image analysis of conventional and thin-layer preparations in endometrial cytology. Diagn Cytopathol 2013;41:527-532.
14.
Buccoliero AM, Gheri CF, Castiglione F, Garbini F, Barbetti A, Fambrini M, Bargelli G, Pappalardo S, Taddei A, Boddi V, Scarselli GF, Marchionni M, Taddei GL: Liquid-based endometrial cytology: cytohistological correlation in a population of 917 women. Cytopathology 2007;18:241-249.
15.
Buccoliero AM, Castiglione F, Gheri CF, Garbini F, Fambrini M, Bargelli G, Pappalardo S, Scarselli G, Marchionni M, Taddei GL: Liquid-based endometrial cytology: its possible value in postmenopausal asymptomatic women. Int J Gynecol Cancer 2007;17:182-187.
16.
Weintraub J, Morabia A: Efficacy of a liquid-based thin layer method for cervical cancer screening in a population with a low incidence of cervical cancer. Diagn Cytopathol 2000;22:52-59.
17.
Fremont-Smith M, Marino J, Griffin B, Spencer L, Bolick D: Comparison of the SurePath liquid-based Papanicolaou smear with the conventional Papanicolaou smear in a multisite direct-to-vial study. Cancer 2004 25;102:269-279.
18.
Bentz JS, Rowe LR, Gopez EV, Marshall CJ: The unsatisfactory ThinPrep Pap test: missed opportunity for disease detection? Am J Clin Pathol 2002;117:457-463.
19.
Beerman H, van Dorst EB, Kuenen-Boumeester V, Hogendoorn PC: Superior performance of liquid-based versus conventional cytology in a population-based cervical cancer screening program. Gynecol Oncol 2009;112:572-576.
20.
Michael CW, McConnel J, Pecott J, Afify AM, Al-Khafaji B: Comparison of ThinPrep and TriPath PREP liquid-based preparations in nongynecologic specimens: a pilot study. Diagn Cytopathol 2001;25:177-184.
21.
Belsley NA, Tambouret RH, Misdraji J, Muzikansky A, Russell DK, Wilbur DC: Cytologic features of endocervical glandular lesions: comparison of SurePath, ThinPrep, and conventional smear specimen preparations. Diagn Cytopathol 2008;36:232-237.
22.
Norimatsu Y, Sakamoto S, Ohsaki H, Ozaki S, Yokoyama T, Shimizu K, Yanoh K, Akiyama M, Bamba M, Kobayashi TK: Cytologic features of the endometrial adenocarcinoma: comparison of ThinPrep and BD SurePath preparations. Diagn Cytopathol 2013;41:673-681.
23.
Garcia F, Barker B, Davis J, Shelton T, Harrigill K, Schalk N, Meyer J, Hatch K: Thin-layer cytology and histopathology in the evaluation of abnormal uterine bleeding. J Reprod Med 2003;48:882-888.
24.
Kurman RJ, Kaminski PF, Norris HJ: The behavior of endometrial hyperplasia: a long-term study of ‘untreated' hyperplasia in 170 patients. Cancer 1985;56:403-412.
25.
Meisels A, Jolicoeur C: Criteria for the cytologic assessment of hyperplasia in endometrial samples obtained by the Endopap endometrial sampler. Acta Cytol 1985;29:297-302.
26.
Skaarland E: New concept in diagnostic endometrial cytology: diagnostic criteria based on composition and architecture of large tissue fragments in smears. J Clin Pathol 1986;39:36-43.
27.
Coscia-Porrazzi LO: Cytologic criteria of hyperplastic lesions in endometrial samples obtained by the endocyte sampler. Diagn Cytopathol 1988;4:283-287.
28.
Buckley CH, Fox H: Biopsy Pathology of the Endometrium, ed 2. New York, Arnold, 2002.
29.
Scully RE, Bonfiglio TA, Kurman RJ, Silverber SG, Wilkinson EJ (eds): Histological Typing of Female Genital Tract Tumours: WHO International Histological Classification of Tumours, ed 2. New York, Springer, 1994, pp 1-189.
30.
Ronnett BM, Kurman RJ: Precursor lesions of endometrial carcinoma; in Kurman RJ (ed): Blaustein's Pathology of the Female Genital Tract, ed 5. New York, Springer, 2001, pp 467-484.
31.
Kurman RJ, Norris HJ: Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer 1982;49:2547-2559.
32.
Silva M, Grinblat S, Sommers SC: 3-D reconstruction of endometrial carcinoma in situ. Am J Clin Pathol 1986;86:493-498.
33.
Silverberg SG, Kurman RJ: Endometrial carcinoma, tumors of the uterine corpus and gestational trophoblastic disease; in Silverberg SG, Kurman RJ (eds): Atlas of Tumor Pathology, series 3. Washington, Armed Forces Institute of Pathology, 1992, pp 15-90.
34.
Byren AJ: Endocyte endometrial smears in the cytodiagnosis of endometrial carcinoma. Acta Cytol 1990;34:373-381.
35.
Morse AR: The value of endometrial aspiration in gynecological practice; in Koss LG, Coleman DV (eds): Advances in Clinical Cytology. London, Butterworth, 1981, pp 44-63.
36.
Ehrmann RL: Atypical endometrial cells and stromal breakdown tow case reports. Acta Cytol 1975;19:465-469.
37.
Sherman ME, Mazur MT, Kurman RJ: Benign disease of the endometrium; in Kurman RJ (ed): Blaustein's Pathology of the Female Genital Tract, ed 5. New York, Springer, 2001, pp 431-439.
38.
Vakiani M, Vavilis D, Agorastos T, Stamatopoulos P, Assimaki A, Bontis J: Histopathological findings of the endometrium in patients with dysfunctional uterine bleeding. Clin Exp Obstet Gynecol 1996;23:236-239.
39.
Livingstone M, Fraser IS: Mechanisms of abnormal uterine bleeding. Hum Reprod Update 2002;8:60-67.
40.
Shimizu K, Norimatsu Y, Kobayashi TK, Ogura S, Miyake Y, Ohno E, Sakurai T, Moriya T, Sakurai M: Endometrial glandular and stromal breakdown, part 1: cytomorphological appearance. Diagn Cytopathol 2006;34:609-613.
41.
Frenczy A: Pathophysiology of endometrial bleeding. Maturitas 2003;45:1-14.
42.
Hendrickson MR, Kempson RL: Endometrial epithelial metaplasias: proliferations frequently misdiagnosed as adenocarcinoma: report of 89 cases and proposed classification. Am J Surg Pathol 1980;4:525-542.
43.
Andersen WA, Taylor PT Jr, Fechner RE, Pinkerton JA: Endometrial metaplasia associated with endometrial adenocarcinoma. Am J Obstet Gynecol 1987;157:597-604.
44.
Kaku T, Tsukamoto N, Tsuruchi N, Sugihara K, Kamura T, Nakano H: Endometrial metaplasia associated with endometrial carcinoma. Obstet Gynecol 1992;80:812-816.
45.
Jacques SM, Qureshi F, Lawrence WD: Surface epithelial changes in endometrial adenocarcinoma: diagnostic pitfalls in curettage specimens. Int J Gynecol Pathol 1995;14:191-197.
46.
Ronnett BM, Kurman RJ: Precursor lesions of endometrial carcinoma; in Kurman RJ (ed): Blaustein's Pathology of the Female Genital Tract, ed 5. New York, Springer, 2001, pp 484-493.
47.
Lehman MB, Hart WR: Simple and complex hyperplastic papillary proliferations of the endometrium: a clinicopathologic study of nine cases of apparently localized papillary lesions with fibrovascular stromal cores and epithelial metaplasia. Am J Surg Pathol 2001;25:1347-1354.
48.
Gribaudi G, Alasio L: Cytological changes caused by intrauterine devices. Pathologica 1981;73:207-216.
49.
Norimatsu Y, Shimizu K, Kobayashi TK, Moriya T, Kaku T, Tsukayama C, Miyake Y, Ohno E: Endometrial glandular and stromal breakdown, part 2: cytomorphology of papillary metaplastic changes. Diagn Cytopathol 2006;34:665-669.
50.
Zaman SS, Mazur MT: Endometrial papillary syncytial change: a nonspecific alteration associated with active breakdown. Am J Clin Pathol 1993;99:741-745.
51.
Norimatsu Y, Kawai M, Kamimori A, Yuminamochi T, Ohsaki H, Yanoh K, Kawanishi N, Kobayashi TK: Endometrial glandular and stromal breakdown, part 4: cytomorphology of ‘condensed cluster of stromal cells including a light green body'. Diagn Cytopathol 2012;40:204-209.
52.
Maksem JA, Robboy SJ, Bishop JW, Meiers I: Benign endometrial abnormalities; in Rosenthal DL (ed): Endometrial Cytology with Tissue Correlatioms, ed 1. New York, Springer Science and Business Media, 2009, pp 97-152.
53.
Kuzu I, Bicknell R, Harris AL, Jones M, Gatter KC, Mason DY: Heterogeneity of vascular endothelial cells with relevance to diagnosis of vascular tumours. J Clin Pathol 1992;45:143-148.
54.
Sadler JE: A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1994;71:520-525.
55.
Cranmer SL, Ulsemer P, Cooke BM, Salem HH, de la Salle C, Lanza F, Jackson SP: Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow: importance of the GPIb /actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear. J Biol Chem 1999 5;274:6097-6106.
56.
Norimatsu Y, Yuminamochi T, Shigematsu Y, Yanoh K, Ikemoto R, Masuno H, Murakami M, Kobayashi TK: Endometrial glandular and stromal breakdown, part 3: cytomorphology of ‘condensed cluster of stromal cells'. Diagn Cytopathol 2009;37:891-896.
57.
Norimatsu Y, Shigematsu Y, Sakamoto S, Ohsaki H, Yanoh K, Kawanishi N, Kobayashi TK: Nuclear features in endometrial cytology: comparison of endometrial glandular and stromal breakdown and endometrioid adenocarcinoma grade 1. Diagn Cytopathol 2012;40:1077-1082.
58.
Ng ABP: Endpmetrial hyperplasia and carcinoma and extrauterine cancer; in Bibbo M (ed): Comprehensive Cytopathplogy, ed 2. Philadelphia: W.B. Saunders Company, 2001, pp 251-277.
59.
Norimatsu Y, Shigematsu Y, Sakamoto S, Ohsaki H, Yanoh K, Kawanishi N, Kobayashi TK: Nuclear characteristics of the endometrial cytology: liquid-based versus conventional preparation. Diagn Cytopathol 2013;41:120-125.
60.
Boon ME, Drijver JS: Comparing cells in histology and cytology; in Boon ME (ed): Routine Cytological Staining Techniques: Theoretical Background and Practice, ed 1. London, MaCmillian Education, 1986, pp 22-25.
61.
Kaneko M: Fixation and the theory (in Japanese); in Tanaka N (ed): Textbook of Diagnostic Cytology: Its Fundamentals and Practice, ed 6. Tokyo, Uchudo Yagi-Shoten, 1979, pp 66-70.
62.
Wappenschmidt B, Wardelmann E, Gehrig A, Schöndorf T, Maass N, Bonatz G, Gassel AM, Pietsch T, Mallmann P, Weber BH, Schmutzler RK: PTEN mutations do not cause nuclear beta-catenin accumulation in endometrial carcinomas. Hum Pathol 2004;35:1260-1265.
63.
Lax SF: Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 2004;444:213-223.
64.
Hech JL, Mutter GL: Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 2006;24:4783-4791.
65.
Norimatsu Y, Moriya T, Kobayashi TK, Sakurai T, Shimizu K, Tsukayama C, Ohno E: Immunohistochemical expression of PTEN and β-catenin for endometrial intraepithelial neoplasia in Japanese women. Ann Diagn Pathol 2007;11:103-108.
66.
Norimatsu Y, Miyamoto T, Kobayashi TK, Oda T, Moriya T, Yanoh K, Miyake Y, Ohno E: Utility of thin-layer preparations in endometrial cytology: immunocytochemical expression of PTEN, β-catenin and p53 for benign endometrial lesions. Diagn Cytopathol 2008;36:216-223.
67.
Norimatsu Y, Miyamoto M, Kobayashi TK, Moriya T, Shimizu K, Yanoh K, Tsukayama C, Miyake Y, Ohno E: Diagnostic utility of phosphatase and tensin homolog, β-catenin, and p53 for endometrial carcinoma by thin layer endometrial preparations. Cancer 2008;114:155-164.
68.
McCluggage WG, Sumathi VP, Maxwell P: CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology 2001;39:273-278.
69.
Jung CK, Jung JH, Lee A, Lee YS, Choi YJ, Yoon SK, Lee KY: Diagnostic use of nuclear β-catenin expression for the assessment of endometrial stromal tumors. Mod Pathol 2008;21:756-763.
70.
Sumathi VP, Al-Hussaini M, Connolly LE, Fullerton L, McCluggage WG: Endometrial stromal neoplasms are immunoreactive with WT-1 antibody. Int J Gynecol Pathol 2004; 23:241-224.
71.
Oliva E, Young RH, Amin MB, Clement PB: An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am J Surg Pathol 2002;26:403-412.
72.
Shiozawa T, Xin L, Nikaido T, Fujii S: Immunohistochemical detection of cyclin A with reference to p53 expression in endometrial endometrioid carcinomas. Int J Gynecol Pathol 1997;16:348-353.
73.
Shih HC, Shiozawa T, Kato K, Imai T, Miyamoto T, Uchikawa J, Nikaido T, Konishi I: Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor-suppressor gene products, Ki-67, and sex steroid receptors in endometrial carcinoma: positive staining for cyclin A as a poor prognostic indicator. Hum Pathol 2003;34:471-478.
74.
Kounelis S, Kapranos N, Kouri E, Coppola D, Papadaki H, Jones MW: Immunohistochemical profile of endometrial adenocarcinoma: a study of 61 cases and review of the literature. Mod Pathol 2000;13:379-388.
75.
Kyushima N, Watanabe J, Hata H, Jobo T, Kameya T, Kuramoto H: Expression of cyclin A in endometrial adenocarcinoma and its correlation with proliferative activity and clinicopathological variables. J Cancer Res Clin Oncol 2002;128:307-312.
76.
Norimatsu Y, Ohsaki H, Yanoh K, Kawanishi N, Kobayashi TK: Expression of immunoreactivity of nuclear findings by p53 and cyclin a in endometrial cytology: comparison with endometrial glandular and stromal breakdown and endometrioid adenocarcinoma grade 1. Diagn Cytopathol 2013;41:303-307.
77.
Yanoh K, Norimatsu Y, Hirai Y, Takeshima N, Kamimori A, Nakamura Y, Shimizu K, Kobayashi TK, Murata T, Shiraishi T: New diagnostic reporting format for endometrial cytology based on cytoarchitectural criteria. Cytopathology 2009;20:388-394.
78.
Kobayashi TK, Norimatsu Y, Buccoliero AM: Cytology of the body of the uterus; in Gray W, Kocjan G (eds): Diagnostic Cytopathology, ed 3. London, Churchill Livingstone, 2010, pp 689-719.
79.
Yanoh K, Hirai Y, Sakamoto A, Aoki D, Moriya T, Hiura M, Yamawaki T, Shimizu K, Nakayama H, Sasaki H, Tabata T, Ueda M, Udagawa Y, Norimatsu Y: New terminology for intrauterine endometrial samples: a group study by the Japanese Society of Clinical Cytology. Acta Cytol 2012;56:233-241.
80.
Yanoh K, Norimatsu Y, Munakata S, Yamamoto T, Nakamura Y, Murata T, Hirai Y, for the Osaki Study Group (OSG): A pilot study examining the sensitivity and specificity of cytological examinations of uterine endometrium samples prepared with the SurePath method. Acta Cytol 2013, submitted.
81.
Barut A, Barut F, Arikan I, Harma M, Harma MI, Ozmen Bayar U: Comparison of the histopathological diagnoses of preoperative dilatation and curettage and hysterectomy specimens. J Obstet Gynaecol Res 2012;38:16-22.
82.
Jimenez-Ayala M: New terminology for intrauterine endometrial samples: a group study by the Japanese society of cytology. Acta Cytol 2013;57:113-114.
83.
Yanoh K, Hirai Y, Sakamoto A, Aoki D, Moriya T, Hiura M, Yamawaki T, Shimizu K, Nakayama H, Sasaki H, Tabata T, Ueda M, Udagawa Y, Norimatsu Y: Authors' reply. Acta Cytol 2013;57:114.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.