Malignant ascites occurs most often in patients with high-grade serous papillary ovarian cancer at initial diagnosis: a retrospective analysis of 191 women treated at Bayreuth Hospital, 2006–2015

  • Jens Krugmann
  • Corinna Lang Schwarz
  • Balint Melcher
  • William Sterlacci
  • Agne Ozalinskaite
  • Johannes Lermann
  • Abbas Agaimy
  • Michael Vieth
Gynecologic Oncology



Malignant ascites often develops in patients with ovarian cancer, but there is a lack of more detailed characterization of the different histological subtypes.


Ascites specimens from patients with ovarian cancer who were treated at Bayreuth Hospital from 2006 to 2015, with follow-up until December 2016, were reevaluated retrospectively.


A total of 191 women (mean age 64 years, range 48–79) were included, of whom 180 (94.2%) had carcinoma, three (1.6%) had malignant mixed müllerian tumors (MMMTs), four (2.1%) had sex cord–stromal tumors (SCSTs), three (1.6%) had germ cell tumors (GCTs), and one (0.5%) had a sarcoma. The carcinoma group comprised 134 (70.1%) patients with high-grade serous papillary ovarian cancer, 17 (8.9%) with low-grade serous papillary ovarian cancer, 10 (5.3%) with mucinous carcinomas, nine (4.7%) with endometrioid carcinomas, six (3.1%) with clear cell carcinomas, and four (2.1%) with neuroendocrine tumors. The latter group consisted of two patients with mixed neuroendocrine–nonneuroendocrine tumors (MiNENs), one with only a small cell carcinoma (SCCO), and one with a mucinous carcinoid. The noncarcinomatous group of eight patients (4.2%) included three (1.6%) with Sertoli–Leydig cell tumor and mature cystic teratoma (MCT), one (0.5%) with a granulosa cell tumor, and one with a leiomyosarcoma. A statistically significant difference in the proportion of patients with malignant ascites was observed, at 17.7% (3/17) in those with low-grade serous papillary ovarian cancer and 91.8% (123/134) in those with high-grade serous papillary ovarian carcinomas. In both patients with MiNEN, the glandular tumor cell component was found in the ascites. Tumor cells were found in the ascitic fluid in 50% (5/10) of patients with mucinous ovarian carcinomas, 16.7% (1/6) of those with clear cell carcinomas, and 33.3% (1/3) of those with MMMTs. The two patients (2/3; 66.7%) with neoplastic squamous cell components in MCT and the only patient with a granulosa cell tumor in the SCST group (1/4; 25%) had malignant cell populations in the ascites, whereas patients with endometrioid cell carcinoma and leiomyosarcoma lacked tumor cells in the ascites. The malignant ascites was detected at the initial diagnosis in all 138 (100%) patients with ovarian neoplasms.


High-grade serous papillary ovarian cancer was the main histological subtype most frequently found in ascites fluid in this series. The significant difference (P < 0.00001) in the malignancy rate in comparison with low-grade serous papillary carcinoma confirms the histological distinction between the two entities. Initial evidence of ovarian cancer in ascites fluid allows correct primary diagnosis in cytology specimens and is important for staging and prognosis.


Malignant ascites Ovarian tumors Histological subtypes 



The contribution of A. Ozalinskaite to this publication was performed in partial fulfillment of the requirements for obtaining the degree of Doctor of Medicine. Parts of the study published here have been used for her doctoral thesis at the Medical Faculty of the Friedrich-Alexander University Erlangen-Nuremberg.

Author contributions

JK project development, data collection, data analysis, manuscript writing; CLS data collection, data analysis; BM data collection, manuscript writing; WS data analysis, manuscript editing; AO data collection; JL project development, manuscript editing; AA project development, manuscript editing; MV project development, manuscript editing.

Compliance with ethical standards

Conflict of interest

All authors declare that there are no conflicts of interest.


  1. 1.
    Robert Koch Institut. Zentrum für Krebsregisterdaten (2017) Eierstockkrebs (Ovarialkarzinom). Accessed 16 Mar 2018
  2. 2.
    Quirk JT, Natarajan N (2005) Ovarian cancer incidence in the United States, 1992–1999. Gynecol Oncol 97(2):519–523. (PMID:15863154) CrossRefPubMedGoogle Scholar
  3. 3.
    Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177(3):1053–1064. (PMID:20651229) CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Salani R, Bristow RE (2012) Surgical management of epithelial ovarian cancer. Clin Obstet Gynecol 55(1):75–95. (PMID:22343231) CrossRefPubMedGoogle Scholar
  5. 5.
    Wright AA, Bohlke K, Edelson MI (2016) Neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer: Society of Gynecologic Oncology and ASCO clinical practice guideline summary. J Oncol Pract 12(12):1254–1257. (PMID:27624951) CrossRefGoogle Scholar
  6. 6.
    Kurman RJ, International Agency for Research on Cancer, World Health Organization (2014) WHO classification of tumours of female reproductive organs, 4th edn. International Agency for Research on Cancer, LyonGoogle Scholar
  7. 7.
    Arikan SK, Kasap B, Yetimalar H, Yildiz A, Sakarya DK, Tatar S (2014) Impact of prognostic factors on survival rates in patients with ovarian carcinoma. Asian Pac J Cancer Prev 15(15):6087–6094 (PMID:25124578) CrossRefGoogle Scholar
  8. 8.
    Sangisetty SL, Miner TJ (2012) Malignant ascites: a review of prognostic factors, pathophysiology and therapeutic measures. World J Gastrointest Surg 4(4):87–95. (PMID:22590662) CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Runyon BA, Hoefs JC, Morgan TR (1988) Ascitic fluid analysis in malignancy-related ascites. Hepatology 8(5):1104–1109 (PMID:3417231) CrossRefGoogle Scholar
  10. 10.
    Parsons SL, Watson SA, Steele RJ (1996) Malignant ascites. Br J Surg 83(1):6–14 (PMID:8653366) CrossRefGoogle Scholar
  11. 11.
    Krugmann J, Melcher B, Deuerling J, Mühldorfer S, Vieth M (2017) Klinisch-zytologische Korrelation der Aszitesdiagnostik bei gastrointestinalen Erkrankungen am Klinikum Bayreuth—eine retrospektive Untersuchung an 256 Patienten. Verdauungskrankheiten 35(3):129–139. CrossRefGoogle Scholar
  12. 12.
    Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R, Abbruzzese JL (2006) Metastatic patterns in adenocarcinoma. Cancer 106(7):1624–1633. (PMID:16518827) CrossRefPubMedGoogle Scholar
  13. 13.
    Garrison RN, Kaelin LD, Galloway RH, Heuser LS (1986) Malignant ascites. Clinical and experimental observations. Ann Surg 203(6):644–651 (PMID:3718029) CrossRefGoogle Scholar
  14. 14.
    Sorbe B, Frankendal B (1983) Prognostic importance of ascites in ovarian carcinoma. Acta Obstet Gynecol Scand 62(5):415–418 (PMID:6666554) CrossRefGoogle Scholar
  15. 15.
    Fadare O, Mariappan MR, Wang S, Hileeto D, McAlpine J, Rimm DL (2004) The histologic subtype of ovarian tumors affects the detection rate by pelvic washings. Cancer 102(3):150–156. (PMID:15211473) CrossRefPubMedGoogle Scholar
  16. 16.
    Valente PT, Schantz HD, Edmonds PR, Hanjani P (1992) Peritoneal cytology of uncommon ovarian tumors. Diagn Cytopathol 8(2):98–106 (PMID:1314733) CrossRefGoogle Scholar
  17. 17.
    Selvaggi SM (1994) Small-cell carcinoma of the ovary in peritoneal fluid. Diagn Cytopathol 11(3):266–270 (PMID:7867470) CrossRefGoogle Scholar
  18. 18.
    Mandai M, Konishi I, Koshiyama M, Komatsu T, Yamamoto S, Nanbu K, Mori T, Fujii S (1996) Ascitic positive cytology and intraperitoneal metastasis in ovarian dysgerminoma. J Obstet Gynaecol Res 22(1):89–94 (PMID:8624900) CrossRefGoogle Scholar
  19. 19.
    Hirakawa E, Kobayashi S, Miki H, Haba R, Saoo K, Ohkura I, Kira Y (2001) Ascitic fluid cytology of adenosarcoma of the ovary: a case report. Diagn Cytopathol 24(5):343–346 (PMID:11335966) CrossRefGoogle Scholar
  20. 20.
    Davidson B, Abeler VM (2005) Primary ovarian angiosarcoma presenting as malignant cells in ascites: case report and review of the literature. Diagn Cytopathol 32(5):307–309. (PMID:15830366) CrossRefPubMedGoogle Scholar
  21. 21.
    Ikeda K, Tate G, Suzuki T, Mitsuya T (2005) Effusion cytodiagnosis of carcinosarcoma derived from the female genital tract: immunohistochemical features of MMP-7 and Ki-67 and immunofluorescence double staining analyses of eight cases. Gynecol Oncol 97(2):323–329. (PMID:15863125) CrossRefPubMedGoogle Scholar
  22. 22.
    Murugan P, Siddaraju N, Sridhar E, Soundararaghavan J, Habeebullah S (2010) Unusual ovarian malignancies in ascitic fluid: a report of 2 cases. Acta Cytol 54(4):611–617. (PMID:20715666) CrossRefPubMedGoogle Scholar
  23. 23.
    Mensi DW (2011) Cytologic findings in two cases of dermoid cysts with malignant transformation. Diagn Cytopathol 39(12):919–923. (PMID:22081528) CrossRefPubMedGoogle Scholar
  24. 24.
    Omori M, Kondo T, Yuminamochi T, Nakazawa K, Ishii Y, Fukasawa H, Hashi A, Hirata S (2015) Cytologic features of ovarian granulosa cell tumors in pleural and ascitic fluids. Diagn Cytopathol 43(7):581–584. (PMID:25605680) CrossRefPubMedGoogle Scholar
  25. 25.
    Damiani D, Suciu V, Andreiuolo F, Calderaro J, Vielh P (2015) Young investigator challenge: cytomorphologic analysis of cerebrospinal fluid in 70 pediatric patients with medulloblastoma and review of the literature focusing on novel diagnostic and prognostic tests. Cancer Cytopathol 123(11):644–649. (PMID:26769585) CrossRefPubMedGoogle Scholar
  26. 26.
    Harbhajanka A, Bitterman P, Reddy VB, Park JW, Gattuso P (2016) Cytomorphology and clinicopathologic correlation of the recurrent and metastatic adult granulosa cell tumor of the ovary: a retrospective review. Diagn Cytopathol 44(12):1058–1063. (PMID:27493080) CrossRefPubMedGoogle Scholar
  27. 27.
    Social Science Statistics (2018) Chi square test calculator. Accessed 16 Mar 2018
  28. 28.
    Rodriguez EF, Monaco SE, Khalbuss W, Austin RM, Pantanowitz L (2013) Abdominopelvic washings: a comprehensive review. CytoJournal 10:7. (PMID:23858317) CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Živadinović R, Petrić A, Krtinić D, Stevanović Milosević J, Pop Trajković Dinić S (2015) Ascites in ovarian carcinoma—reliability and limitations of cytological analysis. West Indian Med J 64(3):236–240. (PMID:26426176) CrossRefPubMedGoogle Scholar
  30. 30.
    Sedlaczek P, Frydecka I, Gabryś M, Van Dalen A, Einarsson R, Harłozińska A (2002) Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin-2 receptor alpha levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma. Cancer 95(9):1886–1893. (PMID:12404282) CrossRefPubMedGoogle Scholar
  31. 31.
    Prat J (1999) Ovarian tumors of borderline malignancy (tumors of low malignant potential): a critical appraisal. Adv Anat Pathol 6(5):247–274 (PMID:10472378) CrossRefGoogle Scholar
  32. 32.
    Licaj I, Jacobsen BK, Selmer RM, Maskarinec G, Weiderpass E, Gram IT (2017) Smoking and risk of ovarian cancer by histological subtypes: an analysis among 300,000 Norwegian women. Br J Cancer 116(2):270–276. (PMID:27959888) CrossRefPubMedGoogle Scholar
  33. 33.
    Heintz APM, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HYS, Pecorelli S, Beller U (2006) Carcinoma of the ovary. FIGO 26th Annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 95(Suppl 1):S161–S192. (PMID:17161157) CrossRefPubMedGoogle Scholar
  34. 34.
    Prat J, FIGO Committee on Gynecologic Oncology (2015) FIGO’s staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication. J Gynecol Oncol 26(2):87–89. (PMID:25872889) CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Shih IM, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164(5):1511–1518 (PMID:15111296) CrossRefGoogle Scholar
  36. 36.
    Prat J (2012) Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch Int J Pathol 460(3):237–249. (PMID:22322322) CrossRefGoogle Scholar
  37. 37.
    Howitt BE, Kelly P, McCluggage WG (2017) Pathology of neuroendocrine tumours of the female genital tract. Curr Oncol Rep 19(9):59. (PMID:28735441) CrossRefPubMedGoogle Scholar
  38. 38.
    McCluggage WG, Witkowski L, Clarke BA, Foulkes WD (2017) Clinical, morphological and immunohistochemical evidence that small-cell carcinoma of the ovary of hypercalcaemic type (SCCOHT) may be a primitive germ-cell neoplasm. Histopathology 70(7):1147–1154. (PMID:28130795) CrossRefPubMedGoogle Scholar
  39. 39.
    Witkowski L, Donini N, Byler-Dann R, Knost JA, Albrecht S, Berchuk A, McCluggage WG, Hasselblatt M, Foulkes WD (2017) The hereditary nature of small cell carcinoma of the ovary, hypercalcemic type: two new familial cases. Fam Cancer 16(3):395–399. (PMID:27866340) CrossRefPubMedGoogle Scholar
  40. 40.
    Perren TJ (2016) Mucinous epithelial ovarian carcinoma. Ann Oncol 27(Suppl 1):i53–i57. (PMID:27141073) CrossRefPubMedGoogle Scholar
  41. 41.
    Waldstrøm M, Grove A (2005) Immunohistochemical expression of Wilms tumor gene protein in different histologic subtypes of ovarian carcinomas. Arch Pathol Lab Med 129(1):85–88 (PMID:15628914) PubMedGoogle Scholar
  42. 42.
    Tabrizi AD, Kalloger SE, Köbel M, Cipollone J, Roskelley CD, Mehl E, Gilks CB (2010) Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases. Int J Gynecol Pathol 29(2):99–107. (PMID:20173494) CrossRefPubMedGoogle Scholar
  43. 43.
    Hu A, Li H, Zhang L, Ren C, Wang Y, Liu Y, Liu C (2015) Differentiating primary and extragenital metastatic mucinous ovarian tumours: an algorithm combining PAX8 with tumour size and laterality. J Clin Pathol 68(7):522–528. (PMID:25827135) CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Strickland S, Wasserman JK, Giassi A, Djordjevic B, Parra-Herran C (2016) Immunohistochemistry in the diagnosis of mucinous neoplasms involving the ovary: the added value of SATB2 and biomarker discovery through protein expression database mining. Int J Gynecol Pathol 35(3):191–208. (PMID:26535987) CrossRefPubMedGoogle Scholar
  45. 45.
    Badyal RK, Khairwa A, Rajwanshi A, Nijhawan R, Radhika S, Gupta N, Dey P (2016) Significance of epithelial cell clusters in pseudomyxoma peritonei. Cytopathology 27(6):418–426. (PMID:27121698) CrossRefPubMedGoogle Scholar
  46. 46.
    Malpica A (2016) How to approach the many faces of endometrioid carcinoma. Mod Pathol 29(Suppl 1):S29–S44. (PMID:26715172) CrossRefPubMedGoogle Scholar
  47. 47.
    Goldberg A, Hand L, DeCotiis D, Rosenblum N, Chan J (2018) Microcystic, elongated, and fragmented pattern invasion in ovarian endometrioid carcinoma: immunohistochemical profile and prognostic implications. Int J Gynecol Pathol 37(1):44–51. (PMID:28319570) CrossRefPubMedGoogle Scholar
  48. 48.
    Storey DJ, Rush R, Stewart M, Rye T, Al-Nafussi A (2008) Endometrioid epithelial ovarian cancer: 20 years of prospectively collected data from a single center. Cancer 112(10):2211–2220. (PMID:18344211) CrossRefPubMedGoogle Scholar
  49. 49.
    Hirasawa T, Yasuda M, Muramatsu T, Itoh H, Shinozuka T, Makino T, Tsutsumi Y, Osamura RY (1997) Cytologic study of ascites and the endometrium in ovarian carcinoma. Clinical significance. Acta Cytol 41(5):1451–1455. (PMID:9305383) CrossRefPubMedGoogle Scholar
  50. 50.
    Takeda T, Banno K, Okawa R, Yanokura M, Iijima M, Irie-Kunitomi H, Nakamura K, Iida M, Adachi M, Umene K, Nogami Y, Masuda K, Kobayashi Y, Tominaga E, Aoki D (2016) ARID1A gene mutation in ovarian and endometrial cancers (review). Oncol Rep 35(2):607–613. (PMID:26572704) CrossRefPubMedGoogle Scholar
  51. 51.
    Vera-Alvarez J, García-Prats MD, Marigil-Gómez M, Abascal-Agorreta M, López-López JI, Ramón-Cajal JM (2007) Clear cell carcinoma of the ovary diagnosed in ascitic fluid. A case report. Acta Cytol 51(1):107–112. (PMID:17328509) CrossRefPubMedGoogle Scholar
  52. 52.
    Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M, Takahashi S (2015) Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Mod Pathol 28(1):111–117. (PMID:24721826) CrossRefPubMedGoogle Scholar
  53. 53.
    Iwamoto M, Nakatani Y, Fugo K, Kishimoto T, Kiyokawa T (2015) Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium. Hum Pathol 46(7):957–962. (PMID:25971546) CrossRefPubMedGoogle Scholar
  54. 54.
    Lim D, Ip PPC, Cheung ANY, Kiyokawa T, Oliva E (2015) Immunohistochemical comparison of ovarian and uterine endometrioid carcinoma, endometrioid carcinoma with clear cell change, and clear cell carcinoma. Am J Surg Pathol 39(8):1061–1069. (PMID:25871622) CrossRefPubMedGoogle Scholar
  55. 55.
    del Carmen MG, Birrer M, Schorge JO (2012) Carcinosarcoma of the ovary: a review of the literature. Gynecol Oncol 125(1):271–277. (PMID:22155675) CrossRefPubMedGoogle Scholar
  56. 56.
    George EM, Herzog TJ, Neugut AI, Lu YS, Burke WM, Lewin SN, Hershman DL, Wright JD (2013) Carcinosarcoma of the ovary: natural history, patterns of treatment, and outcome. Gynecol Oncol 131(1):42–45. (PMID:23838036) CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Shah SP, Köbel M, Senz J et al (2009) Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 360(26):2719–2729. (PMID:19516027) CrossRefPubMedGoogle Scholar
  58. 58.
    Seagle BLL, Ann P, Butler S, Shahabi S (2017) Ovarian granulosa cell tumor: a National Cancer Database study. Gynecol Oncol 146(2):285–291. (PMID:28532858) CrossRefPubMedGoogle Scholar
  59. 59.
    Lin KY, Bryant S, Miller DS, Kehoe SM, Richardson DL, Lea JS (2014) Malignant ovarian germ cell tumor—role of surgical staging and gonadal dysgenesis. Gynecol Oncol 134(1):84–89. (PMID:24836278) CrossRefPubMedGoogle Scholar
  60. 60.
    Rathore R, Sharma S, Arora D (2017) Clinicopathological evaluation of 223 cases of mature cystic teratoma, ovary: 25-year experience in a single tertiary care centre in India. J Clin Diagn Res 11(4):EC11–EC14. (PMID:28571142) CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Abhilasha N, Bafna UD, Pallavi VR, Rathod PS, Krishnapa S (2016) A review of squamous cell carcinoma arising in mature cystic teratoma of the ovary. Indian J Cancer 53(4):612–614. (PMID:28485364) CrossRefPubMedGoogle Scholar
  62. 62.
    Junaid TA (1981) Ovarian neoplasms in children and adolescents in Ibadan, Nigeria. Cancer 47(3):610–614 (PMID:6261913) CrossRefGoogle Scholar
  63. 63.
    Akakpo PK, Derkyi-Kwarteng L, Gyasi RK, Quayson SE, Naporo S, Anim JT (2017) A pathological and clinical study of 706 primary tumours of the ovary in the largest tertiary hospital in Ghana. BMC Women’s Health 17(1):34. (PMID:28415994) CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of PathologyKlinikum BayreuthBayreuthGermany
  2. 2.Department of Obstetrics and GynecologyKlinikum BayreuthBayreuthGermany
  3. 3.Institute of PathologyUniversity of ErlangenErlangenGermany

Personalised recommendations