Table of Contents    
Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): Pathogenesis and clinical significance
Giovanna Giordano
Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit, University of Parma, Parma, Italy, Viale A Gramsci 14 43126 Parma.

Article ID: 100002M12GG2015

Address correspondence to:
Giovanna Giordano
MD, Ph.D, Department of Biomedical, Biotechnological and Translational Sciences
Pathological, Anatomy and Histology Unit, University of Parma
Parma, Italy, Viale A Gramsci 14, 43126 Parma
Phone: +39 0521 702625
Fax: 39 0521 292710

Access full text article on other devices

  Access PDF of article on other devices

[HTML Abstract]   [PDF Full Text] [Print This Article]
[Similar article in Pumed] [Similar article in Google Scholar]

How to cite this article
Giordano G. Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): Pathogenesis and clinical significance. Edorium J Mol Pathol 2015;1:5–8.

Back in 1929, Taylor first described borderline ovarian tumors (BOTs) as "semi-malignant ovarian tumors", since an ovarian hyperplastic cyst could mimic malignancy with relatively favorable outcome even when associated with widespread peritoneal dissemination [1].

In 1973, the World Health Organization (WHO)proposed the term of "borderline tumor" and added the synonym 'carcinoma with low malignant potential' (LMP) in their classification of ovarian tumors [2] [3].

According to the WHO definition, an ovarian borderline epithelial tumor histologically lacks obvious invasion of the stroma, while its mitotic activity and nuclear abnormalities intermediate between clearly benign and unquestionably malignant tumors.

In 1999, combined classification of the International Society of Gynecologic Pathologists and the WHO, the term 'LMP Tumor' replaced 'LMP carcinoma' as a synonym of BOT [3].

Serous BOTs are the most common type, bilaterality is seen in 25–50% of histotypes [4].

Histologically, typical borderline serous tumors are noninvasive proliferative neoplasms characterized by multiple fibrous papillae with extensive and complex hierarchical branching. Moreover, the epithelium of papillae shows multi-layering of more than four cell layers. Neoplastic cells show mild nuclear atypia (slight pleomorphism, sometimes prominent nucleoli).

Detachment and exfoliation of cells from the papillae is another feature of neoplasm. Mitotic figures may be absent or found in very small numbers, and are not abnormal [5].

Although BOTs are tumors without invasion, foci of stromal micro-invasion (invasive foci smaller than 10 mm2 and less than 3 mm in their longest linear dimension) have been observed.

Recognition of lymph node involvement in BOT has engendered discussion about its pathogenesis and prognostic significance in the international literature

Pathogenesis of lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors)

To explain the occurrence of lymph node involvement in the lymph nodes of patients with ovarian serous borderline tumors (SBTs), two theories have been suggested, designated respectively "endosalpingiosis" and "metastatic".

According to the "Endosalpingiosis Theory", nodal SBTs could develop from nodal endosalpingiotic glands, which are non-neoplastic inclusions of the Müllerian type that possess neoplastic potential. In support of this theory, there are cases in which some authors have observed morphologic transitions between endosalpingiotic deposits and borderline tumors within the same node [6] [7]. Moreover, this ectopic Müllerian epithelium could be susceptible to the same hormonal and genetic alterations as their native counterparts.

In fact, Emerson et al. observed that the same X chromosome inactivation patterns were identical among ovarian and nodal lesions in many cases [8].

In addition, Alvarez et al. found an identical mutation in the K-ras gene in ovarian SBTs and their synchronous endosalpingiotic deposits in 2 out of the 3 cases that they evaluated [9].

The metastatic theory suggests that nodal SBT-type lesions might originate from synchronous ovarian SBTs. In these instances, lymph node metastases might be occurring as the result of micro-invasion, which would provide the tumor cells with access to the lymphovascular system of the subjacent stroma. Thus, in these cases, neoplastic elements could produce mediators such as Type IV collagenase and plasminogen activators, which facilitate the destruction of the basement membrane and the extracellular matrix with resultant invasion of the subjacent stroma, and invasion of the lymphovascular system [10] [11] [12][13]. However, many studies have found remarkably low frequency of nodal involvement in micro-invasive SBT types [14] [15] [16] [17] [18].

Other authors have suggested that ovarian SBTs might be transported to the lymph nodes only after exiting the ovary, most likely via the lymphatics of the peritoneal surfaces [19] [20].

This hypothesis might be supported by the observations of Camatte et al., who found nodal involvement in all serous BOT with peritoneal implants [21].

Clinical significance of lymph node involvement in ovarian serous tumors of low malignant potential

The behavior of ovarian serous borderline tumors (SBTs) and the significance of various prognostic factors are unclear and difficult to evaluate.

Many studies have suggested that the most important prognostic indicators for SBTs are the surgical pathological stage and the sub-classification of extra-ovarian disease into invasive and noninvasive implants [22].

In addition, the clinical outcomes of lymph node involvement in patients treated for borderline ovarian tumor have engendered discussion about its prognostic significance.

Several investigators have suggested that lymph node involvement in SBTs has no impact on overall survival [21] [22] [23] [24] [25]. Instead, other authors have demonstrated that lymph node involvement in SBTs can increase the incidence of disease recurrence [26].

More recently, some studies have suggested that the histologic diversity of lymph node involvement patterns is very important for overall survival.

Indeed, these studies observed a decrease in disease-free survival for cases of SBTs that featured lymph node involvement as discrete nodular aggregates of epithelium greater than 1 mm in linear dimension [27].

The role of lymphadenectomy in SBOTs as a therapeutic procedure remains unclear. Some authors have suggested that routine lymphadenectomy should not be performed in patients with early-stage disease, but could be useful in cases with enlarged lymph nodes [21].

Since lymph node involvement is the only indication of extra-ovarian disease, and since the neoplasm can recur exclusively in the lymph nodes as low-grade serous carcinoma, some researchers underline the importance of lymphadenectomy as a necessary part of a staging procedure and for the purposes of tumor reduction in all cases of SBOT [26] [27]. Moreover, since pelvic lymph nodes are most commonly involved, these could be removed when complete lymph node sampling cannot be carried out because of technical reasons or concerns over morbidity [26] [27].

All hypothesis about pathogenesis and the clinical and pathologic features of lymph node involvement in SBOT cannot explain the prognostic significance of this neoplasm. Thus, further studies are necessary, using large series and molecular investigations.

Keywords: Borderline tumor, Lymph node, Ovarian tumor, Serous tumor

  1. Taylor Jr HC. Malignant and semi-malignant tumors of the ovary. Surg Gynecol Obstet 1929;48:204–30.    Back to citation no. 1
  2. Serov SF, Scully RE, Sobin LH. International Histologic Classification of Tumours. No. 9. Histological Typing of Ovarian Tumours. World Health Organization: Geneva, 1973.    Back to citation no. 2
  3. Scully RE, Sobin LH. Histologic Typing of Ovarian Tumors, 2nd edn. In: World Health Organization International Histological Classification of Tumors. Springer-Verlag: Berlin, Heidelberg, 1999.    Back to citation no. 3
  4. Tinelli R, Tinelli A, Tinelli FG, Cicinelli E, Malvasi A. Conservative surgery for borderline ovarian tumors: a review. Gynecol Oncol 2006 Jan;100(1):185–91.   [CrossRef]   [Pubmed]    Back to citation no. 4
  5. Dietel M, Hauptmann S. Serous tumors of low malignant potential of the ovary. 1. Diagnostic pathology. Virchows Arch 2000 May;436(5):403–12.   [Pubmed]    Back to citation no. 5
  6. Kadar N, Krumerman M. Possible metaplastic origin of lymph node "metastases" in serous ovarian tumor of low malignant potential (borderline serous tumor). Gynecol Oncol 1995 Dec;59(3):394–7.   [CrossRef]   [Pubmed]    Back to citation no. 6
  7. Prade M, Spatz A, Bentley R, Duvillard P, Bognel C, Robboy SJ. Borderline and malignant serous tumor arising in pelvic lymph nodes: evidence of origin in benign glandular inclusions. Int J Gynecol Pathol 1995 Jan;14(1):87–91.   [CrossRef]   [Pubmed]    Back to citation no. 7
  8. Emerson RE, Wang M, Liu F, Lawrence WD, Abdul-Karim FW, Cheng L. Molecular genetic evidence of an independent origin of serous low malignant potential implants and lymph node inclusions. Int J Gynecol Pathol 2007 Oct;26(4):387–94.   [CrossRef]   [Pubmed]    Back to citation no. 8
  9. Alvarez AA, Moore WF, Robboy SJ, et al. K-ras mutations in Müllerian inclusion cysts associated with serous borderline tumors of the ovary. Gynecol Oncol 2001 Feb;80(2):201–6.   [CrossRef]   [Pubmed]    Back to citation no. 9
  10. Nathanson SD. Insights into the mechanisms of lymph node metastasis. Cancer 2003 Jul 15;98(2):413–23.   [CrossRef]   [Pubmed]    Back to citation no. 10
  11. Carr I. Lymphatic metastasis. Cancer Metastasis Rev 1983;2(3):307–17.   [CrossRef]   [Pubmed]    Back to citation no. 11
  12. Petruzzelli GJ, Benefield J, Yong S. Mechanism of lymph node metastases: current concepts. Otolaryngol Clin North Am 1998 Aug;31(4):585–99.   [CrossRef]   [Pubmed]    Back to citation no. 12
  13. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991 Jan 25;64(2):327–36.   [CrossRef]   [Pubmed]    Back to citation no. 13
  14. Bell DA, Scully RE. Ovarian serous borderline tumors with stromal microinvasion: a report of 21 cases. Hum Pathol 1990 Apr;21(4):397–403.   [CrossRef]   [Pubmed]    Back to citation no. 14
  15. Tavassoli FA. Serous tumor of low malignant potential with early stromal invasion (serous LMP with microinvasion). Mod Pathol 1988 Nov;1(6):407–14.   [Pubmed]    Back to citation no. 15
  16. Kennedy AW, Hart WR. Ovarian papillary serous tumors of low malignant potential (serous borderline tumors). A long-term follow-up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma. Cancer 1996 Jul 15;78(2):278–86.   [CrossRef]   [Pubmed]    Back to citation no. 16
  17. Nayar R, Siriaunkgul S, Robbins KM, McGowan L, Ginzan S, Silverberg SG. Microinvasion in low malignant potential tumors of the ovary. Hum Pathol 1996 Jun;27(6):521–7.   [CrossRef]   [Pubmed]    Back to citation no. 17
  18. Prat J, De Nictolis M. Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion. Am J Surg Pathol 2002 Sep;26(9):1111–28.   [CrossRef]   [Pubmed]    Back to citation no. 18
  19. Wassilev W, Wedel T, Michailova K, Kühnel W. A scanning electron microscopy study of peritoneal stomata in different peritoneal regions. Ann Anat 1998 Apr;180(2):137–43.   [CrossRef]   [Pubmed]    Back to citation no. 19
  20. Parungo CP, Soybel DI, Colson YL, et al. Lymphatic drainage of the peritoneal space: a pattern dependent on bowel lymphatics. Ann Surg Oncol 2007 Feb;14(2):286–98.   [CrossRef]   [Pubmed]    Back to citation no. 20
  21. Camatte S, Morice P, Atallah D, et al. Lymph node disorders and prognostic value of nodal involvement in patients treated for a borderline ovarian tumor: an analysis of a series of 42 lymphadenectomies. J Am Coll Surg 2002 Sep;195(3):332–8.   [CrossRef]   [Pubmed]    Back to citation no. 21
  22. Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol 2000 May;31(5):539–57.   [CrossRef]   [Pubmed]    Back to citation no. 22
  23. Bell DA, Longacre TA, Prat J, et al. Serous borderline (low malignant potential, atypical proliferative) ovarian tumors: workshop perspectives. Hum Pathol 2004 Aug;35(8):934–48.   [CrossRef]   [Pubmed]    Back to citation no. 23
  24. Di Re F, Paladini D, Fontanelli R, Feudale EA, Raspagliesi F. Surgical staging for epithelial ovarian tumors of low malignant potential. Int J Gynecol Cancer 1994 Sep;4(5):310–314.   [CrossRef]   [Pubmed]    Back to citation no. 24
  25. Longacre TA, McKenney JK, Tazelaar HD, Kempson RL, Hendrickson MR. Ovarian serous tumors of low malignant potential (borderline tumors): outcome-based study of 276 patients with long-term (> or =5-year) follow-up. Am J Surg Pathol 2005 Jun;29(6):707–23.   [CrossRef]   [Pubmed]    Back to citation no. 25
  26. Leake JF, Rader JS, Woodruff JD, Rosenshein NB. Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential. Gynecol Oncol 1991 Aug;42(2):124–30.   [CrossRef]   [Pubmed]    Back to citation no. 26
  27. McKenney JK, Balzer BL, Longacre TA. Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): pathology, prognosis, and proposed classification. Am J Surg Pathol 2006 May;30(5):614–24.   [CrossRef]   [Pubmed]    Back to citation no. 27

[HTML Abstract]   [PDF Full Text]

Author Contributions:
Giovanna Giordano – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Guarantor of submission
The corresponding author is the guarantor of submission.
Source of support
Conflict of interest
Authors declare no conflict of interest.
© 2015 Giovanna Giordano. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.

  Terms of Service line Privacy policy line Disclaimer line FAQ line Contact: Journal line Contact: Edorium Journals line Site Map  
  Copyright © 2018. Edorium. All rights reserved.