eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
vol. 72
Case report

Serous borderline tumor with distant mediastinal metastasis? An Exceptional presentation of ovarian tumor

Julia M. Sołek
Aleksandra Zielińska
Magdalena Sobczak
Urszula Czernek
Robert Kubiak
Radzisław Kordek
Dorota Jesionek-Kupnicka

Department of Pathology, Medical University of Lodz, Lodz, Poland
Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
Department of Pathology, SYNEVO, Lodz, Poland
Pol J Pathol 2021; 72 (3): 272-276
Online publish date: 2022/01/19
Article file
- PJP-01934.pdf  [1.74 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero


Ovarian cancer is a leading cause cancer-related death in woman with a 5-years survival below 50% [1]. Historically, it is called “silent killer” because more than 62% of the disease occurs in IV stage with distant metastasis without previous warning symp- toms [2]. According to the Surveillance, Epidemiology, and End Results (SEER) database, 10-year survival for patients with IV stage of disease with distant metastasis is 15%, whereas 10-year survival for patients with early stage is 55%. This fact presents a high need to find an effective screening test and also calls for deeper understanding molecular mechanism of metastasis. Here we present an unusual presentation of distant metastasis during very early clinical stage of ovarian cancer i.e. borderline tumor with microinvasion which constituted a huge diagnostic dilemma and required profound diagnostic workup with large panel of immunohistochemistry and molecular study. The comprehensive analyses provided here gives us a deeper insight in enigmatic mechanism of ovarian distant metastasis.

Case presentation

The 48-year-old Caucasian women presented in Department of Oncology with 12-weeks history of shortness of breath and reduced exercised tolerance. She had no significant past medical history. Due to the breathing problems, pulmonary function test and imaging study were performed. In spirometry all values fell within the normal range. Radiography imaging showed enlarged lung hilum what suggested that suspicious lesion is localized in lymph nodes. Subsequent surgical biopsy of affected lymph nodes around tracheal bifurcation was performed. On high magnification an adenocarcinoma papillary structures and psammoma bodies were seen (Fig.1 A, B). The immunohistochemical (IHC) study showed positive expression for cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), Wilms’ tumor 1 (WT1) and paired box 8 (PAX8) by tumor cells and negative expression for thyroid transcription factor 1 (TTF1), thyroglobulin, gross cystic disease fluid protein (GCDFP-15), and mammaglobulin (Fig.1 C-E). The differential diagnosis included: primary lung papillary adenocarcinoma as well as metastatic tumors – breast carcinoma metastasis, papillary thyroid carcinoma metastasis and eventually very rare presentation of ovarian tumor metastasis. Molecular examination gave positive results for BRAF mutation, whereas negative for EGFR, ALK, ROS1 mutations. Additional pharmacodiagnostic test found a negative PD-L1 expression. Most molecular studies were performed in National Research Institute of Oncology in Warsaw. Increased concentration of cancer antigen 125 (CA-125) was detected (124,0 U/ml; cut off value 35,0 U/ml) what together with analysis of IHC and molecular study results strongly suggested ovarian tumour as a most probable metastatic tumor source. All results of performed diagnostic examinations are visible in Table I. Finally, positron emission tomography-computed tomography (PET/CT) scan showed approximately 20 mm in diameter mass of increased metabolic activity in right ovary (SUVmax = 5,4) and surgical resection of ovary was performed (Fig.2). Surprisingly, histopathological analysis of resected ovary mass displayed features typical for serous borderline tumour: papillae covered by single- or multi-layered, non-atypical epithelium (Fig. 1F). Within tumour tissue there were a large areas of necrosis (Fig. 1G). Detailed pathological diagnosis and positive immunohistochemical staining for pan type cytokeratin AE1/AE3 shown a diminutive, 4 mm in diameter, focus of invasion, what, according to WHO recommendation confirmed the final diagnosis of ovarian serous borderline tumor with microinvasion (Fig. 1H). Moreover negative staining for P53 highly suggests a non-mutational TP53 “wild type”– pattern. The patient was referred for palliative chemotherapy recommended for IVth stage of invasive ovarian carcinoma with 6 cycles of carboplatin, paclitaxel and bevacizumab and 1 consisting only bevacizumab. During therapy patient showed gradual decrease in CA-125 level (Fig. 3). After seven cycles of combined chemotherapy and immunotherapy tumor mediastinal mass disappeared as well as patient’s breathing disturbances were resolved.


Recent classification of serous ovarian carcinoma is based on molecular biology and distinguishes two types of serous ovarian carcinoma: low-grade and high-grade. Low grade carcinoma arises from benign or borderline lesion and progresses slowly in stepwise manner to become an invasive carcinoma. These tumors are associated with certain mutation pattern which involves EGFR signaling pathway (BRAF, KRAS, ERBB2 gene) and are characterized by young age at diagnosis and prolonged overall survival time (median 82 months). High grade tumors are characterized by aggressive behavior, shorter time of overall survival (30 months) and lack of precursor lesion [3, 5]. TP53 mutation are virtually ubiquitous in high-grade serous cancers, being present in over 95% of cases [6]. Other frequently mutated genes include the tumor suppressors NF1 and RB, as well as BRCA1 and BRCA2 in familiar ovarian cancers [3]. Here we present an unusual case of borderline tumor with distant metastasis to mediastinum in which only the microinvasion was detected. On molecular level, it showed BRAF mutation and lack of P53 staining what is characterized for low grade pathway. However, clinically it presented an aggressive course with distant metastasis from very diminutive site of invasion and very good response to chemotherapy what is more characteristic for high-grade lesion. Dehari et al. have shown that it is a possible for high grade carcinoma to come from low grade pathway. They presented that BRAF mutation is shared between low and high grade tumor what indicates clonal relationship. Moreover, in those tumors which arose from low grade lesion, P53 mutation was undetectable what allows the possibility that some of the high-grade serous carcinomas could have a different molecular pathogenesis compared with conventional high-grade carcinomas that develop along the type II pathway [18].
The biological behavior of ovarian carcinoma is unique, markedly different from hematogenous metastasis found in most other cancers. Most of ovarian metastases are found within peritoneal cavity [3]. Once the cancer cells have detached as single cells or clusters from the primary ovarian tumor, they metastasize through a passive mechanism, carried by the physiological movement of peritoneal fluid to the peritoneum and omentum and invade the mesothelial cell layers. Metastases outside the peritoneum, through the vasculature are less common in ovarian cancer (16%) and are related with IV stage of disease and poor prognosis [1, 4]. Most common sites of distant metastasis are liver (12.6%), pleura (6.6%) and lungs (4.6%) [7]. Here we present a case where distant mediastinal metastases was the only metastatic site without accompanying peritoneal involvement. Moreover, according to the previous research, site of distant metastasis is an independent prognostic factor and lung metastases are associated with the worst overall survival compared to the other sites [2]. Patient in our case presented complete response to the treatment with resolution of breathing symptoms and regression of tumor mass.
The stromal invasion is a hallmark that distinguishes a serous invasive carcinoma from a serous borderline tumor. A standardized quantitative criteria for distinguishing microinvasion from frankly invasive carcinoma within borderline tumor has not been established and varying definitions have been used in different studies including 1 mm, 2 mm, 3 mm, 5 mm, 10 mm [8, 9, 10, 11, 12]. Current WHO Classification suggests a cut-off of 5 mm [12]. However, according to the literature, neither a presence nor the size of microinvasion should alter the outcome [12, 19]. Here we present a focus of microinvasion 4mm in diameter which was found only in one section. This could be perceived as a limitation of the histopathological examination. However, the tumor was carefully examined with numerous sections and the borderline lesion was dominant. This case strongly suggests that even small diameter of invasion could influence the clinical behavior and should be considered as a very important prognostic factor.
There are only single cases of metastatic borderline tumor reported in the literature with sites of metastasis in brain, bone marrow and internal mammary lymph nodes [13, 14, 15, 16, 17]. To our knowledge, this is the first reported case of borderline tumor with microinvasion and mediastinal metastasis with such a distinct clinical presentation. Unforeseen course of the borderline tumor presented here brings us to an important conclusion that the very diminutive focus of invasion has a possibility to give a distant metastasis characteristic for IV stage of disease what indicates that there is a huge gap in knowledge about mechanism of ovarian cancer metastasis. The lesson learned from this case is that the borderline tumors of ovary with any features of invasion could present an aggressive course and metastasize to parenchymal organs in an occult fashion what the clinicians and pathologists should bear in mind.

We would like to thank dr Piotr Wiœniewski and Marcin Braun for supportive discussions. We are especially grateful to Ireneusz So³ek for proofreading and linguistic review.
The authors declare no conflict of interest.


1. Thomakos N, Diakosavvas M, Machairiotis N, et al. Rare distant metastatic disease of ovarian and peritoneal carcinomatosis: A review of the literature. Cancers (Basel) 2019; 11: 1-17.
2. Deng K, Yang C, Tan Q, et al. Sites of distant metastases and overall survival in ovarian cancer: A study of 1481 patients. Gynecol Oncol 2018; 150: 460-465.
3. Lengyel E. Ovarian cancer development and metastasis. Am J Pathol 2010; 177: 1053-1064.
4. Pradeep S, Kim S, Wu S, et al. Hematogenous metastasis of ovarian cancer: Rethinking mode of spread. Cancer Cell 2015; 26: 77-91.
5. Singer G, Oldt R, Cohen Y, et al. BRIEF Mutations in BRAF and KRAS Characterize the. Communication 2003; 95: 6-8.
6. Malpica A, Wong KK. The molecular pathology of ovarian serous borderline tumors. Ann Oncol 2016; 27: i16-i19.
7. Cormio G, Rossi C, Cazzolla E, et al. Distant metastases in ovarian carcinoma. Int J Gynecol Cancer 2003; 13: 125-129.
8. Hogg R, Scurry J, Kim, SN, et al. Microinvasion links ovarian serous borderline tumor and grade 1 invasive carcinoma. Gynecol Oncol 2007; 106: 44-51.
9. Abascal-Saiz A, Sotillo-Mallo L, De Santiago J, et al. Management of borderline ovarian tumours: A comprehensive review of the literature. Ecancermedicalscience 2014; 8: 1-8.
10. Inoue M, Takenaka M, Fukunaga, et al. Concurrent high-grade serous carcinoma and borderline tumor demonstrating different chemo-sensitivity. Int Cancer Conf J 2017; 6: 65-69.
11. Dehari R, Kurman RJ, Logani S, et al. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: A morphologic and molecular genetic analysis. Am J Surg Pathol 2007; 31: 1007-1012.
12. Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO classification of tumours of female reproductive organs. Lyon, IARC 2014.
13. Narod, S. Can advanced-stage ovarian cancer be cured? Nat Rev Clin Oncol 2016; 13: 255-261.
14. Martina M, Grishama R, Turashvilic G, et al. Brain metastasis in advanced serous borderline tumor of the ovary: A case presentation. Gynecol Oncol Reports 2017; 22: 9-12.
15. Geisler JP, Geisler HE. Brain metastases in epithelial ovarian carcinoma. Gynecol Oncol 1995; 57: 246-249.
16. Chamberlin MD, Eltabbakh GH, Mount, et al. Metastatic serous borderline ovarian tumor in an internal mammary lymph node: A case report and review of the literature. Gynecol Oncol 2001; 82: 212-215.
17. Kubo C, Nagata S, Fukuda T, et al. Late recurrence of pStage 1 low-grade serous ovarian tumor presenting as a symptomatic bone metastasis: a case report. Diagn Pathol 2018; 13: 43.
18. Dehari R, Kurman RJ, Logani S, et al. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: A morphologic and molecular genetic analysis. Am J Surg Pathol 2007; 31: 1007-1012.
19. McKenney JK, Balzer B, Longacre TA, Patterns of stromal invasion in ovarian serous tumors of low malignant potential (borderline tumors): A reevaluation of the concept of stromal microinvasion. Am J Surg Pathol 2006; 30: 1209-1221.
Copyright: © 2022 Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.