The results of conservative (fertility-sparing) treatment in borderline ovarian tumors vary depending on age and histological type.

Abstract

Epithelial ovarian tumors are heterogeneous neoplasms and are primarily classified according to cell type into: serous, mucinous, endometrioid, clear-cell, transitional, and squamous cell tumors [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar, 2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar, 3.Prat J. Pathology of the Ovary. Saunders, Philadelphia2004: 83-109Google Scholar]. Paradoxically, none of these cell types are found in the normal ovary and their development has long been attributed to Müllerian ‘neometaplasia’ of the ovarian surface epithelium (mesothelium) or, alternatively, to a germ-cell origin in cases of mucinous tumors [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar]. Most endometrioid and clear-cell tumors are thought to arise from endometriosis [4.Sato N. Tsunoda H. Nishida M. et al.Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary.Cancer Res. 2000; 60: 7052-7056PubMed Google Scholar]. Over the last decade, there has been increasing evidence that many early-stage high-grade serous carcinomas from BRCA+ patients arise from precursor epithelial lesions in the fimbriated end of the fallopian tube [5.Kindelberger D.W. Lee Y. Miron A. et al.Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship.Am J Surg Pathol. 2007; 31: 161-169Crossref PubMed Scopus (860) Google Scholar]. Recently, however, it has been hypothesized that embryonic/stem cells would be capable of Müllerian differentiation in inclusion cysts resulting from ovarian surface epithelium invaginations [6.Crum C.P. Herfs M. Ning G. et al.Through the glass darkly: intraepithelial neoplasia, top-down differentiation, and the road to ovarian cancer.J Pathol. 2013; 231: 402-412Crossref PubMed Scopus (53) Google Scholar]. Epithelial ovarian tumors differ not only morphologically, but also from the viewpoint of epidemiology, molecular genetic events during oncogenesis, and biologic behavior. In other words, these tumors are inherently different diseases. Epithelial ovarian tumors are further subdivided into benign, borderline, and malignant (carcinoma), and this subdivision is the most important since it correlates with behavior [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar, 2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar, 3.Prat J. Pathology of the Ovary. Saunders, Philadelphia2004: 83-109Google Scholar]. Borderline ovarian tumors show epithelial proliferation greater than that seen in their benign counterparts and variable nuclear atypia; however, in contrast to carcinomas, there is no destructive stromal invasion, and their prognosis is much better than that of carcinomas. In spite of the lack of stromal invasion, serous borderline tumors, particularly those with exophytic growth, can implant on peritoneal surfaces and, rarely (about 10% of peritoneal implants), progress to low-grade serous carcinoma (LGSC) and invade the underlying tissues [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar]. Although favorable in the vast majority of cases, the biologic behavior of the borderline tumors differs from that of the obviously benign tumors of the same cell type(s) and, rarely (<1%–3%), progression to invasive carcinoma occurs justifying the term ‘borderline tumor’. Alternative terms such as ‘proliferating’, ‘atypical’, and ‘atypical proliferative’ [9.Seidman J.D. Kurman R.J. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic factors.Hum Pathol. 2000; 31: 539-557Crossref PubMed Scopus (336) Google Scholar] are not recommended since they are nonspecific; i.e. all non-benign epithelial tumors (borderline and carcinomas) are proliferative neoplasms which exhibit nuclear atypia; also, these terms are misleading as they do not take into account the malignant potential of a small but significant number of these tumors and discourage follow-up [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar]. Similarly, the subdivision of the serous borderline group into benign and malignant, based on the presence of a micropapillary architecture [10.Seidman J.D. Kurman R.J. Subclassification of serous borderline tumors of the ovary into benign and malignant types. A clinicopathologic study of 65 advanced stage cases.Am J Surg Pathol. 1996; 20: 1331-1345Crossref PubMed Scopus (277) Google Scholar], is artificial since serous borderline tumors (SBT) with or without micropapillary pattern may rarely be associated with invasive peritoneal implants and poor outcome [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar]. A recent study of gene expression profiling of 13 SBTs and 3 low-grade serous carcinomas showed that SBTs with (one case) and without micropapillary pattern were equally distributed between benign-like and malignant-like subgroups [11.Curry E.W.J. Stronach E.A. Rama N.R. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.Mod Pathol. 2014; 27: 433-442Crossref PubMed Scopus (7) Google Scholar]. Although the term ‘borderline’ may suggest uncertainty, it accurately describes the ambiguous histologic and biologic features of these neoplasms and remains the most appropriate term. Accordingly, it has been recommended by the World Health Organization (WHO) for the last four decades [2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar]. The majority of these tumors are associated with a favorable prognosis and the term ‘tumors of low malignant potential’ is not recommended. With the exception of squamous cell tumors, the borderline concept applies to all types of ovarian epithelial tumors listed before; however, most data in the literature refer to the serous and mucinous gastrointestinal categories which are the two most common types and show striking clinicopathological differences. SBTs account for from 5% to 10% of ovarian serous tumors and occur at an average of 42 years. Approximately 70% are confined to one or both ovaries (stage I) at the time of diagnosis; the remaining tumors have spread within the pelvis (stage II) or upper abdomen (stage III). One-third of stage I tumors are bilateral [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar, 2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar, 3.Prat J. Pathology of the Ovary. Saunders, Philadelphia2004: 83-109Google Scholar]. Mucinous borderline tumors (MBTs) of intestinal type account for 10%–15% of ovarian mucinous tumors and are more common in the first two decades than their serous counterparts [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar, 2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar, 3.Prat J. Pathology of the Ovary. Saunders, Philadelphia2004: 83-109Google Scholar]. MBTs are confined to one or both ovaries (stage I) in almost all cases. Nearly all stage II–III MBTs are associated with pseudomyxoma peritonei and, in these patients, the ovarian tumor is virtually always secondary (metastatic) from a primary appendiceal tumor [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar, 2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar, 3.Prat J. Pathology of the Ovary. Saunders, Philadelphia2004: 83-109Google Scholar]. However, in contrast to serous tumors which are usually homogeneous, primary mucinous tumors often are heterogeneous. Benign-appearing, borderline, and invasive patterns may coexist within an individual neoplasm; this continuum suggests that progression occurs from cystadenoma and borderline tumor to noninvasive, microinvasive, and invasive carcinoma [1.Scully R.E. Young R.H. Clement P.B. Rosai J. Sobin L.H. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.Atlas of Tumor Pathology. 3rd edition. Vol. 23. Armed Forces Institute of Pathology, Washington, DC1998Google Scholar, 2.Lee K.R. Tavassoli F.A. Prat J. Tavassoli F.A. Devilee P. et al.Tumours of the Ovary and Peritoneum: surface epithelial-stromal tumours.World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, France2003: 117-145Google Scholar, 3.Prat J. Pathology of the Ovary. Saunders, Philadelphia2004: 83-109Google Scholar, 12.Rodriguez I.M. Prat J. Mucinous tumors of the ovary: a clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas.Am J Surg Pathol. 2002; 26: 139-152Crossref PubMed Scopus (179) Google Scholar]. This is supported by studies of K-RAS mutations, which represent an early event in mucinous ovarian tumorigenesis. MBTs have a higher frequency of K-RAS mutations than that of mucinous cystadenomas, but lower than mucinous carcinomas [13.Cuatrecasas M. Villanueva A. Matias-Guiu X. et al.K-ras mutations in mucinous ovarian tumors. A clinicopathologic and molecular study of 95 cases.Cancer. 1997; 79: 1581-1586Crossref PubMed Scopus (184) Google Scholar]. Surgery is the cornerstone of treatment of patients with SBTs and MBTs. Whereas in menopausal and postmenopausal women and in those who have completed their childbearing, the standard treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO), in young women with unilateral tumors and normal-appearing contralateral ovaries who wish to preserve their reproductive capacity, unilateral oophorectomy, or even an ovarian cystectomy, is usually carried out [14.Kennedy A.W. Hart W.R. 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; 78: 278-286Crossref PubMed Scopus (184) Google Scholar, 15.Lim-Tan S.K. Cajigas H.E. Scully R.E. Ovarian cystectomy for serous borderline tumors: a follow-up study of 35 cases.Obstet Gynecol. 1988; 72: 775-781PubMed Google Scholar]. Although a staging procedure for SBTs is often thought to be too radical, comprehensive surgical staging is recommended in patients with apparent stage I SBTs to exclude the presence of invasive peritoneal implants [16.Lin P.S. Gershenson D.M. Bevers M.W. et al.The current status of surgical staging of ovarian serous borderline tumors.Cancer. 1999; 85: 905-911Crossref PubMed Scopus (124) Google Scholar]. Prolonged follow-up is mandatory to exclude development of a similar tumor in the contralateral ovary. After the patient's family is complete, hysterectomy with residual salpingo-oophorectomy has been advocated, but its value has been questioned [17.Papadimitriou D.S. Martin-Hirsch P. Kitchener H.C. et al.Recurrent borderline tumors after conservative treatment management in women wishing to retain their fertility.Eur J Gynecol Oncol. 1999; 20: 94-97PubMed Google Scholar]. If a similar tumor develops in the contralateral ovary (5%–10% of the cases), the patient can be successfully treated in most cases by reoperation alone [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 14.Kennedy A.W. Hart W.R. 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; 78: 278-286Crossref PubMed Scopus (184) Google Scholar]. The overall outcome of SBTs is very favorable. The 5-year survival rates for patients with disease that is stages I–IIIb are between 88% and >95% [18.Heintz A.P. Odicino F. Maisonneuve P. et al.Carcinoma of the ovary. FIGO 6th Annual Report on the Results and Treatment in Gynecological Cancer.Int J Gynaecol Obstet. 2006; 95S: 161-192Crossref Scopus (921) Google Scholar]. For patients with stage I tumors, the risk of recurrence or the development of a second SBT has been estimated to be only 5%–10% [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar, 14.Kennedy A.W. Hart W.R. 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; 78: 278-286Crossref PubMed Scopus (184) Google Scholar]. Other than the adverse effect of invasive implants, there is no agreement in the literature as to which prognostic factors are important [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar, 14.Kennedy A.W. Hart W.R. 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; 78: 278-286Crossref PubMed Scopus (184) Google Scholar, 19.Park J.Y. Kim D.Y. Kim J.H. et al.Micropapillary pattern in serous borderline ovarian tumors: does it matter?.Gynecol Oncol. 2011; 123: 511-516Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar]. According to most investigators, SBTs with micropapillary pattern or SBTs with microinvasion have a prognosis similar to that of tumors lacking these features [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar, 20.Avril S. Hahn E. Specht K. et al.Histopathologic features of ovarian borderline tumors are not predictive of clinical outcome.Gynecol Oncol. 2012; 127: 516-524Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. Likewise, focal lymph node involvement has not demonstrated any effect on survival. The 5-year survival rate for patients with stage I MBT nears 100%. In a recent report, 6 of 144 patients (4.2%) had tumor recurrence. Risk factors for recurrence included FIGO stage IC, microinvasive carcinoma, age <45 years, and intraepithelial carcinoma [21.Khunamornpong S. Settakorn J. Sukpan K. et al.Mucinous tumor of low malignant potential (‘borderline’ or ‘atypical proliferative’ tumor) of the ovary: a study of 171 cases with the assessment of intraepithelial carcinoma and microinvasion.Int J Gynecol Pathol. 2011; 30: 218-230Crossref PubMed Scopus (50) Google Scholar]. The article by Uzan et al. [22.Uzan C. Nikpayam M. Ribassin-Majed L. et al.Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.Ann Oncol. 2014; 25: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar] in the current issue of Annals of Oncology focuses on risk factors for recurrence and, more specifically, for recurrence in the form of invasive carcinoma in a large series (n = 254) of macroscopic stage I borderline ovarian tumors (140 MBTs and 114 SBTs). This article stands out as it includes the largest number (n = 191) of conservatively treated patients reported to date. Even if all cases included were macroscopic stage I tumors, and considering that the median follow-up interval was only 3.7 years, the reported 17% overall recurrence rate appears to be much higher than the corresponding figures in the literature for stage I SBT and MBT of intestinal type; i.e. 5%–10% and 4.2%, respectively [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar, 14.Kennedy A.W. Hart W.R. 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; 78: 278-286Crossref PubMed Scopus (184) Google Scholar]. However, the higher rate may be partly attributed to the fact that 75% of patients were treated conservatively, either by unilateral salpingo-oophorectomy (n = 121) or cystectomy (n = 70). In fact, the risk factors for overall recurrence included conservative treatment, particularly cystectomy, bilaterality (stage IB), and incomplete staging. In SBTs, the presence of tumor at the resection margin of the cystectomy specimen and multifocality with removal of more than one cyst are strong predictors of failure of cystectomy to control the disease [15.Lim-Tan S.K. Cajigas H.E. Scully R.E. Ovarian cystectomy for serous borderline tumors: a follow-up study of 35 cases.Obstet Gynecol. 1988; 72: 775-781PubMed Google Scholar]. Furthermore, the frequency of microscopic SBT in a grossly normal-appearing contralateral ovary is 5%–10% [15.Lim-Tan S.K. Cajigas H.E. Scully R.E. Ovarian cystectomy for serous borderline tumors: a follow-up study of 35 cases.Obstet Gynecol. 1988; 72: 775-781PubMed Google Scholar]. The most interesting finding of this investigation is the influence of the histological type on the nature of the recurrent tumor in young patients who underwent fertility-sparing surgery. In these patients, MBTs of intestinal type recurred less frequently than SBTs, but when they did it was more often as an invasive carcinoma. Most SBTs maintain their microscopic features and usually do not progress to frankly invasive carcinoma [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 14.Kennedy A.W. Hart W.R. 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; 78: 278-286Crossref PubMed Scopus (184) Google Scholar]. In a recent study, progression of SBT to low-grade serous carcinoma occurred in 6%–7% of patients late in the course of the disease [8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar]. Almost 80% occurred in patients without prior history of invasive implants [8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar]. Of eight cases of SBT with malignant behavior, three exhibited focal stromal invasion greater than microinvasion, and only two were SBT with micropapillary pattern [23.Lee K.R. Castrillon D.H. Nucci M.R. Pathologic findings in eight cases of ovarian serous borderline tumors, three with foci of serous carcinoma, that preceded death or morbidity from invasive carcinoma.Int J Gynecol Pathol. 2001; 20: 329-334Crossref PubMed Scopus (12) Google Scholar]. In contrast, MBTs of intestinal type represent intermediate stages of mucinous tumorigenesis and, even if a MBT per se is essentially a benign neoplasm, it may be accompanied by or may progress to intraepithelial and frankly invasive carcinoma [12.Rodriguez I.M. Prat J. Mucinous tumors of the ovary: a clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas.Am J Surg Pathol. 2002; 26: 139-152Crossref PubMed Scopus (179) Google Scholar]. The findings of Uzan et al. [22.Uzan C. Nikpayam M. Ribassin-Majed L. et al.Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.Ann Oncol. 2014; 25: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar] clearly confirm the different nature of SBTs and MBTs of intestinal type. The so-called malignant recurrences, which occurred in the contralateral ovary in five of eight patients with MBTs initially treated by unilateral salpingo-oophorectomy, most likely represent independent primary mucinous tumors, typically heterogeneous, containing benign-appearing, borderline, and carcinomatous elements. Noteworthy, three of the five MBTs initially resected already had intraepithelial carcinoma. In contrast, the recurrences of the three SBTs that progressed to carcinoma typically occurred in the peritoneum as invasive implants; i.e. low-grade serous carcinoma. The only patient from this subgroup who underwent conservative treatment (bilateral cystectomy) had a SBT with micropapillary pattern which was incompletely staged. Her tumor first recurred as SBT 6 months postoperatively and as invasive carcinoma 4 years later. As recognized by the authors, the prognostic value of the micropapillary pattern in this single case is limited. The term ‘micropapillary’ is flawed as all SBTs have micropapillae descriptively, and their extension may range from a few papillae to a huge number of them. Bilaterality, ovarian surface growth, and advanced stage (mainly noninvasive peritoneal implants) are more common features of extensively micropapillary SBTs than of typical SBTs, but a strong association of the former tumors with invasive implants and poor outcome has been inconsistent [7.Prat J. de Nictolis M. Serous borderline tumors of the ovary. A long-term follow-up study of 137 cases, including 18 with micropapillary pattern and 20 with microinvasion.Am J Surg Pathol. 2002; 26: 1111-1128Crossref PubMed Scopus (239) Google Scholar, 8.Longacre T.A. McKenney J.K. Tazelaar H.D. et al.Ovarian serous tumors of low malignant potential borderline tumors). Outcome based study of 276 patients with long-term (≥5-year) follow-up.Am J Surg Pathol. 2005; 29: 707-723Crossref PubMed Scopus (254) Google Scholar, 19.Park J.Y. Kim D.Y. Kim J.H. et al.Micropapillary pattern in serous borderline ovarian tumors: does it matter?.Gynecol Oncol. 2011; 123: 511-516Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 20.Avril S. Hahn E. Specht K. et al.Histopathologic features of ovarian borderline tumors are not predictive of clinical outcome.Gynecol Oncol. 2012; 127: 516-524Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. Uzan et al. [22.Uzan C. Nikpayam M. Ribassin-Majed L. et al.Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.Ann Oncol. 2014; 25: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar] demonstrate that the results of fertility-sparing surgery in patients with borderline ovarian tumors depend not only on the possibility of residual tumor and/or multicentric tumorigenesis, but also on the tumor's histological type. Whereas SBTs usually recur as such and rarely progress to low-grade serous carcinomas (i.e. invasive peritoneal implants), MBTs of intestinal type are more frequently associated with carcinoma either in retained tumor or within independent primary MBTs developing in the contralateral ovary. In other words, SBTs and MBTs of intestinal type are different diseases with different biologic behavior. Also in this issue, the study by Trillsch et al. [24.Trillsch F. Mahner S. Woelber L. et al.Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a subanalysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT Study.Ann Oncol. 2014; 25: 1320-1327Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar] investigates the safety of fertility-sparing surgery in a large number of patients selected from a cohort of 950 women with borderline ovarian tumors collected over 11-year period from 24 German institutions. Patients younger and older than 40 years (n = 280 and 670, respectively) were analyzed separately and subsequently compared regarding clinicopathological variables, site of recurrence, and malignant transformation. Fertility-sparing surgery was carried out in 149 of 280 (53.2%) patients <40 years with preservation of some ovarian tissue from the ovary involved by tumor in 32 (21.5%) cases. Recurrence was more frequent in patients <40 years (18% versus 4%). However, it occurred mainly in the retained ovarian tissue, and there were no cases of cancer recurrence in this site. Therefore, it appears that the higher recurrence rate may be partly explained by the fact that younger patients are more likely to have ovarian tissue left. The older patients had a higher number of extraovarian recurrences and, significantly, more cancer recurrences (15/21 versus 6/18). Similar to the findings of Uzan et al., MBTs of intestinal type recurred as invasive carcinoma more frequently than SBTs (60% versus 22.4%). The recurrence rates after fertility-sparing surgery in the two series of borderline ovarian tumors reported by Uzan et al. [22.Uzan C. Nikpayam M. Ribassin-Majed L. et al.Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.Ann Oncol. 2014; 25: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar] and Trillsch et al. [24.Trillsch F. Mahner S. Woelber L. et al.Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a subanalysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT Study.Ann Oncol. 2014; 25: 1320-1327Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar] are similar (17% and 18%, respectively) and higher than those in the literature; however, most ‘recurrent’ tumors, particularly in young patients, were SBTs that regrew as such in retained ovarian tissue and were safely controlled by additional surgery. A word of caution: in both studies, a significant number of recurrent MBTs of intestinal type were associated with invasive carcinoma reflecting the characteristic heterogeneity of ovarian mucinous tumors. This finding raises the issue of completing surgery after childbirth in patients with MBTs of intestinal type. The author has declared no conflict of interest.