Serous Borderline Tumor vs. Mucinous Borderline Tumor: What’s the Difference?

July 1, 2024

Serous Borderline Tumor vs. Mucinous Borderline Tumor: What’s the Difference?

Imagine being told you have a growth on your ovary, but it’s not quite as invasive as traditional cancer. This is the reality for many women diagnosed with borderline ovarian tumors. These tumors, which fall somewhere between benign and malignant, can be confusing and scary. But don’t worry, we’re here to help you understand the differences between the two main types: serous borderline tumor and mucinous borderline tumor. 

We’ll explore these unique ovarian tumors’ characteristics, causes, symptoms, diagnosis, treatment, and prognosis. We’ll also touch on some of the ongoing research and support resources available for women affected by borderline tumors.

What are Borderline Ovarian Tumors?

Borderline ovarian tumors are a unique group of growths that have some features of cancer but don’t behave like aggressive malignancies. They tend to grow slowly and are less likely to spread than the most common types of ovarian cancer. About 10-20% of all ovarian tumors are borderline, and they usually affect women in their 30s and 40s.

To understand borderline tumors, it helps to know a bit about ovarian tumors in general. Most ovarian tumors fall into one of three categories: benign (non-cancerous), malignant (cancerous), or borderline

Benign tumors, such as cystadenomas, are usually harmless and can often be left alone. Malignant tumors, like high-grade serous carcinoma, are aggressive cancers that require extensive treatment. Borderline tumors lie in between: they have some abnormal features under the microscope, but they don’t invade deeply into the ovary or spread as readily as malignant ovarian tumors.

Borderline tumors can arise from different types of ovarian cells, but the two most common types are serous and mucinous. Serous borderline tumors develop from the cells that line the surface of the ovary, while mucinous borderline tumors arise from cells that produce mucus. 

Serous Borderline Ovarian Tumor (SBOT)

Serous borderline ovarian tumors, or SBOTs, are the most common type of borderline tumor, accounting for about 50-60% of cases. Under the microscope, they have a distinctive “borderline” appearance with complex papillary structures and mildly abnormal cells. The cells in SBOTs are called “atypical proliferative” because they show some features of malignancy, such as increased growth and mild nuclear atypia (abnormal cell appearance). However, they lack the severe atypia and invasive growth patterns typically seen in high-grade serous carcinomas.

There are two main subtypes of SBOT:

  • Typical SBOT: This is the more common subtype, characterized by branching papillae (finger-like projections) lined by mildly atypical cells. The cells are usually arranged in a single or a few layers, with minimal crowding or overlap. Psammoma bodies (round calcifications) are often present.
  • Micropapillary variant: This less common subtype has a more complex, lace-like appearance with elongated micropapillae and increased cell crowding. Micropapillary SBOTs may be associated with a higher risk of recurrence and progression to low-grade serous carcinoma, although this is still an area of debate among pathologists.

Stages and Prognosis

SBOTs are usually diagnosed early, with about 75% confined to the ovary (stage I). The prognosis for stage I SBOTs is excellent, with a 10-year survival rate of over 95%.

However, about 15-40% of SBOTs are diagnosed at advanced stages, with tumor deposits (implants) present on the peritoneum (lining of the abdominal cavity) or other pelvic organs. The prognosis for advanced-stage SBOTs is still generally good, with a 5-year survival rate of around 80-90%, but close follow-up is important as late recurrences can occur.

Is a Serous Borderline Tumor Cancerous?

While SBOTs exhibit some features associated with malignancy, they are classified as borderline tumors or tumors of low malignant potential, as they lack destructive stromal invasion. However, SBOTs have the potential to progress to invasive low-grade serous ovarian carcinoma (LGSOC) in a small proportion of cases, emphasizing the need for long-term follow-up and surveillance.

Symptoms of Serous Borderline Tumor

Many women with SBOTs have no symptoms, and the tumor is discovered incidentally during imaging or surgery for another reason. When symptoms do occur, they can include:

  • Pelvic pain or pressure
  • Bloating or abdominal swelling
  • Irregular menstrual periods
  • Pain during intercourse
  • Urinary symptoms (frequency, urgency)

These symptoms are nonspecific and can also occur with many other conditions, so it’s essential to see your ovarian cancer doctor for proper evaluation if you experience any persistent or worrisome symptoms.

Mucinous Borderline Ovarian Tumor (MBOT)

Mucinous borderline ovarian tumors, or MBOTs, are less common than SBOTs, accounting for about 35-45% of borderline tumors. These tumors arise from the cells that normally produce mucus in the reproductive tract. Under the microscope, MBOTs have a complex, multi-cystic appearance with mucus-filled spaces and various cell types. Like SBOTs, MBOTs show atypical proliferative features but lack frank invasion.

There are two main subtypes of MBOT:

  • Intestinal type: This is the more common subtype, resembling the lining of the intestines. The cells may be tall and columnar, with irregular nuclei and abundant apical mucin (mucus at the top of the cell). Goblet cells (mucus-secreting cells) and neuroendocrine cells may also be present.
  • Endocervical-like (Mullerian) type: This rare subtype looks more like the lining of the endocervix (lower part of the uterus). The cells are usually taller and more crowded than the intestinal type, with less mucin production. This subtype is often mixed with serous or endometrioid (uterine-like) components.

Stages and Prognosis

Like SBOTs, most MBOTs (75-90%) are diagnosed at stage I and have an excellent prognosis, with a 5-year survival rate of over 95%. However, advanced-stage MBOTs with invasive implants (deposits of tumor that invade into the underlying tissue) can behave more aggressively, with a higher risk of recurrence and a lower overall survival rate. Pseudomyxoma peritonei, a condition in which mucus and tumor cells accumulate in the abdominal cavity, is a rare but serious complication of some advanced MBOTs.

Symptoms of Mucinous Borderline Tumor

MBOTs can cause similar symptoms to SBOTs, such as pelvic pain and bloating. However, because MBOTs often grow larger than SBOTs (sometimes over 20 cm), they may be more likely to cause abdominal discomfort, distension, or a visible mass. In some cases, MBOTs may cause abnormal vaginal bleeding or discharge. As with SBOTs, these symptoms are nonspecific and require evaluation by a healthcare provider.

Causes and Risk Factors: What Causes Borderline Ovarian Tumors?

The exact causes of borderline ovarian cancers and tumors are not fully understood, but some factors are thought to play a role:

  • Genetics: Certain genetic ovarian cancer mutations, such as in the KRAS and BRAF genes, are found in many SBOTs. These mutations are considered early events in the development of SBOTs, occurring in the benign precursor lesions (serous cystadenomas). For MBOTs, mutations in the KRAS gene are also common, but the role of other genetic factors is less clear.
  • Hormones: Exposure to estrogen and progesterone may influence the development of borderline tumors. Some studies have found a higher risk of borderline tumors in women who have used hormone replacement therapy or fertility drugs. However, the relationship between hormones and borderline tumors is complex and not yet fully understood.
  • Lifestyle factors: Some studies suggest that smoking and obesity may increase the risk of borderline tumors, particularly MBOTs. However, the evidence is limited, and more research is needed to confirm these associations.

It’s important to note that having one or more of these risk factors doesn’t necessarily mean you will develop a borderline tumor. Many women with borderline tumors have no known ovarian cancer risk factors, and most women with these risk factors will never develop a tumor.

Genetic and Molecular Factors

Researchers have made significant progress in understanding the genetic and molecular changes that underlie borderline ovarian tumors. These findings provide insight into how these tumors develop and behave and potentially affect diagnosis, prognosis, and targeted therapy.

  • KRAS and BRAF mutations in SBOT: The KRAS and BRAF genes are part of the MAP kinase pathway, which regulates cell growth and division. Mutations in these genes lead to uncontrolled cell growth and are found in many SBOTs. KRAS mutations are present in about 20-40% of SBOTs, while BRAF mutations occur in about 30-50%. These mutations are considered early events in SBOT development, as they are also found in benign precursor lesions (serous cystadenomas). Interestingly, KRAS and BRAF mutations are usually mutually exclusive in SBOTs, suggesting they have similar effects on tumor growth. BRAF mutations may be associated with a lower risk of recurrence or progression to LGSOC.
  • Molecular pathogenesis of MBOT: The molecular landscape of MBOTs is less well-defined than that of SBOTs, but some key alterations have been identified. KRAS mutations are the most common, found in about 30-50% of MBOTs. These mutations are thought to play a role in developing intestinal and endocervical-type MBOTs. Other genes that may be involved in MBOT pathogenesis include TP53 (a tumor suppressor gene), CDKN2A (a cell cycle regulator), and RNF43 (a regulator of cell signaling). However, the significance of these alterations and their potential as therapeutic targets remains to be determined.

As our understanding of the molecular basis of borderline tumors continues to grow, it is hoped that this knowledge will translate into more precise diagnostic and prognostic tools, as well as novel targeted therapies for women with these tumors.

Borderline Ovarian Tumors: Diagnosis and Staging

Suppose your doctor suspects a borderline ovarian tumor based on your symptoms or imaging findings. In that case, they will likely recommend further testing to confirm the diagnosis and determine the extent of the tumor.

Imaging: Imaging tests, such as ultrasound or CT scan, can help determine the size, location, and characteristics of the ovarian mass. Borderline tumors often appear as complex cystic masses with solid components or septations (internal walls). However, imaging alone cannot definitively diagnose a borderline tumor or distinguish it from other types of ovarian tumors.

Tumor and ovarian cancer biomarkers: Blood tests for specific proteins or hormones (tumor markers) may be elevated in some cases of borderline tumors. The most commonly used tumor marker for ovarian tumors is CA-125, which is elevated in about 50-60% of SBOTs and 30-40% of MBOTs.

However, CA-125 can also be elevated in many other conditions, such as endometriosis, fibroids, and menstruation, so it is not a specific test for borderline tumors. Other potential tumor markers include CA 19-9 (for MBOTs) and HE4 (for SBOTs), but their role in borderline tumors is still being studied.

Surgery: The definitive diagnosis and staging of a borderline ovarian tumor requires surgical removal of the tumor (usually via laparoscopy or laparotomy) and thorough examination of the pelvic and abdominal cavities.

During surgery, the surgeon will carefully inspect the ovaries, fallopian tubes, uterus, and other pelvic organs for any signs of tumor spread. Samples of peritoneal fluid (ascites) or washings will be taken to look for tumor cells. Biopsies of suspicious areas on the peritoneal surfaces or lymph nodes may also be performed. The ovarian tumor itself will be removed intact (if possible) and sent to a pathologist for detailed examination under the microscope. This is the gold standard for diagnosing borderline tumors and determining the histological subtype (serous or mucinous, typical or micropapillary/cribriform).

The staging of borderline tumors is similar to that of ovarian cancer, based on the FIGO (International Federation of Gynecology and Obstetrics) system:

Stage I: Tumor confined to the ovaries

  • IA: Tumor limited to one ovary, capsule intact, no surface tumor
  • IB: Tumor limited to both ovaries, capsules intact, no surface tumor
  • IC: Tumor limited to one or both ovaries, with capsule rupture, surface tumor, or positive washings/ascites

Stage II: Tumor involves one or both ovaries with pelvic extension

  • IIA: Extension/implants on uterus/fallopian tubes
  • IIB: Extension/implants on other pelvic tissues

Stage III: Tumor involves one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis and/or regional lymph node metastasis

  • IIIA: Microscopic peritoneal metastasis beyond the pelvis
  • IIIB: Macroscopic peritoneal metastasis beyond pelvis ≤2 cm
  • IIIC: Macroscopic peritoneal metastasis beyond pelvis >2 cm and/or regional lymph node metastasis

 Stage IV: Distant metastasis (excluding peritoneal metastasis)

The accuracy of staging is important for determining prognosis and guiding treatment decisions. In general, borderline tumors diagnosed at an earlier stage have a better prognosis than those diagnosed at more advanced stages.

Treatment Options

Surgical management: The primary treatment for borderline ovarian tumors is surgical removal of the tumor and any visible disease in the pelvis or abdomen. The extent of surgery depends on several factors, including the stage of the tumor, the patient’s age and general health, and their desire for future fertility.

Fertility-sparing surgery: For younger women who wish to preserve their ability to have children, fertility-sparing surgery may be an option. This typically involves unilateral salpingo-oophorectomy (removal of the affected ovary and fallopian tube) and careful inspection of the remaining ovary, uterus, and pelvic organs. 

Oophorectomy surgery may be sufficient treatment if the tumor appears confined to one ovary (stage IA). However, suppose there is a concern for higher-stage disease. In that case, the surgeon may also perform biopsies of peritoneal surfaces, omentum (a fatty apron covering the abdominal organs), and lymph nodes to check for microscopic spread. 

The decision to preserve fertility should be made after careful discussion with the patient about the potential risks and benefits, as well as close follow-up to monitor for recurrence.

Complete staging surgery: For women who have completed childbearing or are postmenopausal, complete staging surgery is usually recommended. This involves bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes), hysterectomy (removal of the uterus), and comprehensive staging of the pelvic and abdominal cavities. Staging typically includes omentectomy (omentum removal), peritoneal biopsies, pelvic and para-aortic lymph node sampling, and peritoneal washings. Complete staging aims to accurately determine the extent of the disease and remove as many visible tumors as possible, which can help guide further treatment decisions and provide prognostic information.

The Role of Chemotherapy and Targeted Therapies

Unlike invasive ovarian cancers, borderline ovarian tumors are generally not responsive to traditional chemotherapy regimens. Borderline tumors have a lower growth rate and less genomic instability than high-grade cancers, making them less susceptible to drugs that target rapidly dividing cells. As a result, chemotherapy is not routinely recommended for the treatment of borderline tumors, even in advanced-stage disease.

However, there are some specific situations where chemotherapy may be considered:

  • Recurrent disease: In rare cases where a borderline tumor recurs after initial treatment, particularly if it has transformed into a low-grade invasive carcinoma, chemotherapy may be an option. The most commonly used regimens are platinum-based, such as carboplatin and paclitaxel, which have shown some activity in low-grade serous carcinomas.
  • Targeted therapies: As our understanding of the molecular alterations driving borderline tumors improves, there is growing interest in the use of targeted therapies that specifically inhibit these abnormal pathways. One promising target is the MAP kinase pathway, activated by KRAS and BRAF mutations in many SBOTs. Drugs that inhibit MEK, a downstream effector of this pathway, have shown some activity in preclinical studies and early clinical trials of low-grade serous carcinomas. However, their role in borderline tumors remains to be established.

It’s important to note that the use of chemotherapy or targeted therapies in borderline tumors is still considered experimental and should only be done in the context of a clinical trial or after careful discussion with a gynecologic oncologist.

Follow-up and Recurrence Monitoring

After treatment for a borderline ovarian tumor, regular follow-up is essential. We’re not just checking boxes here – this is about staying vigilant and catching potential issues early.

In general, follow-up for borderline tumors includes:

  • Physical examination: Your doctor will perform a pelvic exam to check for any signs of tumor recurrence or new ovarian masses.
  • Imaging: Ultrasound, CT, or MRI scans will be your eyes on the inside, looking for any evidence of tumor recurrence or spread. Expect these every 3-6 months for the first few years, then annually.
  • Tumor markers: If CA-125 or other relevant markers were initially elevated, blood tests are conducted to determine their level. Rising levels of these markers could signal a recurrence.
  • Symptom assessment: Any new or persistent symptoms, such as pelvic pain, bloating, or changes in bowel/bladder habits, must be evaluated.

Now, let’s talk about recurrence rates: 

  • Stage I: About 5-10% recurrence rate
  • Stage II: Around 15-20% recurrence rate
  • Stage III: Approximately 20-30% recurrence rate

Even if you’ve had a hysterectomy and oophorectomy, recurrence is still possible. Tumors can return in the pelvis, abdomen, or even distant sites like the lungs or liver. It’s not common, but it’s crucial to be aware.

Here’s something important to note: serous borderline ovarian tumors (SBOTs) and low-grade serous ovarian cancer (LGSOC) are more closely related than we once thought. While the exact transformation rate isn’t known, research suggests that some SBOTs can progress to LGSOC. Many patients diagnosed with advanced LGSOC also have SBOTs present, highlighting the connection between these two tumor types.

The bottom line is to stay proactive. Adhere to your follow-up schedule and promptly report any concerning symptoms. Long-term vigilance is critical — these tumors can recur even years after initial diagnosis.

Mucinous and Serous Borderline Tumors: Challenges and Future Directions

Borderline ovarian tumors, whether serous or mucinous, represent a unique subset of ovarian neoplasms that challenge our traditional dichotomy of benign versus malignant. While these tumors share some features with invasive ovarian cancers, they generally have a much more favorable prognosis and require a distinct approach to management and surveillance.

Despite the generally favorable prognosis of borderline ovarian tumors, there are still several challenges and unanswered questions that require further research and clinical attention.

One ongoing challenge is the lack of consensus on the optimal classification and nomenclature for borderline ovarian tumors. The term “borderline” itself is somewhat misleading, as it implies a tumor that is on the verge of becoming malignant when, in reality, most borderline tumors do not progress to invasive cancer. Some experts prefer alternative terms such as “atypical proliferative tumor” or “low malignant potential tumor,” but these have not been universally adopted. 

There is also debate about whether specific subtypes, such as micropapillary SBOTs or cribriform MBOTs, should be classified as low-grade carcinomas rather than borderline tumors. Resolving these issues will require further studies on these tumors’ natural history and molecular features and collaboration among pathologists, oncologists, and research scientists.

Another challenge is the relative lack of clinical trials specifically focused on borderline ovarian tumors. Because these tumors are less common than invasive ovarian cancers and have a better prognosis, they are often excluded from large-scale clinical trials of new therapies. 

However, this means that there is limited data on the optimal treatment approaches for patients with advanced-stage or recurrent borderline tumors, particularly those with invasive implants or low-grade carcinomas. Conducting clinical trials in this population is challenging due to the rarity of the disease and the long follow-up times required to assess outcomes. 

Ovarian cancer nonprofit organizations like Not These Ovaries are committed to supporting collaborative efforts among gynecologic oncology research groups, frontline researchers and scientists, and patients. We are helping develop and implement clinical trials tailored to borderline ovarian tumors, which may focus on novel surgical techniques, targeted therapies, or immunotherapies. The goal is to improve outcomes for patients with high-risk or recurrent disease.

By funding innovative research projects, facilitating collaborations among scientists and clinicians, and providing education and support to patients and families, we hope to accelerate progress in diagnosing, treating, and preventing these complex tumors.

With a robust support system, an experienced medical team, and a commitment to self-advocacy and education, it is possible to navigate the challenges of diagnosis and treatment and emerge with a renewed sense of strength and resilience. By sharing their stories and connecting with others in the borderline ovarian tumor community, patients can help to break down the isolation and stigma that too often accompany a rare disease diagnosis and inspire hope for a brighter future.