Ovarian Mucinous Carcinoma: Epidemiology, Etiology, Pathogenesis, Histopathology, Diagnosis, Symptoms, Staging, Management and Prevention

Ovarian Mucinous Carcinoma

~Introduction

Ovarian cancer is one of the leading causes of gynecological cancer-related mortality worldwide due to its often late presentation and nonspecific symptoms. Among the various histological subtypes of epithelial ovarian tumors, ovarian mucinous carcinoma (OMC) represents a distinct and relatively rare entity. It is characterized by the production of mucin and histological resemblance to gastrointestinal epithelium. Although mucinous tumors constitute a significant proportion of benign ovarian neoplasms, their malignant counterparts are comparatively uncommon.

Ovarian mucinous carcinoma differs from other ovarian carcinomas in terms of pathogenesis, molecular profile, clinical behavior, prognosis, and treatment response. Accurate diagnosis is critical, as metastatic mucinous tumors from the gastrointestinal tract frequently mimic primary ovarian mucinous carcinoma. This article discusses the epidemiology, etiology, pathogenesis, clinical features, histopathology, staging, diagnosis, management, prognosis, and recent advances related to ovarian mucinous carcinoma.

~Epidemiology

Ovarian mucinous tumors account for approximately 10–15% of all epithelial ovarian tumors, but true primary mucinous carcinomas constitute less than 3–5% of ovarian cancers. Most mucinous ovarian tumors are benign or borderline, with invasive carcinomas being relatively rare.

• Age: Typically occurs in younger women compared to serous carcinoma, often between 30 and 50 years

• Geographic variation: Incidence varies globally, with lower prevalence compared to high-grade serous carcinoma

• Laterality: Usually unilateral, which helps differentiate primary tumors from metastatic disease

~Etiology and Risk Factors

The exact cause of ovarian mucinous carcinoma remains unclear, but several risk factors and associations have been identified:

Risk Factors

• Nulliparity

• Early menarche and late menopause

• Genetic mutations (KRAS)

• Smoking (strongly associated with mucinous tumors)

• Hormonal factors

Protective Factors

• Oral contraceptive use

• Multiparity

• Breastfeeding

• Tubal ligation

Unlike high-grade serous carcinoma, ovarian mucinous carcinoma is not strongly associated with BRCA1 or BRCA2 mutations.

~Pathogenesis

Ovarian mucinous carcinoma is believed to arise through a stepwise progression:

Benign mucinous cystadenoma → Borderline mucinous tumor → Invasive mucinous carcinoma

This progression supports the adenoma-carcinoma sequence, similar to colorectal cancer.

Molecular Pathogenesis

• KRAS mutations: Present in a majority of mucinous tumors and considered an early event

• HER2 amplification: Seen in a subset of tumors

• TP53 mutations: Less common than in serous carcinoma

• Mismatch repair deficiency: Rare

The molecular profile of mucinous carcinoma resembles gastrointestinal malignancies more than other ovarian cancers.

~Gross Pathology

• Tumors are often large, sometimes exceeding 20–30 cm

• Typically unilateral

• Multiloculated cystic masses filled with thick, gelatinous mucin

• Solid areas suggest invasive carcinoma

• Capsular rupture may be present in advanced cases

~Histopathology

Microscopic Features

Ovarian mucinous carcinoma is characterized by:

• Glands lined by tall columnar epithelial cells

• Abundant intracellular mucin

• Nuclear atypia and stratification

• Stromal invasion

Patterns of Invasion

1. Expansile (confluent) invasion

   • Crowded glands without destructive stromal invasion

   • Better prognosis

2. Infiltrative (destructive) invasion

   • Irregular glands infiltrating the stroma

   • Worse prognosis

Histological Subtypes

• Intestinal type (most common)

• Endocervical (Müllerian) type (rare)

~Differential Diagnosis

A major diagnostic challenge is distinguishing primary ovarian mucinous carcinoma from metastatic mucinous carcinoma of gastrointestinal origin.

Features Favoring Primary Ovarian Tumor

• Unilateral

• Large size (>10 cm)

• Smooth capsule

• Expansile invasion

• Absence of surface implants

Features Favoring Metastatic Tumor

• Bilateral ovarian involvement

• Smaller size

• Nodular surface

• Extensive infiltrative invasion

• History of gastrointestinal malignancy

~Immunohistochemistry

Immunohistochemical markers aid diagnosis:

Marker	Expression
CK7	Positive
CK20	Variable
PAX8	Usually negative
CDX2	Often positive
SATB2	Suggests colorectal origin
ER/PR	Negative

A combination of markers is used rather than relying on a single stain.

~Clinical Features

Symptoms are often nonspecific, leading to delayed diagnosis:

• Abdominal distension

• Pelvic or abdominal pain

• Early satiety

• Gastrointestinal discomfort

• Menstrual irregularities (rare)

Because tumors are often large, patients may present earlier compared to serous carcinoma.

~Diagnosis

Clinical Evaluation

• Pelvic examination

• Abdominal examination

Imaging

• Ultrasound: Multiloculated cystic mass

• CT/MRI: Large unilateral ovarian mass, septations, solid components

• PET-CT: Useful for detecting metastasis

Tumor Markers

• CA-125: Often normal or mildly elevated

• CEA: Frequently elevated

• CA 19-9: May be increased

Definitive Diagnosis

• Histopathological examination following surgical removal

~Staging

Staging follows the FIGO staging system for ovarian cancer:

• Stage I: Tumor confined to ovaries

• Stage II: Pelvic extension

• Stage III: Peritoneal metastasis outside pelvis

• Stage IV: Distant metastasis

Most mucinous carcinomas are diagnosed at early stages (Stage I).

~Management

Surgical Treatment

Surgery is the cornerstone of management.

Standard Surgical Procedure

• Total abdominal hysterectomy

• Bilateral salpingo-oophorectomy

• Omentectomy

• Peritoneal washings

• Lymph node assessment (selective)

Fertility-sparing surgery may be considered in young women with early-stage disease.

Chemotherapy

Unlike serous carcinoma, ovarian mucinous carcinoma shows poor response to standard platinum-based chemotherapy.

• Stage IA: Surgery alone may suffice

• Advanced stages: Platinum-based regimens used, but with limited benefit

• Gastrointestinal-type chemotherapy (e.g., oxaliplatin-based regimens) is under investigation

~Prognosis

Prognosis depends on:

• Stage at diagnosis

• Pattern of invasion

• Completeness of surgical resection

Survival Rates

• Stage I: Excellent prognosis (5-year survival >90%)

• Advanced stages: Poor prognosis due to chemoresistance

Expansile invasion has a better outcome compared to infiltrative invasion.

~Complications

• Tumor rupture leading to pseudomyxoma peritonei (rare)

• Recurrence

• Intestinal obstruction

• Ascites in advanced disease

~Recent Advances and Research

• Molecular profiling for targeted therapy

• HER2-directed therapy in HER2-amplified tumors

• Immunotherapy trials (limited success so far)

• Improved pathological criteria to distinguish primary vs metastatic tumors

~Prevention and Screening

There is no effective screening test for ovarian mucinous carcinoma.

• Regular gynecological examinations

• Awareness of symptoms

• Risk-reducing surgery in high-risk individuals (limited role)

~Conclusion

Ovarian mucinous carcinoma is a rare but distinct subtype of epithelial ovarian cancer with unique clinical, pathological, and molecular characteristics. Accurate diagnosis, particularly differentiation from metastatic gastrointestinal tumors, is essential for appropriate management. While early-stage disease carries an excellent prognosis, advanced disease remains challenging due to poor chemotherapy response. Ongoing research into molecular targets and tailored therapies holds promise for improving outcomes in this uncommon malignancy.