Residency · Residency · Pathology
Ovarian Epithelial Tumors and Peritoneal Pathology
Introduction
Epithelial ovarian tumors account for approximately 60% of all ovarian neoplasms and over 90% of ovarian malignancies. The current WHO classification recognizes five major histologic types with a dualistic model dividing them into Type I (low-grade, indolent) and Type II (high-grade, aggressive) pathways. Understanding the relationship between the ovary, fallopian tube, and peritoneum is essential for accurate diagnosis and staging.
The Five Major Histologic Types
High-Grade Serous Carcinoma (HGSC)
HGSC is the most common and most lethal subtype, accounting for roughly 70% of epithelial ovarian cancers. TP53 mutation is virtually universal, found in over 96% of cases. The architecture is a mix of solid, papillary, and slit-like glandular patterns with marked nuclear atypia. Immunohistochemically, the tumor is p53 aberrant (showing either overexpression or a null pattern), WT1 positive, PAX8 positive, and frequently ER positive. BRCA1/2 mutations (germline or somatic) occur in approximately 25% of cases, and homologous recombination deficiency (HRD) testing guides eligibility for PARP inhibitor therapy.
Low-Grade Serous Carcinoma (LGSC)
LGSC shows uniform, low-grade nuclei with papillary and micropapillary architecture, and psammoma bodies are often abundant. The molecular profile includes KRAS, BRAF, and NRAS mutations with wild-type p53. It may arise from a serous borderline tumor. Although indolent in behavior, LGSC tends to be chemoresistant.
Endometrioid Carcinoma
Ovarian endometrioid carcinoma resembles its endometrial counterpart, with glandular architecture and squamous differentiation. It is commonly associated with endometriosis, often ipsilateral. Key molecular alterations include ARID1A, PIK3CA, PTEN, and CTNNB1 mutations, with microsatellite instability in a subset of cases.
Clear Cell Carcinoma
This subtype features hobnail cells, tubulocystic and papillary patterns, and hyalinized stroma. It is Napsin A positive and HNF1-beta positive, with p53 wild-type in most cases. Like endometrioid carcinoma, it is associated with endometriosis and is relatively chemoresistant. ARID1A and PIK3CA mutations are common.
Mucinous Carcinoma
Before diagnosing a primary ovarian mucinous carcinoma, metastasis from the GI tract or pancreaticobiliary system must be excluded. Primary ovarian mucinous carcinoma is typically unilateral and large (over 10 cm), with expansile or infiltrative invasion patterns. The immunophenotype is CK7 positive with variable CK20, and SATB2 negativity helps exclude a colorectal origin. KRAS mutations are frequent.
Serous Tubal Intraepithelial Carcinoma (STIC)
STIC is recognized as the precursor of most high-grade serous carcinomas. It is identified in the fimbriated end of the fallopian tube and shows p53 aberrant staining with an elevated Ki-67 index (typically over 70%). The systematic SEE-FIM protocol (Sectioning and Extensively Examining the Fimbriated end) is essential for its detection.
Borderline (Atypical Proliferative) Tumors
Borderline tumors exist in serous, mucinous, endometrioid, and clear cell types. They show epithelial proliferation and atypia without destructive stromal invasion. Serous borderline tumors may have non-invasive peritoneal implants (which carry a favorable prognosis) or invasive implants (which lead to upstaging). The prognosis is excellent in most cases, and fertility-sparing surgery may be appropriate.
Peritoneal Pathology
Primary Peritoneal Carcinoma
Primary peritoneal carcinoma is morphologically identical to HGSC but with minimal or no ovarian involvement. It shares the same molecular profile (TP53, BRCA) and is treated with the same regimens used for ovarian HGSC.
Peritoneal Staging
Peritoneal biopsies are critical for staging, as FIGO Stage III is defined by peritoneal spread. The report should document the presence, size, and location of peritoneal deposits. It is important to distinguish tumor implants from endosalpingiosis, which is benign tubal-type epithelium on the peritoneal surface.
Immunohistochemistry Panel
| Marker | HGSC | LGSC | Endometrioid | Clear Cell | Mucinous |
|---|---|---|---|---|---|
| WT1 | + | + | - | - | - |
| p53 abn | + | - | -/+ | - | - |
| PAX8 | + | + | + | + | -/+ |
| Napsin A | - | - | - | + | - |
| ER | + | + | + | - | - |
| CK7 | + | + | + | + | + |
Clinical Pearls
The SEE-FIM protocol should be applied to all fallopian tubes from risk-reducing or cancer surgery to detect STIC lesions. A metastatic origin must always be excluded before diagnosing primary ovarian mucinous carcinoma. BRCA and HRD testing are standard of care for HGSC and guide PARP inhibitor eligibility. The distinction between invasive and non-invasive peritoneal implants in borderline tumors is prognostically important and should be clearly documented.
References
- WHO Classification of Tumours Editorial Board. Female Genital Tumours. 5th ed. Lyon: IARC Press; 2020.
- Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012;460(3):237-249.
- Medeiros F, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol. 2006;30(2):230-236.
- Soslow RA. Histologic subtypes of ovarian carcinoma: an overview. Int J Gynecol Pathol. 2008;27(2):161-174.