Normal Histological Structure of the Ovary
The normal ovary in premenopausal women consists of three main anatomical compartments: the outer cortex containing follicles at various stages of development, the inner medulla with blood vessels and stromal tissue, and a surface epithelium derived from modified peritoneal mesothelium. 1, 2
Cortical Architecture
The ovarian cortex demonstrates significant histological variation both within a single ovary and between bilateral ovaries in the same patient 1:
- Primordial follicles are distributed throughout the cortex, though their density varies considerably; interestingly, primordial follicles frequently appear in the medulla, particularly in cases with multiple follicular cysts 1
- Developing follicles at various stages (primary, secondary, and antral) undergo dynamic morphologic changes during the menstrual cycle, with evidence supporting multiple waves of antral follicle recruitment rather than a single cohort 3
- Follicular cysts are common normal findings that show variable distribution patterns 1
- Corpus luteum structures form after ovulation and subsequently transform into stromal cells 4
Medullary Components
The medulla contains 2:
- Loose connective tissue stroma with abundant blood vessels and lymphatics
- Hilar cells (Leydig-like cells) that may be present near the ovarian hilum
- Primordial follicles that frequently extend into medullary regions, contrary to traditional teaching that restricts them to cortex 1
Surface Epithelium Characteristics
The ovarian surface epithelium represents modified peritoneal mesothelium with distinct features 5:
- Single-layer cuboidal to low columnar cells that may be focally pseudostratified
- Müllerian differentiation potential based on embryologic origin from coelomic mesothelium during the 6th week of embryonic development 5
- Cortical invaginations and inclusion cysts are common findings that must be distinguished from pathologic endosalpingiosis 1
Stromal Elements
The ovarian stroma undergoes continuous transformation 6, 4:
- Sex cord-stromal derivatives include specialized cells such as granulosa cells, thecal cells, Sertoli cells, and Leydig cells that arise from embryonic gonadal sex cords 6
- Progressive stromal transformation occurs with aging, converting the ovary from a follicle-rich organ to a stroma-rich structure with reduced follicular activity 4
Age-Related Variations
Critical pitfall: Ovarian histology varies dramatically with reproductive age 1, 4:
- Premenopausal ovaries show active folliculogenesis with primordial follicles readily identifiable and multiple developing follicles at various stages 1
- Postmenopausal ovaries demonstrate stromal predominance, obliterative arteriolar sclerosis, surface epithelial cysts, and absence of active follicles 4
Endosalpingiosis vs. Inclusion Cysts
Important distinction: Endosalpingiosis (tubal-type epithelium within ovarian stroma) is frequently present in normal premenopausal ovaries and is closely associated with low-grade serous neoplasia, whereas simple inclusion cysts lined by surface-type epithelium have no known disease association 1. Pathologists must use updated definitions to distinguish these entities accurately 1.
Clinical Implications
Understanding normal histological variation is essential because 1:
- Significant inter-ovarian variation exists even within the same patient
- Follicular distribution patterns do not follow strict anatomical boundaries
- Pathologic processes can only be confirmed when normal variations are thoroughly understood