What is the normal histology of the uterus?

Normal Histology of the Uterus

The human uterus consists of three distinct histological layers: the endometrium (innermost mucosal layer), the myometrium (thick muscular wall), and the perimetrium (outer serosal covering) 1.

Endometrium

The endometrium is composed of a surface epithelium with underlying glands and a specialized stroma that undergoes cyclic changes in response to hormonal stimulation.

Epithelial Components

• The endometrial surface is lined by simple columnar epithelium that extends into tubular glands penetrating the underlying stroma 1, 2
• Two main cell types populate the epithelium: ciliated cells and secretory (microvillous) cells, with the latter predominating in most phases 3
• The glands exhibit a complex three-dimensional architecture, forming a plexus network in the basalis layer that resembles a grass rhizome structure, rather than simple tubular structures 2

Stromal Components

• The endometrial stroma contains specialized stromal cells that can undergo decidualization during the secretory phase and pregnancy 1
• A rich vascular network with spiral arterioles supplies the functional layer, while straight arterioles supply the basalis 3
• Subepithelial capillary plexuses develop in the lamina propria to support the metabolically active endometrium 3

Functional Layers

• Functionalis (superficial layer): undergoes cyclic proliferation, secretory transformation, and menstrual shedding in response to ovarian hormones 2
• Basalis (deep layer): remains relatively stable throughout the menstrual cycle and serves as the regenerative source for the functionalis after menstruation 2

Myometrium

The myometrium comprises the bulk of the uterine wall and consists of interlacing bundles of smooth muscle cells with intervening connective tissue.

• Average myometrial thickness measures approximately 0.3-0.33 mm in the non-pregnant state (based on rodent models) 4
• Smooth muscle fibers are arranged in multiple orientations (circular, longitudinal, and oblique) to enable coordinated contractions 1, 4
• The muscle bundles are interspersed with elastic fibers, collagen, and blood vessels that provide structural support 4
• The depth of myometrial invasion is a critical prognostic factor in endometrial carcinoma staging, measured as the ratio of invasion depth to total myometrial thickness 5

Perimetrium (Serosa)

• The outermost layer consists of visceral peritoneum covering most of the uterine surface 1
• This thin serosal layer contains mesothelial cells and underlying connective tissue 1
• Blood vessels, including branches of the uterine arteries, course along the serosal surface 5

Cervical Histology

While not part of the uterine corpus proper, the cervix exhibits distinct histological features:

• The endocervical canal is lined by mucus-secreting columnar epithelium 5
• The ectocervix is covered by stratified squamous epithelium 5
• The cervical stroma is dense fibromuscular tissue, and its invasion is a key staging criterion (FIGO Stage II) in endometrial carcinoma 5

Clinical Relevance for Pathological Assessment

When evaluating uterine specimens, pathologists must assess:

• Endometrial thickness and architecture to identify hyperplasia or malignancy 5
• Depth of myometrial invasion as a percentage of total myometrial thickness for cancer staging 5
• Lymphovascular space invasion (LVSI) within the myometrium, with substantial LVSI defined as ≥4 involved vessels 5
• Cervical stromal involvement to distinguish Stage I from Stage II disease 5

Histological Variations

• The endometrium undergoes predictable cyclic changes during the menstrual cycle, with proliferative phase showing straight glands and secretory phase showing tortuous, saw-toothed glands 6
• During pregnancy, the endometrium transforms into decidua, with stromal cells becoming large and polygonal 1
• Postmenopausal endometrium is typically thin and atrophic, with an endometrial thickness ≤3-4 mm on ultrasound considered normal 6, 7