Uterine Corpus

Slide 1 · Uterine Corpus

Normal endometrial histology and functional disorders

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals

Identify the histologic compartments of the uterine corpus.

Recognize proliferative, secretory, and menstrual endometrium.

Relate cyclic morphology to ovarian steroid signaling.

Explain the pathogenesis and biopsy features of anovulatory bleeding.

Structure and cycle

Histologic phase recognition

Hormonal signaling

Anovulatory bleeding

Schematic: Qualitative relationships only

Slide 3 · Two complementary uterine compartments

Myometrium: Interwoven smooth muscle bundles forming the wall.

Endometrium: Glands embedded in specialized cellular stroma lining the cavity.

Their organization explains why hormone responses and disease patterns differ.

Uterine cavity

Endometrium

Myometrium

Slide 4 · Myometrium: Structural smooth muscle

Comprises tightly interwoven smooth muscle bundles.

Forms the muscular wall surrounding the uterine cavity.

Distinguished from the glandular and stromal endometrium.

Uterine cavity

Endometrium

Myometrium

Slide 5 · Endometrium: Glands within stroma

Glands provide the epithelial compartment of the lining.

A cellular stromal network supports glands and spiral arterioles.

Both compartments undergo coordinated cycle-dependent changes.

SCHEMATIC • Proliferative: Tubular glands / cellular stroma

Slide 6 · Two functional levels of endometrium

Functionalis: Superficial layer shed during menstruation.

Basalis: Deeper residual layer from which glands and stroma regrow.

Cyclic regeneration depends on retention of the basalis.

Uterine cavity

Endometrium

Myometrium

Functionalis

Basalis

Slide 7 · The corpus is affected by several disease pathways

Endocrine imbalance produces altered cyclic maturation and bleeding.

Pregnancy-related complications can disturb the uterine lining.

Neoplastic proliferation may involve either glandular or smooth-muscle tissue.

Disorder pathways

Endocrine disturbance

Pregnancy complication

Neoplastic proliferation

Schematic • associated categories, not a differential algorithm

Slide 8 · Normal histology is the interpretive reference

Endometrial gland shape changes across the cycle.

Epithelial activity changes from mitosis to secretion.

Stromal edema and predecidualization develop after ovulation.

Menses: Superficial shedding

Proliferation: Regrowth

Secretory: Differentiation

Progesterone withdrawal

Schematic: Qualitative relationships only

Slide 9 · A coordinated hypothalamic–pituitary–ovarian axis

Hypothalamic signals influence pituitary hormone secretion.

Pituitary and ovarian factors regulate follicular maturation and ovulation.

Ovarian steroid hormones determine endometrial morphology.

Hypothalamic signals

Pituitary hormonal response

Ovarian follicle / corpus luteum

Endometrial response

Schematic: Qualitative relationships only

Slide 10 · Steroid hormone exposure changes tissue phenotype

Estrogen promotes proliferation of endometrial glands and stroma.

Progesterone, following ovulation, promotes glandular and stromal differentiation.

Withdrawal of progesterone precedes menstrual breakdown.

Estrogen → proliferation

Progesterone → differentiation

Withdrawal / anovulation → altered shedding

Schematic: Qualitative relationships only

Slide 11 · A cyclical sequence, not a fixed morphology

Menses removes the superficial functionalis.

Proliferation reconstructs endometrium from the basalis.

Postovulatory differentiation creates secretory features.

Late luteal progesterone loss initiates another menses.

Menses: Superficial shedding

Proliferation: Regrowth

Secretory: Differentiation

Progesterone withdrawal

Schematic: Qualitative relationships only

Slide 12 · Endometrial appearance provides functional evidence

Microscopic morphology reflects recent ovarian steroid activity.

Typical secretory change supports a postovulatory progesterone effect.

The pattern can aid evaluation of abnormal bleeding or infertility.

Menses

Breakdown

Proliferative

Mitoses

Early secretory

Vacuoles

Late secretory

Predecidual stroma

Normal menstrual-cycle patterns • conceptual

Slide 13 · The four major morphologic patterns

Menstrual: Stromal breakdown and shedding.

Proliferative: Straight tubular glands with frequent mitoses.

Early secretory: Subnuclear epithelial vacuoles.

Late secretory: Serrated glands and predecidualized stroma.

Menses

Breakdown

Proliferative

Mitoses

Early secretory

Vacuoles

Late secretory

Predecidual stroma

Normal menstrual-cycle patterns • conceptual

Slide 14 · Menstruation sheds the functionalis

The superficial endometrium is lost during menses.

The deeper basalis remains to support the next cycle.

The process resets glandular and stromal organization.

Uterine cavity

Endometrium

Myometrium

Functionalis

Basalis

Slide 15 · Progesterone withdrawal precedes breakdown

The corpus luteum regresses when its hormonal support ends.

Progesterone concentrations decrease.

Functionalis degeneration, stromal bleeding, and breakdown follow.

Corpus luteum dissolution

Progesterone decline

Functionalis degeneration

Stromal bleeding / breakdown

Schematic: Qualitative relationships only

Slide 16 · Menstrual endometrium: Tissue-level clues

Stromal hemorrhage accompanies degeneration.

Fragmented glands and stromal breakdown may coexist.

The pattern must be interpreted in relation to cycle timing.

SCHEMATIC • Menstrual: Gland and stromal breakdown

Slide 17 · Not every leukocyte indicates inflammation

Sparse neutrophils and lymphocytes may occur in late secretory endometrium.

The source describes these cells as normal in that phase.

Their presence alone should not be equated with endometritis.

Physiological

Endometritis

Sparse late-cycle leukocytes

Phase-appropriate context

Requires specific evidence

Separate disease topic

Comparison: Teaching schematic

Slide 18 · Regeneration begins in the basalis

The retained deeper endometrium provides a regenerative substrate.

Both glands and stroma increase after menstruation.

Hormonal stimulation coordinates restoration of the functionalis.

Uterine cavity

Endometrium

Myometrium

Functionalis

Basalis

Slide 19 · The proliferative phase is a growth program

Rapid glandular and stromal growth follows menstruation.

Estrogen is the major proliferative stimulus.

Glands and supporting stroma remain morphologically coordinated.

Estrogenic stimulation

Gland / stroma proliferation

Tubular glands + mitoses

Schematic: Qualitative relationships only

Slide 20 · Proliferative glands are predominantly tubular

Glands appear relatively straight rather than serrated.

The epithelium consists of tall, regular pseudostratified columnar cells.

No overt secretory vacuolation is expected.

SCHEMATIC • Proliferative: Tubular glands / cellular stroma

Slide 21 · Proliferative epithelial mitoses are expected

Mitotic figures are numerous during active regrowth.

Proliferation occurs within an otherwise regular glandular lining.

Mitotic activity alone does not establish neoplastic change.

SCHEMATIC • Proliferative: Tubular glands / cellular stroma

Slide 22 · Proliferative stroma also expands

Spindle-shaped cells with scant cytoplasm form the cellular stroma.

Stromal cells undergo mitotic activity alongside glandular epithelium.

Growth is thus a two-compartment response.

SCHEMATIC • Proliferative: Tubular glands / cellular stroma

Slide 23 · Absence of secretory activity is informative

Proliferative glands lack conspicuous mucin secretion and vacuolation.

A biopsy with active mitoses but no secretory differentiation suggests estrogenic dominance.

Cycle history remains essential to interpretation.

Proliferative

Secretory

Tubular glands

Mitoses

Vacuoles / tortuosity

Predecidual stroma

Comparison: Teaching schematic

Slide 24 · Integrated proliferative-phase recognition

Straight glands + pseudostratified epithelium.

Frequent epithelial and stromal mitoses.

Cellular stroma without progesterone-dependent predecidual change.

SCHEMATIC • Proliferative: Tubular glands / cellular stroma

Slide 25 · Ovulation changes the hormonal environment

After ovulation, the corpus luteum produces progesterone.

Proliferative growth gives way to differentiation.

The first microscopic signs develop in glandular epithelial cells.

Ovulation

Corpus luteum forms

Progesterone exposure

Secretory differentiation

Schematic: Qualitative relationships only

Slide 26 · Early secretory change: Subnuclear vacuoles

Cytoplasmic vacuoles initially accumulate below glandular nuclei.

This follows the emergence of postovulatory progesterone effects.

Location of vacuoles is a useful phase-specific clue.

Gland lumen (apical side)

Nucleus

Subnuclear vacuole

SCHEMATIC • enlarged epithelial cells; Not a micrograph

Slide 27 · Secretory vacuoles migrate toward the lumen

Basally located vacuoles move toward the apical cell surface.

The sequence accompanies increasing glandular secretory activity.

It differs from the nonsecretory proliferative epithelium.

Early: Subnuclear vacuoles

Progressive vacuole redistribution

Apical secretory activity

Schematic: Qualitative relationships only

Slide 28 · Secretory activity predominates in the third week

The text describes the greatest secretory activity during week three.

Epithelial vacuoles change location during gland maturation.

Both hormonal context and morphology determine phase interpretation.

Gland lumen (apical side)

Nucleus

Subnuclear vacuole

SCHEMATIC • enlarged epithelial cells; Not a micrograph

Slide 29 · Late secretory glands acquire tortuosity

Glandular profiles become more convoluted toward week four.

A serrated or “sawtooth” luminal contour may emerge.

Secretory exhaustion and gland shrinkage accentuate this shape.

SCHEMATIC • Late secretory: Tortuous, serrated glands

Slide 30 · The serrated contour has a morphologic basis

A gland changes from a relatively smooth tube to a tortuous structure.

As secretion wanes and glands shrink, luminal folds become conspicuous.

This appearance is characteristic of late secretory endometrium.

Proliferative

Secretory

Tubular glands

Mitoses

Vacuoles / tortuosity

Predecidual stroma

Comparison: Teaching schematic

Slide 31 · Progesterone transforms the endometrial stroma

Late secretory changes are particularly prominent in stroma.

Edema increases as ground substance accumulates.

Spiral arterioles become more conspicuous.

Stromal proliferation

Ground substance / edema

Spiral arteriole prominence

Predecidual cell change

Schematic: Qualitative relationships only

Slide 32 · Stromal edema precedes predecidual change

Extracellular ground substance and edema increase.

Stromal cells subsequently enlarge and change cytoplasmic appearance.

This sequence reflects hormone-dependent tissue maturation.

Earlier stroma

Late secretory

Spindle cells

Limited edema

Stromal edema

Increasing ground substance

Comparison: Teaching schematic

Slide 33 · Spiral arterioles are a late-cycle clue

Prominent spiral arterioles appear during the secretory phase.

They occur alongside stromal edema and subsequent predecidualization.

Vascular development is part of the coordinated tissue response.

Spiral arteriole profiles

(conceptual vessels)

Schematic • not a tissue section

Slide 34 · Predecidualization changes stromal cells

Stromal cells undergo hypertrophy.

Cytoplasm becomes more eosinophilic.

The change reflects progesterone-driven stromal differentiation.

Pre-ovulatory

Late secretory

Small spindle cells

Scant cytoplasm

Enlarged cells

Eosinophilic cytoplasm

Comparison: Teaching schematic

Slide 35 · Predecidual change spreads across functionalis

Initially recognizable stromal transformation becomes more extensive.

Changes spread through the functionalis in late secretory endometrium.

This is physiological and must not be confused with abnormal stromal proliferation.

Pre-ovulatory

Late secretory

Small spindle cells

Scant cytoplasm

Enlarged cells

Eosinophilic cytoplasm

Comparison: Teaching schematic

Slide 36 · Late-cycle stromal mitoses can reappear

A resurgence of stromal mitoses accompanies late secretory change.

Mitoses must be interpreted by cell compartment and phase.

Concurrent predecidual transformation supports a physiological response.

Stromal proliferation

Ground substance / edema

Spiral arteriole prominence

Predecidual cell change

Schematic: Qualitative relationships only

Slide 37 · Late secretory leukocytes have physiological context

Sparse neutrophils and lymphocytes may accompany predecidualization.

These are normal findings description.

The diagnosis of inflammation requires more than leukocytes alone.

Physiological

Endometritis

Sparse late-cycle leukocytes

Phase-appropriate context

Requires specific evidence

Separate disease topic

Comparison: Teaching schematic

Slide 38 · Integrated secretory-phase recognition

Early: Subnuclear vacuoles in gland epithelium.

Late: Serrated glands and prominent stromal changes.

Edema, spiral arterioles, and predecidualization support progesterone effect.

Menses

Breakdown

Proliferative

Mitoses

Early secretory

Vacuoles

Late secretory

Predecidual stroma

Normal menstrual-cycle patterns • conceptual

Slide 39 · Morphology changes in two coordinated compartments

Epithelial sequence: Mitosis → vacuolation → secretion → exhaustion.

Stromal sequence: Proliferation → edema → predecidualization.

A discordance requires careful cycle and sampling interpretation.

EPITHELIUM

Mitosis

Vacuolation

Secretory exhaustion

STROMA

Proliferation

Edema

Predecidualization

Parallel hormone-associated pathways

Slide 40 · Ovarian steroids act through nuclear receptors

Endometrial hormone effects are primarily receptor-mediated.

Estrogen produces cellular proliferation and paracrine signaling.

Progesterone shifts the tissue toward differentiation.

Ovarian steroid hormone

Nuclear hormone receptor

Transcriptional response

Gland / stromal phenotype

Schematic: Qualitative relationships only

Slide 41 · Estrogen stimulates both glands and stroma

Estrogenic signaling drives proliferative regrowth.

Stromal responses can amplify epithelial growth.

Both compartments should be assessed in a proliferative-phase specimen.

Estrogenic stimulation

Gland / stroma proliferation

Tubular glands + mitoses

Schematic: Qualitative relationships only

Slide 42 · Stromal–epithelial cross-talk mediates growth

Estrogen-stimulated stromal cells produce growth factors.

The text names insulin-like growth factor-1 and epidermal growth factor.

These ligands activate receptors on glandular epithelium.

Estrogen-responsive stroma

IGF-1 / EGF growth factors

Glandular epithelial receptors

Epithelial proliferation

Schematic: Qualitative relationships only

Slide 43 · Progesterone attenuates estrogen responsiveness

Progesterone down-regulates estrogen receptor expression.

This occurs in glandular and stromal compartments.

Reduced estrogen responsiveness suppresses further proliferation.

Postovulatory progesterone

Estrogen-receptor down-regulation

Reduced proliferation

Gland / stromal differentiation

Schematic: Qualitative relationships only

Slide 44 · Progesterone promotes glandular differentiation

Following ovulation, glands develop secretory morphology.

Vacuoles and glandular tortuosity reflect the changing program.

Differentiation, not continued rapid growth, dominates.

Gland lumen (apical side)

Nucleus

Subnuclear vacuole

SCHEMATIC • enlarged epithelial cells; Not a micrograph

Slide 45 · Progesterone promotes stromal differentiation

Late secretory stroma accumulates edema and ground substance.

Stromal cells undergo predecidualization.

The morphological effect is readily recognized in tissue sections.

Stromal proliferation

Ground substance / edema

Spiral arteriole prominence

Predecidual cell change

Schematic: Qualitative relationships only

Slide 46 · Endometrial stem cells may contribute to renewal

Likely regenerative roles for stem cells.

They may also participate in ectopic endometrial tissue and malignancy.

These proposed contributions should not be treated as established causal proof.

Uterine cavity

Endometrium

Myometrium

Functionalis

Basalis

Slide 47 · Cycle histology: A consolidated comparison

Phase

Glandular features

Stromal features

Menstrual

Gland breakdown / fragments

Hemorrhage and breakdown

Proliferative

Tubular; Mitotic; Nonsecretory

Spindle cells; Mitoses

Early secretory

Subnuclear vacuoles

Early luteal change

Late secretory

Tortuous / serrated

Edema; Predecidual cells

Slide 48 · When abnormal bleeding lacks a structural lesion

The textbook uses the term dysfunctional uterine bleeding.

It denotes uterine bleeding without an underlying structural abnormality.

Disruption of normal hormonal coordination is a frequent cause.

Hormonal dysregulation

Altered endometrial maturation

Abnormal / irregular shedding

Schematic: Qualitative relationships only

Slide 49 · Bleeding also has structural causes

Structural causes

Functional causes

Endometritis, polyps

Hormonal dysregulation

Submucosal leiomyomas

Anovulatory cycles

Endometrial neoplasms

Endocrine / ovarian disturbance

Slide 50 · Physiological coordination is necessary

Normal cycles require appropriate timing of hormonal signals.

Abnormal release or response can alter proliferation and shedding.

Functional bleeding represents disturbed regulation rather than a single lesion.

Hypothalamic signals

Pituitary hormonal response

Ovarian follicle / corpus luteum

Endometrial response

Schematic: Qualitative relationships only

Slide 51 · Anovulation is the commonest functional mechanism

Anovulation is failure to ovulate.

The source identifies it as the most frequent cause of dysfunctional bleeding.

The absence of normal luteal progesterone is central to the mechanism.

Hormonal dysregulation

Altered endometrial maturation

Abnormal / irregular shedding

Schematic: Qualitative relationships only

Slide 52 · Anovulatory bleeding clusters at transition ages

It is especially common around menarche.

It also occurs in the perimenopausal period.

These settings are associated with altered ovulatory hormonal regulation.

Menarche: Ovulatory transitions

Reproductive intervals

Perimenopause: Ovulatory transitions

Schematic: Qualitative relationships only

Slide 53 · Endocrine disease can impair ovulation

Associated disorders include thyroid disease.

Adrenal disease and pituitary tumors are additional causes.

The ultimate endometrial response reflects abnormal ovarian steroid exposure.

Endocrine associations

Thyroid disease

Adrenal disease

Pituitary tumor

Schematic • associated categories, not a differential algorithm

Slide 54 · Ovarian abnormalities can impair ovulation

Polycystic ovaries are a recognized setting of anovulation.

Functioning ovarian tumors, including granulosa cell tumors, are cited.

Clinical etiology must be distinguished from the downstream biopsy pattern.

Ovarian associations

Polycystic ovaries

Functioning ovarian tumor

Altered ovulatory physiology

Schematic • associated categories, not a differential algorithm

Slide 55 · Metabolic and systemic disturbances matter

Obesity and malnutrition are named in the source.

Other chronic systemic diseases may disturb ovulation.

A uterine biopsy documents an endometrial response, not the full endocrine cause.

Systemic associations

Obesity

Malnutrition

Chronic systemic disease

Schematic • associated categories, not a differential algorithm

Slide 56 · Anovulation removes the luteal progesterone phase

Failure of ovulation prevents formation of a functional corpus luteum.

Normal progesterone-dependent maturation does not occur.

Estrogenic stimulation is therefore not opposed in the usual cyclic manner.

Anovulation

No functional corpus luteum

Progesterone absent

Unopposed estrogenic effect

Schematic: Qualitative relationships only

Slide 57 · Unopposed estrogen changes gland architecture

Persistent estrogenic effects maintain proliferative epithelium.

Endometrial glands may become cystically dilated.

These mild changes can regress after a later ovulatory cycle.

SCHEMATIC • Anovulatory: Cystic dilatation (simplified)

Slide 58 · Repeated anovulation can lead to bleeding

Persistent failure to ovulate changes the timing of shedding.

Repeated cycles can produce irregular endometrial bleeding.

Clinical circumstances may lead to endometrial biopsy.

Hormonal dysregulation

Altered endometrial maturation

Abnormal / irregular shedding

Schematic: Qualitative relationships only

Slide 59 · Typical anovulatory biopsy pattern

Pseudostratified endometrial glands predominate.

Scattered epithelial mitoses may still be present.

Cystic dilation may accompany estrogen-stimulated proliferation.

SCHEMATIC • Anovulatory: Cystic dilatation (simplified)

Slide 60 · Anovulatory breakdown can mimic menstruation

Stromal condensation occurs with bleeding.

Eosinophilic epithelial metaplasia may accompany breakdown.

These changes can resemble aspects of menstrual endometrium.

Menstrual

Anovulatory

Withdrawal after luteal phase

Secretory features may precede

No corpus luteum

No secretory / predecidual change

Comparison: Teaching schematic

Slide 61 · The absent progesterone effect is decisive

Normal secretory glandular features are lacking.

Stromal predecidualization is also absent.

These negative findings distinguish anovulatory breakdown from a normal luteal cycle.

Menstrual

Anovulatory

Withdrawal after luteal phase

Secretory features may precede

No corpus luteum

No secretory / predecidual change

Comparison: Teaching schematic

Slide 62 · The menstrual-versus-anovulatory distinction

Finding

Menstrual endometrium

Anovulatory breakdown

Hormonal context

Progesterone withdrawal

No luteal progesterone

Gland differentiation

Postsecretory context

Proliferative; Nonsecretory

Stromal state

Breakdown after luteal phase

Condensation; No predecidualization

Typical epithelial context

May follow sawtooth glands

Pseudostratified glands; Mitoses

Slide 63 · Case: Identify the proliferative pattern

Biopsy shows regularly arranged tubular glands.

Pseudostratified epithelium and mitoses are evident.

No secretory vacuoles or predecidual stromal change are present.

SCHEMATIC • Proliferative: Tubular glands / cellular stroma

Slide 64 · Case: Recognize a progesterone response

Biopsy shows glandular subnuclear vacuoles.

A subsequent sample shows tortuous glands and stromal edema.

Interpret the sequential findings as postovulatory maturation.

Gland lumen (apical side)

Nucleus

Subnuclear vacuole

SCHEMATIC • enlarged epithelial cells; Not a micrograph

Slide 65 · Case: Bleeding without secretory maturation

Patient has irregular uterine bleeding and repeated anovulation.

Biopsy shows pseudostratified glands, focal cystic dilation, and breakdown.

The absent luteal differentiation is central to interpretation.

SCHEMATIC • Anovulatory: Cystic dilatation (simplified)

Slide 66 · Four diagnostic reasoning checkpoints

Assess whether the glands are proliferative or secretory.

Read stromal features alongside epithelial morphology.

Look for evidence of postovulatory progesterone effect.

Correlate the biopsy with bleeding history and structural evaluation.

Examine gland phenotype

Examine stromal phenotype

Identify progesterone effect

Correlate bleeding / structure

Schematic: Qualitative relationships only

Slide 67 · Summary: Structure, hormones, morphology

Basalis supports restoration; Functionalis undergoes shedding.

Estrogen produces glandular and stromal proliferation.

Progesterone shifts the endometrium toward secretory and predecidual change.

Anovulation can cause bleeding without these luteal-phase features.

Estrogen → proliferation

Progesterone → differentiation

Withdrawal / anovulation → altered shedding

Schematic: Qualitative relationships only

Slide 68 · Limits of histologic interpretation

An endometrial pattern documents tissue responses to hormonal exposure.

It does not, by itself, identify the upstream cause of anovulation.

Structural causes must remain in the differential diagnosis of uterine bleeding.