Endometriosis and Adenomyosis

Slide 1 · Endometriosis and adenomyosis

Pathology | etiopathogenesis · morphology · clinical correlations

Ectopic endometrial tissue

Endometrial tissue in myometrium

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Localize ectopic endometrial tissue and compare endometriosis with adenomyosis.

Explain proposed origins and mechanisms sustaining lesions.

Identify morphology, clinical consequences and neoplastic associations.

Distribution

Pathogenesis

Morphology

Clinical relevance

Slide 3 · The central anatomic distinction

Feature

Endometriosis

Adenomyosis

Location

Outside the uterus

Within uterine myometrium

Relation to endometrium

Ectopic at extrauterine sites

Continues with endometrium

Slide 4 · Endometriosis: Defining components

Ectopic implants usually contain endometrial glands and stroma.

In some lesions, only endometrial stroma is evident.

An anatomic definition—not merely a symptom complex.

Endometrial glands

Surrounding endometrial stroma

Illustrative geometry — not a diagnostic specimen

Slide 5 · Endometriosis is predominantly pelvic

Listed distribution begins with ovaries and uterine ligaments.

Other frequent pelvic sites include rectovaginal septum, cul-de-sac and peritoneum.

Ovary

Uterine ligaments

Rectovaginal septum

Pelvic peritoneum

Slide 6 · Sites beyond the principal pelvic locations

Bowel and appendiceal serosa may be involved.

Cervical, vaginal and tubal mucosa can contain endometriotic foci.

Laparotomy scars are an additional recognized site.

Bowel / appendix

Genital-tract mucosa

Surgical scars

Slide 7 · Clinical context and prevalence

Most commonly encountered during active reproductive life.

Typical age distribution: Third and fourth decades.

Textbook estimate: Approximately 10% of females are affected.

Reproductive-age disease

Third and fourth decades

Approx. 10%

Slide 8 · Three morphologic forms of endometriosis

Superficial peritoneal endometriosis.

Ovarian endometriosis.

Deep infiltrating endometriosis.

Superficial peritoneal

Ovarian

Deep infiltrating

Slide 9 · Superficial peritoneal endometriosis

Implants occur on or just under peritoneal surfaces.

Periodic hemorrhage contributes to visible lesion color and local inflammation.

Endometrial cavity

Ectopic implant outside uterus

Slide 10 · Ovarian endometriosis

Ovarian lesions may accumulate altered blood within cystic spaces.

The resulting endometriotic cyst is an endometrioma (chocolate cyst).

Altered hemorrhagic fluid

Ovarian endometrioma — schematic

Slide 11 · Deep infiltrating endometriosis

Lesions invade tissues and induce fibrosis and adhesions.

The deep form can behave locally aggressively without implying invasive carcinoma.

Deep extension into tissue

Fibrotic response

Adhesions

Slide 12 · Phenotypes and malignant association

Form

Characteristic location

Textbook malignant association

Superficial

Peritoneal surface

Occasional

Ovarian

Ovarian tissue / cyst

Occasional

Deep infiltrating

Deep tissue involvement

Extremely rare

Slide 13 · Pathogenesis: Origins remain unresolved

Uterine endometrium

Extrauterine precursor cells

Ectopic tissue

Proposals fall into uterine-endometrium–derived and extrauterine-cell–derived origins.

No single theory accounts for all observed presentations.

Slide 14 · Regurgitation theory

Uterine shedding

Retrograde tubal flow

Peritoneal implantation

Retrograde menstrual flow carries endometrial tissue through the fallopian tubes.

Cells are proposed to implant on peritoneal or pelvic surfaces.

Slide 15 · Regurgitation: Mechanistic sequence

Ectopic deposition

Implant survival

Persistent lesion

The source of the tissue is intrauterine endometrium.

Pelvic distribution is compatible with reflux through the tubes.

Sustained ectopic growth still requires permissive local factors.

Slide 16 · Why regurgitation is plausible

Retrograde menstruation is common.

Most endometriosis occurs in the peritoneal cavity.

The theory directly connects these observations, but is incomplete.

Common retrograde flow

Frequent pelvic disease

Partial explanation

Slide 17 · Regurgitation cannot explain every patient

Cases are described in amenorrheic patients, including gonadal dysgenesis.

The occurrence of lesions without ordinary menstrual reflux indicates other mechanisms.

Amenorrhea

No conventional menstruation

Alternative origins needed

Slide 18 · Unusual distribution challenges reflux

Endometriotic tissue has been observed in distant organs, including lung, brain and bone.

Urogenital endometriosis has also been described in males receiving high-dose estrogen.

Distant organ sites

Estrogen-treated male cases

Reflux alone insufficient

Slide 19 · Frequency paradox of retrograde flow

Observation

Approximate frequency

Interpretive implication

Retrograde flow

Up to 90%

Common phenomenon

Endometriosis

About 10%

Additional susceptibility / survival mechanisms

Slide 20 · Benign metastasis hypothesis

Uterine endometrium

Blood / lymphatic routes

Distant deposits

Uterine endometrial cells may disseminate in blood vessels or lymphatic channels.

This theory addresses rare endometriosis in organs far from the pelvis.

Slide 21 · Metaplastic theory

Extrauterine epithelium

Endometrial differentiation

Ectopic tissue

Coelomic epithelium may differentiate toward endometrial tissue.

Mesonephric remnants also may undergo endometrial differentiation.

Slide 22 · Extrauterine stem/progenitor-cell theory

Bone marrow progenitor

Ectopic differentiation

Endometrial-like tissue

Bone-marrow-derived stem/progenitor cells have been proposed as a source.

Endometrial differentiation at extrauterine sites is hypothesized.

Slide 23 · Origin theories: Complementary explanations

Hypothesis

Cell source / movement

Principal explanatory strength

Regurgitation

Retrograde uterine tissue

Common pelvic implants

Benign metastasis

Vascular / lymphatic spread

Distant sites

Metaplasia

Coelomic / embryonic remnants

Nonuterine origins

Stem/progenitor

Extrauterine progenitors

Alternative cell origin

Slide 24 · Establishing an ectopic implant

Tissue deposition

Local survival signals

Vascular support

Implant persistence

Arrival of cells alone is insufficient for persistence.

Survival involves inflammatory signaling, angiogenesis, and matrix remodeling.

Slide 25 · Inflammatory mediator network

Implants and associated macrophages release proinflammatory factors.

The source includes PGE₂, IL-1, TNF, IL-6 and IL-8.

Endometriotic implant

Activated macrophages

Cytokines / PGE₂

Inflammatory milieu

Slide 26 · Macrophages amplify the lesion environment

Implant signaling

Macrophage recruitment

Amplified local factors

Inflammatory mediators recruit macrophages to implants.

Activated macrophages can release additional inflammatory and growth-promoting factors.

Slide 27 · Local chemokines and cytokines

Monocyte chemoattractant protein-1 (MCP-1/CCL2) participates in the network.

IL-6 and IL-8 are among the inflammatory factors detected.

MCP-1 / CCL2

IL-6

IL-8

Slide 28 · Angiogenesis supports ectopic survival

Endometriotic implant

VEGF signaling

Angiogenesis

Sustained survival

Establishment and continued growth require a blood supply.

VEGF is a representative proangiogenic mediator.

Slide 29 · Matrix remodeling permits implantation

Local extracellular matrix

MMP / TIMP activity

Remodeling

Implant anchorage

Matrix metalloproteinases (MMPs) remodel extracellular matrix.

Tissue inhibitors of metalloproteinases (TIMPs) also participate in this regulated system.

Slide 30 · Immune persistence is multifactorial

Inflammatory and tissue-remodeling factors may help lesions avoid immune clearance.

This as a proposed contribution, not a fully established universal mechanism.

Inflammation

Tissue remodeling

Possible immune evasion

Slide 31 · Nerve growth factor in endometriosis

NGF is among the factors found in the implant inflammatory environment.

It is a biologic link to neural signaling; The textbook does not specify an exact clinical dose-response.

NGF

Local microenvironment

Neural signaling

Slide 32 · Local aromatase production

Ectopic stromal aromatase

Local estrogen

Tissue persistence

Ectopic endometriotic stromal cells produce aromatase.

Normal endometrial stroma lacks this activity.

Local estrogen synthesis favors implant survival and persistence.

Slide 33 · Inflammation–estrogen coupling

Inflammation / PGE₂

Estrogen synthesis

Implant survival

Prostaglandin E₂ can stimulate local estrogen synthesis.

Estrogen in turn promotes maintenance of ectopic endometrial tissue.

Slide 34 · Increased estrogen responsiveness

Epigenetic changes are associated with enhanced estrogen responses.

In a hormonally responsive tissue, this supports proliferation and survival.

Epigenetic alterations

Estrogen responsiveness

Enhanced survival

Slide 35 · Decreased progesterone responsiveness

Endometriotic tissue has reduced responsiveness to progesterone.

This alteration is described alongside heightened estrogen responsiveness.

Reduced progesterone response

Altered hormonal balance

Ectopic persistence

Slide 36 · Retinoic acid and paracrine support

Stromal retinoic acid

Paracrine signal

Epithelial survival

Retinoic acid produced by stromal cells promotes epithelial-cell survival.

The effect is described as paracrine signaling from stroma to epithelium.

Slide 37 · Epigenetic changes in endometriosis

DNA methylation changes

Altered receptor responses

Implant advantage

DNA methylation changes are described in affected tissue.

They contribute to increased estrogen and reduced progesterone responses.

Slide 38 · The uterine endometrium may also differ

Related abnormalities are found at lower levels in eutopic endometrium of affected patients.

These observations suggest endometrial susceptibility beyond the ectopic site alone.

Ectopic lesion changes

Milder eutopic changes

Potential field susceptibility

Slide 39 · Integrated model of implant persistence

Proinflammatory recruitment, neovascularization and tissue remodeling cooperate.

Local estrogen synthesis and altered hormonal responsiveness reinforce survival.

Inflammation

Angiogenesis

Matrix remodeling

Estrogenic persistence

Slide 40 · Somatic genetic alterations are documented

Deep infiltrating lesions may harbor KRAS, PIK3CA, PPP2R1A or ARID1A mutations.

These alterations are described in the epithelial component.

KRAS / PIK3CA

PPP2R1A / ARID1A

Epithelial somatic changes

Slide 41 · Genetic findings require careful interpretation

The significance of driver-like mutations in deep lesions is uncertain.

They may contribute to local aggressive behavior, but malignancy is not inferred from mutation alone.

Somatic mutation

Possible local growth advantage

Not automatically cancer

Slide 42 · Association with specific ovarian cancers

Epidemiologic studies link endometriosis to ovarian endometrioid and clear cell carcinomas.

The histotype association is more informative than a nonspecific statement about ovarian cancer.

Endometriosis

Ovarian endometrioid carcinoma

Ovarian clear cell carcinoma

Slide 43 · Shared mutations suggest clonal relationships

Endometriotic epithelium

Shared driver alterations

Related carcinoma

In some patients, a carcinoma and adjacent endometriosis share somatic mutations.

These observations support a pathogenic relationship in a subset of cases.

Slide 44 · Malignant progression is not inevitable

Ovarian carcinoma may develop in association with an endometriotic cyst.

Atypical endometriosis is considered a likely precursor in this setting.

Most lesions are not presented as malignant in the source.

Typical endometriosis

Atypical endometriosis

Associated carcinoma

Slide 45 · Why endometriotic lesions change color

Ectopic tissue can bleed in response to hormonal stimulation.

Repeated hemorrhage produces red-blue to yellow-brown lesions.

Repeated hemorrhage

Pigment / organization

Illustrative geometry — not a diagnostic specimen

Slide 46 · Gross lesions: Nodules and superficial foci

Nodules may lie on or immediately below mucosal and serosal surfaces.

Hue reflects hemorrhage and its evolution over time.

Serosal / mucosal implant

Periodic hemorrhage

Red-blue / yellow-brown focus

Slide 47 · Organized hemorrhage causes adhesions

Repeated bleeding and organizing tissue repair promote fibrous adhesions.

Adhesions may join the tubes, ovaries and adjacent pelvic structures.

Adhesions after organized hemorrhage

Slide 48 · Obliteration of the pouch of Douglas

Widespread lesions can produce dense pelvic adhesions.

Organization and fibrosis can obliterate the cul-de-sac (pouch of Douglas).

Numerous ectopic foci

Hemorrhage + fibrosis

Cul-de-sac obliteration

Slide 49 · Endometrioma: The chocolate cyst

Ovarian cysts may be distorted by repeated bleeding.

Cystic masses roughly 3–5 cm filled with brown fluid.

Altered hemorrhagic fluid

Ovarian endometrioma — schematic

Slide 50 · Deep lesions produce tissue distortion

Deep infiltration may involve adjacent tissue planes.

Fibrosis and adhesions are major morphologic consequences.

Deep lesion extension

Fibrotic response

Anatomic distortion

Slide 51 · Histology: Endometrial glands and stroma

Coexistence of endometrial glands and endometrial stroma is the characteristic pattern.

Hemosiderin may or may not be identified.

Endometrial glands

Surrounding endometrial stroma

Illustrative geometry — not a diagnostic specimen

Slide 52 · Hemosiderin indicates previous bleeding

Blood products can persist as hemosiderin after cyclic hemorrhage.

Its presence is supportive, but the source does not require it in every diagnostic case.

Repeated hemorrhage

Pigment / organization

Illustrative geometry — not a diagnostic specimen

Slide 53 · Long-standing lesions can be difficult

Secondary fibrosis may obscure the endometrial glands and stroma.

Histologic recognition becomes harder in heavily scarred foci.

Sparse tissue obscured by fibrosis

Illustrative geometry — not a diagnostic specimen

Slide 54 · Endometriosis may be stromal-only

Occasionally only the endometrial stromal component is identifiable.

Absence of identifiable glands does not necessarily exclude an endometriotic focus.

Recognizable stroma

Glands not seen

Possible stromal-only lesion

Slide 55 · Glands alone prompt a differential diagnosis

Histologic pattern

Implication

Important caveat

Glands + stroma

Characteristic endometriosis

Hemosiderin not obligatory

Stroma only

Possible endometriosis

May be difficult in fibrosis

Glands only

Do not assume endometriosis

Consider endosalpingiosis

Slide 56 · Atypical endometriosis: Cytologic pattern

The cyst-lining epithelium shows cytologic atypia.

Major architectural changes are absent in this described pattern.

Endometriotic cyst lining

Cytologic atypia

Architecture largely preserved

Slide 57 · Atypical endometriosis: Proliferative pattern

Excessive epithelial proliferation produces glandular crowding.

Cytologic atypia may accompany the crowded glands.

Epithelial proliferation

Glandular crowding

Possible cytologic atypia

Slide 58 · The two atypical patterns are not identical

Atypical pattern

Cytology

Architecture

Cytologic

Atypical lining cells

No major changes

Proliferative

Often atypical

Crowded glands

Slide 59 · Endometriosis causes cyclic pelvic pain

Cyclic bleeding

Inflammation / adhesions

Pelvic pain

Dysmenorrhea is commonly severe.

Intrapelvic bleeding and periuterine adhesions are recognized contributors to pain.

Slide 60 · Dyspareunia has a structural correlate

Pain with intercourse is a typical presentation.

Pelvic adhesions and deep lesions can be considered in the clinicopathologic explanation.

Pelvic lesion

Fibrosis / adhesions

Dyspareunia

Slide 61 · Infertility may be the presenting problem

Infertility as the presenting complaint in 30–40% of patients.

This statistic concerns presenting complaint—not population infertility prevalence.

Tubal / ovarian adhesions

Distorted pelvic anatomy

Infertility presentation

Slide 62 · Diagnosis requires anatomic and histologic context

Clinical symptoms support suspicion but are not histologic proof.

Characteristic ectopic endometrial glands and stroma establish the tissue pattern.

Fibrosis, stroma-only foci and gland-only mimics complicate interpretation.

Location

Glands + stroma

Mimics / fibrosis

Slide 63 · Adenomyosis: Endometrial tissue in myometrium

Adenomyosis is defined by endometrial tissue within the uterine wall.

Unlike extrauterine endometriosis, it remains continuous with uterine endometrium.

Endometrial cavity

Endometrial tissue within myometrium

Slide 64 · Adenomyosis: Proposed down-growth

Endometrial lining

Down-growth

Myometrial nests

Endometrial tissue is thought to grow downward into the myometrium.

It extends between smooth-muscle fascicles rather than forming an extrauterine implant.

Slide 65 · Adenomyosis: Microscopic pattern

Irregular nests of endometrial stroma occur in the myometrium.

Glands may be present or absent within those stromal foci.

Myometrial smooth muscle

Gland + stroma

Illustrative geometry — not a diagnostic specimen

Slide 66 · Adenomyosis: Frequency in the source

Adenomyosis occurs in up to 20% of uteri.

This description should not be conflated with a population-based prevalence estimate.

Intrauterine wall involvement

Up to 20% of uteri

Context matters

Slide 67 · Adenomyosis: Abnormal bleeding

Menometrorrhagia denotes heavy, irregular menstrual bleeding.

Bleeding symptoms are part of the clinical adenomyosis spectrum.

Myometrial involvement

Abnormal bleeding

Menometrorrhagia

Slide 68 · Adenomyosis: Characteristic pain

Colicky dysmenorrhea and pelvic pain are described.

Symptoms may be especially prominent premenstrually.

Dyspareunia can occur.

Colicky dysmenorrhea

Premenstrual pelvic pain

Dyspareunia

Slide 69 · The two disorders can coexist

Adenomyosis and endometriosis are not mutually exclusive diagnoses.

Shared symptoms do not establish the anatomic location of ectopic tissue.

Endometriosis

Adenomyosis

Possible coexistence

Slide 70 · Endometriosis versus adenomyosis

Feature

Endometriosis

Adenomyosis

Tissue location

Outside uterus

Within myometrium

Relation to uterine lining

Ectopic, separated

Continuity / down-growth

Structural hallmark

Implants, cysts, adhesions

Endometrial nests in muscle

Common symptoms

Dysmenorrhea, pelvic pain, infertility

Abnormal bleeding, dysmenorrhea, pelvic pain

Slide 71 · Clinicopathologic case: Ovarian cyst

A reproductive-age patient has severe dysmenorrhea and an ovarian cyst containing brown fluid.

What lesion best explains the finding—and what process produced the cyst content?

Altered hemorrhagic fluid

Ovarian endometrioma — schematic

Slide 72 · Case interpretation: Endometrioma

Ovarian endometriosis can create a chocolate cyst.

Repeated hemorrhage produces the characteristic brown contents.

Histology may demonstrate endometrial glands, stroma and hemosiderin.

Endometrial glands

Surrounding endometrial stroma

Illustrative geometry — not a diagnostic specimen

Slide 73 · Clinicopathologic case: Uterine wall

A hysterectomy shows endometrial stroma with glands embedded among myometrial smooth-muscle fascicles.

What is the diagnosis, and how does this differ from endometriosis?

Myometrial smooth muscle

Gland + stroma

Illustrative geometry — not a diagnostic specimen

Slide 74 · Case interpretation: Adenomyosis

Endometrial tissue within the myometrium identifies adenomyosis.

Continuity with the endometrium differentiates it from extrauterine endometriosis.

Endometrial cavity

Endometrial tissue within myometrium

Slide 75 · Synthesis: Disease mechanism to morphology

Cell origin

Implant persistence

Cyclic hemorrhage

Clinical sequelae

Ectopic survival requires more than retrograde tissue movement alone.

Inflammatory and hormonal conditions contribute to persistence.

Hemorrhage, adhesions and fibrosis translate biology into symptoms.

Slide 76 · Four findings to remember

Endometriosis is extrauterine; Adenomyosis is intramyometrial.

Endometriosis characteristically contains ectopic glands and stroma.

Repeated hemorrhage explains pigment, endometriomas and adhesions.

Atypical endometriosis and some ovarian carcinoma share a pathogenic relationship.

Location

Morphology

Consequences

Neoplastic link

Slide 77 · Primary reference and image provenance

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th ed. (2026).

Chapter 22, The Female Genital Tract: Endometriosis and Adenomyosis, pp. 912–914.

All visible illustrations in this deck are original editable schematics, not photomicrographs.

Textbook source

Native PowerPoint diagrams

Figure traceability in notes