Polycystic Ovaries and Stromal Hyperthecosis

Slide 1 · Polycystic ovaries and

stromal hyperthecosis

Ovarian morphology • androgen excess • clinical correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish polycystic ovarian morphology from the syndrome PCOS.

Trace androgen excess and insulin resistance to reproductive and metabolic consequences.

Recognize the gross and microscopic phenotype of ovarian stromal hyperthecosis.

Compare the clinical and pathologic implications of the two conditions.

Slide 3 · Two disorders, two diagnostic starting points

Aspect

Primary process

Typical setting

Characteristic ovarian clue

Clinical concern

Polycystic ovary syndrome

Complex endocrine–metabolic syndrome

Reproductive age

Numerous cystic follicles

Anovulation; Metabolic disease

Stromal hyperthecosis

Diffuse ovarian stromal disorder

Usually postmenopausal

Luteinized stromal-cell nests

Marked androgen excess; Virilization

Slide 4 · Place in ovarian pathology

Non-neoplastic ovarian disorders

Follicular functional changes

PCOS-associated polycystic morphology

Stromal hyperthecosis

The core entities here are not primary epithelial ovarian neoplasms.

Slide 5 · Follicles, stroma, and steroidogenesis

Schematic—not a histologic specimen

Developing follicles provide the structural setting for ovulatory function.

Theca-associated steroidogenesis contributes to ovarian androgen production.

The surrounding stromal compartment may undergo hyperplasia and luteinization.

Slide 6 · PCOS is a syndrome, not an ultrasound finding

Hyperandrogenism and ovulatory dysfunction are central clinical features.

Polycystic ovarian morphology can accompany the syndrome.

An isolated morphologic appearance cannot establish PCOS.

Diagnostic assessment must integrate history and endocrine findings.

Slide 7 · PCOS: Population burden

6–10%

Reproductive-age females affected (textbook estimate)

Prevalence depends on diagnostic definition and population.

The disorder has reproductive and metabolic manifestations.

Do not equate population prevalence with the frequency of polycystic ovarian morphology.

Slide 8 · PCOS phenotype spans multiple organ systems

Ovarian androgen excess

Menstrual and ovulatory dysfunction

Subfertility

Metabolic comorbidity

One patient need not express every feature with the same severity.

Slide 9 · Why etiology remains incomplete

PCOS as an incompletely understood complex disorder.

Disordered ovarian androgen biosynthesis is a central finding.

Insulin resistance and adipose metabolism contribute to the phenotype.

Avoid attributing all cases to a single initiating lesion.

Slide 10 · Dysregulated androgen biosynthesis

Ovarian steroidogenic dysregulation

Excess androgen production

Clinical / biochemical hyperandrogenism

Disturbance of ovulatory function

Conceptual causal model; Mechanistic heterogeneity is acknowledged.

Slide 11 · Androgen excess: The clinical signal

Hirsutism and acne are important manifestations of hyperandrogenism.

Female-pattern hair loss may be present, but alone is less specific.

Severity and rate of progression inform the differential diagnosis.

Marked or rapidly progressive virilization warrants investigation beyond typical PCOS.

Slide 12 · Insulin resistance is a distinct PCOS axis

Insulin resistance

Compensatory hyperinsulinemia

Metabolic dysregulation

Increased risk of type 2 diabetes

Insulin resistance is common but not an obligatory feature in every patient.

Slide 13 · Adipose metabolism modifies the phenotype

Altered adipose metabolism with obesity and diabetes.

Adiposity and insulin resistance can amplify metabolic burden.

Normal body mass does not exclude a diagnosis of PCOS.

The reproductive and metabolic phenotypes need separate assessment.

Slide 14 · Endocrine and metabolic pathways interact

Ovarian androgen excess

Insulin resistance / adipose dysfunction

Reproductive and metabolic manifestations

Bidirectional associations; Simplified conceptual representation.

Slide 15 · Chronic anovulation produces cycle disruption

Disordered follicular development

Failure of regular ovulation

Irregular or absent menstrual bleeding

Reduced fertility

Not every irregular cycle is PCOS; Evaluate alternative causes.

Slide 16 · Menstrual abnormalities: What to establish

Characterize cycle intervals, pattern, and duration of irregularity.

Relate ovulatory dysfunction to the endocrine phenotype.

Assess pregnancy and alternative endocrine causes where relevant.

In adolescents, normal pubertal transition must not be overcalled as PCOS.

Slide 17 · Subfertility is linked to anovulation

Inconsistent ovulation reduces predictable opportunities for conception.

Anovulation is a functional consequence, not direct proof of ovarian neoplasia.

Fertility assessment also considers non-PCOS contributors.

Clinical management is individualized; Pathology identifies the underlying pattern.

Slide 18 · How multiple cystic follicles arise

Schematic—not a histologic specimen

Persistent or arrested follicular structures create a multifollicular appearance.

Numerous follicle cysts may enlarge the ovarian outline.

This structural finding must be interpreted alongside the clinical syndrome.

Slide 19 · Gross PCOS morphology

Schematic—not a histologic specimen

Ovarian enlargement may be associated with multiple cystic follicles.

The ovarian cut surface emphasizes the abundance of follicular structures.

Gross morphology alone does not prove a syndromic diagnosis.

Slide 20 · Microscopic interpretation of polycystic ovaries

Schematic—not a histologic specimen

A follicular-cyst pattern explains the many rounded cystic profiles.

Microscopy describes ovarian architecture; It does not substitute for endocrine history.

Avoid diagnosing PCOS from a single cystic follicle.

Slide 21 · Polycystic morphology is not specific

20–30%

Females with polycystic ovaries in the Robbins estimate

An ovarian morphology finding may occur without clinical PCOS.

This is why ovarian imaging is not a stand-alone endocrine diagnosis.

The denominator differs from the quoted PCOS prevalence.

Slide 22 · Functional follicular cysts are a different category

Feature

Pathologic unit

Interpretive basis

Diagnostic implication

Functional follicular cyst

Individual unruptured or resealed follicle

Non-neoplastic functional change

Does not establish PCOS

Polycystic ovarian pattern

Numerous follicular structures

Pattern requiring clinicopathologic context

Does not alone establish PCOS

Slide 23 · Avoid the ovary-to-syndrome fallacy

Polycystic morphology on scan

Assess cycles and hyperandrogenism

Exclude relevant mimics

Decide whether clinical PCOS criteria are met

Structural observation is the beginning of an evaluation, not its conclusion.

Slide 24 · Adult PCOS diagnostic framework (2023)

Hyperandrogenism

Ovulatory dysfunction

Polycystic morphology

Any two of three after exclusion of other causes

Adults: Two of three features after excluding other causes.

Features: Hyperandrogenism; Ovulatory dysfunction; Polycystic morphology (ultrasound or AMH alternative).

If hyperandrogenism and ovulatory dysfunction coexist, ultrasound or AMH is unnecessary.

Slide 25 · Ultrasound criteria are technology-dependent

≥20

Follicles per ovary in at least one ovary: 2023 adult guideline

Preferred follicle-number measure with adequate imaging technology.

Where image quality/older technology limits counts, ovarian volume ≥10 mL or follicles/section ≥10 can be used.

Do not transfer adult sonographic thresholds to adolescents.

Slide 26 · AMH has a circumscribed diagnostic role

In adults, anti-Müllerian hormone can define the polycystic-morphology component.

AMH alone is not a test for the entire PCOS syndrome.

Ultrasound and AMH should not both be used merely to increase case detection.

AMH is not recommended for PCOS diagnosis in adolescents.

Slide 27 · Adolescent PCOS requires greater specificity

Criterion

Hyperandrogenism

Ovulatory dysfunction

Ultrasound / AMH

Caution

Adults

Clinical or biochemical

One of three components

May assess morphology

Exclude other causes

Adolescents

Required

Required

Not recommended to diagnose

Avoid normal pubertal misclassification

Slide 28 · Biochemical androgen measurement matters

Total and free testosterone are recommended for assessment of biochemical hyperandrogenism.

Validated LC–MS/MS is preferred for total testosterone over low-precision direct immunoassays.

Laboratory-specific reference intervals and method matter.

Markedly increased levels or rapid progression prompt search for an alternative cause.

Slide 29 · Hyperandrogenism is not pathognomonic

Possibility

PCOS

Androgen-secreting neoplasm

Ovarian hyperthecosis

Adrenal / other endocrine source

Typical diagnostic clue

Reproductive-age chronic course

Rapid progression / virilization

Often postmenopausal, stromal

Biochemistry + clinical context

Key caution

Exclude other disorders

May have variable hormone levels

Imaging can be subtle

Requires targeted workup

Slide 30 · A practical initial assessment

History: Tempo + cycles

Examination: Androgen signs

Appropriate biochemical evaluation

Targeted ovarian/adrenal assessment

Clinical framework based on contemporary guideline recommendations.

Slide 31 · Cardiometabolic significance

PCOS to obesity and type 2 diabetes.

Insulin resistance and altered adipose metabolism are pathophysiologic contributors.

Cardiometabolic risk requires evaluation beyond reproductive symptoms.

Risk is not adequately characterized by ovarian morphology alone.

Slide 32 · Glycaemic assessment in PCOS (2023)

A 75-g oral glucose tolerance test is recommended as the most accurate glycaemic test in PCOS.

Fasting glucose or HbA1c can be used if OGTT is unavailable, with lower accuracy.

Routine insulin assays are not recommended as clinical measures of insulin resistance.

The recommendation applies regardless of BMI.

Slide 33 · Why cardiovascular risk assessment matters

Premature atherosclerosis is an association noted by Robbins.

Blood pressure, adiposity, glucose status, and other risk factors add clinical context.

Metabolic risk is not equivalent to diagnosing atherosclerosis histologically.

Clinical monitoring should address the whole cardiometabolic phenotype.

Slide 34 · Estrone links ovarian dysfunction to the endometrium

Chronic anovulation / androgen excess

Increased free serum estrone

Prolonged estrogenic stimulation

Endometrial hyperplasia risk

Endometrial carcinoma risk is increased in PCOS.

Slide 35 · Endometrial risk is important—but not absolute

Increased risk of endometrial hyperplasia and carcinoma.

The 2023 guideline recognizes increased relative risk while overall endometrial cancer probability remains low.

Routine endometrial cancer screening is not recommended for every person with PCOS.

Persistent abnormal bleeding or suspicious endometrial findings require clinical assessment.

Slide 36 · Endometrial vigilance is clinically selective

Prolonged untreated amenorrhea

Additional risks: High weight / diabetes

Abnormal bleeding or persistent thickening

Consider endometrial sampling when indicated

Guideline context: Risk-adapted evaluation is distinct from universal screening.

Slide 37 · Case 1: Incidental polycystic morphology

Case vignette

An adult with regular cycles and no clinical hyperandrogenism has an ultrasound reporting numerous small ovarian follicles.

Reasoning prompt

Is PCOS established by this finding?

No. Morphology by itself does not establish the endocrine syndrome.

Slide 38 · Case 1: An evidence-based interpretation

Document the ovarian morphology as observed.

Evaluate symptoms and cycle history before invoking PCOS.

Do not use ovarian cyst number as a substitute for syndrome criteria.

Avoid automatic endocrine labels in a pathology or imaging report.

Slide 39 · Stromal hyperthecosis: Defining lesion

A non-neoplastic disorder characterized by hypercellular ovarian stroma.

Stromal luteinization produces identifiable nests of steroidogenic-appearing cells.

Robbins also uses the term cortical stromal hyperplasia.

Often associated with clinically important androgen excess.

Slide 40 · Age distribution changes the differential

Reproductive age

Postmenopause

PCOS most typical

Hyperthecosis most typical

Overlap exists; Neither age group is absolute.

Slide 41 · Gross appearance in stromal hyperthecosis

Schematic—not a histologic specimen

Uniform, often bilateral enlargement of ovaries.

White-to-tan cut surface reflects increased stromal tissue.

Enlargement up to approximately 7 cm.

Slide 42 · The key microscopic lesion is stromal

Schematic—not a histologic specimen

Hypercellular, expanded ovarian stroma.

Discrete nests of luteinized cells with vacuolated cytoplasm.

The process may involve both ovaries, even without a mass-forming tumor.

Slide 43 · Recognizing luteinized stromal cells

Schematic—not a histologic specimen

Look for nests or clusters within a hypercellular stromal background.

Vacuolated or pale cytoplasm reflects the luteinized cell phenotype.

Interpret these cells within overall ovarian architecture—not as an isolated neoplasm.

Slide 44 · Stromal hyperplasia versus luteinization

Morphologic feature

Increased stromal cellularity

Luteinized cell nests

Bilateral ovarian expansion

What to look for

More prominent spindle-cell compartment

Rounded cells with clear/vacuolated cytoplasm

Diffuse rather than a dominant focal mass

Interpretation

Stromal hyperplasia

Hyperthecosis phenotype

Supports diffuse process

Slide 45 · Why hyperthecosis causes androgen excess

Luteinized stromal-cell population

Ovarian androgen production

Hirsutism ± virilization

Potential endometrial effects

The morphologic finding supplies a tissue correlate for endocrine activity.

Slide 46 · Postmenopausal virilization is a red flag

Hyperthecosis may cause more pronounced virilization than typical PCOS.

New or progressive deepening of voice, clitoromegaly, and androgenic alopecia merit assessment.

An androgen-producing tumor remains an essential competing diagnosis.

Clinical tempo and hormone assessment are more informative than morphology alone.

Slide 47 · An apparently normal scan does not exclude it

Ovarian hyperthecosis is often diffuse rather than a discrete mass.

Published case reports document histologic hyperthecosis despite subtle imaging.

Interpret ovarian dimensions in relation to age and menopausal state.

Do not assert that normal-appearing imaging excludes stromal disease.

Slide 48 · Endometrial consequences can parallel PCOS

Hyperandrogenic ovarian disorder

Peripheral estrogenic effects

Endometrial stimulation

Bleeding / hyperplasia concern

Similar endometrial effects in PCOS and stromal hyperthecosis.

Slide 49 · Hyperthecosis versus androgenic neoplasm

Clinical / pathologic clue

Distribution

Microscopy

Hormonal phenotype

Diagnostic limitation

Stromal hyperthecosis

Often diffuse / bilateral

Hypercellular stroma with luteinized nests

Androgen excess; Sometimes marked

Imaging may be inconspicuous

Androgenic ovarian tumor

May be a localized mass

Tumor-specific architecture

May also cause marked excess

Mass may be small or occult

Slide 50 · Morphology alone is not a serum diagnosis

Histopathology can establish stromal-cell changes in resected ovarian tissue.

An endocrine phenotype requires clinical and biochemical correlation.

Immunostains can support steroidogenic differentiation but are not substitutes for architecture.

One cannot infer an exact testosterone concentration from a slide.

Slide 51 · PCOS and hyperthecosis side by side

Dimension

Ovarian lesion

Typical life stage

Endocrine theme

Metabolic link

Endometrium

PCOS

Multiple cystic follicles

Reproductive age

Hyperandrogenism + anovulation

Insulin resistance and obesity

Hyperplasia / carcinoma risk

Stromal hyperthecosis

Stromal expansion / luteinization

Most often after menopause

Often prominent androgen excess

Metabolic comorbidity may coexist

Similar endometrial effects

Slide 52 · Case 2: Postmenopausal androgen excess

Case vignette

A postmenopausal patient develops progressive hirsutism and virilization. Imaging does not show a convincing unilateral ovarian mass.

Reasoning prompt

Which ovarian stromal disorder must remain in the differential?

Stromal hyperthecosis—while excluding an androgen-producing ovarian or adrenal tumor.

Slide 53 · Case 2: Morphology-directed reasoning

Evaluate the tempo and severity of androgenic changes.

Seek biochemical localization and exclude relevant adrenal/ovarian neoplasia.

If tissue is available, inspect for diffuse stromal hypercellularity and luteinized nests.

Correlate endometrial findings with bleeding history.

Slide 54 · Case 3: Longstanding anovulation

Case vignette

An adult with clinical hyperandrogenism has chronic oligomenorrhea and prolonged intervals without bleeding.

Reasoning prompt

Which downstream tissue is at risk, and why?

Endometrium: Sustained estrogenic stimulation in anovulatory states increases hyperplasia risk.

Slide 55 · Case 3: Clinical inference from pathology

Establish the reproductive and endocrine phenotype first.

Recognize estrogenic endometrial exposure as a distinct organ-level consequence.

Investigate abnormal uterine bleeding based on clinical indications.

Do not confuse increased relative risk with inevitable carcinoma.

Slide 56 · Pathology reporting: What belongs in the report

Describe actual ovarian architecture and stromal features seen on tissue.

Specify whether follicular cysts, stromal hypercellularity, or luteinized nests are identified.

Avoid diagnosing an endocrine syndrome from morphology alone.

Suggest clinicopathologic correlation when an androgenic condition is suspected.

Slide 57 · Common diagnostic pitfalls

Pitfall

Polycystic appearance automatically labeled PCOS

Single cyst treated as polycystic syndrome

Severe virilization attributed to routine PCOS

Normal imaging taken to rule out hyperthecosis

Endometrial cancer presented as inevitable

Correction

Apply clinical diagnostic criteria

Describe follicular lesion accurately

Evaluate tumors / hyperthecosis

Review endocrine context; Disease may be diffuse

Risk is increased, not deterministic

Slide 58 · Mechanistic synthesis

PCOS

Stromal hyperthecosis

Follicular cysts + anovulation

Stromal nests + androgen excess

Both: Endocrine effects on the endometrium

Slide 59 · Five clinicopathologic statements to retain

PCOS is an endocrine–metabolic syndrome, not a histologic synonym.

Polycystic follicles are common and nonspecific in isolation.

Insulin resistance and disordered androgen production are central PCOS themes.

Hyperthecosis shows luteinized stromal nests in expanded ovarian stroma.

Severe postmenopausal androgen excess demands exclusion of neoplasia.

Slide 60 · Evidence limits and proper attribution

Robbins provides the core ovarian morphology and endocrine associations.

The 2023 international guideline supplies updated diagnostic testing recommendations.

Published hyperthecosis cases illustrate variability but do not determine population-level accuracy.

Schematic illustrations in this deck are not clinical specimens or histology images.

Slide 61 · Selected references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. Elsevier; 2026. Chapter 22, p. 923.

Teede HJ et al. Recommendations from the 2023 International Evidence-Based Guideline for the Assessment and Management of PCOS. Hum Reprod. 2023;38:1655–1679.

Shah S, Torres C, Gharaibeh N. Diagnostic Challenges in Ovarian Hyperthecosis. Case Rep Endocrinol. 2022;2022:9998807.

Yousaf S et al. A Case of Ovarian Hyperthecosis in a Postmenopausal Woman. JCEM Case Rep. 2023;1:luad142.