Other Sex Cord Stromal Tumors

Slide 1 · Other Sex Cord–Stromal Tumors

Ovarian Leydig cell tumors · Pregnancy luteoma · Gonadoblastoma

Ovarian pathology • Morphology, endocrine effects and clinicopathologic interpretation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Identify the defining tissue components of three uncommon ovarian tumors.

Connect steroid production to the characteristic clinical presentations.

Distinguish a pure Leydig cell neoplasm from a mixed germ-cell/sex-cord lesion.

Interpret key morphologic clues, associations and stated prognosis.

Slide 3 · The primary diagnostic scope

Three uncommon lesions are described together.

Their shared context is ovarian sex cord or stromal differentiation.

Gonadoblastoma has an additional, essential germ-cell component.

Ovarian sex cord–stromal context

Leydig cell tumor / Pregnancy luteoma

Gonadoblastoma: Germ cells + sex cord cells

Schematic — conceptual relationship, not specimen imagery

Slide 4 · Developmental basis of sex cord–stromal tumors

Ovarian stroma develops from the sex cords of the embryonic gonad.

The precursor mesenchyme produces cell types such as granulosa, theca, Sertoli and Leydig cells.

Tumors can resemble these differentiated gonadal cell populations.

Undifferentiated gonadal mesenchyme

Sex cord and stromal differentiation

Corresponding ovarian tumors

Schematic — conceptual relationship, not specimen imagery

Slide 5 · Why some ovarian stromal tumors alter hormones

Normal granulosa/theca cells participate in estrogen production.

Normal Leydig cells are androgen-producing cells.

Neoplastic differentiation may preserve steroid-producing function.

Granulosa / theca lineage

Estrogenic phenotype

Leydig lineage → androgenic phenotype

Schematic — conceptual relationship, not specimen imagery

Slide 6 · Hormone phenotype is a diagnostic clue

Virilization can direct attention toward an androgen-producing ovarian lesion.

Estrogenic effects suggest a different functional lineage.

Clinical phenotype is informative but does not replace morphologic classification.

Slide 7 · The three entities are biologically distinct

Entity

Defining context

Central clue

Leydig cell tumor

Unilateral ovarian hilar tumor

Lipid-rich cells; Reinke crystalloids

Pregnancy luteoma

Ovarian lesion of pregnancy

Corpus luteum-like tumor; virilization possible

Gonadoblastoma

Germ cells + sex cord derivatives

Abnormal sexual development; dysgerminoma association

Slide 8 · Separate lineage from clinical manifestation

An androgenic presentation describes endocrine effect, not a single tumor type.

A pregnancy-associated ovarian lesion requires interpretation in gestational context.

A mixed germ-cell/sex-cord lesion requires recognition of both populations.

Slide 9 · Four-domain review of an ovarian lesion

Localize the lesion and establish clinical context.

Characterize hormonal manifestations.

Identify the constituent cell populations.

Use behavior and associated tumors to complete interpretation.

Clinical setting and site

Endocrine effects and morphology

Classification and behavior

Schematic — conceptual relationship, not specimen imagery

Slide 10 · Claims supported by the textbook excerpt

Leydig tumors: Location, cellular morphology, androgenic manifestations and benign course.

Pregnancy luteoma: Similarity to pregnancy corpus luteum and possible virilization.

Gonadoblastoma: Biphasic composition, clinical context, coexistence and prognosis.

The excerpt does not provide a comprehensive immunohistochemical algorithm for these three lesions.

Slide 11 · Leydig cell tumor: Defining entity

A rare ovarian tumor of Leydig-cell differentiation.

Located in the ovarian hilus and usually unilateral.

Dominant secreted steroid: Testosterone.

True Leydig cell tumors are almost always benign.

Slide 12 · The ovarian hilus is a discriminating site

The textbook specifically locates Leydig cell tumors in the ovarian hilus.

Location complements rather than substitutes for histologic examination.

The tumor is described as unilateral.

Ovary

Hilar region

Leydig cell neoplasm

Schematic — conceptual relationship, not specimen imagery

Slide 13 · Unilateral occurrence is characteristic

The lesion is described as rare and unilateral.

Side and exact size are not specified by the source as diagnostic criteria.

Retain gross laterality and anatomic relationship in pathology documentation.

Slide 14 · Leydig cell cytology: Large cells

The neoplasm comprises large Leydig-type cells.

Individual cell borders are distinct.

Cells contain abundant cytoplasmic lipid.

The combined constellation supports the differentiation.

Slide 15 · Lipid-rich cytoplasm is a lineage clue

The source explicitly describes lipid-laden Leydig cells.

Lipid content is consistent with their steroid-producing phenotype.

Cytoplasmic character should be interpreted with location and cell identity.

Large Leydig-type cell

Lipid-containing cytoplasm

Androgen-producing phenotype

Schematic — conceptual relationship, not specimen imagery

Slide 16 · Reinke crystalloids: Hallmark clue

Characteristic cytoplasmic structures are called Reinke crystalloids.

Their intracytoplasmic location is the relevant structural feature.

The text identifies them as a feature of true ovarian Leydig cell tumors.

Slide 17 · Diagnostic reasoning from morphology

Hilar position suggests the correct anatomic setting.

Large lipid-rich cells with distinct borders suggest Leydig differentiation.

Reinke crystalloids add characteristic cytoplasmic evidence.

Hilar location

Leydig-type cells

Reinke crystalloids

Schematic — conceptual relationship, not specimen imagery

Slide 18 · Morphology cannot be inferred from virilization

Hirsutism, voice changes and clitoral enlargement are clinical effects.

None of these findings independently demonstrates Reinke crystalloids.

Histologic examination establishes tumor morphology and classification.

Slide 19 · Functional output: Testosterone predominates

Leydig cell tumors primarily produce testosterone.

An excess of androgenic signaling explains the masculinizing syndrome.

Clinical recognition requires connecting secretion to target-tissue effects.

Testosterone-producing tumor

Increased androgenic effects

Masculinization / virilization

Schematic — conceptual relationship, not specimen imagery

Slide 20 · Hirsutism: Visible androgenic expression

Hirsutism is a listed presentation of ovarian Leydig cell tumor.

Interpret the sign as part of a broader endocrine syndrome.

Hormonal signs should be matched with an appropriate ovarian lesion.

Slide 21 · Voice change: Systemic endocrine effect

Voice change is a characteristic masculinizing feature in the source.

It illustrates the systemic influence of tumor steroid production.

The finding is not unique to Leydig cell tumors.

Slide 22 · Clitoral enlargement: Another virilization feature

Clitoral enlargement is explicitly described in the clinical presentation.

It belongs to the same testosterone-dominant symptom complex.

It should not be interpreted separately from the total clinical context.

Slide 23 · Clinical triad described for ovarian Leydig tumor

Clinical sign

Interpretive significance

Hirsutism

Androgen-dependent hair growth

Voice changes

Systemic masculinization

Clitoral enlargement

Androgenic genital change

Slide 24 · Severity compared with Sertoli–Leydig tumors

Leydig cell tumor–associated masculinization is usually milder.

Sertoli–Leydig tumors may cause striking virilization.

The relative degree is an association, not a stand-alone diagnostic test.

Slide 25 · Leydig versus Sertoli–Leydig tumors

Feature

Leydig cell tumor

Sertoli–Leydig tumor

Cell identity

Large lipid-rich Leydig cells

Sertoli tubules ± Leydig cells

Typical location

Ovarian hilus

Unilateral ovarian tumor

Androgenic effects

Often milder

May be striking

Behavior in source

Almost always benign

Recurrence/metastasis <5%

Slide 26 · Behavior of true Leydig cell tumors

The primary source states that true ovarian Leydig cell tumors are almost always benign.

This differs from the potentially malignant behavior of granulosa cell tumors.

Biologic expectations must follow the established histologic category.

Establish true Leydig morphology

Distinguish related tumor types

Predominantly benign course

Schematic — conceptual relationship, not specimen imagery

Slide 27 · Management stated

Surgical excision is the treatment described for Leydig cell tumors.

Almost-always-benign behavior provides the stated prognostic context.

The source excerpt does not specify an operative extent or follow-up protocol.

Slide 28 · Applied case: Ovarian hilus and virilization

Hypothetical teaching vignette: An ovarian lesion in the hilus accompanies progressive hirsutism and voice changes. Histology shows large lipid-laden cells with discrete borders.

Discussion prompts

Which ovarian tumor is most strongly suggested?

Which characteristic cytoplasmic structure would support it?

Hypothetical educational case; No patient data

Slide 29 · Case resolution: Ovarian Leydig cell tumor

The ovarian hilar location fits the source description.

Lipid-laden Leydig-type cells explain the morphologic identity.

Reinke crystalloids are the characteristic cytoplasmic structures.

Testosterone output accounts for the virilization.

Slide 30 · Morphology exercise: Avoid premature naming

Hypothetical review: An androgenic ovarian mass is submitted without reliable anatomic localization or adequate microscopy.

Discussion prompts

Can the hormonal phenotype alone establish a Leydig cell tumor?

What further information is required from the specimen?

Hypothetical educational case; No patient data

Slide 31 · Morphology exercise: Reasoning answer

No: Androgenic activity is shared by more than one ovarian sex cord–stromal neoplasm.

Establish the tumor location and inspect the differentiated cell populations.

Look for the defining Leydig cell features before applying the category.

Slide 32 · Pregnancy luteoma: Clinical context

Pregnancy luteoma is a rare ovarian tumor discussed in the source.

It closely resembles the corpus luteum of pregnancy.

The gestational setting is part of the essential interpretation.

Slide 33 · The corpus luteum is the morphologic comparator

Pregnancy luteoma closely resembles the corpus luteum of pregnancy.

The name and pregnancy context help establish the appropriate comparison.

The excerpt does not supply detailed formal microscopic criteria.

Pregnancy

Corpus luteum-like ovarian lesion

Pregnancy luteoma

Schematic — conceptual relationship, not specimen imagery

Slide 34 · Gestational context is diagnostically important

A lesion occurring during pregnancy has a different clinical setting from the hilar Leydig tumor.

A luteal resemblance is explicitly emphasized in the source.

Assess a gestational ovarian mass without importing unsupported criteria.

Slide 35 · Pregnancy luteoma can produce androgenic effects

The source records virilization in pregnant patients.

This supports possible hormonal function during gestation.

The source does not quantify the frequency or biochemical hormone levels.

Pregnancy luteoma

Steroid-hormone effect

Maternal virilization may occur

Schematic — conceptual relationship, not specimen imagery

Slide 36 · Maternal virilization during pregnancy

Virilization in the pregnant patient is an important possible manifestation.

The association does not establish that every pregnancy luteoma is hormonally active.

Clinical interpretation requires pregnancy context and lesion identification.

Slide 37 · Female infants may also be virilized

The source specifically mentions virilization in female infants.

Maternal and infant effects may coexist in the same pregnancy.

The excerpt does not specify predictors or severity of fetal effects.

Slide 38 · Two clinical recipients of a gestational endocrine effect

A pregnancy luteoma can affect the pregnant patient.

It may also be associated with virilization in a female infant.

This diagram represents the clinical association, not a verified hormone-transfer pathway.

Pregnancy luteoma

Maternal virilization

Virilization of female infant

Schematic — conceptual relationship, not specimen imagery

Slide 39 · Pregnancy luteoma versus Leydig cell tumor

Domain

Pregnancy luteoma

Leydig cell tumor

Clinical context

Pregnancy

Ovarian hilus

Morphologic clue

Corpus luteum resemblance

Reinke crystalloids; lipid-rich cells

Possible endocrine effect

Virilization of pregnant patient / female infant

Testosterone-predominant masculinization

Behavior in excerpt

Not detailed

Almost always benign

Slide 40 · Limits of the source on pregnancy luteoma

The supplied excerpt does not state diagnostic IHC or molecular markers.

It does not specify lesion regression, natural history or detailed treatment.

These cannot be presented as verified Robbins statements from this excerpt.

Slide 41 · Applied case: Virilization in pregnancy

Hypothetical teaching vignette: During pregnancy, an ovarian lesion resembles the corpus luteum. The pregnant patient has virilizing features; A female infant is also affected.

Discussion prompts

Which named lesion is consistent with the description?

Which two clinical subjects may be affected?

Hypothetical educational case; No patient data

Slide 42 · Case resolution: Pregnancy luteoma

The pregnancy context and corpus luteum resemblance match pregnancy luteoma.

Virilization may affect the pregnant patient.

The source also describes possible virilization of female infants.

A clinical example cannot establish incidence or treatment response.

Slide 43 · Gonadoblastoma: A mixed-cell lesion

Gonadoblastoma is an uncommon gonadal tumor.

Its composition combines germ cells and sex cord–stromal derivatives.

Its mixed lineage is the central morphologic concept.

Slide 44 · Component one: Germ cells

Germ cells constitute one essential population in gonadoblastoma.

The diagnosis is therefore not purely sex cord–stromal.

The source ultimately places gonadoblastoma among noninvasive germ-cell neoplasias.

Germ-cell component

Mixed gonadoblastoma

Noninvasive germ-cell neoplasia

Schematic — conceptual relationship, not specimen imagery

Slide 45 · Component two: Immature Sertoli-like cells

Some sex cord–stromal derivatives resemble immature Sertoli cells.

This provides one element of the mixed gonadal differentiation.

Cell resemblance does not make gonadoblastoma a pure Sertoli tumor.

Slide 46 · Component three: Immature granulosa-like cells

Other stromal derivatives resemble immature granulosa cells.

Both male-type and female-type sex cord resemblance may be present.

The mixed pattern matters more than assigning a single differentiated lineage.

Slide 47 · Gonadoblastoma: Composite rather than pure lineage

A correct conceptual model includes both germ cells and sex cord cells.

Sertoli-like and granulosa-like differentiation describes the latter population.

The graphic is a lineage schematic, not a histologic section.

Germ cells

Immature sex cord elements

Composite gonadoblastoma

Schematic — conceptual relationship, not specimen imagery

Slide 48 · Association with abnormal sexual development

The source associates gonadoblastoma with abnormal sexual development.

Gonads of indeterminate nature are a recognized context.

This clinical setting distinguishes it from the usual presentation of a hilar Leydig tumor.

Slide 49 · Indeterminate gonads: An essential setting

Gonadoblastoma may arise in a gonad whose nature is indeterminate.

The source emphasizes the relationship to atypical gonadal development.

Clinical anatomy should be documented alongside the histologic diagnosis.

Abnormal sexual development

Gonad of indeterminate nature

Gonadoblastoma

Schematic — conceptual relationship, not specimen imagery

Slide 50 · Phenotypic distribution reported

Phenotypic females

80%

Phenotypic males

20%

The percentages describe the patients statement. They are not percentages of all ovarian tumors.

Slide 51 · Phenotypic females: Interpretation

The source describes 80% of patients as phenotypic females.

Phenotypic appearance does not negate an associated disorder of gonadal development.

Phenotype and gonadal histology supply different diagnostic information.

Slide 52 · Phenotypic males: Distinctive associated anatomy

The source states that 20% are phenotypic males.

The described setting includes undescended testes.

Female internal secondary organs are also described in these patients.

Slide 53 · Avoid oversimplifying gonadal phenotype

Both phenotypic females and phenotypic males are represented in the source.

The shared diagnostic context is abnormal sexual development / indeterminate gonads.

External phenotype alone is insufficient to infer the tumor’s cell populations.

Slide 54 · Coexistent dysgerminoma is common in the excerpt

With dysgerminoma

50%

Other cases

50%

The source reports dysgerminoma in 50% of gonadoblastoma cases. The second bar category denotes the remainder and does not define its histology.

Slide 55 · Why coexistent dysgerminoma matters

The source reports a substantial association with dysgerminoma.

A mixed neoplasm should not be assumed to consist only of the gonadoblastoma component.

Careful evaluation for a concurrent germ-cell tumor follows logically.

Identify gonadoblastoma

Consider reported 50% coexistence

Evaluate for dysgerminoma

Schematic — conceptual relationship, not specimen imagery

Slide 56 · Classification: Noninvasive germ-cell neoplasia

The source explicitly classifies gonadoblastoma as a noninvasive germ-cell neoplasia.

Its sex cord elements do not remove the importance of the germ-cell population.

Do not label this mixed lesion as a conventional pure sex cord–stromal tumor.

Slide 57 · Favorable outcome requires complete excision

The source states that prognosis is excellent if the tumor is completely excised.

This is a conditional statement about the lesion’s behavior.

Coexisting dysgerminoma must be recognized rather than ignored.

Gonadoblastoma recognized

Complete surgical excision

Excellent prognosis described

Schematic — conceptual relationship, not specimen imagery

Slide 58 · Applied case: An indeterminate gonad

Hypothetical teaching vignette: Histology from a gonad of indeterminate type shows germ cells intermingled with sex cord elements resembling immature Sertoli and granulosa cells.

Discussion prompts

What named neoplasm matches this mixed pattern?

Which germ-cell tumor may coexist?

Hypothetical educational case; No patient data

Slide 59 · Case resolution: Gonadoblastoma

The combination of germ cells and immature sex cord elements is defining.

The described setting of abnormal gonadal development is supportive.

Dysgerminoma is the important associated neoplasm.

The source reports excellent prognosis after complete excision.

Slide 60 · Three lesions: Diagnostic morphology

Feature

Leydig tumor

Pregnancy luteoma

Gonadoblastoma

Composition

Large Leydig cells

Corpus luteum-like

Germ + sex cord cells

Clue

Reinke crystalloids

Pregnancy resemblance

Immature Sertoli / granulosa-like cells

Context

Ovarian hilus

Gestation

Abnormal gonadal development

Slide 61 · Three lesions: Clinical and prognostic priorities

Entity

Characteristic association

Outcome statement

Leydig cell tumor

Testosterone → masculinization

Almost always benign; excision

Pregnancy luteoma

Maternal / female infant virilization may occur

Not provided in excerpt

Gonadoblastoma

Indeterminate gonad; dysgerminoma often coexists

Excellent after complete excision

Slide 62 · Granulosa cell tumor: An estrogenic comparator

Granulosa tumors may elaborate estrogen and produce hyperestrogenic effects.

Endometrial hyperplasia and carcinoma are important associations.

Late recurrence is possible even 10–20 years after resection.

This behavior contrasts with the almost-always-benign true Leydig cell tumor.

Slide 63 · Fibroma/thecoma: Stromal comparators

Tumor

Cells / gross clue

Endocrine pattern

Fibroma

Fibroblasts; typically firm gray-white mass

Generally hormonally inactive

Thecoma

Plump lipid-containing spindle cells

May be hormonally active

Leydig cell tumor

Hilar lipid-rich Leydig cells + crystalloids

Predominantly testosterone

Slide 64 · Sertoli–Leydig tumor: Key comparison

Sertoli–Leydig tumors resemble testicular Sertoli and Leydig differentiation.

Well-differentiated examples may have Sertoli cell tubules.

Virilization is often more marked than in pure Leydig cell tumors.

The source reports recurrence or metastasis in fewer than 5%.

Slide 65 · Clinical reasoning: Three different entry points

Androgenic symptoms outside pregnancy suggest a functional ovarian tumor such as Leydig or Sertoli–Leydig.

Virilization during pregnancy and corpus luteum resemblance suggest pregnancy luteoma.

Abnormal gonadal development with mixed germ/sex cord elements suggests gonadoblastoma.

Androgenic hilar lesion

Gestational luteal lesion

Mixed lesion in atypical gonad

Schematic — conceptual relationship, not specimen imagery

Slide 66 · Integrated case: What is not established?

Hypothetical teaching vignette: A unilateral ovarian mass causes virilization, but the pathology report contains only “steroid-producing tumor” and no descriptive morphology.

Discussion prompts

Can Leydig cell tumor be definitively assigned?

What discriminators would you request?

Hypothetical educational case; No patient data

Slide 67 · Integrated case: Answer and next evidence

Do not equate androgenic phenotype with a specific histologic entity.

Request site, cellular differentiation and characteristic structures.

Evaluate for Leydig-type cells/Reinke crystalloids versus Sertoli-type tubules.

Use clinical pregnancy status and gonadal-development context where relevant.

Slide 68 · Final high-yield diagnostic matrix

Question

Best-supported response

Hilar tumor with Reinke crystalloids?

Ovarian Leydig cell tumor

Corpus luteum-like lesion of pregnancy?

Pregnancy luteoma

Germ cells plus immature sex cord elements?

Gonadoblastoma

Gonadoblastoma-associated malignancy?

Coexistent dysgerminoma (reported 50%)

Slide 69 · Five distinctions worth retaining

Leydig tumor: Unilateral/hilar, lipid-laden cells, Reinke crystalloids, testosterone.

Pregnancy luteoma: Corpus luteum resemblance; Maternal and fetal virilization possible.

Gonadoblastoma: Germ cells plus immature sex cord derivatives.

Gonadoblastoma: Associated atypical gonadal development; Dysgerminoma reported in half.

Only gonadoblastoma is explicitly called a noninvasive germ-cell neoplasia here.

Slide 70 · References and source boundaries

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

Chapter 22, The Female Genital Tract: Sex Cord–Stromal Tumors, pp. 931–933.

Primary section: Other Sex Cord–Stromal Tumors, p. 933.

Selected comparisons: Granulosa tumors, Fibromas/Thecomas, Sertoli–Leydig tumors, pp. 931–933.

Source boundary: original chapter PDF and authentic histology assets were not available for verification or insertion. No unsupported IHC panel, cutoff, treatment protocol or classification update is asserted.