Tumors of Sex Cord Gonadal Stroma

Slide 1 · Tumors of Sex Cord–Gonadal Stroma

Testicular Leydig cell and Sertoli cell neoplasms

Morphology · Endocrine manifestations · Associated syndromes · Malignancy-associated features

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish sex cord–gonadal stromal tumors from germ cell tumors.

Recognize the clinical and hormonal presentations of Leydig and Sertoli cell tumors.

Describe the gross and microscopic features of each tumor.

Identify the histopathologic features correlated with malignant behavior.

Apply morphology and clinicopathologic context to realistic diagnostic problems.

Slide 3 · Two normal cellular compartments explain the tumor types

Leydig cells are the interstitial steroid-producing population.

Sertoli cells are the supporting population within seminiferous tubules.

Neoplasms retain features of their presumed lineages.

Tubular compartment

Interstitial cells

Schematic — not tissue micrograph

Slide 4 · The broader testicular tumor classification

Testicular neoplasms

Germ cell tumors

Sex cord–stromal tumors

Seminoma; Nonseminomatous types

Leydig cell; Sertoli cell; Other

The present lecture addresses the right-hand branch, not a new germ cell tumor subtype.

Slide 5 · Differentiation, not clinical symptoms, defines the classification

Tumor lineage

Categories follow the presumed histogenesis and differentiation of the neoplastic cells.

Morphology

Leydig tumors resemble interstitial Leydig cells; Sertoli tumors form cord-like and tubular patterns.

Function

Hormonal activity varies. It supplements recognition but does not replace morphologic classification.

Slide 6 · Two principal entities have different dominant phenotypes

Feature

Leydig cell tumor

Sertoli cell tumor

Functional tendency

Often elaborates androgens; Other steroids possible

Most are hormonally silent

Characteristic architecture

Large polygonal eosinophilic cells

Trabeculae, cords and tubules

Common clinical entry point

Testicular swelling ± endocrine symptoms

Testicular mass

Slide 7 · The clinical presentation can be mass-driven or hormone-driven

A testicular mass or swelling

Evaluate morphology and lineage

Endocrine manifestations may guide suspicion

Interpretive principle

Some Leydig tumors present through endocrine changes.

Most Sertoli tumors present as hormonally silent masses.

Slide 8 · Features correlated with malignant behavior

Tumor extent

Large size (>5 cm), infiltrative border, extratesticular extension

Cellular activity

Anaplasia and mitotic activity

Destruction or access

Necrosis and vascular–lymphatic invasion

Slide 9 · Size is a warning feature—not a stand-alone diagnosis

A size greater than 5 cm correlates with malignant behavior.

Leydig cell tumors are usually less than 5 cm at gross examination.

The typical size and the concerning size threshold serve different purposes.

Typical description

>5 cm: Concerning

Schematic; Not drawn to scale

Slide 10 · Margins and necrosis assess destructive growth

Infiltrative border

A poorly confined edge suggests invasion of the surrounding testicular tissue.

This is listed among malignancy-associated features.

Necrosis

Tumor necrosis is another adverse histopathologic feature.

Interpret in the setting of tumor type and other features.

Slide 11 · Anaplasia and mitoses assess cell-level aggressiveness

Anaplasia

Pronounced cytologic atypia is a malignancy-associated feature in this group.

Mitotic activity

Increased proliferation is another feature associated with adverse behavior.

The source provides no numeric mitotic cutoff or grading algorithm.

Slide 12 · Vascular invasion and extratesticular extension

Vascular–lymphatic invasion

Tumor within a vascular or lymphatic channel is one concerning observation.

Extratesticular extension

Tumor spreading beyond the testicular confines is a separate adverse observation.

Both correlate with malignancy; The source does not define them as a sequential pathway.

Slide 13 · Integrate malignancy-associated features, do not invent a score

Domain

Features to document

Size

Greatest dimension; Specifically note whether >5 cm

Growth pattern

Infiltrative margins; Extratesticular extension

Tumor biology

Necrosis, anaplasia, mitotic activity

Vascular spread

Vascular–lymphatic invasion

Slide 14 · Morphologic risk does not equal an established stage

Correlations with malignant behavior, not a validated points-based prediction score.

A tumor may display endocrine activity without having established malignant behavior.

Conversely, a hormonally silent tumor can have aggressive pathologic features.

Distinguish the tumor’s lineage, its functional phenotype and its behavior.

Slide 15 · Leydig cell tumors: Steroid-producing differentiation

The cells resemble the normal Leydig endocrine population.

Androgen production is common; Estrogens and corticosteroids are also possible.

Secretory function explains why the first symptom need not be a palpable mass.

Leydig tumor

Steroid elaboration

Possible endocrine symptoms

Slide 16 · Leydig cell tumors arise in children and adults

Children

The entity is not confined to adulthood; Precocious puberty can bring it to clinical attention.

Adults

Presentation may include swelling, gynecomastia, decreased libido or other endocrine symptoms.

Slide 17 · Leydig cell tumors produce a spectrum of steroid hormones

Leydig cell tumor

Androgens

(often)

Estrogens

(some cases)

Corticosteroids

(some cases)

These are products reported; The figure is not a quantitative secretion profile.

Slide 18 · Testicular swelling is the most common Leydig presentation

A mass or swelling can be the first clinical observation.

An endocrine presentation should not distract from evaluation of the testicular lesion.

The presentation overlaps with other testicular tumors: Morphology remains essential.

Circumscribed intratesticular nodule

Schematic — not a gross specimen

Slide 19 · Gynecomastia may be the clue to a Leydig tumor

Observable symptom

Gynecomastia can bring an otherwise unsuspected testicular lesion to attention.

Why it matters

Leydig cell neoplasms may elaborate estrogenic as well as androgenic products.

Interpretation

An endocrine symptom supports clinical suspicion; It is not diagnostic by itself.

Slide 20 · Decreased libido can accompany a Leydig tumor

Decreased libido is an explicitly reported presenting feature.

The tumor may have functional endocrine effects even when testicular swelling is subtle.

The source does not supply a specific serum-hormone pattern for this presentation.

Interpret the symptom in the broader clinicopathologic setting.

Slide 21 · Precocious puberty is a pediatric presentation

Childhood Leydig cell tumor

Hormone elaboration

Clinical recognition through early puberty

This presentation links endocrine differentiation to patient age; It does not define malignancy.

Slide 22 · The same tumor can enter care by different clinical routes

Presentation

Source-based clinical implication

Testicular swelling

Mass-driven detection; Occurs most commonly

Gynecomastia

Endocrine manifestation can trigger examination

Decreased libido

Functional symptoms may accompany a tumor

Precocious puberty

A pediatric clue to steroid-producing tumor

Slide 23 · Reported associations with Leydig cell tumors

Gonadal setting

Klinefelter syndrome and cryptorchidism

Inherited predisposition

Hereditary leiomyomatosis and renal cell carcinoma syndrome

Molecular association

Germline alteration in fumarate hydratase (FH) in the inherited syndrome

Slide 24 · Klinefelter syndrome and cryptorchidism

Klinefelter syndrome

Reported association with Leydig cell tumors.

An association does not establish the mechanism for an individual tumor.

Cryptorchidism

Reported association with Leydig cell tumors.

This background is also encountered in broader testicular pathology.

Slide 25 · Fumarate hydratase links an inherited syndrome to Leydig tumors

Germline FH mutation

Hereditary leiomyomatosis and renal cell carcinoma syndrome

Association with Leydig cell tumor

The supplied text identifies the inherited association, not its tumor-specific biochemical mechanism.

Slide 26 · The Leydig gross specimen: A sharply defined brown nodule

Typically circumscribed and nodular.

Golden-brown, homogeneous cut surface is characteristic.

The gross appearance reflects a recognizable tumor phenotype but does not alone establish behavior.

Circumscribed intratesticular nodule

Schematic — not a gross specimen

Slide 27 · Most Leydig nodules are smaller than 5 cm

Descriptive observation

Interpretive boundary

Usually <5 cm

Common gross morphology of Leydig cell tumors

>5 cm

One malignancy-associated feature for sex cord–stromal tumors

Size alone

Not presented as a definitive diagnosis of malignancy

Slide 28 · Leydig cytology: Polygonal cells with ample cytoplasm

Large tumor cells resemble normal Leydig cells.

Cell outlines are round to polygonal.

Abundant cytoplasm is a defining visual feature.

Polygonal cell outline

Schematic — not an H&E specimen

Slide 29 · Granular eosinophilic cytoplasm is a major histologic clue

The cytoplasm is abundant, granular and eosinophilic.

This cytoplasmic phenotype helps identify Leydig differentiation.

Interpret cytology together with gross findings and other microscopic details.

Granular eosinophilic cytoplasm

Schematic — not an H&E specimen

Slide 30 · The Leydig cell nucleus is usually central and round

Histologic description emphasizes a round, centrally placed nucleus.

This nuclear appearance sits within a large polygonal cell.

Anaplasia, when present, must be distinguished from the ordinary tumor phenotype.

Round, centrally located nucleus

Schematic — not an H&E specimen

Slide 31 · Lipid droplets and cytoplasmic vacuoles are common

Leydig tumor cells frequently contain lipid droplets or vacuoles.

These are additional cytoplasmic clues to endocrine cell differentiation.

Neither feature is presented as individually pathognomonic.

Schematic — not an H&E specimen

Slide 32 · Lipofuscin pigment adds another cytoplasmic clue

Intracytoplasmic lipofuscin pigment is described in these neoplasms.

It may coexist with eosinophilic granular cytoplasm and lipid-related spaces.

A combination of findings supports recognition more than a single feature.

Schematic — not an H&E specimen

Slide 33 · Reinke crystalloids are distinctive but not universal

Characteristic rod-shaped structures may be seen in the tumor cytoplasm.

They are called crystalloids of Reinke.

Them in about 25% of Leydig cell tumors.

Schematic — not an H&E specimen

Slide 34 · A negative search for Reinke crystalloids does not exclude the tumor

Positive finding

Reinke crystalloids are highly characteristic when encountered.

Frequency

The reported frequency is about one quarter of Leydig cell tumors.

Diagnostic restraint

Most tumors will not demonstrate them; Use the overall morphology.

Slide 35 · Combine the gross and histologic Leydig signatures

Level

Signature

Gross

Circumscribed, homogeneous golden-brown nodule

Cell architecture

Large round-to-polygonal cells

Cytoplasm

Abundant granular eosinophilic material; Lipid/vacuoles; Lipofuscin

Occasional clue

Rod-shaped crystalloids of Reinke (~25%)

Slide 36 · A minority of adult Leydig cell tumors behave malignantly

Behavior estimate

Approximately 10% of Leydig cell tumors in adults are malignant.

Consequences

Malignant Leydig cell tumors can produce metastases.

Pathology review

Examine size, necrosis, growth pattern, cytology and vascular invasion.

Slide 37 · Metastatic capability makes behavior assessment essential

Recognize Leydig differentiation

Assess malignancy-associated morphology

Identify tumors warranting concern for aggressive behavior

A hormonal presentation does not substitute for assessment of malignant features.

Slide 38 · Sertoli cell tumors: Characteristic architectural differentiation

Most Sertoli tumors are hormonally silent.

They commonly present as a testicular mass.

Microscopy emphasizes trabeculae, cords and tubules rather than a Leydig-like sheet of polygonal cells.

Schematic — not histologic evidence

Slide 39 · Hormonal silence explains the usual Sertoli presentation

Hormone activity

Most Sertoli cell tumors are described as hormonally silent.

Presentation

The usual clinical entry point is a testicular mass.

Diagnostic emphasis

Morphology and associated clinical context are central to recognition.

Slide 40 · Several inherited syndromes are linked to Sertoli cell tumors

Associated syndrome

Specific point supported by Robbins

Carney complex

PRKAR1A germline mutation association

Peutz–Jeghers syndrome

Reported tumor association

Familial adenomatous polyposis

Reported tumor association

Slide 41 · Carney complex involves PRKAR1A

Germline PRKAR1A mutation

Carney complex

Association with Sertoli cell tumor

Carney complex with germline PRKAR1A mutation and cAMP-dependent protein kinase signaling.

Slide 42 · Peutz–Jeghers and familial adenomatous polyposis

Peutz–Jeghers syndrome

An association with Sertoli cell tumors.

A precise genotype-specific tumor risk is not provided in the source.

Familial adenomatous polyposis

Also included among reported associations.

Do not infer a specific molecular pathway from this excerpt alone.

Slide 43 · The Sertoli gross specimen: Firm and gray-white to yellow

Typically a small, firm, circumscribed nodule.

The cut surface is homogeneous.

The color is described as gray-white to yellow.

Circumscribed intratesticular nodule

Schematic — not a gross specimen

Slide 44 · Sertoli tumors organize into trabeculae and tubules

Histology commonly shows distinctive trabeculae.

Trabeculae may give rise to cord-like structures.

Tubular structures are another characteristic pattern.

Schematic — not histologic evidence

Slide 45 · Cord-like architecture is a key Sertoli pattern

The neoplastic cells form elongated cords and trabeculae.

Cord-like structures are not simply a color or cytoplasmic characteristic.

Identify the architecture before relying on individual cell features.

Schematic — not histologic evidence

Slide 46 · Cellular morphology and architecture distinguish the types

Diagnostic axis

Leydig

Sertoli

Principal visual clue

Large polygonal cells

Trabecular, cord-like and tubular pattern

Cytoplasm

Granular eosinophilic; Possible vacuoles/pigment

Not specifically characterized in this excerpt

Distinctive finding

Reinke crystalloids in a subset

Architectural tubules and cords

Slide 47 · Most Sertoli tumors are benign; Some are malignant

Common behavior

The majority of Sertoli cell tumors follow a benign course.

Malignant minority

Approximately 10% are reported to pursue a malignant course.

Assessment

The general sex cord–stromal adverse morphology list remains relevant.

Slide 48 · A clinically useful side-by-side tumor profile

Domain

Leydig cell tumor

Sertoli cell tumor

Presentation

Mass ± endocrine effects

Most often a mass

Functional tendency

Often steroid-producing

Most often hormonally silent

Gross

Golden-brown nodule

Gray-white to yellow nodule

Micro

Polygonal eosinophilic cells

Cords, trabeculae, tubules

Slide 49 · General malignancy-associated features apply across lineages

Behavior concern

Morphologic observations

Concerning bulk or spread

>5 cm; Extratesticular extension

Invasive growth

Infiltrative border; Vascular–lymphatic invasion

High-grade histology

Anaplasia; Increased mitotic activity; Necrosis

Slide 50 · A source-faithful interpretation pathway

Testicular sex cord–stromal tumor

Leydig-like cell morphology

± steroid symptoms

Sertoli-like cords,

Trabeculae or tubules

For either lineage: Assess malignancy-associated features

Slide 51 · Case 1 — identify the probable tumor

A boy develops precocious puberty and a unilateral testicular nodule. The resected mass is circumscribed and golden brown.

Which interpretation is most strongly supported?

A. Leydig cell tumor

B. Sertoli cell tumor

C. Testicular lymphoma

Slide 52 · Case 1 — the endocrine and gross clues converge

Childhood onset is explicitly possible for Leydig cell tumors.

Precocious puberty is a recognized Leydig presentation.

The golden-brown, circumscribed nodule matches its classic gross appearance.

Supported interpretation

Leydig cell tumor

Slide 53 · Case 2 — interpret the microscopic pattern

An adult has a hormonally silent testicular mass. Histology demonstrates trabeculae with cords and tubular structures.

Which interpretation is most strongly supported?

A. Sertoli cell tumor

B. Leydig cell tumor

C. Hormone secretion proves germ cell origin

Slide 54 · Case 2 — the architectural pattern is discriminating

Most Sertoli tumors are hormonally silent.

Trabeculae, cords and tubules are the textbook Sertoli pattern.

A secretory phenotype is not necessary for Sertoli lineage.

Supported interpretation

Sertoli cell tumor

Slide 55 · Case 3 — assess behavior

A sex cord–stromal tumor measures 6 cm and has focal necrosis, infiltrative growth and vascular–lymphatic invasion.

Which interpretation is most strongly supported?

A. These are malignant-associated pathologic findings

B. A hormone level is required before interpreting the findings

C. A size of 6 cm excludes malignant potential

Slide 56 · Case 3 — several adverse features are present

Tumor size exceeds the source threshold of >5 cm.

Necrosis, infiltrative margins and vascular–lymphatic invasion are on the adverse-feature list.

The findings raise concern; The excerpt supplies no validated numerical scoring rule.

Supported interpretation

Morphology concerning for malignant behavior

Slide 57 · Three recurrent diagnostic errors to avoid

Pitfall

Safer interpretation

“Any Reinke crystals must be present”

They occur in about 25%; Absence does not rule out Leydig tumor

“No hormone symptoms means no stromal tumor”

Most Sertoli tumors are hormonally silent

“Size alone proves malignancy”

Use the overall set of pathology-associated features

Slide 58 · What this source does—and does not—establish

Directly supported

Key clinical presentations and associated syndromes

Gross and cellular morphology for Leydig and Sertoli tumors

Listed malignant-associated features and approximate malignant proportions

Not specified in this excerpt

Immunohistochemistry panels or sensitivity estimates

Molecular classification beyond stated associations

Formal scoring, staging or specific treatment algorithms

Slide 59 · Core clinicopathologic distinctions

Leydig

Golden-brown circumscribed mass; Eosinophilic polygonal cells; Endocrine manifestations may dominate.

Sertoli

Small firm gray-white/yellow mass; Cords, trabeculae and tubules; Mostly hormonally silent.

Behavior

Inspect size, necrosis, invasion, anaplasia, mitotic activity and extension.

Slide 60 · References and source scope

Primary reference

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 21, “The Lower Urinary Tract and Male Genital System,” p. 886: “Tumors of Sex Cord–Gonadal Stroma.”

Parent context

Chapter classification of testicular tumors (Table 21.6) and the surrounding testicular tumor discussion.

Histopathology is illustrated by original native schematics, not reproduced photomicrographs.