Cryptorchidism

Slide 1 · Cryptorchidism

Testicular descent • morphology • fertility • malignancy

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain the phases and regulation of testicular descent.

Relate undescended position to tubular pathology and fertility.

Identify cancer risk, clinical presentations, and important differentials.

Apply contemporary assessment and timing recommendations.

Slide 3 · Cryptorchidism: Defining lesion

Failure of testicular descent

One or both testes fail to reach the scrotal sac completely or partially. The clinical problem is an abnormal position with functional and oncologic implications.

Slide 4 · Why cryptorchidism matters

Anatomic anomaly

Extrascrotal location

Functional injury

Tubular loss and reduced sperm production

Oncologic association

Higher germ cell tumor risk

A congenital malposition can be a marker of underlying abnormal gonadal development.

Slide 5 · A common congenital testicular abnormality

Cryptorchidism is the main congenital anomaly of the testis discussed in this section.

Absence of a testis and fusion of testes (synorchism) are much less frequent.

An empty hemiscrotum requires distinction between undescended and absent testes.

Slide 6 · Frequency at one year

~1%

Approximately 1% of male children have an undescended testis at one year of age,. This is a point prevalence, not incidence at birth.

Slide 7 · Unilateral or bilateral?

25%

Bilateral cryptorchidism in approximately one quarter of affected patients; Most cases are unilateral.

Slide 8 · Isolated and associated presentations

Most cases occur as isolated anomalies.

Coexisting genitourinary malformations should prompt wider assessment.

Hypospadias is an example specifically mentioned.

Associated findings can change the diagnostic pathway.

Slide 9 · Syndromic associations

Prader–Willi syndrome

Recognized inherited syndrome associated with undescended testes.

Cryptorchidism is not sufficient alone for syndromic diagnosis.

Noonan syndrome

Another inherited syndrome specifically listed.

Assess other developmental findings if present.

Slide 10 · Two phases of normal descent

Transabdominal

Movement to lower abdomen or pelvic brim

Inguinoscrotal

Passage through canal into scrotum

Failure can occur at different points along the descent pathway.

Slide 11 · First phase: Transabdominal descent

Testis shifts within the abdomen toward the pelvic brim.

Endocrine control to Müllerian-inhibiting substance.

This phase precedes passage through the inguinal canal.

Slide 12 · Müllerian-inhibiting substance

Also termed anti-Müllerian hormone (AMH).

It as a hormonal regulator of the transabdominal phase.

Its role in descent should not be confused with later androgen-dependent inguinoscrotal movement.

Slide 13 · Second phase: Inguinoscrotal descent

Testis moves through the inguinal canal to the scrotum.

This phase is androgen-dependent.

Neural signaling is implicated in the pathway.

Slide 14 · Neural mediator of inguinoscrotal descent

Androgen signal

Dependent second phase

Genitofemoral nerve

Androgen-related neural response

CGRP release

Calcitonin gene–related peptide, proposed mediator

CGRP-mediated control is presented as a proposed mechanism, not proven exclusive causation.

Slide 15 · Where descent can arrest

Abdominal position

Lower abdomen / pelvic brim

Inguinal canal

Scrotal sac

Stylized descent pathway — not to anatomical scale

Slide 16 · Most frequent arrest site

Inguinal canal

A cryptorchid testis is most commonly arrested along the inguinal portion of the descent pathway.

Slide 17 · Intra-abdominal arrest

5–10%

Only a minority of affected testes arrest within the abdomen; This figure refers to location among cases rather than all boys.

Slide 18 · Hormonal regulation does not imply endocrine disease

Normal descent depends on hormonal and neural signals.

Yet a well-defined endocrine disorder explains only a minority of cryptorchid presentations.

An isolated undescended testis does not establish an identifiable hormonal deficiency.

Slide 19 · Two mechanisms worth distinguishing

Descent pathway problem

Testis remains outside scrotum

Gonadal developmental defect

Germ cell maturation may also be abnormal

The textbook argues that malposition alone does not explain all fertility and cancer risk.

Slide 20 · Palpable versus nonpalpable testes

Palpable

Often located along the inguinal route.

Clinical examination identifies testis.

Management usually begins with an inguinal surgical approach.

Nonpalpable

Testis may be intra-abdominal, absent, or occasionally inguinal.

Surgical evaluation establishes its status.

Diagnostic laparoscopy can localize an intra-abdominal testis.

Slide 21 · Undescended versus retractile testis

True undescended

Cannot be maintained in a normal scrotal position on examination.

Persistent abnormal position warrants specialist assessment.

Retractile

Can be positioned in the scrotum and remain transiently without tension.

EAU advises observation and examination through puberty rather than routine surgery.

Slide 22 · Acquired ascending testis

Some testes documented previously in the scrotum subsequently ascend.

This is distinct from a congenital failure to reach the scrotum.

Acquired cryptorchidism can also threaten germ cell development.

Slide 23 · Why a testis may be nonpalpable

Intra-abdominal

Above the inguinal route

Inguinal, not felt

Not always demonstrable clinically

Absent / vanishing

No viable testis identified

The examination answers “can it be palpated?” — not automatically “where is it?”.

Slide 24 · Typical clinical discovery

Cryptorchidism is often asymptomatic.

A parent or clinician notices an empty scrotal compartment.

The finding is usually made during routine physical examination.

Symptoms are not required for meaningful long-term risk.

Slide 25 · Focused clinical examination

Inspect both hemiscrota for symmetry and testicular presence.

Palpate systematically along the expected inguinal descent pathway.

Document laterality, palpability, and associated penile/genital findings.

Differentiate a retractile testis from persistent undescended location.

Slide 26 · Clinical red flags

Isolated unilateral undescended testis

Usually a focused pediatric urology problem.

Record location and corrected postnatal age.

Bilateral nonpalpable testes or associated hypospadias

Requires consideration of a disorder/difference of sex development.

Endocrine and genetic evaluation may be indicated.

Slide 27 · Routine imaging is not the central diagnostic step

The pathway starts with careful examination and specialist referral.

Ultrasonography cannot reliably establish absence of a nonpalpable testis.

A nonpalpable testis may require examination under anesthesia and laparoscopy.

Slide 28 · Nonpalpable testis: Clinical logic

An empty hemiscrotum is identified

Examination defines palpable versus nonpalpable status

Bilateral nonpalpable: Assess endocrine / DSD concerns

Specialist examination, often under anesthesia

Surgical localization / management when indicated

Stylized reasoning pathway; Individual evaluation depends on clinical findings.

Slide 29 · Gross morphology of the cryptorchid testis

Typically smaller than a normally descended testis.

Parenchyma may be firm.

Gross atrophy corresponds to progressive microscopic tubular injury.

Slide 30 · When does germ cell injury develop?

Robbins pathology description

Histologic changes may become evident by approximately two years of age.

Early lesion: Tubular basement membrane thickening.

Contemporary clinical evidence

Subtle germ cell deterioration may occur earlier.

Early correction is recommended to protect fertility potential.

Slide 31 · Normal seminiferous tubule: Structural baseline

Schematic — not a histologic specimen

Germ cells occupy multiple stages of differentiation.

Sertoli cells support developing germ cells.

The tubule maintains organized spermatogenesis.

Slide 32 · Early atrophy: Basement membrane thickening

Schematic — not a histologic specimen

Basement membrane thickening can be an early microscopic change.

Tubular remodeling accompanies abnormal testicular position.

The tubule may still retain some germ cells at this stage.

Slide 33 · Progressive loss of spermatogonia

Schematic — not a histologic specimen

Germ cell depletion reduces future spermatogenic capacity.

The luminal germ cell population becomes sparse.

The seminiferous epithelium loses its normal multilayered appearance.

Slide 34 · Sertoli-cell-only tubular profiles

Schematic — not a histologic specimen

Sertoli cells remain while the germ cell population is lost.

Spermatogenesis is absent in affected tubules.

This pattern helps explain impaired fertility.

Slide 35 · Advanced lesion: Tubular hyalinization

Schematic — not a histologic specimen

Severely damaged tubules may resemble hyaline connective tissue cords.

Basement membrane and stromal remodeling become prominent.

Such tubules are no longer functional units of spermatogenesis.

Slide 36 · Tubular evolution in persistent cryptorchidism

Early

Thickened tubular basement membrane

Intermediate

Germ cell depletion; Sertoli-cell-only profiles

Late

Tubular hyalinization and increased stroma

A schematic continuum; Findings vary between patients and tubules.

Slide 37 · Interstitial changes

The interstitial stroma becomes more conspicuous as tubules atrophy.

Leydig cells are relatively spared compared with germ cells.

Relative Leydig prominence need not imply a primary Leydig-cell neoplasm.

Slide 38 · Histologic features: Normal and cryptorchid testis

Germinal epithelium

Active spermatogenesis → depletion or absence of germ cells

Tubular wall

Ordinary basement membrane → thickening / hyalinization

Tubular profile

Functioning seminiferous units → Sertoli-cell-only tubules

Interstitial compartment

Relatively increased stroma and prominent spared Leydig cells

Slide 39 · Germ cell neoplasia in situ

GCNIS may occur in a cryptorchid testis.

It is a precursor associated with postpubertal-type testicular germ cell tumors.

Its presence cannot be inferred from atrophy alone.

Diagnosis requires appropriate histologic assessment rather than clinical location alone.

Slide 40 · The descended contralateral testis may be abnormal

Tubular changes are not always confined to the undescended side.

Similar histologic alterations in the contralateral scrotal testis.

This observation argues against a purely local position-dependent mechanism.

Slide 41 · Testicular dysgenesis: An interpretive model

In utero gonadal development is disturbed

Testicular descent and germ cell maturation may both be affected

Contralateral testis may share a developmental vulnerability

Reduced spermatogenesis and increased germ cell tumor susceptibility

Model derived from the textbook explanation; Not a proof of one exclusive mechanism.

Slide 42 · Why spermatogenesis becomes deficient

Germ cell attrition reduces the spermatogonial reserve.

Tubular atrophy compromises the architecture needed for spermatogenesis.

The underlying developmental abnormality may affect both testes.

Earlier treatment may mitigate injury but cannot reverse all prenatal abnormalities.

Slide 43 · Unilateral and bilateral fertility consequences

Unilateral cryptorchidism

The ipsilateral testis can have severe tubular atrophy.

The contralateral descended testis may also be affected.

Adult paternity may be relatively preserved in many treated patients.

Bilateral cryptorchidism

Both testes may show compromised germ cell maturation.

Greater risk of impaired fertility and lower paternity rate.

Evaluation of nonpalpable bilateral testes needs added care.

Slide 44 · Persistent spermatogenic deficit

10–60%

Deficient spermatogenesis after correction in 10%–60% of patients across cited observations. This broad range should not be treated as a single pooled estimate.

Slide 45 · Associated inguinal hernia

10–20%

Inguinal hernia in approximately 10%–20% of cryptorchidism cases, linking the descent anomaly with inguinal morbidity.

Slide 46 · Inguinal trauma and vulnerability

An inguinal testis may be vulnerable to external compression.

Crushing injury as a possible complication.

Abnormal position creates a risk independent of infertility or neoplasia.

Slide 47 · Relative testicular cancer risk

4–10×

A four- to tenfold higher testicular cancer risk in cryptorchidism. This is a relative risk range, not an absolute lifetime probability.

Slide 48 · Why orchiopexy does not abolish cancer risk

The malpositioned testis remains at elevated risk even after relocation.

The descended contralateral testis may also show increased vulnerability.

A prenatal or developmental component is therefore plausible.

Correction improves access to examination but is not a cancer guarantee.

Slide 49 · Spontaneous descent: Timing matters

Early infancy

Many initially undescended testes descend

After 6 months

Spontaneous descent becomes uncommon

Persistent UDT

Specialist management and early surgery

The EAU uses age corrected for gestation when making the 6-month decision.

Slide 50 · Why early correction is recommended

Preservation of germ cell potential motivates intervention before later childhood.

Germ cell loss and abnormal maturation may precede obvious advanced atrophy.

Positioning the testis in the scrotum facilitates later surveillance.

Slide 51 · Contemporary timing of orchiopexy

By 6 months

Refer if descent remains incomplete

6–12 months

Preferred period for orchiopexy

No later than 18 months

EAU latest recommended age

Recommendations apply to persistent undescended testes, with gestational age correction.

Slide 52 · Orchiopexy: Pathologic purpose and limits

Surgical fixation places the testis within the scrotum.

It can reduce later fertility and malignancy risk relative to prolonged untreated retention.

The procedure does not guarantee normal spermatogenesis.

A pre-existing developmental cancer susceptibility may remain.

Slide 53 · Hormonal treatment: Source versus current guidance

Robbins text (2026 edition)

Describes hormone injections followed by early orchiopexy if medical treatment fails.

This is the treatment sequence as written in the supplied chapter.

Contemporary EAU guidance (2026)

Do not routinely use hormones for unilateral descent.

Orchiopexy is the treatment of choice.

Specialist consideration of endocrine therapy for bilateral cases is a separate weak recommendation.

Slide 54 · Long-term follow-up and counseling

The patient and caregivers should understand residual neoplasia risk.

Examination becomes easier once the testis is in the scrotum.

EAU recommends self-examination and surveillance awareness during and after puberty.

Fertility counseling should reflect unilateral/bilateral status.

Slide 55 · Clinical application I: Persistent inguinal testis

A 9-month-old child has an empty left hemiscrotum. A testis is palpable in the inguinal canal and cannot be maintained in the scrotal position. The other testis is in the scrotum.

How should an undescended testis be classified and managed?

Slide 56 · Clinical application I: Reasoning

This is a unilateral palpable undescended testis, not a retractile testis.

Persisting undescended position beyond 6 months supports referral and treatment.

Early orchiopexy is recommended, ideally in the first year of life.

Slide 57 · Clinical application II: Bilateral nonpalpable testes

A newborn has an empty scrotum bilaterally. Neither testis can be palpated; External genital findings also raise a concern for a disorder of sex development.

What additional diagnostic priority is present?

Slide 58 · Clinical application II: Reasoning

Bilateral nonpalpable testes require assessment beyond the unilateral algorithm.

Consider endocrine and genetic evaluation for a possible disorder/difference of sex development.

Specialist evaluation precedes definitive localization and surgery.

Slide 59 · Pathology application: Interpreting a biopsy

An undescended testis shows small seminiferous tubules, prominent thickened basement membranes, no recognizable spermatogenesis, and relatively visible interstitial Leydig cells.

Which changes support cryptorchid-associated tubular atrophy?

Slide 60 · Pathology application: Interpretation

The dominant lesion is seminiferous tubular atrophy with germ cell depletion.

Sertoli-cell-only tubules and peritubular thickening explain absent spermatogenesis.

Relative Leydig cell prominence reflects sparing of interstitial endocrine cells.

These findings do not establish or exclude GCNIS without specific histologic evaluation.

Slide 61 · Core clinicopathologic synthesis

Definition

Incomplete descent of one or both testes into the scrotum

Mechanism

Abnormal descent with possible intrinsic gonadal developmental defects

Microscopy

Germ cell depletion, Sertoli-only tubules, basement thickening

Clinical risk

Impaired fertility, inguinal morbidity, germ cell malignancy

Management

Early orchiopexy; Continued fertility/cancer awareness

Slide 62 · References and evidence boundaries

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 21, pp. 879–880; Fig. 21.15.

European Association of Urology. EAU Guidelines on Paediatric Urology. 2026. Section 4: Management of Undescended Testes.

Thorup J, et al. The fate of germ cells in cryptorchid testis. Front Endocrinol. 2024;14:1305428. doi:10.3389/fendo.2023.1305428.

Textbook morphology and statistics are kept distinct from updated clinical recommendations.