Cryptorchidism

Testis and epididymis
Development
Cryptorchidism

Authors: Christopher Dall, M.D., Debra Zynger, M.D.

Topic Completed: 1 June 2017

Revised: 27 March 2019

Copyright: 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Cryptorchidism [title] Testis and epididymis

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Table of Contents

Cite this page: Dall C, Zynger D. Cryptorchidism. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testiscryptorchidism.html. Accessed February 20th, 2020.

Definition / general

Absence of one or both testes in the scrotum
Most common congenital abnormality of the genitourinary tract (Transl Pediatr 2016;5:233)
Associated with infertility and subfertility, testicular germ cell tumor, testicular torsion and inguinal hernia

Terminology

Cryptorchidism: absence of one or both testes in the scrotum most commonly due to failure of descent into the scrotum during fetal development
- May occur with gonadal dysgenesis or following testicular ascent later in life
Anorchia or vanishing testis syndrome: absence of one or both testes
Orchiopexy or orchidopexy: procedure that tethers the testicle into the scrotum
Ectopic testis: testis is situated away from normal path of descent, differs from undescended testicle

ICD coding

Q53.1: undescended testicle, unilateral
Q53.2: undescended testicle, bilateral
Q53.9: undescended testicle, unspecified

Epidemiology

3% in full term newborns, decreases to 1% by the first year (Transl Pediatr 2016;5:233)
Incidence varies by region, increased rates in United Kingdom, Denmark and Lithuania (Hum Reprod Update 2008;14:49)
Rates may be increasing (Acta Paediatr 2007;96:611)

Pathophysiology

Testicular descent from initial position on abdominal wall is divided into two stages (Endocr Rev 2008;29:560) with abnormalities of migration thought to be associated with undescended testicle
- Transabdominal descent: the gubernaculum, a caudal ligament connecting the testicle to the internal ring, holds testicle near internal ring as abdominal cavity develops; insulin-like factor 3 (INSL3) and anti-Müllerian hormone dependent
- Inguinoscrotal descent: the gubernaculum shortens, pulling testicle through inguinal canal to position within scrotum; androgen dependent
May be a component of testicular dysgenesis syndrome, which includes increased levels of testicular malignancy, poor semen quality and hypospadias

Etiology

Numerous genes implicated in cryptorchidism, lack of a clear association in human studies suggests multifactorial causes
More common in preterm (30%) (Transl Pediatr 2016;5:233) and low birth weight infants (J Urol 1999;161:1606)
Concordance in sibling studies (Fertil Steril 2010;93:124)
Chromosomal abnormalities are associated with cryptorchidism with increased rates in genetic syndromes, such as Klinefelter and Prader-Willi syndrome (Lancet 2004;364:273)
Environmental factors likely play a role; diethylstilbestrol and pesticide exposure have been associated with increased rates (Mol Cell Endocrinol 2012;355:208)

Clinical features

80% of undescended testicles palpated within inguinal canal or high scrotal area
20% of undescended testicles not palpated
- 50% lie in abdomen, 50% are atrophic (Am Fam Physician 2000;62:2047)
Associated with increased risk of testicular germ cell tumor
- Increasing risk of malignancy with delayed treatment (J Urol 2009;181:452)
- Relative risk of malignancy is 2 - 8; higher risks associated with delayed repair, bilateral cryptorchidism, additional endocrinopathies, abnormal karyotype and intra-abdominal testes
- Seminoma is most common malignancy

Diagnosis

Laparoscopy is gold standard in diagnosing a nonpalpable testis
- Ultrasound and other radiologic imaging are not sensitive in diagnosing a nonpalpable testis (Pediatrics 2011;127:119, Pediatrics 2013;131:e1908)
Must exclude retractile testis, a testis that has descended into the scrotum but has been pulled superiorly by cremaster muscle
In bilateral cryptorchidism, must exclude congenital adrenal hyperplasia and persistent Müllerian duct syndrome

Laboratory

In cases of bilateral undescended testicles, hormonal studies (LH, FSH, Müllerian inhibiting substance/MIS and testosterone) may support diagnosis of gonadal dysgenesis with abnormal hCG stimulation test (Am Fam Physician 2000;62:2037)

Radiology description

Diagnostic imaging is not recommended in most cases (J Pediatr Surg 2011;46:2406)

Prognostic factors

Delayed repair reduces fertility, which is worse with bilateral cryptorchidism
Relative risk for testicular germ cell tumor is 2.2 with prepubertal repair vs 5.4 with postpubertal repair (N Engl J Med 2007;356:1835)

Case reports

2 year old boy with pure yolk sac tumor in a cryptorchid testis diagnosed by fine needle aspiration (J Cytol 2015;32:53)
19 year old man with an ectopic testis after treatment for retractile testes (International Journal of Case Reports and Images 2012;3:21)
28 year old man with bilateral synchronous seminomas in bilateral cryptorchidism (BMJ Case Rep. 2014 Feb 12;2014)

Treatment

Orchiopexy may be performed at 3 - 6 months as it is unlikely that testicle will spontaneously descend after this time
American Urological Association does not recommend hormonal therapy (hCG) to promote the descent of the undescended testicle due to low response rates (AUA: evaluation and treatment of cryptorchidism guidelines, amended 2015)

Clinical images

Images hosted on other servers:

Intra-abdominal mass

Abdominal testis

Mass with right gonadal vein

Scrotum with cryptorchidism

Gross description

Smaller and atrophic compared to descended testis

Gross images

Images hosted on PathOut server:

Images contributed by Debra L. Zynger, M.D.

Cryptorchid testicle gross image

Images hosted on other servers:

Atrophic testis

Microscopic (histologic) description

Differences in histology become much more pronounced after 2 years of life and are increased with delayed orchiopexy (J Urol 2009;182:704)
Decreased / abnormal spermatogenesis, seminiferous tubule atrophy, peritubular fibrosis and increased incidence of microliths (Nistal: Clues in the Diagnosis of Non-tumoral Testicular Pathology, First Edition, 2017)
Sertoli cell only seminiferous tubules: eosinophilic granular cytoplasmic lysosomes may be present (Nistal: Clues in the Diagnosis of Non-tumoral Testicular Pathology, First Edition, 2017)
Sertoli cell nodules: nodules composed of immature Sertoli cells ("Pick's adenoma"), can have microliths (Nistal: Clues in the Diagnosis of Non-tumoral Testicular Pathology, First Edition, 2017)
Retained Leydig cells give appearance of hyperplasia (Nistal: Clues in the Diagnosis of Non-tumoral Testicular Pathology, First Edition, 2017)
Germ cell neoplasia in situ (GCNIS): large, pleomorphic, basally located cells within the seminiferous tubules may be present; use immunostains for confirmation

Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Debra L. Zynger, M.D.

Seminiferous tubule with Sertoli cells, no spermatogenesis; left: medium power; right: high power

Peritubular fibrosis

Sertoli cell nodule

Retained Leydig cells

Granular cell change within Sertoli cells

Microliths

Cytology description

Used to evaluate metastases of subsequent germ cell tumor, not primary tumor or cryptorchid testis

Positive stains

Germ cell neoplasia in situ (GCNIS) is positive for CD117 (c-kit), PLAP, D2-40 and OCT3 / 4 but these stains may be falsely positive in boys < 2 years old with cryptorchidism (J Urol 2014;191:1084)

Differential diagnosis

Germ cell neoplasia in situ (GCNIS): confirm with immunostains: CD117, PLAP, D2-40, OCT3 / 4
Atrophy
Sex cord tumor with annular tubules (SCTAT): tubules surrounding hyaline material, calcifications common

Board review style question #1

A 24 year old man with a history of untreated cryptorchidism presents with a painful abdominal mass. Pathology is most likely to be consistent with which of the following:

Dermoid cyst
Germ cell neoplasia in situ
Mixed germ cell tumor
Seminoma
Sertoli cell tumor

Board review answer #1

D. Seminoma is the most common malignancy.

Board review style question #2

What histological changes are most likely to be observed in a cryptorchid testis?

Atrophic seminiferous tubules, peritubular fibrosis, and nodules of cells containing dark nucleoli and eosinophilic granular cytoplasm
Bland appearing cysts lined with cuboidal epithelium and ciliated cells
Calcified lesions adjacent to areas of necrosis
Glycogen rich cells with large, irregular nuclei arranged in sheets
Rod-like cytoplasmic inclusions with a diffuse growth pattern and rare mitotic cells

Board review answer #2

A. These findings are consistent with an undescended testicle

These might be the findings associated with benign glands, such as those seen in endometriosis or endosalpingiosis
This histology may be associated with teratoma
These might be the findings of a seminoma, which are more common in undescended testicles
Leydig cell tumors often contain Reinke crystals, described in this answer choice