Testis & epididymis
Development
Cryptorchidism
Authors: Christopher Dall, M.D., Debra L. Zynger, M.D.
Topic Completed: 1 June 2017
Minor changes: 29 December 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Cryptorchidism [title] Testis and epididymis
Table of Contents
Definition / general | Terminology | ICD coding | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Dall C, Zynger D. Cryptorchidism. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testiscryptorchidism.html. Accessed January 18th, 2021.
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
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
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 style 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 style 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
