Testis

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The Testes are important for survival of the species. Tumours occasionally arise in 'em. They generally are not biopsied. If they are biopsied, it is usually for fertility -- to understand whether they are really azoospermic.

Normal

Seminiferous tubules

  • Sertoli cells (AKA sustentacular cell AKA nurse cell).
    • Large cells with oval nucleus.
  • Primary spermatocyte.
    • Small cells with dark nucleus on basement membrane.
  • Secondary spermatocyte.
    • Rarely seen on light microscopy.
  • Spermatids.
    • Round small.
    • Usually close to the centre of the lumen.
  • Spermatozoa.
    • You don't see the tail on light microscopy.

Interstitium

  • Leydig cell (AKA interstitial cell).
    • Large eosinophilic cell.
  • Blood vessels.

Associated structures

  • Epididymis - stores the sperm.
    • Pseudostratified epithelium with cilia.

Image:

Rete testis

  • Receives stuff from the tubules.

Microscopic:

  • Delicate anastomosing channels lined by cuboid epithelium.

Image:

Appendix of testis

Muellerian duct remnant.

Microscopic:

  • Polypoid structure.

Images:

Diagnoses

  • Benign.
    • Spermatid present/not present.
  • Infertility - azoospermic.
    • No sperm present.
  • Germ cell tumours (GCTs).
    • Intratubular germ cell neoplasia.
    • Seminoma.
    • Spermatocytic seminoma.
    • Yolk sac tumour (endodermal sinus tumour).
    • Embryonal carcinoma.
    • Choriocarcinoma.
    • Teratoma.
    • Mixed GCT - 60% of GCTs are mixed.
      • Common combinations:
        1. teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE).
        2. seminoma + embryonal (SE).
        3. embryonal + teratoma (TE).
  • Sex-cord stromal tumour.
    • Leydig cell tumour.
    • Sertoli cell tumour.

IHC for GCTs

ABCDs of GCTs:

  • AFP - yolk sac tumour.
  • Beta-hCG - choriocarcinoma.
  • CD30 - embryonal carcinoma.
  • D2-40 - seminoma.

Tabular summary of GCTs

Tumour Key feature Microscopic IHC Other Image
Intratubular germ cell neoplasia (IGCN) nests of small fried egg cells large central nucleus, clear
cytoplasm, squared-off nuclear membrane, nucleoli[1]
CD117 appearance similar to seminoma ?
Seminoma fried egg cells fried egg-like cells (central nucleus, clear
cytoplasm) with squared-off nuclear
membrane, nucleoli, lymphocytic infiltrate, granulomata,
syncytiotrophoblastic giant cells[2]
D2-40 Dysgerminoma Image
Yolk sac tumour (endodermal sinus tumour) Schiller-Duval bodies Schiller-Duval b. = central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells, variable arch. AFP patterns: microcystic, solid, hepatoid hepatoid YST
Embryonal carcinoma prominent nucleoli, vescicular nuclei var. arch.: tubulopapillary, glandular, solid, embryoid bodies (ball of cells in surrounded by empty space on three sides), +/-nuclear overlap, mitoses common CD30 usu. part of a mixed GCT [1], [2]
Choriocarcinoma key feature detailed micro beta-hCG other image
Teratoma key feature detailed micro None other image
Spermatocytic seminoma population of 3 cells pop.: (1) small cell with high NC ratio (mature lymphocyte-like), (2) medium with nucleoli, (3) large cells with filamentous chromatin - few present ? does not arise ITGCN, no lymphocytic infiltrate (like in seminoma) [3]
Mixed germ cell tumour NA common combinations: teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE); seminoma + embryonal (SE); embryonal + teratoma (TE) NA - -

Tabular summary of (male) SCSTs

Tumour Key feature Microscopic IHC Other Image
Leydig cell tumour intersitial cell cluster with eosinophilic cytoplasm cytoplasmic vacuolization, uniform nuclei with nucleoli MART-1, calretin, inhibin +/-Reinke crystals (cylindrical crystalloid eosinophilic cytoplasmic bodies) [4]
Sertoli cell tumour cells in cords or trabeculae light staining bubbly cytoplasm +/- large cytoplasmic vacuoles, granular chromatin ? usu. no significant nuclear atypia, no mitoses [5]

Intratubular germ cell neoplasia

  • Considered the precursor lesion for germ cell tumours.
  • Not all germ cell tumours (GCTs) arise from intratubular germ cell neoplasia.

The following testicular GCTs do not arise from ITCGN:

Microscopic

Features:[5]

  • Enlarged nuclei, vesicular.
  • Clear cytoplasm.
  • Nucleoli, prominent.

Image(s):

Seminoma

General

Epidemiology & etiology

  • Arises from intratubular germ cell neoplasia (ITGCN).

Microsopy

Features:

  • Cells with fried egg appearance.
    • Clear cytoplasm.
    • Central nucleus, with prominent nucleolus.
      • Nucleus has "corners", i.e. it is not round.
  • Lymphoctyes common, not essential.
  • May see syncytiotrophoblasts, AKA syncytiotrophoblastic giant cells (STGCs).[6]
    • Large + irregular, vesicular nuclei.
    • Eosinophilic vacuolated cytoplasm (contains hCG).
      • Syncytiotrophoblasts = closest to mom in normal chorionic villi - covers cytotrophoblast.[7]
  • May see florid granulomatous reaction.

Memory device: 3 Cs - clear cytoplasm, central nucleus, corners on the nuclear membrane.

DDx:

  • Mixed germ cell tumour.
  • Solid variant of yolk sac tumour.
    • Lacks fibrous septae and lymphocytes.[8]

IHC

  • D2-40 +ve.
  • CD117 +ve (ckit).
  • CD30 -ve.[9]
    • Done to r/o embryonal carcinoma.
  • Cytokeratins usu. -ve, may have weak focal positivity.[9]

Spermatocytic seminoma

General

  • Rare tumour.
  • Only one case of metastases in 200 cases.[10]
  • Orchiectomy is curative.
  • Not reported/found in females.[10]

Epidemiology

  • Does NOT arise from intratubular germ cell neoplasia (ITGCN)[11] - not considered a subtype of seminoma.

Microscopy

Features:[12]

  • Population of three cells.
    1. Small cells (6-8 µm) - with a large NC ratio.
      • Look like secondary spermatocytes.
      • May be confused with (mature) lymphocytes.
    2. Medium cells (15-18 µm) with prominent nucleoli.
      • Filamentous chromatin (AKA spireme chromatin).[10]
    3. Large cells (50-100 µm).
      • Filamentous chromatin.
  • Mucoid lakes.
  • Intratubular spread.

Notes:

  • Spireme = the tangle of filaments in prophase portion of mitosis.[13]

Images:

Yolk sac tumour

General

  • Tumour also known as endodermal sinus tumour.

Epidemiology

  • Most common GCT in infants and young boys.

Microscopy

Classic feature:

  • Schiller-Duval bodies.
    • Look like glomerulus - central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells
  • Architecure - variable.
    • Most common microcystic pattern.[14]

Image:

Variants:

  • Hepatoid pattern.[15]
    • Vaguely resembles liver.
      • Hyaline globules (light red well-circumscribed globs).
      • Bile canaculi.
  • Solid pattern.[16]
    • Vaguely resembles seminoma.

Image:

IHC

  • AFP +ve
  • Alpha-1 AT +ve.
  • Cytokeratin +ve. ???

DDx

  • Embryonal carcinoma.

Embryonal carcinoma

General

  • Affects young adults.
    • May be seen in women.

Microscopy

Features:[17]

  • Indistinct cell borders
  • Mitoses - common.
  • Nuclei overlap.
  • Variable architecture:
    • Tubulopapillary.
    • Glandular.
    • Solid.
    • Embryoid bodies - ball of cells in surrounded by empty space on three sides.

Notes:

  • Cytoplasmic staining variable (eosinophilic to basophilic).

Images:

DDx

  • Yolk sac tumour.

IHC

  • AE1/AE3 +ve.
  • CD30 +ve.

Choriocarcinoma

Clinical

  • Aggressive clinical course.

Microscopy

  • Syncytiotrophoblasts:
    • Large + many irreg. or lobular hyperchromatic nuclei.
    • Eosinophilic vacuolated cytoplasm (contains hCG).
  • Cytotrophoblasts:
    • Clear cytoplasm.
    • Polygonal shaped cells in cords/masses.
    • Distinct cell borders.
    • Single uniform nucleus.
  • +/-Hemorrhage.
  • +/-Necrosis.

Image(s):

Notes:

IHC

  • beta-hCG +ve.

Teratoma

General

  • Consists of all three germ layers.
    • Endoderm.
    • Mesoderm.
    • Ectoderm.

Classification

  • Divided into:
    • Mature.
    • Immature.

Immature

  • Immature if neural tissue is present:[18]
    • Vaguely resembles pseudostratified respiratory epithelium.
  • Islands of small hyperchromatic cells - "blastema".
  • +/-Cartilage.
  • +/-Adipocytes.
  • +/-Colonic type mucosa.
  • +/-Stratified squamous epithelium (skin).

Images:

Other images:

Grading

Based on quantity of immature neuroepithelium:[19][20][21]

  • G0 - mature teratoma; no immature neuroepithelium.
  • G1 - less than one lower power field (LPF) of immature neuroepithelium; LPF defined field at 4X magnification.
  • G2 - 1-3 LPFs.
  • G3 - more than 3 LPFs.

Note:

  • LPF - this is the same BS as HPF... see rant in basics article.

IHC (immature)

Features:

  • Primitive neuroepithelium:[22]
    • Neuron-specific enolase (NSE) +ve.
    • Neuron-specific B tubulin +ve.
    • Synaptophysin +ve.

Leydig cell tumour

  • Arises from interstitial cell.
  • AKA interstitial cell tumour.

Microscopic

Features:[23]

  • Vacuolization - key feature.
  • Cytoplasm - clear to eosinophilic.
  • Nucleoli common.
  • Reinke crystals, cylindrical crystalloid eosinophilic cytoplasmic bodies (not always present).

Images:

IHC

  • Inhibin-alpha.
  • Calretinin.[24][25]
  • Melan A.[26]
    • AKA MART-1.
    • Expressed in melanoma, adrenal tissue, steroid-secreting tumours.

Sertoli cell tumour

  • Arises from Sertoli cells (AKA nurse cells).

Microscopic

Features:

  • Groups of cells in cords or trabeculae (beam-like arrangement).
  • Cells have:
    • Light staining bubbly cytoplasm +/- large cytoplasmic vacuoles.
    • Slightly irregular nucleoli.
    • Granular irregular appearing chromatin.

Negatives:

  • Mitoses are rare.
  • No significant nuclear atypia.

Image(s):

See also

References

  1. GUP P.538.
  2. GUP P.542.
  3. Müller J, Skakkebaek NE, Parkinson MC (February 1987). "The spermatocytic seminoma: views on pathogenesis". Int. J. Androl. 10 (1): 147–56. PMID 3583416.
  4. Manivel JC, Simonton S, Wold LE, Dehner LP (June 1988). "Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study". Arch. Pathol. Lab. Med. 112 (6): 641–5. PMID 2837162.
  5. URL: http://www.webpathology.com/image.asp?case=30&n=1. Accessed on: 18 May 2010.
  6. GUP P.542.
  7. URL: http://upload.wikimedia.org/wikipedia/commons/4/45/Gray37.png. Accessed on: 31 May 2010.
  8. URL: http://webpathology.com/image.asp?case=34&n=8. Accessed on: March 8, 2010.
  9. 9.0 9.1 PMID 16867864.
  10. 10.0 10.1 10.2 Eble JN (October 1994). "Spermatocytic seminoma". Hum. Pathol. 25 (10): 1035–42. PMID 7927308.
  11. Müller J, Skakkebaek NE, Parkinson MC (February 1987). "The spermatocytic seminoma: views on pathogenesis". Int. J. Androl. 10 (1): 147–56. doi:10.1111/j.1365-2605.1987.tb00176.x. PMID 3583416.
  12. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN 0-7216-0187-1.
  13. URL: http://www.thefreedictionary.com/spireme. Accessed on: 4 June 2010.
  14. URL: http://webpathology.com/image.asp?case=34&n=1. Accessed on: March 8, 2010.
  15. URL: http://webpathology.com/image.asp?case=34&n=6. Accessed on: March 8, 2010.
  16. URL: http://webpathology.com/image.asp?case=34&n=8. Accessed on: March 8, 2010.
  17. GUP P.549
  18. RS. 2 May 2010.
  19. PMID 17080330.
  20. PMID 15761467 http://www.nature.com/modpathol/journal/v18/n2s/full/3800310a.html
  21. PMID 7814189.
  22. PMID 11598856.
  23. GUP P.581.
  24. URL: http://www.antibodybeyond.com/reviews/cell-markers/leydig-cell-marker.htm. Accessed on: 18 May 2010.
  25. Bar-Shira Maymon B, Yavetz H, Yogev L, et al. (2005). "Detection of calretinin expression in abnormal immature Sertoli cells in non-obstructive azoospermia". Acta Histochem. 107 (2): 105–12. doi:10.1016/j.acthis.2005.02.002. PMID 15950053.
  26. PMID 12966351.

External links