Testis

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The testes, singular testis, are important for survival of the species. Tumours occasionally arise in 'em. They generally are not biopsied.

If the testis is biopsied, it is usually for fertility -- to understand whether the man is 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 (ITGCN) nests of small fried egg cells large central nucleus, clear
cytoplasm, squared-off nuclear membrane, nucleoli[1] 		CD117 appearance similar to seminoma [1], [2]
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 = female version of this tumour [3], [4]
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 [5], [6], [7]
Choriocarcinoma marked nuclear atypia ??? detailed micro beta-hCG other image
Teratoma, immature primitive neuroepithelium pseudostratified epithelium in rosettes (gland-like arrangement) None teratoma are always malignant in males [8]
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 from ITGCN, no lymphocytic infiltrate (like in seminoma) [9]
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, calretinin, inhibin +/-Reinke crystals (cylindrical crystalloid eosinophilic cytoplasmic bodies) [10]
Sertoli cell tumour cells in cords or trabeculae light staining bubbly cytoplasm +/- large cytoplasmic vacuoles, granular chromatin ? usu. no significant nuclear atypia, no mitoses [11]

Intratubular germ cell neoplasia

General

  • 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).[2]
    • Large + irregular, vesicular nuclei.
    • Eosinophilic vacuolated cytoplasm (contains hCG).
      • Syncytiotrophoblasts = closest to mom in normal chorionic villi - covers cytotrophoblast.[6]
  • May see florid granulomatous reaction.

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

Images:

DDx:

  • Mixed germ cell tumour.
  • Solid variant of yolk sac tumour.
    • Lacks fibrous septae and lymphocytes.[7]

IHC

  • D2-40 +ve.
  • CD117 +ve (ckit).
  • CD30 -ve.[8]
    • Done to r/o embryonal carcinoma.
  • Cytokeratins usu. -ve, may have weak focal positivity.[8]
  • OCT3/4 +ve.[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.
  • Glypican 3 +ve.
    • More sensitive than AFP.[9]
  • Alpha-1 AT +ve.
  • Cytokeratin +ve. ???

DDx

  • Embryonal carcinoma.

Embryonal carcinoma

General

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

Microscopic

Features:[17]

  1. Nucleoli - key feature.
  2. Vesicular nuclei (clear, empty appearing nuclei) - key feature.
  3. Nuclei overlap.
  4. Necrosis - common.
    • Not commonly present in seminoma.
  5. Indistinct cell borders
  6. Mitoses - common.
  7. 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:[18]
    1. Endoderm:
      • Skin, CNS.
    2. Mesoderm:
      • Muscle, bone, connective tissue, blood.
    3. Ectoderm:
      • Internal organs.

Classification

  • Divided into:
    • Mature.
    • Immature.

Immature

  • Immature if neural tissue is present:[19]
    • 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:[20][21][22]

  • 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 not adequately defined - see LPFitis. Same BS as HPF.

IHC (immature)

Features:

  • Primitive neuroepithelium:[23]
    • 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:[24]

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

Images:

IHC

Sertoli cell nodule

General

  • AKA Pick's adenoma, AKA testicular tubular adenoma, AKA tubular adenoma of the testis.
  • Benign proliferation of Sertoli cells - associated with cryptorchidism (undescended testis).
  • Not composed of a clonal cell population, i.e. not neoplastic; thus, technically, should not be called an adenoma.[28]

Microscopic

Features:[28][29]

  • Unencapsulated nodules composed of well-formed tubules.
    • May contain eosinophilic (hyaline) blob in lumen (centre).
  • Cells - vaguely resemble immature Sertoli cells:
    • Bland hyperchromatic oval/round nuclei that are stratified.

Images:

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. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 538. ISBN 978-0443066771.
  2. ↑ 2.0 2.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 542. ISBN 978-0443066771.
  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. ↑ URL: http://upload.wikimedia.org/wikipedia/commons/4/45/Gray37.png. Accessed on: 31 May 2010.
  7. ↑ URL: http://webpathology.com/image.asp?case=34&n=8. Accessed on: March 8, 2010.
  8. ↑ 8.0 8.1 PMID 16867864.
  9. ↑ 9.0 9.1 Emerson, RE.; Ulbright, TM. (Jun 2010). "Intratubular germ cell neoplasia of the testis and its associated cancers: the use of novel biomarkers.". Pathology 42 (4): 344-55. doi:10.3109/00313021003767355. PMID 20438407.
  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. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 549. ISBN 978-0443066771.
  18. ↑ Moore, Keith L.; Persaud, T.V.N. (2002). The Developing Human: Clinically Oriented Embryology (7th ed.). Saunders. pp. 83. ISBN 978-0721694122.
  19. ↑ RS. 2 May 2010.
  20. ↑ Harms D, Zahn S, Göbel U, Schneider DT (2006). "Pathology and molecular biology of teratomas in childhood and adolescence". Klin Padiatr 218 (6): 296–302. doi:10.1055/s-2006-942271. PMID 17080330.
  21. ↑ Ulbright TM (February 2005). "Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues". Mod. Pathol. 18 Suppl 2: S61–79. doi:10.1038/modpathol.3800310. PMID 15761467. http://www.nature.com/modpathol/journal/v18/n2s/full/3800310a.html.
  22. ↑ O'Connor DM, Norris HJ (October 1994). "The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading". Int. J. Gynecol. Pathol. 13 (4): 283–9. PMID 7814189.
  23. ↑ Craver RD, Lipscomb JT, Suskind D, Velez MC (October 2001). "Malignant teratoma of the thyroid with primitive neuroepithelial and mesenchymal sarcomatous components". Ann Diagn Pathol 5 (5): 285–92. doi:10.1053/adpa.2001.27918. PMID 11598856.
  24. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 581. ISBN 978-0443066771.
  25. ↑ URL: http://www.antibodybeyond.com/reviews/cell-markers/leydig-cell-marker.htm. Accessed on: 18 May 2010.
  26. ↑ 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.
  27. ↑ Yao DX, Soslow RA, Hedvat CV, Leitao M, Baergen RN (September 2003). "Melan-A (A103) and inhibin expression in ovarian neoplasms". Appl. Immunohistochem. Mol. Morphol. 11 (3): 244–9. PMID 12966351.
  28. ↑ 28.0 28.1 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 227. ISBN 978-0470519035.
  29. ↑ Ricco R, Bufo P (October 1980). "[Histologic study of 3 cases of so-called tubular adenoma of the testis]" (in Italian). Boll. Soc. Ital. Biol. Sper. 56 (20): 2110–5. PMID 6109541.

External links

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