Difference between revisions of "Testis"

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Image:Seminoma_high_mag.jpg |Seminoma - high mag. (WC/Nephron)
Image:Seminoma_high_mag.jpg |Seminoma - high mag. (WC/Nephron)
Image:Seminoma_intermed_mag.jpg |Seminoma - intermed. mag. (WC/Nephron)
Image:Seminoma_intermed_mag.jpg |Seminoma - intermed. mag. (WC/Nephron)
Image:Rete_testis_with_seminoma.jpg |Seminoma in the rete testis (WC/Nephron)
Image:Rete_testis_with_seminoma.jpg |Seminoma in the rete testis. (WC/Nephron)
Image:Seminoma_with_syncytiotrophoblasts_-_intermed_mag.jpg |Seminoma with syncytiotrophoblasts - intermed. mag. (WC/Nephron)
Image:Seminoma_with_syncytiotrophoblasts_-_intermed_mag.jpg |Seminoma with syncytiotrophoblasts - intermed. mag. (WC/Nephron)
Image:Seminoma_with_syncytiotrophoblasts_-_very_high_mag.jpg |Seminoma with syncytiotrophoblasts - very high mag. (WC/Nephron)
Image:Seminoma_with_syncytiotrophoblasts_-_very_high_mag.jpg |Seminoma with syncytiotrophoblasts - very high mag. (WC/Nephron)
</gallery>
</gallery>
===IHC===
===IHC===
*D2-40 +ve ~100% of cases.<ref name=pmid17277761>{{Cite journal  | last1 = Lau | first1 = SK. | last2 = Weiss | first2 = LM. | last3 = Chu | first3 = PG. | title = D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30. | journal = Mod Pathol | volume = 20 | issue = 3 | pages = 320-5 | month = Mar | year = 2007 | doi = 10.1038/modpathol.3800749 | PMID = 17277761 }}</ref>
*D2-40 +ve ~100% of cases.<ref name=pmid17277761>{{Cite journal  | last1 = Lau | first1 = SK. | last2 = Weiss | first2 = LM. | last3 = Chu | first3 = PG. | title = D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30. | journal = Mod Pathol | volume = 20 | issue = 3 | pages = 320-5 | month = Mar | year = 2007 | doi = 10.1038/modpathol.3800749 | PMID = 17277761 }}</ref>

Revision as of 03:14, 19 May 2013

The testis, plural testes, 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 testis

Gross

Anatomy - deep to superficial:

  • Tunica albuginea - fibrous layer.
  • Tunica vaginalis - thin mesothelial layer.

Microscopic

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.

Images

Interstitial

Image

Associated structures

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

Image:

Rete testis

Microscopic:

  • Delicate anastomosing channels lined by cuboid epithelium.

Images

www:

Appendix of testis

Muellerian duct remnant.

Microscopic:

  • Polypoid structure.

Images:

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 TESTICLE, RIGHT, ORCHIECTOMY:
- TESTICLE WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR INTRATUBULAR GERM CELL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.

Diagnoses (overview)

  • 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, round or polygonal nuclear membrane, nucleoli[2]
CD117 appearance similar to seminoma
ITGCN (WC)
Seminoma fried egg cells fried egg-like cells (central nucleus, clear
cytoplasm) with squared-off nuclear
membrane, nucleoli, lymphocytic infiltrate, granulomata,
syncytiotrophoblastic giant cells[3]
D2-40 Dysgerminoma = female version of this tumour
Seminoma (WC)
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
Yolk sac tumour (WC)
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
Embryonal carcinoma (WC)
Choriocarcinoma marked nuclear atypia cells with clear cytoplasm (cytotrophoblast), multinucleated cells (syncytiotrophoblast) beta-hCG not commonly pure, usu. a component of a mixed GCT
Choriocarcinoma (WC)
Teratoma skin, GI tract-like epithelium skin (epidermis, adnexal structures - sebaceous glands, hair follicles), GI tract-like glands (simple tall columnar epithelium), fat +/-primitive neuroepithelium (pseudostratified epithelium in rosettes) None testicular teratomas in post-pubertal males are all considered malignant[4]
Primitive neuroepithelium (WC)
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)
Spermatocytic seminoma (WC)
Mixed germ cell tumour NA common combinations: teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE); seminoma + embryonal (SE); embryonal + teratoma (TE) NA -
Mixed GCT (WC)

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)
Leydig cell tumour (WC)
Sertoli cell tumour cells in cords or trabeculae light staining bubbly cytoplasm +/- large cytoplasmic vacuoles, granular chromatin ? usu. no significant nuclear atypia, no mitoses
Sertoli cell tumour (WC)

Benign

Testicular atrophy

Cryptorchidism redirects here.
  • AKA atrophic testis.
  • AKA atrophy of the testis.

General

  • Microscopic appearance identical to cryptorchidism (undescended testis).[5]

Gross

  • Decreased size.

Microscopic

Features:[5]

  • Thickening of seminiferous tubule basement membrane.
  • Intertubular fibrosis.
  • Decreased sperm/no sperm present.

Note:

  • End-stage testicle - only has Sertoli cell within the seminiferous tubules.

Image:

Sign out

TESTICLE, RIGHT, ORCHIECTOMY:
- ATROPHIC TESTICLE.
- NEGATIVE FOR INTRATUBULAR GERM CELL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.

Micro

The sections show seminiferous tubules surrounded by thick hyaline sleeves. In a large number of sections only Sertoli cells are found in the tubules.

In some sections poorly defined paucicellular tubular structures reminiscent of seminiferous tubules composed of hyaline material are present; these probably represent obsolete seminiferous tubules. Focally, fibrosis is seen without definite tumour outlines. There is no significant inflammation. The rete testis is identified.

Rare seminiferous tubules have spermatid within. The germ cells seen do not have appreciable nuclear atypia.

Numerous small Leydig cell clusters are seen in some sections.

Spermatocele

General

  • Benign.
  • Cyst of the epididymis (classic).

Clinical:

  • Often asymptomatic.
  • Excised due to pain or mass effect.[7]

Microscopic

Features:

  • Cyst lined by a simple ciliated epithelium.
  • Contain sperm.
    • Head: ~1/2 the size of a RBC, black.
    • Tail: infrequently seen.

Note:

DDx:

Images

www:

Hydrocele testis

General

  • Benign.

Clinical:

  • Scrotal mass.

Microscopic

Features:

  • Cyst lined by a simple ciliated epithelium.
  • Does not contain sperm.

DDx:

Idiopathic granulomatous orchitis

Granulomatous orchitis redirects here.

General

  • Rare.
  • Unknown etiology -- possibly trauma + immune reaction to sperm.[9]

Microscopic

Features:[9]

  • Granulomas +/- necrosis.
  • +/-Destruction of seminiferous tubules.
  • Prominent collagen fibrosis.

DDx:

Stains

Premalignant

Intratubular germ cell neoplasia

  • Abbreviated ITGCN.

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 ITGCN:

Classification:[14]

  • Undifferentiated ITGCN.
  • Differentiated ITGCN.[15]
    • Intratubular embryonal carcinoma.
    • Intratubular seminoma.

Microscopic

Features:[16][17]

  • "Large" round or polygonal nuclei.
    • Size in relation to normal often not defined.
      • Rakheja et al. say >= 5x a lymphocyte for intratubular embryonal carcinoma.[14]
    • Polygonal nuclei = squared-off nuclear membrane.
  • Prominent nucleoli - key feature.
  • Clear cytoplasm.
  • +/-Cells fill the tubule.

DDx:

  • Sertoli cell-only syndrome - Sertoli cells also have nucleoli, wind swept appearance.[18]

Images

www:

IHC

Features:[19]

  • PLAP +ve.[20]
  • CD117 +ve.
    • Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann et al.[21]
  • OCT3/4 +ve.

Note:

  • Normal testis PLAP -ve, CD117 -ve.[22]

Germ cell tumours

Seminoma

Should not be confused with the unrelated tumour called spermatocytic seminoma.

General

Clinical:

  • Elevated serum LDH.
  • Normal serum alpha fetoprotein.
  • Usually normal beta-hCG.

Note:

  • Rarely, it may present a retroperitoneal mass.[23]

Epidemiology & etiology

Microsopic

Features:

  • Cells with fried egg appearance - key feature:
    • Clear cytoplasm.
    • Central nucleus, with prominent nucleolus.
      • Nucleus may have "corners", i.e. it is not round.
  • +/-Lymphoctyes - interspersed (very common).
  • +/-Syncytiotrophoblasts, AKA syncytiotrophoblastic giant cells (STGCs),[3] present in ~10-20% of seminoma.[24]
    • Large + irregular, vesicular nuclei.
    • Eosinophilic vacuolated cytoplasm (contains hCG).
  • +/-Florid granulomatous reaction.

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

DDx:

Images

IHC

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RETROPERITONEAL SOFT TISSUE, RIGHT, CORE BIOPSY:
- SEMINOMA.

Micro

The sections show large atypical, discohesive cells with prominent nucleoli, central nuclei and moderate clear cytoplasm, intermixed with mature lymphocytes. Mitotic activity is present.

Small biopsy

A mixed germ cell tumour cannot be excluded; given the small quantity of tumour, this biopsy is at a high risk for having undersampled other tumour components should they be present. Correlation with serology and consideration of re-biopsy is suggested.

Spermatocytic seminoma

General

  • Rare tumour.
  • Only one case of metastases in 200 cases.[31]
  • Orchiectomy is curative.
  • Not reported/found in females.[31]
  • Typically older - mean age 50s.[31]

Epidemiology

Microscopic

Features:[33]

  • 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).[31]
    3. Large cells (50-100 µm).
      • Filamentous chromatin.
  • Mucoid lakes.
  • Intratubular spread.

Notes:

  • Spireme = the tangle of filaments in prophase portion of mitosis.[34]
  • May have eosinophilic cytoplasm (dependent on lab).

DDx:

Images

IHC

Features:[35]

  • PLAP -ve (0 positive/17).
  • CD117 -ve (7 positive/17).
  • CAM5.2 -ve (1 positive/17).

Yolk sac tumour

  • Most common GCT in infants and young boys.

Microscopic

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.[36]

Embryonal carcinoma

These often look like a poorly differentiated carcinoma.

General

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

Microscopic

Features:[37]

  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).

Choriocarcinoma

These are aggressive tumours.

Microscopic

Features:

  • 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.

Teratoma of the testis

In post-pubertal males these (testicular) tumours are considered malignant. They usually consist of all three germ layers.[38]

Sex cord stromal tumours

Leydig cell tumour

  • AKA interstitial cell tumour.

General

  • Arises from interstitial cell.
  • May be associated with increased testosterone.

Gross

  • Solid, lobulated.
  • Red/tan.

Image:

Microscopic

Features:[39]

  • Vacuolization (cytoplasm) - key feature.
  • Cytoplasm - clear to eosinophilic - important.
  • Reinke crystals - classic finding, usually not present.
    • Cylindrical crystalloid eosinophilic cytoplasmic bodies.
  • Nucleoli common.
  • Round nuclei.

DDx:

Images

www:

IHC

Sertoli cell nodule

  • AKA Pick's adenoma.
  • AKA testicular tubular adenoma.
  • AKA tubular adenoma of the testis.

General

  • 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.[43]

Gross

  • Usually an incidental finding, rarely presents as a testicular mass.[44]

Microscopic

Features:[43][45]

  • 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.

DDx:[44]

Images

IHC

Features:[44]

  • Alpha-inhibin +ve (5/5 cases).
  • OCT3/4 -ve (5/5 cases).

Sertoli cell tumour

General

  • Arises from Sertoli cells (AKA nurse cells).

May be seen in several syndrome - esp. if there is calcification:

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.

DDx:

Images

www:

IHC

  • Alpha-inhibin +ve. (???)

Other

These tumours are rare.

Adenocarcinoma of the rete testis

General

  • Extremely rare - a few dozen cases in the world literature.[47]
  • Possible association of diethylstilbestrol.[47]

Microscopic

Features:

  • Adenocarcinoma:
    • Tubular or papillary architecture.[47]
    • Columnar cells with cigar-shaped nuclei.

Images

See also

References

  1. Soper, MS.; Hastings, JR.; Cosmatos, HA.; Slezak, JM.; Wang, R.; Lodin, K. (Dec 2012). "Observation Versus Adjuvant Radiation or Chemotherapy in the Management of Stage I Seminoma: Clinical Outcomes and Prognostic Factors for Relapse in a Large US Cohort.". Am J Clin Oncol. doi:10.1097/COC.0b013e318277d839. PMID 23275274.
  2. 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.
  3. 3.0 3.1 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.
  4. Carver, BS.; Al-Ahmadie, H.; Sheinfeld, J. (May 2007). "Adult and pediatric testicular teratoma.". Urol Clin North Am 34 (2): 245-51; abstract x. doi:10.1016/j.ucl.2007.02.013. PMID 17484929.
  5. 5.0 5.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 506-7. ISBN 978-1416054542.
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  21. Biermann, K.; Stoop, H.; Looijenga, L. (May 2012). "c-KIT protein expression does not discriminate neoplastic from non-neoplastic intratubular germ cells.". Histopathology 60 (6): 1017-9. doi:10.1111/j.1365-2559.2011.04157.x. PMID 22340755.
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  32. 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.
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  35. Kraggerud, SM.; Berner, A.; Bryne, M.; Pettersen, EO.; Fossa, SD. (Mar 1999). "Spermatocytic seminoma as compared to classical seminoma: an immunohistochemical and DNA flow cytometric study.". APMIS 107 (3): 297-302. PMID 10223302.
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  40. URL: http://www.antibodybeyond.com/reviews/cell-markers/leydig-cell-marker.htm. Accessed on: 18 May 2010.
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