Difference between revisions of "Testis"

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[[Image:Seminoma_of_the_Testis.jpg|thumb|150px|Orchiectomy specimen showing testis replaced by tumour (proven to be [[seminoma]]). (WC/Ed Uthman)]]
The '''testis''', plural '''testes''',  are important for survival of the species.  Tumours occasionally arise in 'em.  They generally are not biopsied.   
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.
If the testis is biopsied, it is usually for [[male infertility|fertility]].  The [[cut-up]] of orchiectomy specimens is dealt with in ''[[orchiectomy grossing]]''.


=Gross=
=Normal testis=
===Gross===
Anatomy - deep to superficial:
Anatomy - deep to superficial:
*Tunica albuginea - fibrous layer.
*Tunica albuginea - fibrous layer.
*Tunica vaginalis - thin mesothelial layer.
*Tunica vaginalis - thin mesothelial layer.
**This layer is important in the [[cancer staging|staging]] of testicular tumours.


=Normal histology=
===Microscopic===
===Seminiferous tubules===
====Seminiferous tubules====
*Sertoli cells ([[AKA]] sustentacular cell [[AKA]] nurse cell).  
*Sertoli cells ([[AKA]] sustentacular cell [[AKA]] nurse cell).  
**Large cells with oval nucleus.  
**Large cells with oval nucleus.  
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**You don't see the tail on light microscopy.
**You don't see the tail on light microscopy.


===Interstitium===
=====Images=====
<gallery>
Image:Seminiferous_tubule_and_sperm_low_mag.jpg | Seminiferous tubule and sperm - low mag. (WC/Nephron)
Image:Seminiferous_tubule_and_sperm.jpg | Seminiferous tubule and sperm - high mag. (WC/Nephron)
Image:Intratubular_germ_cell_neoplasia_-_2_-_very_high_mag.jpg | Benign seminiferous tubules and GCNIS (ITGCN). (WC/Nephron)
</gallery>
====Interstitial====
*Leydig cell ([[AKA]] interstitial cell).
*Leydig cell ([[AKA]] interstitial cell).
**Large eosinophilic cell.
**Large eosinophilic cell.
*Blood vessels.
*[[Blood vessel]]s.


===Associated structures===
=====Image=====
*Epididymis - stores the sperm.
<gallery>
Image:Leydig_cells_-_very_high_mag.jpg | Leydig cells - very high mag. (WC/Nephron)
</gallery>
====Associated structures====
*[[Epididymis]] - stores the sperm.
**Pseudostratified epithelium with cilia.
**Pseudostratified epithelium with cilia.


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*[http://www.webpathology.com/image.asp?n=3&Case=27 Epididymis (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=3&Case=27 Epididymis (webpathology.com)].


===Rete testis===
====Rete testis====
*Receives stuff from the tubules.
*Receives stuff from the tubules.
*Occasionally afflicted by ''[[adenomatous hyperplasia of the rete testis]]''.
*Very rarely give rise to an ''[[adenocarcinoma of the rete testis]]''.
*May be involved by [[seminoma]].
**Increases risk of relapse in a univariate analysis.<Ref>{{Cite journal  | last1 = Soper | first1 = MS. | last2 = Hastings | first2 = JR. | last3 = Cosmatos | first3 = HA. | last4 = Slezak | first4 = JM. | last5 = Wang | first5 = R. | last6 = Lodin | first6 = K. | title = 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. | journal = Am J Clin Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2012 | doi = 10.1097/COC.0b013e318277d839 | PMID = 23275274 }}</ref>
**More common with (sometimes subtle) intertubular pattern of seminoma.<ref name=pmid16021570>{{Cite journal  | last1 = Browne | first1 = TJ. | last2 = Richie | first2 = JP. | last3 = Gilligan | first3 = TD. | last4 = Rubin | first4 = MA. | title = Intertubular growth in pure seminomas: associations with poor prognostic parameters. | journal = Hum Pathol | volume = 36 | issue = 6 | pages = 640-5 | month = Jun | year = 2005 | doi = 10.1016/j.humpath.2005.03.011 | PMID = 16021570 }}</ref>


Microscopic:
Microscopic:
*Delicate anastomosing channels lined by cuboid epithelium.
*Delicate anastomosing channels lined by cuboid epithelium.


Image:
=====Images=====
*[http://commons.wikimedia.org/wiki/File:Rete_testis_high_mag.jpg Rete testis (WC)].
<gallery>
Image:Rete_testis_high_mag.jpg | Rete testis (WC/Nephron)
*[Image:Rete_testis_with_seminoma.jpg | Seminoma in the rete testis (WC/Nephron)
</gallery>
www:
*[http://www.webpathology.com/image.asp?case=27&n=5 Rete testis (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=27&n=5 Rete testis (webpathology.com)].


===Appendix of testis===
====Appendix of testis====
Muellerian duct remnant.
*Muellerian duct remnant.


Microscopic:
Microscopic:
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*[http://www.webpathology.com/image.asp?case=27&n=8 Appendix of testis (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=27&n=8 Appendix of testis (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=27&n=7 Appendix of testis (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=27&n=7 Appendix of testis (webpathology.com)].
===Sign out===
<pre>
TESTICLE, RIGHT, ORCHIECTOMY:
- TESTICLE WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR INTRATUBULAR GERM CELL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>
====Alternate====
<pre>
RIGHT TESTICLE, ORCHIDECTOMY:
- BENIGN TESTIS WITH SPERMATOGENESIS.
- NEGATIVE FOR INTRATUBULAR GERM CELL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>


=Diagnoses (overview)=
=Diagnoses (overview)=
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*Infertility - azoospermic.
*Infertility - azoospermic.
**No sperm present.
**No sperm present.
*Germ cell tumours (GCTs).
*[[Germ cell tumours]] (GCTs).
**Intratubular germ cell neoplasia.
**[[Intratubular germ cell neoplasia]].
**Seminoma.
**[[Seminoma]].
**Spermatocytic seminoma.
**[[Spermatocytic seminoma]].
**Yolk sac tumour (endodermal sinus tumour).
**[[Yolk sac tumour]] (endodermal sinus tumour).
**Embryonal carcinoma.
**[[Embryonal carcinoma]].
**Choriocarcinoma.
**[[Choriocarcinoma]].
**Teratoma.
**[[Teratoma]].
**Mixed GCT - 60% of GCTs are mixed.
**[[Mixed GCT]] - 60% of GCTs are mixed.
***Common combinations:  
***Common combinations:  
***# teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE).
***# teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE).
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***# embryonal + teratoma (TE).
***# embryonal + teratoma (TE).
*Sex-cord stromal tumour.
*Sex-cord stromal tumour.
**Leydig cell tumour.
**[[Leydig cell tumour]].
**Sertoli cell tumour.
**[[Sertoli cell tumour]].


===IHC for GCTs===
===IHC for GCTs===
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*Beta-hCG - choriocarcinoma.
*Beta-hCG - choriocarcinoma.
*CD30 - embryonal carcinoma.
*CD30 - embryonal carcinoma.
*D2-40 - seminoma.
*[[D2-40]] - seminoma.


===Tabular summary of GCTs===
===Tabular summary of GCTs===
{| class="wikitable"
{| class="wikitable sortable"
!| Tumour
! Tumour
!| Key feature
! Key feature
!| Microscopic
! Microscopic
!| IHC
! IHC
!| Other
! Other
!| Image
! Image
|-  
|-  
| [[Intratubular germ cell neoplasia]] (ITGCN)
| [[Germ cell neoplasia in situ]] (GCNIS)
| nests of small fried egg cells
| nests of small fried egg cells
| large central nucleus, clear <br>cytoplasm, squared-off nuclear membrane, [[nucleoli]]<ref name=Ref_GUP538>{{Ref GUP|538}}</ref>
| large central nucleus, clear <br>cytoplasm, round ''or'' polygonal nuclear membrane, [[nucleoli]]<ref name=Ref_GUP538>{{Ref GUP|538}}</ref>
| CD117
| CD117
| appearance similar to seminoma
| appearance similar to seminoma
| [http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag.jpg], [http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg]
| [[Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg|thumb|center|150px|GCNIS (WC)]]
|-  
|-  
| [[Seminoma]]
| [[Seminoma]]
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| D2-40
| D2-40
| Dysgerminoma = female version of this tumour
| Dysgerminoma = female version of this tumour
| [http://commons.wikimedia.org/wiki/File:Seminoma_high_mag.jpg], [http://commons.wikimedia.org/wiki/File:Seminoma_intermed_mag.jpg]
| [[Image:Seminoma_high_mag.jpg|thumb|center|150px|Seminoma (WC)]]
|-  
|-  
| [[Yolk sac tumour]] (endodermal sinus tumour)
| [[Yolk sac tumour]] (endodermal sinus tumour)
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| AFP
| AFP
| patterns: microcystic, solid, hepatoid
| patterns: microcystic, solid, hepatoid
| [http://webpathology.com/image.asp?case=34&n=6 hepatoid YST]
| [[Image:Mixed_germ_cell_tumour_-_very_high_mag.jpg|thumb|center|150px|Yolk sac tumour (WC)]]
|-  
|-  
| [[Embryonal carcinoma]]
| [[Embryonal carcinoma]]
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| CD30
| CD30
| usu. part of a mixed GCT  
| usu. part of a mixed GCT  
| [http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_intermed_mag.jpg], [http://www.webpathology.com/image.asp?case=33&n=1], [http://www.webpathology.com/image.asp?n=4&Case=37]
| [[Image:Embryonal_carcinoma_high_mag.jpg|thumb|center|150px|Embryonal carcinoma (WC)]]
|-  
|-  
| [[Choriocarcinoma]]
| [[Choriocarcinoma]]
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| cells with clear cytoplasm (cytotrophoblast), multinucleated cells (syncytiotrophoblast)
| cells with clear cytoplasm (cytotrophoblast), multinucleated cells (syncytiotrophoblast)
| beta-hCG
| beta-hCG
| other
| not commonly pure, usu. a component of a mixed GCT
| [http://www.webpathology.com/image.asp?case=36&n=1]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|150px|Choriocarcinoma (WC)]]
|-  
|-  
| [[Teratoma]], immature
| [[Teratoma]]
| primitive neuroepithelium  
| skin, GI tract-like epithelium
| pseudostratified epithelium in rosettes (gland-like arrangement)
| skin (epidermis, adnexal structures - sebaceous glands, hair follicles), GI tract-like glands (simple tall columnar epithelium), fat +/-primitive neuroepithelium (pseudostratified epithelium in [[rosettes]])
| None
| None
| teratoma are always malignant in males
| testicular teratomas in post-pubertal males are all considered malignant<ref>{{Cite journal  | last1 = Carver | first1 = BS. | last2 = Al-Ahmadie | first2 = H. | last3 = Sheinfeld | first3 = J. | title = Adult and pediatric testicular teratoma. | journal = Urol Clin North Am | volume = 34 | issue = 2 | pages = 245-51; abstract x | month = May | year = 2007 | doi = 10.1016/j.ucl.2007.02.013 | PMID = 17484929 }}</ref>
| [http://commons.wikimedia.org/wiki/File:Primitive_neuroepithelium_intermed_mag.jpg]
| [[Image:Teratoma_2_low_mag.jpg|thumb|center|150px|Teratoma (WC)]]
|-  
|-  
| [[Spermatocytic seminoma]]
| [[Spermatocytic tumour]] (previously ''spermatocytic seminoma'')
| population of 3 cells  
| 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
| 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)
| does not arise from GCNIS, no lymphocytic infiltrate (like in seminoma)
| [http://commons.wikimedia.org/wiki/File:Spermatocytic_seminoma_high_mag.jpg]
| [[Image:Spermatocytic_seminoma_high_mag.jpg|thumb|center|150px|Spermatocytic tumour (WC)]]
|-  
|-  
| [[Mixed germ cell tumour]]
| [[Mixed germ cell tumour]]
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| NA
| NA
| -
| -
| -
| [[Image:Mixed_germ_cell_tumour_-_intermed_mag.jpg|thumb|center|150px|Mixed GCT (WC)]]
|}
|}


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| MART-1, calretinin, inhibin
| MART-1, calretinin, inhibin
| +/-Reinke crystals (cylindrical crystalloid eosinophilic cytoplasmic bodies)
| +/-Reinke crystals (cylindrical crystalloid eosinophilic cytoplasmic bodies)
| [http://commons.wikimedia.org/wiki/File:Leydig_cell_tumour2.jpg]
| [[Image:Leydig_cell_tumour3.jpg|thumb|center|150px|Leydig cell tumour (WC)]]
|-  
|-  
| [[Sertoli cell tumour]]
| [[Sertoli cell tumour]]
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| ?
| ?
| usu. no significant nuclear atypia, no mitoses  
| usu. no significant nuclear atypia, no mitoses  
| [http://commons.wikimedia.org/wiki/File:Sertoli_cell_tumour_low_mag.jpg]
| [[Image:Sertoli_cell_tumour_high_mag.jpg|thumb|center|150px|Sertoli cell tumour (WC)]]
|}
|}


=Premalignant=
=Benign=
==Intratubular germ cell neoplasia==
==Testicular atrophy==
*Abbreviated ''ITGCN''.
*[[AKA]] ''atrophic testis''.
===General===
*[[AKA]] ''atrophy of the testis''.
*Considered the precursor lesion for germ cell tumours.
{{Main|Testicular atrophy}}
*Not all germ cell tumours (GCTs) arise from ''intratubular germ cell neoplasia''.  


The following testicular GCTs do not arise from ITCGN:
==Male infertility==
*[[Spermatocytic seminoma]].<ref>{{cite journal |author=Müller J, Skakkebaek NE, Parkinson MC |title=The spermatocytic seminoma: views on pathogenesis |journal=Int. J. Androl. |volume=10 |issue=1 |pages=147–56 |year=1987 |month=February |pmid=3583416 |doi= |url=}}</ref>
*This is a [[clinical diagnosis]].
*[[Yolk sac tumour]]s (endodermal sinus tumour).<ref>{{cite journal |author=Manivel JC, Simonton S, Wold LE, Dehner LP |title=Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study |journal=Arch. Pathol. Lab. Med. |volume=112 |issue=6 |pages=641–5 |year=1988 |month=June |pmid=2837162 |doi= |url=}}</ref>
{{Main|Male infertility}}
*Teratoma. (???)


===Microscopic===
==Spermatocele==
Features:<ref>URL: [http://www.webpathology.com/image.asp?case=30&n=1 http://www.webpathology.com/image.asp?case=30&n=1]. Accessed on: 18 May 2010.</ref>
{{Main|Spermatocele}}
*Enlarged nuclei, vesicular.
*Clear cytoplasm.
*Prominent nucleoli - '''key feature'''.


Images:
==Hydrocele testis==
*[http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg ITGCN - cropped (WC)].
*[[AKA]] ''hydrocele''.
*[http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag.jpg ITGCN (WC)].
{{Main|Hydrocele testis}}
*[http://www.webpathology.com/image.asp?case=30&n=1 ITGCN (webpathology.com)].


=Germ cell tumours=
==Idiopathic granulomatous orchitis==
{{Main|Germ cell tumours}}
:''Granulomatous orchitis'' redirects here.
==Seminoma==
===General===
===General===
*Male counterpart of the [[dysgerminoma]], which arise in the [[ovary]].
*Rare.
*Most common [[germ cell tumour]] of the testis.
*Unknown etiology -- possibly trauma + immune reaction to sperm.<ref name=pmid21458170>{{Cite journal  | last1 = Roy | first1 = S. | last2 = Hooda | first2 = S. | last3 = Parwani | first3 = AV. | title = Idiopathic granulomatous orchitis. | journal = Pathol Res Pract | volume = 207 | issue = 5 | pages = 275-8 | month = May | year = 2011 | doi = 10.1016/j.prp.2011.02.005 | PMID = 21458170 }}</ref>


Clinical:
===Microscopic===
*Elevated serum LDH.
Features:<ref name=pmid21458170/>
*Normal serum alpha fetoprotein.  
*[[Granuloma]]s +/- [[necrosis]].
*Usually normal beta-hCG.
*+/-Destruction of seminiferous tubules.
*Prominent collagen fibrosis.


===Epidemiology & etiology===
DDx:
*Arises from ''intratubular germ cell neoplasia'' (ITGCN).
*[[GCNIS]] (ITGCN).
*[[Seminoma]].
*Tertiary [[syphilis]] - classically, plasma cell rich.<ref name=pmid22343746>{{Cite journal  | last1 = Sekita | first1 = N. | last2 = Nishikawa | first2 = R. | last3 = Fujimura | first3 = M. | last4 = Sugano | first4 = I. | last5 = Mikami | first5 = K. | title = [Syphilitic orchitis: a case report]. | journal = Hinyokika Kiyo | volume = 58 | issue = 1 | pages = 53-5 | month = Jan | year = 2012 | doi =  | PMID = 22343746 }}</ref>
**Syphilis, unlike other infections of the GU tract, is said to affect the testis before the epididymis.<ref name=Ref_WMSP364>{{Ref WMSP|364}}</ref>
*[[Tuberculosis]].
*[[Lymphoma]].<ref name=pmid21458170/>
*[[Malakoplakia]].<ref name=pmid21458170/>
*BCG-associated orchitis.<ref name=pmid23856256>{{Cite journal  | last1 = Parker | first1 = SG. | last2 = Kommu | first2 = SS. | title = Post-intravesical BCG epididymo-orchitis: Case report and a review of the literature. | journal = Int J Surg Case Rep | volume = 4 | issue = 9 | pages = 768-70 | month =  | year = 2013 | doi = 10.1016/j.ijscr.2013.05.017 | PMID = 23856256 }}</ref><ref name=pmid12841318>{{Cite journal  | last1 = Bulbul | first1 = MA. | last2 = Hijaz | first2 = A. | last3 = Beaini | first3 = M. | last4 = Araj | first4 = GF. | last5 = Tawil | first5 = A. | title = Tuberculous epididymo-orchitis following intravesical BCG for superficial bladder cancer. | journal = J Med Liban | volume = 50 | issue = 1-2 | pages = 67-9 | month =  | year =  | doi =  | PMID = 12841318 }}</ref>


===Microsopic===
===Stains===
Features:
*AFB -ve -- for tuberculosis.
*Cells with fried egg appearance.
*[[Dieterle stain]] -ve -- for syphilis.
**Clear cytoplasm.
 
**Central nucleus, with prominent nucleolus.
==Testicular scar==
***Nucleus has "corners", i.e. it is ''not'' round.
{{Main|Testicular scar}}
*Lymphoctyes common, not essential.
*May see [[syncytiotrophoblast]]s, AKA ''syncytiotrophoblastic giant cells'' (STGCs).<ref name=Ref_GUP542>{{Ref GUP|542}}</ref>
**Large + irregular, vesicular nuclei.
**Eosinophilic vacuolated cytoplasm (contains hCG).
***Syncytiotrophoblasts = closest to mom in normal [[chorionic villi]] - covers cytotrophoblast.<ref>URL: [http://upload.wikimedia.org/wikipedia/commons/4/45/Gray37.png http://upload.wikimedia.org/wikipedia/commons/4/45/Gray37.png]. Accessed on: 31 May 2010.</ref>
*May see florid granulomatous reaction.


Memory device: 3 Cs - clear cytoplasm, central nucleus, corners on the nuclear membrane.
==Testicular abscess==
{{Main|Testicular abscess}}


Images:
==Testicular torsion==
*[http://commons.wikimedia.org/wiki/File:Seminoma_high_mag.jpg Seminoma - high mag. (WC)].
{{Main|Testicular torsion}}
*[http://commons.wikimedia.org/wiki/File:Seminoma_intermed_mag.jpg Seminoma - intermed. mag. (WC)].


DDx:
==Adenomatous hyperplasia of the rete testis==
*[[Mixed germ cell tumour]].
{{Main|Adenomatous hyperplasia of the rete testis}}
*Solid variant of [[yolk sac tumour]].
**Lacks fibrous septae and lymphocytes.<ref>URL: [http://webpathology.com/image.asp?case=34&n=8 http://webpathology.com/image.asp?case=34&n=8]. Accessed on: March 8, 2010.</ref>
*[[Choriocarcinoma]] - esp. if (multinucleated) syncytiotrophoblasts are present.
*Granulomatous orchitis - if [[granuloma]]s are present.


===IHC===
==Epidermoid cyst of the testis==
*D2-40 +ve.
{{Main|Epidermoid cyst of the testis}}
*CD117 +ve (ckit).
*CD30 -ve.<ref name=pmid16867864>PMID 16867864.</ref>
**Done to r/o embryonal carcinoma.
*Cytokeratins usu. -ve, may have weak focal positivity.<ref name=pmid16867864/>
*OCT3/4 +ve.<ref name=pmid20438407>{{Cite journal  | last1 = Emerson | first1 = RE. | last2 = Ulbright | first2 = TM. | title = Intratubular germ cell neoplasia of the testis and its associated cancers: the use of novel biomarkers. | journal = Pathology | volume = 42 | issue = 4 | pages = 344-55 | month = Jun | year = 2010 | doi = 10.3109/00313021003767355 | PMID = 20438407 }}</ref>


==Spermatocytic seminoma==
==Testicular trauma==
===General===
===General===
*Rare tumour.
*May lead to orchitectomy.
*Only one case of metastases in 200 cases.<ref name=pmid7927308>{{cite journal |author=Eble JN |title=Spermatocytic seminoma |journal=Hum. Pathol. |volume=25 |issue=10 |pages=1035–42 |year=1994 |month=October |pmid=7927308 |doi= |url=}}</ref>
*Orchiectomy is curative.
*Not reported/found in females.<ref name=pmid7927308/>
*Typically older - mean age 50s.<ref name=pmid7927308/>


====Epidemiology====
===Gross===
*Does NOT arise from ''intratubular germ cell neoplasia'' (ITGCN)<ref>{{cite journal |author=Müller J, Skakkebaek NE, Parkinson MC |title=The spermatocytic seminoma: views on pathogenesis |journal=Int. J. Androl. |volume=10 |issue=1 |pages=147–56 |year=1987 |month=February |pmid=3583416 |doi= 10.1111/j.1365-2605.1987.tb00176.x|url=}}</ref> - '''not''' considered a subtype of seminoma.
*Hemorrhagic.


===Microscopic===
===Microscopic===
Features:<ref>{{cite book |author=Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2005 |pages= |edition=7th |isbn=0-7216-0187-1 |oclc= |doi= |accessdate=}}</ref>
Features:
*Population of three cells.
*Necrotic seminiferous tubules.
*#Small cells (6-8 µm) - with a large NC [[ratio]].  
*Intratubular blood in keeping with hemorrhage.
*#*Look like secondary spermatocytes.
 
*#*May be confused with (mature) lymphocytes.
Note:
*#Medium cells (15-18 µm) with prominent nucleoli.
*Normal spermatogenesis in background - if viable tissue present.
*#*Filamentous chromatin (AKA ''spireme chromatin'').<ref name=pmid7927308>{{cite journal |author=Eble JN |title=Spermatocytic seminoma |journal=Hum. Pathol. |volume=25 |issue=10 |pages=1035–42 |year=1994 |month=October |pmid=7927308 |doi= |url=}}</ref>
*#Large cells (50-100 µm).
*#*Filamentous chromatin.
*Mucoid lakes.
*Intratubular spread.


Notes:
===Sign out===
*''Spireme'' = the tangle of filaments in prophase portion of mitosis.<ref>URL: [http://www.thefreedictionary.com/spireme http://www.thefreedictionary.com/spireme]. Accessed on: 4 June 2010.</ref>
<pre>
*May have eosinophilic cytoplasm (dependent on lab).
Right Testicle Tissue, Debridement:
**Usually larger than [[Leydig cell tumour]].
    - Hemorrhagic testicular tissue and necrotic seminiferous tubules.
    - Small amount of viable seminiferous tubules with spermatogenesis.
    - NEGATIVE for germ cell neoplasia in situ.
    - NEGATIVE for malignancy.


Images:
Comment:
*[http://commons.wikimedia.org/wiki/File:Spermatocytic_seminoma_high_mag.jpg Spermatocytic seminoma - high mag. (WC)].
The clinical history of trauma is noted.
*[http://commons.wikimedia.org/wiki/File:Spermatocytic_seminoma_intermed_mag.jpg Spermatocytic seminoma - intermed. mag. (WC)].
</pre>
 
=Premalignant=
==Germ cell neoplasia in situ==
*Previously ''intratubular germ cell neoplasia'' (abbreviated ''ITGCN'').
{{Main|Germ cell neoplasia in situ}}
 
=Germ cell tumours=
{{Main|Germ cell tumours}}
==Seminoma==
{{Main|Seminoma}}
 
==Spermatocytic tumour==
*Previously ''spermatocytic seminoma''.
{{Main|Spermatocytic tumour}}


==Yolk sac tumour==
==Yolk sac tumour==
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{{Main|Embryonal carcinoma}}
{{Main|Embryonal carcinoma}}
These often look like a poorly differentiated carcinoma.
These often look like a poorly differentiated carcinoma.
===General===
*Affects young adults.
**May be seen in women.
===Microscopic===
Features:<ref name=Ref_GUP549>{{Ref GUP|549}}</ref>
#Nucleoli - '''key feature'''.
#Vesicular nuclei (clear, empty appearing nuclei) - '''key feature'''.
#Nuclei overlap.
#[[Necrosis]] - common.
#*Not commonly present in seminoma.
#Indistinct cell borders
#Mitoses - common.
#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==
==Choriocarcinoma==
Line 318: Line 329:
These are aggressive tumours.
These are aggressive tumours.


===Microscopic===
==Teratoma of the testis==
Features:
*Syncytiotrophoblasts:
**Large + many irreg. or lobular hyperchromatic nuclei.
**Eosinophilic vacuolated cytoplasm (contains hCG).
*'''C'''ytotrophoblasts:
**'''C'''lear cytoplasm.
**Polygonal shaped cells in cords/masses.
**Distinct cell borders.
**Single uniform nucleus.
*+/-Hemorrhage.
*+/-Necrosis.
 
==Teratoma==
{{Main|Teratoma}}
{{Main|Teratoma}}
In males these tumours are always malignant.  They consist of all three [[germ layers]].<ref>{{cite book |author=Moore, Keith L.; Persaud, T.V.N.|title=The Developing Human: Clinically Oriented Embryology |publisher=Saunders |location= |year=2002 |pages= 83 |edition=7th |isbn=978-0721694122 |oclc= |doi= |accessdate=}}</ref>  
In post-pubertal males these (testicular) tumours are considered malignant.  They usually consist of all three [[germ layers]].<ref>{{cite book |author=Moore, Keith L.; Persaud, T.V.N.|title=The Developing Human: Clinically Oriented Embryology |publisher=Saunders |location= |year=2002 |pages= 83 |edition=7th |isbn=978-0721694122 |oclc= |doi= |accessdate=}}</ref>


=Sex cord stromal tumours=
=Sex cord stromal tumours=
==Leydig cell tumour==
==Leydig cell tumour==
*Arises from interstitial cell.
*[[AKA]] ''interstitial cell tumour''.
*[[AKA]] ''interstitial cell tumour''.
 
{{Main|Leydig cell tumour}}
===Microscopic===
Features:<ref name=Ref_GUP581>{{Ref GUP|581}}</ref>
*Vacuolization - ''key feature''.
*Cytoplasm - clear to eosinophilic.
*Nucleoli common.
*''Reinke crystals'', cylindrical crystalloid eosinophilic cytoplasmic bodies (not always present).
 
DDx:
*[[Spermatocytic seminoma]] - may have eosinophilic cytoplasm.
*[[Pregnancy luteoma]] - occurs during pregnancy, as the name implies.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Leydig_cell_tumour1.jpg Leydig cell tumour - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Leydig_cell_tumour2.jpg Leydig cell tumour - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Leydig_cell_tumour3.jpg Leydig cell tumour - high mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case404.html Leydig cell tumour - several images (upmc.edu)].
 
===IHC===
*Inhibin-alpha.
*Calretinin.<ref>URL: [http://www.antibodybeyond.com/reviews/cell-markers/leydig-cell-marker.htm http://www.antibodybeyond.com/reviews/cell-markers/leydig-cell-marker.htm]. Accessed on: 18 May 2010.</ref><ref name=pmid15950053>{{cite journal |author=Bar-Shira Maymon B, Yavetz H, Yogev L, ''et al.'' |title=Detection of calretinin expression in abnormal immature Sertoli cells in non-obstructive azoospermia |journal=Acta Histochem. |volume=107 |issue=2 |pages=105–12 |year=2005 |pmid=15950053 |doi=10.1016/j.acthis.2005.02.002 |url=}}</ref>
*Melan A.<ref name=pmid12966351>{{cite journal |author=Yao DX, Soslow RA, Hedvat CV, Leitao M, Baergen RN |title=Melan-A (A103) and inhibin expression in ovarian neoplasms |journal=Appl. Immunohistochem. Mol. Morphol. |volume=11 |issue=3 |pages=244–9 |year=2003 |month=September |pmid=12966351 |doi= |url=}}</ref>
**AKA ''MART-1''.
**Expressed in [[melanoma]], [[adrenal gland|adrenal tissue]], steroid-secreting tumours.


==Sertoli cell nodule==
==Sertoli cell nodule==
*[[AKA]] Pick's adenoma, AKA testicular tubular adenoma, AKA tubular adenoma of the testis.
*Abbreviated ''SCN''.
===General===
*[[AKA]] ''Pick's adenoma''.
*Benign proliferation of Sertoli cells - associated with cryptorchidism (undescended testis).
*AKA ''testicular tubular adenoma''.
*Not composed of a clonal cell population, i.e. ''not'' neoplastic; thus, technically, should not be called an ''adenoma''.<ref name=Ref_DCHH227>{{Ref DCHH|227}}</ref>
*AKA ''tubular adenoma of the testis''.
 
{{Main|Sertoli cell nodule}}
===Microscopic===
Features:<ref name=Ref_DCHH227>{{Ref DCHH|227}}</ref><ref>{{cite journal |author=Ricco R, Bufo P |title=[Histologic study of 3 cases of so-called tubular adenoma of the testis] |language=Italian |journal=Boll. Soc. Ital. Biol. Sper. |volume=56 |issue=20 |pages=2110–5 |year=1980 |month=October |pmid=6109541 |doi= |url=}}</ref>
*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:
*[http://commons.wikimedia.org/wiki/File:Sertoli_cell_nodule_high_mag.jpg Sertoli cell nodule - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Sertoli_cell_nodule_low_mag.jpg Sertoli cell nodule - low mag. (WC)].


==Sertoli cell tumour==
==Sertoli cell tumour==
 
{{Main|Sertoli cell tumour}}
===General===
*Arises from ''Sertoli cells'' ([[AKA]] nurse cells).
 
May be seen in several syndrome - esp. if there is calcification:
*[[Carney complex]].<ref name=pmid21047926>{{Cite journal  | last1 = Libé | first1 = R. | last2 = Horvath | first2 = A. | last3 = Vezzosi | first3 = D. | last4 = Fratticci | first4 = A. | last5 = Coste | first5 = J. | last6 = Perlemoine | first6 = K. | last7 = Ragazzon | first7 = B. | last8 = Guillaud-Bataille | first8 = M. | last9 = Groussin | first9 = L. | title = Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype. | journal = J Clin Endocrinol Metab | volume = 96 | issue = 1 | pages = E208-14 | month = Jan | year = 2011 | doi = 10.1210/jc.2010-1704 | PMID = 21047926 }}</ref>
*[[Peutz-Jeghers syndrome]].
 
===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:
*[[Granulosa cell tumour]] - may be very similar.  Often has nuclear grooves.
*Epithelioid [[adenomatoid tumour]].
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Sertoli_cell_tumour_high_mag.jpg Sertoli cell tumour - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Sertoli_cell_tumour_low_mag.jpg Sertoli cell tumour - low mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case275/micro.html Sertoli cell tumour with calcification in Carney complex - several images (upmc.edu)].
 
===IHC===
*Alpha-inhibin +ve. (???)


=Other=
=Other=
Line 422: Line 352:


==Adenocarcinoma of the rete testis==
==Adenocarcinoma of the rete testis==
===General===
{{Main|Adenocarcinoma of the rete testis}}
*Extremely rare - a few dozen cases in the world literature.<ref name=pmid3799821>{{Cite journal  | last1 = Newbold | first1 = RR. | last2 = Bullock | first2 = BC. | last3 = McLachlan | first3 = JA. | title = Adenocarcinoma of the rete testis. Diethylstilbestrol-induced lesions of the mouse rete testis. | journal = Am J Pathol | volume = 125 | issue = 3 | pages = 625-8 | month = Dec | year = 1986 | doi =  | PMID = 3799821 | PMC = 1888460 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1888460/?page=1}}</ref>
 
*Possible association of diethylstilbestrol.<ref name=pmid3799821/>
==Testicular adrenal rest tumour==
:Abbreviated ''TART''.
{{Main|Testicular adrenal rest tumour}}
 
==Fibrous pseudotumour of the paratesticular region==
{{Main|Fibrous pseudotumour of the paratesticular region}}


===Microscopic===
==Testicular metastasis==
Features:
{{Main|Testicular metastasis}}
*Adenocarcinoma:
**Tubular or papillary archictecture.<ref name=pmid3799821/>
**Columnar cells with cigar-shaped nuclei.


=See also=
=See also=
Line 438: Line 370:
*[[Vas deferens]].
*[[Vas deferens]].
*[[Spermatic cord]].
*[[Spermatic cord]].
*[[Paratesticular region]].


=References=
=References=
Line 446: Line 379:


[[Category: Genitourinary pathology]]
[[Category: Genitourinary pathology]]
[[Category: Testis]]

Latest revision as of 19:26, 9 September 2021

Orchiectomy specimen showing testis replaced by tumour (proven to be seminoma). (WC/Ed Uthman)

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. The cut-up of orchiectomy specimens is dealt with in orchiectomy grossing.

Normal testis

Gross

Anatomy - deep to superficial:

  • Tunica albuginea - fibrous layer.
  • Tunica vaginalis - thin mesothelial layer.
    • This layer is important in the staging of testicular tumours.

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

  • Seminiferous tubule and sperm - low mag. (WC/Nephron)

  • Seminiferous tubule and sperm - high mag. (WC/Nephron)

  • Benign seminiferous tubules and GCNIS (ITGCN). (WC/Nephron)

Interstitial

Image

  • Leydig cells - very high mag. (WC/Nephron)

Associated structures

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

Image:

Rete testis

Microscopic:

  • Delicate anastomosing channels lined by cuboid epithelium.
Images

  • Rete testis (WC/Nephron)

www:

Appendix of testis

  • Muellerian duct remnant.

Microscopic:

  • Polypoid structure.

Images:

Sign out

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

Alternate

RIGHT TESTICLE, ORCHIDECTOMY:
- BENIGN TESTIS WITH SPERMATOGENESIS.
- NEGATIVE FOR INTRATUBULAR GERM CELL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.

Diagnoses (overview)

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
Germ cell neoplasia in situ (GCNIS) nests of small fried egg cells large central nucleus, clear
cytoplasm, round or polygonal nuclear membrane, nucleoli[3] 		CD117 appearance similar to seminoma
GCNIS (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[4] 		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[5]
Teratoma (WC)
Spermatocytic tumour (previously 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 GCNIS, no lymphocytic infiltrate (like in seminoma)
Spermatocytic tumour (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

  • AKA atrophic testis.
  • AKA atrophy of the testis.
Main article: Testicular atrophy

Male infertility

Main article: Male infertility

Spermatocele

Main article: Spermatocele

Hydrocele testis

Main article: Hydrocele testis

Idiopathic granulomatous orchitis

Granulomatous orchitis redirects here.

General

  • Rare.
  • Unknown etiology -- possibly trauma + immune reaction to sperm.[6]

Microscopic

Features:[6]

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

DDx:

Stains

Testicular scar

Main article: Testicular scar

Testicular abscess

Main article: Testicular abscess

Testicular torsion

Main article: Testicular torsion

Adenomatous hyperplasia of the rete testis

Main article: Adenomatous hyperplasia of the rete testis

Epidermoid cyst of the testis

Main article: Epidermoid cyst of the testis

Testicular trauma

General

  • May lead to orchitectomy.

Gross

  • Hemorrhagic.

Microscopic

Features:

  • Necrotic seminiferous tubules.
  • Intratubular blood in keeping with hemorrhage.

Note:

  • Normal spermatogenesis in background - if viable tissue present.

Sign out

Right Testicle Tissue, Debridement:
     - Hemorrhagic testicular tissue and necrotic seminiferous tubules.
     - Small amount of viable seminiferous tubules with spermatogenesis.
     - NEGATIVE for germ cell neoplasia in situ.
     - NEGATIVE for malignancy.

Comment:
The clinical history of trauma is noted.

Premalignant

Germ cell neoplasia in situ

  • Previously intratubular germ cell neoplasia (abbreviated ITGCN).
Main article: Germ cell neoplasia in situ

Germ cell tumours

Main article: Germ cell tumours

Seminoma

Main article: Seminoma

Spermatocytic tumour

  • Previously spermatocytic seminoma.
Main article: Spermatocytic tumour

Yolk sac tumour

Main article: 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.[11]

Embryonal carcinoma

Main article: Embryonal carcinoma

These often look like a poorly differentiated carcinoma.

Choriocarcinoma

Main article: Choriocarcinoma

These are aggressive tumours.

Teratoma of the testis

Main article: Teratoma

In post-pubertal males these (testicular) tumours are considered malignant. They usually consist of all three germ layers.[12]

Sex cord stromal tumours

Leydig cell tumour

  • AKA interstitial cell tumour.
Main article: Leydig cell tumour

Sertoli cell nodule

  • Abbreviated SCN.
  • AKA Pick's adenoma.
  • AKA testicular tubular adenoma.
  • AKA tubular adenoma of the testis.
Main article: Sertoli cell nodule

Sertoli cell tumour

Main article: Sertoli cell tumour

Other

These tumours are rare.

Adenocarcinoma of the rete testis

Main article: Adenocarcinoma of the rete testis

Testicular adrenal rest tumour

Abbreviated TART.
Main article: Testicular adrenal rest tumour

Fibrous pseudotumour of the paratesticular region

Main article: Fibrous pseudotumour of the paratesticular region

Testicular metastasis

Main article: Testicular metastasis

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. ↑ Browne, TJ.; Richie, JP.; Gilligan, TD.; Rubin, MA. (Jun 2005). "Intertubular growth in pure seminomas: associations with poor prognostic parameters.". Hum Pathol 36 (6): 640-5. doi:10.1016/j.humpath.2005.03.011. PMID 16021570.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 6.0 6.1 6.2 6.3 Roy, S.; Hooda, S.; Parwani, AV. (May 2011). "Idiopathic granulomatous orchitis.". Pathol Res Pract 207 (5): 275-8. doi:10.1016/j.prp.2011.02.005. PMID 21458170.
  7. ↑ Sekita, N.; Nishikawa, R.; Fujimura, M.; Sugano, I.; Mikami, K. (Jan 2012). "[Syphilitic orchitis: a case report].". Hinyokika Kiyo 58 (1): 53-5. PMID 22343746.
  8. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 364. ISBN 978-0781765275.
  9. ↑ Parker, SG.; Kommu, SS. (2013). "Post-intravesical BCG epididymo-orchitis: Case report and a review of the literature.". Int J Surg Case Rep 4 (9): 768-70. doi:10.1016/j.ijscr.2013.05.017. PMID 23856256.
  10. ↑ Bulbul, MA.; Hijaz, A.; Beaini, M.; Araj, GF.; Tawil, A.. "Tuberculous epididymo-orchitis following intravesical BCG for superficial bladder cancer.". J Med Liban 50 (1-2): 67-9. PMID 12841318.
  11. ↑ URL: http://webpathology.com/image.asp?case=34&n=1. Accessed on: March 8, 2010.
  12. ↑ Moore, Keith L.; Persaud, T.V.N. (2002). The Developing Human: Clinically Oriented Embryology (7th ed.). Saunders. pp. 83. ISBN 978-0721694122.

External links

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