Difference between revisions of "Ovarian tumours"

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[[Image:Ovarian carcinoma.JPG|thumb|250px|right|[[Gross pathology|Gross]] photo of a [[malignant]] ovarian tumour. (WC/Doc James)]]
The article examines '''ovarian tumours''' including '''ovarian cancer'''.   
The article examines '''ovarian tumours''' including '''ovarian cancer'''.   


An introduction to the ovary is in the ''[[ovary]]'' article, which also deals benign cysts.   
An introduction to the ovary is in the ''[[ovary]]'' article, which also deals benign cysts.   


==Clinical==
What was labeled "ovarian cancer" in the past may really arise from [[fallopian tube]].<ref name=pmid19574767>{{Cite journal  | last1 = Hirst | first1 = JE. | last2 = Gard | first2 = GB. | last3 = McIllroy | first3 = K. | last4 = Nevell | first4 = D. | last5 = Field | first5 = M. | title = High rates of occult fallopian tube cancer diagnosed at prophylactic bilateral salpingo-oophorectomy. | journal = Int J Gynecol Cancer | volume = 19 | issue = 5 | pages = 826-9 | month = Jul | year = 2009 | doi = 10.1111/IGC.0b013e3181a1b5dc | PMID = 19574767 }}</ref> The label ''tubo-ovarian cancer''
has been advocated to address this change.  These tumours are dealt with in this article.
 
=Clinical=
Gynecologists use a scoring system to help decide which patients need surgery and estimate their pre-op risk of malignancy.
Gynecologists use a scoring system to help decide which patients need surgery and estimate their pre-op risk of malignancy.


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*There are two versions.<ref name=ukguide>URL: [http://www.sign.ac.uk/guidelines/fulltext/75/section3.html http://www.sign.ac.uk/guidelines/fulltext/75/section3.html]. Accessed on: 16 September 2011.</ref>  
*There are two versions.<ref name=ukguide>URL: [http://www.sign.ac.uk/guidelines/fulltext/75/section3.html http://www.sign.ac.uk/guidelines/fulltext/75/section3.html]. Accessed on: 16 September 2011.</ref>  


Elements & points (RIM 2):<ref name=ukguide>URL: [http://www.sign.ac.uk/guidelines/fulltext/75/section3.html http://www.sign.ac.uk/guidelines/fulltext/75/section3.html]. Accessed on: 16 September 2011.</ref>  
====Definition====
:<math>RMI\ score = ultrasound\ score\ *\ menopausal\ score\ *\ CA125\ level\ [U/ml].</math>
 
====Elements====
Elements & points (RMI 2):<ref name=ukguide>URL: [http://www.sign.ac.uk/guidelines/fulltext/75/section3.html http://www.sign.ac.uk/guidelines/fulltext/75/section3.html]. Accessed on: 16 September 2011.</ref>  
#Ultrasound features.  
#Ultrasound features.  
#*Significant findings: multilocular cyst, solid component, bilateral lesions, ascites, suspected intra-abdominal metastases (one finding=1 point, two or more findings=4 points).
#*Significant findings: multilocular cyst, solid component, bilateral lesions, ascites, suspected intra-abdominal [[metastases]] (one finding=1 point, two or more findings=4 points).
#Menopause/pre-menopause status (menopausal=4 points, pre-menopausal=1 point).
#Menopause/pre-menopause status (menopausal=4 points, pre-menopausal=1 point).
#CA-125 (blood test) in ''U/ml''.
#CA-125 (blood test) in ''U/ml''.


<math>RMI\ score = ultrasound\ score\ x\ menopausal\ score\ x\ CA125\ level\ [U/ml].</math>
====Interpretation====
 
Interpretation:
*RMI > 200 -- predicts malignancy.
*RMI > 200 -- predicts malignancy.


==Classification==
=Classification=
===The Latta rule of fives===
===The Latta rule of fives===
Can be divided as follows:<ref name=Ref_PBoD1093>{{Ref PBoD|1093}}</ref><ref>LAE. 22 October 2009.</ref>
Can be divided as follows:<ref name=Ref_PBoD1093>{{Ref PBoD|1093}}</ref><ref>LAE. 22 October 2009.</ref>
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# [[Germ cell tumours]] (GCTs).
# [[Germ cell tumours]] (GCTs).
# Metastatic tumours.
# Metastatic tumours.
# Rare stuff that doesn't fit in any of the above (e.g. [[leiomyoma]], [[angiosarcoma]]).
# Rare stuff that doesn't fit in any of the above (e.g. [[leiomyoma]], [[angiosarcoma]], [[ovarian small cell carcinoma of the hypercalcemic type]]).


Surface epithelial tumours:
Surface epithelial tumours:
# Serous.
# [[Serous carcinoma of the ovary|Serous carcinoma]].
# Endometrioid.
#* High-grade serous carcinoma. †
# Mucinous.
#* Low-grade serous carcinoma.
# Transitional cell tumours<ref name=Ref_WMSP401>{{Ref WMSP|401}}</ref> ([[Brenner tumour]]).
# [[Endometrioid carcinoma of the ovary|Endometrioid carcinoma]].
# Clear cell carcinoma.
# [[Mucinous carcinoma of the ovary|Mucinous carcinoma]].
# [[Clear cell carcinoma of the ovary|Clear cell carcinoma]].
# [[Brenner tumour]].
 
Note:
* † Transitional cell tumours<ref name=Ref_WMSP401>{{Ref WMSP|401}}</ref> are now grouped with high-grade serous carcinoma.<ref name=pmid23681072>{{Cite journal  | last1 = Takeuchi | first1 = T. | last2 = Ohishi | first2 = Y. | last3 = Imamura | first3 = H. | last4 = Aman | first4 = M. | last5 = Shida | first5 = K. | last6 = Kobayashi | first6 = H. | last7 = Kato | first7 = K. | last8 = Oda | first8 = Y. | title = Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma. | journal = Am J Surg Pathol | volume = 37 | issue = 7 | pages = 1091-9 | month = Jul | year = 2013 | doi = 10.1097/PAS.0b013e3182834d41 | PMID = 23681072 }}</ref><ref name=pmid23018212>{{Cite journal  | last1 = Ali | first1 = RH. | last2 = Seidman | first2 = JD. | last3 = Luk | first3 = M. | last4 = Kalloger | first4 = S. | last5 = Gilks | first5 = CB. | title = Transitional cell carcinoma of the ovary is related to high-grade serous carcinoma and is distinct from malignant brenner tumor. | journal = Int J Gynecol Pathol | volume = 31 | issue = 6 | pages = 499-506 | month = Nov | year = 2012 | doi = 10.1097/PGP.0b013e31824d7445 | PMID = 23018212 }}</ref>


Sex cord stromal tumours:
Sex cord stromal tumours:
#[[Granulosa cell tumour]] (adult type, juvenile type).
#[[Granulosa cell tumour]] ([[Adult granulosa cell tumour|adult type]], [[Juvenile granulosa cell tumour|juvenile type]]).
#[[Sertoli cell tumour]].
#[[Sertoli cell tumour]].
#[[Leydig cell tumour]].
#[[Leydig cell tumour]].
#Fibroma.
#[[Ovarian fibroma|Fibroma]].
#Thecoma.
#[[Thecoma]].


[[Germ cell tumours]]:
[[Germ cell tumours]]:
#[[Dysgerminoma]].
#[[Dysgerminoma]].
#Endodermal sinus tumour ([[yolk sac tumour]]).
#Endodermal sinus tumour ([[yolk sac tumour]]).
#[[Embryonal tumour]].
#[[Embryonal carcinoma]].
#[[Choriocarcinoma]].
#[[Choriocarcinoma]].
#[[Teratoma]].
#[[Teratoma]].


=Common special tumours=
===Endometriosis-related tumours===
===Endometriosis-related tumours===
Tumours associated with endometriosis:<ref>LAE. 22 October 2009.</ref>
Tumours associated with endometriosis:<ref>LAE. 22 October 2009.</ref>
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**Granulosa-theca cell tumour.
**Granulosa-theca cell tumour.


==Approach==
=A morphologic approach=
Where is the tumour arising?
Where is the tumour arising?
*Central location -- think GCTs and SCST.
*Central location -- think GCTs and SCST.
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*Characteristic of colorectal adenocarcinoma, may be absent in ovarian tumours -- limited value.<ref name=pmid9421090>{{cite journal |author=DeCostanzo DC, Elias JM, Chumas JC |title=Necrosis in 84 ovarian carcinomas: a morphologic study of primary versus metastatic colonic carcinoma with a selective immunohistochemical analysis of cytokeratin subtypes and carcinoembryonic antigen |journal=Int. J. Gynecol. Pathol. |volume=16 |issue=3 |pages=245–9 |year=1997 |month=July |pmid=9421090 |doi= |url=}}</ref>
*Characteristic of colorectal adenocarcinoma, may be absent in ovarian tumours -- limited value.<ref name=pmid9421090>{{cite journal |author=DeCostanzo DC, Elias JM, Chumas JC |title=Necrosis in 84 ovarian carcinomas: a morphologic study of primary versus metastatic colonic carcinoma with a selective immunohistochemical analysis of cytokeratin subtypes and carcinoembryonic antigen |journal=Int. J. Gynecol. Pathol. |volume=16 |issue=3 |pages=245–9 |year=1997 |month=July |pmid=9421090 |doi= |url=}}</ref>


==Grading of ovarian cancer==
=Grading of ovarian cancer=
*Silverberg grading system,<ref>{{cite journal |author=Silverberg SG |title=Histopathologic grading of ovarian carcinoma: a review and proposal |journal=Int. J. Gynecol. Pathol. |volume=19 |issue=1 |pages=7-15 |year=2000 |month=January |pmid=10638449 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-1691&volume=19&issue=1&spage=7}}</ref> aka ''universal grading system''.
*Silverberg grading system,<ref>{{cite journal |author=Silverberg SG |title=Histopathologic grading of ovarian carcinoma: a review and proposal |journal=Int. J. Gynecol. Pathol. |volume=19 |issue=1 |pages=7-15 |year=2000 |month=January |pmid=10638449 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-1691&volume=19&issue=1&spage=7}}</ref> aka ''universal grading system''.
*Based on ''pattern'', ''cytologic atypia'' and ''mitotic rate''.
*Based on ''pattern'', ''cytologic atypia'' and ''mitotic rate''.
*System somewhat similar to [[breast]] grading, which can be remembered as: ''TMN'' (tubular formation, mitotic rate, nuclear atypia).
*System somewhat similar to [[breast]] grading, which can be remembered as: ''TNM'' (tubular formation, [[nuclear atypia]], mitotic rate).


===Silverberg system===
===Silverberg system===
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*Grade III = 8-9.
*Grade III = 8-9.


Note 1:
Note:
*Most resident microscopes have an eyepiece diameter of 22 mm.  Thus, the approximate field diameter is 0.55 mm (22 mm/40 X = 0.55 mm), at highest magnification, and the field area is 0.23758 mm^2 (pi*(0.55/2)^2=0.23758 mm^2).  
*Most resident microscopes have an eyepiece diameter of 22 mm.  Thus, the approximate field diameter is 0.55 mm (22 mm/40 X = 0.55 mm), at highest magnification, and the field area is 0.23758 mm^2 (pi*(0.55/2)^2=0.23758 mm^2).  
*The number of HPFs should be adjusted if the area per field is different than 0.345 mm^2.
*The number of HPFs should be adjusted if the area per field is different than 0.345 mm^2.
**If the field diameter is 0.55 mm and the sample area is 3.45 mm^2, this is equivalent to 14.52 HPFs (3.45 mm^2 / 0.23758 mm^2 = 14.52); thus, it would be appropriate to use 15 HPFs and the cut points above.
**If the field diameter is 0.55 mm and the sample area is 3.45 mm^2, this is equivalent to 14.52 HPFs (3.45 mm^2 / 0.23758 mm^2 = 14.52); thus, it would be appropriate to use 15 HPFs and the cut points above.


Note 2:
===Predictive power of Silverberg grading===
*A not-so-good alternative is to adjust the number of mitotic counts a keep the number of HPFs (10) constant.
**If the mitotic rate per area is held constant, and the cut points are 9, 10 and 24, the equivalent mitoses per area are:
***0-4 mitoses/((HPF of 0.345 mm^2) x 10) = 1.
***5-11 mitoses/((HPF of 0.345 mm^2) x 10) = 2.
***12+ mitoses/((HPF of 0.345 mm^2) x 10) = 3.
 
===Value of Silverberg...===
Good correlation with five year survival (rounded values):<ref name=pmid12496698>{{cite journal |author=Sato Y, Shimamoto T, Amada S, Asada Y, Hayashi T |title=Prognostic value of histologic grading of ovarian carcinomas |journal=Int. J. Gynecol. Pathol. |volume=22 |issue=1 |pages=52-6 |year=2003 |month=January |pmid=12496698 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-1691&volume=22&issue=1&spage=52}}</ref>
Good correlation with five year survival (rounded values):<ref name=pmid12496698>{{cite journal |author=Sato Y, Shimamoto T, Amada S, Asada Y, Hayashi T |title=Prognostic value of histologic grading of ovarian carcinomas |journal=Int. J. Gynecol. Pathol. |volume=22 |issue=1 |pages=52-6 |year=2003 |month=January |pmid=12496698 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-1691&volume=22&issue=1&spage=52}}</ref>
*Grade I = 90%.
*Grade I = 90%.
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*Grade III = 40%.
*Grade III = 40%.


==Implants==
==Peritoneal implants==
===General===
===General===
*In the setting of borderline tumours there is much ado about implants.
Applies only to:
*[[Serous borderline tumour]].
*[[Seromucinous borderline tumour]].


There are two types:
====Classification====
*Non-invasive implants -- look like lymphovascular invasion.
There are two types:<ref name=pmid17727474>{{Cite journal  | last1 = Stewart | first1 = CJ. | last2 = Brennan | first2 = BA. | last3 = Crook | first3 = ML. | last4 = Russell | first4 = P. | title = Value of elastin staining in the assessment of peritoneal implants associated with ovarian serous borderline tumours. | journal = Histopathology | volume = 51 | issue = 3 | pages = 313-21 | month = Sep | year = 2007 | doi = 10.1111/j.1365-2559.2007.02789.x | PMID = 17727474 }}</ref>
*Invasive implants -- malignant cells within the stromal.
#Non-invasive implants.
#*Subdivided into:
#*#Epithelial.
#*#Desmoplastic.
#Invasive implants -- malignant cells within the stroma.


Notes:
Notes:
*Invasive implants are significant clinically.
*Invasive implants are significant clinically.
*Non-invasive implants have little clinical significance.
*Non-invasive implants have little clinical significance.
===Microscopic===
====Non-invasive implant====
Features (non-invasive implant epithelial-type):<ref name=pmid3179935>{{Cite journal  | last1 = Bell | first1 = DA. | last2 = Weinstock | first2 = MA. | last3 = Scully | first3 = RE. | title = Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis. | journal = Cancer | volume = 62 | issue = 10 | pages = 2212-22 | month = Nov | year = 1988 | doi =  | PMID = 3179935 }}</ref>
*Papillary proliferation on surface.
*+/-Smooth contoured invagination into:
**Submesothelium.
**Omental fat lobules.
*No "stromal response":
**Fibrosis.
*+/-[[Psammoma bodies]].
Features (non-invasive implant desmoplastic-type):<ref name=pmid3179935>{{Cite journal  | last1 = Bell | first1 = DA. | last2 = Weinstock | first2 = MA. | last3 = Scully | first3 = RE. | title = Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis. | journal = Cancer | volume = 62 | issue = 10 | pages = 2212-22 | month = Nov | year = 1988 | doi =  | PMID = 3179935 }}</ref>
*Stromal reaction restricted to the:
**Serosal surface.
**Fibrous septae.
*+/-[[Psammoma bodies]].
Note:
*No "destructive invasion".
**Irregular infiltration.
====Invasive implant====
Features (invasive implant):<ref name=pmid3179935/>
*Irregular infiltration of tumour into the submesothelial tissue - '''key feature''' - characterized by:
**+/-Solid nests.
**+/-Small glands +/- irregular "bridging" connections between glands - '''common'''.
*Nuclear atypia - '''common'''.
*+/-[[Psammoma bodies]].
===Stains===
*Elastin stain:<ref name=pmid17727474/>
**Non-invasive implants are sit superficial to the peritoneal elastic lamina (PEL).
**Invasive implants are deep to the PEL.
Note:
*Elastin layer is '''not''' present in the omentum.
===IHC===
*Elastin stain.
=Staging of ovarian cancer=
*The CAP protocol talks of in the pelvis and outside the pelvis - pT2 versus pT3.
*Omental involvement is considered outside the pelvis; it is pT3.<ref>URL: [http://ovariancancer.about.com/od/testsdiagnosis/a/FIGO_stages.htm http://ovariancancer.about.com/od/testsdiagnosis/a/FIGO_stages.htm]. Accessed on: 8 July 2013.</ref>


=Surface epithelial tumours=
=Surface epithelial tumours=
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'''Where to start when considering a malignant (epithelial) tumour of the ovary:'''
'''Where to start when considering a malignant (epithelial) tumour of the ovary:'''
{| class="wikitable"
{| class="wikitable sortable"
| || '''Serous''' || '''Endometrioid'''  || '''Mucinous'''
!Features
! Serous
! Endometrioid
! Mucinous
|-
|-
|Characteristics || cilia, columnar cells<br>psammoma bodies, papillary arch. || gland forming, endometrium-like || mucinous glands, colon-like
|Histology
| low grade: cilia, columnar cells, [[psammoma bodies]], papillary arch.; high grade: marked nuclear pleomorphism, prominent [[red nucleoli]], [[psammoma bodies]]
| gland forming - esp. cribriforming, endometrium-like
| mucinous glands, colon-like
|-
|-
|Differentiators || cilia, psammoma bodies || squamous metaplasia || mucin, lack of necrosis
|Differentiators
| cilia, [[psammoma bodies]]
| squamous metaplasia
| mucin, often lack of [[necrosis]]
|-
|-
|Associations || atrophy || endometriosis, endometrial hyperplasia || (?)
|Associations
| atrophy
| [[endometriosis]], [[endometrial hyperplasia]]
| (?)
|-
|-
|Typical age || usually 60s+ || 40-60 || varies (?)
|Typical age
| usually 60s+
| 40-60
| varies (?)
|-
|-
|Grade || typically high grade || typically low grade || often low
|Grade
| typically high grade
| typically low grade
| often low
|-
|-
|IHC || p53 +ve (diffuse), WT-1 +ve, CA-125 +ve, D2-40 +ve || WT-1 -ve || CK7 +ve, CK20 +ve (other tumours CK7 +ve, CK20 -ve)
|IHC
| p53 +ve (diffuse), WT-1 +ve, CA-125 +ve, D2-40 +ve
| WT-1 -ve
| CK7 +ve, CK20 +ve (other tumours CK7 +ve, CK20 -ve)
|-
|-
|Main DDx || poorly diff. endometrioid  || serous || metastatic tumour (usually GI)
|Main DDx
| poorly diff. endometrioid   
| serous
| metastatic tumour (usually GI)
|-
|-
|}
|}


==Serous tumours==
==Serous tumours - overview==
===Classification<ref>PBoD P.1096???</ref>===
===General===
*Most common malignant ovarian tumour.
 
====Classification====
Based on features predictive of behaviour:<ref name=Ref_PBoD1096>{{Ref PBoD |1096}}</ref>
*Benign.
*Benign.
*Borderline.
*Borderline.
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*Malignant.
*Malignant.
**Cytologic atypia.
**Cytologic atypia.
**Many papillae.
**+/-Papillae.


===Microscopic===
===Microscopic===
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**Columnar.
**Columnar.
*Papillae.
*Papillae.
*Psammoma bodies (concentric calcifications).
*[[Psammoma bodies]] (concentric [[calcification]]s).


Note:  
Note:  
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*Psammoma bodies may be seen in [[endosalpingiosis]].<ref name=pmid1774734>{{cite journal |author=Hallman KB, Nahhas WA, Connelly PJ |title=Endosalpingiosis as a source of psammoma bodies in a Papanicolaou smear. A case report |journal=J Reprod Med |volume=36 |issue=9 |pages=675–8 |year=1991 |month=September |pmid=1774734 |doi= |url=}}</ref>
*Psammoma bodies may be seen in [[endosalpingiosis]].<ref name=pmid1774734>{{cite journal |author=Hallman KB, Nahhas WA, Connelly PJ |title=Endosalpingiosis as a source of psammoma bodies in a Papanicolaou smear. A case report |journal=J Reprod Med |volume=36 |issue=9 |pages=675–8 |year=1991 |month=September |pmid=1774734 |doi= |url=}}</ref>


==Mucinous tumours==
==Serous carcinoma of the ovary==
*May arise in [[endometriosis]].<ref name=Ref_PBoD1097>{{Ref PBoD |1097}}</ref>
*[[AKA]] ''ovarian [[serous carcinoma]]''.
{{Main|Serous carcinoma of the ovary}}
 
==Serous cystadenoma of the ovary==
*[[AKA]] ''ovarian serous cystadenoma''.
*Related to ''adenofibroma'' and ''serous cystadenofibroma''.
{{Main|Serous cystadenoma of the ovary}}
 
==Ovarian serous borderline tumour==
*[[AKA]] ''serous borderline tumour of the ovary''.
*[[AKA]] ''serous tumour of low malignant potential of the ovary'', abbreviated ''SLMP''.<ref name=pmid10836293>{{Cite journal  | last1 = Seidman | first1 = JD. | last2 = Kurman | first2 = RJ. | title = Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. | journal = Hum Pathol | volume = 31 | issue = 5 | pages = 539-57 | month = May | year = 2000 | doi =  | PMID = 10836293 }}</ref><ref name=pmid10881733>{{Cite journal  | last1 = Dietel | first1 = M. | last2 = Hauptmann | first2 = S. | title = Serous tumors of low malignant potential of the ovary. 1. Diagnostic pathology. | journal = Virchows Arch | volume = 436 | issue = 5 | pages = 403-12 | month = May | year = 2000 | doi =  | PMID = 10881733 }}</ref>
{{Main|Serous borderline tumour}}


===Gross===
==Mucinous ovarian tumours==
Features:
*Multiloculated.
*Sticky, gelatinous fluid (glycoprotein).


===Microscopic===
==General==
Features:
*Common.
*Tall [[columnar cell]]s in glands.
*Tumours may be heterogenous; benign appearing epithelium may be beside clearly malignant epithelium.
**Apical mucin.
*Good sampling of mucinous tumours, i.e. many blocks, is important to lessen the chance of undercalling them.
**May vaguely resemble colorectal adenocarcinoma.
*Glands have mucin.
*+/-Nuclear atypia.
*NO [[cilia]].


===Subtypes===
===Subtypes===
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Comparison of mucosa:
Comparison of mucosa:
*Normal endocervical mucosa: [http://pathology.mc.duke.edu/research/Histo_course/endocx.jpg endocervical mucosa].
*Normal endocervical mucosa: [http://pathology.mc.duke.edu/research/Histo_course/endocx.jpg endocervical mucosa (duke.edu)].
*Normal colonic mucosa: [http://cellbio.utmb.edu/microanatomy/epithelia/00004493.jpg colonic type mucosa].
*Normal gastric mucosa: [http://commons.wikimedia.org/wiki/File:Normal_gastric_mucosa_intermed_mag.jpg gastric mucosa (WC)].


===Classification===
===Classification===
*Benign. (Dx: mucinous cystadenoma)
*Benign. (Dx: [[Mucinous_cystadenoma_of_the_ovary|mucinous cystadenoma]] ''or'' mucinous adenofibroma ''or'' mucinous cystadenofibroma)
**Single layer of cells.
**Single layer of cells.
*Borderline. (Dx: ''mucinous tumour of uncertain malignant potential'' or ''borderline mucinous tumour'')
*Borderline. (Dx: ''mucinous tumour of uncertain malignant potential'' or ''borderline mucinous tumour'')
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**Usually intestinal subtype.
**Usually intestinal subtype.


Note:
==Seromucinous borderline tumour of the ovary==
*Tumours may be heterogenous; benign appearing epithelium may be beside clearly malignant epithelium. 
*[[AKA]] ''endocervical-type mucinous and mixed cell-type tumour''.<ref name=pmid12459620>{{Cite journal  | last1 = Shappell | first1 = HW. | last2 = Riopel | first2 = MA. | last3 = Smith Sehdev | first3 = AE. | last4 = Ronnett | first4 = BM. | last5 = Kurman | first5 = RJ. | title = Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas. | journal = Am J Surg Pathol | volume = 26 | issue = 12 | pages = 1529-41 | month = Dec | year = 2002 | doi = | PMID = 12459620 }}</ref>
*Good sampling of mucinous tumours, i.e. many blocks, is important to lessen the chance of undercalling them.
===General===
 
*Rare.
==Endometrioid tumours of the ovary==
*Associated with [[endometriosis]].
===Epidemiology===
===Gross===
*Associated with [[endometriosis]], i.e. people with endometriosis are more likely to have 'em.
*Mucin-filled cysts.
 
===Histology===
*Tubular glands.  
**Cribriform pattern common.<ref>Khalifa 2008.</ref>
* May see mucinous secretion.<ref name=pmid18580313>{{cite journal |author=Baker P, Oliva E |title=A practical approach to intraoperative consultation in gynecological pathology |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=3 |pages=353-65 |year=2008 |month=July |pmid=18580313 |doi=10.1097/PGP.0b013e31815c24fe |url=}}</ref>
* May have squamous differentiation/squamous metaplasia (useful for differentiating from sex-cord stromal tumours and germ cell tumours).<ref name=pmid18580313/> - very useful feature.


==Clear cell adenocarcinoma==
Image:
*[[AKA]] clear cell carcinoma.
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=009520 Seromucinous borderline tumor of the ovary (unibas.ch)].
===General===
* Thought to be related to endometrioid carcinoma.<ref name=Ref_PBoD1098>{{Ref PBoD |1098}}</ref>
** Increased risk of CC adenoca in people with endometriosis.
* Worse prognosis vs. other surface epithelial tumours<ref>{{cite journal |author=Hauptmann S, Köbel M |title=[Prognostic factors in ovarian carcinoma] |language=German |journal=Verh Dtsch Ges Pathol |volume=89 |issue= |pages=92-100 |year=2005 |pmid=18035678 |doi= |url=}}</ref>


===Microscopic===
===Microscopic===
Features:
Features:
*Cystic/tubular architecture - important low power feature.
#Simple mucinous epithelium - endocervical type.<ref>{{Cite journal  | last1 = Shappell | first1 = HW. | last2 = Riopel | first2 = MA. | last3 = Smith Sehdev | first3 = AE. | last4 = Ronnett | first4 = BM. | last5 = Kurman | first5 = RJ. | title = Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas. | journal = Am J Surg Pathol | volume = 26 | issue = 12 | pages = 1529-41 | month = Dec | year = 2002 | doi =  | PMID = 12459620 }}</ref>
*Clear cells - cytoplasm is clear - '''key feature'''.
#*Tall columnar epithelium with apical pale cytoplasm.
*[[Hobnail morphology]] - apical surface larger than basal surface.<ref>URL: [http://www.pathologyoutlines.com/ovary.html http://www.pathologyoutlines.com/ovary.html]. Accessed on: 8 February 2011.</ref>  
#Simple serous epithelium - with cilia.
**"Nuclei bulge into the lumen".
 
*Hyaline droplets -- common, as in ''clear cell [[renal cell carcinoma]]''.
==Mucinous cystadenoma of the ovary==
**Eosinophilic bodies within lumen.
*[[AKA]] ''ovarian mucinous cystadenoma''.
*Nucleoli - prominent.
{{Main|Mucinous cystadenoma of the ovary}}


Note:
==Mucinous borderline tumour of the ovary==
*Clear cell adenocarcinoma does not have to have clear cells... yes, this is stupid; it is like ''papillary thyroid carcinoma'' -- which often isn't papillary.
*[[AKA]] ''ovarian mucinous borderline tumour''.
**The ''hobnail morphology'' is important if this is the case.
*[[AKA]] ''ovarian mucinous tumour of low malignant potential''.<ref name=pmid21464732>{{Cite journal  | last1 = Khunamornpong | first1 = S. | last2 = Settakorn | first2 = J. | last3 = Sukpan | first3 = K. | last4 = Suprasert | first4 = P. | last5 = Siriaunkgul | first5 = S. | title = Mucinous tumor of low malignant potential (borderline or atypical proliferative tumor) of the ovary: a study of 171 cases with the assessment of intraepithelial carcinoma and microinvasion. | journal = Int J Gynecol Pathol | volume = 30 | issue = 3 | pages = 218-30 | month = May | year = 2011 | doi = 10.1097/PGP.0b013e3181fcf01a | PMID = 21464732 }}</ref>
{{Main|Mucinous borderline tumour of the ovary}}


Images:
==Mucinous adenocarcinoma of the ovary==
*[http://commons.wikimedia.org/wiki/File:Ovarian_clear_cell_carcinoma_-a-_very_high_mag_-_cropped.jpg Clear cell carcinoma - very high mag. - cropped (WC)].
*[[AKA]] ''ovarian mucinous adenocarcinoma''.
*[http://commons.wikimedia.org/wiki/File:Ovarian_clear_cell_carcinoma_-a-_intermed_mag.jpg Clear cell carcinoma - intermed. mag. (WC)].
*[[AKA]] ''ovarian mucinous carcinoma''.
*[http://commons.wikimedia.org/wiki/File:Ovarian_clear_cell_carcinoma_-_low_mag.jpg Clear cell carcinoma - low mag. (WC)].
{{Main|Mucinous adenocarcinoma of the ovary}}


===IHC===
==Endometrioid carcinoma of the ovary==
*HNF-1beta +ve.<ref>{{Cite journal  | last1 = Tsuchiya | first1 = A. | last2 = Sakamoto | first2 = M. | last3 = Yasuda | first3 = J. | last4 = Chuma | first4 = M. | last5 = Ohta | first5 = T. | last6 = Ohki | first6 = M. | last7 = Yasugi | first7 = T. | last8 = Taketani | first8 = Y. | last9 = Hirohashi | first9 = S. | title = Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. | journal = Am J Pathol | volume = 163 | issue = 6 | pages = 2503-12 | month = Dec | year = 2003 | doi =  | PMID = 14633622 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892387/?tool=pubmed }}</ref><ref name=omim189907>{{OMIM|189907}}</ref>
*[[AKA]] ''endometrioid ovarian carcinoma''.
**Usu. -ve in serous carcinoma.
*[[AKA]] ''endometrioid adenocarcinoma of the ovary''.
*WT-1 -ve.
*[[AKA]] ''ovarian endometrioid adenocarcinoma''.
**Usu. +ve in serous carcinoma.
{{Main|Endometrioid carcinoma of the ovary}}


Panel for high grade serous vs. clear cell:<ref name=pmid18830127>{{cite journal |author=Köbel M, Kalloger SE, Carrick J, ''et al.'' |title=A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary |journal=Am. J. Surg. Pathol. |volume=33 |issue=1 |pages=14–21 |year=2009 |month=January |pmid=18830127 |doi=10.1097/PAS.0b013e3181788546 |url=}}</ref>
==Clear cell carcinoma of the ovary==
*ER, HNF-1beta, WT-1.
*[[AKA]] ''ovarian clear cell adenocarcinoma'', abbreviated ''OCCC''.
*[[AKA]] ''ovarian clear cell carcinoma''.
*[[AKA]] ''clear cell adenocarcinoma of the ovary''.
{{Main|Clear cell carcinoma of the ovary}}


==Transitional cell carcinoma of the ovary==
==Transitional cell carcinoma of the ovary==
===General===
{{Main|Transitional cell carcinoma of the ovary}}
*Rare.
*Fits into the ''transistional cell tumours'' category - in the surface epithelial group of ovarian tumours.<ref name=Ref_WMSP401>{{Ref WMSP|401}}</ref>
 
===Microscopic===
Features:<ref name=pmid15087664>{{Cite journal  | last1 = Eichhorn | first1 = JH. | last2 = Young | first2 = RH. | title = Transitional cell carcinoma of the ovary: a morphologic study of 100 cases with emphasis on differential diagnosis. | journal = Am J Surg Pathol | volume = 28 | issue = 4 | pages = 453-63 | month = Apr | year = 2004 | doi =  | PMID = 15087664 }}</ref>
*Cystic spaces:
**Small - punched-out border - very common.
**Large.
*Papillae, usu. large, blunt.
**Occasionally small and filiform.
*+/-Bizarre giant cells (35%)
*+/-Gland-like tubules.
*+/-Squamous differentiation.
*+/-[[Psammoma bodies]].
*Cells:
**Moderate basophilic cytoplasm and little intervening stroma.
**Marked nuclear pleomorphism.
**Mitoses - common.
 
Notes:
#Resembles [[urothelial carcinoma]].<ref name=pmid21073751>{{Cite journal  | last1 = Tazi | first1 = EM. | last2 = Lalya | first2 = I. | last3 = Tazi | first3 = MF. | last4 = Ahellal | first4 = Y. | last5 = M'rabti | first5 = H. | last6 = Errihani | first6 = H. | title = Transitional cell carcinoma of the ovary: a rare case and review of literature. | journal = World J Surg Oncol | volume = 8 | issue =  | pages = 98 | month =  | year = 2010 | doi = 10.1186/1477-7819-8-98 | PMID = 21073751 }}</ref>
#'''No''' Brenner tumour component (benign or malignant) should be present.<ref name=pmid21073751/>
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Transitional_cell_carcinoma_of_the_ovary_-_very_low_mag.jpg TCC - very low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Transitional_cell_carcinoma_of_the_ovary_-_intermed_mag.jpg TCC - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Transitional_cell_carcinoma_of_the_ovary_-_very_high_mag.jpg TCC - very high mag. (WC)].
 
===IHC===
Features:<ref name=pmid21073751>{{Cite journal  | last1 = Tazi | first1 = EM. | last2 = Lalya | first2 = I. | last3 = Tazi | first3 = MF. | last4 = Ahellal | first4 = Y. | last5 = M'rabti | first5 = H. | last6 = Errihani | first6 = H. | title = Transitional cell carcinoma of the ovary: a rare case and review of literature. | journal = World J Surg Oncol | volume = 8 | issue =  | pages = 98 | month =  | year = 2010 | doi = 10.1186/1477-7819-8-98 | PMID = 21073751 }}</ref>
#Vimentin +ve,
#CA-125 +ve.
#WT1 +ve.
#CK20 -ve.
#Thrombomodulin -ve.
#Uroplakin III -ve.
 
Notes:
*1-6 usu. opposite pattern in urothelial cell carcinoma.


==Brenner tumour==
==Brenner tumour==
===General===
{{Main|Brenner tumour}}
*Fits into the ''transistional cell tumours'' category - in the surface epithelial group of ovarian tumours.
 
====Epidemiology====
*Mostly benign clinical course.
*Thought to arise from [[Walthard cell rest]].
*Frequently an incidental finding, i.e. oophorectomy was done for another reason.
 
===Gross===
Features:
*Solid.
 
===Microscopic===
Features:
*Nests of transitional epithelium.<ref name=Ref_PBoD1098>{{Ref PBoD|1098}}</ref>
*"Coffee bean nucleus".
**Elliptical shape (nucleus).
**Nuclear grooves.<ref name=pathout_brenner>URL: [http://www.pathologyoutlines.com/ovarytumor.html#brennergen http://www.pathologyoutlines.com/ovarytumor.html#brennergen]. Accessed on: 8 February 2011.</ref>
*Distinct nucleoli.<ref name=pathout_brenner/>
 
Notes:
*DDx of Coffee bean nucleus = granulosa cell tumour.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Brenner_tumour_high_mag.jpg "Coffee bean" nuclei (WC)].
*[http://commons.wikimedia.org/wiki/File:Brenner_tumour_intermed_mag.jpg Brenner tumour - intermed. magnifiction (WC)].


=Germ cell tumours=
=Germ cell tumours=
Line 404: Line 419:
Dysgerminoma vs lymphoma:
Dysgerminoma vs lymphoma:
* Dysgerminoma has "squared-off" nuclei,<ref>{{cite journal |author=Baker P, Oliva E |title=A practical approach to intraoperative consultation in gynecological pathology |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=3 |pages=353?65 |year=2008 |month=July |pmid=18580313 |doi=10.1097/PGP.0b013e31815c24fe |url=}}</ref> i.e. the nuclei look are polygonal-shaped.
* Dysgerminoma has "squared-off" nuclei,<ref>{{cite journal |author=Baker P, Oliva E |title=A practical approach to intraoperative consultation in gynecological pathology |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=3 |pages=353?65 |year=2008 |month=July |pmid=18580313 |doi=10.1097/PGP.0b013e31815c24fe |url=}}</ref> i.e. the nuclei look are polygonal-shaped.
*[http://path.upmc.edu/cases/case356.html Dysgerminoma - several cases (upmc.edu)].


==Gonadoblastoma==
==Gonadoblastoma==
Line 418: Line 435:


=Metastatic ovarian tumours=
=Metastatic ovarian tumours=
==Generally==
{{Main|Ovarian metastasis}}
* Mostly Muellerian origin (uterus, fallopian tube) or pelvic peritoneum.
 
==Extramuellerian metastatic tumours==
DDx:
* [[Breast]].
* [[Gastrointestinal pathology|Gastrointestinal (GI) tract]].
** Pseudomyxoma peritonei, usu. [[appendix|appendiceal]] origin.
** Krukenberg tumour = [[signet ring cell]] cancer with mucin production of GI origin.
 
===Microscopic===
Features:
*Predominantly surface involvement and nodular at low power.
*Signet ring cells (suggestive of GI or breast primary).
*Lymphovascular invasion.
 
===Mucinous carcinoma - [[GI tract]] metastasis vs. primary ovarian===
Features favouring metastatic disease:<ref name=pmid18162780>{{Cite journal  | last1 = Yemelyanova | first1 = AV. | last2 = Vang | first2 = R. | last3 = Judson | first3 = K. | last4 = Wu | first4 = LS. | last5 = Ronnett | first5 = BM. | title = Distinction of primary and metastatic mucinous tumors involving the ovary: analysis of size and laterality data by primary site with reevaluation of an algorithm for tumor classification. | journal = Am J Surg Pathol | volume = 32 | issue = 1 | pages = 128-38 | month = Jan | year = 2008 | doi = 10.1097/PAS.0b013e3180690d2d | PMID = 18162780 }}</ref>
*Bilaterality -- both ovaries involved.
*Small unilateral tumour size -- <10 cm = metastatic.
**>13 cm = primary ovarian.


=Sex cord stromal tumours=
=Sex cord stromal tumours=
Line 455: Line 452:
*Abbreviated ''SCTAT''.
*Abbreviated ''SCTAT''.
*'''NOT''' ''sex cord tumour with angulated tubules''.
*'''NOT''' ''sex cord tumour with angulated tubules''.
 
{{Main|Sex cord tumour with annular tubules}}
===General===
*Associated with [[Peutz-Jeghers syndrome]].<ref name=pmid7358344>{{Cite journal  | last1 = Purohit | first1 = RC. | last2 = Alam | first2 = SZ. | title = Sex cord tumour of the ovary with annular tubules (SCTAT). | journal = Histopathology | volume = 4 | issue = 2 | pages = 147-54 | month = Mar | year = 1980 | doi =  | PMID = 7358344 }}
</ref>
**Large tumours more likely sporadic.
**Small tumours more likely Peutz-Jeghers syndrome and incidental.
 
===Microscopic===
Features:
*Well-circumscribed nests of cells with nuclei at the periphery.
*Annular tubules (ring-shaped tubules) with dense hyaline material.
 
Notes:
*''Annular'' = shape of a ring.<ref>URL: [http://dictionary.reference.com/browse/annular http://dictionary.reference.com/browse/annular]. Accessed on: 6 August 2011.</ref>
 
DDx:
*Sertoli-Leydig tumour - has double palisading with overlap of the layers.
*[[Granulosa cell tumour]] - have Call-Exner bodies, which don't have a well-defined/solid content.
*[[Brenner tumour]] - coffee-bean nuclei.
 
Images:
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=10&cat2=120&cat3=1015&cat4=3&stype=n SCTAT - image collection (gfmer.ch)].
*[http://www.pathology.cn/bbs/forum.php?mod=viewthread&tid=57445 Possible SCTAT (pathology.cn)].


==Juvenile granulosa cell tumour==
==Juvenile granulosa cell tumour==
===General===
{{Main|Juvenile granulosa cell tumour}}
*May secrete estrogen.
**May present with endometrial pathology, e.g. [[endometrial hyperplasia]] ''or'' endometrioid [[endometrial carcinoma]].
 
===Gross===
*Classically solid.
 
===Microscopic===
Features:
*Microcystic spaces.
*Moderate-to-marked nuclear atypia.
*Cuboidal-to-polygonal cell in sheets or stands or cords.
*Basophilic cytoplasm.
 
Notes:
*Juvenile variant of GCT has more nuclear pleomorphism.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Juvenile_granulosa_cell_tumour_-_intermed_mag.jpg Juvenile granulosa cell tumour - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Juvenile_granulosa_cell_tumour_-_very_high_mag.jpg Juvenile granulosa cell tumour - very high mag. (WC)].
 
===IHC===
* Inhibin positive.<ref name=Ref_PBoD1102>{{Ref PBoD|1102}}</ref>
** Inhibin negative in ''[[Brenner tumour]]''.
*Calretinin +ve.


==Adult granulosa cell tumour==
==Adult granulosa cell tumour==
*[[AKA]] ''granulosa cell tumour''.
*[[AKA]] ''granulosa cell tumour''.
**Should not be confused with ''[[juvenile granulosa cell tumour]]''.
**Should '''not''' be confused with ''[[granular cell tumour]]''.
 
**Ideally, it should be called ''adult granulosa cell tumour'' to avoid confusion with ''[[juvenile granulosa cell tumour]]''.
===General===
{{Main| Adult granulosa cell tumour}}
*May secrete estrogen.
**May present with endometrial pathology, e.g. [[endometrial hyperplasia]] ''or'' endometrioid [[endometrial carcinoma]].
 
===Gross===
*Classically solid.
 
===Microscopic===
Features:
* Classic appearance includes gland-like structures filled with acidophilic material (Call-Exner bodies).
* Small cuboidal to polygonal cell in sheets or stands or cords.
* Nuclear grooves.
 
Note:
*There is a "10% rule" -- if less than 10% of a SCST is granulosa cells... it isn't granulosa cell tumour.
*Juvenile variant of GCT has more nuclear pleomorphism.
 
DDx:
* [[Urothelial cell carcinoma]] (UCC).
** UCC usually has extensive necrosis.
* [[Brenner tumour]].
* [[Sertoli cell tumour]].
 
===IHC===
* Inhibin positive.<ref name=Ref_PBoD1102>{{Ref PBoD|1102}}</ref>
** Inhibin negative in ''[[Brenner tumour]]''.
*Calretinin +ve.


==Fibroma-thecoma group==
==Fibroma-thecoma group==
Line 544: Line 468:


Note:
Note:
*Some discourage the use of the term ''fibrothecoma'' and sugguest calling tumours in the fibrom-thecoma group ''fibroma'' unless there are lipid-laden cells and more than minimal alpha-inhibin positivity.<ref name=pmid16810055/>
*Some discourage the use of the term ''fibrothecoma'' and sugguest calling tumours in the fibroma-thecoma group ''fibroma'' unless there are lipid-laden cells and more than minimal alpha-inhibin positivity.<ref name=pmid16810055/>


==Ovarian fibroma==
==Ovarian fibroma==
===General===
{{Main|Ovarian fibroma}}
*May be a part of:
*#Meigs syndrome (mnemonic ''FAR'': fibroma, [[ascites]], right pleural [[effusion]]).
*#[[Nevoid basal cell carcinoma syndrome]] (NBCCS), AKA ''Gorlin syndrome''.<ref name=Ref_PBoD1103>{{Ref PBoD |1103}}</ref>
*#*In NBCCS classically - calcified and bilateral.<ref name=pmid6385289>{{Cite journal  | last1 = Tytle | first1 = T. | last2 = Rosin | first2 = D. | title = Bilateral calcified ovarian fibromas. | journal = South Med J | volume = 77 | issue = 9 | pages = 1178-80 | month = Sep | year = 1984 | doi =  | PMID = 6385289 }}</ref>
*Very rarely transform to [[adult fibrosarcoma|fibrosarcoma]] <1%.<ref>URL: [http://brighamrad.harvard.edu/Cases/bwh/hcache/353/full.html http://brighamrad.harvard.edu/Cases/bwh/hcache/353/full.html]. Accessed on: 4 October 2011.</ref>
 
===Microscopic===
Features:<ref>[http://www.pathologyoutlines.com/ovarytumor.html#fibroma http://www.pathologyoutlines.com/ovarytumor.html#fibroma]</ref><ref name=pmid16810055/>
*Spindle-shaped cells.
*Central nuclei.
*Stainable lipid - minimal or none.<ref name=pmid16810055/>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Ovarian_fibroma_-_intermed_mag.jpg Ovarian fibroma - intermed mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Ovarian_fibroma_-_high_mag.jpg Ovarian fibroma - high mag. (WC)].
 
===IHC===
*Inhibin -ve (~75%).<ref name=pmid16810055/>


==Thecoma==
==Thecoma==
===General===
{{Main|Thecoma}}
*Associated with compression & atrophy of ovarian cortex, thought to arise from medulla.<ref name=pmid18164409/>
*Approx. 50% have symptoms related to estrogen secretion.<ref name=pmid16810055/>
**May also be viralizing.
 
===Microscopic===
Features:<ref name=pmid16810055/>
*Nuclei with oval to spindle morphology.
*Abundant cytoplasm that is pale, vaculolated -- '''key feature'''.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Thecoma_low_mag.jpg Thecoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Thecoma_high_mag.jpg Thecoma - high mag. (WC)].
 
===IHC===
*Alpha-inhibin +ve (90%+).<ref name=pmid16810055/>


==Sertoli-Leydig cell tumour==
==Sertoli-Leydig cell tumour==
*[[AKA]] ''androblastoma''.
*[[AKA]] ''androblastoma''.
{{Main|Sertoli-Leydig cell tumour}}
==Hilus cell tumour==
{{Main|Leydig cell tumour}}
*[[AKA]] ''Leydig cell tumour''.<ref name=pmid19697637>{{Cite journal  | last1 = Zafrakas | first1 = M. | last2 = Venizelos | first2 = ID. | last3 = Theodoridis | first3 = TD. | last4 = Zepiridis | first4 = L. | last5 = Agorastos | first5 = T. | last6 = Bontis | first6 = JN. | title = Virilizing ovarian hilus (Leydig) cell tumor with concurrent contralateral hilus cell hyperplasia: a rare diagnosis. | journal = Eur J Gynaecol Oncol | volume = 30 | issue = 3 | pages = 338-40 | month =  | year = 2009 | doi =  | PMID = 19697637 }}</ref>
===General===
===General===
*Sertoli and leydig cells are normal in the [[testis]].
*Rare.<ref name=pmid19697637/>
*Poorly differentiated tumours have sarcomatous features.<ref name=Ref_PBoD1103>{{Ref PBoD|1103}}</ref>
*May cause virilization.
**Development of male (sexual) characteristics in a female.
*Arise from [[hilus cells]].


===Microscopic===
===Microscopic===
Features:
Features - see ''[[Leydig cell tumour]]'':
# Sertoli ''or'' Leydig cells.<ref name=Ref_PBoD1103>{{Ref PBoD|1103}}</ref>
*Moderate eosinophilic cytoplasm.
#* Leydig cells:
*+/-Reinke crystalloids (cytoplasmic inclusions).
#** Abundant solid eosinophilic cytoplasm.
#** Round nuclei with fine chromatin and a small or indistinct [[nucleolus]].
#** Often in small clusters ~ 5-25 cells/cluster.
#* Sertoli cells:
#** Pale/clear vacuolated cytoplasm.
#** Irregular nuclei with irregular/vacuolated-appearing chromatin.
#** Architecture: tubules, cords or sheets.
# Stroma.
# +/- Sarcomatous features (mucinous glands, bone, cartilage).


Images:
DDx:
*[http://commons.wikimedia.org/wiki/File:Sertoli-Leydig_cell_tumour_-_intermed_mag.jpg Sertoli-Leydig cell tumour - intermed. mag. (WC)].
*Hilus hyperplasia.
*[http://commons.wikimedia.org/wiki/File:Sertoli-Leydig_cell_tumour_-_very_high_mag.jpg Sertoli-Leydig cell tumour - very high mag. (WC)].
*[[Sertoli-Leydig tumour]].
 
==Pure Leydig cell tumour==
===General===
*AKA ''Hilus cell tumour''.
 
===Microscopy===
*Reinke crystalloids - in the cytoplasm of Leydig cells - ''[[testis]] article''.


=Benign=
=Benign=

Latest revision as of 16:35, 1 March 2018

Gross photo of a malignant ovarian tumour. (WC/Doc James)

The article examines ovarian tumours including ovarian cancer.

An introduction to the ovary is in the ovary article, which also deals benign cysts.

What was labeled "ovarian cancer" in the past may really arise from fallopian tube.[1] The label tubo-ovarian cancer has been advocated to address this change. These tumours are dealt with in this article.

Clinical

Gynecologists use a scoring system to help decide which patients need surgery and estimate their pre-op risk of malignancy.

Risk of malignancy index

  • Abbreviated RMI.
  • There are two versions.[2]

Definition

Elements

Elements & points (RMI 2):[2]

  1. Ultrasound features.
    • Significant findings: multilocular cyst, solid component, bilateral lesions, ascites, suspected intra-abdominal metastases (one finding=1 point, two or more findings=4 points).
  2. Menopause/pre-menopause status (menopausal=4 points, pre-menopausal=1 point).
  3. CA-125 (blood test) in U/ml.

Interpretation

  • RMI > 200 -- predicts malignancy.

Classification

The Latta rule of fives

Can be divided as follows:[3][4]

  1. Surface epithelial tumours (most common).
  2. Sex cord stromal tumours (SCSTs).
  3. Germ cell tumours (GCTs).
  4. Metastatic tumours.
  5. Rare stuff that doesn't fit in any of the above (e.g. leiomyoma, angiosarcoma, ovarian small cell carcinoma of the hypercalcemic type).

Surface epithelial tumours:

  1. Serous carcinoma.
    • High-grade serous carcinoma. †
    • Low-grade serous carcinoma.
  2. Endometrioid carcinoma.
  3. Mucinous carcinoma.
  4. Clear cell carcinoma.
  5. Brenner tumour.

Note:

  • † Transitional cell tumours[5] are now grouped with high-grade serous carcinoma.[6][7]

Sex cord stromal tumours:

  1. Granulosa cell tumour (adult type, juvenile type).
  2. Sertoli cell tumour.
  3. Leydig cell tumour.
  4. Fibroma.
  5. Thecoma.

Germ cell tumours:

  1. Dysgerminoma.
  2. Endodermal sinus tumour (yolk sac tumour).
  3. Embryonal carcinoma.
  4. Choriocarcinoma.
  5. Teratoma.

Common special tumours

Endometriosis-related tumours

Tumours associated with endometriosis:[8]

  1. Endometrioid.
  2. Clear cell carcinoma.
  3. Endocervical mucinous (AKA Seroumucinous type and Muellerian type).

Solid ovarian tumours

Simple version: basically anything sex cord stromal.

List:[9]

  • Brenner tumour.
  • SCSTs:
    • Fibroma.
    • Thecoma.
    • Fibrothecoma.
    • Leydig tumour.
    • Sertoli cell tumour.
    • Sertoli-Leydig tumour.
    • Granulosa cell tumour.
    • Granulosa-theca cell tumour.

A morphologic approach

Where is the tumour arising?

  • Central location -- think GCTs and SCST.
  • Surface of ovary -- think surface epithelial tumour.
    • If no surface is apparent... possibly obliterated by tumour.

Spindle cell morphology?

  • Consider sex cord stromal tumours.

Nests of cells?

  • Consider Brenner tumour.

Gland-like structures?

  • Endometrioid carcinoma.
  • Granulosa cell tumour.

"Dirty necrosis":

  • Definition: cellular debris within gland lumen.[10]
  • Characteristic of colorectal adenocarcinoma, may be absent in ovarian tumours -- limited value.[11]

Grading of ovarian cancer

  • Silverberg grading system,[12] aka universal grading system.
  • Based on pattern, cytologic atypia and mitotic rate.
  • System somewhat similar to breast grading, which can be remembered as: TNM (tubular formation, nuclear atypia, mitotic rate).

Silverberg system

  • Pattern:
    • Glandular = 1.
    • Papillary = 2.
    • Solid = 3.
  • Cytologic atypia:
    • Slight = 1.
    • Moderate = 2.
    • Marked = 3.
  • Mitoses (see note below):
    • 0-9/(0.345 x10 mm^2) = 1.
    • 10-24/(0.345 x10 mm^2) = 2.
    • >=25/(0.345 x10 mm^2) = 3.

Composite score (pattern score + cytologic score + mitotic score):

  • Grade I = 3-5.
  • Grade II = 6-7.
  • Grade III = 8-9.

Note:

  • Most resident microscopes have an eyepiece diameter of 22 mm. Thus, the approximate field diameter is 0.55 mm (22 mm/40 X = 0.55 mm), at highest magnification, and the field area is 0.23758 mm^2 (pi*(0.55/2)^2=0.23758 mm^2).
  • The number of HPFs should be adjusted if the area per field is different than 0.345 mm^2.
    • If the field diameter is 0.55 mm and the sample area is 3.45 mm^2, this is equivalent to 14.52 HPFs (3.45 mm^2 / 0.23758 mm^2 = 14.52); thus, it would be appropriate to use 15 HPFs and the cut points above.

Predictive power of Silverberg grading

Good correlation with five year survival (rounded values):[13]

  • Grade I = 90%.
  • Grade II = 65%.
  • Grade III = 40%.

Peritoneal implants

General

Applies only to:

Classification

There are two types:[14]

  1. Non-invasive implants.
    • Subdivided into:
      1. Epithelial.
      2. Desmoplastic.
  2. Invasive implants -- malignant cells within the stroma.

Notes:

  • Invasive implants are significant clinically.
  • Non-invasive implants have little clinical significance.

Microscopic

Non-invasive implant

Features (non-invasive implant epithelial-type):[15]

  • Papillary proliferation on surface.
  • +/-Smooth contoured invagination into:
    • Submesothelium.
    • Omental fat lobules.
  • No "stromal response":
    • Fibrosis.
  • +/-Psammoma bodies.

Features (non-invasive implant desmoplastic-type):[15]

  • Stromal reaction restricted to the:
    • Serosal surface.
    • Fibrous septae.
  • +/-Psammoma bodies.

Note:

  • No "destructive invasion".
    • Irregular infiltration.

Invasive implant

Features (invasive implant):[15]

  • Irregular infiltration of tumour into the submesothelial tissue - key feature - characterized by:
    • +/-Solid nests.
    • +/-Small glands +/- irregular "bridging" connections between glands - common.
  • Nuclear atypia - common.
  • +/-Psammoma bodies.

Stains

  • Elastin stain:[14]
    • Non-invasive implants are sit superficial to the peritoneal elastic lamina (PEL).
    • Invasive implants are deep to the PEL.

Note:

  • Elastin layer is not present in the omentum.

IHC

  • Elastin stain.

Staging of ovarian cancer

  • The CAP protocol talks of in the pelvis and outside the pelvis - pT2 versus pT3.
  • Omental involvement is considered outside the pelvis; it is pT3.[16]

Surface epithelial tumours

Most common subtypes - in short:[17]

  • Serous:
  • Endometrioid:
    • Tubular glands.
    • Squamous differentiation (eosinophilic cytoplasm, well-defined cell borders, +/-keratin).
  • Mucinous:
    • Tall columnar cells with mucin.
    • Glands with mucin.

Where to start when considering a malignant (epithelial) tumour of the ovary:

Features Serous Endometrioid Mucinous
Histology low grade: cilia, columnar cells, psammoma bodies, papillary arch.; high grade: marked nuclear pleomorphism, prominent red nucleoli, psammoma bodies gland forming - esp. cribriforming, endometrium-like mucinous glands, colon-like
Differentiators cilia, psammoma bodies squamous metaplasia mucin, often lack of necrosis
Associations atrophy endometriosis, endometrial hyperplasia (?)
Typical age usually 60s+ 40-60 varies (?)
Grade typically high grade typically low grade often low
IHC p53 +ve (diffuse), WT-1 +ve, CA-125 +ve, D2-40 +ve WT-1 -ve CK7 +ve, CK20 +ve (other tumours CK7 +ve, CK20 -ve)
Main DDx poorly diff. endometrioid serous metastatic tumour (usually GI)

Serous tumours - overview

General

  • Most common malignant ovarian tumour.

Classification

Based on features predictive of behaviour:[18]

  • Benign.
  • Borderline.
    • May have pseudostratification of epithelial cells.
    • "Usually, borderline if first impression is borderline."[19]
  • Malignant.
    • Cytologic atypia.
    • +/-Papillae.

Microscopic

Features:[18]

Note:

  • In serous borderline tumours, micropapillae are thought to have significance -- assoc. with increased risk of distant recurrence[20][21][22] - though is disputed.[23]
  • Psammoma bodies may be seen in endosalpingiosis.[24]

Serous carcinoma of the ovary

Main article: Serous carcinoma of the ovary

Serous cystadenoma of the ovary

  • AKA ovarian serous cystadenoma.
  • Related to adenofibroma and serous cystadenofibroma.
Main article: Serous cystadenoma of the ovary

Ovarian serous borderline tumour

  • AKA serous borderline tumour of the ovary.
  • AKA serous tumour of low malignant potential of the ovary, abbreviated SLMP.[25][26]
Main article: Serous borderline tumour

Mucinous ovarian tumours

General

  • Common.
  • Tumours may be heterogenous; benign appearing epithelium may be beside clearly malignant epithelium.
  • Good sampling of mucinous tumours, i.e. many blocks, is important to lessen the chance of undercalling them.

Subtypes

  1. Endocervical type.
    • Less likely to be malignant.
    • More common than malignant type.
  2. Intestinal type.
    • More likely to be malignant.
    • Goblet cells. (???)
      • One large clear apical vacuole.
    • If it doesn't look like intestine to you... it probably isn't.
    • May vaguely resemble colorectal adenocarcinoma (hyperchromatic, columnar nuclei, nuclear pleomorphism).

Comparison of mucosa:

Classification

  • Benign. (Dx: mucinous cystadenoma or mucinous adenofibroma or mucinous cystadenofibroma)
    • Single layer of cells.
  • Borderline. (Dx: mucinous tumour of uncertain malignant potential or borderline mucinous tumour)
    • Papillae.
  • Malignant. (Dx: mucinous adenocarcinoma)
    • Usually intestinal subtype.

Seromucinous borderline tumour of the ovary

  • AKA endocervical-type mucinous and mixed cell-type tumour.[27]

General

Gross

  • Mucin-filled cysts.

Image:

Microscopic

Features:

  1. Simple mucinous epithelium - endocervical type.[28]
    • Tall columnar epithelium with apical pale cytoplasm.
  2. Simple serous epithelium - with cilia.

Mucinous cystadenoma of the ovary

  • AKA ovarian mucinous cystadenoma.
Main article: Mucinous cystadenoma of the ovary

Mucinous borderline tumour of the ovary

  • AKA ovarian mucinous borderline tumour.
  • AKA ovarian mucinous tumour of low malignant potential.[29]
Main article: Mucinous borderline tumour of the ovary

Mucinous adenocarcinoma of the ovary

  • AKA ovarian mucinous adenocarcinoma.
  • AKA ovarian mucinous carcinoma.
Main article: Mucinous adenocarcinoma of the ovary

Endometrioid carcinoma of the ovary

  • AKA endometrioid ovarian carcinoma.
  • AKA endometrioid adenocarcinoma of the ovary.
  • AKA ovarian endometrioid adenocarcinoma.
Main article: Endometrioid carcinoma of the ovary

Clear cell carcinoma of the ovary

  • AKA ovarian clear cell adenocarcinoma, abbreviated OCCC.
  • AKA ovarian clear cell carcinoma.
  • AKA clear cell adenocarcinoma of the ovary.
Main article: Clear cell carcinoma of the ovary

Transitional cell carcinoma of the ovary

Main article: Transitional cell carcinoma of the ovary

Brenner tumour

Main article: Brenner tumour

Germ cell tumours

Main article: Germ cell tumours

These tumour are relatively uncommon, though are the most common grouping for young women.

Overview

  • Dysgerminoma (most common).
  • 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).

Mnemonic: SEE CT, S=Seminoma, Embryonal carcinoma, Endodermal Sinus Tumour, Choriocarcinoma, Teratoma.

Teratoma

Main article: Teratoma
  • May be benign or malignant.
  • Skin component only called "dermoid".

Dysgerminoma

General

Epidemiology:

  • Most common GCT in females.
  • Prognosis usually good.

Microscopic

Features:

  • Fried egg appearance (clear cytoplasm, central nucleus).
  • Nuclear membrane has "corners", i.e. is "squared-off" - or "polygonal".
  • +/- Lymphocytes - often prominent.
  • +/- Granulomata.

Dysgerminoma vs lymphoma:

  • Dysgerminoma has "squared-off" nuclei,[31] i.e. the nuclei look are polygonal-shaped.

Gonadoblastoma

Main article: Gonadoblastoma

Details dealt with in the main article.

Microscopic

Features:[32][33]

  • Immature germ cells resembling Sertoli cells or granulosa cells.
    • Cells with moderate cytoplasm is a trabecular or tubular architecture.
  • Primitive germ cells resemble those of a dysgerminoma.
    • Polygonal cells with a central nucleus, squared-off nuclear membrane and clear cytoplasm.
  • +/-Calcification (very common).

Metastatic ovarian tumours

Main article: Ovarian metastasis

Sex cord stromal tumours

General

  • Most are unilateral.[34]

IHC

  • Most are positive for alpha-inhibin.[34]
  • Most are positive for calretinin -- considered more sensitive than alpha-inhibin.[35]
  • Melan A +ve.
  • CD99 +ve.

Memory device MAC = melan A, alpha-inhibin, calretinin.

Sex cord tumour with annular tubules

  • Abbreviated SCTAT.
  • NOT sex cord tumour with angulated tubules.
Main article: Sex cord tumour with annular tubules

Juvenile granulosa cell tumour

Main article: Juvenile granulosa cell tumour

Adult granulosa cell tumour

Main article: Adult granulosa cell tumour

Fibroma-thecoma group

  • Some say fibromas and thecomas are related,[36] while others believe they should be considered distinct entities.[37]
  • A combination of a fibroma and a thecoma is known as a fibrothecoma.

Note:

  • Some discourage the use of the term fibrothecoma and sugguest calling tumours in the fibroma-thecoma group fibroma unless there are lipid-laden cells and more than minimal alpha-inhibin positivity.[34]

Ovarian fibroma

Main article: Ovarian fibroma

Thecoma

Main article: Thecoma

Sertoli-Leydig cell tumour

  • AKA androblastoma.
Main article: Sertoli-Leydig cell tumour

Hilus cell tumour

Main article: Leydig cell tumour

General

  • Rare.[38]
  • May cause virilization.
    • Development of male (sexual) characteristics in a female.
  • Arise from hilus cells.

Microscopic

Features - see Leydig cell tumour:

  • Moderate eosinophilic cytoplasm.
  • +/-Reinke crystalloids (cytoplasmic inclusions).

DDx:

Benign

See also

References

  1. ↑ Hirst, JE.; Gard, GB.; McIllroy, K.; Nevell, D.; Field, M. (Jul 2009). "High rates of occult fallopian tube cancer diagnosed at prophylactic bilateral salpingo-oophorectomy.". Int J Gynecol Cancer 19 (5): 826-9. doi:10.1111/IGC.0b013e3181a1b5dc. PMID 19574767.
  2. ↑ 2.0 2.1 URL: http://www.sign.ac.uk/guidelines/fulltext/75/section3.html. Accessed on: 16 September 2011.
  3. ↑ 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. pp. 1093. ISBN 0-7216-0187-1.
  4. ↑ LAE. 22 October 2009.
  5. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 401. ISBN 978-0781765275.
  6. ↑ Takeuchi, T.; Ohishi, Y.; Imamura, H.; Aman, M.; Shida, K.; Kobayashi, H.; Kato, K.; Oda, Y. (Jul 2013). "Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma.". Am J Surg Pathol 37 (7): 1091-9. doi:10.1097/PAS.0b013e3182834d41. PMID 23681072.
  7. ↑ Ali, RH.; Seidman, JD.; Luk, M.; Kalloger, S.; Gilks, CB. (Nov 2012). "Transitional cell carcinoma of the ovary is related to high-grade serous carcinoma and is distinct from malignant brenner tumor.". Int J Gynecol Pathol 31 (6): 499-506. doi:10.1097/PGP.0b013e31824d7445. PMID 23018212.
  8. ↑ LAE. 22 October 2009.
  9. ↑ NEED REF.
  10. ↑ http://www.cancer.gov/cancertopics/genetics-terms-alphalist/all#D. Accessed on: 14 September 2011.
  11. ↑ DeCostanzo DC, Elias JM, Chumas JC (July 1997). "Necrosis in 84 ovarian carcinomas: a morphologic study of primary versus metastatic colonic carcinoma with a selective immunohistochemical analysis of cytokeratin subtypes and carcinoembryonic antigen". Int. J. Gynecol. Pathol. 16 (3): 245–9. PMID 9421090.
  12. ↑ Silverberg SG (January 2000). "Histopathologic grading of ovarian carcinoma: a review and proposal". Int. J. Gynecol. Pathol. 19 (1): 7-15. PMID 10638449. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-1691&volume=19&issue=1&spage=7.
  13. ↑ Sato Y, Shimamoto T, Amada S, Asada Y, Hayashi T (January 2003). "Prognostic value of histologic grading of ovarian carcinomas". Int. J. Gynecol. Pathol. 22 (1): 52-6. PMID 12496698. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0277-1691&volume=22&issue=1&spage=52.
  14. ↑ 14.0 14.1 Stewart, CJ.; Brennan, BA.; Crook, ML.; Russell, P. (Sep 2007). "Value of elastin staining in the assessment of peritoneal implants associated with ovarian serous borderline tumours.". Histopathology 51 (3): 313-21. doi:10.1111/j.1365-2559.2007.02789.x. PMID 17727474.
  15. ↑ 15.0 15.1 15.2 Bell, DA.; Weinstock, MA.; Scully, RE. (Nov 1988). "Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis.". Cancer 62 (10): 2212-22. PMID 3179935.
  16. ↑ URL: http://ovariancancer.about.com/od/testsdiagnosis/a/FIGO_stages.htm. Accessed on: 8 July 2013.
  17. ↑ 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. pp. 1096-7. ISBN 0-7216-0187-1.
  18. ↑ 18.0 18.1 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. pp. 1096. ISBN 0-7216-0187-1.
  19. ↑ LAE. 19 February 2009.
  20. ↑ LAE. 19 February 2009.
  21. ↑ URL: http://www.ncbi.nlm.nih.gov/pubmed/15897738. Accessed on: 7 April 2011.
  22. ↑ Piura B, Rabinovich A, Yanai-Inbar I (2000). "Micropapillary serous carcinoma of the ovary: case report and review of literature". Eur. J. Gynaecol. Oncol. 21 (4): 374–6. PMID 11055486.
  23. ↑ Prat J, De Nictolis M (September 2002). "Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion". Am. J. Surg. Pathol. 26 (9): 1111-28. PMID 12218568. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=26&issue=9&spage=1111.
  24. ↑ Hallman KB, Nahhas WA, Connelly PJ (September 1991). "Endosalpingiosis as a source of psammoma bodies in a Papanicolaou smear. A case report". J Reprod Med 36 (9): 675–8. PMID 1774734.
  25. ↑ Seidman, JD.; Kurman, RJ. (May 2000). "Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators.". Hum Pathol 31 (5): 539-57. PMID 10836293.
  26. ↑ Dietel, M.; Hauptmann, S. (May 2000). "Serous tumors of low malignant potential of the ovary. 1. Diagnostic pathology.". Virchows Arch 436 (5): 403-12. PMID 10881733.
  27. ↑ Shappell, HW.; Riopel, MA.; Smith Sehdev, AE.; Ronnett, BM.; Kurman, RJ. (Dec 2002). "Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas.". Am J Surg Pathol 26 (12): 1529-41. PMID 12459620.
  28. ↑ Shappell, HW.; Riopel, MA.; Smith Sehdev, AE.; Ronnett, BM.; Kurman, RJ. (Dec 2002). "Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas.". Am J Surg Pathol 26 (12): 1529-41. PMID 12459620.
  29. ↑ Khunamornpong, S.; Settakorn, J.; Sukpan, K.; Suprasert, P.; Siriaunkgul, S. (May 2011). "Mucinous tumor of low malignant potential (borderline or atypical proliferative tumor) of the ovary: a study of 171 cases with the assessment of intraepithelial carcinoma and microinvasion.". Int J Gynecol Pathol 30 (3): 218-30. doi:10.1097/PGP.0b013e3181fcf01a. PMID 21464732.
  30. ↑ 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. pp. 1101. ISBN 0-7216-0187-1.
  31. ↑ Baker P, Oliva E (July 2008). "A practical approach to intraoperative consultation in gynecological pathology". Int. J. Gynecol. Pathol. 27 (3): 353?65. doi:10.1097/PGP.0b013e31815c24fe. PMID 18580313.
  32. ↑ 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. pp. 1104. ISBN 0-7216-0187-1.
  33. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970245-5. Accessed on: 8 April 2011.
  34. ↑ 34.0 34.1 34.2 Roth LM (July 2006). "Recent advances in the pathology and classification of ovarian sex cord-stromal tumors". Int. J. Gynecol. Pathol. 25 (3): 199–215. doi:10.1097/01.pgp.0000192271.22289.e6. PMID 16810055.
  35. ↑ Movahedi-Lankarani, S.; Kurman, RJ. (Nov 2002). "Calretinin, a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases.". Am J Surg Pathol 26 (11): 1477-83. PMID 12409724.
  36. ↑ http://www.pathologyoutlines.com/ovarytumor.html#fibroma
  37. ↑ Nocito AL, Sarancone S, Bacchi C, Tellez T (February 2008). "Ovarian thecoma: clinicopathological analysis of 50 cases". Ann Diagn Pathol 12 (1): 12–6. doi:10.1016/j.anndiagpath.2007.01.011. PMID 18164409.
  38. ↑ 38.0 38.1 Zafrakas, M.; Venizelos, ID.; Theodoridis, TD.; Zepiridis, L.; Agorastos, T.; Bontis, JN. (2009). "Virilizing ovarian hilus (Leydig) cell tumor with concurrent contralateral hilus cell hyperplasia: a rare diagnosis.". Eur J Gynaecol Oncol 30 (3): 338-40. PMID 19697637.
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