Difference between revisions of "Sertoli-Leydig cell tumour"

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'''Sertoli-Leydig cell tumour''', also '''Sertoli-Leydig tumour''', is a rare tumour of the gonad in the sex cord stromal group of tumours.
'''Sertoli-Leydig cell tumour''', also '''Sertoli-Leydig tumour''', is a rare tumour of the gonad in the [[Sex cord-stromal tumours|sex cord-stromal group of tumours]].


==General==
==General==
*Sertoli and leydig cells are normal in the [[testis]].
*Sertoli and leydig cells are normal in the [[testis]].
*Poorly differentiated tumours have sarcomatous features.<ref name=Ref_PBoD1103>{{Ref PBoD|1103}}</ref>
**Tumor was called androblastoma or arrhenoblastoma in the past
*May present with masculinization (virilization).<ref name=pmid23173550>{{Cite journal  | last1 = Xiao | first1 = H. | last2 = Li | first2 = B. | last3 = Zuo | first3 = J. | last4 = Feng | first4 = X. | last5 = Li | first5 = X. | last6 = Zhang | first6 = R. | last7 = Wu | first7 = L. | title = Ovarian Sertoli-Leydig cell tumor: a report of seven cases and a review of the literature. | journal = Gynecol Endocrinol | volume = 29 | issue = 3 | pages = 192-5 | month = Mar | year = 2013 | doi = 10.3109/09513590.2012.738723 | PMID = 23173550 }}</ref>
*May present with masculinization (virilization).<ref name=pmid23173550>{{Cite journal  | last1 = Xiao | first1 = H. | last2 = Li | first2 = B. | last3 = Zuo | first3 = J. | last4 = Feng | first4 = X. | last5 = Li | first5 = X. | last6 = Zhang | first6 = R. | last7 = Wu | first7 = L. | title = Ovarian Sertoli-Leydig cell tumor: a report of seven cases and a review of the literature. | journal = Gynecol Endocrinol | volume = 29 | issue = 3 | pages = 192-5 | month = Mar | year = 2013 | doi = 10.3109/09513590.2012.738723 | PMID = 23173550 }}</ref>
*May present as abdominal swelling or pain.
*Generally a tumor of younger women and can present in children.<ref>{{Cite journal  | last1 = Young | first1 = RH. | last2 = Scully | first2 = RE. | title = Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases. | journal = Am J Surg Pathol | volume = 9 | issue = 8 | pages = 543-69 | month = Aug | year = 1985 | doi =  | PMID = 3911780 }}</ref>
**75% younger than 30 years of age
**10% over 50 years of age.
*[[DICER1 mutation]] common in moderately and poorly differentiated Sertoli-Leydig cell tumours.<ref name=pmid28654427>{{Cite journal  | last1 = de Kock | first1 = L. | last2 = Terzic | first2 = T. | last3 = McCluggage | first3 = WG. | last4 = Stewart | first4 = CJR. | last5 = Shaw | first5 = P. | last6 = Foulkes | first6 = WD. | last7 = Clarke | first7 = BA. | title = DICER1 Mutations Are Consistently Present in Moderately and Poorly Differentiated Sertoli-Leydig Cell Tumors. | journal = Am J Surg Pathol | volume = 41 | issue = 9 | pages = 1178-1187 | month = Sep | year = 2017 | doi = 10.1097/PAS.0000000000000895 | PMID = 28654427 }}</ref>


==Microscopic==
==Microscopic==
Features:
Features:
# Sertoli ''or'' Leydig cells.<ref name=Ref_PBoD1103>{{Ref PBoD|1103}}</ref>  
* Sertoli ''or'' Leydig cells.<ref name=Ref_PBoD1103>{{Ref PBoD|1103}}</ref>  
#* Leydig cells:
** Leydig cells:
#** Abundant solid eosinophilic cytoplasm.
***Polygonal pink cells
#** Round nuclei with fine chromatin and a small or indistinct [[nucleolus]].
*** Abundant solid or somewhat granular eosinophilic cytoplasm.
#** Often in small clusters ~ 5-25 cells/cluster.
*** Round nuclei with fine chromatin and a small or indistinct [[nucleolus]].
#* Sertoli cells:
*** Often in small clusters ~ 5-25 cells/cluster.
#** Pale/clear vacuolated cytoplasm.
** Sertoli cells:
#** Irregular nuclei with irregular/vacuolated-appearing chromatin.
*** Pale/clear vacuolated cytoplasm.
#** Architecture: tubules, cords or sheets.
*** Irregular nuclei with irregular/vacuolated-appearing chromatin.
# Stroma.  
*** Architecture: tubules, cords or sheets.
# +/- Sarcomatous features (mucinous glands, bone, cartilage).
****Classic Sertoli tubule shows an 'antipodal arrangement of nuclei'
*****Nuclei sit near the basement membrane away from the tubule lumen.
*****A fair bit of cytoplasm sits above the nucleus.
*****Lumen is round.
***Mitotic activity may be much lower than expected for the degree of atypia (in comparison to adenocarcinoma).
**Stroma
***Varies from fibrous pink stroma in well differentiated tumors to cellular primative stroma in poorly differentiated tumors.
***+/-Stromal edema may be prominent
 
*Growth Patterns:
**Well-differentiated.
***Hollow or solid tubules of mature Sertoli cells with Leydig cells in the intervening stroma.
**Intermediate (most common).
***Jumbled admixture of dark blue Sertoli cells and Leydig cells.
***Lobules comprising sheets of Sertoli cells.
***Some areas of tubules.
**Poorly differentiated.
***Masses of malignant spindle cells – sheets of cells can be reminiscent of fibrosarcoma or granulosa cell tumour.
***Tubules may be a very minor element.
***Poorly differentiated tumours have sarcomatous features.<ref name=Ref_PBoD1103>{{Ref PBoD|1103}}</ref>
**Retiform.<ref>{{Cite journal  | last1 = Young | first1 = RH. | last2 = Scully | first2 = RE. | title = Ovarian Sertoli-Leydig cell tumors with a retiform pattern: a problem in histopathologic diagnosis. A report of 25 cases. | journal = Am J Surg Pathol | volume = 7 | issue = 8 | pages = 755-71 | month = Dec | year = 1983 | doi =  | PMID = 6660351 }}</ref>
***Tumour resembles rete testis/ovary with an irregular network of elongated slit-like tubules and cysts, which may contain papillae.
**With heterologous element.
***Mucinous intestinal-type epithelium, cartilage, skeletal muscle.
***Heterologous elements can occur in retiform or poorly differentiated tumours.
***+/-Sarcomatous features (mucinous glands, bone, cartilage).
 


DDx:
DDx:
*[[Endometrioid carcinoma of the ovary]].
*[[Endometrioid carcinoma of the ovary]] (sertoliform variant)
*Luteinized [[adult granulosa cell tumour]] - super rare, 50% of cell with eosinophilic cytoplasm, other findings of granulosa cell tumour, e.g. Call-Exner bodies.<ref name=pmid21804396>{{Cite journal  | last1 = Ganesan | first1 = R. | last2 = Hirschowitz | first2 = L. | last3 = Baltrušaitytė | first3 = I. | last4 = McCluggage | first4 = WG. | title = Luteinized adult granulosa cell tumor--a series of 9 cases: revisiting a rare variant of adult granulosa cell tumor. | journal = Int J Gynecol Pathol | volume = 30 | issue = 5 | pages = 452-9 | month = Sep | year = 2011 | doi = 10.1097/PGP.0b013e318214b17f | PMID = 21804396 }}</ref>
**Should be positive for EMA, CK7 and negative for inhibin and calretinin.<ref>{{Cite journal  | last1 = McCluggage | first1 = WG. | last2 = Young | first2 = RH. | title = Ovarian sertoli-leydig cell tumors with pseudoendometrioid tubules (pseudoendometrioid sertoli-leydig cell tumors). | journal = Am J Surg Pathol | volume = 31 | issue = 4 | pages = 592-7 | month = Apr | year = 2007 | doi = 10.1097/01.pas.0000213365.56498.72 | PMID = 17414107 }}</ref>
**Should have some characteristic areas of endometriod carcinoma and may have some typical features
***Cilia, squamous metaplasia, mucin production
*Luteinized [[adult granulosa cell tumour]] - super rare, 50% of cell with eosinophilic cytoplasm, other findings of granulosa cell tumour, e.g. Call-Exner bodies. More likely to be keratin negative than a Sertoli-Leydig cell tumor. <ref name=pmid21804396>{{Cite journal  | last1 = Ganesan | first1 = R. | last2 = Hirschowitz | first2 = L. | last3 = Baltrušaitytė | first3 = I. | last4 = McCluggage | first4 = WG. | title = Luteinized adult granulosa cell tumor--a series of 9 cases: revisiting a rare variant of adult granulosa cell tumor. | journal = Int J Gynecol Pathol | volume = 30 | issue = 5 | pages = 452-9 | month = Sep | year = 2011 | doi = 10.1097/PGP.0b013e318214b17f | PMID = 21804396 }}</ref>
*Ovarian carcinosarcoma - especially considering poorly differentiated versions with heterologous areas.


Retiform variant
*Ovarian serous carcinoma - generally carcinoma patients are older.
*Ovarian yolk sac tumor
===Images===
===Images===
<gallery>
<gallery>
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Image:Sertoli-Leydig_cell_tumour_-_high_mag.jpg | Sertoli-Leydig cell tumour - high mag. (WC)
Image:Sertoli-Leydig_cell_tumour_-_high_mag.jpg | Sertoli-Leydig cell tumour - high mag. (WC)
Image:Sertoli-Leydig_cell_tumour_-_very_high_mag.jpg | Sertoli-Leydig cell tumour - very high mag. (WC)
Image:Sertoli-Leydig_cell_tumour_-_very_high_mag.jpg | Sertoli-Leydig cell tumour - very high mag. (WC)
Image:Ovary SertoliLeydigCellTumor 4 PA.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated - low power (SKB)
Image:Ovary SertoliLeydigCellTumor 5 PA.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated - low power (SKB)
Image:Ovary SertoliLeydigCellTumor 7 PA.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated - medium power (SKB)
Image:Ovary SertoliLeydigCellTumor 6 PA.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated (SKB)
Image:Ovary SertoliLeydigCellTumor.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated (SKB)
Image:Ovary SertoliLeydigCellTumor 3 PA.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated - see how much cytoplasm is between the nucleus and the lumen?  See the crisp outline of the lumen by the apical membrane of the cells - this is a typical Leydig tubule. (SKB)
Image:Ovary SertoliLeydigCellTumor PA.jpg|Ovarian Sertoli Leydig Cell Tumor - Well differentiated (SKB)
Image:Ovary SertoliLeydigCellTumor MP2 CTR.jpg|Ovarian Sertoli Leydig Cell Tumor - medium power - This example is somewhat between the previous well differentiated and following intermediate differentiated examples (SKB)
Image:Ovary SertoliLeydigCellTumor MP3 CTR.jpg|Ovarian Sertoli Leydig Cell Tumor - medium power (SKB)
Image:Ovary SertoliLeydigCellTumor MP CTR.jpg|Ovarian Sertoli Leydig Cell Tumor - medium power (SKB)
Image:Ovary SertoliLeydig Intermediate MP CTR.jpg|Ovarian Sertoli-Leydig Cell Tumor - Intermediate differentiation - Medium power (SKB)
Image:Ovary SertoliLeydig Intermediate HP CTR.jpg|Ovarian Sertoli-Leydig Cell Tumor - Intermediate differentiation - High power (SKB)
Image:Ovary SertoliLeydig Intermediate HP2 CTR.jpg|Ovarian Sertoli-Leydig Cell Tumor - Intermediate differentiation - High power (SKB)
</gallery>
</gallery>
www:
www:
*[http://path.upmc.edu/cases/case270/micro.html Sex cord stromal tumour with Sertoli-Leydig component - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case270/micro.html Sex cord stromal tumour with Sertoli-Leydig component - several images (upmc.edu)].
==Prognosis==
*Dependant on degree of differentiation and stage at presentation.<ref>{{Cite journal  | last1 = Young | first1 = RH. | last2 = Scully | first2 = RE. | title = Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases. | journal = Am J Surg Pathol | volume = 9 | issue = 8 | pages = 543-69 | month = Aug | year = 1985 | doi =  | PMID = 3911780 }}</ref>
*Heterologous mesenchymal elements may portend a worse outcome.<ref>{{Cite journal  | last1 = Zaloudek | first1 = C. | last2 = Norris | first2 = HJ. | title = Sertoli-Leydig tumors of the ovary. A clinicopathologic study of 64 intermediate and poorly differentiated neoplasms. | journal = Am J Surg Pathol | volume = 8 | issue = 6 | pages = 405-18 | month = Jun | year = 1984 | doi =  | PMID = 6731664 }}</ref>


==IHC==
==IHC==
Features:<ref name=pmid19033865>{{Cite journal  | last1 = Zhao | first1 = C. | last2 = Vinh | first2 = TN. | last3 = McManus | first3 = K. | last4 = Dabbs | first4 = D. | last5 = Barner | first5 = R. | last6 = Vang | first6 = R. | title = Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. | journal = Am J Surg Pathol | volume = 33 | issue = 3 | pages = 354-66 | month = Mar | year = 2009 | doi = 10.1097/PAS.0b013e318188373d | PMID = 19033865 }}</ref>
Features:<ref name=pmid19033865>{{Cite journal  | last1 = Zhao | first1 = C. | last2 = Vinh | first2 = TN. | last3 = McManus | first3 = K. | last4 = Dabbs | first4 = D. | last5 = Barner | first5 = R. | last6 = Vang | first6 = R. | title = Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. | journal = Am J Surg Pathol | volume = 33 | issue = 3 | pages = 354-66 | month = Mar | year = 2009 | doi = 10.1097/PAS.0b013e318188373d | PMID = 19033865 }}</ref>
*'''Inhibin''' +ve
*'''Calretinin''' +ve.
*WT-1 +ve.  
*WT-1 +ve.  
*Melan A (MART-1) +ve - marks the Leydig component.
*Melan A (MART-1) +ve - marks the Leydig component.
*Vimentin +ve.<ref name=pmid20349790>{{Cite journal  | last1 = Kondi-Pafiti | first1 = A. | last2 = Grapsa | first2 = D. | last3 = Kairi-Vassilatou | first3 = E. | last4 = Carvounis | first4 = E. | last5 = Hasiakos | first5 = D. | last6 = Kontogianni | first6 = K. | last7 = Fotiou | first7 = S. | title = Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases. | journal = Eur J Gynaecol Oncol | volume = 31 | issue = 1 | pages = 94-8 | month =  | year = 2010 | doi =  | PMID = 20349790 }}</ref>
*Vimentin +ve.<ref name=pmid20349790>{{Cite journal  | last1 = Kondi-Pafiti | first1 = A. | last2 = Grapsa | first2 = D. | last3 = Kairi-Vassilatou | first3 = E. | last4 = Carvounis | first4 = E. | last5 = Hasiakos | first5 = D. | last6 = Kontogianni | first6 = K. | last7 = Fotiou | first7 = S. | title = Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases. | journal = Eur J Gynaecol Oncol | volume = 31 | issue = 1 | pages = 94-8 | month =  | year = 2010 | doi =  | PMID = 20349790 }}</ref>
*Calretinin +ve.
*CD99 +ve.
*CD99 +ve.
*[[AE1/AE3]] and [[pankeratin]] +ve


Others:<ref name=pmid20349790/>
Others:<ref name=pmid20349790/>
*CD34 -ve.
*CD34 -ve.
*Cytokeratin -ve (usually).
*'''[[EMA]]''' -ve.
*[[CK7]] -ve.
 
Keep in mind that this is a biphasic tumor - Leydig cells will not be Pan-keratin positive - Sertoli cells do not express calretinin - Both components express inhibin - etcetera - interpreting this immunopanal requires correlation with the histomorphology.  Immunoreactivity may be focal.
 
Pan-keratins and AE1/AE3 may mark granulosa cell tumors and Sertoli cell tumors causing confusion with adenocarcinoma. EMA is a better marker to exclude an epithelial tumor as EMA is negative in sex cord-stromal tumors.  Highlighting why a panel of stains is needed, endometrioid adenocarcinomas may occasionally weakly express inhibin, calretinin or WT-1.


==See also==
==See also==

Latest revision as of 09:43, 11 September 2018

Sertoli-Leydig cell tumour, also Sertoli-Leydig tumour, is a rare tumour of the gonad in the sex cord-stromal group of tumours.

General

  • Sertoli and leydig cells are normal in the testis.
    • Tumor was called androblastoma or arrhenoblastoma in the past
  • May present with masculinization (virilization).[1]
  • May present as abdominal swelling or pain.
  • Generally a tumor of younger women and can present in children.[2]
    • 75% younger than 30 years of age
    • 10% over 50 years of age.
  • DICER1 mutation common in moderately and poorly differentiated Sertoli-Leydig cell tumours.[3]

Microscopic

Features:

  • Sertoli or Leydig cells.[4]
    • Leydig cells:
      • Polygonal pink cells
      • Abundant solid or somewhat granular 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.
        • Classic Sertoli tubule shows an 'antipodal arrangement of nuclei'
          • Nuclei sit near the basement membrane away from the tubule lumen.
          • A fair bit of cytoplasm sits above the nucleus.
          • Lumen is round.
      • Mitotic activity may be much lower than expected for the degree of atypia (in comparison to adenocarcinoma).
    • Stroma
      • Varies from fibrous pink stroma in well differentiated tumors to cellular primative stroma in poorly differentiated tumors.
      • +/-Stromal edema may be prominent
  • Growth Patterns:
    • Well-differentiated.
      • Hollow or solid tubules of mature Sertoli cells with Leydig cells in the intervening stroma.
    • Intermediate (most common).
      • Jumbled admixture of dark blue Sertoli cells and Leydig cells.
      • Lobules comprising sheets of Sertoli cells.
      • Some areas of tubules.
    • Poorly differentiated.
      • Masses of malignant spindle cells – sheets of cells can be reminiscent of fibrosarcoma or granulosa cell tumour.
      • Tubules may be a very minor element.
      • Poorly differentiated tumours have sarcomatous features.[4]
    • Retiform.[5]
      • Tumour resembles rete testis/ovary with an irregular network of elongated slit-like tubules and cysts, which may contain papillae.
    • With heterologous element.
      • Mucinous intestinal-type epithelium, cartilage, skeletal muscle.
      • Heterologous elements can occur in retiform or poorly differentiated tumours.
      • +/-Sarcomatous features (mucinous glands, bone, cartilage).


DDx:

  • Endometrioid carcinoma of the ovary (sertoliform variant)
    • Should be positive for EMA, CK7 and negative for inhibin and calretinin.[6]
    • Should have some characteristic areas of endometriod carcinoma and may have some typical features
      • Cilia, squamous metaplasia, mucin production
  • Luteinized adult granulosa cell tumour - super rare, 50% of cell with eosinophilic cytoplasm, other findings of granulosa cell tumour, e.g. Call-Exner bodies. More likely to be keratin negative than a Sertoli-Leydig cell tumor. [7]
  • Ovarian carcinosarcoma - especially considering poorly differentiated versions with heterologous areas.

Retiform variant

  • Ovarian serous carcinoma - generally carcinoma patients are older.
  • Ovarian yolk sac tumor

Images

www:

Prognosis

  • Dependant on degree of differentiation and stage at presentation.[8]
  • Heterologous mesenchymal elements may portend a worse outcome.[9]

IHC

Features:[10]

  • Inhibin +ve
  • Calretinin +ve.
  • WT-1 +ve.
  • Melan A (MART-1) +ve - marks the Leydig component.
  • Vimentin +ve.[11]
  • CD99 +ve.
  • AE1/AE3 and pankeratin +ve

Others:[11]

Keep in mind that this is a biphasic tumor - Leydig cells will not be Pan-keratin positive - Sertoli cells do not express calretinin - Both components express inhibin - etcetera - interpreting this immunopanal requires correlation with the histomorphology. Immunoreactivity may be focal.

Pan-keratins and AE1/AE3 may mark granulosa cell tumors and Sertoli cell tumors causing confusion with adenocarcinoma. EMA is a better marker to exclude an epithelial tumor as EMA is negative in sex cord-stromal tumors. Highlighting why a panel of stains is needed, endometrioid adenocarcinomas may occasionally weakly express inhibin, calretinin or WT-1.

See also

References

  1. Xiao, H.; Li, B.; Zuo, J.; Feng, X.; Li, X.; Zhang, R.; Wu, L. (Mar 2013). "Ovarian Sertoli-Leydig cell tumor: a report of seven cases and a review of the literature.". Gynecol Endocrinol 29 (3): 192-5. doi:10.3109/09513590.2012.738723. PMID 23173550.
  2. Young, RH.; Scully, RE. (Aug 1985). "Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases.". Am J Surg Pathol 9 (8): 543-69. PMID 3911780.
  3. de Kock, L.; Terzic, T.; McCluggage, WG.; Stewart, CJR.; Shaw, P.; Foulkes, WD.; Clarke, BA. (Sep 2017). "DICER1 Mutations Are Consistently Present in Moderately and Poorly Differentiated Sertoli-Leydig Cell Tumors.". Am J Surg Pathol 41 (9): 1178-1187. doi:10.1097/PAS.0000000000000895. PMID 28654427.
  4. 4.0 4.1 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. 1103. ISBN 0-7216-0187-1.
  5. Young, RH.; Scully, RE. (Dec 1983). "Ovarian Sertoli-Leydig cell tumors with a retiform pattern: a problem in histopathologic diagnosis. A report of 25 cases.". Am J Surg Pathol 7 (8): 755-71. PMID 6660351.
  6. McCluggage, WG.; Young, RH. (Apr 2007). "Ovarian sertoli-leydig cell tumors with pseudoendometrioid tubules (pseudoendometrioid sertoli-leydig cell tumors).". Am J Surg Pathol 31 (4): 592-7. doi:10.1097/01.pas.0000213365.56498.72. PMID 17414107.
  7. Ganesan, R.; Hirschowitz, L.; Baltrušaitytė, I.; McCluggage, WG. (Sep 2011). "Luteinized adult granulosa cell tumor--a series of 9 cases: revisiting a rare variant of adult granulosa cell tumor.". Int J Gynecol Pathol 30 (5): 452-9. doi:10.1097/PGP.0b013e318214b17f. PMID 21804396.
  8. Young, RH.; Scully, RE. (Aug 1985). "Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases.". Am J Surg Pathol 9 (8): 543-69. PMID 3911780.
  9. Zaloudek, C.; Norris, HJ. (Jun 1984). "Sertoli-Leydig tumors of the ovary. A clinicopathologic study of 64 intermediate and poorly differentiated neoplasms.". Am J Surg Pathol 8 (6): 405-18. PMID 6731664.
  10. Zhao, C.; Vinh, TN.; McManus, K.; Dabbs, D.; Barner, R.; Vang, R. (Mar 2009). "Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors.". Am J Surg Pathol 33 (3): 354-66. doi:10.1097/PAS.0b013e318188373d. PMID 19033865.
  11. 11.0 11.1 Kondi-Pafiti, A.; Grapsa, D.; Kairi-Vassilatou, E.; Carvounis, E.; Hasiakos, D.; Kontogianni, K.; Fotiou, S. (2010). "Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases.". Eur J Gynaecol Oncol 31 (1): 94-8. PMID 20349790.