Ovarian tumours

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The article examines ovarian tumours including ovarian cancer.

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

Classification

The Latta rule of fives

Can be divided as follows:[1][2]

  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).

Surface epithelial tumours:

  1. Serous.
  2. Endometrioid.
  3. Mucinous.
  4. Transitional cell tumours[3] (Brenner tumour).
  5. Clear cell carcinoma.

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 tumour.
  4. Choriocarcinoma.
  5. Teratoma.

Endometriosis-related tumours

Tumours associated with endometriosis:[4]

  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:[5]

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

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":

  • Def'n: Cellular debris within gland lumen.[6]
  • Characteristic of colorectal adenocarcinoma, may be absent in ovarian tumours -- limited value.[7]

Grading of ovarian cancer

  • Silverberg grading system,[8] aka universal grading system.
  • 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).

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 1:

  • 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.

Note 2:

  • 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):[9]

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

Implants

General

  • In the setting of borderline tumours there is much ado about implants.

There are two types:

  • Non-invasive implants -- look like lymphovascular invasion.
  • Invasive implants -- malignant cells within the stromal.

Notes:

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

Surface epithelial tumours

Most common subtypes - in short:[10]

  • 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:

Serous Endometrioid Mucinous
Characteristics cilia, columnar cells
psammoma bodies, papillary arch.		 gland forming, endometrium-like mucinous glands, colon-like
Differentiators cilia, psammoma bodies squamous metaplasia mucin, 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

Classification[11]

  • Benign.
  • Borderline.
    • May have pseudostratification of epithelial cells.
    • "Usually, borderline if first impression is borderline."[12]
  • Malignant.
    • Cytologic atypia.
    • Many papillae.

Microscopic

Features:[13]

  • Tubal like epithelium:
    • Ciliated.
    • Columnar.
  • Papillae.
  • Psammoma bodies (concentric calcifications).

Note:

  • In serous borderline tumours, micropapillae are thought to have significance -- assoc. with increased risk of distant recurrence[14][15][16] - though is disputed.[17]
  • Psammoma bodies may be seen in endosalpingiosis.[18]

Mucinous tumours

Gross

Features:

  • Multiloculated.
  • Sticky, gelatinous fluid (glycoprotein).

Microscopic

Features:

  • Tall columnar cells in glands.
    • Apical mucin.
    • May vaguely resemble colorectal adenocarcinoma.
  • Glands have mucin.
  • +/-Nuclear atypia.
  • NO cilia.

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

Note:

  • 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.

Endometrioid tumours of the ovary

Epidemiology

  • Associated with endometriosis, i.e. people with endometriosis are more likely to have 'em.

Histology

  • Tubular glands.
    • Cribriform pattern common.[20]
  • May see mucinous secretion.[21]
  • May have squamous differentiation/squamous metaplasia (useful for differentiating from sex-cord stromal tumours and germ cell tumours).[21] - very useful feature.

Clear cell adenocarcinoma

  • AKA clear cell carcinoma.

General

  • Thought to be related to endometrioid carcinoma.[22]
    • Increased risk of CC adenoca in people with endometriosis.
  • Worse prognosis vs. other surface epithelial tumours[23]

Microscopic

Features:

  • Cystic/tubular architecture - important low power feature.
  • Clear cells - cytoplasm is clear - key feature.
  • Hobnail morphology - apical surface larger than basal surface.[24]
    • "Nuclei bulge into the lumen".
  • Hyaline droplets -- common, as in clear cell renal cell carcinoma.
    • Eosinophilic bodies within lumen.
  • Nucleoli - prominent.

Note:

  • 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.
    • The hobnail morphology is important if this is the case.

Images:

IHC

  • HNF-1beta +ve.[25][26]
    • Usu. -ve in serous carcinoma.
  • WT-1 -ve.
    • Usu. +ve in serous carcinoma.

Panel for high grade serous vs. clear cell:[27]

  • ER, HNF-1beta, WT-1.

Transitional cell carcinoma

General

  • Rare.
  • Fits into the transistional cell tumours category - in the surface epithelial group of ovarian tumours.[3]

Microscopic

Features:

  • Resembles urothelial carcinoma:
    • Large nest of cells with moderate basophilic cytoplasm and little intervening stroma.
    • Marked nuclear pleomorphism.
    • Mitoses - common.

Brenner tumour

General

  • 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.[22]
  • "Coffee bean nucleus".
    • Elliptical shape (nucleus).
    • Nuclear grooves.[28]
  • Distinct nucleoli.[28]

Notes:

  • DDx of Coffee bean nucleus = granulosa cell tumour.

Images:

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,[30] i.e. the nuclei look are polygonal-shaped.

Gonadoblastoma

Main article: Gonadoblastoma

Details dealt with in the main article.

Microscopic

Features:[31][32]

  • 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

Generally

  • Mostly Muellerian origin (uterus, fallopian tube) or pelvic peritoneum.

Extramuellerian metastatic tumours

DDx:

Mucinous carcinoma - GI tract metastasis vs. primary ovarian

Features favouring metastatic disease:[33]

  • Bilaterality -- both ovaries involved.
  • Small unilateral tumour size -- <10 cm = metastatic.
    • >13 cm = primary ovarian.

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]

Sex cord tumour with annular tubules

  • Abbreviated SCTAT.

General

Microscopic

Features:

  • Annular tubules.

Notes:

  • Annular = shape of a ring.[37]

Images:

Granulosa cell tumour

General

Gross

  • Solid.
  • May be cystic. (???)

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.

Note:

  • There is a "10% rule" -- if less than 10% of a SCST is granulosa cells... it isn't granulosa cell tumour.

DDx:

IHC

Fibroma-thecoma group

  • Some say fibromas and thecomas are related,[39] while others believe they should be considered distinct entities.[40]
  • 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 fibrom-thecoma group fibroma unless there are lipid-laden cells and more than minimal alpha-inhibin positivity.[34]

Ovarian fibroma

General

Microscopic

Features:[43][34]

  • Spindle-shaped cells.
  • Central nuclei.
  • Stainable lipid - minimal or none.[34]

Images:

IHC

  • Inhibin -ve (~75%).[34]

Thecoma

General

  • Associated with compression & atrophy of ovarian cortex, thought to arise from medulla.[40]
  • Approx. 50% have symptoms related to estrogen secretion.[34]
    • May also be viralizing.

Microscopic

Features:[34]

  • Nuclei with oval to spindle morphology.
  • Abundant cytoplasm that is pale, vaculolated -- key feature.

Images:

IHC

  • Alpha-inhibin +ve (90%+).[34]

Sertoli-Leydig tumour

  • AKA androblastoma.

General

  • Sertoli and leydig cells are normal in the testis.

Microscopic

Features:[41]

  • Tubules with Sertoli or Leydig cells + stroma.
  • +/- Sarcomatous features (mucinous glands, bone, cartilage).

See: Sertoli cell tumour, Leydig cell tumour.

Pure Leydig cell tumour

General

  • AKA Hilus cell tumour.

Microscopy

  • Reinke crystalloids - in the cytoplasm of Leydig cells - testis article.

Benign

See also

References

  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. 1093. ISBN 0-7216-0187-1.
  2. ↑ LAE. 22 October 2009.
  3. ↑ 3.0 3.1 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.
  4. ↑ LAE. 22 October 2009.
  5. ↑ NEED REF.
  6. ↑ http://www.cancer.gov/cancertopics/genetics-terms-alphalist/all#D
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ PBoD P.1096???
  12. ↑ LAE. 19 February 2009.
  13. ↑ 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.
  14. ↑ LAE. 19 February 2009.
  15. ↑ URL: http://www.ncbi.nlm.nih.gov/pubmed/15897738. Accessed on: 7 April 2011.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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. 1097. ISBN 0-7216-0187-1.
  20. ↑ Khalifa 2008.
  21. ↑ 21.0 21.1 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.
  22. ↑ 22.0 22.1 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. 1098. ISBN 0-7216-0187-1. Cite error: Invalid <ref> tag; name "Ref_PBoD1098" defined multiple times with different content
  23. ↑ Hauptmann S, Köbel M (2005). "[Prognostic factors in ovarian carcinoma]" (in German). Verh Dtsch Ges Pathol 89: 92-100. PMID 18035678.
  24. ↑ URL: http://www.pathologyoutlines.com/ovary.html. Accessed on: 8 February 2011.
  25. ↑ Tsuchiya, A.; Sakamoto, M.; Yasuda, J.; Chuma, M.; Ohta, T.; Ohki, M.; Yasugi, T.; Taketani, Y. et al. (Dec 2003). "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.". Am J Pathol 163 (6): 2503-12. PMID 14633622. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892387/?tool=pubmed.
  26. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 189907
  27. ↑ Köbel M, Kalloger SE, Carrick J, et al. (January 2009). "A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary". Am. J. Surg. Pathol. 33 (1): 14–21. doi:10.1097/PAS.0b013e3181788546. PMID 18830127.
  28. ↑ 28.0 28.1 URL: http://www.pathologyoutlines.com/ovarytumor.html#brennergen. Accessed on: 8 February 2011.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970245-5. Accessed on: 8 April 2011.
  33. ↑ Yemelyanova, AV.; Vang, R.; Judson, K.; Wu, LS.; Ronnett, BM. (Jan 2008). "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.". Am J Surg Pathol 32 (1): 128-38. doi:10.1097/PAS.0b013e3180690d2d. PMID 18162780.
  34. ↑ 34.0 34.1 34.2 34.3 34.4 34.5 34.6 34.7 34.8 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. ↑ Purohit, RC.; Alam, SZ. (Mar 1980). "Sex cord tumour of the ovary with annular tubules (SCTAT).". Histopathology 4 (2): 147-54. PMID 7358344.
  37. ↑ URL: http://dictionary.reference.com/browse/annular. Accessed on: 6 August 2011.
  38. ↑ 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. 1102. ISBN 0-7216-0187-1.
  39. ↑ http://www.pathologyoutlines.com/ovarytumor.html#fibroma
  40. ↑ 40.0 40.1 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.
  41. ↑ 41.0 41.1 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. Cite error: Invalid <ref> tag; name "Ref_PBoD1103" defined multiple times with different content
  42. ↑ Tytle, T.; Rosin, D. (Sep 1984). "Bilateral calcified ovarian fibromas.". South Med J 77 (9): 1178-80. PMID 6385289.
  43. ↑ http://www.pathologyoutlines.com/ovarytumor.html#fibroma
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