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.

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]

Elements & points (RIM 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..
  2. Endometrioid carcinoma.
  3. Mucinous carcinoma.
  4. Transitional cell tumours[5] (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 carcinoma.
  4. Choriocarcinoma.
  5. Teratoma.

Common special tumours

Endometriosis-related tumours

Tumours associated with endometriosis:[6]

  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:[7]

  • 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.[8]
  • Characteristic of colorectal adenocarcinoma, may be absent in ovarian tumours -- limited value.[9]

Grading of ovarian cancer

  • Silverberg grading system,[10] 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):[11]

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

Peritoneal implants

General

Classification

There are two types:[12]

  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):[13]

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

Features (non-invasive implant desmoplastic-type):[13]

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

Note:

  • No "destructive invasion".
    • Irregular infiltration.

Invasive implant

Features (invasive implant):[13]

  • 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:[12]
    • 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.

Surface epithelial tumours

Most common subtypes - in short:[14]

  • 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:[15]

  • Benign.
  • Borderline.
    • May have pseudostratification of epithelial cells.
    • "Usually, borderline if first impression is borderline."[16]
  • Malignant.
    • Cytologic atypia.
    • +/-Papillae.

Microscopic

Features:[15]

  • 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[17][18][19] - though is disputed.[20]
  • Psammoma bodies may be seen in endosalpingiosis.[21]

Serous carcinoma of the ovary

General

  • Most common malignant ovarian tumour in the eldery.
  • Poor prognosis.

Microscopic

Features:

  • Marked nuclear pleomorphism:
    • Variation in size - usually marked.
    • Variation in staining.
    • Variation in shape.
  • Prominent nucleolus - key feature.
  • Eccentric nucleus.
  • Architecture:
    • Solid.
    • Papillary - classic.
    • Glandular - uncommon.
  • +/-Psammoma bodies - uncommon.
  • +/-Necrosis - often extensive.

DDx:

Images:

IHC

  • CK7 +ve.
  • WT-1 +ve.
  • CA-125 +ve.
  • ER +ve.[22]
  • p53 +ve.

Others:

Serous cystadenoma of the ovary

General

Gross

  • Usually unilocular.

Microscopic

Features:

  • Simple epithelium with cilia - key feature.
    • Cell morphology: columnar, cuboidal or flatted.

DDx:

Ovarian serous borderline tumour

  • AKA serous borderline tumour of the ovary.
  • AKA serous tumour of low malignant potential of the ovary, abbreviated SLMP.[27][28]
  • AKA serous ovarian tumour of low malignant potential.[28]

General

  • Usually benign.
  • Require long term follow-up.

Microscopic

Features:

  • Simple serous epithelium - with cilia.
  • +/-Micropapillary architecture - often described as a medusa head pattern.

DDx:

Images:

Subclassification

Typical subdivided into:[29]

  • Micropapillary serous borderline tumour.
  • Typical serous borderline tumour (SBOT).

Seromucinous borderline tumor of the ovary

  • AKA endocervical-type mucinous and mixed cell-type tumour.[30]

General

Gross

  • Mucin-filled cysts.

Image:

Microscopic

Features:

  1. Simple mucinous epithelium - endocervical type.[31]
    • Tall columnar epithelium with apical pale cytoplasm.
  2. Simple serous epithelium - with cilia.

Mucinous tumours - overview

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.

Mucinous adenocarcinoma of the ovary

  • AKA ovarian mucinous adenocarcinoma.
  • AKA ovarian mucinous carcinoma.

General

  • Malignant.
  • May arise in endometriosis.[32]
  • Poor response to chemotherapy vis-à-vis serous carcinoma.[33]

Gross

Features:

  • Multiloculated.
  • Sticky, gelatinous fluid (glycoprotein).
  • +/-Necrosis.
  • Typically unilateral.[34]

Microscopic

Features:

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:

IHC

  • CK7 +ve.
  • CK20 +ve.

Endometrioid carcinoma of the ovary

  • AKA endometrioid ovarian carcinoma.
  • AKA endometrioid adenocarcinoma of the ovary.
  • AKA ovarian endometrioid adenocarcinoma.

General

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

Gross

  • Usually solid and cystic.

Image:

Microscopic

Features:

  • Tubular glands.
    • Cribriform pattern common.
  • May see mucinous secretion.[35]
  • May have squamous differentiation/squamous metaplasia (useful for differentiating from sex-cord stromal tumours and germ cell tumours).[35] - very useful feature.

DDx:

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.

General

Prognosis:

  • Worse prognosis versus other surface epithelial tumours.[36]
    • Poor response to platinum-based chemotherapy.[34]
    • ~2.5x risk for thromboembolism compared to other ovarian carcinomas.[37]

Epidemiology:

  • Asians appear to be at an increased risk.[34]
  • Thought to be related to endometrioid carcinoma.[38]
  • Association with endometriosis:[34]
    • Increased risk of ovarian clear cell carcinoma ~ 3x.
    • Seen in 50-70% of ovarian CCC.

Gross

Features:[34]

Microscopic

Features:

  • Cystic/tubular architecture - important low power feature.
    • May be papillary and/or solid.
  • Clear cells - cytoplasm is clear - key feature. †
  • Hobnail morphology - apical surface larger than basal surface.
    • "Nuclei bulge into the lumen".
  • Hyaline droplets -- common, as in clear cell renal cell carcinoma.
    • Eosinophilic bodies within lumen.
    • Seen in approximately 1/4 of cases.[34]
  • 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 -- see no truth in names.
    • The hobnail morphology is important if this is the case.

DDx:

Images:

IHC

  • HNF-1beta +ve.[39][24]
    • Usu. -ve in serous carcinoma.
  • WT-1 -ve.
    • Usu. +ve in serous carcinoma.

Panel for high grade serous vs. clear cell:[40]

  • ER (+ve in serous),[22] HNF-1beta (+ve in clear cell), WT-1 (+ve in serous).

Others:[34]

Transitional cell carcinoma of the ovary

General

  • Rare.
  • Fits into the transistional cell tumours category - in the surface epithelial group of ovarian tumours.[5]

Microscopic

Features:[41]

  • 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:

  1. Resembles urothelial carcinoma.[42]
  2. No Brenner tumour component (benign or malignant) should be present.[42]

Images:

IHC

Features:[42]

  1. Vimentin +ve,
  2. CA-125 +ve.
  3. WT1 +ve.
  4. CK20 -ve.
  5. Thrombomodulin -ve.
  6. Uroplakin III -ve.

Notes:

  • 1-6 usu. opposite pattern in urothelial cell carcinoma.

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.
  • May be malignant.

Gross

Features:[43]

  • Classically solid, well-circumscribed, light yellow.
  • May be cystic.

Note:

  • Borderline tumours classically solid and cystic with papillary projections into the cystic component.[43]

Microscopic

Features:

  • Nests of transitional epithelium with cells that have:[38]
    • A "coffee bean nucleus".
      • Elliptical shape (nucleus).
      • Nuclear grooves.[44]
      • Distinct nucleoli.
    • Moderate-to-abundant gray/pale cytoplasm.
  • Dense fibrous stroma around nests.

Notes:

DDx:

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

Gonadoblastoma

Main article: Gonadoblastoma

Details dealt with in the main article.

Microscopic

Features:[47][48]

  • 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: Metastases

Generally

Extramuellerian metastatic tumours

DDx:

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

Gross

Features favouring metastatic disease:[49]

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

IHC

Ovarian tumours:

  • Dipeptidase 1 (DPEP1) +ve.[50]
  • CK7 +ve.

Sex cord stromal tumours

General

  • Most are unilateral.[51]

IHC

  • Most are positive for alpha-inhibin.[51]
  • Most are positive for calretinin -- considered more sensitive than alpha-inhibin.[52]
  • 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.

General

  • Associated with Peutz-Jeghers syndrome.[53]
    • Large tumours more likely sporadic.
    • Small tumours more likely Peutz-Jeghers syndrome and incidental.
  • Usually benign.
    • Malignant cases reported.[54]

Microscopic

Features:

  • Well-circumscribed nests of cells with nuclei at the periphery.
  • Annular tubules (ring-shaped tubules) with dense hyaline material.

Notes:

DDx:

Images:

Juvenile granulosa cell tumour

General

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:

IHC

Molecular

Currently not used for the diagnosis.

Adult granulosa cell tumour

General

Note:

  • Normal granulosa cells convert androgen from the theca cells to estrogen and/or progesterone.[63]

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:

IHC

Molecular

Currently not used for diagnosis.
  • FOXL2 point mutation[64] seen in 86 of 89 tumours.[65]

Fibroma-thecoma group

  • Some say fibromas and thecomas are related,[66] while others believe they should be considered distinct entities.[67]
  • 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.[51]

Ovarian fibroma

General

Gross

Features:

  • Solid white mass, usu. well-circumscribed.[71]

Note:

  • Thecoma = yellow solid mass.[71]

Images:

Microscopic

Features:[72][51]

  • Spindle-shaped cells.
  • Central nuclei.
  • Stainable lipid - minimal or none.[51]

Images:

IHC

  • Inhibin -ve (~75%).[51]

Thecoma

General

  • Associated with compression & atrophy of ovarian cortex, thought to arise from medulla.[67]
  • Approx. 50% have symptoms related to estrogen secretion.[51]
    • May also be viralizing.

Gross

Features:

  • Solid yellow mass, usu. well-circumscribed.[71]

DDx:

Microscopic

Features:[51]

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

Images:

IHC

  • Alpha-inhibin +ve (90%+).[51]

Sertoli-Leydig cell tumour

  • AKA androblastoma.

General

  • Sertoli and leydig cells are normal in the testis.
  • Poorly differentiated tumours have sarcomatous features.[68]

Microscopic

Features:

  1. Sertoli or Leydig cells.[68]
    • Leydig cells:
      • 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.
  2. Stroma.
  3. +/- Sarcomatous features (mucinous glands, bone, cartilage).

DDx:

  • Endometrioid carcinoma of the ovary.
  • Luteinized adult granulosa cell tumour - super rare, 50% of cell with eosinophilic cytoplasm, other findings of granulosa cell tumour, e.g. Call-Exner bodies.[73]

Images:

IHC

Features:[74]

  • WT-1 +ve.
  • Melan A (MART-1) +ve - marks the Leydig component.
  • Vimentin +ve.[75]
  • Calretinin +ve.
  • CD99 +ve.

Others:[75]

  • CD34 -ve.
  • Cytokeratin -ve (usually).

Hilus cell tumour

Main article: Leydig cell tumour

General

  • Rare.[76]
  • 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. ↑ 5.0 5.1 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.
  6. ↑ LAE. 22 October 2009.
  7. ↑ NEED REF.
  8. ↑ http://www.cancer.gov/cancertopics/genetics-terms-alphalist/all#D. Accessed on: 14 September 2011.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 12.0 12.1 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.
  13. ↑ 13.0 13.1 13.2 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.
  14. ↑ 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.
  15. ↑ 15.0 15.1 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.
  16. ↑ LAE. 19 February 2009.
  17. ↑ LAE. 19 February 2009.
  18. ↑ URL: http://www.ncbi.nlm.nih.gov/pubmed/15897738. Accessed on: 7 April 2011.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 22.0 22.1 DeLair, D.; Oliva, E.; Köbel, M.; Macias, A.; Gilks, CB.; Soslow, RA. (Jan 2011). "Morphologic spectrum of immunohistochemically characterized clear cell carcinoma of the ovary: a study of 155 cases.". Am J Surg Pathol 35 (1): 36-44. doi:10.1097/PAS.0b013e3181ff400e. PMID 21164285.
  23. ↑ 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.
  24. ↑ 24.0 24.1 Online 'Mendelian Inheritance in Man' (OMIM) 189907
  25. ↑ Feeley, KM.; Wells, M. (Feb 2001). "Precursor lesions of ovarian epithelial malignancy.". Histopathology 38 (2): 87-95. PMID 11207821.
  26. ↑ Okamoto, S.; Okamoto, A.; Nikaido, T.; Saito, M.; Takao, M.; Yanaihara, N.; Takakura, S.; Ochiai, K. et al. (May 2009). "Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts.". Oncol Rep 21 (5): 1209-14. PMID 19360296.
  27. ↑ 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.
  28. ↑ 28.0 28.1 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.
  29. ↑ Park, JY.; Kim, DY.; Kim, JH.; Kim, YM.; Kim, KR.; Kim, YT.; Nam, JH. (Dec 2011). "Micropapillary pattern in serous borderline ovarian tumors: does it matter?". Gynecol Oncol 123 (3): 511-6. doi:10.1016/j.ygyno.2011.08.008. PMID 21917305.
  30. ↑ 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.
  31. ↑ 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.
  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. 1097. ISBN 0-7216-0187-1.
  33. ↑ Shimada, M.; Kigawa, J.; Ohishi, Y.; Yasuda, M.; Suzuki, M.; Hiura, M.; Nishimura, R.; Tabata, T. et al. (Jun 2009). "Clinicopathological characteristics of mucinous adenocarcinoma of the ovary.". Gynecol Oncol 113 (3): 331-4. doi:10.1016/j.ygyno.2009.02.010. PMID 19275957.
  34. ↑ 34.0 34.1 34.2 34.3 34.4 34.5 34.6 34.7 34.8 Offman, SL.; Longacre, TA. (Sep 2012). "Clear cell carcinoma of the female genital tract (not everything is as clear as it seems).". Adv Anat Pathol 19 (5): 296-312. doi:10.1097/PAP.0b013e31826663b1. PMID 22885379.
  35. ↑ 35.0 35.1 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.
  36. ↑ Hauptmann S, Köbel M (2005). "[Prognostic factors in ovarian carcinoma]" (in German). Verh Dtsch Ges Pathol 89: 92-100. PMID 18035678.
  37. ↑ Duska, LR.; Garrett, L.; Henretta, M.; Ferriss, JS.; Lee, L.; Horowitz, N. (Mar 2010). "When 'never-events' occur despite adherence to clinical guidelines: the case of venous thromboembolism in clear cell cancer of the ovary compared with other epithelial histologic subtypes.". Gynecol Oncol 116 (3): 374-7. doi:10.1016/j.ygyno.2009.10.069. PMID 19922988.
  38. ↑ 38.0 38.1 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
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ Eichhorn, JH.; Young, RH. (Apr 2004). "Transitional cell carcinoma of the ovary: a morphologic study of 100 cases with emphasis on differential diagnosis.". Am J Surg Pathol 28 (4): 453-63. PMID 15087664.
  42. ↑ 42.0 42.1 42.2 Tazi, EM.; Lalya, I.; Tazi, MF.; Ahellal, Y.; M'rabti, H.; Errihani, H. (2010). "Transitional cell carcinoma of the ovary: a rare case and review of literature.". World J Surg Oncol 8: 98. doi:10.1186/1477-7819-8-98. PMID 21073751.
  43. ↑ 43.0 43.1 Borah, T.; Mahanta, RK.; Bora, BD.; Saikia, S. (Jan 2011). "Brenner tumor of ovary: An incidental finding.". J Midlife Health 2 (1): 40-1. doi:10.4103/0976-7800.83273. PMC 3156501. PMID 21897739. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156501/.
  44. ↑ URL: http://www.pathologyoutlines.com/ovarytumor.html#brennergen. Accessed on: 8 February 2011.
  45. ↑ 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.
  46. ↑ 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.
  47. ↑ 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.
  48. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970245-5. Accessed on: 8 April 2011.
  49. ↑ 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.
  50. ↑ Okamoto, T.; Matsumura, N.; Mandai, M.; Oura, T.; Yamanishi, Y.; Horiuchi, A.; Hamanishi, J.; Baba, T. et al. (Feb 2011). "Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1.". Mod Pathol 24 (2): 267-76. doi:10.1038/modpathol.2010.204. PMID 21076463.
  51. ↑ 51.0 51.1 51.2 51.3 51.4 51.5 51.6 51.7 51.8 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.
  52. ↑ 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.
  53. ↑ Purohit, RC.; Alam, SZ. (Mar 1980). "Sex cord tumour of the ovary with annular tubules (SCTAT).". Histopathology 4 (2): 147-54. PMID 7358344.
  54. ↑ Lele, SM.; Sawh, RN.; Zaharopoulos, P.; Adesokan, A.; Smith, M.; Linhart, JM.; Arrastia, CD.; Krigman, HR. (Apr 2000). "Malignant ovarian sex cord tumor with annular tubules in a patient with Peutz-Jeghers syndrome: a case report.". Mod Pathol 13 (4): 466-70. doi:10.1038/modpathol.3880079. PMID 10786816.
  55. ↑ URL: http://dictionary.reference.com/browse/annular. Accessed on: 6 August 2011.
  56. ↑ Young, RH.; Welch, WR.; Dickersin, GR.; Scully, RE. (Oct 1982). "Ovarian sex cord tumor with annular tubules: review of 74 cases including 27 with Peutz-Jeghers syndrome and four with adenoma malignum of the cervix.". Cancer 50 (7): 1384-402. PMID 7104978.
  57. ↑ Hashemipour, M.; Moaddab, MH.; Nazem, M.; Mahzouni, P.; Salek, M. (Jul 2010). "Granulosa cell tumor in a six-year-old girl presented as precocious puberty.". J Res Med Sci 15 (4): 240-2. PMID 21526089.
  58. ↑ URL: http://path.upmc.edu/cases/case631.html. Accessed on: 26 January 2012.
  59. ↑ 59.0 59.1 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. 1102. ISBN 0-7216-0187-1.
  60. ↑ Schofield, DE.; Fletcher, JA. (Dec 1992). "Trisomy 12 in pediatric granulosa-stromal cell tumors. Demonstration by a modified method of fluorescence in situ hybridization on paraffin-embedded material.". Am J Pathol 141 (6): 1265-9. PMID 1466394.
  61. ↑ Mayr, D.; Kaltz-Wittmer, C.; Arbogast, S.; Amann, G.; Aust, DE.; Diebold, J. (Sep 2002). "Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors.". Mod Pathol 15 (9): 951-7. doi:10.1097/01.MP.0000024290.55261.14. PMID 12218213.
  62. ↑ Patel, SS.; Carrick, KS.; Carr, BR. (Mar 2009). "Virilization persists in a woman with an androgen-secreting granulosa cell tumor.". Fertil Steril 91 (3): 933.e13-5. doi:10.1016/j.fertnstert.2008.10.038. PMID 19062005.
  63. ↑ Havelock, JC.; Rainey, WE.; Carr, BR. (Dec 2004). "Ovarian granulosa cell lines.". Mol Cell Endocrinol 228 (1-2): 67-78. doi:10.1016/j.mce.2004.04.018. PMID 15541573.
  64. ↑ Jamieson, S.; Fuller, PJ. (Feb 2012). "Molecular pathogenesis of granulosa cell tumors of the ovary.". Endocr Rev 33 (1): 109-44. doi:10.1210/er.2011-0014. PMID 22240241.
  65. ↑ Shah, SP.; Köbel, M.; Senz, J.; Morin, RD.; Clarke, BA.; Wiegand, KC.; Leung, G.; Zayed, A. et al. (Jun 2009). "Mutation of FOXL2 in granulosa-cell tumors of the ovary.". N Engl J Med 360 (26): 2719-29. doi:10.1056/NEJMoa0902542. PMID 19516027.
  66. ↑ http://www.pathologyoutlines.com/ovarytumor.html#fibroma
  67. ↑ 67.0 67.1 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.
  68. ↑ 68.0 68.1 68.2 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 Cite error: Invalid <ref> tag; name "Ref_PBoD1103" defined multiple times with different content
  69. ↑ Tytle, T.; Rosin, D. (Sep 1984). "Bilateral calcified ovarian fibromas.". South Med J 77 (9): 1178-80. PMID 6385289.
  70. ↑ URL: http://brighamrad.harvard.edu/Cases/bwh/hcache/353/full.html. Accessed on: 4 October 2011.
  71. ↑ 71.0 71.1 71.2 71.3 Rose, Alan G. (2008). Atlas of Gross Pathology with Histologic Correlation (1st ed.). Cambridge University Press. pp. 398. ISBN 978-0521868792.
  72. ↑ URL: http://www.pathologyoutlines.com/ovarytumor.html#fibroma. Accessed on: 7 May 2012.
  73. ↑ 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.
  74. ↑ 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.
  75. ↑ 75.0 75.1 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.
  76. ↑ 76.0 76.1 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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