Ovarian tumours

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The article examines ovarian tumours including ovarian cancer.

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. 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:[3]

  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:[4]

  • 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.
  • Granuloma cell tumour.

"Dirty necrosis":

  • Def'n: Cellular debris within gland lumen.[5]
  • Characteristic of colorectal adenocarcinoma, may be absent in ovarian tumours -- limited value.[6]

Grading of ovarian cancer

  • Silverberg grading system,[7] 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):[8]

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

Surface epithelial tumours

Most common subtypes - in short:[9]

  • Serous:
    • Columnar cells,
    • Cilia,
    • Psammoma bodies,
    • Papillae;
  • Endometrioid:
    • Tubular glands;
  • 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[10]

  • Benign.
  • Borderline.
    • May have pseudostratification of epithelial cells.
    • "Usually, borderline if first impression is borderline."[11]
  • Malignant.
    • Cytologic atypia.
    • Many papillae.

Microscopy[12]

  • 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[13][14] - though is disputed.[15]

Mucinous tumours

Gross

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

Micro

  • 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.[17]
  • May see mucinous secretion.[18]
  • May have squamous differentiation/squamous metaplasia (useful for differentiating from sex-cord stromal tumours and germ cell tumours).[18] - very useful feature.

Clear cell adenocarcinoma

General

  • Thought to be related to endometrioid carcinoma.[19]
    • Increased risk of CC adenoca in people with endometriosis.
  • Worse prognosis vs. other surface epithelial tumours[20]

Histology

  • Hobnail morphology (apical surface larger than basal surface)[21] -- key feature
    • "Nuclei bulge into the lumen".
  • Hyaline droplet -- common, as in clear cell renal cell carcinoma
  • Clear cells -- cytoplasm is clear.

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).

Brenner tumour

Epidemiology

  • Mostly benign clinical course.
  • Thought to arise from Walthard cell nest.
  • Frequently an incidental finding, i.e. oophorectomy was done for another reason.

Gross

  • Solid.

Microscopy

  • Nests of transitional epithelium.[22]
  • "Coffee bean nucleus".
    • Elliptical shape (nucleus).
    • nuclear grooves.[23]
  • distinct nucleoli.[24]

Images:

Note:

  • DDx of Coffee bean nucleus = granulosa cell tumour

Germ cell tumours

These tumour are relatively uncommon, though are the most common grouping for young women.[25]

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

Three types:

  1. Mature (benign) - common.
  2. Immature (malignant).
  3. Monodermal (highly specialized).

Specialized teratomas

  • Struma ovarii (thyroid tumour).
    • Thyroid tissue - colloid is seen.
  • Carcinoid - rare.
    • 'Typical neuroendocrine appearance' - nuclei with stippled chromatin (salt-and-pepper chromatin).

Dysgerminoma

General

Microscopy

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

Epidemiology

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

Dysgerminoma vs lymphoma:

  • dysgerminoma has "squared-off" nuclei,[27] i.e. the nuclei look are polygonal-shaped.

Sex cord stromal tumours

  • IHC: most are positive for inhibin.[28]
  • Most are unilateral.[28]

Granulosa-theca tumours

NEED TO FIX.

Granulosa component

General

Gross

  • Solid.

Microscopy

  • Classic appearance includes gland-like structures filled with acidophilic material (Call-Exner bodies).
  • Small cuboidal to polygonal cell in sheets or stands or cords.

IHC

DDx:

  • UCC.
    • UCC usually has extensive necrosis.
  • Brenner tumour (???).

Fibroma-thecoma group

  • Some say fibromas and thecomas are related,[30] while others believe they should be considered distinct entities.[31]
  • 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.[28]

Fibroma

General

  • Part of Meigs syndrome (mnemonic FAR: fibroma, ascites, right pleural effusion).
  • Assoc. with basal cell nevus syndrome.[32]

Microscopy

Features:[33][28]

  • Spindle-shaped cells.
  • Central nuclei.
  • Stainable lipid - minimal or none.[28]

IHC

  • Inhibin -ve (~75%).[28]

Thecoma

  • Assoc. with compression & atrophy of ovarian cortex, thought to arise from medulla.[31]
  • Alpha-inhibin +ve (90%+).[28]
  • Approx. 50% have symptoms related to estrogen secretion.[28]
    • May also be viralizing.

Histology

Features:[28]

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

Sertoli-Ledydig tumour

General

  • AKA androblastoma.

Microscopy[34]

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

Pure Leydig cell tumour

General

  • AKA Hilus cell tumour.

Microscopy

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

Gonadoblastoma

General

  • Abnormal sexual development.
  • Often coexist with dysgerminoma.

Microscopy

  • Immature germ cells resembling Sertoli cells and granulosa cells.[35]

Metastatic ovarian tumours

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

Extramuellerian metastatic tumours

Benign

Benign mesothelial inclusion cyst

Epidemiology

  • Assoc. with previous surgery.
  • May be found incidentally, e.g. during C-section.

Gross

  • May mimic mucinous tumour - to unexperienced.[36]
  • Thin-wall.[37]
  • Clear/translucent fluid.

Microscopy

  • Benign mesothelium.
    • Single layer of squamoid or cuboid mesothelial cells.[37]

IHC

See also

References

  1. ↑ PBoD P.1093.
  2. ↑ LAE. 22 October 2009.
  3. ↑ LAE. 22 October 2009.
  4. ↑ NEED REF.
  5. ↑ http://www.cancer.gov/cancertopics/genetics-terms-alphalist/all#D
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ PBoD PP.1096-7.
  10. ↑ PBoD P.1096???
  11. ↑ LAE 19 Feb 2009.
  12. ↑ PBoD P.1096.
  13. ↑ [LAE 19 Feb 2009]
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ PBoD P.1097.
  17. ↑ Khalifa 2008.
  18. ↑ 18.0 18.1 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.
  19. ↑ PBoD P.1098.
  20. ↑ Hauptmann S, Köbel M (2005). "[Prognostic factors in ovarian carcinoma]" (in German). Verh Dtsch Ges Pathol 89: 92-100. PMID 18035678.
  21. ↑ [1]
  22. ↑ PBoD P.1098.
  23. ↑ [2]
  24. ↑ [3]
  25. ↑ NEED REF.
  26. ↑ PBoD P.1101
  27. ↑ 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.
  28. ↑ 28.0 28.1 28.2 28.3 28.4 28.5 28.6 28.7 28.8 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.
  29. ↑ PBoD P.1102.
  30. ↑ http://www.pathologyoutlines.com/ovarytumor.html#fibroma
  31. ↑ 31.0 31.1 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.
  32. ↑ PBoD P.1103.
  33. ↑ http://www.pathologyoutlines.com/ovarytumor.html#fibroma
  34. ↑ PBoD P.1103.
  35. ↑ PBoD P.1104.
  36. ↑ GAG 26 Feb 2009.
  37. ↑ 37.0 37.1 37.2 Urbanczyk K, Skotniczny K, Kucinski J, Friediger J (2005). "Mesothelial inclusion cysts (so-called benign cystic mesothelioma)--a clinicopathological analysis of six cases". Pol J Pathol 56 (2): 81-7. PMID 16092670.
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