Uterine tumours

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This article deals with uterine tumours, with the exception of the tumours that arise from the endometrium.

Uterine tumours are like water in the sea - very very common. Many hysterectomies are done for them. The most common are leiomyomata (AKA fibroids).

Pre-malignant endometrium and endometrial tumours are dealt with in the articles, endometrial hyperplasia and endometrial carcinoma.

Common benign

Uterine leiomyoma

  • Often called "fibroids".

General

  • Extremely common... 40% of women by age 40.
  • Benign.
    • Can be a cause of abnormal uterine bleeding (commonly abbreviated AUB).
  • Large & multiple associated with infertility.

Gross

Feature:

  • Sharply circumscribed.
  • Gray-white.
  • Whorled appearance.

Factor that raise concern for leiomyosarcoma:

  • Haemorrhage.
  • Cystic degeneration.
  • Necrosis.

Microscopic

Features:

  • Spindle cells arranged in fascicles.
    • Fascicular appearance: adjacent groups of cells have their long axis perpendicular to one another; looks somewhat like a braided hair that was cut.
  • Whorled arrangement of cells.

Negatives:

  • Necrosis (low power) - suggestive of leiomyosarcoma.
  • Hypercellularity.
  • Nuclear atypia seen at low power.
  • Few mitoses.

Images:

Variants

  • Lipoleiomyoma - with adipose tissue.
  • Hypercellular leiomyoma - hypercellularity associated with more mutations.[1]
  • Atypical leiomyoma (AKA symplastic leiomyoma) - leiomyoma with nuclear atypia.
  • Benign metastasizing leiomyoma.[2]
    • This is just what it sounds like. Some believe these are low grade leiomyosarcomas.

IHC

Work-up of suspicious leiomyomas:[3]

  • CD10 (+ve).
  • Ki-67 (-ve).
  • SMA (+ve).
  • Desmin (+ve).

Uncommon benign

Uterine adenofibroma

General

  • Uncommmon.
  • Benign looking lesions can reoccur.[4]
    • It has been proposed that these lesions are in fact well-differentiated adenosarcomas.[5]

Microscopic

Features:

  • Moderately demarcated lesion with:
    • Pale stroma and epithelioid/spindle cells.
    • Simple cuboidal (or columnar) epithelium with eosinophilic cytoplasm.
  • Low mitotic rate.
  • Nuclear atypia minimal.

Note:

DDx:

  • Adenosarcoma.

Images:

Adenomatoid tumour

Should not be confused with Adamantinoma - a bone tumour.

General

  • Grossly mimics leiomyoma.[6]
  • Benign tumour - derived from mesothelium.
  • May be seen paratesticular.[7]

Microscopic

Features:[8]

  • Well-circumscribed lesion; however, not encapsulated.
  • Small tubulocystic spaces lined by cytologically normal mesothelium.
    • These pseudotubular spaces are crossed by "thread-like bridging strands" - key feature.[9][10]

Images:

DDx:

IHC

Features:[11]

  • Calretinin +ve.
  • AE1/AE3 +ve.
  • CD31 -ve.
  • CK7 +ve.[12]

Uncertain malignant potential

Smooth muscle tumour of uncertain malignant potential

  • Abbreviated STUMP.

General

  • Like ASAP and ASCUS - a waffle category... when one isn't sure it is a leiomyoma vs. leiomyosarcoma.
  • Clinical behaviour: usually benign.[13]
  • Can be subclassified into four groups - as per Stanford.

Management:

  • Long-term follow-up.[13]

Microscopic

Features associated with recurrence:[13]

  • Nuclear atypia.

DDx:

IHC

Features associated with recurrence:[13]

  • p16 +ve.
  • p53 +ve.

Malignant

Uterine carcinosarcoma

  • AKA malignant mixed muellerian tumour, abbreviated MMMT.

General

  • Associated with previous radiation exposure.
  • Metstasize as adenocarcinoma.
  • Aggressive/poor prognosis;[14] in one series 5 year survival ~= 30-35%.[15]
  • Considered to be a poorly differentiated endometrial carcinoma with metaplastic changes.[16]
  • Case reports of MMMT in ovary and fallopian tube.

Microscopic

Features:[17]

DDx:

Images:

Adenosarcoma of the uterus

  • AKA uterine adenocarcinoma.

General

Features:[18]

  • Uncommon.
  • May prolapse through cervical os and thus present as cervical polyp.
  • Most commonly uterine corpus, occasionally cervix and ovary, rarely in the vagina, fallopian tube, peritoneal surfaces, intestine.
  • Typically 30-40 years old.

Clinical:[19]

  • Most common presentations of Müllerian adenosarcoma (percentages based on series of 41 individuals[20]):
    • Vaginal bleeding ~ 70%.
    • Pelvic mass ~ 40%.
    • Uterine polyp ~ 30%.
  • Prognosis (based on series of ~500 individuals[21]):
    • Favourable outcome - most detected at an early stage.
      • ~80% five year survival for stage I tumours.
    • Outcome better than carcinosarcoma.

Treatment:

  • TAH-BSO.
    • Tumours are estrogen responsive.
  • Chemotherapy (platin-based).[20]

Microscopic

Features:[22][18]

  • "Malignant stroma" - key feature.
    • Stromal nuclear pleomorphism - usually low grade.
    • WHO criteria: 2+ mitoses / 10 HPF -- definition suffers from HPFitis.
      • Mitotic rate criteria often ignored as mitotically inactive tumours metastasize.[18]
  • Benign glands with an abnormal shape.
  • "Cambium layer" = increased cellularity around the epithelial elements.[18][23]

Notes:

DDx:

Images:

IHC

  • CD10 +ve.[18]
  • ER +ve.
  • PR +ve.

Uterine leiomyosarcoma

General

  • Poor prognosis.
  • Do not (generally) arise from leiomyomas.
  • Often singular, i.e. one tumour; unlike leiomyomas (which are often multiple).

Gross

Features:

  • "Fleshy" appearance.
  • Necrosis.
  • Large size.
  • Often singular, i.e. one lesion; leiomyomata are often multiple.

Microscopic

Features:

  • Smooth muscle differentiation - key feature.
    • Fascicular architecture.
      • Whorled look at low power.
      • Groups of spindle cells cut peripendicular to their long axis adjacent to groups of spindle cells cut in the plane of their long axis.
    • May rely on IHC - if poorly differentiated.
  • Malignant histomorphologic features - all three required:
    1. Nuclear pleomorphism.
    2. Necrosis.
      • Should be patchy/multifocal.
      • Zonal necrosis is suggestive of vascular cause and may be a degenerative change.
        • Zonal necrosis may be seen in (benign) leiomyomas.
    3. Mitoses.
      • 10 mitoses/HPF.
      • 5 mitoses/HPF - if epithelioid.
      • 2 mitoses/HPF - if myxoid.

DDx:

IHC

  • CD10 -ve.
  • Positive for SMC markers.
    • Desmin - present in all three types of muscle.
    • Caldesmon.
    • Smooth muscle myosin.

Endometrial stromal tumours

This grouping includes the gamut from benign to malignant.

Overview

WHO classification:[24]

  • Endometrial stromal nodule - not a tumour.
  • Endometrial stromal sarcoma (ESS), low grade.
  • Undifferentiated endometrial sarcoma (UES).

Notes:

  • Some believe in a "high grade ESS"... some don't.[25]

Endometrial stromal nodule

  • Abbreviated ESN.

General

  • Benign.

Microscopic

Features:

  • Well-circumscribed - key feature.
    • The interface of the lesion may not have more than three finger-like irregularities/projections into the surround myometrium that are >= 3 mm.[26]
      • If it does... it is an ESS.
  • No vascular invasion.

DDx:

Images:

Endometrial stromal sarcoma

  • Abbreviated ESS.
  • AKA low-grade endometrial stromal sarcoma.

General

Microscopic

Features:

  • Highly cellular Islands with a wavy irregular border.
    • Border has finger-like projections/tongue-like projections.
    • Benign uterine smooth muscle between islands of tumour cells.
  • Epithelioid cells.
  • High NC ratio.
  • Thin blood vessels within islands of cells.
    • Tumour cells pallisade around the vessels.

Notes:

  • Vaguely resembles the stroma of proliferative endometrium.

DDx:

Images:

IHC

Features:[28]

  • CD10 +ve.
  • h-caldesmin -ve.
  • PR +/-ve.
  • ER +/-ve.

Molecular

May be associated a recurrent translocation:[29]

  • t(7;17)(p15;q21).
    • JAZF1 - chromosome 7.[30]
    • SUZ12 - chromosome 17.[31]

Undifferentiated endometrial sarcoma

  • Abbreviated as UES.

General

Microscopic

Features:

  1. Marked nuclear atypia.
  2. Mitoses+++.
  3. Poorly differentiated - key feature
    • Looks nothing like low grade endometrial stromal sarcoma.
    • Negative for smooth muscle markers (to exclude leiomyosarcoma).

Notes:

  • Need IHC to diagnose.

DDx:

IHC

Features:[32]

  • SMA ~50% +ve.

Typically negative:[32]

  • Smooth muscle markers: desmin, h-caldesmon.
  • Skeletal muscle markers: Myf4, actin.
  • Melanoma: S100, HMB-45.
  • GIST: CD117.

Weird stuff

Trophoblastic tumours

Uterine tumors resembling ovarian sex cord tumours

  • Abbreviated UTROSCT.

General

  • Super rare.

Microscopic

Features:

  • Look like sex cord tumour:[33]
    • May have: anastomosing cords, trabeculae, small nests and/or tubules.

Atypical polypoid adenomyoma of the uterus

  • Abbreviated APA.
  • AKA atypical polypoid adenomyoma.

General

  • Very rare.[34]
  • Benign.[35]
  • Reproductive age women.

Gross

  • Lower uterine segment.

Microscopic

Features:[35]

  • Glands with irregular (non-ovoid) shapes.
  • Benign smooth muscle around the glands - key feature.
  • Morular squamous metaplasia - balls of squamous cells - very common.
  • Nuclear atypia (mild).

DDx:

Images:

IHC

Features (glandular component):[34]

  • AE1/AE3 +ve.
  • CK7 +ve.
  • ER +ve.
  • PR +ve.

Significant negative (glandular component):[34]

  • CK20 -ve.
  • CEA -ve.

See also

References

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  2. Patton, KT.; Cheng, L.; Papavero, V.; Blum, MG.; Yeldandi, AV.; Adley, BP.; Luan, C.; Diaz, LK. et al. (Jan 2006). "Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis.". Mod Pathol 19 (1): 130-40. doi:10.1038/modpathol.3800504. PMID 16357844. http://www.nature.com/modpathol/journal/v19/n1/full/3800504a.html.
  3. STC. 25 February 2009.
  4. Seltzer, VL.; Levine, A.; Spiegel, G.; Rosenfeld, D.; Coffey, EL. (Jun 1990). "Adenofibroma of the uterus: multiple recurrences following wide local excision.". Gynecol Oncol 37 (3): 427-31. PMID 2351327.
  5. Gallardo, A.; Prat, J. (Feb 2009). "Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases challenging the existence of adenofibroma.". Am J Surg Pathol 33 (2): 278-88. doi:10.1097/PAS.0b013e318181a80d. PMID 18941402.
  6. Huang, CC.; Chang, DY.; Chen, CK.; Chou, YY.; Huang, SC. (Sep 1995). "Adenomatoid tumor of the female genital tract.". Int J Gynaecol Obstet 50 (3): 275-80. PMID 8543111.
  7. González Resina, R.; Carranza Carranza, A.; Congregado Córdoba, J.; Conde Sánchez, JM.; Congregado Ruiz, CB.; Medina López, R. (Jan 2010). "[Paratesticular adenomatoid tumor: a report of nine cases].". Actas Urol Esp 34 (1): 95-100. PMID 20223139.
  8. Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 346. ISBN 978-0443069208.
  9. Sangoi, AR.; McKenney, JK.; Schwartz, EJ.; Rouse, RV.; Longacre, TA. (Sep 2009). "Adenomatoid tumors of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases.". Mod Pathol 22 (9): 1228-35. doi:10.1038/modpathol.2009.90. PMID 19543245.
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  12. Latta, E. 9 December 2009.
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  27. Chew, I.; Oliva, E. (Mar 2010). "Endometrial stromal sarcomas: a review of potential prognostic factors.". Adv Anat Pathol 17 (2): 113-21. doi:10.1097/PAP.0b013e3181cfb7c2. PMID 20179433.
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  30. Online 'Mendelian Inheritance in Man' (OMIM) 606246
  31. Online 'Mendelian Inheritance in Man' (OMIM) 606245
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  33. URL: http://www.nature.com/modpathol/journal/v19/n1/full/3800475a.html. Accessed on: 5 August 2010.
  34. 34.0 34.1 34.2 Terada, T. (Oct 2011). "Atypical polypoid adenomyoma of the uterus: an immunohistochemical study on 5 cases.". Ann Diagn Pathol 15 (5): 338-41. doi:10.1016/j.anndiagpath.2011.03.008. PMID 21684185.
  35. 35.0 35.1 Jakus, S.; Edmonds, P.; Dunton, C.; Holland, G. (Jan 2002). "Atypical polypoid adenomyoma mimicking cervical adenocarcinoma.". J Low Genit Tract Dis 6 (1): 33-8. PMID 17050990.