Uterine tumours

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This article deals with uterine tumours, excluding tumours that arise from the endometrium. Uterine tumours are like water in the sea - very very common. Many hysterectomies are done for 'em... 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

Main article: 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 assoc. 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

  • AKA adenofibroma of the uterus.

General

  • Uncommmon.
  • Benign looking lesions can reoccur.[4]

Microscopic

Features:

  • Moderately demarcated lesion with:
    • Pale stroma and epithelioid/spindle cells.
    • Simple cuboidal (or columnar) epithelium with eosinophilic cytoplasm.

Note:

DDx:

  • Adenosarcoma.

Adenomatoid tumour

Should not be confused with Adamantinoma - a bone tumour.

General

  • Grossly mimics leiomyoma.[5]
  • Benign tumour - derived from mesothelium.
  • May be seen paratesticular.[6]

Microscopic

Features:[7]

  • 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.[8][9]

Images:

DDx:

IHC

Features:[10]

  • Calretin +ve.
  • AE1/AE3 +ve.
  • CD31 -ve.
  • CK7 +ve.[11]

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.[12]
  • Can be subclassified into four groups - as per Stanford.

Management:

  • Long-term follow-up.[12]

Microscopic

Features associated with recurrence:[12]

  • Nuclear atypia.

IHC

Features associated with recurrence:[12]

  • 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;[13] in one series 5 year survival ~= 30-35%.[14]
  • Considered to be a poorly differentiated endometrial carcinoma with metaplastic changes.[15]
  • Case reports of MMMT in ovary and fallopian tube.

Microscopic

Features:[16]

Images:

Adenosarcoma

General

Features:[17]

  • 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.

Treatment:

  • TAH-BSO.
    • Tumours are estrogen responsive.

Microscopic

Features:[18][17]

  • "Malignant stroma" - key feature.
    • Stromal nuclear pleomorphism - usu. low grade.
    • WHO criteria: 2+ mitoses / 10 HPF -- definition suffers from HPFitis.
  • Benign glands with an abnormal shape.
  • "Cambium layer" = increased cellularity around the epithelial elements.[17][19]

DDx:

Notes:

  • Cambium layer - seen in: adenosarcoma, botryoid RMS.[19]

Uterine leiomyosarcoma

Main article: 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.

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:[20]

  • 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.[21]

Endometrial stromal nodule

  • Abbreviated ESN.

General

  • Benign.

Microscopic

Features:

  • Well-circumscribed - key feature.
    • The interface of lesion may not have more than three finger-like irregularities/projections into the surround myometrium that are >= 3 mm.[22]
  • No vascular invasion.

Notes:

  • Myometrial invasion or vascular invasion = ESS or UES.

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:[24]

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

Molecular

May be associated a recurrent translocation:[25]

  • t(7;17)(p15;q21).
    • JAZF1 - chromosome 7.[26]
    • SUZ12 - chromosome 17.[27]

Undifferentiated endometrial sarcoma

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:

Weird stuff

Trophoblastic tumours

Uterine tumors resembling ovarian sex cord tumours

  • Abbreviated UTROSCT.

General

  • Super rare.

Microscopic

Features:

  • Look like sex cord tumour:[28]
    • 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.[29]
  • Reproductive age women.

Gross

  • Lower uterine segment.

Microscopic

Features:[30]

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

DDx:

Images:

IHC

Features (glandular component):[29]

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

Significant negative (glandular component):[29]

  • CK20 -ve.
  • CEA -ve.

See also

References

  1. ↑ http://www3.interscience.wiley.com/journal/119360394/abstract
  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. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Hes, O.; Perez-Montiel, DM.; Alvarado Cabrero, I.; Zamecnik, M.; Podhola, M.; Sulc, M.; Hora, M.; Mukensnabl, P. et al. (Oct 2003). "Thread-like bridging strands: a morphologic feature present in all adenomatoid tumors.". Ann Diagn Pathol 7 (5): 273-7. PMID 14571427.
  10. ↑ Canedo-Patzi, AM.; León-Bojorge, B.; de Ortíz-Hidalgo, C.. "[Adenomatoid tumor of the genital tract. Clinical, pathological and immunohistochemical study in 9 cases]". Gac Med Mex 142 (1): 59-66. PMID 16548294.
  11. ↑ LAE. 9 December 2009.
  12. ↑ 12.0 12.1 12.2 12.3 Ip PP, Cheung AN, Clement PB (July 2009). "Uterine smooth muscle tumors of uncertain malignant potential (STUMP): a clinicopathologic analysis of 16 cases". Am. J. Surg. Pathol. 33 (7): 992–1005. doi:10.1097/PAS.0b013e3181a02d1c. PMID 19417585.
  13. ↑ Ivy, JJ.; Unger, JB.. "Malignant mixed mullerian sarcomas of the uterus--the LSUHSC Shreveport experience.". J La State Med Soc 156 (6): 324-6. PMID 15688674.
  14. ↑ Callister, M.; Ramondetta, LM.; Jhingran, A.; Burke, TW.; Eifel, PJ. (Mar 2004). "Malignant mixed Müllerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome.". Int J Radiat Oncol Biol Phys 58 (3): 786-96. doi:10.1016/S0360-3016(03)01561-X. PMID 14967435.
  15. ↑ D'Angelo, E.; Prat, J. (Jan 2010). "Uterine sarcomas: a review.". Gynecol Oncol 116 (1): 131-9. doi:10.1016/j.ygyno.2009.09.023. PMID 19853898.
  16. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 428. ISBN 978-0781765275.
  17. ↑ 17.0 17.1 17.2 McCluggage, WG. (Mar 2010). "Mullerian adenosarcoma of the female genital tract.". Adv Anat Pathol 17 (2): 122-9. doi:10.1097/PAP.0b013e3181cfe732. PMID 20179434.
  18. ↑ 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. 1089. ISBN 0-7216-0187-1.
  19. ↑ 19.0 19.1 URL: http://www.medilexicon.com/medicaldictionary.php?t=48297. Accessed on: 9 August 2011.
  20. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 426. ISBN 978-0781765275.
  21. ↑ Amant F, Vergote I, Moerman P (November 2004). "The classification of a uterine sarcoma as 'high-grade endometrial stromal sarcoma' should be abandoned". Gynecol. Oncol. 95 (2): 412–3; author reply 413. doi:10.1016/j.ygyno.2004.07.021. PMID 15491769. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WG6-4DF46J8-3&_user=1166899&_coverDate=11%2F01%2F2004&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1204975755&_rerunOrigin=google&_acct=C000051839&_version=1&_urlVersion=0&_userid=1166899&md5=d6ec1eee2941460a085d1dac6615b5a5.
  22. ↑ 22.0 22.1 Baker, P.; Oliva, E. (Mar 2007). "Endometrial stromal tumours of the uterus: a practical approach using conventional morphology and ancillary techniques.". J Clin Pathol 60 (3): 235-43. doi:10.1136/jcp.2005.031203. PMID 17347285. http://jcp.bmj.com/content/60/3/235.full.
  23. ↑ 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.
  24. ↑ Zhu, XQ.; Shi, YF.; Cheng, XD.; Zhao, CL.; Wu, YZ. (Jan 2004). "Immunohistochemical markers in differential diagnosis of endometrial stromal sarcoma and cellular leiomyoma.". Gynecol Oncol 92 (1): 71-9. PMID 14751141.
  25. ↑ Amant, F.; Moerman, P.; Cadron, I.; Hagemeijer, A.; Vergote, I.; Debiec-Rychter, M. (Mar 2003). "Endometrial stromal sarcoma with a sole t(X;17) chromosome change: report of a case and review of the literature.". Gynecol Oncol 88 (3): 459-62. PMID 12648605.
  26. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 606246
  27. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 606245
  28. ↑ URL: http://www.nature.com/modpathol/journal/v19/n1/full/3800475a.html. Accessed on: 5 August 2010.
  29. ↑ 29.0 29.1 29.2 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.
  30. ↑ 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.
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