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

Main article: Leiomyoma
  • Often called fibroids.
  • Fibroid uterus redirects here.

General

  • Extremely common... 40% of women by age 40.
  • Benign.
  • Large & multiple associated with infertility.
  • May be treated medically with a selective progesterone receptor modulator, e.g. ulipristal (Fibristal).[1]

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.[2]
  • Atypical leiomyoma (AKA symplastic leiomyoma) - leiomyoma with nuclear atypia.
  • Benign metastasizing leiomyoma.[3]
    • This is just what it sounds like. Some believe these are low grade leiomyosarcomas.

IHC

Work-up of suspicious leiomyomas:[4]

  • CD10 +ve.[5]
  • SMA +ve.
  • Desmin +ve.
  • Ki-67 -ve.

Others:

  • p16 usually -ve.[6]
    • Often +ve in leiomyosarcoma.
  • H-caldesmon +ve.[5]

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UTERUS WITH CERVIX, UTERINE TUBES AND LEFT OVARY, TOTAL HYSTERECTOMY, BILATERAL SALPINGECTOMY 
AND LEFT OOPHRECTOMY:
- LEIOMYOMATA WITH FOCAL CALCIFICATION AND HYALINE CHANGE.
- SECRETORY PHASE ENDOMETRIUM.
- LEFT OVARY WITHIN NORMAL LIMITS.
- UTERINE TUBES WITHIN NORMAL LIMITS.
- UTERINE CERVIX WITHIN NORMAL LIMITS.

Myomectomy

UTERINE MASSES ("FIBROIDS"), MYOMECTOMY:
- LEIOMYOMATA.

UTERINE MASS, HYSTEROSCOPIC MYOMECTOMY:
- BENIGN SMOOTH MUSCLE FRAGMENTS COMPATIBLE WITH LEIOMYOMA.
- SECRETORY PHASE ENDOMETRIUM.

Uncommon benign

Uterine adenofibroma

General

  • Uncommmon.
  • Benign looking lesions can reoccur.[7]
    • It has been proposed that these lesions are in fact well-differentiated adenosarcomas.[8]

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 the bone tumour adamantinoma.
Main article: Adenomatoid tumour

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 in uterus: usually benign.[9]
  • Can be subclassified into four groups - as per Stanford.
  • May be seen in the prostate gland.[10]

Management:

  • Long-term follow-up.[9]

Microscopic

Features associated with recurrence:[9]

  • Nuclear atypia.

DDx:

IHC

Features associated with recurrence:[9]

  • 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;[11] in one series 5 year survival ~= 30-35%.[12]
  • Considered to be a poorly differentiated endometrial carcinoma with metaplastic changes.[13]
  • Case reports of MMMT in ovary and fallopian tube.

Microscopic

Features:[14]

DDx:

Images

  • MMMT - low mag. (WC)

  • MMMT - high mag. (WC)

  • MMMT - crappy (WC)

www:

Adenosarcoma of the uterus

  • AKA uterine adenocarcinoma.

General

Features:[15]

  • 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:[16]

  • Most common presentations of Müllerian adenosarcoma (percentages based on series of 41 individuals[17]):
    • Vaginal bleeding ~ 70%.
    • Pelvic mass ~ 40%.
    • Uterine polyp ~ 30%.
  • Prognosis (based on series of ~500 individuals[18]):
    • 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).[17]

Microscopic

Features:[19][15]

  • "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.[15]
  • Benign glands with an abnormal shape.
  • "Cambium layer" = increased cellularity around the epithelial elements.[15][20]

Notes:

DDx:

Images

  • Uterine adenosarcoma - low mag. (WC)

  • Uterine adenosarcoma - intermed. mag. (WC)

  • Uterine adenosarcoma - high mag. (WC)

IHC

  • CD10 +ve.[15]
  • ER +ve.
  • PR +ve.

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 - essential.
    • 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 - two of three required - key features:[21]
    1. Nuclear pleomorphism.
    2. Coagulative tumour cell 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.

Note:

  • The mitotic rate seems to be a relatively weak predictor; a modest rate may be malignant and a high rate benign.[22]

DDx:

IHC

  • CD10 -ve.
  • Positive for SMC markers.
    • Desmin - present in all three types of muscle.
    • Caldesmon.
    • Smooth muscle myosin.
  • p16 +ve.[6]
    • Useful for differentiation from leiomyoma.

Endometrial stromal tumours

This grouping includes the gamut from benign to malignant.

Overview

WHO classification:[23]

  • 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.[24]

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.[25]
      • If it does... it is an ESS.
  • No vascular invasion.

DDx:

Images:

Endometrial stromal sarcoma

  • Abbreviated ESS.
  • Previously known as low-grade endometrial stromal sarcoma.
Main article: Endometrial stromal sarcoma

Undifferentiated endometrial sarcoma

  • Abbreviated as UES.
  • Previously known as high-grade endometrial stromal sarcoma.[26]

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:[27]

  • SMA ~50% +ve.

Typically negative:[27]

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

Weird stuff

Trophoblastic tumours

Uterine tumour resembling an ovarian sex cord stromal tumour

  • Abbreviated UTROSCT.
Main article: Uterine tumour resembling an ovarian sex cord stromal tumour

Atypical polypoid adenomyoma of the uterus

  • Abbreviated APA.
  • AKA atypical polypoid adenomyoma.
Main article: Atypical polypoid adenomyoma of the uterus

See also

References

  1. ↑ Delev, DP.. "Ulipristal acetate--a review of the new therapeutic indications and future prospects.". Folia Med (Plovdiv) 55 (3-4): 5-10. PMID 24712276.
  2. ↑ Pandis, N.; Heim, S.; Willén, H.; Bardi, G.; Flodérus, U-M.; Mandahl, N.; Mitelman, F. (Jan 1991). "Histologic—cytogenetic correlations in uterine leiomyomas.". International Journal of Gynecological Cancer 1 (4): 163-68. http://www3.interscience.wiley.com/journal/119360394/abstract.
  3. ↑ 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.
  4. ↑ STC. 25 February 2009.
  5. ↑ 5.0 5.1 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.
  6. ↑ 6.0 6.1 Gannon, BR.; Manduch, M.; Childs, TJ. (Jan 2008). "Differential Immunoreactivity of p16 in leiomyosarcomas and leiomyoma variants.". Int J Gynecol Pathol 27 (1): 68-73. doi:10.1097/pgp.0b013e3180ca954f. PMID 18156978.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 9.3 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.
  10. ↑ Nagar, M.; Epstein, JI. (Jun 2011). "Epithelial proliferations in prostatic stromal tumors of uncertain malignant potential (STUMP).". Am J Surg Pathol 35 (6): 898-903. doi:10.1097/PAS.0b013e318214f2f2. PMID 21572264.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 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.
  16. ↑ Abu, J.; Ireland, D.; Brown, L. (Apr 2007). "Adenosarcoma of an endometrial polyp in a 27-year-old nulligravida: a case report.". J Reprod Med 52 (4): 326-8. PMID 17506376.
  17. ↑ 17.0 17.1 Verschraegen, CF.; Vasuratna, A.; Edwards, C.; Freedman, R.; Kudelka, AP.; Tornos, C.; Kavanagh, JJ.. "Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience.". Oncol Rep 5 (4): 939-44. PMID 9625851.
  18. ↑ Arend, R.; Bagaria, M.; Lewin, SN.; Sun, X.; Deutsch, I.; Burke, WM.; Herzog, TJ.; Wright, JD. (Nov 2010). "Long-term outcome and natural history of uterine adenosarcomas.". Gynecol Oncol 119 (2): 305-8. doi:10.1016/j.ygyno.2010.07.001. PMID 20688363.
  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. 1089. ISBN 0-7216-0187-1.
  20. ↑ 20.0 20.1 URL: http://www.medilexicon.com/medicaldictionary.php?t=48297. Accessed on: 9 August 2011.
  21. ↑ Ip, PP.; Cheung, AN. (Dec 2011). "Pathology of uterine leiomyosarcomas and smooth muscle tumours of uncertain malignant potential.". Best Pract Res Clin Obstet Gynaecol 25 (6): 691-704. doi:10.1016/j.bpobgyn.2011.07.003. PMID 21865091.
  22. ↑ Guo, L.; Liu, T.; Huang, H. (Oct 1996). "[Reappraisal of the pathological criteria for uterine leiomyosarcoma].". Zhonghua Bing Li Xue Za Zhi 25 (5): 266-9. PMID 9388868.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ Feng, W.; Malpica, A.; Skaland, I.; Gudlaugsson, E.; Robboy, SJ.; Dalen, I.; Hua, K.; Zhou, X. et al. (2013). "Can proliferation biomarkers reliably predict recurrence in world health organization 2003 defined endometrial stromal sarcoma, low grade?". PLoS One 8 (10): e75899. doi:10.1371/journal.pone.0075899. PMID 24146786.
  27. ↑ 27.0 27.1 Abeler, VM.; Nenodovic, M. (May 2011). "Diagnostic immunohistochemistry in uterine sarcomas: a study of 397 cases.". Int J Gynecol Pathol 30 (3): 236-43. doi:10.1097/PGP.0b013e318200caff. PMID 21464730.
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