Endometrial hyperplasia

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See Endometrium for dating and benign pathologies.

Endometrial hyperplasia, abbreviated EH, is a precursor to endometrial carcinoma.

Overview

The most widely used system is from the World Health Organization (WHO).

WHO classification - overview

The WHO system is based on determining:

  1. Gland density (normal = simple hyperplasia, high density = complex hyperplasia).
  2. Presence/absence of nuclear atypia.

Alternate classifications - overview

Two alternative grading systems exist, that are (currently) not widely used:[1]

  1. European group of experts (1999).
  2. Endometrial collaborative group/Harvard (2000).

Both consist of two categories, as opposed to four found in the WHO classification.

European group of experts classification

  1. Endometrial hyperplasia.
  2. Endometrioid neoplasia.

Endometrial collaborative group/Harvard classification

  1. Endometrial hyperplasia.
  2. Endometrial intraepithelial neoplasia (EIN).

WHO classification

Management of endometrial hyperplasia

  • Endometrial hyperplasia with atypia is usually treated with hysterectomy.[2]
    • In women who want to maintain fertility it may be treated with progestin + short interval re-biopsies (q3 months).[3]
  • Endometrial hyperplasia without atypia is treated by:
    • Progestins + close follow-up OR hysterectomy.

Risk of progression to carcinoma

Approximate risk of progression to endometrial carcinoma - Latta rule of 3s:[4]

Simple Complex
Without atypia 1% 3%
With atypia 9% † 27% ‡

Notes:

  • † 8% is the true number.[5]
  • ‡ 29% is the true number.[5]

WHO system

Almost all hyperplasia is seen in the context of proliferative-type endometrium. Hyperplasia in the secretory-type endometrium is extremely rare and something diagnosed by or in consultation with an expert in gynecologic pathology.

Simple endometrial hyperplasia

  • AKA simple hyperplasia.

General

Microscopic

Features:[6]

  • Irregular dilated glands (with large lumens) - key feature.
    • Glands described as "animal shapes".
  • Variation of gland size.
  • No nuclear atypia.
    • Uniform columnar nuclei.
  • Normal gland density (gland area in plane of section/total area ~= 1/3).

DDx:

Images:

Simple endometrial hyperplasia with atypia

General

  • Very uncommon.

Microscopic

Features:[6]

  • Irregular dilated glands (with large lumens) - important feature.
    • Glands described as "animal shapes".
  • Variation of gland size.
  • No nuclear atypia.
    • Uniform columnar nuclei.
  • Normal gland density (gland area in plane of section/total area ~= 1/3).
  • Nuclear atypia:[8]
    • Loss of basal nuclear stratification.
    • Nuclear size variation.
    • Nuclear rounding.
      • Nuclei lacking atypical = uniform columnar nuclei.
    • Nucleoli.
    • Hyperchromasia or vesicular nuclei.

Notes:

  • There are no clear criteria for atypia. Different sources list different features.
  • VL criteria for atypia (all should be present):
    1. Increased NC ratio.
      • Atypical: ~ 1:2
      • Not atypical: ~1:3.
    2. Oval nuclei with small major axis to minor axis ratio.
      • Atypical: major axis:minor axis = <=2:1.
      • Not atypical: major axis:minor axis = >=3:1
        • NB: round nuclei: major axis:minor axis = 1:1.
    3. Small nucleoli (~1/5 the size of the nucleus).

Complex endometrial hyperplasia

Microscopic

Features:

  • Increase in size & number of glands + irregular shape - key feature.
  • Cell stratification.
  • Nuclear enlargement.
  • Mitoses common.
  • No nuclear atypia.

Notes:

  • Normal "gland-to-stroma ratio" is 1:3.
  • Two "touching" glands may be one gland in section.

DDx:

Image:

Endometrial carcinoma versus complex endometrial hyperplasia

Complex endometrial hyperplasia:

  • Non-confluent - glands distinct from one another.
Classic criteria for endometrial carcinoma

This is pimping material that shows up on exams.

Endometrial carcinoma has one of the following:[9][10][11]

  1. Desmoplastic stromal response.
  2. Confluent cribriform growth. †
  3. Extensive papillary growth. †
  4. Severe cytologic atypia. †

Note:

  • † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.[10]

How to remember ABCDE:

  • Atypia Bad.
  • Confluent cribriform growth.
  • Desmoplasia.
  • Extensive papillary growth.

Complex endometrial hyperplasia with atypia

  • AKA complex atypical hyperplasia.

General

Microscopic

Features:

  • Increase in size & number of glands + irregular shape - key feature.
  • Cell stratification.
  • Nuclear enlargement.
  • Nuclear atypia:
    • Round nuclei ~ 2-3x the size of a lymphocyte.
    • Grey/translucent chromatin.
    • Nucleoli.
  • Mitoses common.

Note:

  • Atypical nuclei often hide between non-typical nuclei, like peg cells in the fallopian tube.

DDx:

Image:

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Insufficient confluence for carcinoma

ENDOMETRIUM, BIOPSY: 
- COMPLEX ENDOMETRIAL HYPERPLASIA WITH ATYPIA, SEE COMMENT. 

COMMENT: 
The sections show architecturally complex crowded glands with focal 
morular squamous metaplasia and focal cribriforming.  Desmoplasia 
is not identified. The degree of gland confluence is not considered 
sufficient for the diagnosis of endometrial carcinoma. Nuclear atypia 
is present focally.

Insufficient extent for carcinoma

ENDOMETRIUM, BIOPSY: 
- COMPLEX ENDOMETRIAL HYPERPLASIA WITH ATYPIA, SEE COMMENT. 

COMMENT: 
The sections show architecturally complex back-to-back glands with focal 
morular squamous metaplasia and cribriforming. Desmoplasia is not present. 
The extent, i.e. the size of the abnormality, is not considered sufficient 
for the diagnosis of endometrial carcinoma.

Other

Endometrial hyperplasia with secretory changes

General

  • Rare.
  • Secretory changes seen in 1-2% of endometrial hyperplasias/endometrial carcinomas.[12]

Microscopic

Features:[13]

  • Secretory changes - includes at least one of three following:[14]
    1. Stromal decidualization.
    2. Cytoplasmic vacuolization.
    3. Intraluminal secretions.
  • Proliferative-type epithelium. †
    • Mitoses.
    • Nuclear atypia.
    • Pseudostratified epithelium.

Notes:

  • † This is not precisely defined. I suppose it is some of the things Bell and Ostrezega[15] mention (mitoses, nuclear atypia, pseudostratified epithelium).
    • Bell and Ostrezega[15] give a laundry list for differentiating benign secretory endometrium from hyperplasia with secretory changes: focal architectural abnormalities, metaplastic ciliated & "clear" cells, sharp luminal border, epithelial pseudopalisading, nuclear atypia, vesicular nuclei, mitoses.

DDx:

See also

References

  1. ↑ Dietel, M. (Nov 2001). "The histological diagnosis of endometrial hyperplasia. Is there a need to simplify?". Virchows Arch 439 (5): 604-8. PMID 11764378.
  2. ↑ URL: http://www.aafp.org/afp/990600ap/3069.html.
  3. ↑ URL: http://www.aafp.org/afp/20060801/practice.html.
  4. ↑ Latta, E. January 2009.
  5. ↑ 5.0 5.1 Kurman, RJ.; Kaminski, PF.; Norris, HJ. (Jul 1985). "The behavior of endometrial hyperplasia. A long-term study of untreated hyperplasia in 170 patients.". Cancer 56 (2): 403-12. PMID 4005805.
  6. ↑ 6.0 6.1 Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 236. ISBN 978-0443069208.
  7. ↑ 7.0 7.1 McCluggage, WG. (Aug 2006). "My approach to the interpretation of endometrial biopsies and curettings.". J Clin Pathol 59 (8): 801-12. doi:10.1136/jcp.2005.029702. PMC 1860448. PMID 16873562. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860448/.
  8. ↑ Silverberg, SG. (Mar 2000). "Problems in the differential diagnosis of endometrial hyperplasia and carcinoma.". Mod Pathol 13 (3): 309-27. doi:10.1038/modpathol.3880053. PMID 10757341.
  9. ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 239. ISBN 978-0443069208.
  10. ↑ 10.0 10.1 Kurman, RJ.; Norris, HJ. (Jun 1982). "Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma.". Cancer 49 (12): 2547-59. PMID 7074572.
  11. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf. Accessed on: 12 January 2012.
  12. ↑ Simon RA, Hansen K, Xiong JJ, et al. PTEN status and frequency of endometrial carcinoma and its precursors arising in functional secretory endometrium; an immunohistochemical study of 29 cases. Mod Pathol. 2012;25(Suppl 2): 1248A.
  13. ↑ Simon RA. CAP Today. June 2012. Accessed on: 24 April 2013.
  14. ↑ Tresserra, F.; Lopez-Yarto, M.; Grases, PJ.; Ubeda, A.; Pascual, MA.; Labastida, R. (Mar 2003). "Endometrial hyperplasia with secretory changes.". Gynecol Oncol 88 (3): 386-93. PMID 12648591.
  15. ↑ 15.0 15.1 Bell, CD.; Ostrezega, E. (Aug 1987). "The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens.". Hum Pathol 18 (8): 830-8. PMID 3610133.
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