Endometrial hyperplasia

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See Endometrium for an introduction to the topic.

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]

Ki-67

There is one paper that looks at Ki-67:[6]

Diagnosis Percent positive
Secretory phase endometrium
15%
Proliferative phase endometrium
42%
Simple hyperplasia
26%
Simple hyperplasia with atypia
23%
Complex hyperplasia
16%
Complex hyperplasia with atypia
42%

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:[7]

  • 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:[7]

  • 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:[9]
    • 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

  • Abbreviated CEH.

Complex endometrial hyperplasia with atypia

  • AKA complex atypical hyperplasia.

Other

Endometrial hyperplasia with secretory changes

General

  • Rare.
  • Secretory changes seen in 1-2% of endometrial hyperplasias/endometrial carcinomas.[10]

Microscopic

Features:[11]

  • Secretory changes - includes at least one of three following:[12]
    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[13] mention (mitoses, nuclear atypia, pseudostratified epithelium).
    • Bell and Ostrezega[13] 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:

Images:

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. Abike, F.; Tapisiz, OL.; Zergeroglu, S.; Dunder, I.; Temizkan, O.; Temizkan, I.; Payasli, A. (2011). "PCNA and Ki-67 in endometrial hyperplasias and evaluation of the potential of malignancy.". Eur J Gynaecol Oncol 32 (1): 77-80. PMID 21446331.
  7. 7.0 7.1 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.
  8. 8.0 8.1 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/.
  9. 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.
  10. 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.
  11. Simon RA. CAP Today. June 2012. Accessed on: 24 April 2013.
  12. 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.
  13. 13.0 13.1 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.