Polyps. Hyperplasias. CAP 2011: Course AP104. The High Risk Benign Endometrium. Mutter and Nucci 1

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1 Course AP104 Endometrial Hyperplasia A morphologic Definition Hyperplasias Hormonal Effect or Precancer? George L. Mutter, MD Harvard Medical School and Brigham and Women s Hospital Boston, MA Endometrial Hyperplasia A morphologic Definition Properties of Normal, Premalignant, and Malignant lesions Mechanism Estrogen Mutation More Mutation Histology Effect Baseline Polyclonal Field Effect Clonal Neoplasm Aggressive Clonal Neoplasm Anovulatory Polyp (intraepithelial neoplasia) E2 Effect (EM=Normal) Stromal Neoplasm Premalignant neoplasm HR=2-4 HR=1-1.5 HR=45 Diagnosis Normal Proliferative with cysts Disordered proliferative Benign Hyperplasia Anovulatory Carcinoma Polyps Dx background separately May contain other lesions () Do not cycle normally. (Do not date). Not a gross (or hysteroscopic) Dx Endometrial Polyp: A Clonal Stromal Neoplasm Mutter and Nucci 1

2 Endometrial Polyp: A Clonal Stromal Neoplasm Dx Criteria 1. Not Basalis or LUS 2. 2 of three Irregular glands Altered Stroma Thick Vessels Polyp, Mixed endometrial-endocervical endocervical type Senile polyp Senile polyp Diagnostic Classes Nomenclature Benign endometrial hyperplasia (Unopposed Estrogen effect) Topography Diffuse Functional Category Estrogen Effect Treatment Hormonal therapy ICD Diffuse (Field) Lesions Hormonal Changes Endometrial Intraepithelial Neoplasia Carcinoma Focal progressing to diffuse Focal progressing to diffuse Precancer Cancer Hormonal or surgical Surgical stagebased Neoplasm that replaces Compartment Mutter and Nucci 2

3 Unopposed estrogen effect Regularly Irregular Proliferative cysts Disordered Proliferative remodeling thrombi variable density Benign Endometrial Hyperplasia Estrogen over Time * * Disordered Proliferative * Benign Endometrial Hyperplasia Benign Hyperplasia Sequence E2 loss exhausted shedding Benign Endometrial Hyperplasia unopposed E2 unopposed E2 established progestin Benign Endometrial Hyperplasia superimposed prog Mutter and Nucci 3

4 Anovulatory, Exhausted type Anovulatory, Exhausted type Delayed Ovulation Delayed Ovulation Delayed Ovulatory With Breakdown Localized Lesions Neoplasm Cancer Precancer () Polyp (stromal tumor) Sampling (LUS, Cervix,basalis) Secondary effect (fibroid) Mutter and Nucci 4

5 : PTEN PAX2 H&E Concurrent Cancer 39% (43/110) Carcinoma <1 year (Retrospective, Baak 2005) 37% (56/153) Carcinoma at hysterectomy (Prospective Clinical Trial: GOG167, Trimble 2006) >1-Year Cancer Progression Following Biopsy Diagnosis Proportion Cancer Free Benign (DS>1) 2/359 (DS<1) 22/118 Hazard Ratio: 45:1 32% (18/56) of concurrent CA myoinvasive (Prospective Clinical Trial: GOG167, Mutter 2008 n=477 FU months HR Followup Time, Months Baak, Mutter, et al, 2005 (Cancer) BWH Experience new cases on Bx Dx by clinical pool of 8 pathologists, 1 hospital. 88% had some followup (median 74 days) Overall Cancer incidence 35.7% (56/157) 26 initial Bx, 30 during f/u Criterion Architecture Cytology Size >1 mm Exclude mimics Exclude Cancer Diagnostic Criteria Comments Area of Glands>Stroma (VPS<55%) Cytology differs between architecturally crowded focus and background. Maximum linear dimension exceeds 1mm. Benign conditions with overlapping criteria: Basalis, secretory, polyps, repair, etc.. Carcinoma if mazelike glands, solid areas, or significant cribriforming Semere et al, 2011 Mutter and Nucci 5

6 Architecture Area of glands exceeds that of stroma benign benign Turning point 30% 40% 50% Percentage of specimen that is glandular 60% 70% Cytologic Demarcation Minimum Size Region with glands>stroma and altered cytology 1mm minimum diameter Correlates with outcome Exclusions 1mm Normal Tissue LUS/Basalis Secretory endometrium Artifact Polyp Reactive Cancer Mutter and Nucci 6

7 Carcinoma vs. Rambling Glands Extensive Cribriforming Large Solid Areas Myometrial Invasion Mazelike Carcinoma (not ) Villoglandular Solid Cribriform Non-Localizing Involves entire compartment About 20% of all Overrun background glands Cancer vs.? with residual background glands with residual background glands vs. Carcinoma Mutter and Nucci 7

8 Endometrial Polyp Features can overlap with Should be excluded as mimic 1/3 of within Polyp Usually localizing lesion Need substantial cytologic change to Dx?Clinical repercussions of location Polyp in Polyp Subdiagnostic : Gland Crowding n=143 (0.3% of 71,579 specimens) A B Altered cytology Size<1mm Glands < stroma Secretory/Polyp Recommend 3-6 mo f/u Bx or EMC Outcomes (n=143) 77% Benign 19% 4% Cancer C D Nucci et al, 2010 Figure 2 (a, b) Endometrial polyp with focal gland crowding. (c, d) Follow-up sampling showed endometrial intraepithelial neoplasia with crowded glands and cytological demarcation. Inset: : background glands with normal cytology for comparison. Nucci et al, 2010 Progesterone effect Stromal expansion decreases gland density Makes neoplastic cytology bland Nuclear enlargement and rounding in normal cells Withdrawal synchronizes shed PRE-Rx Rx POST-Rx Progesterone effect on cytology Mutter and Nucci 8

9 Management : like atypical hyperplasia (roca, hyst, hormones) Estrogen effect (non-) Symptomatic and/or endocrine Endometrial polyps Symptomatic. Resample if worried. Uncertain Dx. Depends on the problem Mutter and Nucci 9