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Interpretation of endometrial biopsy
- 2. What’s different about EB? Variety of changes due to hormones Biopsy induces artifacts Blind Procedure Multiple, irregularly oriented tissue fragments Mixed with blood and contaminating cervical tissue and mucus
- 3. Indications Determine cause of AUB Status of endometrium in infertile (DATING) POC : spontaneous abortions or MTP • Estrogen replacement in perimenopausal and postmenopausal women • Tamoxifen therapy for breast cancer Assessment of the response to hormonal therapy
- 4. EB as a screening tool for cancer Very low yield of significant abnormalities Not cost effective Hence NOT Recommended
- 5. Causes of AUB (age wise) Adolescence • DUB • Pregnancy Reproductive years • Pregnancy • Endometritis • DUB • Organic lesions • Polyps • Leiomyoma • Adenomyosis • Exogenous hormones Perimenopausal • DUB • Oragnic lesions • Hyperplasia • Polyps • Exogenous hormones • Endometrial carcinoma Postmenopausal • Atrophy • Organic lesions • Hyperplasia • Polyps • Endometrial carcinoma • Exogenous hormones
- 6. Type of biopsy Curettage better than biopsy • Polyps • Low-grade adenocarcinomas • Artifactually distorted normal endometrium Irregular glands of hyperplasia
- 7. Abnormal uterine bleeding Document histologic evidence of glandular and stromal breakdown Foci of stromal foam cells or hemosiderin, sometimes with fibrosis Important when there is no organic cause : conveys endometrial origin of bleed
- 8. EB for infertility evaluation LMP : useful but not precise Ovulatory frequency and length of follicular phase are variable Objective : Evidence of ovulation and histologic date
- 9. Dating The secretory phase is constant (14 days from ovulation) Variations in cycle length occur because of proliferative phase Based on the time of onset of the upcoming menstrual period, not the last menstrual period.
- 10. Stratum compactum Stratum Functionalis Stratum Basalis Secretory endometrium
- 11. LUS Poorly developed glands Plump eosinophilic fibroblastic stroma
- 12. Dating Glandular changes • Tortuosity • Mitosis • Pseudostratification of nuclei • Subnuclear vacuolations • Luminal secretions Stromal changes • Edema • Mitoses • Predecidua • Granular lymphocyte infiltrate
- 13. Regular spacing of glands Intact stroma Proliferative Endometrium Perivascular lymphocytes
- 15. Proliferative endometrium Diagnosis of proliferative phase alone is sufficient
- 16. Interval endometrium Rule of 50% - 50% cells & 50% glands – subnuclear vacuolation (first recognizable changes of ovulation)
- 18. Day 16-17 / POD 2-3 Regular distribution of subnuclear vacuoles
- 19. Day 17-18 / POD 3-4 Secretions + Few supra-nuclear vacuolation
- 20. Day20-21/POD6-7 Peak Secretions + Few vacuoles Peak secretions day 20 Stromal edema from day 21 (naked nuclei) No mitosis or pseudostratification from day 19
- 21. Day 23 -24 / POD 9-10 Perivasuclar pre-decidual changes around spiral arteries Glands show secretory exhaustion Stromal mitosis recur on day 24
- 22. Day 25 / POD 11 Predecidualized oval stromal cells and Granulated lymphocytes (K cells)
- 23. Day 26-27 / POD 12-13 Decidualised stroma with numerous lymphocytes
- 24. Day 28 / POD 14 Menstrual endometrium
- 25. Pitfalls in Dating Absence of surface epithelium compromises the interpretation Lower uterine segment or basalis is not satisfactory for dating (not hormonally responsive) Straight, tubular glands beneath the surface are normal even during secretory phase Presence of secretions does not indicate secretory endometrium Focal glandular crowding caused by tangential sectioning Focal cystic glands or nonreactive glands can occur in normal endometrium
- 26. Pitfalls in Dating Patchy stromal edema is normal by days 17 to 18 Identifying very early pregnancy based on endometrial changes alone is very difficult Stromal changes around spiral arteries assists in the identification of predecidua Lymphocytes and granular lymphocytes do not signify menstruation Difficult to date due to discordance: possible chronic endometritis or polyp
- 27. Fragmentation
- 28. Telescoping
- 32. Artifacts • Adipose tissue: perforation • Colonic mucosa: perforation Emergency !
- 33. Luteal phase defect Histologic date lags > 2 days LPD is clinically significant if it occurs in at least two consecutive biopsies
- 35. Abnormal secretory phase pattern
- 40. Dysfunctional uterine bleeding Indicates ovulatory dysfunction • Inflammation • Polyps • Hyperplasia • Carcinoma • Exogenous hormones • Complications of pregnancy Excludes pathologic processes
- 41. Glandular and Stromal Breakdown
- 42. Stromal collapse
- 44. Stromal collapse with clusters
- 45. Fibrin thrombi
- 48. Esoinophilic papillary syncytial change with stromal blue balls
- 49. Debirs in lumen
- 56. Decidual effect
- 57. Vascular ectasia
- 58. Secretory change and fibrin thrombi
- 60. Plump stromal cells with secretory glands
- 61. Atrophic secretory glands in dense stroma
- 62. Atrophic – stromal nodule in a myxoid stroma
- 63. Signet cell morphology of decidua
- 64. Estrogen + progestin effect Under- developed secretory glands
- 65. Polyp – tamoxifen induced
- 66. Endometritis
- 67. Acute on chronic endometritis
- 71. Reactive change in stromal cells Interlacing fibroblast like
- 72. Reactive change in epithelial cells
- 74. CMV inclusion
- 75. Herpes virus
- 77. Actniomycosis
- 78. Polyp
- 83. Squamous change
- 84. Atrophic change
- 86. Mixed endocervical – endometrial
- 91. Simple hyperplasia : cytological features
- 96. Complex hyperplasia with atypia
- 97. Complex hyperplasia with atypia Cytological features
- 98. Complex hyperplasia with atypia
- 99. Complex hyperplasia with atypia Cytological features
- 100. Simple hyperplasia with atypia
- 101. Complex hyperplasia with atypia With squamous metaplasia
- 104. P53 staining
- 105. Ciliated change
- 106. Eosinophilic change
- 107. Mucinous change
- 108. Secretory change
- 116. Grade 1 Endometrioid adenocarcinoma Confluent pattern, desmoplastic stroma
- 117. Grade 1 Endometrioid adenocarcinoma Bridging / Cribriform
- 118. Grade 1 Endometrioid adenocarcinoma Interconnecting confluent glands
- 119. Grade 1 Endometrioid adenocarcinoma Desmoplastic stroma
- 120. Grade 1 Endometrioid adenocarcinoma Extensive papillary pattern
- 121. Grade 2 Endometrioid adenocarcinoma Solid areas <50%
- 122. Grade 3 Endometrioid adenocarcinoma Solid areas >50%
- 123. Endometrioid adenocarcinoma with squamous morules
- 125. Serous adenocarcinoma Complex papillary pattern
- 126. Serous adenocarcinoma Gaping spaces and high nuclear grade
- 129. Clear cell adenocarcinoma Vacuolated cytoplasm and high grade nuclei with smudged chromatin
- 130. Clear cell adenocarcinoma Hobnail nuclei and sclerosis
- 131. Role of IHC Marker Hyperplasia EIN EIC P53 Patchy Patchy +++ (diffuse) PTEN + - + PAX2 + - +
- 132. Role of IHC Marker Endometrioid Serous Clear cell ER/PR + (>90%) +/- (50%) -/+ (<50%) Ki67 Low High Intermediate p53 Patchy weak positivity +++ (diffuse) - p16 Patchy weak +++ (diffuse) Patchy HNF 1 beta - - +
- 133. Role of IHC Marker Endometrioid Endocervical p16 and HPV Patchy +++ (diffuse) ER/PR + - CEA - + Vimentin + -
- 134. Role of IHC Marker Serous (Endometrial) Serous (Ovarian) WT-1 Patchy or negative +