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Approach to endometrial biopsy

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Endometrial biopsy interpretation for post graduate students in Pathology.

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Approach to endometrial biopsy

  1. 1. Approach to Endometrial Biopsy Dr.CSBR.Prasad, MD., Professor & HOD Deptt. of Pathology Sri Devaraj Urs Medical College Kolar-563101
  2. 2. What do you think of this EM biopsy?
  3. 3. What is the finding here?
  4. 4. What is your impresion on this biopsy? http://www.webpathology.com/image.asp?n=1&Case=568
  5. 5. Some fundamentals • Only endometrium from the fundus is suitable for diagnosis • The functionalis layer is particularly ideal • Basalis layer is generally of little diagnostic value except in two conditions: 1. Carcinoma 2. Irregular shedding • Irregular development is best detected in larger fragments of tissue where structural units retain their relationship • EM from the isthmic region is unsuitable for functional diagnosis as they fail to respond to hormonal changes
  6. 6. Some fundamentals • Proliferative phase may fluctuate between 10- 20days – Dating is not possible • Secretory phase is fixed and hence dating is possible • Cystic dilatation of an occasional gland is not necessarily a sign of hyperplasia • Ovulation may recur sporadically, even years after menopause, the associated corpus luteum is insufficient
  7. 7. EM Biopsy • Different methods of obtaining endometrial sample – Curetting (D&C) – Pipelle biopsy or other equivalent technique – Hysteroscopy and direct biopsy – Endometrial cytology
  8. 8. Adequacy • There are no definitive guidelines / agreements * • If you can make a diagnosis, it is adequate • Clinical details are very important – Eg: Strips of endometrium in a post menopausal woman • Don’t write “inadequate” – Sign out • No stroma • Proliferative without definite stroma • No endometrium • No tissue *Phillips V, McCluggage WG. Results of a questionnaire regarding criteria for adequacy of endometrial biopsies. J Clin Pathol 2005;58:417–9.
  9. 9. EM biopsy, Post menopausal
  10. 10. Algorithm for assessment of the adequacy of an endometrial biopsy specimen McCluggage WG. My approach to the interpretation of endometrial biopsies and curettings . J Clin Pathol 2006;59:801–12.
  11. 11. Indications for EM Biopsy* 4 Main INDICATIONS Other Indications Determine the cause of AUB AGC /EM cells in PAP smear Assessment of response of the EM to hormone Tx Finding thickened EM in US in post menopausal women Status of EM in infertile patients / dating Evacuation of POC (Spontaneous or MTP) *Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach By Michael Mazur, Robert J. Kurman
  12. 12. DDs for presence of adipose tissue in EM samples • Uterine Perforation (Critical value) • Lipoleiomyoma
  13. 13. Myometrium in the curettings • Notify the clinician how much myometrium was there in the curettings • This helps in two ways: 1. Gives info regarding the consistency of myometrium 2. Gives information about the technique of curettage
  14. 14. Artefacts • Telescoping (glands within glands) • Artefactual crowding and compression of glands • Pseudopapillary architecture of superficial strips of EM • Crushed endometrial glands and stroma may be extremely cellular and can cause concern
  15. 15. Telescoping (gland within gland)
  16. 16. Crushed endometrial glands
  17. 17. Pseudopapillary architecture of superficial strips of EM
  18. 18. Normal EM
  19. 19. Proliferative endometrium
  20. 20. Proliferative endometrium
  21. 21. Mitosis - indicator of proliferative activity • Non-reactive endometrium (No mitosis) • Mitosis in post menopausal EM – May be associated with hyperplasia – If there is no hyperplasia: • Continued estrogen stimulation • Prolapse • EM polyp
  22. 22. EM – Status Post menopusal
  23. 23. Secretory endometrium
  24. 24. Endometritis Common components in EM: • Lymphocytes, including natural killer cells and lymphoid aggregates • PMNs: Premenstrual and menstrual phases Plasma cells: * • Plasma cells: Is it always endometritis? • Other morphological features that favour endometritis: – Disturbance in maturation—focal areas that are out of cycle with other areas – Stromal edema and – Characteristically, a spindle-cell alteration of the stroma, especially around glands – Glandular architectural complexity and cytological atypia *Bayer-Garner IB, Korourian S. Plasma cells in chronic endometritis are easily identified when stained with syndecan-1. Mod Pathol 2001;14:877–9
  25. 25. Lymphoid aggregate
  26. 26. Spindle-cell alteration of the stroma, especially around glands
  27. 27. Endometritis In the absence of other morphological features exhaustive search for plasma cells is unnecessary
  28. 28. Endometritis • Focal necrotising endometritis* • Granulomatous endometritis – Tuberculosis – Sarcoidosis – Others *Bennett AE, Rathore S, Rhatigan RM. Focal necrotizing endometritis: a clinicopathologic study of 15 cases. Int J Gynecol Pathol 1999;18:220–5.
  29. 29. EM polyp • 40-50yrs (rare before menarche, can occur after menopause) • Site: Fundus and cornua • Often pedunculated • Histology: – Composed of glands and stroma – Mostly proliferative changes (cyclical changes are rare) – Foci of squamous metaplasia – Smooth muscle may form a component – Blood vessels are thick walled and tortuous • Rarely carcinoma can arise (3%) – Through examination of polyp / stalk is important – Atypicalities in a post menopausal woman warrants hysterectomy
  30. 30. EM polyp • Proliferative activity is common in endometrial polyps, even in postmenopausal women • A diagnosis of simple hyperplasia should not be made in the case of an endometrial polyp • Carcinomas may arise in endometrial polyps • Endometrial polyps are particularly common in association with tamoxifen • There is a peculiar tendency for serous carcinoma and EIC to arise within endometrial polyps whether sporadic or associated with tamoxifen* *Silva EG, Jenkins R. Serous carcinoma in endometrial polyps. Mod Pathol 1990;3:120–8.
  31. 31. EM polyp
  32. 32. Metaplasias - Epithelial • Epithelial metaplasias: Squamous or mucinous – Associated with hyperplasia / carcinoma • Ciliated metaplasia: Applicable only when extensive resembling fallopian tube • Papillary syncytial metaplasia: – May be a reparative response – When florid, this may be suggestive of a serous carcinoma or an EIC • Mucinous metaplasia • Benign papillary proliferations
  33. 33. Squamous metaplasia
  34. 34. Tubal metaplasia
  35. 35. Benign papillary proliferation
  36. 36. Simple mucinous metaplasia in the basalis of an atrophic endometrium
  37. 37. Include ichthyosis uteri
  38. 38. Metaplasias - Stromal • Formation of smooth muscle, cartilage and bone Importance: May be it difficult to assess myometrial invasion in carcinoma. What are the differentials for stromal metaplasia? Retained fetal parts Int J Gynecol Pathol 2007;26:115
  39. 39. Metaplasias - Stromal Endometrial stromal nodule with smooth muscle metaplasia
  40. 40. Effects of Tamoxifen on the Endometrium • Tamoxifen is widely used as adjuvant therapy in the management of breast cancer • Tamoxifen may exert a proliferative effect on the endometrium • The risk increases with increasing duration and dosage of tamoxifen EFFECTS: • Benign polyps (most common) • Stromal fibrosis • Stromal condensation around glands (DD Adenosarcoma) • Endometrial hyperplasia • Endometrioid and Non-Endometrioid carcinomas • Tamoxifen-associated polyps should be extensively sampled
  41. 41. EM Hyperplasia Def: Endometrial proliferation with an increase in gland to stroma ratio (from 2:1 to 3:1). Classification of endometrial hyperplasia: – WHO 1994 - Four tier system – WHO 2014 – Two tier system Atypia: • Vesicular nuclei • Prominent nucleoli • Rounding of nuclei • Increased cytoplasmic eosinophilia
  42. 42. New WHO classification of endometrial hyperplasias - 2014 New term Synonym Genetic changes Coexistent invasive endometrial carcinoma Progression to invasive carcinoma Hyperplasia withoutatypia Non-atypical EM hyperplasias Low level of somatic mutations < 1 % RR: 1.01– 1.03 Atypical hyperplasia/en dometrioid intraepithelial neoplasia Atypical EM hyperplasias, EIN Many of the genetic changes typical for endometrioid endometrial cancer are present 25–33 % 2 59 % 1 RR: 14–45 1. Antonsen S L, Ulrich L, Hogdall C. Patients with atypical hyperplasia of the endometrium should be treated in oncological centers. Gynecol Oncol. 2012;125:124–128 2. Zaino R, Carinelli S G, Ellenson L H, Lyon: WHO Press; 2014. Tumours of the uterine Corpus: epithelial Tumours and Precursors; pp. 125–126.
  43. 43. EM hyperplasia
  44. 44. Simple hyperplasia without atypia http://www.webpathology.com/image.asp?n=1&Case=568
  45. 45. Complex hyperplasia without atypia http://www.webpathology.com/image.asp?n=1&Case=568
  46. 46. Complex hyperplasia without atypia
  47. 47. Atypical hyperplasia
  48. 48. Atypical hyperplasia
  49. 49. Atypical hyperplasia
  50. 50. Complex hyperplasia without nuclear atypia & Carcinoma
  51. 51. Complex hyperplasia with atypia • Regresses in about 57% of cases • Progression to adenocarcinoma occurs in about 30% of cases • Hysterectomy soon after biopsy: between 23% and 48% harbor EM adenocarcinoma http://www.webpathology.com/image.asp?n=8&Case=568
  52. 52. Benign mimics of EM hyperplasia • Artefacts • Endometritis • Endometrial polyp • Arias-Stella reaction • Disordered proliferative endometrium • Benign papillary proliferations • Lower uterine segment endometrium
  53. 53. Disordered proliferative endometrium
  54. 54. Immunohistochemical staining of FOXA1 and AR in normal endometrium, atypical hyperplasias, and endometrial cancer Qiu, Meiting, Bao, Wei, Wang, Jingyun, Yang, Tingting, He, Xiaoying, Liao, Yun, Wan, Xiaoping . FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer BMC Cancer 2014; 14:78 ·
  55. 55. Cyclin D1 staining 1-Surface epithelium 2-Complex hyperpasia 3-Endometrioid adenocarcinoma (+) and adenomyosis(-)
  56. 56. Arias – Stella reaction
  57. 57. Extensive regions of necrosis in curettings - Causes • Degenerating carcinoma • Septic abortion • Infarcted polyp • Degenerated submucosal leiomyoma
  58. 58. Extensive regions of necrosis better microscopic evidence must be sought before making a definitive diagnosis of carcinoma
  59. 59. Adenocarcinoma of endometrium • Criteria helpful in distinguishing carcinoma from hyperplasia: The tumor is probably malignant if: – Glands are closely packed without intervening stroma for at least half the low power field – If gland Lumina containing multiple thin branching papillary projections with a collagenous core with neoplastic epithelium occupying more than half of low-power field – If sheets of squamous cells occupy more than half of low- power field – Bridging between the adjacent glands – Cribriform pattern – Luminal necrosis with PMN infiltration – If stroma between the glands is collagenous
  60. 60. Some tips • Interact with your clinician / History is important for interpretation • Separate the endometrial tissue proper from the blood clots for processing • Endometrium with surface epithelium is best for interpretation. Absence of surface epithelium compromises interpretation • Do not report hyperplasia on secretory endometrium • In all cases of abnormal uterine bleeding, consider the possibility of polyp • Finding fat in EM curetting is a critical value. It should be intimated to the clinician • Aware of the mimics • All endometrial cancers should be typed and, if appropriate, graded, even for small biopsy specimens
  61. 61. Thank you

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