Pathology of the Upper Genital Tract and Endometriosis

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1 Pathology of the Upper Genital Tract and Endometriosis Richard W. Lieberman, MD, FCAP, FACOG University of Michigan Medical School Dept of Pathology and Obstetrics & Gynecology

2 Clinical Significance of Uterine Pathology Indications for Hysterectomy in the United States Leiomyoma uteri Dysfunctional uterine bleeding Genital prolapse Endometriosis Chronic pelvic pain Endometrial hyperplasia Carcinoma (cx, endo, other) Pelvic inflammatory disease 30% 20% 15% 15% 10% 6% <5% <5% N=590,000 hysterectomies annually NEJM 328: 856, 1993

3 Uterine Pathology Overview Endometrial (Epithelial) Pathology Estrogen-related related Pathology Non-hormonally Mediated Pathology Mesenchymal Pathology of the Uterus Endometrial Stromal Smooth muscle

4 Normal Uterus

5 Hormonal Effects on the Endometrium End Organ of the Reproductive Cycle General estrogen proliferation of glands, stroma, and spiral arteries progesterone glandular secretion stromal decidualization

6 Ovulatory, Endometrial, and Hormonal Cycle Summary Estrogen Ovulation Follicular Phase Luteal Phase Progesterone 1 28 Day of Cycle

7 Proliferative Endometrium

8 Secretory Endometrium

9 Menstrual Endometrium

10 Abnormal Uterine Bleeding Differential Diagnosis menstrual cycle endocrine dysfunction pregnancy related causes benign conditions of the genital tract malignant conditions of the genital tract

11 Anovulatory Bleeding

12 Endometrial Progression to Carcinoma: A Spectrum of Proliferative Changes Disordered Proliferative Hyperplasia Atypical Hyperplasia Carcinoma

13 ISGYP & WHO Classification of Endometrial Hyperplasia Hyperplasia without cytologic atypia simple complex Atypical Hyperplasia simple complex Kurman & Silverberg, AFIP Fascicle 3, p. 13, 1992.

14 Non-atypical Hyperplasia Simple Complex

15 Atypical Hyperplasia

16 Follow-up of Untreated Hyperplasia: Progression to Endometrial Adenocarcinoma Type Regression Persistence Progression Simple 80% 19% 1% } 2% Complex 80% 17% 3% Simple Atypical Complex Atypical 70% 57% 23% 14% 8% 29% } 23% Cancer 56: 403, 1985

17 Endometrial Adenocarcinoma: Destructive Stromal Invasion Desmoplasia

18 Adenocarcinoma: Cribriform Gland Formation

19 Endometrial Carcinoma Type I estrogen excess endometrioid grade tumors good prognosis caucasian 5th & 6th decade Type II NOT estrogen related high grade tumors UPSC, clear cell poor prognosis African-American American 6th & 7th decade

20 Endometrial Carcinoma Histologic Classification Endometrioid Typical Variants with squamous differentiation secretory carcinoma Mucinous adenocarcinoma Type I Uterine papillary serous carcinoma Clear cell adenocarcinoma Undifferentiated carcinoma } Type II

21 Type I Endometrioid Adenocarcinoma Prototype Polycystic Ovarian Disease & Endometrial Cancer

22 Type II Endometrial Cancer Serous Clear Cell

23 Type II Uterine Serous Adenocarcinoma

24 Mesenchymal Uterine Tumors Smooth Muscle leiomyoma leiomyosarcoma Endometrial Stroma stromal nodules endometrial stromal sarcoma

25 Leiomyoma Uteri a.k.a fibroids Clinical hereditary predilection slowly enlarge until menopause, then regress estrogenic stimulation treat with anti-estrogen (GnRh agonist) variable symptomatology

26 Uterine Fibroids

27 Leiomyoma Estrogen Sensitive

28 Leiomyosarcoma Clinical usually post-menopausal rapidly enlarging uterus NO association with prior radiation Gross solitary mass hemorrhagic with areas of necrosis Other Notables rare, 1 for every 800 leiomyomas Stage I-II I II 50% five year survival

29 Leiomyosarcoma

30 Tumor Uterine Mixed Mesodermal Tumors Epithelial Component Mesenchymal Component Adenofibroma (myoma) Adenosarcoma MMMT, homologous MMMT, heterologous Benign Benign Malignant Malignant Benign Malignant Sarcoma, homologous Sarcoma, heterologous MMMT = Malignant Mixed Mesodermal (Müllerian) Tumor heterologous elements = skeletal muscle, cartilage, adipose, bone homologous elements = smooth muscle, stroma, blood vessels

31 MMT - Adenomyoma

32 Carcinosarcoma Homologous MMMT

33 MMMT - Carcinosarcoma Heterologous

34 Uterine Sarcoma Survival* 120 % Low Grade ESS High Grade ESS MMMT, homologous Leiomyosarcoma MMMT, heterologous YEARS *all stages

35 Endometriosis Definitions endometriosis presence of glands and stroma adenomyosis (endometriosis interna) same as above, within the myometrium endosalpingiosis glands only

36 Endometriosis Implant: glands & stroma Powder Burns

37 Adenomyosis: Endometriosis Interna

38 Endometriosis Clinical Clinical familial predilection commonly associated with infertility Symptoms symptoms variable range: asymptomatic incapacitating chronic pelvic pain

39 Endometriosis Endometrioma uterus Ovarian Endometriosis Chocolate Cyst

40 Endometriosis: Theories of Origin Retrograde Menstruation Coelomic Metaplasia Hematogenous or Lymphatic Spread Combination of Above

41 Endometriosis Malignant Behavior 99+% benign, but inflammatory conditions mimic carcinoma true malignant transformation <1% of all patients with endometriosis