PATHOLOGY OF THE UTERINE CERVIX SUMALEE SIRIAUNGKUL, M.D. DEPARTMENT OF PATHOLOGY
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1 PATHOLOGY OF THE UTERINE CERVIX SUMALEE SIRIAUNGKUL, M.D. DEPARTMENT OF PATHOLOGY
2 PATHOLOGY OF THE UTERINE CERVIX Anatomy and physiology Benign diseases 1. Infections 2. Benign tumors and tumor-like lesions Premalignant lesions Malignant tumors
3 Endometrium Myometrium
4 UTERINE CERVIX Lower part of the uterus Exocervix and Endocervix Stratified nonkeratinizing squamous epithelium and Simple columnar mucin-secreting epithlium Fibrous,muscular and elastic tissue
5
6 Exocervix
7 Endocervix
8 Endocervix
9 Location of squamocolumnar junction in relation to the external os varies depending upon age, menstrual status, pregnancy and oral contraceptive use Ectropion = eversion of the columnar epithelium onto the ectocervix, when the cervix grows rapidly and enlarges under the influence of estrogen, after menarche and during pregnancy
10 Squamous metaplasia = physiological replacement of the everted columnar epithelium on the ectocervix by a newly formed squamous epithelium from the subcolumnar reserve cells. Transformation zone = region of the cervix where squamous metaplasia occurs Identifying the transformation zone is of great importance in colposcopy, as almost all manifestations of cervical neoplasia occur in this zone.
11 Squamocolumnar junction (SCJ) The point where the squamous epithelium meets the columnar epithelium 11
12 Location of the squamocolumnar junction and transformation zone 12 (a) Before menarche (b) After puberty / early reproductive age
13 (c) women in her 30s 13 (d) Perimenopausal (e) Post-menopausal
14 Transformation zone 14
15
16
17 Normal cervix
18 Cervical ectopion
19 Diseases of The Uterine Cervix Infections : Bacterias, Viruses ( HPV, HSV ), Others Benign Tumors and Tumor-like Lesions : Polyp / Microglandular Hyperplasia : Leiomyoma Premalignant and Malignant Lesions
20 Classification of HPVs Low risk HPV HPV types: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81 High risk HPV HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 Baseman and Koutsky JCV 32S, 2005, S16-S24 REVIEW
21 Human Papillomavirus 72 Capsomers HPV Particle HPV Genome L1 protein ----> HPV genotyping -----> Prophylactic HPV vaccine
22 The Relationship HPV is An Infection Lesion is A Disease No HPV No Cervical Cancer
23 How does HPV cause cervical precancer & cancer? Persistent infections with high-risk HPV types Schiller, J. T. (2010). "Current understanding of the mechanism of HPV infection". Gynecologic Oncology 118 (1 Suppl): S12. doi: /j.ygyno
24 Premalignant Lesions Squamous lesion 1. Dysplasia- Carcinoma in situ ( CIS ) (mild / moderate / severe) - CIS 2. Cervical Intraepithelial Neoplasia ( CIN ) (CIN 1 / CIN 2 / CIN 3) 3. Squamous Intraepithelial Lesion ( SIL ) (Low- / High- grade SIL) Adenocarcinoma in situ ( AIS )
25 * Classification of Precancerous Lesions * Dysplasia System CIN System Bethesda System Mild Moderate Severe CIS CA CIN 1 CIN 2 CIN 3 CA LSIL HSIL CA
26 Host factors Environmental factors The three steps of cervical carcinogenesis
27 Disease progression Time Months Years Normal epithelium HPV infection; koilocytosis CIN I CIN II CIN III Carcinoma Screening Treatment Low-grade squamous intraepithelial lesions (LSILs) High-grade squamous intraepithelial lesions (HSILs)
28 Squamous Intraepithelial Lesions The Bethesda System ( TBS ) Current concepts of pathogenesis and clinical behavior Two grades : Low- grade SIL / low-risk HPV / Follow : High-grade SIL / high-risk HPV / Treat Use for both cytologic ( Pap Smear) and histologic diagnosis
29 Criteria for Grading SIL Degree of nuclear abnormality Location of mitotic figures and undifferentiated cells Abnormal mitotic figures Koilocytes
30 CONDYLOMA ( LSIL ) HPV infection HPV 6, 11 (exophytic lesion) HPV 16,18,31,33 (flat lesion) Koilocytes frequently present Mostly diploid / polyploid No abnormal mitotic figures Undifferentiated cell / mitosis : Lower third Natural history : Spontaneous regression
31 High-grade SIL = Precancer High risk types of HPV (16,18,58,52,33,45,) Koilocytes - occasionally present Usually aneuploid Abnormal mitotic figures Undifferentiated cells / mitosis : upper two thirds Natural history : Persistence / Progression
32 Age and disease severity correlation Age ( X+SD) Yrs. P <0.001, p for trend
33 EXOPHYTIC CONDYLOMA
34
35 Squamous Intraepithelial Lesion
36 LSIL
37 HSIL
38 Squamous Intraepithelial Lesions Age years No abnormal symptoms ( Bleed / Leukorrhea ) Diagnosis1. Screening (Cytology / HPV test / VIA ) 2. Colposcopy 3. Biopsy
39 Screening Conventional pap smear (CP) : กรมการแพทย /สปสช Liquid-based cytology (LBC) HPV test (Hybrid Capture 2, Cervista, Cobas 4800) aged 30 years or older with HPV genotyping (HPV16/18) Tumor markers (P16 / Ki67 / DNA methylation) VIA (visual inspection aided by acetic acid) ใช ในประเทศก ำล งพ ฒนำ(เอเช ย/อ ฟร กำ) / กรมอนาม ย (อาย ไม เก น 45 / บ านไกล)
40 Sensitivity for Detection of HSIL & Cancer Conventional Pap 53% Liquid-based cytology (LBC) 74% HPV testing (HC 2) HPV testing + Liquid-based cytology 96-99% 100%*** 10 %Sensitivity for CIN ***Negative predictive value ~ % Ref: 1. Clavel C, e tal. BJC 2001;89: Cuzick J, e tal. IJC 2006;119: Ronco G, et al. JNCI 2006;98:765
41 PAP Smaer
42 Comparison between LBC and Conventional Pap LBC
43 Plastic spatula Cytobrush / Bloom
44 LBC
45 Fixation for cytologic smear 95% alcohol
46 Pap LBC ASC LSIL HSIL
47 NORMAL
48 LSIL
49 HSIL
50 Colposcope
51 Adenocarcinoma In Situ (AIS) Precursor of invasive adenocarcinoma Asssociated with SIL (30-60 % of cases) Invasive carcinoma must be excluded by deep CONE biopsy (Conization)
52
53
54 Before fixation in formalin 1.Insert forceps in the os gently 2.Cut through 12 o clock or other 3.Avoid touching on the mucosa and lesion
55 Fixative for tissue specimens Formalin The best = 10% Buffered formalin Use true 10% formalin If false = Disaster How much is formalin volume? 10 x volume How fast is the penetration rate? 1 mm / hour
56
57
58
59 Microinvasive Squamous Cell Carcinoma Age years No abnormal symptoms ( Abnormal bleed / Leukorrhea) Diagnosis 1. Screening (cytology +/- HPV test) 2. Colpolscopy 3. Definite Dx. need Conization (LEEP) / Hysterectomy
60 WHO 2003 A B A=Horizontal spread 7 mm B=Depth 5 mm
61 Measurement of invasion อพน
62
63 Invasive Squamous Cell Carcinoma (80%) Mean age 45 years ( CMU data 2556: 22-90, mean 54 ) Abnormal bleeding or Leukorrhea ( minority of asymptomatic cases) Diagnosis : Biopsy Treatment : Surgery/ Radiation / Chemotherapy
64 Invasive Squamous Cell Cercinoma Gross features 1. Exophytic mass 2. Ulcerative infiltrative 3. Noduloinfiltrative Histologic subtypes 1. Keratinizing SCC / Nonkeratinizing SCC 2. Well / Moderately / Poorly Differentiated SCC
65
66
67 Histologic Classification : WHO 2014 Epithelial Tumors Squamous cell carcinoma (75-80% / 80%) Adenocarcinoma (20-25% / 15%) Other Epithelial tumors adenosquamous carcinoma (2%) adenoid cystic adenoid basal neuroendocrine carcinoma (2%) undifferentiated
68 Histologic Classification : WHO 2014 Squamous tumors (Early invasive) Microinvasive SCC (MICA) or Superficially invasive SCC Squamous cell carcinoma Typical Keratinizing (well differentiated) Non-keratinizing (moderately / poorly) Variants Basaloid* Verrucous Warty Papillary Lymphoepithelioma-like Squamotransitional*
69 Chula/Siriraj Squamous cell carcinoma, moderately differentiated Squamous cell carcinoma, well differentiated Squamous cell carcinoma, poorly differentiated
70 Adenocarcinoma
71 * มะเร งปากมดล กในประเทศไทย : จากอด ตส ป จจ บ น * คศ./พศ. รายใหม (คน/ว น) เส ยช ว ต (คน/ว น) 2008/ (27) 5216 (14) 2010/ (29) 5517 (15) 2015/ (32) 6309 (17)
72 *** มะเร งปากมดล กในจ งหว ดต างๆในประเทศไทย พ.ศ. 2553
73 *Min-Max = years, mean= 50 yrs ผ หญ งไทยเป นมะเร งปากมดล กมากท ส ดเม ออาย เท าไร? (สถ ต ท จ งหว ดเช ยงใหม พศ ) Age (yrs) Number % Total
74 Etiology and risk factors Human papillomavirus (HPV) Others
75 Cervical Cancer Prevention Primary prevention (Risk reduction): Avoid exposure, HPV vaccine Secondary prevention (Early detection) Screening (HPV testing, Cytology) Tertiary prevention (Treatment)
76 ส อประกอบการเร ยน 1. (Training material) 2. Pictures of gross lesion & histopathlogy บร หารหล กส ตร 3. eslide.med.cmu.ac.th Registration : Name / Surname : add. : Activation key repro2016
77 Thank You for your attention
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