Glandular lesions in cervical cytology. Margareta Strojan Fležar Institute of Pathology Faculty of Medicine University of Ljubljana Slovenia
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1 Glandular lesions in cervical cytology Margareta Strojan Fležar Institute of Pathology Faculty of Medicine University of Ljubljana Slovenia 2nd PANNONIA CONGRESS OF PATHOLOGY, SIÓFOK, HUNGARY, MAY 2012
2 Glandular cells in cervical smears 3 rd TUBAL 2 nd ENDOMETRIAL Lower uterine segment 1 st ENDOCERVICAL
3 Glandular cells in cervical smears Transfomation cone junction cone Endocervical cells key component of Pap test No sq metaplastic/ endocervical cells BETHESDA: Smear sufficient for evaluation comment about the smear quality!!! Salomon&Nayar. The Bethesda system for reporting cervical cytology; 2001
4 Glandular cells in cervical smears Cervical cytology primarily screening test for squamous intraepithelial lesion and squamous cell carcinoma Sensitivity for glandular lesions limited by problems with sampling and interpretation Rare findings?brush,?bethesda Squamous cell carcinoma AIS: Adenocarcinoma in situ Moriarity et al. Diagn Cytopathol 2003
5 Endocervical glandular cells - architecture Strips, pallisading (picket fence, palisade)
6 Endocervical glandular cells - architecture Honeycomb pattern
7 Reactive endocervical cells Common Hormonal influences Inflammation Polyps DD: neoplastic cells, 3-D groups!!!, elongated nuclei, uneven granular chromatin BETHESDA: Non-neoplastic changes
8 Reactive endocervical/endometrial cells with IUD Clinical data! BETHESDA: Non-neoplastic changes
9 Tubal metaplasia Cilia: when these you divine, it is a fine benign sign! Richard DeMay cilia BETHESDA: Non-neoplastic changes
10 BETHESDA: Non-neoplastic changes Tubar metaplasia - high endocervical cells? Cilia + terminal plate
11 Endometrial cells - exfoliated Exodus: day 6-10 Glandular and stromal cells?endometrial pathology: second half of cyle (anovulatory cycle, atrophy, post-partum, post-abortum, instrumentation, IUD, endometriosis, tuboendometr. metaplasia, endometritis, pyometra, leiomyoma, polyp, HRT, OHC, carcinoma (5% PM)) Postmenopausal!!! exodus Clinical correlation advised (menstrual history, age) BETHESDA: Endometrial cells in women 40 yrs
12 Endometrial cells in cervical smear Direct sampling-abrasia of the lower uterine segment Not reported...
13 Atypical endocervical cells Benign cellular changes with atypia mimics of glandular neoplasia Inflammation, IUD, RT Polyps, microglandular hyperplasia, tubal metaplasia HG (squamous) lesions: ~10-50% DD: tubal metaplasia, cilia? BETHESDA: Atypical endocervical cells - of unknown significance
14 BETHESDA: Atypical glandular cells - favour neoplastic Histology: CIN 2
15 Endocervical adenocarcinoma in situ Loss of honeycomb Nuclear crowding, overlap Pallisading, feathering Nuclei elongated, coarse chromatin BETHESDA: Endocervical adenocarcinoma in situ
16 Endocervical adenocarcinoma Different histologic types cytology? Tumor diathesis, nuclear clearing, nucleoli BETHESDA: Adenocarcinoma - endocervical
17 Atypical endometrial glandular cells Benign/atypical nuclear size Polyp, IUD, endometritis, endom hyperplasia, carcinoma Pap test is not screening procedure for detection of endometrial carcinoma BETHESDA: Atypical endometrial cells - of unknown significance
18 Endometrial adenocarcinoma Cytology / grade Tumor diathesis finely granular / watery Pap test is not screening procedure for detection of endometrial carcinoma BETHESDA: Adenocarcinoma - endometrial
19 Other glandular cells - mlg Extrauterine adenocarcinoma Ovary Fallopian tube Metastases Serous carcinoma - ovary fallopian tube BETHESDA: Adenocarcinoma - extrauterine
20 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA Major challenge in gynecological cytopathology Rare finding: incidence of AGC 0.46%- 2.5% Limited reproducibility of AGC interpretation Significant underlying pathology: % (CIN2/3) Non-cervical uterine or adnexal carcinoma Zhao et al. Gynecol Oncol 2009, Raab et al. Acta Cytol 2008
21 ZORA slovenian national cervical screening program Zgodnje Odkrivanje predrakavih sprememb na materničnem vratu
22 ZORA To decrease incidence and mortality from cervical cancer in Slovenia Pilot project 1998 LJ, 2001 Izola, Koper, Piran, 2003 nation-wide Aim: to screen at least 70% of women between years of age every 3 years Invitations for non-attenders Gynecological examination and the Pap test (conventional: Ayre s spatula and brush)
23 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA No. of histologically confirmed new cervical cancers in Slovenia 250 No SCC AC OTHER TOTAL ZORA Year : 210 cases = : 129 cases = %
24 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA IP FM UL 2008: cervical smears ZORA Registry: 99 (0.23%) cases, different grades of atypical glandular cells AGC: 77/ % SA-GC/AIS: 12/ % Adenocarcinoma (AC): 10/ %
25 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA HISTOPATHOLOGIC FINDINGS In 52/77 (67.5%) AGC biopsy not performed Follow-up cervical smears (acc. to cytol guidelines) All negative for neoplasia in 2011
26 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA HISTOPATHOLOGIC FINDINGS in 32% AGC CGIN HG only in one case (1.3%) CIN in 12 patients (15.6%), most of them (9 cases, 11.7%) were CIN 2 and CIN3 Benign: 11 (14.3%) EM Adenocarcinoma: 1 (1.3%) CGIN CIN3
27 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA HISTOPATHOLOGIC FINDINGS in SA-GC /AIS Adenocarcinoma (2 EC, 2 EM): 4 patients (33.3%) CIN: 6 patients (50%, 5/6 CIN 2 and CIN 3) Benign: 2 (16.7%) SA-GC EM CA AIS Polyp CIN2 AIS EC CA
28 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA HISTOPATHOLOGIC FINDINGS in ADENOCARCINOMA Malignancy confirmed in 7 patients (70%) EM ca: 4 Meta ovarian ca: 2 SCC: 1 CIN: 3 cases (30%), 2/3 CIN3 EM AC EM CA - meta AC CA SCC CIN3
29 CERVICAL SCREENING FOR GLANDULAR NEOPLASIA ZORA: HPV triage testing (SLO Oct. 2010) Cervical cytology sample in liquid medium HPV DNA Hybrid Capture 2 (hc2): HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 Indications: Atypical squamous cells NOS (5-12% CIN-VS expected) Atypical glandular (endocervical) cells - NOS LSIL after age 35 Follow-up of CIN1 Follow-up after TH of CIN Rabelo-Santos et al. Cytopathology 2008
30 CERVICAL CANCER AUDIT Audit of interval cervical cancers in the context of all the components of the routine screening process Re-screening of negative or low grade smears before the diagnosis of invasive cancer presents an important part of the audit. European guidelines for quality assurance in cervical cancer screening. 2 nd ed., 2008.
31 CERVICAL CANCER AUDIT Slovenia: only cytopathology part of the audit Complete audit of all screening components has not been conducted yet! 1 st cytology audit 2008 for cervical cancer diagnosed in 2006 : negative or low-grade smears reviewed from 2003 (beginning of ZORA) till 2006 Repše Fokter A, Pogačnik A, Snoj V, Primic-Žakelj M, Strojan Fležar M. Cytopathology 2012.
32 CERVICAL CANCER AUDIT Underdiagnosed cervical smears were less likely to be found in endocervical adenocarcinomas compared to squamous cell carcinomas Inadequate sampling (EAC in cervical stroma or deeper in the cervical canal) Repše Fokter A, Pogačnik A, Snoj V, Primic-Žakelj M, Strojan Fležar M. Cytopathology 2012.
33 CERVICAL CANCER AUDIT Underdiagnosed cases: representative highly atypical glandular cells found on the review but not recognized originally Repše Fokter A, Pogačnik A, Snoj V, Primic-Žakelj M, Strojan Fležar M. Cytopathology 2012.
34 Glandular lesions in cervical cytology Cytotechnologists/screeners and cytopathologists alike very rarely see true premalignant and malignant (endocervical) glandular cells in routine everyday practice Continuous medical education in cervical glandular cytology! Hvala za pozornost!
35 XLIIIrd PROFESSOR JANEZ PLEČNIK MEMORIAL MEETING with International Symposium Advances in Cytopathology; Bridge between Clinics and Diagnostic Pathology December 6-7, 2012 Institute of Pathology, Faculty of Medicine University of Ljubljana, Korytkova 2, Ljubljana, Slovenia in cooperation with Department of Cytopathology, Institute of Oncology Ljubljana, Slovenia
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