Gynecologic Cytopathology: Glandular lesions

Transcription

1 Gynecologic Cytopathology: Glandular lesions Lin Wai Fung (MSc, MPH, CMIAC) 17/4/2014

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3 Glandular lesions of the uterus Endocervix Endometrium

4 Normal endocervical cells Sheets, strips well-preserved architecture: honeycomb or palisading Nuclei: may show variation in size (2 x enlarged) and shape Ovulation: secretory and with naked nuclei

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6 Normal endocervical cells: denuded nuclei

7 Benign glandular lesions of cervix

8 Cytopathology of Benign glandular lesions of the cervix Reparative changes Endocervical polyp Tubal Metaplasia Microglandular hyperplasia Cells of Lower Uterine Segment

9 Reparative changes May involve: squamous, metaplastic, columnar epithelium Cytology: nuclear size, prominent nucleoli, monolayer sheet with polymorph infiltration, nuclei oriented in same direction (streaming), occasion mitotic figures, no single cells Marked nuclear anisonucleosis + irregular chromatin distribution: atypical endocervcial cell, atypical squamous cell

10 Repair cells

11 Cervical polyps Common Asymptomatic cause intermittent or post-coital bleeding Histology: central connective tissue stalk linked by endocervical, metaplastic cells No specific cytology pattern except large sheets of endocervical cells Sometimes show atypical or reactive nuclei (AGC)

12 Cervical Polyp with atypical cells / repair cells. F/52 inter-menstrual breeding

13 Tubal Metaplasia Benign, non-neoplastic replacement of normal endocervical (or endometrial) epithelium with cells characteristic of the fallopian tube: ciliated, clear cell, non-ciliated secretory cells, and intercalated cells common, prominent in upper third of endocervical canal. Endocervical brush: increase detection in cervical smears flat sheet, cohesive 3-D aggregates, columnar, apical terminal bar with cilia Nuclei, regular, oval, elongated, hyperchromatic, pseudo-stratification: may mimic adenocarcinoma in situ (AIS)

14 Tubal metaplasia with mild nuclear atypia, F/44

15 Microglandular hyperplasia Benign localized proliferation of endocervical glands Incidental finding or associated with polyp Young women associated with pregnancy and contraceptive use Histology: closely packed irregular glands, lined by benign endocervical cells Cytology features: non-specific 2D or 3D sheets of cuboidal and columnar glandular cells with finely vacuolated cytoplasm May have cytologic atypia due to hyperchromatic crowded groups, pseudostratified strip, nuclear enlargement, hyperchromasia (not to overdiagnosis as adenoca or AIS)

16 Microglandular hyperplasia, F/26, Uterus cervix; mild to moderate glandular hyperplasia

17 Cells of the Lower Uterine Segment (LUS) Isthmus of cervix: short transistional zone between endocervical and endometrium Cone biopsy shortens the endocervcial canal: easier access to LUS Cells: mainly endometrial less responsive to hormonal stimulation Endocervical brushes detection, No need to report LUS do not shed spontaneously Cytology: glandular + stromal element, large irregular branched groups, round nuclei, fine chromatin, nuclear crowding, May be mistaken for AIS, adenca Source:

18 Cytology of the Lower Uterine Segment (LUS)

19 Glandular Abnormalities

20 Glandular Abnormalities Cervical cytology screening test for Squamous intraepithelial lesion (SIL), low sensitivity for glandular lesions because of sampling & interpretation

21 Bethesda system 2001 classified 3 types of atypical endocervical cells: 1. Atypical glandular cells, not otherwise specified (AGC, NOS) 2. Atypical glandular cells, favour neoplastic (AGC, favour neoplastic) (If the endocervical origin of glandular cells is sure, specific atypical endocervical cells (NOS, or neoplasic) 3. Endocervical adenocarcinoma in situ (AIS)

22 Atypical endocervical cells vs reactive Reactive endocervical cells may show 2 x in nuclear size and conspicuous nucleoli The Bethesda 2001 (TBS 2001) defined atypical endocervical cells as endocervical-type cells that display nuclear atypia that exceed obvious reactive / reparative changes, but lack unequivocal features of endocervical adenocarcinoma. Reactive endocervical cells

23 Criteria of Atypical Glandular Cells-NOS (AGC, NOS) Architecture Loss of orderly architecture with minimal nuclei overlapping and crowding Cytology Nuclear enlargement 3 to 5 times the size of normal endocervical nuclei. (2 times nuclear enlargement: reactive) Increase N/C ratio smooth nuclear membrane Uniformly distributed granular chromatin Nucleoli may be presence Mild hyperchromasia Some variation in nuclear size and shape

24 AGC (NOS) F/51 Follow up: CxBx: Acute and chronic inflammation with focal erosion

25 Criteria of Atypical glandular cells, favour neoplastic (AGC, favour neoplastic) Architecture Hyperchromatic crowded groups Sheets, strips, irregular clusters, rosette, papillary Atypical single cells Cytology Increased N/C ratio, Nucleoli usually absent Hyperchromasia Even chromatin with coarse granularity Irregular nuclear membranes (Differentiate from Adenocarcinoma in situ (AIS): e.g. lack feathering or rosette)

26 AGC (favour neoplastic) F/47 Follow up: AIS

27 Cytology of Adenocarcinoma in situ (AIS) Architecture Sheets, clusters, strips, and rosettes Nuclear crowding: hyperchromatic crowded group Loss of honeycomb pattern Palisading, feathering, pseudo-stratification Cytology ( feathering best criterion for predicting glandular neoplasia, differentiation from squamous neoplasm and non-neoplastic diagnosis) Nuclei: enlarged hyperchromatic, variation in size, elongated, stratified Nucleoli: may be present N/C ratio mitosis, apoptotic bodies (may be present) Background: clean or inflammatory

28 Adenocarcinoma in situ: F/48

29 Adenocarcinoma in situ F/33

30 Cytological of Endocervical adenocarcinoma Architecture 3-D clusters with vacuolated cytoplasm 2-D sheets, strips or strands, papillary form Isolated cells may be present Cytology Dominant cancer cell: columnar shape Nuclei appearance: hyperchromiasia, anisokaryosis, clearing of chromatin, loss of polarity, macronucleoli, N/C ratio Background Tumor diathesis may present

31 Endocervical Adenocarcinoma F/52

32 Cytology of endometrial lesions

33 Morphology of Benign endometrial cells Include both the glandular and stromal cells Exfoliate in ball or gland-like clusters, single rare 1st half of menstrual cycle: glandular cells surrounding a core of stromal cells ( exodus ) Nuclei: small, round or bean-shaped, regular, degenerated (nuclei detail not clear) Nucleoli: inconspicuous Scant cytoplasm, cell borders not well defined LBP: 3-D cell ball, better chromatin detail, apoptosis

34 Endocervical Endometrial Cell size ++ + Cytoplasm Abundant ++ Scanty Nucleus Oval / elongated Round /bean shaped

35 Benign endometrial cells from menstruating epithelium exodus Key features bloody background in Conventional smear, less blood in LBP exit ball: glandular cells + stromal cell histiocytes + stromal cells in background

36 Benign endometrial cells Day 6

37 Benign endometrial cells Day 4

38 TBS 2001 describes 3 types of Endometrial lesions Benign endometrial cells in women over 40 years of age Atypical endometrial cells, NOS (not further classified as favour neoplastic because of difficulty and not reproducible) Endometrial adenocarcinoma

39 Benign Endometrial Cells in a woman >=40 years (F/47 prolonged mense, FU: Simple endometrial hyperplasia, no cytological atypia)

40 Cytology of atypical endometrial cells, NOS Architecture Small groups: 5 to 10 cells per group Cytology Nuclei slightly / relatively enlarged Mild hyperchromasia Small nucleoli Occasionally vacuolated cytoplasm Cell borders ill-defined Clean background

41 Atypical endometrial cells (NOS) (F/62. PMB Follow up endometrial biopsy: at least complex hyperplasia with atypia)

42 Cytology of Endometrial adenocarcinoma Architecture Irregular aggregates: usually small tight clusters Isolated cells usually seen Compared with endocervical adenoca (direct scrapping), fewer abnormal cells (exfoliated) Cytology Size varies (best differentiated: smallest) Small to prominent nucleoli Nuclei enlarged and irregular shape,eccentrically placed Granular, reticular, clearing Cytoplasm: scant, often vacuolated, may have intracytoplasmic neutrophils Background Finely granular or watery tumor diathesis may be present

43 Endometrial adenocarcinoma, low grade F/52 Follow up : Uterus: endometrioid adenocarcinoma FIGO grade 1

44 Endometrial adenocaricnma, low grade, F/50, perimenopausal bleeding, Uterus: Endometrioid adenocaricnoma, FIGO grade 1

45 Morphologic features for differentiating endocervical from endometrial adenocarcinoma (modified from Ayala MJ, 2011) Cytological features Microarchitecture Endocervical AdenoCA Palisading, sheets, papillary, strips, single cells (less) Endometrial AdenoCA Acini, small, 3-D clusters, single cells (frequent) Shape of cells columnar Cuboidal, rounded Cell size larger smaller Cytoplasm Granular Vacuolated with occasional polymorph infiltration Nuclear size larger smaller Nuclear chromatin coarse fine Macronucleoli common Rare in low grade No. of abnormal cells more less Tumor diathesis Usually present Less prominent, watery or granular

46 Extrauterine adenocarcinoma

47 Extrauterine adenocarcinoma CA metastatic to cervix: unusual Most frequent extragenital origin: ovary, breast, GI tract Clinical correlation and ancillary tests are needed to reach a correct diagnosis Cytology clean background morphology unusual to that of endocervical or endometrial degenerative changes

48 Adenocarcinoma, extrauterine F/56 PMB FU: Endometrial sampling: Adenocarcinoma, suggestive of metastatic from rectal primary

49 Adenocarcinoma (extrauterine, in keeping with metastasis) F/49 Cervical biopsy: metastatic carcinoma, c/w breast primary

50 The End