Gynecologic Cytopathology:

Glandular lesions
Lin Wai Fung
(MSc, MPH, CMIAC)

17/4/2014

Glandular lesions of the uterus

Endocervix
Endometrium

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

Normal endocervical cells: denuded nuclei

Benign glandular lesions of cervix

Cytopathology of Benign glandular lesions of the cervix

Reparative changes
Endocervical polyp
Tubal Metaplasia
Microglandular hyperplasia
Cells of Lower Uterine Segment

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

Repair cells

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)

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

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)

Tubal metaplasia with mild nuclear atypia, F/44

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)

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

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: www.bpac.org.nz/resources/bt/2009/october.asp

Cytology of the Lower Uterine Segment (LUS)

Glandular Abnormalities

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

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)

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

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

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

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)

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

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
(feathering best criterion for predicting glandular neoplasia, differentiation
from squamous neoplasm and non-neoplastic diagnosis)

Cytology

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

Adenocarcinoma in situ: F/48

Adenocarcinoma in situ F/33

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

Endocervical Adenocarcinoma F/52

Cytology of endometrial lesions

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

Endocervical
Cell size
++
Cytoplasm Abundant ++
Nucleus

Oval / elongated

Endometrial
+
Scanty
Round /bean shaped

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

Benign endometrial cells Day 6

Benign endometrial cells Day 4

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

Benign Endometrial Cells in a woman >=40 years

(F/47 prolonged mense, FU: Simple endometrial hyperplasia, no cytological atypia)

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

Atypical endometrial cells (NOS)

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

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

Endometrial adenocarcinoma, low grade

F/52 Follow up : Uterus: endometrioid adenocarcinoma FIGO grade 1

Endometrial adenocaricnma, low grade,

F/50, perimenopausal bleeding, Uterus: Endometrioid adenocaricnoma, FIGO grade 1

Morphologic features for differentiating endocervical from

endometrial adenocarcinoma (modified from Ayala MJ, 2011)
Cytological
features

Endocervical AdenoCA

Endometrial AdenoCA

Microarchitecture

Palisading, sheets, papillary,

strips, single cells (less)

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

Extrauterine adenocarcinoma

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

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

Adenocarcinoma (extrauterine, in keeping with metastasis)

F/49 Cervical biopsy: metastatic carcinoma, c/w breast primary

The End