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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 over-
diagnosis 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 Endometrial
Cell size ++ +
Cytoplasm Abundant ++ Scanty
Nucleus Oval / elongated 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
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

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GLANDULAR LESIONS CYTOLOGY IN CERVICAL CYTOLOGY.pdf

  • 1. Gynecologic Cytopathology: Glandular lesions Lin Wai Fung (MSc, MPH, CMIAC) 17/4/2014
  • 2.
  • 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
  • 5.
  • 6. Normal endocervical cells: denuded nuclei
  • 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
  • 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 over- diagnosis 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: www.bpac.org.nz/resources/bt/2009/october.asp
  • 18. Cytology of the Lower Uterine Segment (LUS)
  • 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 (“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
  • 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
  • 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
  • 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 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 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
  • 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