Gynecologic cytopathology

A cytology specimen with LSIL. Pap stain. (WC/Nephron)

Gynecologic cytopathology is a subset of cytopathology. Gynecologic usually refers to Pap test specimens, i.e. uterine cervix, vaginal vault; other gynecologic specimens are considered non-gynecologic.

This article deals only with cervical cytopathology. An introduction to cytopathology is in the cytopathology article.

Cervical cytology redirects to this article.

Preparation

The standard for Pap test is the Papanicolaou stain. It is described in the staining article and discussed in the context of cytopathology in the cytopathology article.

Slide marking conventions

Conventions are important for facilitating communication between various team members. They are discussed in the cytopathology article.

Normal cells

Squamous cell types:

1. Intermediate cells:
   • In clusters or single.
   • 30-50 micrometres in diameter.
   • Associated with progesterone - (light) blue.
   • This is the cell of reference in Pap test, i.e. other cells are measured against this cell when assessing a Pap test.
     • Nucleus ~ 7-8 micrometers.
       • Slightly smaller than a neutrophil.
2. Parabasal cells:
   • Blue-grey.
   • Associated with atrophy.
3. Basal cells:
   • Small cells.
   • Rarely seen.
4. Superficial cell:
   • Nucleus smaller than for intermediate cell.
   • Cytoplasm red.
     • Orange staining superficial cells are hypermature - suggests (abnormal) keratinization.

Glandular cells:

• Sheets of cells with regular spacing.
• Relatively high NC ratio (when compared to intermediate cells).
• Nucleoli (like most glandular cells).
• Nucleus approximately the size of an intermediate cell nucleus.

Images

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  Endocervical epithelium - high mag. (WC)

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  Endocervical epithelium - very high mag. (WC)

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  Endocervical epithelium - high mag. (WC)

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  Endocervical epithelium - very high mag. (WC)

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  Endocervical epithelium - high mag. (WC)

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  Endocervical epithelium - very high mag. (WC)

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  Endocervical cells and LSIL. (WC)

Mix of cells

The mix of cells is dependent on age and hormones:

• Progesterone - makes the Pap test blue... more intermediate cells.
• Yonger patients have a mix of cells.
• Menopausal patients... more parabasal cells.
• Older patients... more estrogen, glycogen.

Less common non-malignant cells

• Clue cells.
• Squamous metaplastic cells.
• Endometrial cells.
• Atrophic cells.
• Tingible body macrophages.
• Navicular cells.

Clue cells

Features:

• Purple squamous cell covered with rod-shaped bacteria.

Notes:

• The cytologic finding of bacterial vaginosis.

Image:

• Clue cell (atsu.edu).

Squamous metaplastic cells

Features:

• "Dense" cytoplasm.
• Nucleus ~2X the size of an intermediate cell nucleus.
  • Nucleolus (small) - important.
  • Regular/smooth nuclear membrane.

Note:

• Squamous metaplastic cells have a similar appearance to parabasal cells; they cannot be differentiated on morphologic grounds.
• Squamous metaplastic cells have a high NC ratio - they are differentiated from HSIL via nuclear features (dark staining + irregular nuclear contour = HSIL).
  • Slight nuc. contour irregularies are accepted, may be darker staining.

Images

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  SM - high mag. (WC)

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  SM - very high mag. (WC)

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  SM - very high mag. (WC)

Endometrial cells

Features:

• Cluster of cells with a well-defined border that is bilayered, i.e. a clump of (epithelioid) stromal cells surrounded by (flatted) glandular cells. Classically described as a cluster with a double contour; known as exodus pattern.
• Scant cytoplasm.
• Chromatin clumping.
• Raisin-like nuclei - approximately the size of an intermediate cell nucleus.
  • Nuclei can be considered normal if nucleus less than 2X the size of an intermediate cell nucleus.

Notes:

• Endometrial cells may appear irregular in the context of an intrauterine device (IUD); abnormalities in the context of an IUD are often ignored.
  • Cytology: cytoplasmic vacuolization, +/-multinucleation.
    • May be signet ring cell-like.
• The presence of endometrial cells on a Pap test on a woman >=40 years old (per Bethesda guidelines) should be noted in the pathology report - this prompts an endometrial biopsy.
  • The practise of reporting benign endometrial cells in premenopausal women is not backed by evidence that demonstrates a significant benefit.

Images

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  Endometrial cells - very high mag.

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  Endometrial cells - very high mag.

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  Endometrial cells - very high mag.

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  Endometrial cells - very high mag.

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  Endometrial cells - high mag.

• 

  Endometrial cells - very high mag.

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  Endometrial cells - very high mag.

www:

• Endometrial cells - double contour (techriver.net).
• Endometrial cells with "exodus" pattern (techriver.net).

Atrophic cells

Features:

• Cells smaller.
• Cytoplasm grey/blue.
• No "dancing"/"sparkling" chromatin.
• +/-"Dirty" background - degenerated cells, inflammatory cells (neutrophils, histiocytes).
  • May mimic "dirty" background of tumour, i.e. 'tumour diathesis'.

Notes:

• Usually older women.
• May be a cellular cluster.

DDx:

• HSIL - chromatin pattern irregular.

Tingible body macrophages

Features:

• Abundant cytoplasm with vacuolization.
• May be seen in the context of chlamydia.

Navicular cells

Main article: Navicular cell

Features:

• Intermediate cells with:
  1. Folded edges.
  2. Abundant cytoplasmic glycogen - central yellow.

Images

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  NC - very high mag.

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  NC - very high mag.

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  NC - extremely high mag.

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  NCs - extremely high mag.

Glycogen halos versus HPV effect

	HPV effect (koilocyte)	Glycogen halo
Discolouration of halo	Clear	Yellow
Nuclear changes	Associated with nuc. changes	Normal nuclei
Cell-to-cell variability	No - all clear	Yes - some yellow some clear

Gynecologic pathology in tables

Normal cells

Cell	Architecture	Cell borders	Cytoplasm	DNA	DDx
Intermediate cell (IC)	Single cells	Irregular	Blue, abundant	Small nucleus (~ size of PMN), no nucleolus	-
Superficial cell (SC)	Single cells	Irregular	Red, abundant	Small nucleus, 1/2 size of IC nucleus, no nucleolus	-
Squamous metaplastic cell	Single cells/clumps of cells	Smooth/oviod shape	Dense, dark blue	2X IC nucleus, nucleolus, no membrane irreg., no chromatin changes	DDx: HSIL, basal cell
Endometrial cell	Well-circumscribed clump/ball of cells with squamoid covering cells; referred to as "exodus" pattern	Indistinct within cluster	Blue, small/very scant	Small, dark, nuclear moulding, degenerative changes (chromatin clumping)	DDx: HSIL, basal cell.
Glandular (endocervical) cell	Sheets of cells with regular spacing, columnar morphology may be apparent, +/-palisading at edge of clump	Often distict	Blue, scant-to-moderate	Nucleus ~ size of an IC nucleus, no membrane irreg., no chromatin changes	DDx: endometrial cell
Atrophy	Single cells/groups	Well-circumscribed	Grey/blue dense, may be scant	Large NC ratio, nuc. membrane irregularities, NO chromatin clumping	DDx: HSIL
Radiation changes	Single cells/groups	Well-circumscribed	vacuolated, usu. abundant	Normal NC ratio, enlarged nucleus, no nuclear membrane irregularies, +/-multinucleation	DDx: LSIL, vitamin B12 def.

Note:

• If only normal cells are present the diagnosis is negative for intraepithelial lesion and malignancy (NILM).

Abnormal cells

Cell	Architecture	Cell borders	Cytoplasm	DNA	Other	Image
Low-grade squamous intraepithelial lesion (LSIL)	Single cells/groups	Irregular or moderately-circumscribed	Blue, abundant - NC ratio ~ 1:3	Large nucleus (3-4X IC nuc. - see Note 1), perinuclear clearing, nuc. membrane irregularities, chromatin clumping	DDx: HSIL, reactive changes	LSIL (WC)
High-grade squamous intraepithelial lesion (HSIL)	Often single cells, may be groups	Well-circumscribed	Dark blue, scant - NC ratio ~ 1:2	Large nucleus (3-4X IC nuc. - see Note 1), nuc. membrane irregularities, clumping of coarse chromatin, dark nuc. staining, +/- small nucleoli	DDx: squamous metaplasia, atrophy with atypia, superficial endometrial cells	HSIL (WC)
Atypical squamous cells of undetermined significance (ASC-US)	Single cells/groups	Irregular or moderately-circumscribed	Blue, abundant cytoplasm	Moderately enlarged nucleus (~2.5-3.0X IC nuc.), minimal changes in nuclear membrane and chromatin	DDx: LSIL, reactive changes
Atypical squamous cells, cannot exclude HSIL (ASC-H)	Often single cells, may be groups	Irregular or moderately-circumscribed	Blue, moderate-to-scant cytoplasm	Moderately enlarged nucleus (~1.5-2.0X IC nuc.), minimal changes in nuclear membrane and chromatin	DDx: HSIL, AIS
Atypical glandular cells (AGC)	Usu. groups of cells	Usually well-circumscribed (?)	Dark blue dense, scant	Moderately enlarged nucleus (~2X IC nuc.), nuc. membrane irregularities, chromatin clumping, dark nuc. staining, nucleoli	DDx: AIS, HSIL
Adenocarcinoma in situ (AIS)	groups; rosette formation	Usually well-circumscribed	Dark blue dense, scant	Large nucleus (>=2X IC nuc.), nuc. membrane irregularities, chromatin clumping, dark nuc. staining, nucleoli (very common), pseudostratification (as in endocervical AIS)	DDx: AGC, HSIL	Endocervical AIS (WC)
Features of SCC (see Note 2)	Large clusters of cells with irreg. edge and "streaming", +/-blood, necrotic debris	Poorly seen	Dark blue dense, scant	Large NC ratio, nucleolus, nuc. membrane irregularities, chromatin clumping	DDx: HSIL

Note 1:

• LSIL/HSIL nucleus - at least 3X IC nucleus.
  • ASCUS nucleus - at least 2.5X IC nucleus.
    • 3X is not an absolute requirement to call SIL, i.e. SIL may be called with a smaller nucleus in circumstances where other nuclear features are at the extremus of malignant.
• Large nuclear size, membrane irregularities, "clumpy" chromatin and dark nuc. staining - are the key features.
  • Perinuclear clearing is quite subjective.
    • The best perinuclear halos have a sharp punched-out edge.

Note 2:

• By definition, it is not possible to diagnose squamous cell carcinoma (SCC) on a pap test as one cannot demonstrate stromal invasion.

HSIL versus LSIL

	HSIL	LSIL
NC ratio - see Note 1	~1:2	~1:3
Nuclear membrane irregularities	Marked - distinct notches	Moderate
Chromatin granularity	Coarse, clumped, +/-nucleolus (red)	Coarse, no nucleolus
Cytoplasmic staining	Dark	Light
Perinuclear clearing	Usually absent	Often present
Binucleation	Uncommon	May be present
Maturity of squamous cell	Normal maturity	Hypermature (orangeophilic cell present)
Images (example)	HSIL (WC) HSIL (WC)	LSIL (WC) LSIL & endoCx (WC)

Note 1:

• The single most useful feature is NC ratio but it is not definitive; NC ratio should be evaluated in the context of nuclear irregularities (nuclear membrane smoothness, chromatin pattern, presence of nucleolus).
• It may be easier to think in terms of cell size - approximate values are:
  • HSIL cells: < 1/2 size of IC.
  • LSIL cells: classically the size of IC.

Infectious organisms

Disease	Organism	Group	Dx features	Associated features	Clinical	Reference	Image
Trichomoniasis	Trichomonas vaginalis	Protozoan	Pear-shaped pale-grey fluffy cytoplasm with well-defined nucleus, approx. 30 μm.	Acute inflammation (PMNs), may be seen with Leptothrix (hair-like appearance ~0.5 x 20 μm)	Sexually transmitted		T. vaginalis - Pap stain (WC) Trichomonas - Pap stain (WC)
Candidiasis	Candida albicans	Fungi	Branching hyphae ~= 1/2 the dia. of IC nucleus, red	PMNs	?	?	Candida on Pap test (WC)
Herpes	Herpes simplex virus (HSV 1 - less commonly, HSV 2 - more commonly)	Virus	Large ground glass nuclei then multinucleation with moulding & inclusions with clear halo	?	Sexually transmitted	?	HSV (WC) HSV (WC)
Actinomycetes	Actinomycetes	Gram-positive bacteria	Clusters of cocci in chains - hyphae-like appearance	low power: pom-pom or fuzzy ball-like appearance	Should prompt removal of IUD, if present.		Actinomycetes (gfmer.ch), Actinomycetes (quizlet.com)
Bacterial vaginosis (see Note 1)	Gardnerella vaginalis	Gram-variable rod	"Clue cell": bacterial clusters attached to a purple squamous cell	? Assoc.	Fishy smell	?	Bacterial vaginosis (WC) Clue cell (atsu.edu)

Note 1:

• Usually not reported.

Adequacy of specimens

There is a generally accepted standard for cervical (liquid-based) cytology specimens:

• >5000 squamous cells/slide, if no abnormality is present.
  • If abnormal cells are present, any number of cells is acceptable.
    • This works-out to approx. 4 cells/HPF.
      • Where: HPF = area seen at 400X with an eye piece diameter is ~22 mm.
    • 10 HPFs are counted and a table is used to see whether the sample is adequate.

Note:

• The standard for conventional pap smears is: 8000-12000 (well-visualized) squamous cells.

Transformation zone (TZ)

The presence of the TZ should be commented on:

• An adequate TZ is 10 cells - endocervical cells or squamous metaplastic cells (per Bethesda).

Difficulties in obtaining a TZ may arise in the following populations:

• Pregnant (endocervical canal not sampled).
• Menopausal.
• Young nulliparous.

Specific entities - infectious

Candida

Main article: Candidiasis

General

• Common.
• May be asymptomatic.
• Usually Candida albicans.

Cytology

Features:

• Typically in clusters - lead to darkened clusters of squamous cells (at low power).
• May appear to "shish kabob" the cell; may appear to puncture the cell membrane (as they overlie it).
• Red staining hyphae; width of hyphae ~= 1/2 the diameter of an intermediate cell nucleus; branches.

Notes:

• Presence should be noted in the pathology report.

Images

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  Candida on Pap test - example 1. (WC)

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  Candida on Pap test - example 2. (WC)

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  Candida - high mag. (WC)

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  Candida - very high mag. (WC)

www

• Candida on Pap test (flickr.com).

Trichomoniasis

General

• Caused by Trichomonas vaginalis - a protozoa.
• Sexually transmitted.
• Common.
• Occasionally found in urine cytology specimens.

Cytopathology

Features:

• Low power: grey blob with a nucleus, may be pear-shaped:
  • Size: approximately 30 micrometres.
  • Shape: usually oval, may have teardrop-shaped.
  • Flagellum - hair-thin locomotive stucture, usu. barely visible at 200X - diagnostic feature.

Cytopathological associations:

• Acute inflammation (neutrophils), often marked - key feature at low power.
• Reactive squamous cells with:
  • Nucleoli,
  • Perinuclear halos, and
  • Moth-eaten cytoplasm; cytoplasm that has multiple vacuoles with star-like spaces.

Notes:

• Trichomonas is tricky - it is easy to miss if one is not suspicious, in the context of inflammation.
• May vaguely resemble a neutrophil:
  • Flagellum useful to differentiate.
  • Neutrophil has multiple lobulations of the nucleus.
• May be seen in association of Leptothrix.
  • Appearance: long, hair-like.
  • Size: ~0.5 x 20 micrometres.

Images

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  T. vaginalis - Pap stain. (WC)

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  T. vaginalis - Pap stain. (WC)

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  Trichomonas vaginalis - Giemsa stain. (WC)

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  Trichomonas - high mag.

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  Trichomonas - very high mag.

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  Trichomonas - high mag.

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  Trichomonas - very high mag.

www

• Trichomonas and Leptothrix (nih.techriver.net).
• Trichomonas and Leptothrix (nih.techriver.net).

Herpes simplex virus

Main article: Herpes simplex virus

General

• May be HSV1 or HSV2.
  • Classically HSV2 based on epidemiology and location.

Cytology

Features:

1. Early: Large "ground-glass" nuclei - nuclei with hazy & uniformly dull appearance.
2. Late: multi-nucleation with moulding of nuclei and nuclear inclusions surrounded by a clear halo.

DDx:

• Reactive endocervical cells - may be multinucleated.

Image

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  HSV on pap test. (WC)

Actinomycetes

Main article: Actinomycetes

General

• Presence should prompt removal of intrauterine device (IUD), if present.
• Gram-positive bacteria.
• Microorganism part of the large Actinobacteria group.

Cytopathology

Features:

• Clusters of filamentous bacteria.
  • Hyphae-like appearance/"filamentous".

Notes:

• Mycete = fungus.

DDx - sulfur granule:

• Hematoidin (cockleburr) crystal - radiating crystal, refractile, classically golden-brown.

Bacterial vaginosis

General

• Benign.
• Very common.
• Classically associated with Gardnerella vaginalis.

Clinical:

• Fishy odor.

Treatment:

• Antibiotics (metronidazole or clindamycin).

Cytopathology

Features:

• Purple squamous cell covered with rod-shaped micro-organisms.

Image:

• Clue cell (atsu.edu).

Stains

• Gram stain +ve/-ve.
  • Gardnerella vaginalis is a gram variable rod.

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• Usually not reported.

Squamous intraepithelial lesions

• Abbreviated SIL.

General:

• The nucleus makes it SIL.
• The cytoplasm determines the grade (LSIL vs. HSIL).

Management (in short):

• LSIL = repeat Pap test in 6 months.
• HSIL = referral for coloposcopy.

Low-grade squamous intraepithelial lesion

• Abbreviated LSIL.

Main article: Low-grade squamous intraepithelial lesion

General

• Usually regress, i.e. will disappear on their own.
• Low inter-rater concordance.

Cytopathology

Features:

1. Nuclei 3x size of intermediate cell - key feature. †
2. Irregular nuclear border.
3. +/-Perinuclear 'cavity' (clearing).
   • The best perinuclear halos have a sharp punched-out edge.
4. Chromatin clumping/irregular & granular.

Note:

• † Nucleus diameter ~21-24 μm.
• In the context of exams: 2 of criteria 1-3 is enough to call LSIL.

Images

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  LSIL with HPV effect. (WC)

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  LSIL. (WC)

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  LSIL. (WC)

www:

• Possible LSIL (flickr.com).

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Low grade squamous intraepithelial lesion (LSIL). 

Cannot exclude HSIL

At least low grade squamous intraepithelial lesion; CANNOT EXCLUDE high-grade squamous intraepithelial lesion.

High-grade squamous intraepithelial lesion

• Abbreviated HSIL.

Main article: Squamous intraepithelial lesion of the uterine cervix

General

• Often progress to cervical cancer.

Cytopathology

Features:

• Often single cells, may be in clusters.
• Blue cells - nucleus and cytoplasm.
• Increased NC ratio - key feature.
  • Irregular nuclear border.
  • Chromatin clumping.

Note:

• Nucleoli uncommon - should prompt consideration of squamous carcinoma.

DDx:

• LSIL.
• ASC-H.
• Squamous carcinoma.

Images

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  HSIL. (WC)

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  HSIL. (WC/Nephron)

Squamous cell carcinoma

• Abbreviated SCC.

Main article: Squamous cell carcinoma

• Some believe that one can diagnosis SCC on a pap test.
  • This is nonsense, as SCC implies invasion which cannot be seen on a pap test.

Features suggestive of invasion:

• Loose clumps of ovoid-to-spindled cells with:
  • +/-Orange/red cytoplasm (orangeophilic cytoplasm).
  • Nucleoli - key feature.
  • Coarse chromatin.
  • Nuclear hyperchromasia.
• Necrotic debris - often obscures cell borders:
  • Anucleate, fragmented cells - cytoplasm-like material.
  • Neutrophils.

Note:

• Nucleoli DDx:
  • Reactive changes.
  • Glandular lesions (adenocarcinoma in situ, atypical glandular cells).

Image:

• HSIL with features suggestive of invasion (WC)

Glandular lesions

Adenocarcinoma in situ

• Abbreviated AIS.

Adenocarcinoma in situ on Pap test is classically divided into:

• Endocervical.
• Uterine.
• Extra-uterine.

Adenocarcinoma vs. squamous carcinoma:

• Adenocarcinoma:
  • Mucin vacuole.
  • Eccentric nucleus.
• Endocervical adenocarcinoma in situ:
  • "Feathering" - seen in adenocarcinoma more commonly on smears.
  • "Birdtails" - seen on liquid preparations.
• Squamous carcinoma:
  • Orangeophilic cytoplasm.
  • Central nucleus.

Images

www:

• Feathering in adenocarcinoma (cytology-asc.com).
• AIS (edupathonline.com).

Endocervical adenocarcinoma in situ

Main article: Endocervical adenocarcinoma in situ

• AKA adenocarcinoma in situ of the endocervix.

General

• Associated with HPV.
  • May be seen in conjunction with a SIL.
• Management - like AGC and other types of AIS: coloscopy +/- endometrial biopsy.

Cytopathology

Features:

• Cluster of small cells with:
  • Moderate nuclear enlargement.
  • Coarse chromatin.
  • Nucleoli - prominent - key feature.
  • +/-Mitoses.
• "Feathering" - picket fence-like arrangement of the cells at the edge of the cell cluster.
• Apoptotic/necrotic cells.

Negatives:

• Lack cilia.
  • Cilia on cells is a feature of benignancy and should sway the pathologist away from adenocarcinoma.

DDx:

• AGC - no prominent nucleoli, not 3-dimensional.
• Endometrial adenocarcinoma in situ.
• Metastatic colorectal adenocarcinoma.
• Lower uterine segment epithelium - esp. proliferative phase endometrium - mitoses rare, NC ratio normal.

Image

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  ECAIS - high mag. (WC)

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  ECAIS - very high mag. (WC)

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  ECAIS - very high mag. (WC)

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  ECAIS - high mag. (WC)

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  ECAIS - very high mag. (WC)

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  Endocervical AIS. (WC/euthman)

Endometrial adenocarcinoma in situ

• AKA adenocarcinoma in situ of the endometrium.

General

• Management - like AGC and other types of AIS: coloscopy + endometrial biopsy.

Cytopathology

Features:

• Single cells or cluster of small cells with:
  • Moderate nuclear enlargement ~2x intermediate cell nucleus.
  • Nuclear hyperchromasia.
  • Coarse chromatin.
  • Nucleoli - prominent - key feature.
  • +/-Mitoses.
  • +/-Intracytoplasmic neutrophils.
• Apoptotic/necrotic cells.
• +/-Psammoma bodies.
  • Suggestive of serous carcinoma of the endometrium.

DDx:

• AGC - no prominent nucleoli, not 3-dimensional.
• Endocervical adenocarcinoma in situ.

Waffle categories

• Like all waffle diagnoses, these should be used sparingly.

Atypical squamous cells of undetermined significance

• Abbreviated ASC-US or ASCUS.

General

• This is a waffle category that should be used sparingly.
  • The ASCUS/LSIL rate is used as a quality measure - the specific ratios are dependent on how they specimens are processed.
• Diagnosis may be an indication for HPV testing.

Cytology

Features:

• Squamous differentiation:
  • Central nucleus.
  • Dense/solid-appearing cytoplasm.
• Nuclear size >2.5X IC nucleus, but <3X IC nucleus.
• +/-Orange/red cytoplasmic (orangeophilic cytoplasm).

Note:

• One should not see nucleoli.
  • Nucleoli are seen in reactive changes and squamous cell carcinoma of the uterine cervix.
• The IC nucleus is ~ 8 μm.

DDx:

• NILM.
• LSIL.

Images

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  ASCUS - high mag. (WC)

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  ASCUS - very high mag. (WC)

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  ASCUS - high mag. (WC)

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  ASCUS - very high mag. (WC)

• 

  ASCUS - very high mag. (WC)

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Atypical squamous cells of undetermined significance (ASC-US).

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion

• Abbreviated ASC-H.

General

• This is a waffle category that should be used very rarely.
• Higher HPV positivity vs. ASC-US.
• Management - like HSIL: colposcopy.

Cytology

Features:

• Atypia that falls short of diagnosing HSIL:
  • Increased NC ratio.
• Architecture: cell clusters or rare single cells.

DDx:

• HSIL.
• NILM - atrophy, parabasal cells.
• LSIL.

Atypical glandular cells

• Abbreviated AGC.
• Previously atypical glandular cells of undetermined significance, abbreviated AGUS.

General

• Waffle diagnosis.
• Clinical management, like AIS: coloscopy +/- endometrial biopsy.

May represent either:

• Endocervical cells, i.e. atypical endocervical cells (AEC).
• Endometrial cells, i.e. atypical endometrial cell (AEM).

Microscopic

Features:

• Atypical glandular cells:
  • Cell cluster with cells with a diameter <= 2x intermediate cell nucleus.
  • Some features of nuclear atypia, e.g. irregular nuclear membrane, granular chromatin, nuclear hyperchromasia, nuclear enlargement.

DDx:

• Adenocarcinoma in situ.

Uncommon stuff

Follicular cervicitis

General

• Uncommon. (???)
• Finding may be associated with Chlamydia trachomatis.

Cytology

Features:

• Discohesive clusters of small (lymphoid) cells with interspersed:
  • Tingible-body macrophages.
  • Plasma cells.

DDx:

• AGC - nuclei larger, more cohesive

Image:

• Follicular cervicitis (nih.techriver.net).

Hematoidin crystal

• AKA hematoidin cockleburr.
• AKA cockleburr.

General

• Rare.
• Benign.
• Associated with hemorrhage in pregnancy.

Note:

• Overlap with crystalline bodies. (???)
  • Crystalline bodies associated with pregnancy, and OCP use.

Cytology

Features:

• Radiating crystal.
• Refractile.
• Classically golden-brown.
• +/-Surrounded by macrophages.

DDx:

• Sulfur granule of Actinomycetes.

Images:

• Cockleburr crystal (cytology-asc.com).
• Cockleburr crystal (cytology-asc.com).
• Cockleburr crystal (cytology-asc.com).

Carpet beetle larval parts

General

• Uncommon distinctive contaminant.
• Fragment of a beetle.
• Benign.

Cytology

Features:

• Slender long structure - fern-like.

Note:

• One may have a complete insect.

Image:

• Carpet beetle (archivesofpathology.org).

Radiation changes in cervical cytology

Main article: Radiation changes

General

• Radiation is used to treat cervical cancer.

Cytology

Features:

• Architecture: single cells/groups.
• Cell borders: well-circumscribed.
• Cytoplasm: vacuolated, usually abundant.
• Nucleus:
  • Enlarged nucleus - but normal NC ratio.
  • No nuclear membrane irregularies.
  • Chromatin: "smudgy".
  • +/-Multinucleation.

DDx:

• LSIL.
• Vitamin B12 deficiency.

Images:

• Radiation changes (iarc.fr).
• Radiation changes (iarc.fr).

Cornflaking artifact

General

• Processing artifact - due to air under the cover slip.

Cytology

Features:

• Central brown discolourization in squamous cells.

Images:

• Corn-flaking artifact (cytology-asc.com).
• Corn-flaking artifact (cytology-asc.com).

Endocervical repair

General

• Benign.

Cytology

Features:

• Cluster of (2-dimensional) glandular cells with:
  • Streaming (school of fish-appearance).
  • Prominent nucleoli.
  • Neutrophils.

Image:

• Reactive endocervical cells (nih.techriver.net).

Historical

Maturation index

• Abbreviated MI.

General

• Based on vaginal wall scrape.

Definition

$MI=P:I:S$.

Where:

• P = number of parabasal cells / 300 squamous cells * 100 %.
• I = number of intermediate cells / 300 squamous cells * 100 %.
• S = number of superficial cells / 300 squamous cells * 100 %.

Interpretation

Common patterns:

• Superficial predominant, no parabasal = high estrogen effect.
• Parabasal predominant, no superficial = atrophy.

Examples:

• 70 : 30 : 0 is an atrophic pattern.
• 0 : 30 : 70 is a high estrogen pattern.

Note:

• Significant inflammation distorts the result.

See also

• Cytopathology.
• Basics.
• Cervix.
• Uterus.
• Gynecologic pathology.

External links

• Collection of usual benign findings on pap tests (cytology-asc.com).
• Bethesda system atlas (techriver.net).
• Normal pap test - drawing (i2k.com).