Difference between revisions of "Gynecologic cytopathology"

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[[Image:Low grade squamous intraepithelial lesion.jpg|thumb|right|250px|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''.
'''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.
This article deals only with cervical cytopathology.  An introduction to cytopathology is in the ''[[cytopathology]]'' article.
'''Cervical cytology''' redirects to this article.


=Preparation=
=Preparation=
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*Nucleus approximately the size of an intermediate cell nucleus.
*Nucleus approximately the size of an intermediate cell nucleus.


Image:
===Images===
*[http://commons.wikimedia.org/wiki/File:Low-grade_sil_and_endocx.jpg Endocervical cells and LSIL (WC)].
<gallery>
Image: Benign endocervical epithelium -- high mag.jpg | Endocervical epithelium - high mag. (WC)
Image: Benign endocervical epithelium -- very high mag.jpg | Endocervical epithelium - very high mag. (WC)
Image: Benign endocervical epithelium - 2 -- high mag.jpg | Endocervical epithelium - high mag. (WC)
Image: Benign endocervical epithelium - 2 -- very high mag.jpg | Endocervical epithelium - very high mag. (WC)
Image: Benign endocervical epithelium - 3 -- high mag.jpg | Endocervical epithelium - high mag. (WC)
Image: Benign endocervical epithelium - 3 -- very high mag.jpg | Endocervical epithelium - very high mag. (WC)
</gallery>
<gallery>
Image:Low-grade_sil_and_endocx.jpg | Endocervical cells and LSIL. (WC)
</gallery>


==Mix of cells==
==Mix of cells==
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===Clue cells===
===Clue cells===
Features:
Features:
*Purple squamous cell; squamous cell covered with bacteria.
*Purple squamous cell covered with rod-shaped bacteria.
*Associated with ''bacterial vaginosis'' - which is caused by ''Gardnerella vaginalis''.<ref name="pmid3493202">{{cite journal |author=Scott TG, Smyth CJ, Keane CT |title=In vitro adhesiveness and biotype of Gardnerella vaginalis strains in relation to the occurrence of clue cells in vaginal discharges |journal=Genitourinary medicine |volume=63 |issue=1 |pages=47–53 |year=1987 |month=February |pmid=3493202 |pmc=1194007 |doi= |url=}}</ref>
 
**''Gardnerella vaginalis'' is a rod gram variable.<ref>{{cite journal |author=Taylor-Robinson D |title=The bacteriology of Gardnerella vaginalis |journal=Scand J Urol Nephrol Suppl |volume=86 |issue= |pages=41–55 |year=1984 |pmid=6399409 |doi= |url=}}</ref>
Notes:
*The cytologic finding of ''[[bacterial vaginosis]]''.


Image:
Image:
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*"Dense" cytoplasm.
*"Dense" cytoplasm.
*Nucleus ~2X the size of an intermediate cell nucleus.
*Nucleus ~2X the size of an intermediate cell nucleus.
**Nucleolus - '''key feature'''.
**Nucleolus (small) - '''important'''.
**Regular/smooth nuclear membrane.
**Regular/smooth nuclear membrane.


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*Squamous metaplastic cells have a high NC ratio - they are differentiated from HSIL via nuclear features (dark staining + irregular nuclear contour = HSIL).
*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.
**Slight nuc. contour irregularies are accepted, may be darker staining.
====Images====
<gallery>
Image: Squamous metaplasia - Pap test -- high mag.jpg | SM - high mag. (WC)
Image: Squamous metaplasia - Pap test -- very high mag.jpg | SM - very high mag. (WC)
Image: Squamous metaplasia - Pap test - alt -- very high mag.jpg | SM - very high mag. (WC)
</gallery>


===Endometrial cells===
===Endometrial cells===
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Notes:  
Notes:  
*Endometrial cells may appear irregular in the context of an intrauterine device (IUD); abnormalities in the context of an IUD are often ignored.
*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.
**Cytology: cytoplasmic vacuolization, +/-multinucleation.
***May be [[signet ring cell carcinoma|signet ring cell]]-like.
***May be [[signet ring cell carcinoma|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<ref name=pmid15900572>{{cite journal |author=Thrall MJ, Kjeldahl KS, Savik K, Gulbahce HE, Pambuccian SE |title=Significance of benign endometrial cells in papanicolaou tests from women aged >=40 years |journal=Cancer |volume=105 |issue=4 |pages=207-16 |year=2005 |month=August |pmid=15900572 |doi=10.1002/cncr.21156 |url=}}</ref> - this prompts an endometrial biopsy.
*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<ref name=pmid15900572>{{cite journal |author=Thrall MJ, Kjeldahl KS, Savik K, Gulbahce HE, Pambuccian SE |title=Significance of benign endometrial cells in papanicolaou tests from women aged >=40 years |journal=Cancer |volume=105 |issue=4 |pages=207-16 |year=2005 |month=August |pmid=15900572 |doi=10.1002/cncr.21156 |url=}}</ref> - this prompts an endometrial biopsy.
**In my humble opinion, reporting benign endometrial cells in premenopausal women is ''not'' evidence-based practise; the practise is driven by lawsuit-paranoia in the USA.
**The practise of reporting ''benign'' endometrial cells in premenopausal women is ''not'' backed by evidence that demonstrates a significant benefit.


Images:
====Images====
<gallery>
Image: Endometrial cells on Pap - 2 -- very high mag.jpg | Endometrial cells - very high mag.
Image: Endometrial cells on Pap - 2 -- very high mag.gif | Endometrial cells - very high mag.
Image: Endometrial cells on Pap - 2a -- very high mag.jpg | Endometrial cells - very high mag.
Image: Endometrial cells on Pap - 2a -- very high mag.gif | Endometrial cells - very high mag.
</gallery>
<gallery>
Image: Endometrial cells on Pap -- high mag.jpg | Endometrial cells - high mag.
Image: Endometrial cells on Pap -- very high mag.jpg | Endometrial cells - very high mag.
Image: Endometrial cells on Pap - alt -- very high mag.jpg | Endometrial cells - very high mag.
</gallery>
www:
*[http://rapids001.techriver.net/nih/patientImages/1826.jpg Endometrial cells - double contour (techriver.net)].
*[http://rapids001.techriver.net/nih/patientImages/1826.jpg Endometrial cells - double contour (techriver.net)].
*[http://nih.techriver.net/view.php?patientId=221 Endometrial cells with "exodus" pattern (techriver.net)].
*[http://nih.techriver.net/view.php?patientId=221 Endometrial cells with "exodus" pattern (techriver.net)].
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===Navicular cells===
===Navicular cells===
{{Main|Navicular cell}}
Features:
Features:
*Intermediate cells with:
*Intermediate cells with:
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*#Abundant cytoplasmic glycogen - central yellow.
*#Abundant cytoplasmic glycogen - central yellow.


Notes:  
====Images====
*Cells often described as ''boat-shaped''.
<gallery>
*May resemble the lenses of ''coke bottle glasses''.
Image: Navicular cell -- very high mag.jpg | NC - very high mag.
*Associated with: [[pregnancy]], contraception with medroxyprogesterone acetate (Depo-provera).<ref name=pmid10945902>{{Cite journal  | last1 = Volk | first1 = EE. | last2 = Jax | first2 = JM. | last3 = Kuntzman | first3 = TJ. | title = Cytologic findings in cervical smears in patients using intramuscular medroxyprogesterone acetate (Depo-provera) for contraception. | journal = Diagn Cytopathol | volume = 23 | issue = 3 | pages = 161-4 | month = Sep | year = 2000 | doi =  | PMID = 10945902 }}</ref>
Image: Navicular cell - alt -- very high mag.jpg | NC - very high mag.
Image: Navicular cell -- extremely high mag.jpg | NC - extremely high mag.


Images:
Image: Navicular cells -- extremely high mag.jpg | NCs - extremely high mag.
*[http://www.flickr.com/photos/28287204@N02/3083659626/ Navicular cells (flickr.com)].
</gallery>
*[http://www.flickr.com/photos/28287204@N02/3112533994/ Cluster of navicular cells (flickr.com)].


==Glycogen halos versus HPV effect==
==Glycogen halos versus HPV effect==
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| Irregular
| Irregular
| '''Blue, abundant'''
| '''Blue, abundant'''
| Small nucleus (~ size of PMN), no [[nucleolus]]
| Small nucleus (~ size of [[PMN]]), no [[nucleolus]]
| -
| -
|-  
|-  
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| Dense, dark blue
| Dense, dark blue
| 2X IC nucleus, '''nucleolus''', no membrane irreg., no chromatin changes
| 2X IC nucleus, '''nucleolus''', no membrane irreg., no chromatin changes
| DDx: HSIL, basal cell
| DDx: [[HSIL]], basal cell
|-
|-
| Endometrial cell
| Endometrial cell
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| vacuolated, usu. abundant
| vacuolated, usu. abundant
| '''Normal NC ratio''', enlarged nucleus, no nuclear membrane irregularies, +/-multinucleation
| '''Normal NC ratio''', enlarged nucleus, no nuclear membrane irregularies, +/-multinucleation
| DDx: LSIL, vitamin B12 def.
| DDx: [[LSIL]], vitamin B12 def.
|}
|}
Note:
Note:
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! DNA
! DNA
! Other
! Other
! Image
|-
|-
| [[Low-grade squamous intraepithelial lesion]] (LSIL)
| [[Low-grade squamous intraepithelial lesion]] (LSIL)
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| Large nucleus (3-4X IC nuc. - see ''Note 1''), perinuclear clearing, nuc. membrane irregularities, chromatin clumping  
| Large nucleus (3-4X IC nuc. - see ''Note 1''), perinuclear clearing, nuc. membrane irregularities, chromatin clumping  
| DDx: HSIL, reactive changes
| DDx: HSIL, reactive changes
| [[Image:Low-grade squamous intraepithelial lesion - 3 -- very high mag.jpg| thumb|center|150px|LSIL (WC)]]
|-
|-
| [[High-grade squamous intraepithelial lesion]] (HSIL)
| [[High-grade squamous intraepithelial lesion]] (HSIL)
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| Large nucleus (3-4X IC nuc. - see ''Note 1''), '''nuc. membrane irregularities, clumping of coarse chromatin, dark nuc. staining''', +/- small nucleoli
| 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
| DDx: squamous metaplasia, atrophy with atypia, superficial endometrial cells
| [[Image:High-grade squamous intraepithelial lesion - 2 -- very high mag.jpg |thumb|center|150px|HSIL (WC)]]
|-
|-
| [[Atypical squamous cells of undetermined significance]] (ASC-US)
| [[Atypical squamous cells of undetermined significance]] (ASC-US)
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| '''Moderately enlarged nucleus''' (~2.5-3.0X IC nuc.), minimal changes in nuclear membrane and chromatin
| '''Moderately enlarged nucleus''' (~2.5-3.0X IC nuc.), minimal changes in nuclear membrane and chromatin
| DDx: LSIL, reactive changes
| DDx: LSIL, reactive changes
|
|-
|-
| [[Atypical squamous cells, cannot exclude HSIL]] (ASC-H)
| [[Atypical squamous cells, cannot exclude HSIL]] (ASC-H)
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| '''Moderately enlarged nucleus''' (~1.5-2.0X IC nuc.), minimal changes in nuclear membrane and chromatin
| '''Moderately enlarged nucleus''' (~1.5-2.0X IC nuc.), minimal changes in nuclear membrane and chromatin
| DDx: HSIL, AIS
| DDx: HSIL, AIS
|
|-
|-
| [[Atypical glandular cells]] (AGC)
| [[Atypical glandular cells]] (AGC)
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| Moderately enlarged nucleus (~2X IC nuc.), '''nuc. membrane irregularities, chromatin clumping, dark nuc. staining''', nucleoli
| Moderately enlarged nucleus (~2X IC nuc.), '''nuc. membrane irregularities, chromatin clumping, dark nuc. staining''', nucleoli
| DDx: AIS, HSIL
| DDx: AIS, HSIL
|
|-
|-
| [[Adenocarinoma in situ]] (AIS)
| [[Adenocarcinoma in situ]] (AIS)
| groups; '''rosette formation'''
| groups; '''rosette formation'''
| Usually well-circumscribed
| Usually well-circumscribed
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| Large nucleus (>=2X IC nuc.), '''nuc. membrane irregularities, chromatin clumping, dark nuc. staining''', nucleoli (very common), pseudostratification (as in endocervical AIS)
| Large nucleus (>=2X IC nuc.), '''nuc. membrane irregularities, chromatin clumping, dark nuc. staining''', nucleoli (very common), pseudostratification (as in endocervical AIS)
| DDx: AGC, HSIL
| DDx: AGC, HSIL
| [[Image:Endocervical adenocarcinoma in situ - cyto -- very high mag.jpg|thumb|center|150px|Endocervical AIS (WC)]]
|-
|-
| Features of SCC (see ''Note 2'')
| Features of SCC (see ''Note 2'')
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| Large NC ratio, '''nucleolus''', nuc. membrane irregularities, chromatin clumping
| Large NC ratio, '''nucleolus''', nuc. membrane irregularities, chromatin clumping
| DDx: HSIL
| DDx: HSIL
|
|}
|}


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| Hypermature (orangeophilic cell present)
| Hypermature (orangeophilic cell present)
|-
|-
| Image (example)
| Images (example)
| [http://commons.wikimedia.org/w/index.php?title=File:High-grade_squamous_intraepithelial_lesion.jpg HSIL (WC)]
| [[Image:High-grade_squamous_intraepithelial_lesion.jpg |thumb|center|150px| HSIL (WC)]] [[Image:High-grade squamous intraepithelial lesion - 4 -- very high mag.jpg| thumb|center|150px| HSIL (WC)]]
| [http://commons.wikimedia.org/w/index.php?title=File:Low-grade_squamous_intraepithelial_lesion.jpg LSIL (WC)], [http://commons.wikimedia.org/wiki/File:Low-grade_sil_and_endocx.jpg LSIL & endoCx (WC)]
| [[Image:Low-grade_squamous_intraepithelial_lesion.jpg |thumb|center|150px| LSIL (WC)]] [[Image:Low-grade_sil_and_endocx.jpg |thumb|center|150px| LSIL & endoCx (WC)]]
|}
|}


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| Sexually transmitted
| Sexually transmitted
| <ref name=Ref_WMSP446>{{Ref WMSP|446}}</ref>
| <ref name=Ref_WMSP446>{{Ref WMSP|446}}</ref>
| [http://commons.wikimedia.org/wiki/File:Trichomonas_pap_test.jpg T. vaginalis - Pap stain (WC)], [http://commons.wikimedia.org/wiki/File:Pap_test_trichomonas.JPG Trichomonas - Pap stain (WC)]
| [[Image:Trichomonas_pap_test.jpg |thumb|150px|center|T. vaginalis - Pap stain (WC)]] [[Image:Trichomonas - Pap - 3 -- very high mag.jpg |thumb|150px|center|Trichomonas - Pap stain (WC)]]
|-
|-
| [[Gynecologic_cytopathology#Candida|Candidiasis]]
| [[Gynecologic_cytopathology#Candida|Candidiasis]]
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| ?
| ?
| ?
| ?
| [http://commons.wikimedia.org/w/index.php?title=File:Candida_pap_1.jpg Candida on Pap test (WC)]
| [[Image:Candida_pap_1.jpg|thumb|150px|center| Candida on Pap test (WC)]]
|-
|-
| [[Gynecologic_cytopathology#Herpes simplex virus|Herpes]]
| [[Gynecologic_cytopathology#Herpes simplex virus|Herpes]]
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| Sexually transmitted
| Sexually transmitted
| ?
| ?
| [http://commons.wikimedia.org/wiki/File:Herpes_simplex_virus_pap_test.jpg HSV (WC)],[http://commons.wikimedia.org/wiki/File:Herpes_simplex_virus_pap_test_2.jpg HSV (WC)], [http://www.virology.org/sbpgphoto2.html Herpes simplex virus - surgical (virology.org)]
| [[Image:Herpes_simplex_virus_pap_test.jpg |thumb|center|150px| HSV (WC)]] [[Image:Herpes_simplex_virus_pap_test_2.jpg |thumb|center|150px| HSV (WC)]]
|-
|-
| [[Gynecologic_cytopathology#Actinomycetes|Actinomycetes]]
| [[Gynecologic_cytopathology#Actinomycetes|Actinomycetes]]
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| '''Clusters of cocci in chains - hyphae-like appearance'''
| '''Clusters of cocci in chains - hyphae-like appearance'''
| low power: pom-pom ''or'' fuzzy ball-like appearance
| low power: pom-pom ''or'' fuzzy ball-like appearance
| Should prompt removal of IUD, if present.
| Should prompt removal of [[IUD]], if present.
| <ref name=Ref_WMSP446>{{Ref WMSP|446}}</ref>
| <ref name=Ref_WMSP446>{{Ref WMSP|446}}</ref>
| [http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=4&cat2=23&cat3=552&cat4=6&stype=n Actinomycetes (gfmer.ch)], [http://o.quizlet.com/Swjzk-aC7Ah8aYQmYzQ8Kg_m.jpg Actinomycetes (quizlet.com)]
| [http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=4&cat2=23&cat3=552&cat4=6&stype=n Actinomycetes (gfmer.ch)], [http://o.quizlet.com/Swjzk-aC7Ah8aYQmYzQ8Kg_m.jpg Actinomycetes (quizlet.com)]
|-
|-
| Bacterial vaginosis (see ''Note 1'')
| [[Bacterial vaginosis]] (see ''Note 1'')
| Gardnerella vaginalis
| Gardnerella vaginalis
| Gram-variable rod
| Gram-variable rod
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| Fishy smell
| Fishy smell
| ?
| ?
| [http://commons.wikimedia.org/wiki/File:Vaginose-G15.jpg Bacterial vaginosis (WC)], [http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/image/clue2.jpg Clue cell (atsu.edu)]
| [[File:Vaginose-G15.jpg|thumb|center|150px|Bacterial vaginosis (WC)]] [http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/image/clue2.jpg Clue cell (atsu.edu)]
|}
|}


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*Presence should be noted in the pathology report.
*Presence should be noted in the pathology report.


Images:
====Images====
<gallery>
Image:Candida_pap_1.jpg | Candida on Pap test - example 1. (WC)
Image:Candida_pap_2.jpg | Candida on Pap test - example 2. (WC)
</gallery>
<gallery>
Image: Candida - Pap test -- high mag.jpg | Candida - high mag. (WC)
Image: Candida - Pap test -- very high mag.jpg | Candida - very high mag. (WC)
</gallery>
=====www=====
*[http://www.flickr.com/photos/moorepix4u2c/1425271033/in/set-72157602113534479/ Candida on Pap test (flickr.com)].
*[http://www.flickr.com/photos/moorepix4u2c/1425271033/in/set-72157602113534479/ Candida on Pap test (flickr.com)].
*[http://commons.wikimedia.org/w/index.php?title=File:Candida_pap_1.jpg Candida on Pap test - example 1 (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Candida_pap_2.jpg Candida on Pap test - example 2 (WC)].


==Trichomoniasis==
==Trichomoniasis==
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*Sexually transmitted.
*Sexually transmitted.
*Common.
*Common.
*Occasionally found in [[urine cytology]] specimens.<ref>{{cite journal |authors=Doxtader EE, Elsheikh TM |title=Diagnosis of trichomoniasis in men by urine cytology |journal=Cancer Cytopathol |volume=125 |issue=1 |pages=55–59 |date=January 2017 |pmid=27636204 |doi=10.1002/cncy.21778 |url=}}</ref>


===Cytopathology===
===Cytopathology===
Line 455: Line 505:
**Size: ~0.5 x 20 micrometres.
**Size: ~0.5 x 20 micrometres.


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Trichomonas_pap_test.jpg T. vaginalis - Pap stain (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Pap_test_trichomonas.JPG T. vaginalis - Pap stain (WC)].
Image:Trichomonas_pap_test.jpg | T. vaginalis - Pap stain. (WC)
*[http://commons.wikimedia.org/wiki/File:Trichomonas_vaginalis_01.jpg Trichomonas vaginalis - Giemsa stain (WC)].
Image:Pap_test_trichomonas.JPG | T. vaginalis - Pap stain. (WC)
Image:Trichomonas_vaginalis_01.jpg | Trichomonas vaginalis - Giemsa stain. (WC)
</gallery>
<gallery>
Image: Trichomonas - Pap - 2 -- high mag.jpg | Trichomonas - high mag.
Image: Trichomonas - Pap - 2 -- very high mag.jpg | Trichomonas - very high mag.
</gallery>
<gallery>
Image: Trichomonas - Pap - 3 -- high mag.jpg | Trichomonas - high mag.
Image: Trichomonas - Pap - 3 -- very high mag.jpg | Trichomonas - very high mag.
</gallery>
=====www=====
*[http://nih.techriver.net/view.php?patientId=305 Trichomonas and Leptothrix (nih.techriver.net)].
*[http://nih.techriver.net/view.php?patientId=305 Trichomonas and Leptothrix (nih.techriver.net)].
*[http://nih.techriver.net/view.php?patientId=325 Trichomonas and Leptothrix (nih.techriver.net)].
*[http://nih.techriver.net/view.php?patientId=325 Trichomonas and Leptothrix (nih.techriver.net)].
Line 472: Line 533:
#Early: Large "ground-glass" nuclei - nuclei with hazy & uniformly dull appearance.
#Early: Large "ground-glass" nuclei - nuclei with hazy & uniformly dull appearance.
#Late: multi-nucleation with moulding of nuclei and nuclear inclusions surrounded by a clear halo.
#Late: multi-nucleation with moulding of nuclei and nuclear inclusions surrounded by a clear halo.
DDx:
*[[Reactive endocervical cells]] - may be multinucleated.
====Image====
<gallery>
Image:Herpes simplex virus pap test.jpg | HSV on pap test. (WC)
</gallery>


==Actinomycetes==
==Actinomycetes==
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DDx - sulfur granule:<ref name=asc_cockle>URL: [http://www.cytology-asc.com/cec/normal/index.htm#cockle http://www.cytology-asc.com/cec/normal/index.htm#cockle]. Accessed on: 10 April 2012.</ref>
DDx - sulfur granule:<ref name=asc_cockle>URL: [http://www.cytology-asc.com/cec/normal/index.htm#cockle http://www.cytology-asc.com/cec/normal/index.htm#cockle]. Accessed on: 10 April 2012.</ref>
*Hematoidin (cockleburr) crystal - radiating crystal, refractile, classically golden-brown.
*Hematoidin (cockleburr) crystal - radiating crystal, refractile, classically golden-brown.
==Bacterial vaginosis==
===General===
*Benign.
*Very common.
*Classically associated with ''Gardnerella vaginalis''.<ref name=pmid3493202>{{cite journal |author=Scott TG, Smyth CJ, Keane CT |title=In vitro adhesiveness and biotype of Gardnerella vaginalis strains in relation to the occurrence of clue cells in vaginal discharges |journal=Genitourinary medicine |volume=63 |issue=1 |pages=47–53 |year=1987 |month=February |pmid=3493202 |pmc=1194007 |doi= |url=}}</ref><ref name=pmid22082330>{{Cite journal  | last1 = Polatti | first1 = F. | title = Bacterial vaginosis, Atopobium vaginae and nifuratel. | journal = Curr Clin Pharmacol | volume = 7 | issue = 1 | pages = 36-40 | month = Feb | year = 2012 | doi =  | PMID = 22082330 }}</ref>
Clinical:
*Fishy odor.
Treatment:
*Antibiotics (metronidazole or clindamycin).<ref name=pmid22082330/>
===Cytopathology===
Features:
*Purple squamous cell covered with rod-shaped micro-organisms.
Image:
*[http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/image/clue2.jpg Clue cell (atsu.edu)].
===Stains===
*Gram stain +ve/-ve.
**''Gardnerella vaginalis'' is a gram variable rod.<ref name=pmid6399409>{{cite journal |author=Taylor-Robinson D |title=The bacteriology of Gardnerella vaginalis |journal=Scand J Urol Nephrol Suppl |volume=86 |issue= |pages=41–55 |year=1984 |pmid=6399409 |doi= |url=}}</ref>
===Sign out===
*Usually not reported.


=Squamous intraepithelial lesions=
=Squamous intraepithelial lesions=
Line 504: Line 599:
==Low-grade squamous intraepithelial lesion==
==Low-grade squamous intraepithelial lesion==
*Abbreviated '''LSIL'''.
*Abbreviated '''LSIL'''.
{{Main|Low-grade squamous intraepithelial lesion}}
===General===
===General===
*Usually regress, i.e. will disappear on their own.
*Usually regress, i.e. will disappear on their own.
*Low inter-rater concordance.<ref name=pmid22007754>{{Cite journal  | last1 = Bigras | first1 = G. | last2 = Wilson | first2 = J. | last3 = Russell | first3 = L. | last4 = Johnson | first4 = G. | last5 = Morel | first5 = D. | last6 = Saddik | first6 = M. | title = Interobserver concordance in the assessment of features used for the diagnosis of cervical atypical squamous cells and squamous intraepithelial lesions (ASC-US, ASC-H, LSIL and HSIL). | journal = Cytopathology | volume = 24 | issue = 1 | pages = 44-51 | month = Feb | year = 2013 | doi = 10.1111/j.1365-2303.2011.00930.x | PMID = 22007754 }}</ref>


===Cytopathology===
===Cytopathology===
Line 519: Line 616:
* In the context of exams: 2 of criteria 1-3 is enough to call LSIL.<ref>Chan, S. 26 April 2012.</ref>
* In the context of exams: 2 of criteria 1-3 is enough to call LSIL.<ref>Chan, S. 26 April 2012.</ref>


Images:
====Images====
<gallery>
Image:Low-Grade_SIL_with_HPV_Effect.jpg | LSIL with HPV effect. (WC)
Image:Low_grade_squamous_intraepithelial_lesion.jpg | LSIL. (WC)
Image:ThinPrep_Pap_smear_HPV.jpeg | LSIL. (WC)
</gallery>
www:
*[http://www.flickr.com/photos/moorepix4u2c/1440144102/in/set-72157602113534479/ Possible LSIL (flickr.com)].
*[http://www.flickr.com/photos/moorepix4u2c/1440144102/in/set-72157602113534479/ Possible LSIL (flickr.com)].
*[http://commons.wikimedia.org/wiki/File:Low-Grade_SIL_with_HPV_Effect.jpg LSIL with HPV effect (WC)].
 
===Sign out===
<pre>
Low grade squamous intraepithelial lesion (LSIL).  
</pre>
 
====Cannot exclude HSIL====
<pre>
At least low grade squamous intraepithelial lesion; CANNOT EXCLUDE high-grade squamous intraepithelial lesion.
</pre>


==High-grade squamous intraepithelial lesion==
==High-grade squamous intraepithelial lesion==
*Abbreviated '''HSIL'''.
*Abbreviated '''HSIL'''.
{{Main|Squamous intraepithelial lesion of the uterine cervix}}
===General===
===General===
*Often progress to cervical cancer.
*Often progress to [[cervical cancer]].


===Cytopathology===
===Cytopathology===
Line 544: Line 657:
*[[Squamous carcinoma]].
*[[Squamous carcinoma]].


Image:
====Images====
*[http://commons.wikimedia.org/wiki/File:High-Grade_SIL.jpg HSIL (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:ThinPrep_Pap_smear_HPV.jpeg HSIL (WC)].
Image:High-Grade_SIL.jpg | HSIL. (WC)
Image:High-grade_squamous_intraepithelial_lesion.jpg | HSIL. (WC/Nephron)
</gallery>


===Squamous cell carcinoma===
===Squamous cell carcinoma===
Line 566: Line 681:
Note:
Note:
*Nucleoli DDx:
*Nucleoli DDx:
**Reactive changes.
**[[Reactive squamous epithelium of the uterine cervix|Reactive changes]].
**Glandular lesions (adenocarcinoma in situ, atypical glandular cells).
**Glandular lesions ([[adenocarcinoma in situ]], atypical glandular cells).


Image:
Image:
Line 592: Line 707:
**Central nucleus.
**Central nucleus.


Images:
===Images===
www:
*[http://www.cytology-asc.com/cec/endocx/endo4.html Feathering in adenocarcinoma (cytology-asc.com)].
*[http://www.cytology-asc.com/cec/endocx/endo4.html Feathering in adenocarcinoma (cytology-asc.com)].
*[http://www.edupathonline.com/apps/blog/show/3692069-endocervical-ais AIS (edupathonline.com)].
*[http://www.edupathonline.com/apps/blog/show/3692069-endocervical-ais AIS (edupathonline.com)].
Line 622: Line 738:
*[[Endometrial adenocarcinoma in situ]].
*[[Endometrial adenocarcinoma in situ]].
*Metastatic [[colorectal adenocarcinoma]].
*Metastatic [[colorectal adenocarcinoma]].
*Lower uterine segment epithelium<ref name=Ref_GP167>{{Ref GP|167}}</ref> - esp. [[proliferative phase endometrium]] - mitoses rare, NC ratio normal.


Image:  
===Image===
*[http://commons.wikimedia.org/wiki/File:Cervical_AIS,_ThinPrep.jpg AIS endocervix (wikimedia.org)].
<gallery>
Image: Endocervical adenocarcinoma in situ - cyto -- high mag.jpg | ECAIS - high mag. (WC)
Image: Endocervical adenocarcinoma in situ - cyto -- very high mag.jpg | ECAIS - very high mag. (WC)
Image: Endocervical adenocarcinoma in situ - cyto -- very high mag.gif | ECAIS - very high mag. (WC)
Image: Endocervical adenocarcinoma in situ - cyto - alt -- high mag.jpg | ECAIS - high mag. (WC)
Image: Endocervical adenocarcinoma in situ - cyto - alt -- very high mag.jpg | ECAIS - very high mag. (WC)
</gallery>
<gallery>
Image:Cervical_AIS,_ThinPrep.jpg | Endocervical AIS. (WC/euthman)
</gallery>


==Endometrial adenocarcinoma in situ==
==Endometrial adenocarcinoma in situ==
Line 668: Line 794:
Note:
Note:
*One should '''not''' see [[nucleoli]].
*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.<ref>URL: [http://www.curran.pwp.blueyonder.co.uk/cytology.htm http://www.curran.pwp.blueyonder.co.uk/cytology.htm]. Accessed on: 5 November 2012.</ref>


DDx:
DDx:
*[[NILM]].
*[[NILM]].
*[[LSIL]].
*[[LSIL]].
===Images===
<gallery>
Image: Atypical squamous cell of undetermined significance - 1 -- high mag.jpg | ASCUS - high mag. (WC)
Image: Atypical squamous cell of undetermined significance - 1 -- very high mag.jpg | ASCUS - very high mag. (WC)
Image: Atypical squamous cell of undetermined significance - 1a -- high mag.jpg | ASCUS - high mag. (WC)
Image: Atypical squamous cell of undetermined significance - 1a -- very high mag.jpg | ASCUS - very high mag. (WC)
Image: Atypical squamous cell of undetermined significance - 1b -- very high mag.jpg | ASCUS - very high mag. (WC)
</gallery>
===Sign out===
<pre>
Atypical squamous cells of undetermined significance (ASC-US).
</pre>


==Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion==
==Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion==
Line 774: Line 917:


==Radiation changes in cervical cytology==
==Radiation changes in cervical cytology==
{{Main|Radiation changes}}
===General===
===General===
*Radiation is used to treat cervical cancer.
*Radiation is used to treat cervical cancer.
Line 861: Line 1,005:
*[http://www.cytology-asc.com/cec/normal/index.htm Collection of usual benign findings on pap tests (cytology-asc.com)].
*[http://www.cytology-asc.com/cec/normal/index.htm Collection of usual benign findings on pap tests (cytology-asc.com)].
*[http://nih.techriver.net/ Bethesda system atlas (techriver.net)].
*[http://nih.techriver.net/ Bethesda system atlas (techriver.net)].
*[http://www.i2k.com/~suzanne/normalpap.htm Normal pap test - drawing (i2k.com)].


[[Category:Cytopathology]]
[[Category:Cytopathology]]

Latest revision as of 21:46, 13 August 2024

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]

  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.
  2. Parabasal cells:
    • Blue-grey.
    • Associated with atrophy.
  3. Basal cells:
    • Small cells.
    • Rarely seen.
  4. Superficial cell:[2]
    • Nucleus smaller than for intermediate cell.
    • Cytoplasm red.
      • Orange staining superficial cells are hypermature - suggests (abnormal) keratinization.

Glandular cells:[3]

  • 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

Mix of cells

The mix of cells is dependent on age and hormones:[4]

  • 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:

Image:

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

Endometrial cells

Features:[5]

  • 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.[6]
  • 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.
  • 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[7] - 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

www:

Atrophic cells

Features:[8]

  • 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

Features:

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

Images

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[9] 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[10] 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[11] - 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).[11]
  • 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 [12]
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. [12] 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:[13]

  • >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.[14]

Transformation zone (TZ)

The presence of the TZ should be commented on:[15]

  • 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

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

www

Trichomoniasis

General

  • Caused by Trichomonas vaginalis - a protozoa.
  • Sexually transmitted.
  • Common.
  • Occasionally found in urine cytology specimens.[16]

Cytopathology

Features:

  • Low power: grey blob with a nucleus, may be pear-shaped:
    • Size: approximately 30 micrometres.[12]
    • 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

www

Herpes simplex virus

General

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

Cytology

Features:[12]

  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:

Image

Actinomycetes

General

  • Presence should prompt removal of intrauterine device (IUD), if present.[12]
  • Gram-positive bacteria.
  • Microorganism part of the large Actinobacteria group.

Cytopathology

Features:[12]

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

Notes:

  • Mycete = fungus.[17]

DDx - sulfur granule:[18]

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

Bacterial vaginosis

General

  • Benign.
  • Very common.
  • Classically associated with Gardnerella vaginalis.[19][20]

Clinical:

  • Fishy odor.

Treatment:

  • Antibiotics (metronidazole or clindamycin).[20]

Cytopathology

Features:

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

Image:

Stains

  • Gram stain +ve/-ve.
    • Gardnerella vaginalis is a gram variable rod.[21]

Sign out

  • 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.

General

  • Usually regress, i.e. will disappear on their own.
  • Low inter-rater concordance.[22]

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.[23]

Images

www:

Sign out

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.

General

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:

DDx:

Images

Squamous cell carcinoma

  • Abbreviated SCC.
  • 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:

Image:

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[24] more commonly on smears.[25]
    • "Birdtails" - seen on liquid preparations.
  • Squamous carcinoma:
    • Orangeophilic cytoplasm.
    • Central nucleus.

Images

www:

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:

Image

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.

DDx:

Waffle categories

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[27] - the specific ratios are dependent on how they specimens are processed.[28]
  • 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).[29]

Note:

DDx:

Images

Sign out

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.[31]
  • Management - like HSIL: colposcopy.

Cytology

Features:

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

DDx:[32]

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

Cytology

Features:[34]

  • Discohesive clusters of small (lymphoid) cells with interspersed:

DDx:

  • AGC - nuclei larger, more cohesive

Image:

Hematoidin crystal

  • AKA hematoidin cockleburr.
  • AKA cockleburr.

General

  • Rare.
  • Benign.
  • Associated with hemorrhage in pregnancy.[35]

Note:

  • Overlap with crystalline bodies. (???)
    • Crystalline bodies associated with pregnancy, and OCP use.[35]

Cytology

Features:[18][36]

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

DDx:

Images:

Carpet beetle larval parts

General

  • Uncommon distinctive contaminant.[37]
  • Fragment of a beetle.
  • Benign.

Cytology

Features:

  • Slender long structure - fern-like.

Note:

  • One may have a complete insect.[38]

Image:

Radiation changes in cervical cytology

General

  • Radiation is used to treat cervical cancer.

Cytology

Features:[39]

  • 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:

Cornflaking artifact

General

  • Processing artifact - due to air under the cover slip.[40]

Cytology

Features:[40]

  • Central brown discolourization in squamous cells.

Images:

Endocervical repair

General

  • Benign.

Cytology

Features:

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

Image:

Historical

Maturation index

  • Abbreviated MI.

General

  • Based on vaginal wall scrape.

Definition

.

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

References

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External links