Cervix-cytology
Last revised 3 November 2009
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Table of contents - Cervix-cytology
Primary references, images needed, general, Pap, liquid based, Diff-Quik, Bethesda system
Normal cells / nonneoplastic findings: air drying artifact, Barr body, blue blobs, cilia, cornflakes, degeneration, endocervical cells, endometrial cells, eosinophils, exodus, histiocytes, hyperkeratosis, immature squamous metaplasia, insect parts, intermediate squamous cells, lower uterine segment endometrium, lymphocytes, male cells, maturation index, navicular cells, neutrophils, parabasal cells, parakeratosis, PM cells, post-hysterectomy, psammoma bodies, repair, small blue cells, squamous cells, squamous metaplasia, superficial squamous cells, syncytium, transitional metaplasia, tumor diathesis, unsatisfactory specimen
Inflammation/parasites: actinomycosis, bacterial vaginosis, Candida, Chagas’ disease, chlamydia, chronic cervicitis, CMV, Enterobius, granuloma inguinale, granulomas, herpes, Lactobacillus, Leptothrix, Schistosomiasis, syphilis, Trichomonas, tuberculosis, Wucheria
Benign/non-neoplastic lesions: general, adenomyoma, adenosis, Arias-Stella reaction, atrophy, atypical polypoid adenomyoma, decidual reaction, endocervical polyp, endometrial polyp, endometriosis, endosalpingiosis, florid ectopy, leiomyoma, lobular endocervical hyperplasia, mesonephric rests, mesonephric hyperplasia, microglandular hyperplasia, myofibroblastoma, squamous papilloma
Atypia / Premalignant / preinvasive lesions: HPV, condyloma, atypical glandular cells, atypical repair, atypical reserve cell hyperplasia, atypical squamous cells, chemotherapy effect, radiation atypia, SIL-general, LSIL/CIN I, HSIL/CIN II, HSIL/CINIII, adenocarcinoma in situ, Paget's disease
Carcinoma: squamous cell carcinoma, microinvasive SCC, adenocarcinoma, microinvasive adenocarcinoma, adenoid basal, adenoid cystic, adenosquamous, clear cell, endometrial, glassy cell, lymphoepithelioma-like, metastases to cervix, minimal deviation adenocarcinoma, serous papillary adenocarcinoma, small cell, urothelial, verrucous, villoglandular papillary adenocarcinoma, warty
Sarcoma/lymphoma/other: sarcoma-general, Ewing’s sarcoma/PNET, granulocytic sarcoma, leiomyosarcoma, lymphoma, malignant mixed mullerian tumor, melanoma, plasmacytoma, reticulum cell sarcoma, rhabdomyosarcoma, stromal sarcoma
Go to Cervix chapter/outline
American Journal of Clinical Pathology (AJCP), August 1975 to February 2006
American Journal of Surgical Pathology (AJSP), March 1977 to January 2006
Archives of Pathology and Laboratory Medicine (Archives), June 1976 to January 2006
Human Pathology (Hum Path), May 1974 to January 2006
Modern Pathology (Mod Path), March 1988 to January 2006
DeMay: The Pap Test: Exfoliative Gynecologic Cytology (1st Ed); ASCP, 2005
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby, 2004
Solomon: The Bethesda System for Reporting Cervical Cytology (2nd Ed); Springer, 2005
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
Websites: Histopathology and cytopathology of the Uterine Cervix-Digital Atlas, American Society of Cytopathology-National Cancer Institute Atlas
Journal search terms: cervix, cervicovaginal, smear, cytology
Please refer to these primary references for additional discussion and images
Images needed (for cervical cytology)
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Cytology images are particularly needed for these cervix lesions:
Normal cells / nonneoplastic findings: cornflakes, eosinophils, male cells, PM cells
Inflammation / parasites: Chagas’ disease, Enterobius, syphilis,
Benign/non-neoplastic: adenomyoma of endocervical type, adenosis, Arias-Stella reaction, atypical polypoid adenomyoma, decidual reaction, endocervical polyp, endometrial polyp, endosalpingiosis, leiomyoma, mesonephric rests, mesonephric hyperplasia, myofibroblastoma, squamous papilloma
Atypia/pre-malignant/preinvasive: immature condyloma, atypical repair, atypical reserve cell hyperplasia, chemotherapy effect, keratinizing SIL
Carcinoma: papillary squamotransitional, microinvasive squamous cell carcinoma, signet ring adenocarcinoma, microinvasive adenocarcinoma, adenoid basal, adenoid cystic, adenosquamous, clear cell, lymphoepithelioma-like, minimal deviation adenocarcinoma, serous papillary adenocarcinoma, verrucous, warty (condylomatous)
Sarcoma/lymphoma/other: Ewing’s sarcoma/PNET, granulocytic sarcoma, leiomyosarcoma, rhabdomyosarcoma
Cytology-general
The most successful application of clinical cytology is diagnosing cervical abnormalities before they develop into invasive cervical carcinoma
Used for screening and follow-up of cervical carcinoma, particularly squamous carcinoma
Cytology smears are sensitive to abnormalities, although there is variable interpretation on any particular smear; the most important factor is to detect an abnormality and to start an appropriate management plan
Specimen should be obtained and prepared by trained individuals
False negative tests are often due to poor quality specimens and inadequate sampling (Mod Path 1992;5:337), erroneous interpretation and error by screeners
Endocervical sampling should be performed to confirm that the entire transition zone was sampled, although many studies show no association between absence of endocervical cells / transition zone and a higher risk of squamous lesions on subsequent smears (AJCP 2001;115:851, Acta Cytol 1986;30:258, Cancer 2001;93:237, Lancet 1991;337:265)
For endometrial carcinoma, pap smear is only 50% sensitive; 60% with cervical scrapings, 75% with vaginal pool material; thus, pap smears are not appropriate for screening endometrial abnormalities
Liquid based cytology performed by cytocentrifugation is reported to be efficient and inexpensive (CytoJournal 2005;2:15); is associated with higher rates of LSIL and lower ratios of atypical squamous cells/LSIL (Archives 2004;128:1224, Archives 2003;127:200)
HPV testing may be more sensitive than cytology in detecting HSIL (Br J Cancer 2005;93:575)
HPV testing is an integral part of management of ASCUS (atypical squamous cells of uncertain significance), ASC-H (atypical squamous cells, cannot exclude HSIL) and to evaluate AGUS (atypical glandular cells, Am J Obstet Gynecol 2005;193:559)
Recent study of simultaneous FISH for HPV E6 and E7 mRNA had 83% sensitivity and 91% sensitivity for high grade SIL compared with Pap smear in 231 liquid based cytology samples (AJCP 2005;123:716)
References: screening guidelines from Brigham and Women’s Hospital, Boston, Massachusetts (USA)
Alcohol dried; better for nuclear detail
Stains ribosomes blue green, particularly in parabasal cells, mesothelial cells and metaplastic squamous cells
Stains metabolically inactive cells pink, such as superficial cells
Stains keratinized cells or thick specimens orange (benign or malignant)
Fix quickly and stain carefully; air dried smears are inadequate
Images: smearing and slide preparation; procedure for staining
Cytology images: conventional smears-examples of good cellularity
References: Wikipedia
Head of spatula, where cells are lodged, is broken off into small glass vial containing preservative fluid, or rinsed directly into preservative fluid
Sample is sent to lab, then spun and treated to remove mucus, pus or other obscuring material
Random sample of remaining cells is taken and deposited onto a slide
Reduces number of inadequate smears and need for repeat smears
Thin-Prep appears to be superior to convention Pap test in detecting SIL (Archives 2003;127:200, Archives 1999;123:817, Mod Path 1998;11:837)
Approved by US Food and Drug Administration in 1997
Major companies are Cytyc (ThinPath) and TriPath Imaging (SurePath)
Can use residual material to prepare cell blocks and for immunohistochemistry (Cancer 2004;102:142)
Images: smearing and slide preparation
Cytology images: examples of liquid based samples
Diff-Quik stain in cervical cytology
An air dried, Giemsa-type stain
Better for background material or to assess adequacy of endocervical smears to detect C. trachomatis (J Clin Microbiol 1996;34:2590)
Used for fine needle aspirates, not for cervical smears
Bethesda System 2001 for Cervicovaginal Cytology reporting
Based on workshop held in April/May 2001 at National Cancer Institute (JAMA 2002;287:2140)
By 2003, was implemented by 85% of labs participating in College of American Pathologists’ Interlaboratory Comparison Program in Cervicovaginal Cytology (Archives 2004;128:1224)
Specimen type
Indicate conventional smear (Pap smear), liquid based preparation or other preparation (describe)
Specimen adequacy
Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and all other quality indicators, such as partially obscuring blood, inflammation, etc.)
Assessment of specimen adequacy (satisfactory and unsatisfactory):
1 - Adequate number of squamous cells (conventional smear should have 8000-12000 cells, liquid-based preparation should have 5000 cells)
2 -The presence or absence of endocervical cells should be reported; an adequate number of endocervical cells (at least 10 well-preserved endocervical or metaplastic cells) confirms sampling of transition zone
3 - Specimen with more than 75% of cells obscured by inflammation and bacteria is unsatisfactory (however, should still report presence of abnormal cells)
Unsatisfactory for evaluation (indicate reason)
Specimen rejected/not processed (indicate reason)
Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality (indicate reason)
Interpretation/result
Negative for Intraepithelial Lesion or Malignancy (NILM)
Organisms
• Trichomonas vaginalis
• Fungal organisms morphologically consistent with Candida species
• Shift in flora suggestive of bacterial vaginosis
• Bacteria morphologically consistent with Actinomyces species
• Cellular changes associated with Herpes simplex virus
Other non-neoplastic findings (optional to report, list is not inclusive)
• Reactive cellular changes associated with:
- inflammation (includes typical repair)
- irradiation
- Intrauterine contraceptive device (IUD)
• Glandular cells status post hysterectomy
• Atrophy
Other
• Endometrial cells (in a woman greater than or equal to 40 years of age; specify if “negative for squamous intraepithelial lesion”)
Epithelial Cell Abnormalities
SQUAMOUS CELL
• Atypical squamous cells
- of undetermined significance (ASC-US)
- cannot exclude HSIL (ASC-H)
• Low grade squamous intraepithelial lesion (LSIL)
- encompassing HPV/mild dysplasia/CIN I
• High grade squamous intraepithelial lesion (HSIL)
- encompassing: moderate and severe dysplasia/CIN2/CIN3/CIS
- with features suspicious for invasion (if invasion suspected)
• Squamous cell carcinoma
GLANDULAR CELL
• Atypical
- endocervical cells (NOS or specify in comment)
- endometrial cells (NOS or specify in comment)
- glandular cells (NOS or specify in comment)
• Atypical
- endocervical cells, favor neoplastic
- glandular cells, favor neoplastic
• Endocervical Adenocarcinoma in situ
• Adenocarcinoma
- endocervical
- endometrial
- extrauterine
- not otherwise specified (NOS)
OTHER MALIGNANT NEOPLASMS (Specify)
ANCILLARY TESTING: Describe briefly the test method(s) and report the result so that it is easily understood by the clinician
AUTOMATED REVIEW: If case is examined by automated device, specify the device and result
EDUCATIONAL NOTES/SUGGESTIONS: If provided, should be concise and consistent with clinical guidelines published by professional organizations
References: details from IARC/WHO
Normal cells / non-neoplastic findings
Air drying artifact-cervical cytology
Due to delay in immersion in alcohol fixative
More common on conventional than liquid based smears
Specimen is unsatisfactory if more than 75% of cells show air drying; if less extensive, may be mentioned as a quality indicator
May cause discrepant diagnosis of LSIL or less for HSIL smears (Cancer 2002;96:218)
Associated with ASCUS in perimenopausal women (Cancer 2001;93:100)
Cytology: cells are degenerated, eosinophilic, enlarged and lightly stained; nuclei are pale, flattened and lack chromatin detail
Cytology images: apparently normal #1; #2; atrophy in post-menopausal woman; ASCUS; HSIL
Inactive X chromosome, present on nuclear margin, formed by telomere association (Proc Natl Acad Sci USA 1991;88:6191)
Identified by Dr. Murray Barr
Images: drawing; in squamous epithelial cell #1; #2; #3; crumbled up X chromosome in neutrophil #1; #2; other
References: Barr body
Represent condensed mucus, degenerated bare nuclei, precipitating hematoxylin
In post-menopausal women, represent parabasal/intermediate squamous cells with various degree of degeneration (Acta Cytol 2000;44:547)
Cytology: dark blue, rounded, amorphous masses
Cytology images: liquid based cytology with amorphous basophilic material #1; #2; #3
Almost always implies a benign lesion, such as tubal metaplasia, which may simulate adenocarcinoma in situ
May be associated with endometrioid type of minimal deviation adenocarcinoma of cervix (AJSP 1993;17:660)
Note that the presence of single cells with cilia is insufficient to diagnose tubal metaplasia, according to Bethesda 2001
Case report: ciliated adenocarcinoma of cervix (Acta Cytol 2005;49:187)
Cytology images: various images
Also called “brown artifact”, cornflaking
Distinctive appearance is due to evaporation of xylene before cover slipping, with deposition of air on superficial squamous cells
More common on conventional than liquid based preparations
Cytology images: contributed by Dr. Yao-Wen Liu, Kuo General Hospital, Taiwan - #1; #2
References: National Association of Cytologists
Degeneration-cervical cytology
Occasionally called retroplastic change
Due to delay in transfer of cells to the slide
Also associated with inflammation or atrophy
More common on conventional than liquid based preparations
Cytology: cytoplasm is lost and moth eaten with vacuolization; chromatin is clumped, hazy, smudged or indistinct; chromatin rim has variable thickness and irregular contours, but no sharp angles of malignancy
Cytology images: degenerated cells #1; #2
Endocervical cells-cervical cytology
Most effective device for collection appears to be cytobrush and extended tip spatula (Cochrane Database Syst Rev 2000;CD001036)
Presence of endocervical cells indicates that the upper limit of transformation zone was included, so collection is adequate
Cytology: usually columnar cells (2 mm) with vacuolated or granular cytoplasm, prominent cell borders, basal nuclei with fine granular chromatin and occasional nucleoli; honeycomb appearance en face; ciliated if tubal metaplasia
Cytology images (conventional): various images #1; #2-secretory cells; #3-ciliated; large cluster of cells #1; #2; #3; en face #1; #2; #3; tubal metaplasia #1; #2; #3; reactive #1; #2; #3
Cytology images (liquid based): various images; en face; tubal metaplasia #1; #2; endocervical cells (SurePath)
Endometrial cells-cervical cytology
Reports of associated endometrial pathology in postmenopausal women with benign endometrial cells at pap smear (AJCP 2005;123:571, Diagn Cytopathol 2001;45:153) versus no association (Cancer 2005;105:207, Diagn Cytopathol 2001;25:235)
Most associated carcinomas are in women age 45+ years (AJCP 2005;124:834)
May also be due to hormone replacement therapy (Obstet Gynecol 2002;100:445) or tamoxifen
Resemble histiocytes; easier to identify if in clusters
Cytology images: various images #1; #2; #3; #4; IUD related changes
Cytology images: contributed by Dr. Carmen Luz, Spain - Thin Prep of normal endometrial group-postmenstrual cycle
May be associated with parasites (Diagn Cytopathol 2003;29:167); also allergic reactions to chemicals, medications or sperm
Cytology: pink granular cytoplasm and binucleated
Images: peripheral blood; ankle biopsy for blastomycosis; nasal mucosa in allergic rhinitis
Cytology: menstrual endometrium with central core of densely packed stroma surrounded by degenerated and partially necrotic cells; histiocytes, neutrophils and degenerated cells in a dirty background
During menstrual cycle days 6 to 10 (proliferative phase or exodus phase), the endometrial cells are present in a “double contour” pattern with glandular epithelial cells surrounding the stromal cells in the center
Cytology images: various images of endometrial cells, including during menstruation; page 38-PDF file
Clinical history is more predictive of endometrial pathology than presence of histiocytes (Acta Cytol 2003;47:135, Acta Cytol 2003;47:762)
Cytology: larger than neutrophils, vacuolated or frothy cytoplasm (scant to moderate), round to reniform (bean shaped) nuclei, central or eccentric, chromatin fine to coarse but uniformly distributed, nucleoli variable
Epithelioid histiocytes: usually in aggregates
Multinucleated histiocytes: randomly arranged nuclei with granular chromatin
Cytology images: various images #1; #2; histiocytes #1; #2; #3; multinucleated #1; #2
Hyperkeratosis / keratinization-cervical cytology
top
Extensive hyperkeratosis is patches of anucleated squamous
cells with irregular, angulated edges present in 5+ low power fields on a
conventional smear; for liquid based preparations, in 3+ low power fields
An abnormal finding; may be associated with malignancy (0-2%) or HPV/dysplasia (17-22%) (Acta Cytol 2003;47:749, Am J Obstet Gynecol 2002;187:997); present in 70% of Thin-Prep specimens of invasive squamous cell carcinoma (Diagn Cytopathol 2002;26:1)
SIL cases are difficult to grade (AJCP 2001;115:80); pathology report of prominent atypical keratosis should state “cannot exclude high grade SIL”
Cytology images: various images #1; #2; #3; conventional smear; liquid based smear
DD: SIL (hyperkeratosis is not marked, irregular chromatin clumping, irregular nuclear membranes, disorganized growth pattern, Diagn Cytopathol 1997;17:447)
Immature squamous metaplasia-cervical cytology
Associated with endocervical cells
Cytology: cells are parabasal or basal type; have dense, dark cytoplasm that is reduced in quantity, increased N/C ratio, uniform oval nuclei; often seen in loose aggregates in “jigsaw” configuration; resembles reserve cell hyperplasia
Cytology images: various images; atypical metaplastic squamous cells with increased N/C ratio and nuclear enlargement-biopsy revealed immature squamous metaplasia
Insect parts-cervical cytology
Carpet beetle larval parts may be a contaminant of cotton swabs, wooden swabs or tampons (Acta Cytol 1985;29:345)
Cytology images: carpet beetle parts
References: Archives 2005;129:809, carpet beetle information
Intermediate squamous cells-cervical cytology
Predominate in luteal phase
Nuclear grooves are not associated with inflammation, but are increased in HSIL (Acta Cytol 2003;47:421)
Cytology: cytoplasm is polygonal, transparent, basophilic, flat/thin (due to keratin); nucleus is about the size of a red blood cell, is vesicular, round/oval; nuclear texture and size is reference for dysplasia; may see cytolysis / dirty background, Doderlein bacilli
Cytology images: various images (some are intermediate cells); intermediate cells #1; #2; #3; #4
Lower uterine segment endometrium-cervical cytology
Associated with use of endocervical brush (pushed too high into cervical os) and post-cone biopsies (Diagn Cytopathol 1995;12:263)
May mimic atypical glandular lesions, endometriosis, HSIL or be considered “inconclusive”
Does not warrant reporting according to Bethesda 2001 if seen in absence of exfoliated endometrial cells
Cytology: large groups with gland openings, branched glands, nuclear palisading within fragments; often endometrial stroma and smaller fragments that are densely cellular with nuclear palisading
Cytology images: long tubular branching glands in monomorphic stroma; glandular cells of endometrial origin
References: AJCP 1996;106:511, Australian Society of Cytology
Cytology: mature lymphocytes have dense homogenous nucleus and high N/C ratio; immature lymphocytes have vesicular nuclei, prominent nucleoli, lower N/C ratio
Follicular cervicitis: aggregates of lymphocytes with tingible body macrophages (see also Chronic Cervicitis)
Cytology images: lymphocytes with tingible body macrophage; liquid based cytology #1; #2
Male cells (non sperm)-cervical cytology
FISH can provide evidence of male epithelial and inflammatory cells up to 3 weeks after intercourse (AJCP 1995;104:32, J Forensic Sci 1994;39:1347)
Sperm identification decreases after first postcoital day (J Forensic Sci 1987;32:678)
Maturation index-cervical cytology
Ratio of parabasal to intermediate to superficial cells of vaginal epithelium (sampled at middle third of lateral vaginal wall)
Sample often obtained simultaneous with pap smear
For detecting hormonal effects in menopausal and post-menopausal women
Increased maturation in vaginal epithelium may be due to estrogenic effect of tamoxifen (Clin Exp Obstet Gynecol 1998;25:121)
Navicular cells-cervical cytology
Variant of intermediate cells
Associated with pregnancy or androgenic atrophy (progesterone in women, estrogen in men)
Atrophy: parabasal cell predominance without superficial cells
Estrogenic effect: superficial cell predominance without parabasal cells
Cytology: ellipsoid (boat shaped) squamous epithelial cells with intracytoplasmic glycogen (golden, refractile, granular), folded edges
Nonspecific finding
Neutrophils are associated with and phagocytosed by Trichomonas (Cytopathology 2000;11:326) and Chlamydia infections (CMAJ 1998;158:41)
Cytology: multilobated, hyperchromatic cells, may have background of blood and necrotic debris
Cytology images: neutrophils and histiocytes; numerous neutrophils #1; #2; #3
Parabasal cells-cervical cytology
Associated with atrophy, post-partum or prolonged use of depot-medroxyprogesterone acetate (Cancer 1998;84:328)
Cytology: cytoplasm is round, dense, basophilic; nucleus is vesicular, central, active, round; may see naked nuclei; higher N/C ratio and smaller size than intermediate cells
Cytology images: parabasal cells #1; #2; #3; various images associated with atrophy
Positive stains: Ki-67 (for normal parabasal cells, negative in atrophy)
DD: squamous metaplasia, SIL
Parakeratosis-cervical cytology
Defined histologically as abnormal keratinization of the squamous epithelium with persistence of the cell nuclei in the superficial cells
May be associated with SIL (Am
J Obstet Gynecol 2002;187:997)
SIL cases tend to have irregular chromatin clumping, irregular
nuclear membranes, disorganized growth pattern, less hyperkeratosis (Diagn
Cytopathol 1997;17:447)
Cytology: usually small, round or polygonal squamous cells with dense eosinophilic cytoplasm and pyknotic nuclei; associated with inflammation
Cytology images: various images; parakeratosis #1; #2; #3; liquid based; suggestive of LSIL
Cells from PeriMenopausal women
Significant cause of ASC overdiagnosis in women ages 40 to 55 years (AJCP 2005;124:58)
Cytology: squamous cells with enlarged, smooth, bland nuclei in perimenopausal women
Post-hysterectomy-cervical cytology
Vault smears are obtained for routine follow up
Routine vaginal cuff cytology screening tests may not need to be performed if hysterectomy was performed for benign uterine conditions (J Am Board Fam Pract 2000;13:233)
May display columnar or metaplastic cells (Cytopathology 1999;10:122)
Case reports: post-hysterectomy fallopian tube carcinoma presenting with positive cervicovaginal smear (Obstet Gynecol 1999;94:834)
Cytology images: glandular and squamous cells
Psammoma bodies-cervical cytology
Less than 0.001% of pap smears
Associated with ovarian serous carcinoma (0 to 23%, particularly in post-menopausal women, Gynecol Oncol 2001;83:6); also benign conditions
Recommended to investigate clinically to identify source (Adv Anat Pathol 2004;11:250)
Benign conditions often have a few associated bland glandular cells versus adherent malignant glandular cells in malignant disorders (Acta Cytol 1991;35:81)
Case reports: associated with endosalpingiosis (J Reprod Med 2000;45:526, J Reprod Med 1991;36:675), granulomatous reaction to aluminum silicate (Diagn Cytopathol 1999;21:122), IUD (J Reprod Med 1987;32:147)
Common source of diagnostic error (Archives 2001;125:134)
Changes seen with inflammation, radiation, chemotherapy, trauma
Micro: cohesive monolayered sheets of cells with well defined or indistinct borders, polarity, uniform nuclei, finely granular and evenly distributed chromatin, nuclei may be hypo- to hyperchromatic, but almost all have prominent round nucleoli; almost all cases have chronic inflammatory infiltrate; may see multinucleation
Note: sheets of cells in repair may fold on themselves, giving impression of syncytium
If atypia present, must include diagnosis of ASCUS in cytology report
Cytology images: various images; reparative changes #1; #2 (Pap and Thin Prep); #4; #5; #6; #7; #8; HSIL not repair
liquid based cytology - #1; #2; #3; #4
DD: SIL (pleomorphic nuclei in all cases, usually coarse chromatin and mitotic figures, usually no inflamed stroma), metaplastic epithelium (usually small nucleoli and no inflamed stroma, occasional nuclear pleomorphism or mitotic figures, Int J Gynecol Pathol 1996;15:338)
Small blue cells-cervical cytology
Associated with tamoxifen therapy (present in 40% of Pap smears from patients with tamoxifen therapy) and atrophy
Not associated with malignancy
May represent reserve cells of cervical/vaginal epithelium (Archives 2001;125:1047)
Micro: tight clusters of undifferentiated small cells with minimal cytoplasm or naked nuclei, round to oval nuclei, bland chromatin, indistinct nucleoli
Cytology images: dark, tightly cohesive clusters
DD: endometrial cells (irregular nuclear contours, degenerative appearance, coarse chromatin), endometrial carcinoma (larger cells, hyperchromatic nuclei with coarse chromatin and distinct nucleoli), carcinoid tumor, small cell carcinoma, adenoid cystic carcinoma, adenoid basal carcinoma, lobular breast carcinoma (large plasmacytoid cells with irregular nuclear membrane, coarse chromatin, prominent nucleoli, clinical history)
Squamous cells-cervical cytology
Either superficial, intermediate or parabasal
Cytology: transparent cytoplasm, polygonal
Cytology images: normal squamous cells (superficial, intermediate, parabasal, metaplastic)
Squamous metaplasia-cervical cytology
See also immature squamous metaplasia
Common in transformation zone
Due to proliferation of reserve cells under columnar cells
First immature, then mature squamous metaplasia, which fills endocervical glands
Cytology: single cells, loosely cohesive groups or sheets; variable cell size and shape; cell borders are more defined with maturity; cytoplasm is variable with occasional vacuoles; nuclei is slightly larger than intermediate cell nuclei, has finely granular and evenly distributed chromatin, nuclear membrane is smooth, no prominent nucleoli
Cytology images: various images #1; #2; mature squamous metaplasia; squamous and transitional (urothelial) metaplasia
Superficial squamous cells-cervical cytology
Called squames if keratinized and anucleated
Superficial cell predominance is associated with estrogen and peaks midcycle
Cytology: cytoplasm is polygonal, transparent, eosinophilic, flat/thin; nucleus is pyknotic, round/oval
Cytology images: superficial cells
May be due to HPV or HIV infection or have non-viral cause
Cytology: masses of cytoplasm without visible intact cell borders, nuclei have loss of polarity; may represent benign process of parabasal cells in post menopausal women
DD: SIL, malignancy, repair
Transitional (urothelial) metaplasia-cervical cytology
Associated with atrophy, menopausal women
May be related to HPV (Cancer 2002;96:250)
Cytology: clusters of cells with streaming, oval, bland nuclei containing longitudinal nuclear grooves; may have perinuclear halos and wrinkled contours; no/rare mitotic figures
Cytology images: transitional cell metaplasia; squamous and transitional (urothelial) metaplasia
References: Diagn Cytopathol 1998;18:222, AJSP 1997;21:510, Int J Gynecol Pathol 1997;16:89
Tumor diathesis-cervical cytology
Associated with invasive carcinoma; SIL or benign backgrounds are usually “clean”
Often not present if less than 5 mm of invasive squamous cell carcinoma (Acta Cytol 1997;41:781)
For liquid based (Thin-Prep and Sure-Prep), squamous cell carcinoma may have clinging diathesis (necrotic material at periphery of cell groups) or reduced cellularity (Diagn Cytopathol 2002;26:1)
Cytology: fresh or hemolyzed blood with necrotic cellular debris in background
Cytology images: various images; bloody background in endocervical adenocarcinoma
Unsatisfactory specimen-cervical cytology
Unsatisfactory if more than 75% of specimen is obscured by blood or inflammation
Also due to scant cellularity, or if specimen is rejected, not processed, or unsatisfactory for evaluation due to another reason
For Thin Prep, reprocessing of unsatisfactory slides is useful (AJCP 2002;117:457)
May be fewer unsatisfactory specimens with liquid based cytology (Eur J Gynaecol Oncol 2005;26:646, Expert Rev Mol Diagn 2005;5:857, Gynecol Oncol 2005;99:597)
Cytology images: various images #1; #2
Inflammation of cervix
Actinomycosis-cervical cytology
Associated with intrauterine devices (Obstet Gynecol 1996;87:142)
Cytology: aggregates of pseudofilamentous material, often with acute angle branching; may have wooly appearance; periphery may contain swollen filaments with clubs
Cytology images: various images; actinomyces #1; #2; #3; #4 (SurePath); IUD related changes
Bacterial vaginosis-cervical cytology
Also called "shift in flora", Gardnerella vaginalis, "clue cells"
Pap smear is 80% sensitive and 87% specific; presence of “clue cells” is more sensitive and specific (Acta Cytol 2005;49:634)
Cytology images: conventional - various images; shift in flora suggestive of bacterial vaginosis
liquid based - clue cells
Virtual slides: bacterial vaginosis
Candida / fungi-cervical cytology
Present in 3% of pap smears, doesn’t necessarily indicate a symptomatic infection (Diagn Cytopathol 1999;21:14)
Cytology: pseudohyphae and yeasts; reactive squamous epithelial cells
Cytology images: various images #1; #2
Virtual slides: Candida
Chagas’ disease-cervical cytology
Cytology images: Trypanosoma cruzi #1 (not cervix); #2; #3; #4
Chlamydia trachomatis-cervical cytology
An obligate intracellular parasite with elementary bodies (infectious but incapable of cell division) and reticulate bodies (multiply within cytoplasm, but not infectious until they transfer back into elementary bodies)
Presence of infection is not associated with symptoms (Sex Health 2004;1:115)
Diagnosis is based on molecular tests (PCR or ligase chain reaction)
Cytology: morphologic changes (intracytoplasmic inclusions with central small coccoid bodies) are not specific
Cytology images: various images #1; #2; Thin Prep
Chronic cervicitis-cervical cytology
Also called lymphofollicular cervicitis, pseudolymphoma
Cytology: variably sized lymphocytes, all mature, tingible body macrophages and plasma cells; Thin-Prep specimens show clumps (Cytopathology 2002;13:364)
Cytology images: various images #1; #2; #3
DD: lymphoma
CMV-cervical cytology
Associated with HIV1 infection (J Med Virol 1999;59:469)
Some cases have no associated risk factors (Cytopathology 1993;4:237)
Cytology images: as part of case history; not necessarily cervix
Enterobius (pinworm)-cervical cytology
Cytology images: ovum; fecal smear; eggs in 47-year-old woman’s pap smear #1; #2; #3
References: Acta Cytol 1984;28:468
Granuloma inguinale-cervical cytology
Special stains detect the causative organism, Calymmatobacterium granulomatis, which is gram negative
Cytology: Donovan bodies (intracytoplasmic coccobacilli in macrophages stained by Giemsa or Wright's stain); may have safety-pin appearance (bipolar densities) in smears taken from scrapings of the edge of lesions; are pleomorphic, up to 2 microns; also intact capillaries indicative of ulceration, marked acute inflammatory infiltrate, epithelioid histiocytes (Diagn Cytopathol 1986;2:138)
Cytology images: Diff-Quik #1; #2
References: Sex Transm Infect 2002;78:452
May be due to sutures (Diagn Cytopathol 1995;13:336)
Case reports: producing psammoma bodies, due to aluminum silicate granuloma (Diagn Cytopathol 1999;21:122)
Cytology: inflammatory reaction, foreign body giant cells, phagocytosed refractile suture material (in some cases)
Herpes simplex virus (HSV)-cervical cytology
Cytology, in-situ hybridization and PCR helpful for rapid diagnosis (Diagn Cytopathol 2003;29:246)
Cytology: multinucleated cells with dense, intranuclear Cowdry-type viral inclusions; nuclei have ground glass appearance due to accumulation of viral particles, which causes peripheral margination of chromatin; also nuclear molding
“Three M’s of herpes” - margination of nuclei, molding and multinucleation
Cowdry: intranuclear eosinophilic amorphous or droplet-like bodies surrounded by a clear halo, with (type A, herpes) or without (type B, adenovirus or poliovirus) margination of chromatin on the nuclear membrane
Cytology images: various images #1; #2; #3; #4; #5
DD: inflammatory cells with multiple nuclei (lack discrete nuclear molding)
Lactobacillus-cervical cytology
Normal vaginal flora
Decreased with bacterial vaginosis
More common in second half of menstrual cycle, pregnancy and diabetes mellitus
Cytology images: lactobacilli #1; #2
Associated with Trichomonas infections (may resemble “spaghetti and meat balls”)
Cytology images: #1; various images; non-smear image
Schistosomiasis-cervical cytology
Cervix is most common site of infection in women by S. haematobium
Optimal method of detection is direct examination of cervical tissue obtained by forceps biopsy through quantitative compressed biopsy technique; cytologic examination of cervical smears is least sensitive (Am J Trop Med Hyg 2001;65:233)
Cytology: often granulomatous inflammation
Cytology images: not necessarily cervix - S. mansoni-lateral spine; S. japonicum; various images with case history
References: Int J Gynecol Cancer 2001;11:491
Syphilis-cervical cytology
Cytology: lymphocytes, plasma cells, histiocytes and debris; difficult to visualize organisms without immunostains
Trichomonas vaginalis-cervical cytology
Most common sexually transmitted disease worldwide
Facultative anaerobic protozoan parasite without mitochondria or peroxisomes
Morphologic identification with liquid based preparations is highly accurate and should not require confirmatory testing (Diagn Cytopathol 2005;32:341, Am J Obstet Gynecol 2003;188:354); in contrast, confirmatory tested is recommended for diagnosis based on conventional smears of women without symptoms (Obstet Gynecol 1993;82:425)
More common in ectocervical than endocervical smears (Diagn Cytopathol 1996;14:273)
Women often receive treatment for positive pap smear, even if asymptomatic (Diagn Cytopathol 2001;24:195)
Treatment: metronidazole (Flagyl); reduced inside the parasite by hydrogenase, reacts with oxygen to form radicals that rapidly kill the parasite
Cytology: pear-shaped, oval to round, 15-30 microns; often has eosinophilic cytoplasmic granules; has pale, vesicular and centrally located nuclei; adjacent squamous cells have hyperchromatic nuclei and small, evenly circumscribed, perinuclear halos; background is inflammatory
Note: Cytologic changes mimic ASCUS or LSIL due to pseudomaturation of squamous cells and perinuclear halo
Cytology images: flagella; various images #1; #2; trichomonas #1; #2; #3
Drawing: diagram
Virtual slides: trichomonas
References: Belgian website
Tuberculosis-cervical cytology
Cytology: epithelioid histiocytes and Langhans giant cells (peripheral nuclei), background contains caseous necrosis
Cytology images: epithelioid histiocytes #1; #2; Langhans giant cell with inflammatory background; acid-fast bacilli; not necessarily cervix - auramine-rhodamine
References: Acta Cytol 1989;33:305, J Clin Pathol 1976;29:313
Wuchereria bancrofti microfilariasis
Cytology images: various images
Benign / non-neoplastic lesions
Benign features-cervical cytology-general
Evenly distributed heterochromatin and euchromatin
Chromatin granules are small and uniformly distributed (versus coarse and uniform in lymphocytes and ovarian granulosa cells)
Chromatin is sharp and crisp
No hyperchromasia (lymphocytes are usually hyperchromatic)
Nuclear membranes are smooth
Chromatin rims of uniform thickness
Nucleoli conspicuous but not large and prominent (more conspicuous if biosynthetic activity or reactive)
Honeycomb configuration when viewed en face
Transparent cytoplasm (squamous, transitional cells) suggests benign and mature
Immature benign cells have high N/C ratio, denser cytoplasm, vesicular nuclei
Adenomyoma of endocervical type-cervical cytology
May resemble leiomyosarcoma on smear (Diagn Cytopathol 2005;32:288)
Cytology: clusters or individual spindle cells (smooth muscle cells) with delicate, wispy cytoplasm, oval nuclei with nucleoli; also large and bizarre nuclei; no mitotic figures, no necrosis
DD: atypical polypoid adenomyoma of uterus (tightly backed clusters of glandular cells and loose aggregates of bland smooth muscle cells in premenopausal patients, Diagn Cytopathol 2000;22:176)
Adenosis of cervix-cervical cytology
Associated with intrauterine DES exposure (usually adenosis in vagina, not cervix)
Apparent vaginal adenosis was also identified in vaginal smears of post-hysterectomy patients, not associated with DES exposure (Eur J Gynaecol Oncol 2000;21:43)
Pap smears and colposcopy are used to follow up adenosis to detect adenocarcinoma
Arias-Stella reaction-cervical cytology
Often causes overdiagnosis, but pregnant women with atypical glandular lesions (AGUS) may have SIL on subsequent biopsy (Acta Cytol 2001;45:294)
Changes disappear after pregnancy
Although important (Acta Cytol 1995;39:905), pathologists are often not told patient is pregnant or post-partum
Case reports: cervicovaginal smear of nonpregnant woman undergoing infertility treatment with clomiphene and beta-hCG (Diagn Cytopathol 2005;32:94), associated with cervical pregnancy (Acta Cytol 1994;38:218)
Cytology: cytomegaly with dense variable cytoplasm, nucleomegaly, high N/C ratio, round/oval nuclei with smudgy chromatin, frequent nuclear inclusions
DD: glandular atypia, adenocarcinoma
References: Diagn Cytopathol 1996;14:349
May cause increased incidence of ASCUS in Pap smears of peri- and post-menopausal women (Cancer 2001;93:100)
Associated with scanty smears (Cytopathology 1997;8:274), ASCUS in post-menopausal women (Diagn Cytopathol 2001;24:132)
Changes may disappear after topical estrogen
Micro/cytology: increased number of parabasal cells; pseudokoilocytosis, immature but bland epithelium; may resemble urothelial metaplasia; may have focal nuclear enlargement and hyperchromasia; cells have prominent intercellular bridges; nuclei are uniform, evenly spaced, often elongated with grooves; no atypia in upper epithelial layers, no mitotic figures
Cytology images: various images #1; #2
Virtual slides: Thin-Prep
Negative stains: Ki-67 (Gynecol Oncol 2000;79:225, J Pathol 2000;190:545), cyclin E, p16
DD: SIL (strong Ki-67+ and p16 staining in 75-80%, strong cyclin E+ in 31%, J Low Genit Tract Dis 2005;9:100)
Atypical polypoid adenomyoma of cervix-cervical cytology
Should be considered in differential diagnoses of atypical glandular cells
Cytology: tightly backed clusters of glandular cells and loose aggregates of bland smooth muscle cells in premenopausal patients, (Diagn Cytopathol 2000;22:176)
DD: adenocarcinoma in situ (Acta Cytol 1999;43:637)
Decidual reaction in cervix-cervical cytology
Present cytologically in 1/3 of patients with histologically confirmed decidual reaction (Acta Cytol 1981;25:616)
Cytology: mean 100 cells per smear slide; cells occur in aggregates, have variable size, abundant cytoplasm, marked nuclear enlargement with finely granular chromatin and prominent nucleoli
Cytology images: not necessarily cervix - decidual reaction
DD: repair, SIL, adenocarcinoma
Endocervical polyp-cervical cytology
Either a diagnosis (benign lesion of endocervical type cells) or a physical structure that contains another lesion (SIL, carcinoma, etc.)
Benign polyps may be diagnosed as AGUS on cytologic smear (Acta Cytol 2000;44:41, Acta Cytol 1999;43:351)
Case reports: metastatic serous surface papillary carcinoma of ovary to cervical polyp, initially diagnosed on smear (Acta Cytol 1996;40:765)
Cytology (benign polyp): no feathering, no nuclear palisading, no chromatin clearing
Endometrial polyp in cervix-cervical cytology
Presence of endometrial type cells is associated with endometrial polyps in 5% or more of cases (Diagn Cytopathol 2002;26:123, Gynecol Oncol 2001;81:33)
Also associated with AGUS (Acta Cytol 2000;44:41)
Endometriosis-cervical cytology
Cytology reports may indicate “atypical glandular cells” (Diagn Cytopathol 2004;30:88)
Cytology: sheets and strips of atypical endocervical-like columnar cells; endometrial type cells in solid and cohesive clusters with crowded, overlapping glandular groups; usually retained cell polarity and well defined cytoplasmic edges; no three dimensional cell clusters, no cell feathering, no pseudostratified cell strips (Diagn Cytopathol 1999;21:188)
Cytology images: endometriosis
Positive stains: CD10; reticulin surrounds each cell (Int J Gynecol Pathol 2001;20:173)
DD: HSIL (Diagn Cytopathol 2002;26:35), AGUS (Diagn Cytopathol 2004;30:88), adenocarcinoma in situ
Endosalpingiosis-cervical cytology
May cause psammoma bodies in cervicovaginal smears (J Reprod Med 1991;36:675, J Reprod Med 2000;45:526)
Florid ectopy-cervical cytology
When the squamocolumnar junction is located outside the external os, the glandular mucosa in contact with the vagina is called ectopia or ectropion; “florid” signifies that the glandular mucosa is secretory
Cytology images: florid ectopy
Pap smear diagnosis is usually infectious or otherwise abnormal (J Med Assoc Thai 1991;74:471)
Cytology images: esophageal leiomyoma showing groups of spindled cells with relatively low cellularity #1; #2
Lobular endocervical glandular hyperplasia of cervix, NOS-cervical cytology
Cytology: benign looking glandular cells with intracytoplasmic golden-yellow mucin (Diagn Cytopathol 2002;27:80)
Cytology images: benign glandular cells with golden-yellow mucin (figures c and d)
DD: minimal deviation adenocarcinoma (may also have golden yellow mucin, but has focally malignant cytologic features, Pathol Int 2005;55:412)
Mesonephric rests / remnants of cervix-cervical cytology
May cause abnormal pap smears (Int J Gynecol Pathol 2003;22:121)
Mesonephric hyperplasia-cervical cytology
May cause abnormal pap smears (Cytopathology 2005;16:240, Int J Gynecol Pathol 2003;22:121)
Cytology: abnormal glandular cells in loose clusters with cuboidal outlines and no significant anisocytosis
Positive stains: CD10 (Adv Anat Pathol 2004;11:310)
Microglandular hyperplasia-cervical cytology
Cytology: bi- or tridimensional cellular clusters of cubic or cylindrical glandular cells with vacuolated cytoplasm, also cells with dense cytoplasm and basaloid cells; often has an immature metaplastic pattern (Diagn Cytopathol 2004;30:57); also reserve cells with scant cytoplasm and small, round nuclei; clusters have microlumina or fenestrated spaces, normal polarity (Acta Cytol 1999;43:110); may have cytologic atypia (Diagn Cytopathol 1994;10:326); may have multiple nucleoli, mitotic figures, apoptotic bodies and focal, watery diathesis (Acta Cytol 2000;44:661)
Cytology images: degenerating endocervical cells with streaming; endocervical cells appear pseudokeratotic #1; #2
DD: adenocarcinoma
Myofibroblastoma-cervical cytology
Cytology images - breast: loose groups of cells with abundant eosinophilic granular cytoplasm and bland nuclei
Squamous papilloma-cervical cytology
For cytologic smears, incidence of 1 per 5000, associated with pregnancy (Med J Aust 1975;2:304)
Cytology: dysplasia of squamous cells is often found
Atypia / premalignant / preinvasive lesions
Human papilloma virus (HPV)-cervical cytology
Koilocytosis / koilocytotic atypia: related to expression of viral E4 protein and disruption that this causes in cytoplasmic keratin matrix
Nuclear changes required for diagnosis of koilocytosis since glycogen accumulation is otherwise common (Archives 1990;114:1038)
Note: perinuclear halos can be prominent in postmenopausal cervix without HPV
Low risk HPV subtypes: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, CP6108 (associated with genital condylomas and low grade SIL)
High risk HPV subtypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 (associated with high grade SIL and invasive carcinoma); 26, 53 and 66 are “probably high-risk” (Low Genit Tract Dis 2005;9:154)
HPV 18: associated with lesions of glandular origin, small cell neuroendocrine carcinoma; recommended for patients with HPV18+ cervical smears to have endocervical curettage, even if normal morphology (Best Pract Res Clin Obstet Gynaecol 2005 Dec 12 [Epub ahead of print])
Presence of HPV 16 or 18 confers a 200x relative risk for HSIL for 2 years after first detection (Eur J Obstet Gynecol Reprod Biol 2006;125:114
Uses: HPV testing (Hybrid Capture 2 test) is used to triage ASCUS or LSIL cases (HPV+ are more likely to have HSIL at followup) and to confirm cervical origin of squamous cell carcinoma or adenocarcinoma (AJCP 2005;124:24, Archives 2001;125:1453)
Cytology: koilocytes are superficial or immature squamous cell with large and irregular, well defined perinuclear halos with cookie cutter border and cytoplasmic thickening, nuclei are enlarged with undulating (raisin-like) nuclear membrane and rope-like chromatin; often bi- or multinucleation and variation in nuclear size
Cytology images: various images #1; #2; koilocyte #1; #2
Positive stains: Ki-67 (higher in HPV+ epithelium than inflamed or metaplastic squamous epithelium; very high with high risk HPV types); diffuse and strong p16 associated with high risk HPV (AJSP 2007;31:33)
Molecular: usually detected by Southern blot hybridization (“gold standard”) or in situ hybridization; HPV DNA may be detected by PCR in lesions without koilocytotic atypia (AJSP 1990;14:643)
Condyloma acuminatum-cervical cytology
Usually associated with HPV 6 or 11
Cytology images: koilocytosis
Immature condyloma-cervical cytology
Cytology: metaplastic squamous cells with nuclear enlargement, occasional binucleation, uniform nuclear contours, minimal hyperchromasia (Diagn Cytopathol 1998;18:416)
Atypical glandular cells / atypical cells of undetermined significance (AGUS)-cervical cytology
Bethesda system 2001 uses terminology AGC - Atypical glandular cells
Frequently associated with a clinically significant diagnosis (10-40%, Int J Gynaecol Obstet 2005;91:238, Obstet Gynecol 2005;105:494, AJCP 2004;122:575), including squamous dysplasia (Obstet Gynecol 1992;79:101)
HPV testing recommended on all AGC smears (Diagn Cytopathol 2006;34:235); HPV testing has excellent negative predictive value for the absence of SIL (Am J Obstet Gynecol 2005;193:559)
Cytology: morphological changes of glandular cells which are too pronounced for inflammatory or reactive origin, but insufficient to diagnose an adenocarcinoma; more likely to be neoplastic if decreased cytoplasm, irregular nuclear membranes and nucleoli present (Cytopathology 2005;16:295).
Cytology images: various images #1; #2
Treatment: colposcopic biopsy plus repeat cytology, repeat cytology is often not performed (Obstet Gynecol 2005;105:501)
Atypical repair-cervical cytology
Part of ASC-US category in Bethesda 2001
5% incidence of SIL in one study (Diagn Cytopathol 2005;33:214); higher incidence with liquid based cytology in Hong Kong (Cancer 2003;99:141)
Cytology: uniform nuclei, chromatin with increased chromatin granules, hyperchromasia, mitotic activity, few cohesive tissue fragments
Liquid based cytology: scattered atypical squamous cells with prominent nucleoli and other evidence of reparative change; also more obvious nuclear pleomorphism, anisonucleosis, nuclear outline irregularities, coarsening of chromatin and focal loss of nuclear polarity
DD: poorly differentiated squamous cell carcinoma or adenocarcinoma
Atypical reserve cell hyperplasia-cervical cytology
Cytology: no cytoplasm; cells easily damaged in smear process
DD: artifact; cases with MIB-1 staining are associated with HSIL (Mod Path 1995;8:786)
Atypical squamous cells of undetermined significance (ASCUS)-cervical cytology
May be neoplastic (HPV related, LSIL, HSIL) or reactive
In cervical smears, are often related to SIL (now or at later biopsy, Mod Path 1994;7:920)
Poor reproducibility for this diagnosis
Typical ASCUS/SIL diagnostic ratio for a laboratory is 3:1; often lower for liquid based cytology
HPV testing using Hybrid Capture II test is recommended after ASCUS diagnosis (Gynecol Oncol 2005;99:S7, J Natl Cancer Inst 2002;94:102); may also be helpful for ASC-H diagnosis (Cancer 2005;108:32), particularly if result is negative (Cancer 2005;105:457)
Reflex testing for high risk HPV types has positive rates from 15% (age 35+) to 58% (age 20 years or less, AJCP 2005;123:524)
For liquid based cytology diagnoses of ASCUS, manual reprocessing of residual material often causes reclassification to LSIL or HSIL (Diagn Cytopathol 2005;33:434)
Higher risk for SIL in HIV+ women (Clin Infect Dis 2006;42:855)
Treatment: repeat cytology, colposcopy, or perform DNA testing for high risk HPV subtypes
Micro: nuclear changes more marked than reactive, less than LSIL; nucleus is 2.5-3x size of intermediate cell nucleus or 1.5x size of mature metaplastic cell nucleus
In perimenopausal women (40-55 years), cells with bland nuclear enlargement (2-3x size of intermediate cell nuclei), smooth nuclear membranes and fine chromatin are likely to be negative for SIL/malignancy (AJCP 2005;124:58)
Cytology images: various images #1; #2; #3; mild nuclear enlargement; nuclear enlargement with atrophy; nuclear enlargement with hyperchromasia and irregular nuclear membranes; Herxheimer spiral; keratin pearl; ASCUS possibly LSIL; ASC-H or HSIL; ASC-H #1; #2; ASC-US
References: Mod Path 2000;13:252
Chemotherapy effect-cervical cytology
Chemotherapy is usually associated with a normal cellular pattern; also reactive cellular changes, atrophic pattern (Acta Cytol 1999;43:1027)
Cytology: smudged chromatin, only a few atypical cells
Radiation atypia-cervical cytology
Severe changes less than carcinoma are called radiation dysplasia
Cytology: usually low cellularity; multinucleated giant cells, large atypical cells with marked cytoplasmic vacuoles; intermediate parabasal cells have nuclear enlargement 2.5 to 3.0x normal, but with small N/C ratio due to increased cytoplasm; chromatin is smudgy or finely granular; prominent nucleoli; smear also shows endothelial cells and macrophages (Diagn Cytopathol 1995;13:107), but clear background
Cytology images: various images #1; #2; #3; #4; #5
Squamous intraepithelial lesions (SIL)-cervical cytology-general
SIL cells are usually detected by cytologic examination (Pap smear or liquid based cytology)
SIL morphologic abnormalities correlate with cytogenetics, ploidy, cell proliferation and molecular changes
Increased risk in SLE and HIV patients (Arthritis Rheum 2004;50:3619)
HPV hybrid capture: testing for high-risk HPV with the HCT II test is useful to detect HSIL in LSIL groups and to select ASCUS patients for colposcopy, but not for cervical cancer screening tests (Archives 2001;125:1453); HCT II is more sensitive than a repeat smear in detecting high grade lesions in women with low grade lesions (Acta Obstet Gynecol Scand 2005;84:996)
Can also detect HPV using indirect PCR on Pap smears (Archives 2001;125:353)
Low grade SIL (LSIL): usually euploid or polypoid, 2/3 regress, 1/6 progress, 1/6 are unchanged
High grade SIL (HSIL): usually aneuploid, less regression; 1/3 become invasive at 9 years; associated with HPV types 16, 18, 31, 33; peaks during age 30-39 years; 0.2% develop invasive carcinoma even after treatment; distinction between high grade dysplasia / HSIL and carcinoma in situ is not reproducible between pathologists and is not usually made anymore
Classification systems: (a) mild, moderate or severe dysplasia or carcinoma in situ; (b) cervical intraepithelial neoplasia (CIN) - CIN I, CIN II, CIN III; (c) low grade SIL (LSIL) or high grade SIL (HSIL) - SIL terminology is currently recommended
Treatment for LSIL: controversial since most lesions regress
Treatment for HSIL: cone, LEEP, electrodiathermy, cryosurgery, laser; long term follow up is necessary
Note: treatment of HIV+ patients must be more aggressive (Eur J Obstet Gynecol Reprod Biol 2005;121:226)
Cytology: similar histology as invasive cells, including nuclear enlargement and hyperchromasia, alteration of maturation, increased mitotic activity; also reduction in cytoplasmic glycogen (less iodine staining with Lugol or Schiller’s iodine test); no tumor diathesis
Usually cell borders are NOT well defined (CIN like changes with well defined cell borders implies reactive changes), nuclei are crowded and irregular with smudgy or granular chromatin
Keratinizing or non-keratinizing
Includes cells with HPV cytopathic effect
Drawings: SIL diagram #1; #2; drawing of classification systems
Positive stains: Ki-67/MIB
LSIL / CIN I / low grade dysplasia-cervical cytology
Diagnostic accuracy is improved by Ki-67 staining
Cases with fewer abnormal cells are more likely to be missed (Archives 2005;129:23)
HPV negative LSIL is not a distinct biologic entity; often due to false positive LSIL or false negative HPV (Cancer 2005;105:253)
HPV16+ LSIL or ASC have higher risk for HSIL than HPV16 negative LSIL/ASC (J Natl Cancer Inst 2005;97:1066)
Cases diagnosed antepartum are stable or regress during pregnancy, but may recur postpartum (Cancer 2004;102:228)
Koilocytotic atypia: nuclear pleomorphism, wrinkled nuclei, hyperchromasia, binucleation, perinuclear halos with distinct clear zone around nucleus and condensation of denser cytoplasm around the periphery; few/no mitotic figures, particularly in lower half of epithelium, no atypical mitotic figures
Cytology: usually transparent cytoplasm; enlarged nuclei at least 3x size of nucleus of intermediate cell, but N/C ratio is less than 1/3; hyperchromasia (darker than intermediate cell), cell may be enlarged (largest atypical cells in gynecologic cytology are LSIL), but still has elevated N/C; no nucleoli; binucleation is more common than multinucleation; koilocytes may be present; cytology from immature LSILs may be interpreted as metaplasia, ASCUS or HSIL
Cytology images: various images #1; #2; LSIL; performed by cytocentrifugation #1; #2
Virtual slides: low grade SIL #1; #2; #3; #4
DD of LSIL:
(a) reactive epithelial changes: cytoplasmic halos are associated with glycogenated cells, mild atypia is associated with inflammation, but no pleomorphism is present; small binucleated cells may be seen in a background of metaplasia; reactive changes usually have regular nuclear spacing, distinct nucleoli, no nuclear atypia in upper layers, superficial maturation
(b) postmenopausal squamous atypia: pseudokoilocytosis with uniform/round halos with central nuclei, slightly hyperchromatic, occasional grooves, occasional binucleation; is associated with urothelial metaplasia and atrophy; NOT associated with HPV (Mod Path 1995;8:408
(c) HSIL
HSIL / CIN II / moderate dysplasia-cervical cytology
Cases with a few moderately dysplastic cells may have LSIL or HSIL at followup, which cannot be predicted (Diagn Cytopathol 2000;23:245)
Cytology: N/C ratio is 1/3 to 1/2; cell size is same as squamous metaplastic or parabasal cells; polygonal shape (like intermediate or superficial cell); denser cytoplasm; enlarged and hyperchromatic nucleus; nuclear membranes may be irregular (crinkled paper); no nucleoli; check for variation in nuclear size at basal layer
Cytology images: CIN II #1; #2; #3-air drying; possible CIN II #1; #2
HSIL / CIN III / severe dysplasia-cervical cytology
Also called carcinoma in situ
Cases with fewer abnormal cells are more likely to be missed (Archives 2004;128:746); underdiagnosis may be due to air drying artifact and metaplasia (Indian J Cancer 2004;41:104)
Cases diagnosed antepartum persist postpartum, and 11% develop invasive carcinoma postpartum (Cancer 2004;102:228)
Cytology: Usually single, small, round/oval cells with scant cytoplasm; nuclei same size as dysplastic cells but increased N/C ratio (greater than 1/2) since only minimal rim of cytoplasm; nuclear membrane does not have sharp angles; nuclei vary markedly in contour and have irregular coarsely clumped chromatin; no macronucleoli, no tumor diathesis
Cytology images: various images #1; #2; haphazard nuclei with clumped chromatin and hyperchromasia #1; #2; #3; HSIL in pregnant patient; HSIL and LSIL; HSIL vs. LSIL; HSIL, suspicious for invasion; performed by cytocentrifugation #1; #2
Virtual slides: high grade SIL #1; #2; #3; #4; #5; #6; #7
Keratinized cells are non-specific, associated with benign cellular changes such as parakeratosis or hyperkeratosis, ASCUS, as well as LSIL, HSIL and invasive squamous carcinoma
DD: squamous cell carcinoma (has tumor diathesis, many very atypical cells, bizarre shapes including “tadpoles”, prominent nucleoli, but may be difficult to distinguish, Diagn Cytopathol 2003;28:23)
Adenocarcinoma in situ (AIS)-cervical cytology
Predominantly a screening-detected disease (Acta Cytol 2004;48:595)
False negatives are common, particularly for endometrioid AIS or AIS cells resembling reactive endocervical cells (AJCP 1997;107:30, AJCP 1998;109:738)
False negatives also due to minimal, poorly preserved abnormal material, overly conservative approach in assessing unusual large sheets or aggregates of glandular cells (Cancer 2004;102:280), and inherent difficulty in detection (Archives 2004;128:153)
Cytology: tightly crowded sheets of malignant cells with architectural disarray, often with short strips of pseudostratified columnar cells near edges; nuclei may be partially denuded, causing a feathered appearance; nuclei are enlarged, usually oval, and hyperchromatic; often prominent nucleoli; no tumor diathesis
For endometrioid AIS, most useful criteria for diagnosis are predominance of groups with marked crowding, focal feathering, nuclear hyperchromatism with coarsening of chromatin and occasional mitotic figures
Features favoring a benign diagnosis are sheets of cells, endometrial tubules and endometrial stroma
Micro images: ThinPrep #1; #2; #3; #4
Cytology images: various images #1; #2; #3; adenocarcinoma in situ #1: #2
Paget's disease-cervical cytology
Case reports: extensive disease detected by pap smear (Archives 1988;112:941)
Cytology images: vulvar disease extending into vagina
Carcinoma
Squamous cell carcinoma of cervix-cervical cytology
Reduction in prevalence due to Papanicolaou smear test to detect premalignant lesions (1 million cases of SIL detected per year in US, 13,000 new invasive carcinomas)
Diagnosis in conventional smears is more likely to be missed if fewer malignant cells and not keratinized (Archives 2005;129:1097); also if Trichomonas present (Archives 2004;128:403)
Cytology: highly irregular shaped cells (tadpole, caudate); keratinized are orange, often with squamous pearls; nonkeratinized cells have dense, hard, basophilic cytoplasm; also cannibalism (tumor cells surround other cells); compared to adenocarcinoma, have more irregular cellular and nuclear shapes, more cytoplasmic density, more chromatin granularity, more hyperchromasia
Tumor diathesis in background (necrosis, hemorrhage, inflammatory cells) is suggestive of malignancy
Tumor diathesis in liquid based cytology: more subtle than with conventional smear; consists of necrotic material at peripheral of cell groups (“clinging diathesis”) and not in the background
Other features in liquid based cytology: mild to moderate inflammation, coexistent dysplasia, keratinization; decreased cell coverage is common (Diagn Cytopathol 2002;26:1)
Cytology images: various images #1; #2; keratinizing and nonkeratinizing #1; #2; tumor of endometrium
SurePath images contributed by Frank Melgoza MD and Mai Gu MD PhD, UC Irvine, California (USA): hyperchromatic spindle-like cells with heavy keratinized cytoplasm #1; #2; #3; #4; #5; #6
DD: keratinizing dysplasia involving endocervical glands (Diagn Cytopathol 2003;28:23), atrophic vaginitis with Thin-Prep (similar background, but no malignant squamous epithelial cells, Diagn Cytopathol 2002;27:362), HPV, radiation
Papillary squamotransitional carcinoma of cervix
Liquid based cytology: moderately to highly cellular with three dimensional, arborizing, papillary clusters of basal or parabasal cells; occasional fibrovascular cores; cells vary from bland to SIL; frequent mitotic figures; occasional tumor diathesis and dyskeratotic cells; no koilocytosis (Acta Cytol 2003;47:141)
Microinvasive squamous cell carcinoma of cervix-cervical cytology
DD: endocervical brush sampling of SIL (Diagn Cytopathol 1992;8:18)
Adenocarcinoma of cervix-cervical cytology
Conventional smears that are false negative often have fewer and smaller abnormal cells, small nuclei, less atypia and less hyperchromasia (Archives 2006;130:23)
Cytology: multilayering; may form glandular structures with central lumina or acinar formations with peripheral nuclei; may see morules (also seen with mesothelial cells, benign and malignant lesions); cells are large or small with pleomorphism; have fluffy cytoplasm, cytoplasmic vacuolization, loss of nuclear polarity, true nuclear crowding, nuclei with clumped chromatin, marked variation of nucleoli, occasional mitotic figures; invasion is often characterized by heavy blood with abundant glandular material, even without tumor diathesis or fully malignant nuclear criteria (Cancer 2002;96:5)
Endocervical adenocarcinoma: usually columnar with granular cytoplasm, rosettes, sheets with holes vs. balls, round plump cells, molded groups
Cytology images (mostly endocervical type): various images #1; #2; with repair like features; adenocarcinoma misdiagnosed as repair
Signet ring adenocarcinoma of cervix-cervical cytology
Cytology: large secretory vacuoles push nuclei to periphery; may see prominent nucleoli
Note: squamous cell carcinoma may have distended degenerative vacuoles
DD: metastatic carcinoma from breast or stomach
Microinvasive adenocarcinoma of cervix-cervical cytology
Cytology is 30% sensitive for identification of stromal microinvasion (Diagn Cytopathol 1997;16:430)
Cytology: atypical glandular cells forming pseudosyncytial clusters; may have pleomorphic nuclei, coarse irregular chromatin, karyorrhectic nuclei, cell detritus
Adenoid basal carcinoma-cervical cytology
Case reports: 79 year old black woman with HSIL on pap test (Archives 2004;128:485)
Cytology: often no findings; may be small aggregates of small and uniform cells with hyperchromatic nuclei or atypical basaloid cells (Diagn Cytopathol 1996;14:172); also palisading and three dimensional groups with a “windswept” appearance (Acta Cytol 1995;39:563)
Adenoid cystic carcinoma-cervical cytology
Cytology: small cells in cribriform pattern (Acta Cytol 1996;40:1304)
Cytology images: breast tumor; salivary gland #1 with pseudoglandular space; #2
Positive stains: keratin, type IV collagen, laminin (extracellular basement membrane), HHF45, focal CEA and EMA
Negative stains: usually S100 and actin
Adenosquamous (mixed) carcinoma-cervical cytology
Glandular abnormality often not diagnosed on pap smear (Cancer 2004;102:210)
Cytology: thin-layer - papillary subtype shows high cellularity with papillary clusters of basaloid or columnar cells in fibrovascular cores; also rare, scattered adenocarcinoma cells with intracytoplasmic vacuoles and occasional dyskarytotic squamous cells with bizarre shapes (Acta Cytol 2003;47:649)
Clear cell carcinoma-cervical cytology
Recommended to obtain annual cervical and vaginal smears for DES exposed women, even after menopause (Gynecol Oncol 1999;75:338)
Cytology: FNA - loose, three dimensional clusters and sheets of atypical cells; also dispersed atypical cells; atypical cells are large with abundant, weakly staining cytoplasm, round/oval nuclei with large nucleoli; Pap stain shows a few tumor cells with clear cytoplasm and distinct cell borders
Diff-Quik shows tigroid background and basement membrane material (Acta Cytol 2000;44:251)
Endometrial adenocarcinoma-cervical cytology
Low risk (<2%) of nodal spread if normal cervical smear (Obstet Gynecol 2003;101:445)
Cervical smear is useful in detecting cervical involvement of endometrial carcinoma (Acta Cytol 2002;46:284)
Cervical smear is approximately 45% sensitive in detecting endometrial adenocarcinoma (Acta Cytol 2003;47:410)
Thin-Prep may be more sensitive than conventional smears (Cancer 2002;96:338, Diagn Cytopathol 2000;23:260)
Cytology: glandular component; also scattered single cells with hyperchromatic nuclei, 1-3 nucleoli, mitotic figures, apoptotic bodies, watery diathesis
Thin-Prep: tumor diathesis (53%, usually high grade lesions, Diagn Cytopathol 2005;33:162)
Cytology images: various images #1; #2; recurrent tumor
Cytology images: contributed by Dr. Carmen Luz, Spain - endometrial group with atypia (not necessarily carcinoma) in postmenopausal woman
Positive stains: CEA
DD: microglandular hyperplasia (no scattered single cells with atypia, no mitotic figures, no apoptotic bodies, no watery diatheses, CEA negative, Acta Cytol 2000;44:661)
Glassy cell carcinoma-cervical cytology
Cytology: exfoliative - clusters of cells and single cells with distinct cell borders, moderate to abundant, finely granulated cytoplasm, large, round/oval nuclei with 1 or more prominent nucleoli; background of neutrophils, often frequent eosinophils, necrotic debris and proteinaceous material; high mitotic rate, rare bizarre multinucleated cells, no koilocytes (Acta Cytol 2001;45:407, Acta Cytol 2000;44:551)
liquid based - moderately cellular with small clusters of polygonal to elongated tumor cells mixed with amphophilic and granular necrotic debris; tumor cells have discrete cell borders, abundant cyanophilic cytoplasm, round/oval nuclei, thin nuclear membrane, finely dispersed chromatin, prominent nucleoli; may have tumor phagocytosis of neutrophils; background of mixed inflammatory cells; no dyskeratosis, cytoplasmic vacuoles or koilocytosis (Acta Cytol 2004;48:99)
Cytology images: various images with case history; glassy cell carcinoma
DD: lymphoepithelioma-like carcinoma (Acta Cytol 1999;43:285)
Lymphoepithelioma-like carcinoma-cervical cytology
Cytology: uniform large tumor cells, indistinct cell borders, finely granular cytoplasm, round/oval nuclei and prominent nucleoli,
marginated chromatin; no koilocytes, no gland formation, no keratinization (Acta Cytol 1999;43:285)
Metastases to cervix-cervical cytology
Yield for positive Pap smear diagnoses in extrauterine malignancies is best in patients with an established diagnosis (Acta Cytol 1999;43:806)
Case reports: recurrent colon carcinoma invading into uterus and cervix and presenting with HSIL at pap smear (J Low Genit Tract Dis 2005;9:236), 17 year old with colon cancer metastatic to cervix presenting with abnormal pap smear (J Reprod Med 2005;50:793), 61 year old with metastatic salivary duct carcinoma (Diagn Cytopathol 1999;21:271)
Cytology images: metastatic tumors - breast carcinoma; colon carcinoma #1; #2; gastric carcinoma; melanoma; small cell carcinoma, urothelial carcinoma
Cytology images: contributed by Dr. Carmen Luz, Spain - metastasis from ovarian clear cell carcinoma with psammoma body
Minimal deviation adenocarcinoma-cervical cytology
Cytology: cervical smears often normal; may have glandular cells ranging from atypical to suspicious for well differentiated adenocarcinoma; glandular cells are enlarged and present in honeycombed sheets with abundant cytoplasm, uniform nuclei with fine chromatin and small nucleoli; no pleomorphism, no/rare mitotic figures (AJCP 1996;105:327); may have golden yellow mucin with Pap stain (Diagn Cytopathol 2002;27:80, Cancer 1999;87:245)
Serous papillary adenocarcinoma-cervical cytology
Cytology: hypercellar smears with tumor diathesis, papillae, bulky dense cytoplasm, bare nuclei and cells with large pleomorphic nuclei; also monolayered sheets of mildly atypical glandular cells with papillary branches; also pseudopapillary fragments, tight balls of cells resembling endometrial glandular cells, squamoid cells; marked tumor diathesis with primary disease but not metastatic disease to cervix (Cancer 1997;81:98); also psammoma bodies
DD: endometrioid carcinoma (monomorphic cells with delicate cytoplasm and moderately enlarged oval nuclei)
Small cell (neuroendocrine / undifferentiated) carcinoma-cervical cytology
Cytology: single or groups of small cells or gland-like aggregates with minimal cytoplasm, hyperchromatic nuclei with evenly distributed, finely stippled chromatin, nuclear molding and smearing; often mitotic activity and karyorrhectic debris; no nucleoli; more variation than lymphocytes (Acta Cytol 1998;42:978); may be only a few suspicious epithelial cells or no abnormalities on cervical smear (Cancer 1998;84:281)
Cytology (liquid based): moderate to highly cellular; loose aggregates or isolated small round cells with high N/C ratio, scant cytoplasm, thin but irregular nuclear membrane, hyperchromatic nuclei with salt and pepper (finely stippled) chromatin and prominent chromocenters, usually indistinct nucleoli; often tumor cell cannibalism, variable nuclear molding and smearing; background of tumor diathesis; associated SIL or koilocytosis
Cytology images: various images with case history; #3; #4; Thin-Prep
Virtual slides: small cell carcinoma
References: Acta Cytol 2003;47:56, Acta Cytol 2002;46:637, Diagn Cytopathol 2001;24:46, Diagn Cytopathol 2000;23:14
Urothelial carcinoma-cervical cytology
Cytology: necrotic and hemorrhagic background; urothelial-type cells form cohesive groups in multilayered fashion; have oval or spindled shape with tapered ends; nuclei are hyperchromatic with coarse granules, often wrinkled membrane and nuclear grooves; no/small nucleoli (Acta Cytol 2002;46:585)
Cytology images: metastatic urothelial carcinoma; primary fallopian tube urothelial carcinoma (CytoJournal 2005, 2:20)
Verrucous carcinoma-cervical cytology
Cytology: atypical polygonal and spindle cells with abundant and keratinizing cytoplasm with vacuoles; atypical squamous cells with keratin pearls
References: Acta Cytol 2003;47:1050, Acta Cytol 1983;27:540
Villoglandular papillary adenocarcinoma-cervical cytology
Diagnosis often missed due to bland cytologic features (Malays J Pathol 2003;25:139)
Cytology: large cohesive groups of endocervical cells with nuclear crowding and loss of normal honeycomb pattern; has true papillary structures with long, slender papillae containing stromal cores covered by well polarized columnar cells with intact cytoplasmic borders but no feathered edge; mildly atypical cells with crowding and overlapping of nuclei; nuclei are uniform, small, round/oval with evenly distributed granular chromatin; no/inconspicuous nucleoli; occasional mitotic figures and apoptotic bodies
Cytologic images: villoglandular carcinoma
References: Cancer 1999;87:5, Diagn Cytopathol 2002;26:10, Diagn Cytopathol 1997;17:383, Acta Cytol 1996;40:536
Warty (condylomatous) carcinoma-cervical cytology
Cytology: thin-layer - small, cohesive clusters and syncytial sheets of tumor cells with vague papillary architecture; tumor cells are polygonal or elongated with oval nuclei, coarse chromatin, occasionally distinct nucleoli; also many koilocytes, some with marked nuclear atypia due to pleomorphic nuclei and distinct nuclei; dyskeratotic tumor cells with bizarre shapes; background has dispersed malignant squamous cells and tumor diathesis (Acta Cytol 2003;47:159)
Sarcoma/lymphoma/other of cervix
Sarcoma of cervix-general-cervical cytology
Positive cytology is uncommon; abnormal cells may not be diagnostic of sarcoma (Acta Cytol 2002;46:465)
Cytology: ranges from small, uniform cells in tight and cohesive clusters to bizarre, pleomorphic, spindled cells with long cytoplasmic processes (Acta Cytol 1984;28:93)
Cytology images: not from cervix - cytoplasmic bubbles due to glycogen
Granulocytic sarcoma-cervical cytology
Case reports: relapse diagnosed by cervical smear (Int J Gynecol Cancer 2004;14:553)
Leiomyosarcoma-cervical cytology
Cytology: isolated cells or side by side tumor cells with elongated cytoplasm, oval or cigar shaped nuclei with coarse chromocenters (Tumori 1978;64:205); nuclear atypia, mitotic figures and necrosis are important features
DD: adenomyoma (spindle cells with wispy cytoplasm, elongated nuclei and nucleoli, but no mitosis or necrosis, Diagn Cytopathol 2005;32:288)
Usually presents with abnormal uterine or vaginal bleeding
Cervical smear may be first indication of tumor, but smear is often negative or reported as SIL
Usually diffuse large B cell or follicular subtypes (Mod Path 2000;13:19)
Case reports: Burkitt’s lymphoma with HSIL (Pathol Res Pract 2005;201:521), two patients with diffuse large B cell lymphoma and follicular lymphoma at biopsy but HSIL by pap smear (Gynecol Oncol 2005;98:484), 3 patients with atypical lymphoid cells at pap smear (Am J Hematol 2003;73:176), detection of HTLV-1 (in adult T cell leukemia / lymphoma) by PCR on cytologic smears (Methods Mol Biol 2005;304:183)
Cytology: round, loosely arranged neoplastic cells with scanty cytoplasm (Cytopathology 1996;7:204)
endometrial lymphoma - individual cells with high N/C ratio, coarsely granular chromatin, some chromatin clearing, small nucleoli (Acta Cytol 1997;41:533)
Cytology images: various images; large cell lymphoma; liquid based cytology-recurrent lymphoma
DD: chronic cervicitis (ThinPrep specimens may show clumps of lymphocytes, Cytopathology 2002;13:364)
Malignant mixed Mullerian tumor (MMMT)-cervical cytology
Conventional pap smear is only 60% sensitive for carcinosarcoma (AJCP 2004;122:434)
Diagnosis is often carcinoma without a mesenchymal component (Diagn Cytopathol 1992;8:33)
Cytology: findings are often present if advanced stage uterine disease with involvement of lower uterine segment or cervix; usually large numbers of high grade malignant cells with necrosis, occasional mitotic figures, usually no mesenchymal component present
Cytology images: various images
Positive stains: both components - EMA, keratin, vimentin (most); sarcomatous component - muscle specific actin or smooth muscle actin, desmin
References: Diagn Cytopathol 2003;28:245, Acta Cytol 2002;46:465
Case reports: amelanotic metastatic tumor presenting as cervical polyp (Acta Cytol 1985;29:612)
Cytology: tumor cells with occasional cytoplasmic brown pigment, often bizarre shape; hyperchromatic and irregular nuclei, prominent nucleoli; also necrosis, occasional mitotic figures
Cytology images: metastatic tumor #1; #2; vaginal tumor
Positive stains: S100, HMB45, vimentin, Ki-67 (high percentage)
Negative stains: keratin, CD45, ER, PR
References: Cytopathology 2003;14:153, Diagn Cytopathol 2001;25:108, Acta Cytol 1994;38:65
Plasmacytoma-cervical cytology
Rare in cervix
Case reports: 37 year old woman with tumor in endocervical polyp detected by Pap smear (Archives 2003;127:e28)
Cytology images: pap smear
Reticulum cell sarcoma-cervical cytology
Case reports: cervical tumor diagnosed based on cervicovaginal smear, no mass lesion present (Acta Cytol 1978;22:46)
References: Am J Obstet Gynecol 1976;125:691
Rhabdomyosarcoma-cervical cytology
Divided into embryonal, botyroid, alveolar or pleomorphic (anaplastic) subtypes
Usually embryonal type, which occurs in children
Cytology: loose clusters of spindled cells in a necrotic background; cells have mild nuclear atypia, thin nuclear membrane, fine chromatin pattern, partly clear nucleolus
Stromal sarcoma-cervical cytology
Exfoliated cells may be present in cervicovaginal smears
Cytology: small, rounded malignant cells with occasional tapered “comet” forms, discernable nucleoli and tumor diathesis (Acta Cytol 1981;25:272)
Cytology images: high grade tumor-with case report
End of Cervix-cytology chapter
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