Dr.ARVIND RAJWANSHI Dr.ARVIND RAJWANSHI ( MODERATOR) ( MODERATOR)

Dr.Kunal SEHGALDr.Kunal SEHGAL

Cervical Cytology : Nomenclature & Cervical Cytology : Nomenclature & ClassificationClassification

Papanicolaou’s Classification

Class I : Absence of atypical or abnormal cells

Class II : Atypical cytology but no evidence of malignancy

Class III : Cytology suggestive of but not conclusive for malignancy

Class IV: Cytology strongly suggestive of malignancy

Class V : Cytology conclusive for malignancy

Cytological Classification of Tumors of Female Genital Tract (W.H.O.)

1. CELLS DERIVED FROM CERVICAL LESIONSA. DYSPLASIA

1. Mild2. Moderate3. Severe

B. EPIDERMOID CARCINOMA IN SITUC. EPIDERMOID CARCINOMA IN SITU WITH MINIMAL

STROMAL INVASIOND. INVASIVE EPIDERMOID MICROCARCINOMAE. INVASIVE EPIDERMOID CARCINOMA

1. Keratinizing carcinoma2. Large cell non-keratinizing carcinoma3. Small cell non-keratinizing carcinoma

F. ADENOCARCINOMA OF ENDOCERVIXG. CLEAR CELL (MESONEPHRIC) CARCINOMA OF CERVIXH. ADENOSQUAMOUS (MUCO-EPIDERMOID) CARCINOMA

Terminology of three Nomenclature Systems

WHO (Dysplasia) Richart Bethesda (CIN)

Mild dysplasia CIN I SIL : LowModerate dysplasia CIN II SIL : High Severe dysplasia CIN IIICIS

Current concepts :Cervical Cytology

Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnosis

Bethesda System: Why?

1.Need for standard system of nomenclature so that the results are comparable

2.A clear statement of Adequacy of the specimen

3.General categorization4.Appropriateness of making

recommendations for further evaluation if clinically indicated

Why?Bethesda System

It is important to distinguish cervical intraepithelial neoplasia from benign & reactive atypias. More recent information pointing to an apparent biologic dichotomy between mere “infection” and genuine “neoplasia” has resulted in latest entry:Bethesda System

Why?Bethesda System

• The Bethesda System terminology suggests that the disease is not a continuum but rather a discontinuous two disease system emphasized by terminology of low (6 & 11) and high grade (16-18) squamous intraepithelial lesion.

The 1991 Bethesda SystemAdequacy of the Specimen

Satisfactory for evaluation

Satisfactory for evaluation but limited by … [specify reason]

Unsatisfactory for evaluation …[specify reason]

General Categorization (Optional)

Within normal limits

Benign cellular changes: See Descriptive

Diagnosis

Epithelial cell abnormality: See Descriptive

Diagnosis

Descriptive Diagnosis

Benign Cellular Changes

Infection

Trichomonas vaginalis

Fungal organisms morphologically consistent with Candida species

Predominance of coccobacilli consistent with shift in vaginal flora

Bacteria morphologically consistent with Actinomyces species

Cellular changes associated with herpes simplex virus

Others*

Reactive Changes

Reactive cellular changes associated with:

Inflammation (includes typical repair)

Atrophy with inflammation “”atrophic vaginitis”

Radiation

Intrauterine contraceptive device (IUD)

Other

Epithelial Cell Abnormalities

Squamous Cell

Atypical squamous cells of undetermined significance: [Qualify†]

Low-grade squamous intraepithelial lesion encompassing:HPV* mild dysplasia/CIN I

High-grade squamous intraepithelial lesion encompassing:

Moderate and severe dysplasia, CIS/CIN II and CIN III

Squamous cell acrcinoma

Glandular Cell

Endometrial cells, cytologically benign, in a postmenopausal woman

Atypical glandular cells of undetermined significance : [Qualify†]

Endocervical adenocarcinoma

Endometrial adenocarcinoma

Extrauterine adenocarcinoma

Adenocarcinoma, not otherwise specified

Other Malignant Neoplasms : [Specify]

Hormonal Evaluation (applies to vaginal smears only)

Hormonal pattern compatible with age and history

Hormonal pattern incompatible with age and history: [Specify]

Hormonal evaluation not possible [Specify]

•Cellular changes of human papillomavirus (HPV) previously termed koilocytosis, koilocytotic atypia, or condylomatous atypia are included in the category of low-grade squamous intraepithelial lesion.•† Atypical squamous or glandular cells of undetermined significance should be further qualified, if possible, as to whether a reactive or a premalignant/malignant process is favoured.

Bethesda System 2001

One example of a significant change in this version of The Bethesda System is the incorporation of the new technology called "liquid-based" collection. Instead of taking a conventional smear that spreads the cell specimen across a glass slide, liquid-based collection involves rinsing or dropping the collection instrument in a vial of liquid fixative. Previous versions of Bethesda required an evaluation of whether the specimen was considered adequate, but criteria were based on the conventional smear and did not address the new technologies. The 2001 Bethesda System incorporates new criteria for evaluating liquid-based specimens.

Adequacy: Bethesda 2001

• Bethesda 2001 also proposes new numeric criteria for an adequate squamous component for both conventional and liquid based preparations.

• Conventional smears : “Unsatisfactory” if <8000 well preserved and visualized squamous cells.

• Liquid based preparations : adequate squamous component is 5000 well preserved and visualized cells

JAMA 2002;14:172-177.

Bethesda System 2001There have been a number of studies over the past decade that have identified a subset of women who have ambiguous findings –

•either squamous atypical changes •glandular atypical changes

These women are at higher risk of having an occult, or under diagnosed, high-grade lesion, who need treatment.

To help identify this subset of women, Bethesda 2001 does two things:

•First, it eliminates any kind of false assurance to the clinician, by getting rid of the phrases "favor reactive process" or "favor benign process.“• Second, it focuses clinicians' attention on a subset of women with squamous cell changes who are at highest risk of having a lesion that needs treatment. It does this by creating a new category -- atypical squamous cells -- cannot exclude a high-grade lesion (ASC-H). So these higher-risk cells are now flagged for clinicians - not just in the new terminology but also in the management guidelines. •These women are managed differently than the general pool of women who have ambiguous test results.

THE 2001 BETHESDA SYSTEM

• SPECIMEN TYPE Indicate conventional smear (Pap smear) vs. liquid-based preparation vs. other  

• SPECIMEN ADEQUACY

Satisfactory for evaluation:

(describe presence or absence of endocervical/transformation zone component and any other quality indicators, e.g., partially obscuring blood, inflammation, etc)

• Unsatisfactory for evaluation(specify reason)

• Specimen rejected/not processed (specify reason)

• Specimen processedand examinedbut Unsatisfactory for epithelial abnormality because of (specify reason)

THE 2001 BETHESDA SYSTEM(Cont.)

INTERPRETATION / RESULT • NEGATIVE for Intraepithelial lesion or malignancy• Organisms:• Trichomonas vaginalis• Fungal: Candida • Altered flora:Actinomyces species • Herpes Simplex virus • Other non neoplastic findings • Reactive cellular changes associated with: Inflammation (includes typical repair) Radiation Intrauterine Contraceptive Devices(IUD)• Glandular cells status post hysterectomy• Atrophy• Other:Endometrial cells

(in a woman >= 40 years of age) (Specify if ‘negative for squamous intraepithelial lesion’)

THE 2001 BETHESDA SYSTEM(Cont.)

• Epithelial Cell Abnormalities• Squamous cells Atypical squamous cells Undetermined significance (ASCUS ) Can not exclude H SIL (ASC-H) • Low grade Squamous Intraepithelial Lesion Encompassing: HPV/mild dysplasia/CIN 1• High grade Squamous Intraepithelial Lesion (HSIL)

Encompassing: moderate and severe dysplasia, CIS; CIN 2 and CIN 3

• With features suspicious for Invasion (if invasion is suspected)

• Squamous Cell Carcinoma

THE 2001 BETHESDA SYSTEM(CONT)

GLANDULAR CELL Atypical

Endocervical Cells,NOS or specify in comments Endometrial cells,NOS or specify in comments Glandular cells ,NOS or specify in comments Atypical Endocervical cells,Favour neoplastic Glandular cells,favourneoplastic • Endocervical adenocarcinoma in situ• Adenocarcinoma:Endocervical,Endometrial, Extrauterine,not

otherwise specified(NOS) • OTHER MALIGNANT NEOPLASMS• Ancillary Testing

Comparison of the Categories Specimen Adequacy and Diagnosis in Bethesda 1991 and 2001

Category Modified a Bethesda 1991 Bethesda 2001Specimen adequacy Satisfactory

Satisfactory but limited by… (SBLB)

Unsatisfactory

Satisfactory

Satisfactory with quality indicator

Unsatisfactory

No epithelial cell abnormality

Within normal limits (WNL)

Reactive/reparative cellular changes (R/R)

Negative for intraepithelial lesion or malignancy (NIL)

Negative for intraepithelial lesions or malignancy with reactive / reparative cellular changes

Epithelial cell abnormalities Squamous cells

ASCUS – favor reactive

ASCUS – not otherwise specified (NOS)

ASCUS – favor SIL

Atyical metaplastic cells6

LSIL

HSIL

-

ASC-US

ASC, cannot exclude HSIL (ASC-H)

LSIL

HSIL

Glandular cells AGUS–favor reactive, AEC–favor reactive

AGUS, NOS, AGUS-EC NOS

AGUS-favor neoplastic, AGUS-EC-favor neoplastic AGUS-EM (AMC)

-

-

AGC, AEC

AGC-favor neoplastic,AEC-favor neoplastic

AMC

Adenocarcinoma in situ

Other - Benign endometrial cells over age 40 years

Bethesda 1991 Vs.2001

• Using Bethesda 1991 ‘SBLB’ smears may be classified in “Unsatisfactory” under Bethesda 2001.

Acta Cytol 2004;48:355-362• There will be no ASCUS favour reactive• There will be no AGUS favour reactive• Liquid based preparation will become the

order of the day

DEPARTMENT OF CYTOLOGY & GYNAE PATHOLOGY, P.G.I.M.E.R., CHANDIGARH

(GYNAECOLOGICAL CYTOLOGY FORM)Cytology ________________________________ Date/ _______________________________________Slide No._________________________________ New/ Follow-up _______________________________Name _______________________________________ C.R. No. _______________________________Age ______________Ward/OPD ________________ Unit___________________________________Address _______________________________________________________________________________Chief Complaints _______________________________________________________________________ Contraception Barrier/Harmonal/IUCD/Tubal-ligation/Nil H/O Surgery ________________________________________H/O Treatment - Radiotherapy/ Chemotherapy/ HarmonesCervix - Normal/ Suspicious/ Bleeds on touch/ ErosionColposcopy - Normal/ Abnormal/ Unsatisfactory/ Not doneDiagnosis - _______________________________________    Doctor’s Signature  

FOR LABORATORY USE ONLY

MICROSCOPIN FINDINGS

Satisfactory for interpretation Satisfactory but limited Unsatisfactory

Within normal limits Benign Cellular changes Epithelial cell abnormality

Benign Cellular changes Epithelial cell abnormality

Infection Squamous cells

TV Candida ASCUS

LSIL (mild dysplacia, CIN-I; HPV associated changes

Coccobacilli Actino HSIL

HSV Other Moderate dysplasia (CIN Grade-II)

Severe displasia/CA-in-situ(CIN GradeIII)

Reactive changes associated with:

Inflamm Repair Squamouc cell CA Invasive

Atrophic Radiation Glandular cells

Endometrial cells, cytologically benign in a post menopausal

IUCD effect Other A typical glandular cells of undetermined significance (AGUS)

Adenocarcinoma probable site of origin

Endocervical Endometrial

Extra Uterine Not otherwise

specified

Compatible with age and History Other malignant neoplasm

Incompatible with age and History

Cytodiagnosis _________________________________________________________________________________________________________

_____________________________________________________________________________________________________________________

Recommendation ______________________________________________________________________________________________________

Date __________________________ Cytoscreener ______________________

Cytopathologist ____________________

Proposed Sheffield quantitative criteria in cervical cytology to assist the grading of squamous cell dyskaryosis, as the British Society for Clinical

Cytology definitions require amendmentSlater DN, Rice S, Stewart R, Melling SE, Hewer EM, Smith JH.

CytopathologyVolume 16 Issue 4 Page 179  - August 2005

• in 2002, however, the BSCC recommended on their website that the three-tier model should be replaced by a new two-tier system of low- and high-grade squamous abnormalities. The latter broadly equate with the two-grade Bethesda System (TBS) for reporting squamous intraepithelial lesions

• Differences, however, were noted in area measurements between SurePathTM and ThinPrep® and this has potential implications for classifications (such as TBS) using area comparisons as their basis. In addition, it was found that the increased NC ratio, associated with higher grades of dyskaryosis is more a consequence of progressive cytoplasmic area reduction rather than nuclear area increase. The similar NC ratios of borderline nuclear changes associated with human papilloma virus and mild dyskaryosis support the BSCC proposal that these can be combined to constitute a low-grade category. This study shows that the BSCC area NC ratio criteria of grading squamous cell dyskaryosis require amendment. In addition, this study supports the new BSCC recommendation of low- and high-grade squamous cell categories.

• The study proposes Sheffield quantitative criteria to assist the grading of squamous cell abnormalities. Quantitative diameter NC ratio measurements, however, must always be accompanied by detailed assessment of qualitative morphological features and in particular those relating to nuclear chromatin. This is equally relevant to both two- and three-tier models.

BSCC, Bethesda or other? Terminology in cervical cytology European panel discussionKocjan G, Priollet BC, Desai M, Koutselini H, Mahovlic V, Oliveira MH,

Pohar-Marinsek Z, Sauer T, Schenk U, Shabalova I, Herbert A.Cytopathology. 2005 Jun;16(3):113-9.

The European panel agreed that reproducibility and translatability of terminology in cervical cytology were essential, arguing well for harmonization of reporting systems. The majority at this meeting use a modification of the Bethesda system (BS). Local modifications involved reporting subcategories within high grade and low grade lesions, which would not alter the overall translatability of their systems both with each other and BS. The majority agree that low grade lesions with and without koilocytosis should be managed similarly as should high grade lesions (moderate dysplasia/CIN2 or worse). Those systems linking moderate dysplasia with mild rather than severe dysplasia would need to define moderate dysplasia as such, if their results were to be translatable, which would be preferable to their using a different definition of low grade and high grade lesions. Translation between systems might anyway be facilitated by reporting moderate dysplasia as a subcategory within high grade, which was favoured by most of those present. Therefore, there is no need for exact agreement of terminology if broad principles are agreed.

Eliminating the diagnosis atypical squamous cells of undetermined significance: impact on the accuracy of the Papanicolaou test.

Sodhani P, Gupta S, Singh V, Sehgal A, Mitra AB.Acta Cytol. 2004 Nov-Dec;48(6):783-7.

• To assess eliminating the diagnosis "atypical squamous cells of undetermined significance" (ASCUS) from the Bethesda System for Reporting Cervical/Vaginal Cytological Diagnoses and analyze its impact on the sensitivity and positive predictive value of Pap smears.

• STUDY DESIGN: A total of 166 previously diagnosed ASCUS cases with follow-up biopsy results available were prospectively downgraded to within normal limits/benign cellular changes or upgraded to specific squamous intraepithelial lesions (SILs) or the malignant category. These review cytodiagnoses were compared with the histologic outcome. The impact on the sensitivity and positive predictive value of Pap smears was also assessed.

• RESULTS: Though there was a decrease in the sensitivity of the Pap smear from 100% to 76.3% for SIL overall and from 100% to 80% for high grade SIL (HSIL) alone, there was an improvement in the positive predictive value of diagnosing SIL from 46% to 85% and from 6% to 15% for HSIL alone.

• CONCLUSION: The ASCUS diagnosis can be minimized to a great extent, if not eliminated completely. The "ASCUS-favor reactive" group can be eliminated, while the diagnoses "ASCUS favor SIL" and "ASCUS-not otherwise specified" should be used sparingly.