Indicate conventional smear (Pap smear) vs. liquid based vs. other SPECIMEN TYPE: Indicate conventional smear (Pap smear) vs. liquid based 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 processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason) GENERAL CATEGORIZATION (optional) Negative for Intraepithelial Lesion or Malignancy Epithelial Cell Abnormality: See Interpretation/Result (specify ‘squamous’ or ‘glandular’ as appropriate) Other: See Interpretation/Result (e.g. endometrial cells in a woman ³ 40 years of age)

If case examined by automated device, specify device and result. AUTOMATED REVIEW If case examined by automated device, specify device and result. ANCILLARY TESTING Provide a brief description of the test methods and report the result so that it is easily understood by the clinician. INTERPRETATION/RESULT NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY ORGANISMS: Trichomonas vaginalis Fungal organisms morphologically consistent with Candida spp Shift in flora suggestive of bacterial vaginosis Bacteria morphologically consistent with Actinomyces spp. Cellular changes consistent with Herpes simplex virus OTHER NON NEOPLASTIC FINDINGS (Optional to report; list not inclusive): Reactive cellular changes associated with inflammation (includes typical repair) radiation intrauterine contraceptive device (IUD) Glandular cells status post hysterectomy Atrophy OTHER Endometrial cells (in a woman ³ 40 years of age)

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 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 GLANDULAR CELL Atypical endocervical cells (NOS or specify in comments) endometrial cells (NOS or specify in comments) glandular cells (NOS or specify in comments) endocervical cells, favor neoplastic glandular cells, favor neoplastic Endocervical adenocarcinoma in situ Adenocarcinoma endocervical endometrial extrauterine not otherwise specified (NOS) OTHER MALIGNANT NEOPLASMS: (specify) EDUCATIONAL NOTES AND SUGGESTIONS (optional)

Specimen Adequacy 1991 Bethesda System: Adequacy of the Specimen Satisfactory for evaluation Satisfactory for evaluation but limited by… Unsatisfactory for evaluation The unsatisfactory category should be maintained because it emphasizes specimen unreliability for evaluation of epithelial lesions. Unsatisfactory Specimen Reporting The “Unsatisfactory” category currently includes both specimens that are rejected and specimens that are fully evaluated. Recommendation: Suggested wording to clarify reports follows: Rejected Pap: Specimen rejected (not processed) because ____(specimen not labeled, slide broken, etc.) Fully evaluated unsatisfactory Pap : Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of ____(obscuring blood, etc.) Additional comments/recommendations, as appropriate

Conventional Smear Squamous Cellularity “Well-preserved and well-visualized squamous epithelial cells should cover more than 10% of the slide surface.” Recommendation: Change the criterion to “An adequate conventional specimen has an estimated minimum of approximately 8,000-12,000 well-preserved and well-visualized squamous epithelial cells.” Note: THIS MINIMUM CELL RANGE SHOULD BE ESTIMATED, AND LABORATORIES SHOULD NOT COUNT INDIVIDUAL CELLS IN CONVENTIONAL SMEARS. Provide “reference images” of known cellularity.

Endocervical/Transformation zone component “at a minimum, of two clusters of well-preserved endocervical glandular and/or squamous metaplastic cells, with each cluster composed of at least five cells.” Recommendation: At least 10 well-preserved endocervical or squamous metaplastic cells should be observed to report that a transformation zone component is present. The presence or absence of a transformation zone component should be reported in the specimen adequacy section, but absence does not mean a patient requires early repeat. Parabasal type cells should not be used as an indication of transformation zone sampling. Obscuring factors Current Bethesda criteria are 50-75% of cells obscured for SBLB specimens, and >75% of cells obscured for unsatisfactory specimens Recommendations: No change in criteria is proposed. Specimens with >75% of cells obscured should be termed unsatisfactory (assuming no abnormal cells are present). When 50-75% of cells are obscured, a statement describing the specimen as partially obscured should follow the satisfactory term.

Recommendations and Educational Notes The Cytology Report is a Medical Consultation The cytopathologist has ultimate responsibility for the evaluation and report. The referring physician has an obligation to include all pertinent clinical information in the request for cytopathologic evaluation so that the cytopathologist can consult effectively. The cytopathologist should determine whether the specimen is adequate for evaluation. If it is unsatisfactory or less than optimal, this should be noted on the report The report should include a recommendation for further patient evaluation when appropriate. one of the areas examined by a 2001Bethesda System Working Committee has been the potential use of recommendations and educational notes, including disclaimer-like notes in the cervicovaginal cytology report.

Additional Uses of Educational Notes Recommendation: The use of recommendations is therefore considered appropriate under the following circumstances: 1. When further procedures would be helpful to clarify ambiguous morphologic findings. 2. To improve the quality of a repeat specimen following one of limited adequacy. 3. To identify patients with certain interpretations that require further triage and potential subsequent management. Additional Uses of Educational Notes Recommendations: Educational notes are optional. If used, they should be carefully worded, concise, clear and evidence-based.

-------------------------- Examples of interpretive results with notes and recommendations: Interpretation: Atypical Glandular Cells Recommendation: As a significant percentage of patients with this interpretation have underlying high-grade squamous or glandular intraepithelial abnormalities, further diagnostic patient follow-up procedures are suggested as clinically indicated. -------------------------- Interpretation: Unsatisfactory due to lack of cellular material and air-drying artifact (in a post-menopausal woman). Recommendation: A short course of estrogen cream is suggested before obtaining a repeat specimen in order to induce maturation of the squamous epithelium.

Ancillary Testing Recommendations 1991 Bethesda Terminology None reported for Ancillary Testing Recommendation: For all laboratory based ancillary tests, a brief description of the methods should be provided, and the results should be reported in a manner conducive to clinician understanding. For HPV testing, the results should be reported as positive or negative for HPV DNA of a certain type or class and the laboratory method should be indicated. HPV testing has been shown to lack utility for triage of women who have LSIL or HSIL diagnoses. Thus, given the current data, clinical recommendations associated with HPV testing should be limited to women who have an ASCUS diagnosis.

Benign Cellular Changes: Recommendations after the Bethesda Conference Benign Cellular Changes and Infections GENERAL CATEGORIZATION What terminology should be used for negative and reactive specimens in the General Categorization? "Negative for intraepithelial lesion or malignancy" is preferred in the report so that organisms and other benign cellular changes may be included under this general category.

RECOMMENDATION AFTER THE BETHESDA CONFERENCE GENERAL CATEGORIZATION (Optional) Negative for intraepithelial lesion or malignancy (includes organisms and reactive cellular changes) Epithelial cell abnormality: (Specify squamous or glandular as appropriate) (See interpretation/diagnosis) Other: (See interpretation/diagnosis) (includes conditions that do not fit under the first two categories such as exfoliated endometrial cells in a woman over 40 years of age and non-epithelial malignancies) For Interpretations/Diagnoses include in Bethesda 2001 the following: Reactive cellular changes associated with: Inflammation (includes typical repair) Radiation Intrauterine contraceptive device (IUD) Other Findings

Modification of the infection list Where should infections be listed within the terminology and in the report? RECOMMENDATION : The consensus of opinion at the conference was to change the "infections" category to "organisms". Modification of the infection list Organisms Trichomonas Vaginalis Fungal organisms morphologically consistent with Candida spp Shift in vaginal flora suggestive of bacterial vaginosis Bacteria morphologically consistent with Actinomyces spp Cellular changes associated with Herpes simplex virus Other Chlamydia should not be listed as an infectious entity in the Bethesda System to be diagnosed routinely on Pap smear. (No change) Change the term "Predominance of coccobacilli consistent with shift in vaginal flora" to "Shift in vaginal flora suggestive of bacterial vaginosis" The clinician can then use clinical judgment to determine if additional tests or treatment is indicated.

Recommendations of the ASCUS Replace ASCUS with a new category “Atypical Squamous Cells (ASC)” Eliminate the qualifier, “Favor Reactive” for equivocal cytology. Recommend that pathologists judiciously downgrade many cases formerly classified as “ASCUS, Favor Reactive.” Qualify Atypical Squamous Cells (ASC) as “Undetermined Significance (ASC-US)” or “Cannot Exclude HSIL (ASC-H)”

Atypical Squamous Cells of Undetermined Significance (ASC-US): cytologic changes that are suggestive of a squamous intraepithelial lesion, but lack criteria for a definitive interpretation. The category includes: 1) a minority of cases formally classified as ASCUS, Favor Reactive and 2) most cases formally classified as ASCUS, NOS or ASCUS, Favor SIL. Atypical Squamous Cells; Cannot Exclude HSIL (ASC-H): cytologic changes that are suggestive of HSIL, but lack criteria for definitive interpretation. ASC reports should not exceed 5% of total specimens with ASC:SIL ratios not higher than 2:1 to 3:1 in general screening populations.

LSIL / HSIL Forum Draft 1991 Bethesda System Squamous Intraepithelial Lesion (SIL) Low-grade squamous intraepithelial lesion (LSIL) High-grade squamous intraepithelial lesion (HSIL) 2001 Recommendations Terminology used for squamous intraepithelial lesions. Recommendation: LSIL and HSIL should continue to be included as two separate categories under Epithelial Cell Abnormalities - Squamous Cell. Moreover, the dividing line between LSIL and HSIL should be between CIN 1 (mild dysplasia) and CIN 2 (moderate dysplasia).

Proposed 2001 Bethesda System Squamous Intraepithelial Lesion (SIL) Retention of cellular changes associated with HPV cytopathic effect (so-called koilocytotic atypia) in the LSIL category. Recommendation: No modification should be made to TBS in this regard and cervical cytology specimens with the cellular features associated with HPV cytopathic effect (e.g., koilocytosis) should continue to be included under Epithelial Cell Abnormalities - Squamous Cell – Low-grade squamous intraepithelial lesion (LSIL). Classification of gynecological cytology samples showing HSIL in which invasion cannot be ruled-out. Recommendation: Gynecological cytology cases showing diagnostic HSIL in which there is non-diagnostic cytological evidence of invasion should be diagnosed as HSIL and accompanied by the comment “with features suspicious for invasion”. Proposed 2001 Bethesda System Squamous Intraepithelial Lesion (SIL) Low-grade squamous intraepithelial lesion (LSIL) High-grade squamous intraepithelial lesion (HSIL)

Atypical Glandular Cells –Recommendations revised post-meeting AIS as a discrete entity; Atypical Glandular Cell Qualifiers Recommendations: “Endocervical adenocarcinoma in situ” should be added as a discrete interpretation/diagnosis when criteria are adequate for this interpretation. In cases showing near complete features (criteria) of AIS, an intermediate category of “Atypical endocervical cells, probably AIS” is appropriate The category “Atypical glandular/endocervical/endometrial cells” should be retained, however, The qualifier “of undetermined significance” (AGUS) should be eliminated to avoid confusion with ASCUS. In addition, the qualifier “favor reactive” should be eliminated. The qualifier “favor neoplastic” should be retained; Categories under the “atypical glandular” heading: Atypical Glandular/Endocervical/Endometrial Cells (unqualified) Atypical Glandular/Endocervical Cells, Favor Neoplastic specify further in description

The Presence of Benign Glandular Cells in the Specimens from Post-Hysterectomy Women Data from the literature show that no patient having benign glandular cells in vaginal smears post-hysterectomy developed recurrent or de novo neoplastic lesions regardless of the history of prior malignancy. Recommendations: “Low grade glandular intraepithelial lesion” and/or “endocervical glandular dysplasia” should not be utilized. Proposed criteria for AIS and Atypical Glandular Cells were presented at the meeting.

Bethesda 2001 Endometrial Forum Group Workshop Summary An introductory comment for TBS 2001 was formulated: “Cervical/vaginal cytology is a screening tool for squamous cell carcinoma and its precursor lesions. It is an inaccurate test for detection of endometrial lesions and should not be used to evaluate causes of suspected endometrial abnormalities.” Recommendation: Because of the lack of clinical impact and the unreliable clinical data often supplied with the sample, endometrial cells need not be reported in women less than 40 years.

General Categorization: Reporting benign appearing exfoliated endometrial cells in a woman over 40 years of age General Categorization: Other Descriptive Interpretation: “Endometrial cells present. -See Comment. “ “No evidence of squamous intraepithelial lesion.”(Optional) Educational note: “Endometrial cells after age 40, particularly out of phase or after menopause, may be associated with benign endometrium, hormonal alterations and less commonly, endometrial/ uterine abnormalities. Clinical correlation is recommended.” Hormonal Evaluation Recommendation: Delete this category in the Bethesda System.