Bethesda 2001 Endometrial Forum Group Workshop Summary
Consensus was reached during the Bethesda Conference Workshop (April 30-May 2, 2001) on all issues regarding reporting of benign endometrial cells: what cell constituted a “significant” endometrial cell, in what age group the cells should be reported, how they are reported, and educational notes regarding their significance. Secondarily, hormonal evaluation was reviewed.
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.”
The significant endometrial cell was defined as an exfoliated glandular cell. Because exfoliated glandular endometrial cells are not associated with significant pathology in women less than forty years old, they need not be reported in patients less than age 40. Because menopausal status, hormonal therapy, menstrual data and clinical risk factors are often unknown, endometrial cells should be reported in all women from the age of 40 onward.
The reporting format was resolved by the introduction of the General Categorization of “Other.” This general categorization would be followed by a descriptive interpretation/diagnosis, reporting the presence of endometrial cells, with an optional statement regarding the absence of squamous intraepithelial lesion. An optional, practice-appropriate educational comment was suggested, concisely describing the conditions associated with benign appearing endometrial cells in women age 40 and above: e.g. “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.”
Finally, the consensus was to discontinue reporting hormonal evaluation in TBS 2001.
Issue 1: What constitutes a cytologically benign endometrial cell?
Background: Historically, endometrial glandular cells, stromal cells, and histiocytes have all been considered forms of “normal” endometrial cells. Modern sampling techniques result in an opportunity to see abraded endometrial cells.
Abraded endometrial cells obtained by vigorous sampling techniques are normal and do not have the same significance as exfoliated glandular epithelium. (de Peralta-Venturino. Diagn Cytopathol 1995; 20:263-271) Histiocytes and stromal cells do not have independent significance and should not be considered in the same context as exfoliated endometrial cells. (Zucker PK. Cancer 1985; 56:2256-63)(NguyenTN. Diagn Cytopathol 1998; 19:89-93.)(Chang A. Gynecol Oncol 2001; 80:37-43).
Recommendation:
An exfoliated, intact glandular cell is the cell type that may have clinical significance.
Issue 2: Should women who are premenopausal have endometrial cells reported?
Background: In the past, endometrial cells “out of cycle” in premenopausal women were reported. Bethesda 1991 provided for reporting endometrial cells only in postmenopausal women. Many cervical/vaginal smears are not accompanied by accurate clinical data regarding menstrual cycle, menopausal status or clinical symptoms. Endometrial cells reported in women less than age 40, rarely have associated significant endometrial pathology. (Ng ABP. Acta Cytol 1974; 18:356-61) (Gondos B. Ann Clin Lab Sci 1977; 7: 486-90) (Gray J. Diagn Cytopathol 1999; 20:181-2)
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.
Issue 3: Reporting benign appearing exfoliated endometrial cells in a woman over 40 years of age
Background:
Historically, benign appearing endometrial cells were considered a harbinger of endometrial pathology in postmenopausal women, requiring endometrial sampling, and were reported as an “epithelial cell abnormality.” Although most women with endometrial carcinoma present with bleeding, a small proportion are asymptomatic. (Cherkis RC. Obstet Gynecol 1998; 71:242-44.) (Zucker PK. Cancer 1985; 56:2256-63)(Gomez-Fernandez CR. Gynecol Oncol 1999; 74:381-4)
This perspective was based upon data obtained prior to the widespread use of hormonal replacement therapy and prior to the extensive use of therapeutic hormone manipulation (e.g. tamoxifen.) (Cherkis RC. Obstet Gynecol 1998; 71:242-44.) Whether benign-appearing endometrial cells in a postmenopausal woman receiving hormones have the same predictive value for endometrial neoplasia is currently unknown, or in the early stages of investigation. (Abadi MA. Acta Cytol 2000; 44:141-6) (Sarode VR. Acta Cytol 2001; 45:153-56)
Finally, a patient’s menopausal status or hormone intake may not be documented on the requisition. In addition, clinical information unknown to the laboratory may modify the relative risk of endometrial carcinoma.
Endometrial carcinoma has been detected in a small proportion of women shedding endometrial cells from the age of 40 onward. (Ng ABP. Acta Cytol 1974; 18:356-61) (Yancey M. Obstet Gynecol 1990; 76: 1000-5).
Recommendation:
Include as an introduction to Bethesda 2001 the following comment to underscore the inadequacy of cervical cytology in detecting endometrial pathology:
“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 suspected endometrial abnormalities
.”
Report benign appearing endometrial cells in all women from the age of 40 onward, regardless of hormonal therapy using the following format:
General Categorization:
Other
Descriptive Interpretation:
“Endometrial cells present. -See Comment. “
“No evidence of squamous intraepithelial lesion.”(Optional)
An educational comment appropriate for the local laboratory practice, such as the following, may be used.
“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.”
Issue 4: Hormonal Evaluation
Background:
Evidence of estrogenic effect, maturation indices and other features of “squamous maturation” may have historically been included in the cervical/vaginal report. Hormonal evaluation is a crude measure of estrogen-like effect on squamous cells. It is not reproducible and does not correlate with symptoms or plasma estrogen levels. (Stone SC. Obstet Gynecol 1975;45:625-27). It requires a separate vaginal wall smear and is often inappropriately requested on cervical specimens. Furthermore, requests for hormonal evaluation are rarely accompanied by appropriate clinical information.
Recommendation:
Delete this category in the Bethesda System. Because of the advances of monitoring hormones by other means, practitioners should be discouraged from using this crude evaluation in clinical practice. Estrogen effect should not be used within the context of the cervical vaginal cytology screening report.
The Endometrial Cell Forum Group:
Ann T. Moriarty, MD (Moderator)
Edmund Cibas, MD
Gary W. Gill, CT(ASCP)
Meg McLachlin, MD
Ellen Sheets, MD
Theresa M. Somrak, JD,CT(ASCP)
Rosemary E. Zuna, MD
References:
Abadi MA, Barakat RR, Saigo PE. Effects of tamoxifen on cervical smears from patients with breast cancer. Acta Cytol 2000; 44: 141-6.
Chang A, Sandweiss L, Bose S. Cytologically benign endometrial cells in the Papanicolaou smears of postmenopausal women. Gynecol Oncol 2001; 80:37-43.
Cherkis RC, Patten SF, Andrews TJ et al. Significance of normal endometrial cells detected by cervical cytology. Obstet Gynecol 1998;71:242-244.
de Peralta-Venturino MN, Purslow MJ, Kini SR. Endometrial cells of the “lower uterine segment” (LUS) in cervical smears obtained by endocervical brushings: A source of potential diagnostic pitfall. Diagn Cytopathol 1995; 12:263-271.
Gray J, Nguyen G-K. Cytologic detection of endometrial pathology by Pap smears. Diagn Cytopathol 1999; 20:181-2.
Gomez-Fernandez CR, Ganjei-Azar P, Capote-Dishaw J, Averette HE, Nadjii M. Reporting normal endometrial cells in Pap smears: An outcome appraisal. Gynecol Oncol 1999; 74:381-4.
Gondos B, King EB. Significance of endometrial cells in cervicovaginal smears. Ann Clin Lab Sci 1977; 7: 486-490.
Ng ABP, Reagan JW, Hawliczek S, Wentz BW. Significance of endometrial cells in the detection of endometrial carcinoma and its precursors. Acta Cytol 1974; 18: 356-361.
Nguyen TN, Bourdeau J-L, Ferenczy A, Franco EL. Clinical significance of histiocytes in the detection of endometrial adenocarcinoma and hyperplasia. Diagn Cytopathol 1998; 19: 89-93.
Sarode VR. Rader AE, Rose PG, Rodriguez, Abdul-Karim FW. Significance of cytologically normal endometrial cells in cervical smears from postmenopausal women. Acta Cytol 2001; 45:153-56
Stone SC, Mickal A, Rye PH. Postmenopausal symptomatology, maturation index, and plasma estrogen levels. Obstet Gynecol 1975; 45:625-7.
Yancey M, Magelssen D, Demaurez A, Lee RB. Classification of endometrial cells on cervical cytology. Obstet Gynecol 1990; 76:1000-5.
Zucker PK, Kadson EJ, Feldstein ML. The validity of Pap smear parameters as predictors of endometrial pathology in menopausal women. Cancer 1985; 56: 2256-63.