OB-GYN-L Messages for October, 2003: Re: Benign Endometrial cells on pap smear in Postmenopausal women.

Re: Benign Endometrial cells on pap smear in Postmenopausal women.
From: Terrence.Jones@kp.org
Thu Oct 23 17:28:44 2003

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Maybe in reply to: Braun, R. Daniel: "Benign Endometrial cells on pap smear in Postmenopausal women."
Next in thread: Zachariah Newton: "Re: Benign Endometrial cells on pap smear in Postmenopausal women."

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Yes Harrison, I understood Your concerns WRT ascertainment bias, selection bias, methodology and statistical validation, when first mentioned. What puzzles Me, is why would neoplastic endometrium be assiociated with a greater exfoliation of normal endometrial cells? (Tho, as You've pointed out, we don't know the rate of endometrial Ca, in this study pop, with normal pap and no EM cells.) Our regional cytolopathologist described the sampling achieved by cytobrush (frequently can reach lower segment) - which seemed a reasonable explanation for EM cells on pap. But what is the biologic plausibility for the assoc with neoplasia? I think You're correct in implicating historic confounders. Increased BMI, peripheral conversion of A to E1, insulin resistance (and inc IGFBP1 effects on endometrium), would all be red flags for an endometrium at risk for both benign proliferation, as well as neoplastic. Clinically, it would be of important to know the effects of these variables on predictive value. And, as is the case with asymptomatic Pt on Tamoxifen: what is the relationship to final staging when the currently asymptomatic patient later becomes symptomatic. (I'm not referring to incidence, Dan, but the impact of delay in diagnosis.) Using the cervix as an analogy is not valid, as the symptom we are observing (irregular bleeding) is frequently present in the endometrium lesion, while still pre-invasive. One of our East Bay residents did a study on our regional pop database, as his research project. I'll try to find the numbers. I believe there was an intent to publish, but - who can keep up, nowadays?! And thanks for YOUR interest! tj
Harrison Sheld <hsheld@anv.net> Sent by: ob-gyn-l@obgyn.net 10/23/2003 02:16 PM Please respond to ob-gyn-l
To: Multiple recipients of list OB-GYN-L <ob-gyn-l@dns.obgyn.net> cc: Subject: Re: Benign Endometrial cells on pap smear in Postmenopausal women.
There is the statement: "6 of the 10 patients with EH/CA did not have vaginal bleeding and were referred for evaluation based solely on their cytological abnormality showing benign endometrial cells (four patients) or foamy histiocytes (two patients.)" They did exclude 10 patients who had atypical glandular cells.
It is hard for me to accept that that the sole reason for referral was the cytology when there is no statement that a complete medical history and physical examination was performed on all reported patients; we don't know what confounding factors those patients had.
Neither do we know what in the 34/159 patients' medical histories or physical examinations that may have been responsible for no followup and their exclusion from the study.
There are no details about how the specimens were obtained or by whom. Neither is there indication on who obtained the information about bleeding and HRT. Could have been done by secretarial help in the office checking or not checking a box on the Pap requisition. Thanks for your interest.
Terrence.Jones@kp.org wrote: >
> Thanks Harrison! I hadn't time to hunt down the article, so delayed
> comment. Wonder if there is mention of the cytologic appearance of the
> endometrial cells in the 4 Pts with adenoca? Were they 'benign
> appearing' in every case? Also, any discussion regarding cytobrush, vs
> spatula alone, WRT specificity? tj
>
> Harrison Sheld
> <hsheld@anv.net> To: Multiple recipients
> Sent by: of list OB-GYN-L
> ob-gyn-l@obgyn.net <ob-gyn-l@dns.obgyn.net>
> cc:
> 10/22/2003 04:44 PM Subject: Re: Benign
> Please respond to ob-gyn-l Endometrial cells on pap smear in
> Postmenopausal women.
>
> I have reviewed the article in the JLGTD. I believe there are several
> problems with it.
>
> First, the patients were drawn from the population of a tertiary care
> medical center and may not be representative of the general
> population.
>
> Second, aside from hormone therapy, there are no historical data as to
> reproductive history, previous HRT, current medications including
> those
> considered alternative, concurrent medical conditions, previous
> abnormal
> Paps or previous GYN surgery; all possible confounders in the
> analysis.
>
> Third, the number patients in that hospital's catchment area who did
> not
> have endometrial cells or histiocytes but who had "asymptomatic"
> endometrial carcinoma is not known. Knowing that the sensitivity of
> the
> Pap smear with regard to detecting endometrial pathology is not nearly
> 100%, it may be that the "negative" population also had a 4% or
> greater
> incidence of endometrial cancer. In other words one cannot assume that
> all the patients who did not have endometrial cells or histiocytes on
> their Pap did not have endometrial cancer.
>
> Fourth, 12 patients on followup had insufficient tissue on sampling
> and
> were not included in the analysis. Since a common finding in
> endometrial
> sampling of postmenopausal patients is insufficient tissue commonly
> from
> an atrophic endometrium, these patients could have been included.
> Their
> inclusion would not have substantially changed the findings.
>
> Finally, the Bethesda system as recently revised does not include
> endometrial cells as an epithelial abnormality in women over 40. I
> would
> be hard pressed absent other risks for endometrial cancer to justify
> cell sampling every postmenopausal patient who had one Pap that showed
> histiocytes and/or normal endometrial cells on the basis of this study
> (nor did the authors make that suggestion.)
>
> "Braun, R. Daniel" wrote:
> >
> > They were assymptomatic and there was no relationship to their being
> on
> > estrogen or not according to the study. How many negative samplings
> do
> > you get for every 4 malignancies when you sample 40 yr olds with
> > menomenorrhagia?? I'll bet it is a lot more than 96, still it is the
> > standard of care.
> >
> > Dan
> >
> > -----Original Message-----
> > From: ob-gyn-l@obgyn.net [mailto:ob-gyn-l@obgyn.net] On Behalf Of
> > Harrison Sheld
> > Sent: Tuesday, October 21, 2003 12:18 PM
> > To: Multiple recipients of list OB-GYN-L
> > Subject: Re: Benign Endometrial cells on pap smear in Postmenopausal
> > women.
> >
> > I have not read the article in the ASCCP Journal but there are other
> > articles that have a different statistics. I would advise the
> patient of
> > the statistics (some studies report a only 1% malignancy level in
> > asymptomatic patients), and would let her make the decision. That
> said,
> > patients who are on estrogen, symptomatic, or with risk factors for
> > endometrial CA should be sampled. Doing endometrial sampling on
> > menopausal patients is often times difficult and uncomfortable.
> > According to the article cited, and I don't know if the patients
> were at
> > risk for CA, on estrogen, or symptomatic, 96 out of 100 samplings
> would
> > be unnecessary. If the patient chose not to be sampled I would
> inform
> > her to report in a timely fashion symptoms if they should occur and
> > return for a Pap in 4 months. Just my opinion and I could be wrong.

--=_alternative 0078FD7388256DC8_ Content-Type: text/html; charset="us-ascii"
 Yes Harrison, I understood Your concerns WRT ascertainment bias, selection bias, methodology and statistical validation, when first mentioned. What puzzles Me, is why would neoplastic endometrium be assiociated with a greater exfoliation of  normal endometrial cells? (Tho, as You've pointed out, we don't know the rate of endometrial Ca, in this study pop, with normal pap and no EM cells.) Our regional cytolopathologist described the sampling achieved by cytobrush (frequently can reach lower segment) - which seemed a reasonable explanation for EM cells on pap. But what is the biologic plausibility for the assoc with neoplasia? I think You're correct in implicating historic confounders. Increased BMI, peripheral conversion of A to E1, insulin resistance (and inc IGFBP1 effects on endometrium), would all be red flags for an endometrium at risk for both benign proliferation, as well as neoplastic. Clinically, it would be of important to kn! ow the effects of these variables on predictive value. And, as is the case with asymptomatic Pt on Tamoxifen: what is the relationship to final staging when the currently asymptomatic patient later becomes symptomatic. (I'm not referring to incidence, Dan, but the impact of delay in diagnosis.) Using the cervix as an analogy is not valid, as the symptom we are observing (irregular bleeding) is frequently present in the endometrium lesion, while still pre-invasive. One of our East Bay residents did a study on our regional pop database, as his research project. I'll try to find the numbers. I believe there was an intent to publish, but - who can keep up, nowadays?! And thanks for YOUR interest!  tj         <table width0%> <tr valign=top> <td> <td>Harrison Sheld <hsheld@anv.net> Sent by: ob-gyn-l@obgyn.net 10/23/2003 02:16 PM Please respond to ob-gyn-l <td>                To:        Multiple recipients of list OB-GYN-L <ob-gyn-l@dns.obgyn.net>         cc:                 Subject:        Re: Benign Endometrial cells on pap smear in Postmenopausal women.</table> There is the statement: "6 of the 10 patients with EH/CA did not have vaginal bleeding and were referred for evaluation based solely on their cytological abnormality showing benign endometrial cells (four patients) or foamy histiocytes (two patients.)" They did exclude 10 patients who had atypical glandular cells. It is hard for me to accept that that the sole reason for referral was the cytology when there is no statement that a complete medical history and physical examination was performed on all reported patients; we don't know what confounding factors those patients had. Neither do we know what in the 34/159 patients' medical histories or physical examinations that may have been responsible for no followup and their exclusion from the study. There are no details about how the specimens were obtained or by whom. Neither is there indication on who obtained the information about bleeding and HRT. Could have been done by secretarial help in the office checking or not checking a box on the Pap requisition. Thanks for your interest. Terrence.Jones@kp.org wrote: > > Thanks Harrison! I hadn't time to hunt down the article, so delayed > comment. Wonder if there is mention of the cytologic appearance of the > endometrial cells in the 4 Pts with adenoca? Were they 'benign > appearing' in every case? Also, any discussion regarding cytobrush, vs > spatula alone, WRT specificity? tj > >   Harrison Sheld >   <hsheld@anv.net>                   To:        Multiple recipients >   Sent by:                   of list OB-GYN-L >   ob-gyn-l@obgyn.net         <ob-gyn-l@dns.obgyn.net> >                                      cc: >   10/22/2003 04:44 PM                Subject:        Re: Benign >   Please respond to ob-gyn-l Endometrial cells on pap smear in >                              Postmenopausal women. > > I have reviewed the article in the JLGTD. I believe there are several > problems with it. > > First, the patients were drawn from the population of a tertiary care > medical center and may not be representative of the general > population. > > Second, aside from hormone therapy, there are no historical data as to > reproductive history, previous HRT, current medications including > those > considered alternative, concurrent medical conditions, previous > abnormal > Paps or previous GYN surgery; all possible confounders in the > analysis. > > Third, the number patients in that hospital's catchment area who did > not > have endometrial cells or histiocytes but who had "asymptomatic" > endometrial carcinoma is not known. Knowing that the sensitivity of > the > Pap smear with regard to detecting endometrial pathology is not nearly > 100%, it may be that the "negative" population also had a 4% or > greater > incidence of endometrial cancer. In other words one cannot assume that > all the patients who did not have endometrial cells or histiocytes on > their Pap did not have endometrial cancer. > > Fourth, 12 patients on followup had insufficient tissue on sampling > and > were not included in the analysis. Since a common finding in > endometrial > sampling of postmenopausal patients is insufficient tissue commonly > from > an atrophic endometrium, these patients could have been included. > Their > inclusion would not have substantially changed the findings. > > Finally, the Bethesda system as recently revised does not include > endometrial cells as an epithelial abnormality in women over 40. I > would > be hard pressed absent other risks for endometrial cancer to justify > cell sampling every postmenopausal patient who had one Pap that showed > histiocytes and/or normal endometrial cells on the basis of this study > (nor did the authors make that suggestion.) > > "Braun, R. Daniel" wrote: > > > > They were assymptomatic and there was no relationship to their being > on > > estrogen or not according to the study. How many negative samplings > do > > you get for every 4 malignancies when you sample 40 yr olds with > > menomenorrhagia?? I'll bet it is a lot more than 96, still it is the > > standard of care. > > > > Dan > > > > -----Original Message----- > > From: ob-gyn-l@obgyn.net [mailto:ob-gyn-l@obgyn.net] On Behalf Of > > Harrison Sheld > > Sent: Tuesday, October 21, 2003 12:18 PM > > To: Multiple recipients of list OB-GYN-L > > Subject: Re: Benign Endometrial cells on pap smear in Postmenopausal > > women. > > > > I have not read the article in the ASCCP Journal but there are other > > articles that have a different statistics. I would advise the > patient of > > the statistics (some studies report a only 1% malignancy level in > > asymptomatic patients), and would let her make the decision. That > said, > > patients who are on estrogen, symptomatic, or with risk factors for > > endometrial CA should be sampled. Doing endometrial sampling on > > menopausal patients is often times difficult and uncomfortable. > > According to the article cited, and I don't know if the patients > were at > > risk for CA, on estrogen, or symptomatic, 96 out of 100 samplings > would > > be unnecessary. If the patient chose not to be sampled I would > inform > > her to report in a timely fashion symptoms if they should occur and > > return for a Pap in 4 months. Just my opinion and I could be wrong. 

Next message: Joanne Bulley, MD: "FRI: Humor - Ponderings"
Previous message: Richard Kaplan: "Re: fetal pac"
Maybe in reply to: Braun, R. Daniel: "Benign Endometrial cells on pap smear in Postmenopausal women."
Next in thread: Zachariah Newton: "Re: Benign Endometrial cells on pap smear in Postmenopausal women."

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