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Diagnostic procedures of cervical lesions
CURRENT
OPINION
Clinical problems
/ I I
Diagnostic procedures of cervical lesions
Case
presentation
The patient is a 23-year-old para 2-O-O-2 with a history of abnormal cervical cytoloCgy and biopsies extending over 2 years. In the course of her second pregnancy her physician received two reports of “suspicious malignancy” from Papanicolaou smears. For this reason, consultation was requested at 7 months. Examination at this time showed a slight eversion on the anterior lip which did not stain with the Schiller solution. A biopsy taken of this area showed moderate spinal cell atypia. A Papanicolaou spread showed moderately bizarre cellular changes. Following delivery the patient failed to reappear until 5 months post partum. At that time the Papanicolaou test was “inconclusive with slightly bizarre cellular changes.” A biopsy of the cervix showed mild to moderate spinal cell atypia. Saline suspension showed Trichomonas, and the patient wa> discharged on a course of metronidazolfa (Flagyl) and douches. She again failed to keep her appointment and was not seen for 5 months. At this time the Schiller’s test was negative. Trichomonas and another course oi was still present, metronidazole was administered. Two months later (one year post partum) colposcop~ showed “some abnormal vascular patterns compatible with atypism but with no evidence of carcinoma in situ.” The Papanicolaou spread taken at this time showed “marked bizarre cellular changes.” Three months later examination revealed a small Schiller-white lesion between 12 and
1 o’clock on the portio, not present at the previous visit. The colposcopist reports “a vascular pattern which represents marked atypism but there is no pattern sug,qesting intraepithclial carcinoma.”
Problem: Would you trust this report &Iiciently to omit biopsy at this point? Assuming you have elected to follow this patient, can you assess the relative weights of the following as they might Muence you to interfere: clinical impression; repeated abnormal or positive cytosmears; colposcopic findings; and repeat biopsies. Discussthe value of colposcopy. Consultation
Roger B. Scott, M.D. Cleveland, Ohio Professor of Obstetrics and Gynecology, University Hospitals of Cleveland and Wcstcrn Rewrur School of Medicine Despite the age of this patient, she has been followed much too long without a definitive histologic diagnosis. It is obvious from the case report that she is not a particularly cooperative patient; therefore, all the more reason to proceed with an ad?quate biopsy. i.e.: a sharp conization of thr, cervix. By the fifth postpartum month there had accumulated four consecutive reports of cytologic changes, two “suspicious maligone “moderate nancy,” bizarre cellular changes,” and one “inconclusive with slightly bizarre cellular changes.” The biopsies obtained by this time were simply minimal samplings from accessible areas of the cervix
Volume 93 Number 7
and did not exclude a more serious lesion. The directional signals seem clear and the reasonable question is, why wait? In stating the problem, it is assumed that I had elected to follow this patient. As stated above this is not a fair assumption unless the patient refused hospitalization for sharp conization of the cervix. A very important factor in proper patient care is the confidence the clinician has in his cytologist. Dr. James Reagan in the Cytology Laboratory of University Hospitals of Cleveland does not use the standard Papanicolaou classification and prefers to phrase his reports more specifically, such as “cells compatible with dysplasia,” “cells compatible with dysplasia, but carcinoma in situ cannot be excluded,” “cells compatible with carcinoma in situ,” etc. By such a method of reporting and additional direct contacts with the cytologist, the clinician is in a much better position to plan the timing and the extent of additional diagnostic studies. For example, in 147 patients with histologically proved carcinoma in situ the prior cytologic studies were negative in only 2 (1.4 per cent), no greater than atypical cells in 6 (4.1 per cent), and no greater than dysplasia in 14 (9.1 per cent). In the remaining 125 cases the cytologic suspicion was carcinoma in situ or a more advanced lesion. We followed 223 patients with cytologic changes not greater than dysplasia and punch biopsies which correlated with this for one to 9 years; 2 (0.9 per cent) subsequently developed or were shown to have on more complete diagnostic studies invasive carcinoma and 10 (4.5 per cent) carcinoma in situ. As a consequence of this and other studies and despite our confidence in cytology, we now recommend sharp conization after two cytologic studies compatible with dysplasia or 4 showing only atypical cells. In a recent less than 2 year interval, we found 3 invasive cervical carcinomas beneath a surface change no greater than dysplasia. This is a small, but significant, group where delay in complete diagnostic cone biopsy could have been disastrous. If one uses a cytology laboratory accustomed to reporting only negative, suspicious, or malignant cells the yield of carcinoma in situ or
Clinical
problems
1049
invasive carcinoma can be as much as 35 per cent from the suspicious group, as shown by several reports. The clinical impression from history and gross inspection of the cervix is of minimal value, for well over 80 per cent of patients with carcinoma in situ have no symptoms and cervices which appear normal or show only clinical cervicitis. The Schiller test is of considerable assistance in indicating areas for preferential biopsy. In this particular case the cervix showed only slight eversion during pregnancy and the Schiller’s test was negative 10 months post partum but 5 months later showed a nonstaining area which should be included in the sharp conization specimen. When she was seen 5 months post partum the clinician must have suspected the Trichomonas infestation as an etiologic factor in the cytologic and histologic changes. We studied this relationship in some 30 patients and concluded that metronidazole therapy could frequently change a cytologic report from atypical cells to negative, but has no effect on patients with cytologic evidence of dysplasia. Strangely enough after such treatment and clinical cure of the vaginitis, trichomonads were absent in a saline suspension but frequently identifiable on the cytologic slide. It is evident that I do not see any real value in again repeating punch biopsies. Why study numerous small, traumatized fragments when a properly studied sharp conization specimen gives a much more accurate histologic evaluation and in addition may be the only treatment measure necessary? Until very recently there has been minimal acceptance and enthusiasm for colposcopy (magnification 10 to 20 times) and colpomicroscopy (magnification 110 to 280 times). Since I have not been trained in this technique and have not considered it much more than a way to get a better look at the cervix, any personal evaluation of the colposcopy reports in this case would be presumptuous. Excellent reviews by Ernst Navratil and by T. Antoine of these methods of studying the cervix can be f0und.l These writers, as well as many others here and
1050
Clinical
problems
abroad. feel that colposcopy has ancillar) value, but all admit that cytology is of grcatrr accuracy and that biopsies are necessary to confirm any suspicious changes. When ;I clinician is not satisfied with his cytologist. the use of this technique with appropriatts biopsies could be rewarding. However, the endocervical canal, except during pregnanry. is minimally available for colposcopy and for study by biopsy. Reagan and I have been impressed with the need for adequate studies within the cervical canal, for we found that in 100 cases of carcinoma in situ the cpithefial alteration of greatest magnitude was found in 90 cases to be above a point where a perpendicular line through the canal and a horizontal fine across the visible cervix intersect. The recent awakened interest in cofposcopy in this country may sen-e to better delineate the role of this procedure in cancer detection. REFERENCES
1. Gray, Laman A.: Dysplasia, Carcinoma in situ and microinvasive carcinoma of the cervix uteri, Springfield. Illinois, 1964, Charles C Thomas, Publisher, chap. 10 and 1 I. Hugh J. Davis, M.D. Baltimore, Maryland Assistant Professor Gynecology and Obstetricr Johns Hopkins Uniwrsity School of Medicine The degree of confidence that may be placed in a colposcopic examination is analogous to the confidence limits in cytologic reports: The experience of the examiner is critical, because the judgments involved are subtle. Still, even with optimal cytology and cofposcopy, there is nothing as definitive as a good histologic section. Therefore, granted a sharp-bordered, Schilfer-white, focal fesion at the squamocolumnar junction, displaying atypical vascular pattern, corroborating a cytologic report of marked atypicality. then tissue studies of this lesion seem definitely indicated. Cofposcopy is not a means of replacing histologic examination, but a means of directing biopsies skillfully to the maximum lesion, thus improving the quality of the histology.
‘l’he case citthd has crsrtain tc*;~ttlr~c~scvltic,ii are significant : ‘I‘htb Irsion in qucxstion has persisted. ;md indeed progrt,ssed in the WVerity of tht* cytologic and colposcopic tindings for 15 months. Riologically. sllch a focal IVsion demonstrating proc;rcssi\;v cytohistologic, atypia of markcad degree rcbpresents but a step in rht> evolution of invasivfa cancer. It can he regarded as a differentiated Stage 0 carcinoma. Treatment of such a fusion in a 23-year-old patient is certainly not an emrrgency----one can anticipate a latent period is averaging 20 years. but the potential definite. Positive smear findings would have posed a simpler clinical problem: They are seldom wrong. As with any other clinical test, the significance of inconclusive cytologic reports increases if a series of smears demonstrate persistent bizarre findings. This is particularly true if the inconclusive smear reports persist even after treatment for inflammatory conditions has been carried out. The important distinction to be made cytoIogically. clinically, and histologically is brtween neoplastic atypia and inflammatory atypia. Inflammatory atypia is of no significance cxcept as a source of confusion. Unfortunately. both entities tend to be lumped together today in the vague term dysplasia. which is consequently little mor‘t‘ than a nine 1ettc.r question mark. Major surgery for minor dysplasia is difficult to justify. Some romment is in order regarding the limitations of colposcopy. Inspection of the squamocolumnar junction almost invariably disclose? a focal target lesion if the zone’ of neoplastic. atypia or in situ carcinoma is ,qeographically at least 3 liun. in diameter. ‘I% resolution of the cofposcope is insufficient to regularly identify lesions g:Pographically less extensive. Pari passu, smaller lesions arca of increasinyly doubtful significance. Thermsfore, there are two circumstances in which colposcopy has no value: (a) when the squamocolumnar junction cannot be adequately visualized and (1,) when the area of atypia is less than 3 mm. in diameter. These circumstances apply in less than 10 per cent of patients with neopfastic atypia or Stage 0
Volume Number
93 7
cervical cancer. The false negative rate for a single cervical scraping smear rises to about 50 per cent under the same circumstances. For this reason, we do not regard colposcopy and cytology as competitive, but rather as complementary investigative procedures. When faced with a suspicious, atypical, Class III, inconclusive or doubtful cytologic report, the clinician must answer three questions: ( 1) Is there a significant lesion? (2) Where is the lesion? (3) Can I rule out invasive cancer? Colposcopic inspection of the cervis can answer these questions provisionally and directed biopsies can provide confirmation histologically. For the majority of clinicians, the training and equipment expense involved in colposcopy make it impractical as a supplement to cytology in early cancer detection. However, it is worth noting that if the atypical or positive cytology is reliable, a bottle of Schillcr’s solution in the hands of an experienced gynecologist, plus adequate squamocolumnar biopsies, will answer the foregoing questions almost as efficiently as colposcopically directed biopsies. In major clinical centers, with a volume of atypical smear reports requiring follow-up, a cervical clinic equipped with a colposcope and special instruments for site-specific smears and biopsies can be recommended. Such a clinic provides continuity of follow-
Clinical
problems
1051
up, and improves the quality of additional smears and biopsies. Teaching of residents is facilitated by concentrating the clinical material, and patient care improved by obviating the need of conization as an automatic recourse in the investigation of atypical cytologic reports. In situ carcinoma is no more invisible to the gynecologist equipped with a colposcope than is the fundus of the eye to the ophthalmologist trained in the use of the slit lamp. Just as we have exported cytology to Europe, it is high time we imported colposcopy from Europe and used it to improve the diagnosis and treatment of cervical neoplasia. Editor’s
comment
I would not trust the conclusion of the colposcopist because the procedure he performed did not include a study of the endocervix. In my experience, the endocervix is the site of carcinoma in situ sufficiently often to demand that it be adequately investigated when abnormal smears are encountered. For a similar reason, I would not be content with only biopsies of the cervix in this patient at this time. Conization is indicated and, if the incision is not made high into the cervical canal, a curettage of the endocervix at the higher level should be performed.
OPINION
Clinical problems
/ I I
Diagnostic procedures of cervical lesions
Case
presentation
The patient is a 23-year-old para 2-O-O-2 with a history of abnormal cervical cytoloCgy and biopsies extending over 2 years. In the course of her second pregnancy her physician received two reports of “suspicious malignancy” from Papanicolaou smears. For this reason, consultation was requested at 7 months. Examination at this time showed a slight eversion on the anterior lip which did not stain with the Schiller solution. A biopsy taken of this area showed moderate spinal cell atypia. A Papanicolaou spread showed moderately bizarre cellular changes. Following delivery the patient failed to reappear until 5 months post partum. At that time the Papanicolaou test was “inconclusive with slightly bizarre cellular changes.” A biopsy of the cervix showed mild to moderate spinal cell atypia. Saline suspension showed Trichomonas, and the patient wa> discharged on a course of metronidazolfa (Flagyl) and douches. She again failed to keep her appointment and was not seen for 5 months. At this time the Schiller’s test was negative. Trichomonas and another course oi was still present, metronidazole was administered. Two months later (one year post partum) colposcop~ showed “some abnormal vascular patterns compatible with atypism but with no evidence of carcinoma in situ.” The Papanicolaou spread taken at this time showed “marked bizarre cellular changes.” Three months later examination revealed a small Schiller-white lesion between 12 and
1 o’clock on the portio, not present at the previous visit. The colposcopist reports “a vascular pattern which represents marked atypism but there is no pattern sug,qesting intraepithclial carcinoma.”
Problem: Would you trust this report &Iiciently to omit biopsy at this point? Assuming you have elected to follow this patient, can you assess the relative weights of the following as they might Muence you to interfere: clinical impression; repeated abnormal or positive cytosmears; colposcopic findings; and repeat biopsies. Discussthe value of colposcopy. Consultation
Roger B. Scott, M.D. Cleveland, Ohio Professor of Obstetrics and Gynecology, University Hospitals of Cleveland and Wcstcrn Rewrur School of Medicine Despite the age of this patient, she has been followed much too long without a definitive histologic diagnosis. It is obvious from the case report that she is not a particularly cooperative patient; therefore, all the more reason to proceed with an ad?quate biopsy. i.e.: a sharp conization of thr, cervix. By the fifth postpartum month there had accumulated four consecutive reports of cytologic changes, two “suspicious maligone “moderate nancy,” bizarre cellular changes,” and one “inconclusive with slightly bizarre cellular changes.” The biopsies obtained by this time were simply minimal samplings from accessible areas of the cervix
Volume 93 Number 7
and did not exclude a more serious lesion. The directional signals seem clear and the reasonable question is, why wait? In stating the problem, it is assumed that I had elected to follow this patient. As stated above this is not a fair assumption unless the patient refused hospitalization for sharp conization of the cervix. A very important factor in proper patient care is the confidence the clinician has in his cytologist. Dr. James Reagan in the Cytology Laboratory of University Hospitals of Cleveland does not use the standard Papanicolaou classification and prefers to phrase his reports more specifically, such as “cells compatible with dysplasia,” “cells compatible with dysplasia, but carcinoma in situ cannot be excluded,” “cells compatible with carcinoma in situ,” etc. By such a method of reporting and additional direct contacts with the cytologist, the clinician is in a much better position to plan the timing and the extent of additional diagnostic studies. For example, in 147 patients with histologically proved carcinoma in situ the prior cytologic studies were negative in only 2 (1.4 per cent), no greater than atypical cells in 6 (4.1 per cent), and no greater than dysplasia in 14 (9.1 per cent). In the remaining 125 cases the cytologic suspicion was carcinoma in situ or a more advanced lesion. We followed 223 patients with cytologic changes not greater than dysplasia and punch biopsies which correlated with this for one to 9 years; 2 (0.9 per cent) subsequently developed or were shown to have on more complete diagnostic studies invasive carcinoma and 10 (4.5 per cent) carcinoma in situ. As a consequence of this and other studies and despite our confidence in cytology, we now recommend sharp conization after two cytologic studies compatible with dysplasia or 4 showing only atypical cells. In a recent less than 2 year interval, we found 3 invasive cervical carcinomas beneath a surface change no greater than dysplasia. This is a small, but significant, group where delay in complete diagnostic cone biopsy could have been disastrous. If one uses a cytology laboratory accustomed to reporting only negative, suspicious, or malignant cells the yield of carcinoma in situ or
Clinical
problems
1049
invasive carcinoma can be as much as 35 per cent from the suspicious group, as shown by several reports. The clinical impression from history and gross inspection of the cervix is of minimal value, for well over 80 per cent of patients with carcinoma in situ have no symptoms and cervices which appear normal or show only clinical cervicitis. The Schiller test is of considerable assistance in indicating areas for preferential biopsy. In this particular case the cervix showed only slight eversion during pregnancy and the Schiller’s test was negative 10 months post partum but 5 months later showed a nonstaining area which should be included in the sharp conization specimen. When she was seen 5 months post partum the clinician must have suspected the Trichomonas infestation as an etiologic factor in the cytologic and histologic changes. We studied this relationship in some 30 patients and concluded that metronidazole therapy could frequently change a cytologic report from atypical cells to negative, but has no effect on patients with cytologic evidence of dysplasia. Strangely enough after such treatment and clinical cure of the vaginitis, trichomonads were absent in a saline suspension but frequently identifiable on the cytologic slide. It is evident that I do not see any real value in again repeating punch biopsies. Why study numerous small, traumatized fragments when a properly studied sharp conization specimen gives a much more accurate histologic evaluation and in addition may be the only treatment measure necessary? Until very recently there has been minimal acceptance and enthusiasm for colposcopy (magnification 10 to 20 times) and colpomicroscopy (magnification 110 to 280 times). Since I have not been trained in this technique and have not considered it much more than a way to get a better look at the cervix, any personal evaluation of the colposcopy reports in this case would be presumptuous. Excellent reviews by Ernst Navratil and by T. Antoine of these methods of studying the cervix can be f0und.l These writers, as well as many others here and
1050
Clinical
problems
abroad. feel that colposcopy has ancillar) value, but all admit that cytology is of grcatrr accuracy and that biopsies are necessary to confirm any suspicious changes. When ;I clinician is not satisfied with his cytologist. the use of this technique with appropriatts biopsies could be rewarding. However, the endocervical canal, except during pregnanry. is minimally available for colposcopy and for study by biopsy. Reagan and I have been impressed with the need for adequate studies within the cervical canal, for we found that in 100 cases of carcinoma in situ the cpithefial alteration of greatest magnitude was found in 90 cases to be above a point where a perpendicular line through the canal and a horizontal fine across the visible cervix intersect. The recent awakened interest in cofposcopy in this country may sen-e to better delineate the role of this procedure in cancer detection. REFERENCES
1. Gray, Laman A.: Dysplasia, Carcinoma in situ and microinvasive carcinoma of the cervix uteri, Springfield. Illinois, 1964, Charles C Thomas, Publisher, chap. 10 and 1 I. Hugh J. Davis, M.D. Baltimore, Maryland Assistant Professor Gynecology and Obstetricr Johns Hopkins Uniwrsity School of Medicine The degree of confidence that may be placed in a colposcopic examination is analogous to the confidence limits in cytologic reports: The experience of the examiner is critical, because the judgments involved are subtle. Still, even with optimal cytology and cofposcopy, there is nothing as definitive as a good histologic section. Therefore, granted a sharp-bordered, Schilfer-white, focal fesion at the squamocolumnar junction, displaying atypical vascular pattern, corroborating a cytologic report of marked atypicality. then tissue studies of this lesion seem definitely indicated. Cofposcopy is not a means of replacing histologic examination, but a means of directing biopsies skillfully to the maximum lesion, thus improving the quality of the histology.
‘l’he case citthd has crsrtain tc*;~ttlr~c~scvltic,ii are significant : ‘I‘htb Irsion in qucxstion has persisted. ;md indeed progrt,ssed in the WVerity of tht* cytologic and colposcopic tindings for 15 months. Riologically. sllch a focal IVsion demonstrating proc;rcssi\;v cytohistologic, atypia of markcad degree rcbpresents but a step in rht> evolution of invasivfa cancer. It can he regarded as a differentiated Stage 0 carcinoma. Treatment of such a fusion in a 23-year-old patient is certainly not an emrrgency----one can anticipate a latent period is averaging 20 years. but the potential definite. Positive smear findings would have posed a simpler clinical problem: They are seldom wrong. As with any other clinical test, the significance of inconclusive cytologic reports increases if a series of smears demonstrate persistent bizarre findings. This is particularly true if the inconclusive smear reports persist even after treatment for inflammatory conditions has been carried out. The important distinction to be made cytoIogically. clinically, and histologically is brtween neoplastic atypia and inflammatory atypia. Inflammatory atypia is of no significance cxcept as a source of confusion. Unfortunately. both entities tend to be lumped together today in the vague term dysplasia. which is consequently little mor‘t‘ than a nine 1ettc.r question mark. Major surgery for minor dysplasia is difficult to justify. Some romment is in order regarding the limitations of colposcopy. Inspection of the squamocolumnar junction almost invariably disclose? a focal target lesion if the zone’ of neoplastic. atypia or in situ carcinoma is ,qeographically at least 3 liun. in diameter. ‘I% resolution of the cofposcope is insufficient to regularly identify lesions g:Pographically less extensive. Pari passu, smaller lesions arca of increasinyly doubtful significance. Thermsfore, there are two circumstances in which colposcopy has no value: (a) when the squamocolumnar junction cannot be adequately visualized and (1,) when the area of atypia is less than 3 mm. in diameter. These circumstances apply in less than 10 per cent of patients with neopfastic atypia or Stage 0
Volume Number
93 7
cervical cancer. The false negative rate for a single cervical scraping smear rises to about 50 per cent under the same circumstances. For this reason, we do not regard colposcopy and cytology as competitive, but rather as complementary investigative procedures. When faced with a suspicious, atypical, Class III, inconclusive or doubtful cytologic report, the clinician must answer three questions: ( 1) Is there a significant lesion? (2) Where is the lesion? (3) Can I rule out invasive cancer? Colposcopic inspection of the cervis can answer these questions provisionally and directed biopsies can provide confirmation histologically. For the majority of clinicians, the training and equipment expense involved in colposcopy make it impractical as a supplement to cytology in early cancer detection. However, it is worth noting that if the atypical or positive cytology is reliable, a bottle of Schillcr’s solution in the hands of an experienced gynecologist, plus adequate squamocolumnar biopsies, will answer the foregoing questions almost as efficiently as colposcopically directed biopsies. In major clinical centers, with a volume of atypical smear reports requiring follow-up, a cervical clinic equipped with a colposcope and special instruments for site-specific smears and biopsies can be recommended. Such a clinic provides continuity of follow-
Clinical
problems
1051
up, and improves the quality of additional smears and biopsies. Teaching of residents is facilitated by concentrating the clinical material, and patient care improved by obviating the need of conization as an automatic recourse in the investigation of atypical cytologic reports. In situ carcinoma is no more invisible to the gynecologist equipped with a colposcope than is the fundus of the eye to the ophthalmologist trained in the use of the slit lamp. Just as we have exported cytology to Europe, it is high time we imported colposcopy from Europe and used it to improve the diagnosis and treatment of cervical neoplasia. Editor’s
comment
I would not trust the conclusion of the colposcopist because the procedure he performed did not include a study of the endocervix. In my experience, the endocervix is the site of carcinoma in situ sufficiently often to demand that it be adequately investigated when abnormal smears are encountered. For a similar reason, I would not be content with only biopsies of the cervix in this patient at this time. Conization is indicated and, if the incision is not made high into the cervical canal, a curettage of the endocervix at the higher level should be performed.