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Management of the suspicious cytologic cervical smear to the final diagnosis and therapy
GYNECOLOGIC
ONCOLOGY
1, go-94
(1972)
Management of the Suspicious Cytologic Cervical Smear to the Final Diagnosis and Therapy
M. STUCIN,J. KovA~~, S. BONTA, AND S. RAINER
The diagnostic procedures dictated by suspicious cytologic reports are described. Mass screening by cytologic techniques has yielded 2-2.5 % of Papanicoloau Class III smears. Of this group 45.1 o/cwill be patients with mild or moderate dysplasia and the remainder will have severe dysplasia, carcinoma in situ, and early invasive carcinoma. A reliable diagnosis can be obtained only by histologic examination of serial sections of the cervical cone or of the cervix after hysterectomy. Cervical conization of every patient with a suspicious cytologic smear might expose 45 % of the patients so treated to an unnecessary surgical procedure and would impose a great burden on the gynecologist and the pathologist. By employing colposcopy with selective spot biopsy, or fractional curettage for precise identification of patients with early cervical neoplasia, the number of the conizations can be reduced without increasing the false-negative detection rate.
After obtaining a suspicious cervical smear, the clinician must determine the type, site, and extent of the uterine lesion. In our experience the histologic condition reflected by the suspicious smear usually includes mild to severe dysplasia, carcinoma in situ, and less frequently, early invasive carcinoma. In addition, the suspicious smear may be caused by subcylindrical cell metaplasia of the gland epithelium or even a simple inflammatory process [3]. Because many of these histologic abnormalities present themselves concurrently, it is difficult to presume from the cytologic smear which of the histologic possibilities is most likely in the individual patient. In order to make a correct diagnosis the following sequence is employed in our clinic. Prior to biopsying the cervix of the patient with a suspicious cytologic smear, treatment for cervicitis or vaginitis is effected to eliminate inflammatory disease as an etiologic factor. The cytologic smear is repeated after treatment and if it is negative, repeat cytologic examinations are performed at 2- to 3-month intervals. If the smear remains suspicious after treatment for inflammation, then histologic examination is performed routinely.
We have found colposcopy indispensable in localizing the cellular disorder and directing the biopsy. Magnification of lo-16 x permits reliable evaluations of the portio and reveals fine structural changes in the mucosa. These changes which Hinselmann has called “matrixes” {after Mestwerdt [5,6]} are
90 Copyright 0 1972 by Academic Press, Inc. All rights of reproduction in any form reserved.
SUSPICIOUS
CERVICAL
SMEAR
91
described as leukoplakia, ground, mozaic, and a typical transformation zone. The matrixes are usually located at the squamocolumnar junction from which they extend peripherally to the portio. In young women this zone can be visualized readily, and the site for biopsy can be identified with precision. In menopausal women the squamocolumnar junction is located within the cervical canal and cannot be visualized with the colposcope [1,8,10]. However, in the face of a suspicious smear and colposcopic findings of normal squamous epithelium of the portio vaginalis one may presume the matrix to be located within the endocervical canal. BIOPSY
FOR HISTOLOGIC
EXAMINATION
Histologic examination of serial sections of the cervix have revealed that epithelial abnormalities increase from the periphery of the portio towards the squamocolumnar junction 1111. The most severe epithelial change is always at the squamocolumnar junction, thus histologic examination must include the central border of the matrix (see Figs. l-4). Biopsy is routinely taken with colposcopic direction. If the matrix is detected on the portio, samples may be taken with the scalpel or the biopsy forceps. If the portio is normal, then the corpus and endocervix are curetted. When the cytologic smear is suspicious and the histologic examination of biopsy material reveals only mild or moderate dysplasia, therapy is not prescribed. Instead, reexamination by cytologic and colposcopic techniques is performed. An analysis of 566 biopsies performed from 1960 to 1964 revealed that biopsy failed to detect 18.3% of the most severe histologic changes 19,121. Thus, when the cytologic smear remains suspicious after the biopsy has demonstrated only dysplasia, conization of the cervix with serial histologic examination is usually accomplished.
Wrong
Correct
site
of biopsy
site of biopsy
FIG. 1.
92
STUCIN
ET
FIG. 2. Central
sector.
FIG. 3. Middle
sector.
FIG. 4. Peripheral FIGS. 2-4. The increase orifice.
AL.
in atypia from the periphery
sector. of the portio towards
the external
uterine
SUSPICIOUS
CONIZATION
CERVICAL
93
SMEAR
OR HYSTERECTOMY
Conization is performed in women under 40 years old when the biopsy specimen reveals severe dysplasia or carcinoma in situ. Prior to conization the lesion is measured by colposcopy and by the application of Schiller’s test [7]. If the lesion extends to the vaginal fornices, conization is considered insufficient and instead the patient is subjected to hysterectomy with removal of a vaginal cuff or a small Schauta procedure. These latter techniques are applied to older women. Our technique for conization provides adequate tissue for diagnosis and adequate excision for therapy of severe dysplasia and carcinoma in situ in young women. The conization is performed with a knife to include normal tissue 1 cm from the lesion and at least 0.5 cm of tissue around the external cervical OS. Infiltration with vasoconstrictors is not employed because this maneuver distorts the tissues and diminishes the accuracy of followup examinations. Electroconization is also omitted because the coagulated tissue is unsuitable for histologic examination. The shape of the portio is restored in most cases by four simple sutures. Rarely are additional sutures required for hemostasis. Our experience has been that fewer sutures result in a more complete restoration of the normal appearance of the portio. Occasional stenosis found after conization is treated by simple dilatation. HISTOLOGIC
EXAMINATION
OF SURGICAL
SPECIMENS
After conization or hysterectomy the cervical material is examined by means of serial sections. The specimens are cut into five blocks according to the method of Matuschka [4]. The first central block comprising the entire cervical canal is cut into sections 100 pm apart, whereas, the sections of the lateral blocks are cut 200 pm apart. Because the selective spot biopsy may not be representative even when taken from the central border of the matrix under colposcopic control, the final diagnosis is always rendered by histologic examination of serial sections. Such examination of 448 women whose biopsy specimens revealed carcinoma in situ showed that 61 patients had early invasive carcinoma and seven had significant invasion. Thus, the biopsy report of carcinoma in situ failed to reveal the more significant lesion in 15.1% of the patients in this series. In these patients, radical vaginal hysterectomy was performed after the conization. The bulk of the patients for whom the original biopsy diagnosis was confirmed by serial section of the conization specimen no further therapy was employed. DISCUSSION In our program of mass screening by cytologic techniques between 2 and 2.5% of the smears were suspicious. At an annual yield of 25,000 examinations there is a requirement for further diagnostic investigation in between 500 and 650 patients. Many patients in this “suspicious” group suffer from dysplastic conditions which may not be malignant. The quickest and most reliable technique for precise diagnosis would be conization of the cervix and subsequent histologic examination of serial sections. An added advantage of
94
STUCIN
ET
AL.
such a sequence is the removal of the entire focus of dysplasia or inflammatory process and, thus, the avoidance of clinical inflammation after biopsy. However, in the face of the large number of atypical smears this technique would overburden the gynecologist and the histologist. Moreover, from our experience in 1960 histologic examination of the patient with the suspicious cytologic smear revealed mild or moderate dysplasia in 45.1% [2]. Thus, almost half the patients in the “suspicious” group would be exposed to an unnecessary surgical intervention, a procedure too elaborate and to uneconomical for the extent of the disorder. We, therefore, suggest that if the number of suspicious smears is large, diagnostic procedures should be adopted which guarantee a more precise identification of the patient who requires further investigation. When the cytologic smear is positive (0.5%) we employ the quicker route of conization or hysterectomy. However, for the suspicious smear the colposcopically directed biopsy has proven its value. REFERENCES 1. HAMPERL, H., KAUFMANN, C., ORER, K. G., AND SCHNEPPENHEIM, P. Die “Erosion” der portio (Die Entstehung der Pseudoerosion, das Ektropion und die Plattenepitheliiberhiiutung der Cervixdriisen auf der Portiooberfliche), Virchows AT&. A 331,57 (1958). 2. KOVACIC, J., AND BONTA, S. Znacaj suspektnega citoloskega nalaza kod otkrivanja genitalnog karcinoma, Ginek. Opst. 1, 94 (1961). 3. KOVA&, J., RUOZI BERRETTA, L., AND BONTA, S. Sulla correlazioni fra reperti citologici suspetti e relativi quadri istologici, Minerw Ginecol. 17, 589 (1965). 4. MATUSCHKA, M. V. Unsere histologische Technik zur Aufarbeitung von Konisationen, ganzen Uteri und Uteri mit anhiingenden Parametrien, Geburtsh. Fruuenheilk. 22, 498 (1962). 5. MESTWERDT, G., Atlas der Kolposkopie, 46, Gustav Fischer, Jena (1953). 6. MESTWERDT, G. AND WESPI, H. Atlas der Kolposkopie, 90, Gustav Fischer, Stuttgart (1961). 7. MESTWERDT, G., AND WESPI, H. Atlas der Kolposkopie, 16, Gustav Fischer, Stuttgart (1967). 8. OBER, K. G., SCHNEPPENHEIM, P., HAMPERL, H., AND KAUFMANN, C. Die Epithelgrenze im Bereiche des Isthmus Uteri, Arch. Gynaekol. 190, 346 (1958). 9. RAINER, S., AND STUCIN, M. Directed biopsy or conisation?, Minemu Ginecol. 22, 23, 1158 (1970). 10. SCHNEPPENHEIM, P., HAMPERL, H., KAUFMANN, C., AND OBER, K. G. Die Beziehungen des Schleimepithels zum Plattenepithel an der Cervix uteri im Lebenslauf der Frau, Arch. Gynaekol. 190, 303 (1958). 11. STUCIN, M. Eine Analiyse von 566 histologischen Serienuntersuchungen am Collum uteri, Arch. Gynuekol. 203,234 (1966). 12. STUCIN, M. Morfologija razvoja intraepitelijskega karcinoma maternicnega vratu, Disertacija, 1971.
ONCOLOGY
1, go-94
(1972)
Management of the Suspicious Cytologic Cervical Smear to the Final Diagnosis and Therapy
M. STUCIN,J. KovA~~, S. BONTA, AND S. RAINER
The diagnostic procedures dictated by suspicious cytologic reports are described. Mass screening by cytologic techniques has yielded 2-2.5 % of Papanicoloau Class III smears. Of this group 45.1 o/cwill be patients with mild or moderate dysplasia and the remainder will have severe dysplasia, carcinoma in situ, and early invasive carcinoma. A reliable diagnosis can be obtained only by histologic examination of serial sections of the cervical cone or of the cervix after hysterectomy. Cervical conization of every patient with a suspicious cytologic smear might expose 45 % of the patients so treated to an unnecessary surgical procedure and would impose a great burden on the gynecologist and the pathologist. By employing colposcopy with selective spot biopsy, or fractional curettage for precise identification of patients with early cervical neoplasia, the number of the conizations can be reduced without increasing the false-negative detection rate.
After obtaining a suspicious cervical smear, the clinician must determine the type, site, and extent of the uterine lesion. In our experience the histologic condition reflected by the suspicious smear usually includes mild to severe dysplasia, carcinoma in situ, and less frequently, early invasive carcinoma. In addition, the suspicious smear may be caused by subcylindrical cell metaplasia of the gland epithelium or even a simple inflammatory process [3]. Because many of these histologic abnormalities present themselves concurrently, it is difficult to presume from the cytologic smear which of the histologic possibilities is most likely in the individual patient. In order to make a correct diagnosis the following sequence is employed in our clinic. Prior to biopsying the cervix of the patient with a suspicious cytologic smear, treatment for cervicitis or vaginitis is effected to eliminate inflammatory disease as an etiologic factor. The cytologic smear is repeated after treatment and if it is negative, repeat cytologic examinations are performed at 2- to 3-month intervals. If the smear remains suspicious after treatment for inflammation, then histologic examination is performed routinely.
We have found colposcopy indispensable in localizing the cellular disorder and directing the biopsy. Magnification of lo-16 x permits reliable evaluations of the portio and reveals fine structural changes in the mucosa. These changes which Hinselmann has called “matrixes” {after Mestwerdt [5,6]} are
90 Copyright 0 1972 by Academic Press, Inc. All rights of reproduction in any form reserved.
SUSPICIOUS
CERVICAL
SMEAR
91
described as leukoplakia, ground, mozaic, and a typical transformation zone. The matrixes are usually located at the squamocolumnar junction from which they extend peripherally to the portio. In young women this zone can be visualized readily, and the site for biopsy can be identified with precision. In menopausal women the squamocolumnar junction is located within the cervical canal and cannot be visualized with the colposcope [1,8,10]. However, in the face of a suspicious smear and colposcopic findings of normal squamous epithelium of the portio vaginalis one may presume the matrix to be located within the endocervical canal. BIOPSY
FOR HISTOLOGIC
EXAMINATION
Histologic examination of serial sections of the cervix have revealed that epithelial abnormalities increase from the periphery of the portio towards the squamocolumnar junction 1111. The most severe epithelial change is always at the squamocolumnar junction, thus histologic examination must include the central border of the matrix (see Figs. l-4). Biopsy is routinely taken with colposcopic direction. If the matrix is detected on the portio, samples may be taken with the scalpel or the biopsy forceps. If the portio is normal, then the corpus and endocervix are curetted. When the cytologic smear is suspicious and the histologic examination of biopsy material reveals only mild or moderate dysplasia, therapy is not prescribed. Instead, reexamination by cytologic and colposcopic techniques is performed. An analysis of 566 biopsies performed from 1960 to 1964 revealed that biopsy failed to detect 18.3% of the most severe histologic changes 19,121. Thus, when the cytologic smear remains suspicious after the biopsy has demonstrated only dysplasia, conization of the cervix with serial histologic examination is usually accomplished.
Wrong
Correct
site
of biopsy
site of biopsy
FIG. 1.
92
STUCIN
ET
FIG. 2. Central
sector.
FIG. 3. Middle
sector.
FIG. 4. Peripheral FIGS. 2-4. The increase orifice.
AL.
in atypia from the periphery
sector. of the portio towards
the external
uterine
SUSPICIOUS
CONIZATION
CERVICAL
93
SMEAR
OR HYSTERECTOMY
Conization is performed in women under 40 years old when the biopsy specimen reveals severe dysplasia or carcinoma in situ. Prior to conization the lesion is measured by colposcopy and by the application of Schiller’s test [7]. If the lesion extends to the vaginal fornices, conization is considered insufficient and instead the patient is subjected to hysterectomy with removal of a vaginal cuff or a small Schauta procedure. These latter techniques are applied to older women. Our technique for conization provides adequate tissue for diagnosis and adequate excision for therapy of severe dysplasia and carcinoma in situ in young women. The conization is performed with a knife to include normal tissue 1 cm from the lesion and at least 0.5 cm of tissue around the external cervical OS. Infiltration with vasoconstrictors is not employed because this maneuver distorts the tissues and diminishes the accuracy of followup examinations. Electroconization is also omitted because the coagulated tissue is unsuitable for histologic examination. The shape of the portio is restored in most cases by four simple sutures. Rarely are additional sutures required for hemostasis. Our experience has been that fewer sutures result in a more complete restoration of the normal appearance of the portio. Occasional stenosis found after conization is treated by simple dilatation. HISTOLOGIC
EXAMINATION
OF SURGICAL
SPECIMENS
After conization or hysterectomy the cervical material is examined by means of serial sections. The specimens are cut into five blocks according to the method of Matuschka [4]. The first central block comprising the entire cervical canal is cut into sections 100 pm apart, whereas, the sections of the lateral blocks are cut 200 pm apart. Because the selective spot biopsy may not be representative even when taken from the central border of the matrix under colposcopic control, the final diagnosis is always rendered by histologic examination of serial sections. Such examination of 448 women whose biopsy specimens revealed carcinoma in situ showed that 61 patients had early invasive carcinoma and seven had significant invasion. Thus, the biopsy report of carcinoma in situ failed to reveal the more significant lesion in 15.1% of the patients in this series. In these patients, radical vaginal hysterectomy was performed after the conization. The bulk of the patients for whom the original biopsy diagnosis was confirmed by serial section of the conization specimen no further therapy was employed. DISCUSSION In our program of mass screening by cytologic techniques between 2 and 2.5% of the smears were suspicious. At an annual yield of 25,000 examinations there is a requirement for further diagnostic investigation in between 500 and 650 patients. Many patients in this “suspicious” group suffer from dysplastic conditions which may not be malignant. The quickest and most reliable technique for precise diagnosis would be conization of the cervix and subsequent histologic examination of serial sections. An added advantage of
94
STUCIN
ET
AL.
such a sequence is the removal of the entire focus of dysplasia or inflammatory process and, thus, the avoidance of clinical inflammation after biopsy. However, in the face of the large number of atypical smears this technique would overburden the gynecologist and the histologist. Moreover, from our experience in 1960 histologic examination of the patient with the suspicious cytologic smear revealed mild or moderate dysplasia in 45.1% [2]. Thus, almost half the patients in the “suspicious” group would be exposed to an unnecessary surgical intervention, a procedure too elaborate and to uneconomical for the extent of the disorder. We, therefore, suggest that if the number of suspicious smears is large, diagnostic procedures should be adopted which guarantee a more precise identification of the patient who requires further investigation. When the cytologic smear is positive (0.5%) we employ the quicker route of conization or hysterectomy. However, for the suspicious smear the colposcopically directed biopsy has proven its value. REFERENCES 1. HAMPERL, H., KAUFMANN, C., ORER, K. G., AND SCHNEPPENHEIM, P. Die “Erosion” der portio (Die Entstehung der Pseudoerosion, das Ektropion und die Plattenepitheliiberhiiutung der Cervixdriisen auf der Portiooberfliche), Virchows AT&. A 331,57 (1958). 2. KOVACIC, J., AND BONTA, S. Znacaj suspektnega citoloskega nalaza kod otkrivanja genitalnog karcinoma, Ginek. Opst. 1, 94 (1961). 3. KOVA&, J., RUOZI BERRETTA, L., AND BONTA, S. Sulla correlazioni fra reperti citologici suspetti e relativi quadri istologici, Minerw Ginecol. 17, 589 (1965). 4. MATUSCHKA, M. V. Unsere histologische Technik zur Aufarbeitung von Konisationen, ganzen Uteri und Uteri mit anhiingenden Parametrien, Geburtsh. Fruuenheilk. 22, 498 (1962). 5. MESTWERDT, G., Atlas der Kolposkopie, 46, Gustav Fischer, Jena (1953). 6. MESTWERDT, G. AND WESPI, H. Atlas der Kolposkopie, 90, Gustav Fischer, Stuttgart (1961). 7. MESTWERDT, G., AND WESPI, H. Atlas der Kolposkopie, 16, Gustav Fischer, Stuttgart (1967). 8. OBER, K. G., SCHNEPPENHEIM, P., HAMPERL, H., AND KAUFMANN, C. Die Epithelgrenze im Bereiche des Isthmus Uteri, Arch. Gynaekol. 190, 346 (1958). 9. RAINER, S., AND STUCIN, M. Directed biopsy or conisation?, Minemu Ginecol. 22, 23, 1158 (1970). 10. SCHNEPPENHEIM, P., HAMPERL, H., KAUFMANN, C., AND OBER, K. G. Die Beziehungen des Schleimepithels zum Plattenepithel an der Cervix uteri im Lebenslauf der Frau, Arch. Gynaekol. 190, 303 (1958). 11. STUCIN, M. Eine Analiyse von 566 histologischen Serienuntersuchungen am Collum uteri, Arch. Gynuekol. 203,234 (1966). 12. STUCIN, M. Morfologija razvoja intraepitelijskega karcinoma maternicnega vratu, Disertacija, 1971.