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Squamous cell carcinoma in situ of the vulva. A clinical and histopathological study
GYNECOLOGIC ONCOLOGY 11, 224-229 (1981)
Squamous Cell Carcinoma in Situ of the Vulva. A Clinical and Histopathological
Study
TORBJORN I V E R S E N ) VERA ABELER, AND PER KOLSTAD
Departments of Gynecology and Pathology, The Norwegian Radium Hospital, Oslo 3, Norway Received October 29, 1980 Twenty-nine patients with squamous cell carcinoma in situ of the vulva have been followed 3-20 years. In 21 patients pruritus, usually combined with soreness was the main symptom. Colposcopy was performed in 12 cases with pathological vascular pattern in 7. Three patients had multiple-lesions in the vulva, and 4 had a concomitant carcinoma in situ of the cervix. Only one recurrence was detected after 62 months in a patient with atypical epithelium at the resection border. Carcinoma in situ of the vulva is a relatively innocent condition that should not be overtreated. The standard treatment should include a wide local excision.
Squamous cell carcinoma in situ of the vulva (intraepithelial carcinoma, preinvasive carcinoma) is diagnosed when the epithelium is characterized by "disorientation and loss of architecture throughout the full thickness of the epithelium without evidence of stromal invasion" [1]. The lesion is rare, but an increase in the incidence has been reported in the United States [2]. The present study was prompted by this report. We hoped to clarify some problems concerning the clinical and histopathological diagnosis as well as the treatment.
MATERIAL AND METHODS In the 19-year period 1956-1974, 54 patients were admitted to The Norwegian Radium Hospital with a diagnosis of squamous cell carcinoma in situ of the vulva and 6 patients with Bowen's disease. In the same period 424 patients with invasive squamous cell carcinoma of the vulva were treated. Carcinoma in situ lesions and Bowen's disease are in the present paper grouped under the single heading "carcinoma in situ" according to the recommendation of the International Society for the Study of Vulvar Disease [1]. The diagnosis was based on large biopsies in all cases. One of the authors reviewed all the available histological material. When necessary, new sections were cut and stained with hematoxylin and eosin. Without access to the clinical data reclassification was done according to WHO International Histological Classification of Tumors [3]. Sections from the edges of the operation specimens were carefully studied for the presence of carcinoma in situ lesions. Of 60 patients Address reprint requests to: Torbj¢rn Iversen, M.D., Department of Gynecology, Aker Hospital, Oslo 5, Norway. 224 0090-8258/81/020224-06501.00/0 Copyright© 1981 by AcademicPress, Inc. All rightsof reproductionin any form reserved.
225
CARCINOMA I N SITU OF T H E V U L V A
with a primary diagnosis of carcinoma in situ 31 had to be omitted for various reasons (Table 1) leaving 29 cases for further study. The majority of the rejected cases showed minimal (19) or infiltration less than 3 mm in small tumors (10 cases). (These 29 cases are included in a previous publication on squamous cell carcinoma of the vulva Stage I [4].) Table 2 shows the age distribution. Twentytwo out of the 29 cases were above 50 years. The treatment varied from local excision to vulvectomy. In one case radical vulvectomy with bilateral inguinal lymphadenectomy was performed (Table 3). Follow-up information was collected from the medical records and from The Cancer Registry of Norway.
TABLE 1 REJECTED CASES~ ORIGINALLY DIAGNOSED AS CARCINOMA IN SITU, AFTER REVISED DIAGNOSES
Revised diagnoses
Number
Carcinoma in situ with minimal stromal infiltration Squamous cell carcinoma (small tumors) Paget's disease Histological material not available
19 10
1 1
Total
31
TABLE 2 AGE DISTRIBUTION OF PATIENTS WITH SQUAMOUS CELL CARCINOMAIN SITU OF THE VULVA TREATED IN THE NORWEGIAN RADIUM HOSPITAL 1956--1974
Age (years)
No. of patients
30-39 40-49 50-59 60-69 70-79
4 3 7 5 10
Total
29
TABLE 3 TREATMENT METHODS AND RECURRENCE
Treatment group Excision Hemivulvectomy Vulvectomy Radical vulvectomy with lymphadenectomy Total
Total No. 6 2 20 1 29
Recurrence 1
1
226
IVERSEN, ABELER, AND KOLSTAD RESULTS
Symptoms and clinicalfindings. Pruritus, usually combined with soreness, were the most common symptoms (21 out of 29 patients). Five patients noted a raised plaque in the vulva region. Three patients had their lesions discovered incidently on routine gynecological examination. Only 10 patients sought immediate medical advice whereas the remaining 19 patients had a delay for several months. In 19 cases the doctors performed an adequate examination at the first visit. In the remaining 10 cases there was a doctor's delay of more than 6 months. Colposcopy was performed in 12 cases. Pathological vascular pattern was seen in 7 of these (Figs. la, b). Only 1 out of 7 patients showed a pathological smear by cytological examination. Histology. Single carcinoma in situ lesions of the vulva were found in 26 patients, whereas 3 patients had multiple-lesions. The resection borders were involved by atypical epithelium in 4 patients. Four patients had a concomitant carcinoma in situ of the cervix. Follow-up. One patient died of coronary attack 2 days after simple vulvectomy. No other operative complications were observed. No patient was lost to followup. The follow-up time varied from 3 to 20 years (Table 4). The only recurrence was detected after 62 months in a patient initially treated with hemivulvectomy. Histological examination of the initial lesion showed carcinoma in situ at the resection border where the recurrence developed. Reexcision was performed, but
FIG. la. Punctationpattern in carcinomain situ lesion of the vulva. (16×).
227
C A R C I N O M A IN SITU OF T H E V U L V A TABLE 4 RECURRENCE AND DEATHS IN RELATION TO TIME OF FOLLOW-UP Duration of follow-up (years) Up Up Up Up
Total no. of patients
to 5 to 10 to 15 to 20
21 8 3 2
Total no. of recurrence
Died of other causes
1
6 2 1
histological examination again revealed atypical epithelium at the resection border. The patient therefore received topical 5-fluorouracil cream for 2 weeks. Four years later squamous cell carcinoma developed in the same region. A complete local excision of the lesion was performed. The patient is without sign of disease 18 months after the last resection. Altogether 9 patients (32%) died during the observation period from intercurrent disease.
FIG. lb.
Histological pattern of the same lesion. (40x).
228
IVERSEN, ABELER, AND KOLSTAD
DISCUSSION
It is important to notice that most of the patients with in situ lesions of the vulva had symptoms and objective findings related to their lesions. This is in contrast to patients with intraepithelial neoplasia of the cervix who seldom have symptoms or macroscopically visible changes. In small lesions the clinical differential diagnosis between carcinoma in situ and infiltrating carcinoma may be difficult and requires accurate diagnostic procedures, including histological examination. If epithelial atypia is present in a partial biopsy, it is necessary to perform a wide excision of the entire lesion, mainly in order to exclude areas with an infiltrating carcinoma. In cases of suspected multiplicity it may be necessary to biopsy several areas in the vulva. Colposcopy, cytology, and the toluidine blue test may be useful in searching for suspect lesions. Because of the high coincidence of in situ lesions of the vulva, the cervix, and the vagina it is also important to examine the cervix and the vagina [2,5,6]. Patients with carcinoma in situ lesions of the vulva have an excellent prognosis. Only 1 patient in our material developed recurrence (Table 4). This patient had an inadequate primary resection. If there is atypical epithelium at the resection borders a wider reexcision should be performed. Regarding treatment some authors recommend vulvectomy [7], others "skinning vulvectomy" [8], and some prefer simple local excision [6,9-13]. In young patients topical 5-fluorouracil cream has been recommended [5,9,12,14]. However, Forney et al. [13] reported topical 5-fluorouracil therapy to be unsuccessful in 6 of 6 cases. Our experience with this kind of therapy is limited, and we are not able to state its value, although we have observed complete disappearance of in situ carcinoma of the vulva in a few cases. The follow-up of these patients (not presented in this report) is, however, too short. In our experience carcinoma in situ of the vulva is a relatively innocent condition that should not be overtreated by mutilating surgery. The standard treatment should include a wide local excision in order to obtain an accurate histological evaluation of the entire lesion. With free resection borders no further treatment is necessary. If multiple lesions are present, we recommend simple vulvectomy. Treatment with 5-fluorouracil cream should be restricted to patients for whom surgery is not feasible. In later years, laser treatment has been recommended. However, as yet, we have no experience with that sort of therapy. REFERENCES 1. International Society for the Study of Vulvar Disease. New nomenclature for vulvar disease. Report of the Committee on Terminology, Obstet. Gynecol. 47, 122-124 (1976). 2. Woodruff, J. D., Julian, C., Puray, T., Mermut, S., and Katayama, P. The contemporary challenge of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol. 115, 677-684 (1973). 3. Poulsen, H. E., Taylor, C. W., and Sabin, L. H. Histological typing of female genital tract tumours, in International histological classification of tumours, WHO, Geneva/Albany, N.Y., No. 13 (1975). 4. Iversen, T., Abeler, V., and Aalders, J. Individualized treatment of stage I carcinoma of the vulva, Obstet. Gynecol. 57, 85-89 (1981). 5, Hilliard, G. D., Massey, F. M., and O'Toole, R. V. Vulvar neoplasia in the young, Amer. J. Obstet. Gynecol. 135, 185-188 (1979).
CARCINOMA IN SITU OF THE VULVA
229
6. Buscema, J., Woodruff, J. D., Parmley, T. H., and Genadry, R. Carcinoma in situ of the vulva, Obstet. Gynecol. 55, 225-230 (1980). 7. Parry-Jones, E. The management of premalignant and malignant conditions of the vulva, Clin. Obstet. Gynaecol. 3, 217-227 (1976). 8. Rutledge, F., and Sinclair, M. Treatment of intraepithelial carcinoma of the vulva by skin excision and graft, Amer. J. Obstet. Gynecol. 102, 806 (1968). 9. Dean, R. E., Taylor, E. S., Weisbrod, D. M., and Martin, J. W. Amer. J. Obstet. Gynecol. 119, 59-64 (1974). 10. Kaufman, R. H. Intraepithelial carcinoma of the vulva, in Obstetrics and gynecology annual (R. M. Wynn, ed.), Appleton-Century-Crofts, New York, Vol. 6, pp. 317-339 (1977). 11. Japaze, H., Garcia-Bunuel, R., and Woodruff, J. D. Primary vulvar neoplasia. A review of in situ and invasive carcinoma, 1935-1972, Obstet. Gynecol. 49, 404-411 (1977). 12. Woodruff, J. D. Vulvar atypia and carcinoma in situ, J. Reprod. Med. 17, 155-163 (1976). 13. Forney, J. P., Morrow, C. P., Townsend, D. E., and DiSaia, P. J. Management of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol. 127, 801-806 (1977). 14. Carson, T. E., Hoskins, W. J., and Wurzel, J. F. Topical 5-Fluorouracil in the treatment of carcinoma in situ of the vulva, Obstet. Gynecol. 47, 59s-62s (1976).
Squamous Cell Carcinoma in Situ of the Vulva. A Clinical and Histopathological
Study
TORBJORN I V E R S E N ) VERA ABELER, AND PER KOLSTAD
Departments of Gynecology and Pathology, The Norwegian Radium Hospital, Oslo 3, Norway Received October 29, 1980 Twenty-nine patients with squamous cell carcinoma in situ of the vulva have been followed 3-20 years. In 21 patients pruritus, usually combined with soreness was the main symptom. Colposcopy was performed in 12 cases with pathological vascular pattern in 7. Three patients had multiple-lesions in the vulva, and 4 had a concomitant carcinoma in situ of the cervix. Only one recurrence was detected after 62 months in a patient with atypical epithelium at the resection border. Carcinoma in situ of the vulva is a relatively innocent condition that should not be overtreated. The standard treatment should include a wide local excision.
Squamous cell carcinoma in situ of the vulva (intraepithelial carcinoma, preinvasive carcinoma) is diagnosed when the epithelium is characterized by "disorientation and loss of architecture throughout the full thickness of the epithelium without evidence of stromal invasion" [1]. The lesion is rare, but an increase in the incidence has been reported in the United States [2]. The present study was prompted by this report. We hoped to clarify some problems concerning the clinical and histopathological diagnosis as well as the treatment.
MATERIAL AND METHODS In the 19-year period 1956-1974, 54 patients were admitted to The Norwegian Radium Hospital with a diagnosis of squamous cell carcinoma in situ of the vulva and 6 patients with Bowen's disease. In the same period 424 patients with invasive squamous cell carcinoma of the vulva were treated. Carcinoma in situ lesions and Bowen's disease are in the present paper grouped under the single heading "carcinoma in situ" according to the recommendation of the International Society for the Study of Vulvar Disease [1]. The diagnosis was based on large biopsies in all cases. One of the authors reviewed all the available histological material. When necessary, new sections were cut and stained with hematoxylin and eosin. Without access to the clinical data reclassification was done according to WHO International Histological Classification of Tumors [3]. Sections from the edges of the operation specimens were carefully studied for the presence of carcinoma in situ lesions. Of 60 patients Address reprint requests to: Torbj¢rn Iversen, M.D., Department of Gynecology, Aker Hospital, Oslo 5, Norway. 224 0090-8258/81/020224-06501.00/0 Copyright© 1981 by AcademicPress, Inc. All rightsof reproductionin any form reserved.
225
CARCINOMA I N SITU OF T H E V U L V A
with a primary diagnosis of carcinoma in situ 31 had to be omitted for various reasons (Table 1) leaving 29 cases for further study. The majority of the rejected cases showed minimal (19) or infiltration less than 3 mm in small tumors (10 cases). (These 29 cases are included in a previous publication on squamous cell carcinoma of the vulva Stage I [4].) Table 2 shows the age distribution. Twentytwo out of the 29 cases were above 50 years. The treatment varied from local excision to vulvectomy. In one case radical vulvectomy with bilateral inguinal lymphadenectomy was performed (Table 3). Follow-up information was collected from the medical records and from The Cancer Registry of Norway.
TABLE 1 REJECTED CASES~ ORIGINALLY DIAGNOSED AS CARCINOMA IN SITU, AFTER REVISED DIAGNOSES
Revised diagnoses
Number
Carcinoma in situ with minimal stromal infiltration Squamous cell carcinoma (small tumors) Paget's disease Histological material not available
19 10
1 1
Total
31
TABLE 2 AGE DISTRIBUTION OF PATIENTS WITH SQUAMOUS CELL CARCINOMAIN SITU OF THE VULVA TREATED IN THE NORWEGIAN RADIUM HOSPITAL 1956--1974
Age (years)
No. of patients
30-39 40-49 50-59 60-69 70-79
4 3 7 5 10
Total
29
TABLE 3 TREATMENT METHODS AND RECURRENCE
Treatment group Excision Hemivulvectomy Vulvectomy Radical vulvectomy with lymphadenectomy Total
Total No. 6 2 20 1 29
Recurrence 1
1
226
IVERSEN, ABELER, AND KOLSTAD RESULTS
Symptoms and clinicalfindings. Pruritus, usually combined with soreness, were the most common symptoms (21 out of 29 patients). Five patients noted a raised plaque in the vulva region. Three patients had their lesions discovered incidently on routine gynecological examination. Only 10 patients sought immediate medical advice whereas the remaining 19 patients had a delay for several months. In 19 cases the doctors performed an adequate examination at the first visit. In the remaining 10 cases there was a doctor's delay of more than 6 months. Colposcopy was performed in 12 cases. Pathological vascular pattern was seen in 7 of these (Figs. la, b). Only 1 out of 7 patients showed a pathological smear by cytological examination. Histology. Single carcinoma in situ lesions of the vulva were found in 26 patients, whereas 3 patients had multiple-lesions. The resection borders were involved by atypical epithelium in 4 patients. Four patients had a concomitant carcinoma in situ of the cervix. Follow-up. One patient died of coronary attack 2 days after simple vulvectomy. No other operative complications were observed. No patient was lost to followup. The follow-up time varied from 3 to 20 years (Table 4). The only recurrence was detected after 62 months in a patient initially treated with hemivulvectomy. Histological examination of the initial lesion showed carcinoma in situ at the resection border where the recurrence developed. Reexcision was performed, but
FIG. la. Punctationpattern in carcinomain situ lesion of the vulva. (16×).
227
C A R C I N O M A IN SITU OF T H E V U L V A TABLE 4 RECURRENCE AND DEATHS IN RELATION TO TIME OF FOLLOW-UP Duration of follow-up (years) Up Up Up Up
Total no. of patients
to 5 to 10 to 15 to 20
21 8 3 2
Total no. of recurrence
Died of other causes
1
6 2 1
histological examination again revealed atypical epithelium at the resection border. The patient therefore received topical 5-fluorouracil cream for 2 weeks. Four years later squamous cell carcinoma developed in the same region. A complete local excision of the lesion was performed. The patient is without sign of disease 18 months after the last resection. Altogether 9 patients (32%) died during the observation period from intercurrent disease.
FIG. lb.
Histological pattern of the same lesion. (40x).
228
IVERSEN, ABELER, AND KOLSTAD
DISCUSSION
It is important to notice that most of the patients with in situ lesions of the vulva had symptoms and objective findings related to their lesions. This is in contrast to patients with intraepithelial neoplasia of the cervix who seldom have symptoms or macroscopically visible changes. In small lesions the clinical differential diagnosis between carcinoma in situ and infiltrating carcinoma may be difficult and requires accurate diagnostic procedures, including histological examination. If epithelial atypia is present in a partial biopsy, it is necessary to perform a wide excision of the entire lesion, mainly in order to exclude areas with an infiltrating carcinoma. In cases of suspected multiplicity it may be necessary to biopsy several areas in the vulva. Colposcopy, cytology, and the toluidine blue test may be useful in searching for suspect lesions. Because of the high coincidence of in situ lesions of the vulva, the cervix, and the vagina it is also important to examine the cervix and the vagina [2,5,6]. Patients with carcinoma in situ lesions of the vulva have an excellent prognosis. Only 1 patient in our material developed recurrence (Table 4). This patient had an inadequate primary resection. If there is atypical epithelium at the resection borders a wider reexcision should be performed. Regarding treatment some authors recommend vulvectomy [7], others "skinning vulvectomy" [8], and some prefer simple local excision [6,9-13]. In young patients topical 5-fluorouracil cream has been recommended [5,9,12,14]. However, Forney et al. [13] reported topical 5-fluorouracil therapy to be unsuccessful in 6 of 6 cases. Our experience with this kind of therapy is limited, and we are not able to state its value, although we have observed complete disappearance of in situ carcinoma of the vulva in a few cases. The follow-up of these patients (not presented in this report) is, however, too short. In our experience carcinoma in situ of the vulva is a relatively innocent condition that should not be overtreated by mutilating surgery. The standard treatment should include a wide local excision in order to obtain an accurate histological evaluation of the entire lesion. With free resection borders no further treatment is necessary. If multiple lesions are present, we recommend simple vulvectomy. Treatment with 5-fluorouracil cream should be restricted to patients for whom surgery is not feasible. In later years, laser treatment has been recommended. However, as yet, we have no experience with that sort of therapy. REFERENCES 1. International Society for the Study of Vulvar Disease. New nomenclature for vulvar disease. Report of the Committee on Terminology, Obstet. Gynecol. 47, 122-124 (1976). 2. Woodruff, J. D., Julian, C., Puray, T., Mermut, S., and Katayama, P. The contemporary challenge of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol. 115, 677-684 (1973). 3. Poulsen, H. E., Taylor, C. W., and Sabin, L. H. Histological typing of female genital tract tumours, in International histological classification of tumours, WHO, Geneva/Albany, N.Y., No. 13 (1975). 4. Iversen, T., Abeler, V., and Aalders, J. Individualized treatment of stage I carcinoma of the vulva, Obstet. Gynecol. 57, 85-89 (1981). 5, Hilliard, G. D., Massey, F. M., and O'Toole, R. V. Vulvar neoplasia in the young, Amer. J. Obstet. Gynecol. 135, 185-188 (1979).
CARCINOMA IN SITU OF THE VULVA
229
6. Buscema, J., Woodruff, J. D., Parmley, T. H., and Genadry, R. Carcinoma in situ of the vulva, Obstet. Gynecol. 55, 225-230 (1980). 7. Parry-Jones, E. The management of premalignant and malignant conditions of the vulva, Clin. Obstet. Gynaecol. 3, 217-227 (1976). 8. Rutledge, F., and Sinclair, M. Treatment of intraepithelial carcinoma of the vulva by skin excision and graft, Amer. J. Obstet. Gynecol. 102, 806 (1968). 9. Dean, R. E., Taylor, E. S., Weisbrod, D. M., and Martin, J. W. Amer. J. Obstet. Gynecol. 119, 59-64 (1974). 10. Kaufman, R. H. Intraepithelial carcinoma of the vulva, in Obstetrics and gynecology annual (R. M. Wynn, ed.), Appleton-Century-Crofts, New York, Vol. 6, pp. 317-339 (1977). 11. Japaze, H., Garcia-Bunuel, R., and Woodruff, J. D. Primary vulvar neoplasia. A review of in situ and invasive carcinoma, 1935-1972, Obstet. Gynecol. 49, 404-411 (1977). 12. Woodruff, J. D. Vulvar atypia and carcinoma in situ, J. Reprod. Med. 17, 155-163 (1976). 13. Forney, J. P., Morrow, C. P., Townsend, D. E., and DiSaia, P. J. Management of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol. 127, 801-806 (1977). 14. Carson, T. E., Hoskins, W. J., and Wurzel, J. F. Topical 5-Fluorouracil in the treatment of carcinoma in situ of the vulva, Obstet. Gynecol. 47, 59s-62s (1976).