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Squamous carcinoma in situ of the vulva
GYNECOLOGIC
ONCOLOGY
14, 213-219
(1982)
Squamous Carcinoma in Situ of the Vulva J. L. BENEDET,’
FRCS(C),
AND
K. J.
MUWHY,
M.D.
Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, and Division of Gynaecologic Oncology, Cancer Control Agency of British Columbia, Vancouver, British Columbia, Canada
Received September 9, 1981 Squamous carcinoma in situ of the vulva in 81 patients treated at the Vancouver General Hospital between 1970 and 1980 were reviewed. The patients were assigned to one of two study periods, 1970-1974 or 1975-1980, for the purposes of comparison. Forty-two percent of patients seen in the latter study period were less than 35 years of age, as contrasted to only 14% of patients in the earlier time period. Similar trends were noted in the frequency of involvement of the genital tract by multifocal squamous neoplasia with 51 and 25% of patients having this problem in the two time periods. Those patients under 30 years of age were at particular risk for multiple genital site involvement. Vulvar pruritis or irritation was the most common method of presentation. Abnormalities of cervical or vaginal cytology led to the diagnosis of vulvar carcinoma in 15% of patients. Younger women tended to present with multicentric, often pigmented lesions, whereas unifocal lesions were more common in the older age groups. Treatment methods varied little between the two study periods. Treatment should be individualized and conservative, particularly in younger women until the true neoplastic potential of these lesions is better known.
INTRODUCTION Carcinoma in situ of the vulva, or Bowen’s disease, has traditionally been thought of as a disease of older women. Several recent reports [l-4], however, have suggested a changing age incidence with many younger women now being affected. The reason for this change is not clear but there is some evidence to suggest that the disease seen in the young women, although histologically similar to classical Bowen’s disease, is actually a distinct clinical entity with its own characteristics [5-71. The histologic appearance of vulvar carcinoma in situ is more consistent than the clinical appearance which may be extremely varied. Lesions range from a distinct red velvety patch to diffuse multifocal pigmented and, on occasion, verrucous papular lesions. The multifocal pigmented verrucous lesions are typical of the recently described Bowenoid papulosis. Various authors [5-81 have described this lesion as typically affecting very young women, usually in association with a recent pregnancy, and in some instances a history of prior genital herpes or condylomata accuminata. Although Bowen’s disease itself is ’ To whom reprint requests should be addressed: Department of Obstetrics and Gynaecology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, British Columbia V5Z lM9, Canada. 213 0090-8258/82/050213-07$01.00/O Copyright 8 1982 by Academic Press. Inc. All rights of reproduction in any form reserved.
214
BENEDET
AND
MURPHY
typically benign with a low rate of malignant progression, the natural history and true malignant potential of “Bowenoid papulosis” are unknown as some patients have apparently undergone spontaneous regression; thus the optimum treatment for the condition remains to be defined. Regardless of the clinical appearance of vulvar carcinoma in situ, the disorder is relatively uncommon and frequently presents difficult management problems. Therapy, including topical SFU, local excision, skinning vulvectomy, total or partial vulvar excision, and, more recently, laser cautery have been advocated. Most current reports favor a conservative approach [1,4,9,101. The purpose of this study was to determine any change in the age distribution of this disease over an II-year period. The clinical characteristics of the disease were also assessed in an attempt to provide a better understanding of the disorder and appropriate guidelines for its future management. MATERIAL
AND METHODS
The records of all patients with the diagnosis of carcinoma of the vulva at the Vancouver General Hospital between 1970 and 1980 (inclusive) were reviewed. Eighty-one patients with squamous carcinoma in situ of the vulva were found and comprise the study group. In each case, the age at diagnosis, presenting signs and symptoms, description of the lesion, together with the treatment records and pathology reports were tabulated. In addition, the presence or absence of preexisting, concomitant, or subsequent genital tract neoplasia was recorded. Any history of condylomata accuminata or genital herpes was also noted. The data obtained were divided into two study periods, 1970 to 1974 and 1975 to 1980, for the purposes of comparison. Lesions were classified as unifocal, diffuse, or multicentric. A unifocal lesion was defined as a discrete, well-circumscribed area ranging in size from a few millimeters to several centimeters. Lesions were classified as diffuse if the changes involved most or all of the vulva. Multicentric lesions were multiple, discrete, nonconfluent lesions separated by apparently normal epithelium. RESULTS The age distribution of the patients in the two study periods is displayed in Table 1. The patients’ ages ranged from 19 to 87 years, with mean ages of 60 and 45 years, respectively, for the two time periods under review. Associated squamous neoplasia of the genital tract in the various age groups is documented in Table 2. Of the 24 patients (30%) 35 years of age or less, 17 (71%) had either preexisting, concomitant or subsequent disease involving the cervix and/or vagina, as well as the vulva. Of the 57 patients greater than 35 years, only 14 (25%) had similar involvement. Multiple site involvement is even more striking when considered among women under 30 years of age where 9 of 12 were found to have multiple site genital neoplasia. Multiple site disease occurred in 51% of patients in the latter study group, as compared with only 25% of patients during the earlier years in the study. The methods of presentation and their frequency are shown in Table 3. Vulvar pruritis was the most common presenting complaint. A visible or palpable lesion
CARCINOMA
OF THE
TABLE CARCINOMA
IN SITU
215
VULVA
1
VULVA:
AGE
DISTRIBUTION
Study period 1970-1974 (mean age = 60)
Age
1975-1980 (mean age = 45)
group
Total
<25 25-30 31-35 36-Io 4145 46-50 51-55 X-60 61-65 >65
7 5 12 5 9 7 6 5 4 21
1
6 5 8 1 5 5 3 3 2 7
Total
81
36
45
noted by the patient was the second most frequent form of presentation. In 12 patients, investigation of an abnormal cervical or vaginal Pap smear led to the diagnosis of their coexisting vulvar lesion which had previosly been unrecognized. Five women were asymptomatic and had a suspicious lesion noted during a routine pelvic examination. If the group of patients with abnormal cytology is combined with patients diagnosed at routine examination, then 21% of women were asymptomatic at the time of diagnosis. Not infrequently, a delay in diagnosis resulted from either patient reluctance to seek attention despite symptoms or physician hesitancy to biopsy obvious lesions refractory to various topical agents. TABLE CARCINOMA
IN SITU
VULVA:
ASSXIATED
2
SQUAMOUS
NEOPLASIA
OF GENITAL
1970-1974 (N = 36) Age group
Vulva only
~25 2630 31-35 3wo 4145 4650 51-55 56-60 61-65 >65 Total
Vulva, 2 cervix vagina
Vulva only 3
2 1
2
3 27
1975-1980 (N = 45)
1
1 1
9 (25%)
TRACT
Vulva, f cervix vagina
3 5 1 2 6 22
3 2 1 23 (51%)
216
BENEDET
AND
MURPHY
TABLE CARCINOMA
IN SITU
3
VULVA:
METHOD
OF
PRESENTATION
Presenting complaint
No. of patients
Percentage
Pruritus/irritation Lesion Abnormal cervical/vaginal cytology Incidental finding Discharge Not recorded
35 24
43 29.5
12
15
Total
81
5 3 2
6 4 2.5 100
Six patients had previous pelvic irradiation for cervical malignancy. One patient had chronic leukemia and another had sarcoidosis but neither of these patients nor any other was known to be taking immunosuppressive drugs at the time of diagnosis of their vulvar disease. Of the women less than 35 years of age, three had a history of previous herpes genitalis and six had either preexisting or concomitant condylomata. In the latter years of the study, most patients had colposcopic evaluation. In addition, the 12 patients who presented with abnormal cervical or vaginal cytology had their lesion first noted at the time of colposcopic examination. The various types of lesions seen are presented by age group in Table 4. Multicentric lesions were particularly common in young women, whereas older women tended to have discrete, unifocal lesions. Figure 1 illustrates the location of the lesion in those patients with unifocal lesions. There is a marked preponderance of unifocal lesions involving the posterior half of the vulva. The reason for this apparent predisposition is unclear. Most of the diffuse types of lesions involved the perianal area and were invariably incompletely excised. Treatment methods for the two study eeriods are outlined in Table 5. No apparent differences between the two study periods are noted. Wide local excision or partial vulvectomy is seen to be the most common treatment method. TABLE CARCINOMA
IN SITU
VULVA:
AGE
4 GROUP
VERSUS
LESION
TYPE
Type of lesion Age group
Total patients
=S30 31-50 >50
12 33 36
Total
81
Multicentric
Unifocal
8 (66%) 8 (26%) 9 (25%)
4 (33%) 23 (70%) 16 (44%)
25
43
Diffuse -
Not known -
1 4
1 7
5
8
CARCINOMA
OF THE
217
VULVA
6 patients 8 patients 25 patients
FIG.
1. Locations of lesions in those patients with unifocal lesions.
One patient receiving 5-FU and the patient refusing treatment have persistent disease but continue to refuse surgery. They have had regular clinical evaluations over the past 3 and 6 years, respectively, with no apparent change in lesion size or distribution. Both had cervical intraepithelial neoplasia for which a cone biopsy was done. Information regarding the completeness of excision by treatment method is listed in Table 6. Completeness of excision did not correlate well with the type of procedure done. Those patients with positive margins indicating incomplete excision were then analyzed. It was noted that most had either a diffuse type of lesion with perianal extension or widespread multifocal lesions with clitoral involvement. Attempts to spare these structures from possible damage undoubtedly led to incomplete excision. In 10 patients, no comment regarding the state of the surgical margins was made by the pathologist. Without knowledge of completeness of primary excision, it becomes difficult to distinguish recurrent from persistent disease. This distinction has implications not only for management of specific patients but also for elucidating the natural history of the disease. Though detailed follow-up was not included as part of this study, several patients are known to have developed further disease. Of these, three have gone on to develop invasive vulvar carcinoma 6, 3, and 2 years following treatment of their in situ disease. To date, none of the young patients with multicentric pigmented lesions have shown such progression. TABLE CARCINOMA
IN SITU
VULVA:
5 METHOD
OF TREATMENT
No. of patients Study period Treatment method
Total
1970-1974
1975-1980
Local excision Simple vulvectomy Skinning vulvectomy 5-FU Refused treatment
42 33 3 2 1
20 15 1
22 18 3 1 1
Total
81
36
45
218
BENEDET
AND
TABLE CARCINOMA
IN SITU
VULVA:
TREATMENT
MURPHY
6 METHOD
VERSUS
SURGICAL
MARGINS
Surgical margins No. of patients
Negative
Positive
Local excision Simple vulvectomy Skinning vulvectomy
42 33 3
20 13 1
18 14 2
4 6
Total
78
34
34
10
Treatment method
Not known
DISCUSSION The results of this study show a higher frequency of vulvar neoplasia among young women than has been traditionally expected. It would also appear that, in the past 5 years, the percentage of young patients with this disease has increased. Several of these younger women appear to satisfy the clinical criteria for so-called Bowenoid papulosis. The high frequency of associated genital tract neoplasia, as especially noted in younger women, emphasizes the need for prolonged follow-up and thorough evaluation of the entire genital tract. The frequency of both the multicentric type of lesion and multisite involvement in young women suggests the possibility of a different etiologic agent and perhaps a different disease state in these patients when compared to the clinical patterns seen in older women. Seski et al. [ll], in an in vitro study of lymphocytic transformation in patients with vulvar carcinoma in situ, found cellular immunity of the delayed type to be diminished when compared to age-matched controls. Altered cellular immunity secondary to pregnancy predisposing to neoplastic change is further suggested by reports of patients undergoing spontaneous regression of lesions which developed during their pregnancies [7,9], despite initial aneuploid DNA patterns. These findings, together with the frequent history of preexisting condylomata or herpes genitalis in young women with vulvar carcinoma in situ suggest a viral etiology for this disease but, as yet, this hypothesis remains unproven. Clearly, further studies as to the etiologic role of these viruses are required. Although careful gross inspection may often be sufficient to determine surgical boundaries for excision, colposcopy in certain situations may offer more precise information. Colposcopy may also be of particular value in selecting the most suspicious areas for biopsy in patients with diffuse or multifocal lesions. Incomplete excision was common in the patients studied with all methods of surgical management associated with the development of further vulvar disease. Through histological examination of the margins of any surgical specimen is imperative. This critical information may require that the entire specimen be blocked and serially sectioned. A variety of methods have been used to treat vulvar carcinoma in situ. Some patients may respond to topical 5-FU or laser cautery, both of which have the advantage of producing minimal cosmetic alteration to the appearance of the
CARCINOMA
OF
THE
VULVA
219
vulva. Reports as to their effectiveness and of 5-FU have the disadvantage of failing to provide further tissue so that patients with superficially invasive carcinomas may be missed. Successful utilization of topical 5-FU requires both a persistent physician and a stoical patient as treatment is for 6-8 weeks and often produces intense pruritis, irritation, and discomfort far in excess of that which was present initially. Treatment should be surgical and individualized based on the size, distribution, and extent of the lesion seen. Excision should be superficial removing only epidermis and dermis with minimal disturbance of the underlying subcutaneous tissues which are mainly responsible for maintaining the usual vulvar contours. In many instances, primary closure may be easily affected, whereas others may require skin grafting. More than one session may be needed to successfully treat some patients with multifocal or extensive disease and we believe this approach is preferable to more extensive surgery, particularly in the young patient. REFERENCES 1. Woodruff, T. D., Julian, C. G., Puray, T., Mermatz, S., and Katayama, P. The contemporary challenge of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol 115, 667 (1973). 2 Buscema, J., Woodruff, J. D., Parmley, T. H., and Genadry, R. Carcinoma in situ of the vulva, Obstet. Gynecol. 55, 225 (1980). 3. Hilliard, G. D., Massey, F. M., and O’Toole, R. V. Vulvar neoplasia in the young, Amer. J. Obstet. Gynecol. 135, 18.5 (1979). 4. 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 (1977). 5. Bhawan, J. Multicentric pigmented Bowen’s disease: A clinically benign squamous cell carcinoma in situ, Gynecol. Oncol. 10, 201 (1980). 6. Friedrich, E. G., Reversible vulvar atypia: A case report, Obstet. Gynecol. 39, 173 (1972). 7. Skinner, M. S., Stemberg, W. H., Ichinose, H., and Collins, J. Spontaneous regression of Bowenoid atypia of the vulva, Obstet. Gynecol. 42, 40 (1973). 8. Wade, T. R., Kopk, A. W., Ackerman, A. B. Bowenoid papulosis of the genitalia, Arch. Dermatol. 115, 306 (1979). 9. Friedrich, E. G., Wilkinson, E. J., and Fu, Y. S. Carcinoma in situ of the vulva: A continuing challenge, Amer. J. Obstet. Gynecol. 136, 830 (1980). 10. Iversen, T., Abeler, V., and Kolstad, P. Squamous cell carcinoma in situ of the vulva: A clinical and histopathological study, Gynecol. Oncol. 11, 224 (1981). 11. Seski, J. C., Reinhalter, E. R., and Silva, Jr., J. Abnormalities of lymphocyte transformations in women with intraepithelial carcinoma of the vulva, Obstet. Gynecol. 52, 332 (1978).
ONCOLOGY
14, 213-219
(1982)
Squamous Carcinoma in Situ of the Vulva J. L. BENEDET,’
FRCS(C),
AND
K. J.
MUWHY,
M.D.
Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, and Division of Gynaecologic Oncology, Cancer Control Agency of British Columbia, Vancouver, British Columbia, Canada
Received September 9, 1981 Squamous carcinoma in situ of the vulva in 81 patients treated at the Vancouver General Hospital between 1970 and 1980 were reviewed. The patients were assigned to one of two study periods, 1970-1974 or 1975-1980, for the purposes of comparison. Forty-two percent of patients seen in the latter study period were less than 35 years of age, as contrasted to only 14% of patients in the earlier time period. Similar trends were noted in the frequency of involvement of the genital tract by multifocal squamous neoplasia with 51 and 25% of patients having this problem in the two time periods. Those patients under 30 years of age were at particular risk for multiple genital site involvement. Vulvar pruritis or irritation was the most common method of presentation. Abnormalities of cervical or vaginal cytology led to the diagnosis of vulvar carcinoma in 15% of patients. Younger women tended to present with multicentric, often pigmented lesions, whereas unifocal lesions were more common in the older age groups. Treatment methods varied little between the two study periods. Treatment should be individualized and conservative, particularly in younger women until the true neoplastic potential of these lesions is better known.
INTRODUCTION Carcinoma in situ of the vulva, or Bowen’s disease, has traditionally been thought of as a disease of older women. Several recent reports [l-4], however, have suggested a changing age incidence with many younger women now being affected. The reason for this change is not clear but there is some evidence to suggest that the disease seen in the young women, although histologically similar to classical Bowen’s disease, is actually a distinct clinical entity with its own characteristics [5-71. The histologic appearance of vulvar carcinoma in situ is more consistent than the clinical appearance which may be extremely varied. Lesions range from a distinct red velvety patch to diffuse multifocal pigmented and, on occasion, verrucous papular lesions. The multifocal pigmented verrucous lesions are typical of the recently described Bowenoid papulosis. Various authors [5-81 have described this lesion as typically affecting very young women, usually in association with a recent pregnancy, and in some instances a history of prior genital herpes or condylomata accuminata. Although Bowen’s disease itself is ’ To whom reprint requests should be addressed: Department of Obstetrics and Gynaecology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, British Columbia V5Z lM9, Canada. 213 0090-8258/82/050213-07$01.00/O Copyright 8 1982 by Academic Press. Inc. All rights of reproduction in any form reserved.
214
BENEDET
AND
MURPHY
typically benign with a low rate of malignant progression, the natural history and true malignant potential of “Bowenoid papulosis” are unknown as some patients have apparently undergone spontaneous regression; thus the optimum treatment for the condition remains to be defined. Regardless of the clinical appearance of vulvar carcinoma in situ, the disorder is relatively uncommon and frequently presents difficult management problems. Therapy, including topical SFU, local excision, skinning vulvectomy, total or partial vulvar excision, and, more recently, laser cautery have been advocated. Most current reports favor a conservative approach [1,4,9,101. The purpose of this study was to determine any change in the age distribution of this disease over an II-year period. The clinical characteristics of the disease were also assessed in an attempt to provide a better understanding of the disorder and appropriate guidelines for its future management. MATERIAL
AND METHODS
The records of all patients with the diagnosis of carcinoma of the vulva at the Vancouver General Hospital between 1970 and 1980 (inclusive) were reviewed. Eighty-one patients with squamous carcinoma in situ of the vulva were found and comprise the study group. In each case, the age at diagnosis, presenting signs and symptoms, description of the lesion, together with the treatment records and pathology reports were tabulated. In addition, the presence or absence of preexisting, concomitant, or subsequent genital tract neoplasia was recorded. Any history of condylomata accuminata or genital herpes was also noted. The data obtained were divided into two study periods, 1970 to 1974 and 1975 to 1980, for the purposes of comparison. Lesions were classified as unifocal, diffuse, or multicentric. A unifocal lesion was defined as a discrete, well-circumscribed area ranging in size from a few millimeters to several centimeters. Lesions were classified as diffuse if the changes involved most or all of the vulva. Multicentric lesions were multiple, discrete, nonconfluent lesions separated by apparently normal epithelium. RESULTS The age distribution of the patients in the two study periods is displayed in Table 1. The patients’ ages ranged from 19 to 87 years, with mean ages of 60 and 45 years, respectively, for the two time periods under review. Associated squamous neoplasia of the genital tract in the various age groups is documented in Table 2. Of the 24 patients (30%) 35 years of age or less, 17 (71%) had either preexisting, concomitant or subsequent disease involving the cervix and/or vagina, as well as the vulva. Of the 57 patients greater than 35 years, only 14 (25%) had similar involvement. Multiple site involvement is even more striking when considered among women under 30 years of age where 9 of 12 were found to have multiple site genital neoplasia. Multiple site disease occurred in 51% of patients in the latter study group, as compared with only 25% of patients during the earlier years in the study. The methods of presentation and their frequency are shown in Table 3. Vulvar pruritis was the most common presenting complaint. A visible or palpable lesion
CARCINOMA
OF THE
TABLE CARCINOMA
IN SITU
215
VULVA
1
VULVA:
AGE
DISTRIBUTION
Study period 1970-1974 (mean age = 60)
Age
1975-1980 (mean age = 45)
group
Total
<25 25-30 31-35 36-Io 4145 46-50 51-55 X-60 61-65 >65
7 5 12 5 9 7 6 5 4 21
1
6 5 8 1 5 5 3 3 2 7
Total
81
36
45
noted by the patient was the second most frequent form of presentation. In 12 patients, investigation of an abnormal cervical or vaginal Pap smear led to the diagnosis of their coexisting vulvar lesion which had previosly been unrecognized. Five women were asymptomatic and had a suspicious lesion noted during a routine pelvic examination. If the group of patients with abnormal cytology is combined with patients diagnosed at routine examination, then 21% of women were asymptomatic at the time of diagnosis. Not infrequently, a delay in diagnosis resulted from either patient reluctance to seek attention despite symptoms or physician hesitancy to biopsy obvious lesions refractory to various topical agents. TABLE CARCINOMA
IN SITU
VULVA:
ASSXIATED
2
SQUAMOUS
NEOPLASIA
OF GENITAL
1970-1974 (N = 36) Age group
Vulva only
~25 2630 31-35 3wo 4145 4650 51-55 56-60 61-65 >65 Total
Vulva, 2 cervix vagina
Vulva only 3
2 1
2
3 27
1975-1980 (N = 45)
1
1 1
9 (25%)
TRACT
Vulva, f cervix vagina
3 5 1 2 6 22
3 2 1 23 (51%)
216
BENEDET
AND
MURPHY
TABLE CARCINOMA
IN SITU
3
VULVA:
METHOD
OF
PRESENTATION
Presenting complaint
No. of patients
Percentage
Pruritus/irritation Lesion Abnormal cervical/vaginal cytology Incidental finding Discharge Not recorded
35 24
43 29.5
12
15
Total
81
5 3 2
6 4 2.5 100
Six patients had previous pelvic irradiation for cervical malignancy. One patient had chronic leukemia and another had sarcoidosis but neither of these patients nor any other was known to be taking immunosuppressive drugs at the time of diagnosis of their vulvar disease. Of the women less than 35 years of age, three had a history of previous herpes genitalis and six had either preexisting or concomitant condylomata. In the latter years of the study, most patients had colposcopic evaluation. In addition, the 12 patients who presented with abnormal cervical or vaginal cytology had their lesion first noted at the time of colposcopic examination. The various types of lesions seen are presented by age group in Table 4. Multicentric lesions were particularly common in young women, whereas older women tended to have discrete, unifocal lesions. Figure 1 illustrates the location of the lesion in those patients with unifocal lesions. There is a marked preponderance of unifocal lesions involving the posterior half of the vulva. The reason for this apparent predisposition is unclear. Most of the diffuse types of lesions involved the perianal area and were invariably incompletely excised. Treatment methods for the two study eeriods are outlined in Table 5. No apparent differences between the two study periods are noted. Wide local excision or partial vulvectomy is seen to be the most common treatment method. TABLE CARCINOMA
IN SITU
VULVA:
AGE
4 GROUP
VERSUS
LESION
TYPE
Type of lesion Age group
Total patients
=S30 31-50 >50
12 33 36
Total
81
Multicentric
Unifocal
8 (66%) 8 (26%) 9 (25%)
4 (33%) 23 (70%) 16 (44%)
25
43
Diffuse -
Not known -
1 4
1 7
5
8
CARCINOMA
OF THE
217
VULVA
6 patients 8 patients 25 patients
FIG.
1. Locations of lesions in those patients with unifocal lesions.
One patient receiving 5-FU and the patient refusing treatment have persistent disease but continue to refuse surgery. They have had regular clinical evaluations over the past 3 and 6 years, respectively, with no apparent change in lesion size or distribution. Both had cervical intraepithelial neoplasia for which a cone biopsy was done. Information regarding the completeness of excision by treatment method is listed in Table 6. Completeness of excision did not correlate well with the type of procedure done. Those patients with positive margins indicating incomplete excision were then analyzed. It was noted that most had either a diffuse type of lesion with perianal extension or widespread multifocal lesions with clitoral involvement. Attempts to spare these structures from possible damage undoubtedly led to incomplete excision. In 10 patients, no comment regarding the state of the surgical margins was made by the pathologist. Without knowledge of completeness of primary excision, it becomes difficult to distinguish recurrent from persistent disease. This distinction has implications not only for management of specific patients but also for elucidating the natural history of the disease. Though detailed follow-up was not included as part of this study, several patients are known to have developed further disease. Of these, three have gone on to develop invasive vulvar carcinoma 6, 3, and 2 years following treatment of their in situ disease. To date, none of the young patients with multicentric pigmented lesions have shown such progression. TABLE CARCINOMA
IN SITU
VULVA:
5 METHOD
OF TREATMENT
No. of patients Study period Treatment method
Total
1970-1974
1975-1980
Local excision Simple vulvectomy Skinning vulvectomy 5-FU Refused treatment
42 33 3 2 1
20 15 1
22 18 3 1 1
Total
81
36
45
218
BENEDET
AND
TABLE CARCINOMA
IN SITU
VULVA:
TREATMENT
MURPHY
6 METHOD
VERSUS
SURGICAL
MARGINS
Surgical margins No. of patients
Negative
Positive
Local excision Simple vulvectomy Skinning vulvectomy
42 33 3
20 13 1
18 14 2
4 6
Total
78
34
34
10
Treatment method
Not known
DISCUSSION The results of this study show a higher frequency of vulvar neoplasia among young women than has been traditionally expected. It would also appear that, in the past 5 years, the percentage of young patients with this disease has increased. Several of these younger women appear to satisfy the clinical criteria for so-called Bowenoid papulosis. The high frequency of associated genital tract neoplasia, as especially noted in younger women, emphasizes the need for prolonged follow-up and thorough evaluation of the entire genital tract. The frequency of both the multicentric type of lesion and multisite involvement in young women suggests the possibility of a different etiologic agent and perhaps a different disease state in these patients when compared to the clinical patterns seen in older women. Seski et al. [ll], in an in vitro study of lymphocytic transformation in patients with vulvar carcinoma in situ, found cellular immunity of the delayed type to be diminished when compared to age-matched controls. Altered cellular immunity secondary to pregnancy predisposing to neoplastic change is further suggested by reports of patients undergoing spontaneous regression of lesions which developed during their pregnancies [7,9], despite initial aneuploid DNA patterns. These findings, together with the frequent history of preexisting condylomata or herpes genitalis in young women with vulvar carcinoma in situ suggest a viral etiology for this disease but, as yet, this hypothesis remains unproven. Clearly, further studies as to the etiologic role of these viruses are required. Although careful gross inspection may often be sufficient to determine surgical boundaries for excision, colposcopy in certain situations may offer more precise information. Colposcopy may also be of particular value in selecting the most suspicious areas for biopsy in patients with diffuse or multifocal lesions. Incomplete excision was common in the patients studied with all methods of surgical management associated with the development of further vulvar disease. Through histological examination of the margins of any surgical specimen is imperative. This critical information may require that the entire specimen be blocked and serially sectioned. A variety of methods have been used to treat vulvar carcinoma in situ. Some patients may respond to topical 5-FU or laser cautery, both of which have the advantage of producing minimal cosmetic alteration to the appearance of the
CARCINOMA
OF
THE
VULVA
219
vulva. Reports as to their effectiveness and of 5-FU have the disadvantage of failing to provide further tissue so that patients with superficially invasive carcinomas may be missed. Successful utilization of topical 5-FU requires both a persistent physician and a stoical patient as treatment is for 6-8 weeks and often produces intense pruritis, irritation, and discomfort far in excess of that which was present initially. Treatment should be surgical and individualized based on the size, distribution, and extent of the lesion seen. Excision should be superficial removing only epidermis and dermis with minimal disturbance of the underlying subcutaneous tissues which are mainly responsible for maintaining the usual vulvar contours. In many instances, primary closure may be easily affected, whereas others may require skin grafting. More than one session may be needed to successfully treat some patients with multifocal or extensive disease and we believe this approach is preferable to more extensive surgery, particularly in the young patient. REFERENCES 1. Woodruff, T. D., Julian, C. G., Puray, T., Mermatz, S., and Katayama, P. The contemporary challenge of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol 115, 667 (1973). 2 Buscema, J., Woodruff, J. D., Parmley, T. H., and Genadry, R. Carcinoma in situ of the vulva, Obstet. Gynecol. 55, 225 (1980). 3. Hilliard, G. D., Massey, F. M., and O’Toole, R. V. Vulvar neoplasia in the young, Amer. J. Obstet. Gynecol. 135, 18.5 (1979). 4. 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 (1977). 5. Bhawan, J. Multicentric pigmented Bowen’s disease: A clinically benign squamous cell carcinoma in situ, Gynecol. Oncol. 10, 201 (1980). 6. Friedrich, E. G., Reversible vulvar atypia: A case report, Obstet. Gynecol. 39, 173 (1972). 7. Skinner, M. S., Stemberg, W. H., Ichinose, H., and Collins, J. Spontaneous regression of Bowenoid atypia of the vulva, Obstet. Gynecol. 42, 40 (1973). 8. Wade, T. R., Kopk, A. W., Ackerman, A. B. Bowenoid papulosis of the genitalia, Arch. Dermatol. 115, 306 (1979). 9. Friedrich, E. G., Wilkinson, E. J., and Fu, Y. S. Carcinoma in situ of the vulva: A continuing challenge, Amer. J. Obstet. Gynecol. 136, 830 (1980). 10. Iversen, T., Abeler, V., and Kolstad, P. Squamous cell carcinoma in situ of the vulva: A clinical and histopathological study, Gynecol. Oncol. 11, 224 (1981). 11. Seski, J. C., Reinhalter, E. R., and Silva, Jr., J. Abnormalities of lymphocyte transformations in women with intraepithelial carcinoma of the vulva, Obstet. Gynecol. 52, 332 (1978).