Vulvar carcinoma in situ: A report of 28 cases
Descrição do Produto
GYNECOLOGIC
14, 236-242 (1982)
ONCOLOGY
Vulvar Carcinoma in Situ: A Report of 28 Cases GUILLERMO
R. DI PAOLA, M.D., NIDIA G~MEZ RUEDA-LEVERONE, G. BELARDI, M.D., AND SUSANA VIGHI, M.D.
M.D.,
MARIA First
Chair
of Gynecology,
University of Buenos Aires, Buenos Aires, Argentina
Cbrdoba
2351,
CP 1120,
Received November 6, 1981
Twenty-eight cases of vulvar CIS are reported. The interest of a group of specialists in this pathology notably improves early detection. Biopsy was the basic diagnostic method. The CIS vulvar patients are generally younger than those suffering invasive cancer. The association with other genital or extragenital neoplasias is analyzed. Seven cases were asymptomatic. Unifocal lesions were more frequent than multifocal lesions. Individualized treatment is considered.
An international agreement exists stating that with the exception of extramammary Paget’s disease, all the lesions previously known as Bowen’s disease, simplex carcinoma in situ (CIS), and Queyrat’s erythroplasia have a similar biological behavior and a similar significance and prognosis. That is why they have been universally named carcinoma in situ of the vulva, employing one encompassing name and thus avoiding confusing and inappropriate terms. [21]. In Argentina, as well as in other parts of the world, a significant interest in vulvar pathology has evolved in the last 10 years and considerable experience has been acquired. The vast number of CIS cases diagnosed, treated, and controlled has prompted some modifications in the classical points of view which are analyzed in detail in this study. MATERIALS
AND METHODS
The study population consists of 28 cases of vulvar CIS diagnosed between 1928 and 1981. The interest of a group specializing in this pathology notably improves early detection [3,7,12,14]. In our study, 4 cases of CIS had been diagnosed within the period 1928 through 1967; this means 1 case every 9 years (Table 1). In 1968 a clinic devoted to vulvovaginal pathology was created: 8 cases were diagnosed between 1968 and 1976 (1 case each year). Between 1977 and 1981 16 cases were diagnosed (4 per Year). The basic diagnostic method consisted of biopsy, single or multiple [11,14], our most frequent indicator being the toluidine blue test or the Richart-Collins [IO], and less frequently the tetracycline fluorescence test [8]. 236 0090-8258/82/050236-07$01.00/O Copyright All rights
Q 1982 by Academic Press, Inc. of reproduction in any form reserved.
VULVAR
CARCINOMA
IN
TABLE DIAGNOSIS
192811967 1968/1976 1977/1981
237
SITU
1 CIS
OF VULVAR
Number of cases
Incidence
4 8 16
1 case/9 years 1 case/year 4 cases/year
During the last 10 years we have performed more than 400 biopsies without complications. All squamous lesions have been histologically classified as vulvar CIS when they were characterized by disorganization and loss of epithelial structure spreading throughout the entire thickness of the epithelium and in which could be observed: dyscaryosis, dyskeratosis, corps ronds, giant multinuclear cells, etc. [6,11,14,21,23,25,26]. RESULTS Age. CIS vulvar patients are generally younger than those suffering invasive cancer. As seen in Table 2, 67.9% of the patients were between 40 and 59 years old. The youngest was 19 and the oldest 74. Only three were less than 42 years old. Predisposing factors. In our series no significant data, with respect to obesity, hypertension, menstrual history, parity, and syphillis, were obtained. Oncological alert. Previous, present, or subsequent association of vulvar CIS with other genital carcinomas (endometrial, cervical, and vaginal) or extragenital manifestations (colon and bladder) is up to 25 or 30% of the cases according to published reports (4,6,14,15,19). This finding presupposes an oncological alert in this group of patients in order to eliminate other possible primary carcinomas. On the other hand, patients suffering other types of carcinoma, especially genital types, must undergo a careful vulvar control study even if the patients do not manifest any vulvar symptoms [5,26]. An association of vulvar CIS with other CIS dysplasias or invasive carcinomas, occurred in eight cases (28.5%) (Table 3). Previous neoplasias had been manifested in three of the cases (Table 4). In four cases other neoplasias were diagnosed simultaneously with the vulvar CIS (Table 5). One patient developed an invasive breast carcinoma 2 years after the vulvar CIS diagnosis.
VULVAR
0
0.0..
TABLE CIS AND
2 PATIENT
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l 00
AGE
:
l~~“.“~‘I’,““~~~I~~‘~~~~‘~““‘~“~~’~~~”~’~~’~~~’~ 20 30 40 50
:...
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e
70
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238
DI
PAOLA
TABLE AWXIATION
ET
AL.
3
WITH OTHER NEOPLASIAS OF VULVAR CIS
IN
28 CASES 3 4 1 8 (28.5%)
Previous Simultaneous Subsequent Total
Symptoms. Twenty-one cases (75%) were symptomatic (Table 6). Pruritus was the most frequent symptom (42%). Seven cases were asymptomatic (25%) and diagnosis was made in four patients by the oncological alert, explained above; in the other three cases routine examination revealed hypetpigmented papulous lesions or raised white macular lesions (Table 7). Clinical features. Two cases were totally invisible to the naked eye and diagnoses were reached because the patients were on oncological alert (Table 8). With respect to color, 10 lesions were white, 9 hyperpigmented, 5 velvety red, and 2 erythromatous and hyperpigmented. The Richart-Collins test was used in 16 cases: it has proved useful but not infallible or absolute. Unifocal lesions appeared more frequently in our series than did multifocal ones (Table 9). There were 24 unifocal cases and 4 multifocal cases. Pathology. An exhaustive study was performed in 25 of the 28 cases. The origin of the CIS was unifocal in 24 cases (unicentral or with discontinuous growth zones within the same region); multifocal in 4 cases. The largest lesion was 40 x 20 mm and the maximal diameter of the smallest was 4 mm. Twentyfour of the CIS were highly or medially differentiated, four were poorly differentiated, two of these with no keratinization. An initial invasion of the stroma in one area was present in one case. Treatment. Ten cases underwent total vulvectomy, two underwent partial vulvectomies with conservation of the clitoris. Three cases were treated with radium: two in the perimeatic region and one in the introitus with ulcer. Eleven underwent local excision. Topical candidine was used in one case and one patient refused treatment (Table 10). VULVAR
TABLE 4 CIS IN PREVIOUS ASSXIATION WITH OTHER GENITAL
Neoplasm Case 1. Cervix carcinoma, stage IIB Case 2. Severe cervical dysplasia Severe vaginal dysplasia Case 3. CIS of the cervis CIS of the vagina
Number of years before diagnosis of vulvar CIS
MALIGNANCIES
Observations
Immunosuppressed
patient
239
VULVAR CARCINOMA IN SITU
VULVAR
TABLE 5 CIS IN SIMULTANEOUS ASXXIATION OTHER
Case
GENITAL
WITH
MALIGNANCIES
Malignancy
4
CIS cervix CIS, cervix, planimetrically extended to the uterine cavity and vagina CIS, cervix and vagina Severe dysplasia, cervix (immunosuppressed patient)
5 6 7
VULVAR
TABLE 6 CIS SYM~TOMATOL~GY Number of cases
Percentage
7 12 8 1 28
25 43 28.5 3.5 100
No symptoms Pruritus Tumor Ulcer Total
VULVAR
TABLE 7 CIS DIAGNOSIS IN ASYMITOMATIC PATIENTS
Number of cases 4 3 7
Oncologic alert Papulous lesions Total TABLE
8
MACROSCOPY
Number of cases Papule Macule Ulcer Deceptive Total
16 9 1 2 28 TABLE 9 Focus OF VULVAR
CIS Number of cases
Multifocal Ullifocal Total
4 24 28
240
DI PAOLA
ET AL.
TABLE 10 TREATMENT
OF VULVAR
CIS Number of cases 10 2 11 3 1 1 28
Total simple vulvectomy Partial vulvectomy Local excision Radium Topical candidine No treatment Total
Follow-up. Seventeen cases were followed for 4 to 10 years and 11 for 3 months to 3 years (Table 11). Only one case of recurrence has been observed 1 year after treatment by local excision and the patient, observed for the last 3 years, remains clinically cured. COMMENT
A noticeable increase in the frequency of vulvar CIS has been observed. This fact may be due to a real increase in its incidence, or only to a concentration of the patients into specialized clinics where early lesions can be properly detected. The activity of a group specializing in vulvar pathology notably improves the detection of the vulvar CIS: we have increased our diagnosis from one case every 9 years to four per year after the setting-up of the Vulvar Pathology Clinic. This fact is basically due to the frequent use of biopsy as a diagnostic method in the hands of a specially trained team. The patients with vulvar CIS are generally younger than those suffering from invasive carcinoma. In our series, 67.9% were between 40 and 59 years old. There were only three patients less than 43 years old, whereas in other studies, 40% belonged in this age group. Previous, present, or subsequent association of vulvar CIS with other genital carcinomas (endometrial, cervical, vaginal) or extragenital (breast, colon, bladder) took place in 28.5% of our cases. This fact concurs with others’ statistics [13,14,16,17], where it was observed in 15 to 30% of the cases. This makes an oncological alert necessary in those patients and a detection of other possible primary carcinomas. These are patients at high oncological risk. On the other hand, in patients suffering other genital carcinomas, a thorough TABLE 11 FOLLOW-UP
Number of cases
Period
17 11
4 to 10 years 3 months to 3 years
VULVAR
CARCINOMA
IN
SITU
241
vulvar examination should be performed even in the absence of vulvar symptoms. The Richart-Collins test could be useful in these cases [12], and if it is negative, a biopsy should be performed even on the slightest epithelial lesion. Patients undergoing immunosuppression, either by high-dose corticoids for prolonged periods of time or by chemotherapy, are also at high oncological risk [20]. Diagnostic procedures in the vulva and in the rest of the genital tract should be carefully applied. Vulvar CIS is generally symptomatic and pruritus is the most frequent symptom. It can be asymptomatic in a good number of cases (25% in our experience). The appearance of the vulvar CIS lesions is polymorphous since it depends on local hygiene, previous treatments, and its localization in the mucous membrane or in the skin. Vulvar CIS can sometimes be associated with LS or other vulvar dystrophies. This association may cause difficulties in the identification of the lesion. For this reason it is important to perform the Collins test and biopsies even in the most typical LS cases. In our experience, unifocal lesions were more frequent than multifocal ones; in other series [15,26], the results were opposite. Treatment should be individualized. Simple vulvectomy should be performed especially in the multifocal cases, in which the lesions have ill-defined borders or are associated with dystrophies [1,3,7,11,17,22,23]. Local excision should be reserved for unifocal lesions with well-defined borders [4,9,10,12,14,15,19]. It may be useful in young patients due to the preservation of the vulva for its sexual function or in very old patients because of the lesser surgical aggression. The use of radium needles may be indicated in the perimeatic localizations of vulvar CIS. All the treated CIS cases, by whatever method, must be controlled for life. Local recurrences (of which only one was observed by us) may appear even 13 years after the original treatment [1,4,7,10,16]. New therapeutic methods have been used in the last few years: cryosurgery [24], laser [ 141, topical treatment with 5-fluoruracil [ 181, and some substances with antigenic properties [12,14]. These destructive methods have good cosmetic results but impede a correct histological study and lengthen the treatment. However, they may be useful in special situations. REFERENCES 1. Abell, M. R., and Gosling, J. R. Intraepithelial and invasive carcinoma of the vulva, Cancer 14, 318 (1961). 2. Arrighi, L. A., di Paola, G. R., Balitia, L. M., Gomez Rueda, N., Belardi, M. G., and Illescas, L. Enfermedad de Bowen de la vulva, Rev. Sot. O&et. Ginecol. Buenos Aires 50, 97 (1971). 3. Barclay, D. L., and Collins, C. G. Intraephithelial carcinoma of the vulva, Amer. J. Obstet. Gynecol. 86, 9.5 (1963). 4. Buscema, J., Woodruff, J. D., Parmley, T. H. and Genadry, R. Carcinoma in situ of the vulva, Obstet. Gynecol. 55, 225 (1980). 5. Buscema, J., Stem, J. and Woodruff, J. D. The significance of the histologic alteration adjacent to invasive carcinoma of the vulva, Amer. J. Obstet. Gynecof. 137, 902 (1980). 6. Calandra, D., di Paola, G. R., G6mez Rueda, N., and Balitia L. M. Enfermedades de la vulva, Panamericana, Buenos Aires (1979).
242
DI
PAOLA
ET
AL.
7. Collins, C. G., Roman-L6pez, J. J. and Lee, F. Intraepithelial carcinoma of the vulva, Amer. J. Obstet. Gynecol. 108, 1187 (1970). 8. Collins, C. G., Hansen, L. H., and Theriot, E. A clinical stain for use in selecting biopsy sites in patients with vulvar diseases, Obsrel. Gynecol. 28, 158 (1966). 9. Corscaden, J. A. Gynecological cuncer, Williams & Wilkins, Baltimore (1956). 10. Dean, R. E., Stewart Taylor, E., Weisbrod, D. M., and Martin, J. W. The treatment of premalignant and malignant lesions of the vulva, Amer. J. Obstet. Gynecol. 119, 59 (1974). 11. di Paola, G. R., Consoli, F., and Belardi, M. G. Lesiones premalignas de la vulva, in Lesiones premalignas ginecologicas (L. A. Arrighi, J. E. Otturi, and N. G6mez Rueda, Eds.), p. 270, Ldpez Editores, Buenos Aires (1976). 12. di Paola, G. R., Gbmez Rueda, N., Itala, J. H., Vighi, S., and Provenzano, S. Carcinoma in situ de la vulva, Rev. Sot. Obstet. Ginecol. Buenos Aires 58, 301, (1979). 13. Franklin, E. W., and Rutledge, F. D. Prognostic factors in epidermoid carcinoma of the vulva, Obstet. Gynecol. 37, 892 (1971). 14. Friedrich, E. G., Jr. Vulvar disease, Saunders, Philadelphia (1976). 15. Friedrich, E. G., Jr., Wilkinson, E. J., and Yao Shi Fu. Carcinoma in situ of the vulva: A continuing challenge, Amer. J. Obstet. Gynecol. 136, 830 (1980). 16, Fomey, J. P., Morrow, G. P., Towsend, D. E., and DiSaia, P. J. Management of carcinoma in situ of the vulva, Amer. J. Obstet. Gynecol. 127, 801 (1977). 17. Gardner, H. L., and Kaufman, R. H. Benign diseases ofthe vulva and vagina, Mosby, St. Louis (1969). 18. Krupp, P. J., and Bohm, J. W. 5-Fluoruracil topical treatment of in situ vulvar cancer, Obstet. Gynecol. 51, 702 (1978). 19. Kunscher, A., Kanbour, A. I., and David, B. Early vulvar carcinoma, Amer. J. Obstet. Gynecol. 132, 599 (1978). 20. Porreco, R., Penn, I., Droegmueller, W., Green, B., and Makowki, E. Gynecologic malignancies in immunosuppressed organ homograft recipients, Obstet. Gynecol. 45, 359 (1975). 20. Porreco, R., Penn, I., Droegmueller, W., Green, B., and Makowki, E. Gynecologic malignancies in immunosuppressed organ homograft recipients, Obstet. Gynecol. 45, 359 (1975). 21. In Proceedings, Second international congress of the international society for the study of vulvar disease, Key Biscayne, Florida, (1975). 22. Rutledge, F. D., and Sinclair, M. Treatment of intraepithelial carcinoma of the vulva by skin excision and graft, Amer. J. Obstet. Gynecol. 102, 806 (1%8). 23. Sammartino, R. Estadios iniciales de1 carcinoma de vulva, in Enfermedades de la vulva: enfoque dermato-ginecolo&co (G. R. di Paola and L. M. Balifta, Eds.), p. 111, Panamericana, Buenos Aires (1970). 24. Towsend, D. E. Cryosurgery, in Obstetrics and Gynecology Annual (R. M. Wynn, Ed.), p. 331, Appleton, New York (1975). 25. Woodruff, J. D., and Hildebrandt, E. E. Carcinoma in situ of the vulva, Obstet. Gynecol. 12, 414 (1958). 26. 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 (1973).
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