Prevention of Cancer of the Vulva*

Fred 3. Taussig, M.D.

(From The Barnard Free Skin and Cancer Hospital, Saint Louis, Mo.)

(Received for publication May 7, 1941)

Scientific i~atvestigation concerning the cause and Urethral caruncle.--In urethral caruncle caused by prevention of cancer of the vulva has been retarded chronic infection of the urinary meatus the relation- by the relative rarity of the disease in the human race, ship is more definite. In one patient .the urethral the absence of suitable animals for control experi- caruncle was noted 4 years previous to the onset of mentation, and the absence of records of leukoplakic the cancer of the urinary meatus. So far as I know changes and cancer of the sexual skin in monkeys. no data are available on the frequency with which On the other hand, investigation of cancer of the vulva cancer develops from such a caruncle. Taking into is facilitated by the superficial location of the growth. consideration the relative incidence of these two con- Like other cancers of the skin, its early development ditions in practice, such a malignant change would can be watched and studied in relation to preceding not occur in over 5 per cent of the cases. In all such changes in the areas upon which cancer develops. If deductions we must guard ourselves against the fallacy the general statement is true that cancer does not of "post hoc, ergo propter hoc." It can, however, do ordinarily dewelop from normal healthy tissues, ex- no harm to excise or treat by radiation such chroni- tensive observations, generally accepted, indicate that cally infected urethras. It is reasonable to suppose this doctrine ~r seem to be particularly applicable that to some slight degree the incidence of cancer may in cancer of the vulva. thereby be reduced. Senile warts.--Senile warts are infrequently found. They must be distinguished from the relatively com- CLINICAL OBSERVATIONS mon acuminate warts associated with gonorrheal in- During the past 35 years I have observed i6i cases fection in younger individuals. The gonorrheal wart of cancer of the vulva. Of these, ioi patients had borne is typically cauliflower in structure with multiple small children, 42 were nulliparae, t i were virgins, and in nodular branches. The so-called senile wart on the 7 sufficient data were lacking (I). Approximately an other hand is simpler in structure, with larger nodules, equal number of cases of leukoplakic vulvitis, a condi- and covers a much smaller portion of the vulvar skin. tion which has been generally considered a forerunner It is a cluster of individual units rather than cauli- of this disease, were also observed during this period. flower in its shape. Senile warts are almost always In a report (i) of I55 cancers of the vulva made found in older women of uncleanly habits. Whereas last year the following possible etiologic factors were the ordinary acuminate warts usually appear and dis- listed: appear within a relatively short period of time, usually Leukoplakic vulvitis ...... 72 cases a few months, in the patients with senile warts these Syphilitic or postsyphilitic ulcers ...... 9 cases excrescenses have existed for many years. Since so Senile warts ...... 8 cases many of these women are not inconvenienced by th~se Bartholin gland abscess...... 4 cases warts, they do not seek medical advice. Therefore, Urethral caruncle ...... 3 cases we have no accurate data as to the frequency of this Trauma ...... 3 cases No definite lesions ...... 58 cases lesion. Without having actually counted the number of cases of senile warts seen in my clinical experi- It will be noted that in over one-third of the patients ences, I believe approximately one-half of these patients the history arxd findings gave no possible clew as to did not consult me until there had already developed any etiologic factor. In the 3 cases of trauma we at the site of these warty growths, a well-defined car- must acknowledge the uncertainty of the etiologic cinoma. In the way of prophylaxis the same rules relationship, since a small lesion may have been should apply to these vulvar warts as to warts in other present and the trauma merely served to accelerate portions of the integument. If the wart is subject to the growth. irritation or is enlarging it should be removed. On

* Read at the 34th annual meeting, American Association for the vulvar skin these warts are apt to be abraded by Cancer Research, Inc., Chicago, Illinois, April 15, I94I. the clothing and discharges in that area. In the 6 9oi

Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1941 American Association for Cancer Research. 902 Cancer Research cases reported in my series, the patients stated posi- our series out of i6i. One negress had a Bartholin tively that the warts had existed for months and years gland cancer. It would seem, therefore, that syphilis before the development of the ulcerating tumor. One and its sequellae, especially in the Negro race, play might perhaps assume that both the warts and the an important part in the etiology of vulvar cancer cancer developed from a third unknown underlying starting from the vestibular area. From a standpoint cause. Nevertheless the appearance of such senile of cancer prevention, therefore, the treatment of warts should have been a warning of possible trouble these granulomatous ulcers, so common in the Negro and hence should have justified their simple removal. race, is of great importance. Unfortunately, while we The recognition of this etiologic relationship would possess in the Frei test a reasonably accurate method doubtless serve in some cases to prevent and in others of diagnosis, the cure of the granulomas with tartar to make the early recognition of the disease more emetic and other agencies is still far from effective. likely. Leukoplakia.--The five etiologic factors thus far Abscess of Bartholin's gland.--Cancer of Bartholin's mentioned are relatively infrequent and statements gland is extremely rare. There are only 9 cases in my concerning them must be made with reservations. series. The fact that in 4 of these 9 patients there When it comes to leukoplakic vulvitis, its etiologic had existed an infection of this gland so pronounced relationship to cancer of that region seems established as to necessitate operative incision seems significant beyond any reasonable doubt. And the corollary of from an etiologic standpoint. In some of these patients this statement seems equally certain; namely, that by there was a history of a residual infection in this or- excising the leukoplakic area, we can often prevent gan. To suggest the routine removal of such infected the development of cancer at this point. This clinical glands in women past the menopause would seem a observation was recognized in the nineteenth century. bit too radical, but certainly in routine follow-up ex~ In i898 , J. Veit (2), writing in the Handbuch der aminations of women past the menopause this pos- GynM(ologie, records that from this atrophic vulvitis sible etiologic relationship should be kept in mind which he termed "Kraurosis," cancer eventually would and in the presence of any pain or enlargement, the develop in many instances. Hence, he says, the ex- gland should be excised. cision of the vulva was indicated not merely to relieve Syphilis.--The epithelial covering of the vulva can the pruritis but to reduce the chances for development be divided into the vestibular area between the hymen of cancer. and labia minora and the epidermal area comprising In the series of i6i cases of cancer of the vulva thus the remainder of the vulva. The latter has all the far observed, 74, or approximately 45 per cent, showed histologic characteristics of the skin, whereas the evidence of a preceding leukoplakic vulvitis. Since former resembles the squamous epithelium of the during the same period approximately twice that num- orifices. Cancer may arise from either site. Each has ber of cases of leukoplakic vulvitis were observed with- its distinctive etiology. In 9 out of I I vestibular can- out evidence of carcinoma, we may infer that of the cers, exclusive of those developing at the urinary total number of cases of leukoplakic vulvitis, approxi- meatus, there was a history of preceding syphilis. mately one-third proceded to the development of can- The diagnosis in all cases was established by typical cer. These figures correspond to those given by others skin lesions, positive Wassermann reactions, or a regarding the relationship between leukoplakic vul- combination ~of the two. In 5 patients, the Wasser- vitis and vulvar cancer. If we separate vulvar carci- mann reaction still remained positive. All of these noma according to its site, we find that in our series women showed extensive destructive granulomas or there were IO7 persons in whom the cancer originated hypertrophic masses in the region of the vulva or the in the epidermis itself. Since in other forms of cancer rectum in addition to the cancer. It was difficult to (Bartholin gland, vestibulum, urethra) leukoplakic decide how many of these should be classified as vulvitis did not enter as a possible etiologic factor, gummas and how many were lymphogranuloma the incidence of 74 cases of leukoplakic vulvitis in venereum. The frequency of associated rectovaginal I o 7 epidermal cancers has great significance. fistula and rectal strictures would point to the latter Histologic studies of the tissues removed by vul- diagnosis. The Frei test was positive in 3 instances vectomy in leukoplakic vulvitis and in cancer of the but 4 cases were observed previous to our present vulva associated with Ieukoplakic vulvitis tend to knowledge of such a test. Of the 9 patients with corroborate this etiologic relationship. As far as mor- such syphilitic or postsyphilitic ulcerative granulomas phologic studies go, we can follow step by step in a associated with cancer, 8 were Negroes. From a series of cases (though of course not in the same case) standpoint of racial predisposition it is of interest the gradations between the break in the basement that epidermal cancer of the vulva was very rare membrane in leukoplakic vulvitis to the well- among the Negroes, only 2 such cases occurring in developed carcinoma. In several cases the gross and

histologic picture has been such that I have been at associated with pruritis has developed at some unre- a loss whether to call it cancer or not. Since in either moved portion of the vulvar or peri-anal skin, this event a vulvectomy was advisable, further observa- area should be freely excised to prevent the develop- tion was not possible. Leukoplakic vulvitis has many ment of a cancer. In both cases above cited an inter- of the characters which we attribute to a precancerous val of several years had elapsed with some return of condition, such as epithelial prolongations, breaks in symptoms and when the patient finally came for ex- the basement membrane, irregularity of cell shape, amination cancer was already far advanced. In at round cell infiltration, etc. least 15 per cent of the vulvectomies for leukoplakic The comparison of leukoplakia of the mouth with vulvitis we find a recurrence of the leukoplakia, but leukoplakic vulvitis shows some similarities such as only very seldom does a cancer develop. the piling up of the squamous epithelium with a ten- The etiologic relationship between leukoplakic vul- dency to the subsequent development of a cancer. vitis and cancer of the vulva is further illustrated by There are, however, fundamental differences. In oral the cases in which the cancer is widely excised but leukoplakia the process is essentially hypertrophic some of the leukoplakic skin around the perineum whereas in vulvar leukoplakia a markedly atrophic and anus is allowed to remain. In 5 patients where process with destruction of elastic tissue fibers more such an island of leukoplakia was left or developed commonly precedes the formation of the keratotic in later years, a new carcinoma began to grow at this areas from which in some instances cancer develops. point. In each instance the long interval after the Out of the approximately 75 cases of leukoplakic removal of the original tumor and the gross and vulvitis upon which I have actually done a complete microscopic appearance of the new lesion left no removal of the lesion by partial or complete vul- doubt that we were not dealing with a metastatic re- vectomy, one third, 25, would according to our figures currence but with a fresh neoplasm starting on a re- have been expected to develop a carcinoma. By this maining leukoplakic area. In none of these 5 patients operative excision of the diseased vulvar skin, it seems were there distant glandular metastases or evidence likely, therefore, that 25 cancers were prevented from of other local implants. The relative frequency with development. However, even when a fairly complete which such new tumors developed points to a somatic vulvctomy has been done for the relief of the leuko- factor in addition to the local irritant responsible for plakic vulvitis and the prevention of a carcinoma, it the tumor formation. Such cases emphasize the neces- is not certain that in every case this goal has been sity of persistent re-examination in every patient who achieved, as seen in the following two cases: has had a leukoplakic vulvitis with or without the Case /.--Mrs. M. S. was operated upon by me at the age development of carcinoma. of 6o years for a leukoplakic vulvitis of long standing. A vulvectomy was done, but the pruritis returned one year later In this connection it is important to point out the at a point just beyond the area of skin removed. Unfortunately frequency with which we see multiple points of can- the patient did not return for re-examination as she had been cer development in vulvar leukoplakia. In some in- instructed. She was not seen from September 3 o, 193 o, until stances the lesions are so placed as to suggest a con- November 25, 1936. By this time she had developed an epithelioma 4 cm. in diameter in the right labial region with tact implantation but as a rule they are more widely evidence of leukoplakic change about it and the perineal region. separated. More than once a lesion about the clitoris The radical vulvectomy and double-sided Basset lymph gland has developed simultaneously with one over the removal was followed by a severe local infection aggravated perineo-anal skin. by an acute cholccystitis, and death occurred x4 days after operation. Estrogens.--Mention should be made of the possi- Case 2.--Mrs. K. M. (private paticnt of Dr. McNalley) con- ble influence of the estrogens on the development of suited him in June, i935, for pruritis vulvae. On October 29, leukoplakic vulvitis and cancer of the vulva. The 1935, a vulvectomy was done for a typical leukoplakic vulvitis. Microscopic examination at this time showed no evidence of average age of patients with leukoplakic vulvitis in cancer. In March, x936, she was entirely well. She. did not my series was 49 years and those with cancer was 59 return for further observation until July 25, I938, when years. Leukoplakic vulvitis is hardly ever seen before examination showed a tumor 6 cm. in diameter in the right the age of menopause except in the presence of some labial region rising from a remaining island of leukoplakia. The inguinal glands on the right side were enlarged and hard. ovarian disturbance or where both ovaries have been A right-sided Basset operation was done and radium applied surgically removed. Cancer of the vulva in persons locally. The inguinal glands showed cancer. There was rapid under 4 o years of age is practically never on a leuko- extension of the disease and the patient died 3 months later. plakic basis. If an estrogen deficiency is responsible From these two cases we must conclude that even for the atrophic changes leading to the development after a fairly radical vulvectomy we should insist upon of this so-called precancerous lesion, it is difficult to watching such patients at &month intervals for many explain the cancer itself as due to a carcinogen of years, and if it is found that an area of leukoplakia estrogenic origin.

SU1MMARY AND CONCLUSIONS lesions tending to the development of malignancy, which if promptly removed may lead to an appreci- Clinical observations on I6i cases of cancer of the able lowering in the incidence of cancer. vulva, seen in the author's practice during the past 35 years, are analyzed and discussed from the points REFERENCES of view of etiology and prevention. The chief condi- I. TAUSSlG, F. J. Cancer of the Vulva. An Analysis of 155 tions which appear to have etiological importance in Cases (191I-I94O). Am. J. Obst. & Gynec., 40:764-779. cancer of the vulva are urethral carnncle, senile warts, 194o. 2. VEIT, J. Die Erkrankungen der Vulva. Handbuch der abscess of Bartholin's gland, syphilis, and leukoplakia. Gyn~ikologie. Dritter Band. pp. 111-255. J. F. Berg- This etiologic study points to certain pre-existing mann, Wiesbaden, 1898.

Fred J. Taussig

Cancer Res 1941;1:901-904.

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