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Gynecologic cancer in children
GYNECOLOGIC CANCER IN CHILDREN J O H N A . KELLY, ~V~.D. N E W YORK, N. Y .
E true incidence of gynecologic cancer in children is difficult to T Hdetermine, but figures presented b y individuals and institutions re. porting large series of cases of neoplastic disease show that it is seldom encountered. Compared with its occurrence in adults, cancer of any t y p e is relatively rare in children, and especially in the female reproductive tract. Hall and Bagby, ~ r e p o r t i n g 134 proved cases of cancer in patients ranging f r o m 81/2 to 31 years of age, observed at the B e r n a r d Free Skin and Cancer Hospital f r o m 1908 to 1938, found six cases of cancer of the female genital tract, only one of w h i c h - - a colloid carcinoma of the o v a r y - - o c c u r r e d in a patient 15 years of age or younger. I n contrast to cancer in adults, cancer in children rarely involves the vulva, vagina, cervix, and corpus uteri. A m o n g adults the most common malignant neoplasm occurring in the female genitals is carcinoma of the cervix uteri. At the Memorial H o s p i t a l about 97 per cent of all cases of' p r i m a r y cervical cancer are epidermoid carcinoma. We have not personally observed a case of epidermoid carcinoma of the cervix in a child, though recently we have seen and treated an adenocarcinoma of tile cervix in a girl 16 years of age. Other observers, however, have seen carcinoma of the cervix in younger persons. Morse 2 reports a case of a highly cellular adenocareinoma of the cervix in a girl 10 years old. I n an exhaustive review of the literature he was able to find only one case of carcinoma of the vulva in a child. The lesion a p p a r e n t l y arose in the clitoris. He f o u n d only eight other cases of epithelial neoplasms involving cervix or corpus uteri. H e discusses these cases in detail and concludes that in three cases the diagnosis must be accepted with reservations; in two cases the information was incomplete, and in only three of the eight cases did the clinical and histologic evidence confirm the diagnosis of cancer. Since that time other proved cases have been added to the literature. Baldwin 8 reports a case of p r i m a r y m e d u l l a r y squamous carcinoma of the vagina occurring in a girl 14 years of age. I n 905 cases of cancer of the vulva, vagina, cervix, and corpus, proved by microscopic s t u d y at the University of Michigan Hospital, this was the only case of cancer of the female genitals occurring in a patient u n d e r 20 years of age. Glass ~ reports a case of carcinoma of the cervix in a girl 16 years of age, in which microscopic study showed both squamous and glandular elements From the Department of Gynecology, Memorial Hospital. Service of Dr. ~Villiam P. Healy. 354
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to be present. L u d w i g 5 reports a case of carcinoma of the cervix in a girl 16 years of age, which was treated b y means of r a d i u m and x-ray therapy. The p a t i e n t was alive, well, a n d free f r o m disease five years after treatment. Scheffey and Crawford G r e p o r t a case of adenocarcinoma of the cervix in a n infant 22 months old. Bonner 7 reports a case of p a p i l l a r y adenocarcinoma of the cervix in a Jewish child 13 years of age, though Jewish adults are less likely to develop carcinoma of the cervix t h a n women o3 other races. Gilbert, s in 1932, reported a case of carcinoma of the corpus uteri occurring in a girl 11 years of age. The histology was reviewed and confirmed by several authorities. A t that time Gilbert was able to find in the literature reports of only five other cases of carcinoma of the corpus uteri in patients u n d e r 15 years ol age. Lockhart, 9 in 1935, reported an extremely r a r e ease of adenocarcinoma of the corpus uteri, which occurred in a child 2 years and 3 months of age. Ewing, in confirming the histologic diagnosis, stated: " T h i s is an adenocarcinoma, p a p i l l a r y in type, with considerable infiltration of the uterine wall. I t is not distinctly embryonal, and does not differ greatly f r o m some endometrial carcinomas in a d u l t s . " I n comparison with these rare tumors, ovarian neoplasms in children are more extensively recorded in the literature. Although they occur more frequently, they f o r m only a relatively snm]l percentage of the diseases observed in female children. Histologically, these tumors are classified as embryonal carcinomas, sarcomas, teratomas, granulosa cell tumors, a n d mixed cell types which make accurate classification impossible. Wiel, 1~ in 1905, reported a large series of ovarian neoplasms occurring in children. I n more recent years Downes, ~l H u n t and Simon, 12 B l a n d a n d Goldstein, 1~ Anderson and Sheldon, ~ Levi, ~5 Lanman, 1G and others have reported cases or series of eases of malignant ovarian lesions in children. These tumors m a y occur at a v e r y early age. H u n t ' s p a t i e n t was 17 months old; 16 cases cited b y Downes were in girls u n d e r 10 years of age. I n adult life m a l i g n a n t ovarian neoplasms do not f o r m a large percentage of all cases of cancer of the female genitals. LevP 5 states that in 7,000 eases of cancer of all types observed at the Pondville Hospital, Massachusetts, f r o m 1927 to 1935, only 79 (or 0.011 per cent) were prim a r y m a l i g n a n t ovarian tumors, and not one of these patients was under 20 years of age. L a n m a n , 16 in 1929, reported five cases of ovarian tumors in children u n d e r 12 years of age out of a total of 12,260 admissions in ten years to the Children's Hospital, Boston. He observed, as have others, that difficulty was encountered in accurately classifying some of these tumors ; there were two carcinomas, two teratomas, and one dermoid cyst.
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DIAGNOSIS
Because of the rarity of these tumors the diagnosis is not infrequently missed at an early stage of the disease. This is particularly unfortunate in children, in whom the clinical course of the disease apparently moves to a fatal termination more rapidly than in adults. The importance of considering cancer as a possible diagnosis should be realized when any lesion occurs on the external genitals. Vaginal discharge in a child can be the manifestation of a neoplasm of the cervix or corpus, as well as of a Neisserian infection. Vaginal bleeding should immediately be investigated u n d e r anesthesia, so t h a t vagina, cervix, or corpus can be thoroughly examined. The short history in most eases of ovarian new growths emphasizes the necessity for careful abdominal and rectal examination, also u n d e r anesthesia if necessary, whenever a p a t i e n t complains of abdominal pain or backache. The presence of a pelvic or abdominal tumor calls for immediate surgical investigation. I n the eases of cancer of the genitals observed in children at the Memorial Hospital, there was an average delay of about five months between the onset of the first s y m p t o m and the arrival at a correct diagnosisl ANATOMIC
VARIETIES
In the period from 1930 to 1936, seven cases of cancer of the female genitals in children 15 years of age or younger were observed at the Memorial Hospital. Of these five were ovarian tumors, one was a leiomyosarcoma of the round ligament, and one was a melanoma of the vulva. It will be convenient to discuss the symptoms, the findings, and the treatment under the three separate headings of these type s . Melanoma of the Vulva.--This disease occurred in a child 14 years of age. The first s y m p t o m was the a p p e a r a n c e of a white spot about 13/~ cm. in diameter on the left side of the labium majus, about a year and a half before the patient was admitted to the Memorial Hospital. F o r one year there was no change in this lesion, but it then became bluish in color and enlarged rapidly. The past history was irrelevant, and, except for the lesion on the vulva, the general physical examination was essentially negative. The u p p e r half of the left labium m a j u s was involved by a sessile, ulcerated mass, measuring 6 b y 6 b y 41/2 cm. ( F i g . 1). The remaining skin over the lesion was deep blue in color, and streaks of discoloration extended out f r o m the t u m o r mass into the skin ~of the vulva. There was a firm fixed l y m p h node measuring 2.5 cm. in the left inguinal region. There Was no right inguinal a d e n o p a t h y n o r palpable abdominal masses, X - r a y films of the chest revealed no evidence of metastases. The method o f t r e a t m e n t was excision of the entire left vulva four days a f t e r admission to the hospital and removal of the t u m o r mass. At the same time dissection of tile left groin was carried out.
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The immediate postoperative course was uneventful. For about eight months, the patient was well and showed no evidence of iocal disease. A t this time pigmented lesions appeared on the back and tongue. Several of these were removed at another institution. When seen at the
Fig. L--Melanoma of the vulva in a child aged 14 years. After excision of the entire left vulva and dissection of an inguinal lymph node, the child showed no evidence of disease for a period of about eight months.
s 2.--Pigmented lesions which s h o w n i n F i g . 1, e i g h t m o n t h s a f t e r eralized metastases about ten weeks
appeared on the skin of the back of the patient the excision of the melanoma. She died of genlater.
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Memorial Hospital about this time, the patient showed multiple pigmented lesions of the skin of the back (Fig. 2). The vulva and groins showed no evidence of disease. Rectal examination revealed the presence of a tumor mass about the size of an orange in tile upper left pelvis. X-ray fihns of the chest now showed extensive metastatic disease throughout both lungs. Numerous lesions appeared on the legs, arms, and back, and the patient died about two and a half years after the onset of the first detectable symptom. Leiomyosarcoma.--The only case observed at the Memorial Hospital in this series occurred in all infant aged 16 months. The first indication was the appearance of a lump in the left groin about the size of a marble about four months before the patient was admitted to the Memorial Hospital. The tumor had been removed at another institution one month before the patient had been placed under observation at the Memorial Hospital. Except for the local lesion, the patient was in excellent physical condition. The groin showed considerable induration and thickening. X-ray examination revealed no evidence of pulmonary disease.
F i g . 3 . - - R e c u r r e n c e of a l e l o m y o s a r e o m a in a n i n f a n t e~ged 16 m o n t h s , m o n t h s a f t e r t h e ill'st a p p e a r a n c e of t h e d i s e a s e ,
who
d i e d 32
The treatment consisted of x-ray therapy to which the child responded very well. In less than two months, all evidence of disease had vanished, and the patient remained in good health and free of disease for about eight months, when a recurrent mass was noted in the left groin, extending into the left vulva. X-ray treatment was repeated for about a month, and then radon seeds were implanted in the mass of the left groin and vulva. Again the disease responded to treatment, and in two months there was no evidenee of disease. Nine months later, however, a suspicious area appeared in the left groin (Fig. 3). A course of Coley's toxin was administered, but no improvement was observed from this treatment.
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Films of the chest were repeatedly negative for evidence of metastatic disease, but the local lesion progressed gradually, broke down and ulcerated, and the child died about five months later, thirty-two months a f t e r the first a p p e a r a n c e of the disease. Ovarion Tumors.--Observations at the Memorial Hospital bear out the evidence t h a t these are the most frequent forms of cancer of the genitals in children, while in adult life they f o r m a relatively low pereentage of all eases of cancer of the genital organs. A t the time this s t u d y was made, 5,244~ eases of cancer of the female genitals had been observed at the Memorial Hospital. Of these, 434 cases were malignant ovarian tumors, either p r i m a r y or recurrent. They make up 8.27 per cent of the total. I n our present series of eases in children, five out of seven tumors of the female genitals were ovarian. The average age was 1 3 8 9 years. The oldest child was 15 years of age, a n d the youngest was 12. Histologically, two of these eases were classed as embryonal carcinomas, two as m a l i g n a n t teratomas, and the fifth as a myxoxanthosarcoma. The average period of delay between the onset of the first s y m p t o m and the arrival at a correct diagnosis was about three months.
Fig.
4.--Teratoma
of the ovary months after
r e m o v e d f r o m a c h i l d , a g e d 13 y e a r s . the first appearance of the tumor,
She died nine
I n three of these five eases diagnoses had first been made in other hospitals, and in two of these three eases the tumors had been removed before the girls a p p e a r e d for t r e a t m e n t at the Memorial H o s p i t a l ; the third ease had been inoperable. Of the two remaining eases of ovarian tumors, the diagnosis was made at the Memorial Hospital, where the patients were first treated.
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Of all five eases, only one patient had a history of trauma as a possible etiological factor. Three had symptoms of abnormal menses aeeompanying the onset of their illness. F o u r suffered early symptoms of severe pain, loeated, in two instances, in the lower quadrant of the abdomen in whieh the tumor was found, and in another case across the lower q u a d r a n t of the back. In three cases abdominal swelling was an early manifestation of the disease. Nausea and vomiting oeeurred in only one case in the early history of the onset. In most eases there were no significant general findings other than the lesion. All had palpable masses of either the p r i m a r y or the r e c u r r e n t tumor when observed at the Memorial Hospital. Reetal examination often diselosed their loeation. Of the three eases originally diagnosed elsewhere, only two received treatment. They both had inoperable tumors and were given x-ray therapy. I n one ease---a teratoma of the o v a r y - - t h e diameter of the abdomen was reduced by 3 era. in the course of three weeks. In the other ease--an embryonal eareinoma of the o v a r y - - t h e r e was an apparent reduction in the fluid formation, which had prevented the outlining of the tumor mass. The first patient lived about two years after the first objeetive symptom of the disease appeared, or one year after admission to the Memorial Hospital for treatment. The second patient died about six weeks after completion of x-ray therapy. X-ray t h e r a p y was prescribed for the third of these cases originally diagnosed in other hospit a l s - - a r e c u r r e n t embryonal eareinoma when observed at the Memorial H o s p i t a l - - b u t the patient never r e t u r n e d for treatment and was completely lost to follow-up. Of the two patients with ovarian tmnors first diagnosed at the Memorial Hospital, one was a teratoma, and the other a myxoxanthosareoma. The history of the first case needs special mention. About ten years before the patient was admitted to the Memorial Hospital for treatment of the ovarian tumor, she had an amputation of the leg for a huge eavernous angioma. F o r about seven years she had been having x-radiation t h e r a p y at the Memorial tIospital for recurrent tumor growth. W h e n the patient was 13 years of age, she developed the abdominal tumor whieh was treated as an intraabdominal hemangioma because of the coexisting cavernous hemangioma. The regression in the size of the tumor was so slight after completion of radiation therapy that the diagnosis was thought untenable. The abdomen was consequently explored, and a large lobulated tumor measuring 16 by 13 by 7 era. (Fig. 4) was removed and was identified as a malignant teratoid tumor of the ovary with fibrosareomatous and eareinomatous elements. The operation was :followed by x-radiation therapy, to whieh the patient responded very well. Five weeks after the operation there was no loeal evidence of disease; the patient had gained weight and was markedly improved in health. Six weeks later, however, the p a t i e n t beeame very ill. She had
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moved to the country where treatment was not available, and she died from an apparent recurrence of the tumor, about nine months after its first manifestation. The patient with myxoxanthosareoma was operated on in another hospital and has been well and symptom-free for two years. Thus of the five eases of ovarian tumors, one was lost to follow-up, three died from recurrent growths or generalized metastases after good initial responses to treatment, and one has been well and symptom-free for a period of about two years. TREATMENT
Since no one has the advantage of a wide experience in the treatment of cancer of the genital organs in children, the principles of treatment must be based on the experience gaine~l in the management of the same disease in adults. I t is acknowledged today by all gynecologists, in this country at least, that the best treatment for cancer of the cervix and corpus uteri is based on radiation therapy. The fact of the more rapid growth of tumor tissue in children would aecentuate the importance of instituting p r o m p t and aggressive x-ray and radium t h e r a p y in these cases, rather than resorting to surgery. In the ovarian tumors surgical removal is indicated in operable eases: first, because a fair percentage of ovarian tumors in children are benign, and, second, because cure has resulted from this procedure when the histology has been relatively low in the scale of malignant structure. In highly malignant types of tumors surgery should be p r o m p t l y supplemented by thorough radiation therapy. In inoperable and recurrent cases a fair degree of palliation has frequently been obtained by radiation therapy. E N D R E S U L T S AND PROGNOSIS
Accurate end-result figures in the treatment of cancer cannot be calculated until a given series of patients has been followed for a period of five years. We do not attempt, therefore, to compute an informative figure from the results of our series, because thus f a r no patient has been well and free of disease for that long a time. We may state, however, that the prognosis for gynecologic cancer in children is extremely unfavorable. Of our seven eases, five died in spite of good initial response to treatment, and one who was lost to follow-up without treatment is probably dead. Only one is well and symptom-free two years after treatment. SUMMARY A N D C O N C L U S I O N S
Cancer of the female genitals in children is a rare and usually a rapidly fatal disease. Its presence is to be suspected when vaginal discharge or unusual vaginal bleeding exists. Rectal and abdominal examinations are indicated in all cases of undiagnosed abdominal pain and backache.
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Any pelvic or abdominal tumor requires immediate surgical investigation. E a r l y diagnosis and prompt and efficient radiation therapy may improve the end results of the occasionally encountered ease of cancer of the vagina, cervix, and corpus. The alert pediatrician will always consider cancer as a possible diagnosis when any lesion occurs on the external genitalia of children. REFERENCES
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. ]6.
Hall, N., and Bagby~ J . W . : J . A . 1VL A. llO: 703, 1938. Morse, A . H . : Am. J. Obst. & Gyncc. 19: 520, 1930. Baldwin, L. G.: Am. J. Obst. & Gynec. 21: 728, 1931. Glass, M.: Am. J. Obst. & Gynec. 26: 104, ]933. Ludwig, D . B . : Am. J. Obst. & @ynec. 31: 536, 1936. Seheffey, L. C, ancl Crawford~ B . L . : Am. J. Obst. & G y~nec. 2~: 118, 1932. Bonner~ A.: Am. J. Obst. & Gynec. 14:]75~ 1927. Gilbert, J . B . : Am. J. 0bst. & Gy~ec. 2~: 402, 1932. Lockhart, t t . : Am. J. 0bst. & Gynee. 30: 76, 1935. Wiel, H . I . : Ball. Jolms Hopkins Itosp. 16: 102, 1905. Downes, W . k . : J.A.M.A. 76: 443, 1921. Iiunt, V. C., and Simon, H . E . : Ann. Surg. 87: 84, 1928. Bland, P. B., and Goldstein, L.: Surg. Gy~ee. & Obst. 61: 250, 1935. Anderson, 1Vf. X., and Sheldon, E . A . : Am. J. Obst. & Gynec. 34: ]19, 1937. Levi, A . A . : New England J. Med. 217: 595, 1935. Lanman, T. tI.: New England J. Med. 201: 555, 1929.
121 EAST SIXTIETH STI~EET
E true incidence of gynecologic cancer in children is difficult to T Hdetermine, but figures presented b y individuals and institutions re. porting large series of cases of neoplastic disease show that it is seldom encountered. Compared with its occurrence in adults, cancer of any t y p e is relatively rare in children, and especially in the female reproductive tract. Hall and Bagby, ~ r e p o r t i n g 134 proved cases of cancer in patients ranging f r o m 81/2 to 31 years of age, observed at the B e r n a r d Free Skin and Cancer Hospital f r o m 1908 to 1938, found six cases of cancer of the female genital tract, only one of w h i c h - - a colloid carcinoma of the o v a r y - - o c c u r r e d in a patient 15 years of age or younger. I n contrast to cancer in adults, cancer in children rarely involves the vulva, vagina, cervix, and corpus uteri. A m o n g adults the most common malignant neoplasm occurring in the female genitals is carcinoma of the cervix uteri. At the Memorial H o s p i t a l about 97 per cent of all cases of' p r i m a r y cervical cancer are epidermoid carcinoma. We have not personally observed a case of epidermoid carcinoma of the cervix in a child, though recently we have seen and treated an adenocarcinoma of tile cervix in a girl 16 years of age. Other observers, however, have seen carcinoma of the cervix in younger persons. Morse 2 reports a case of a highly cellular adenocareinoma of the cervix in a girl 10 years old. I n an exhaustive review of the literature he was able to find only one case of carcinoma of the vulva in a child. The lesion a p p a r e n t l y arose in the clitoris. He f o u n d only eight other cases of epithelial neoplasms involving cervix or corpus uteri. H e discusses these cases in detail and concludes that in three cases the diagnosis must be accepted with reservations; in two cases the information was incomplete, and in only three of the eight cases did the clinical and histologic evidence confirm the diagnosis of cancer. Since that time other proved cases have been added to the literature. Baldwin 8 reports a case of p r i m a r y m e d u l l a r y squamous carcinoma of the vagina occurring in a girl 14 years of age. I n 905 cases of cancer of the vulva, vagina, cervix, and corpus, proved by microscopic s t u d y at the University of Michigan Hospital, this was the only case of cancer of the female genitals occurring in a patient u n d e r 20 years of age. Glass ~ reports a case of carcinoma of the cervix in a girl 16 years of age, in which microscopic study showed both squamous and glandular elements From the Department of Gynecology, Memorial Hospital. Service of Dr. ~Villiam P. Healy. 354
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to be present. L u d w i g 5 reports a case of carcinoma of the cervix in a girl 16 years of age, which was treated b y means of r a d i u m and x-ray therapy. The p a t i e n t was alive, well, a n d free f r o m disease five years after treatment. Scheffey and Crawford G r e p o r t a case of adenocarcinoma of the cervix in a n infant 22 months old. Bonner 7 reports a case of p a p i l l a r y adenocarcinoma of the cervix in a Jewish child 13 years of age, though Jewish adults are less likely to develop carcinoma of the cervix t h a n women o3 other races. Gilbert, s in 1932, reported a case of carcinoma of the corpus uteri occurring in a girl 11 years of age. The histology was reviewed and confirmed by several authorities. A t that time Gilbert was able to find in the literature reports of only five other cases of carcinoma of the corpus uteri in patients u n d e r 15 years ol age. Lockhart, 9 in 1935, reported an extremely r a r e ease of adenocarcinoma of the corpus uteri, which occurred in a child 2 years and 3 months of age. Ewing, in confirming the histologic diagnosis, stated: " T h i s is an adenocarcinoma, p a p i l l a r y in type, with considerable infiltration of the uterine wall. I t is not distinctly embryonal, and does not differ greatly f r o m some endometrial carcinomas in a d u l t s . " I n comparison with these rare tumors, ovarian neoplasms in children are more extensively recorded in the literature. Although they occur more frequently, they f o r m only a relatively snm]l percentage of the diseases observed in female children. Histologically, these tumors are classified as embryonal carcinomas, sarcomas, teratomas, granulosa cell tumors, a n d mixed cell types which make accurate classification impossible. Wiel, 1~ in 1905, reported a large series of ovarian neoplasms occurring in children. I n more recent years Downes, ~l H u n t and Simon, 12 B l a n d a n d Goldstein, 1~ Anderson and Sheldon, ~ Levi, ~5 Lanman, 1G and others have reported cases or series of eases of malignant ovarian lesions in children. These tumors m a y occur at a v e r y early age. H u n t ' s p a t i e n t was 17 months old; 16 cases cited b y Downes were in girls u n d e r 10 years of age. I n adult life m a l i g n a n t ovarian neoplasms do not f o r m a large percentage of all cases of cancer of the female genitals. LevP 5 states that in 7,000 eases of cancer of all types observed at the Pondville Hospital, Massachusetts, f r o m 1927 to 1935, only 79 (or 0.011 per cent) were prim a r y m a l i g n a n t ovarian tumors, and not one of these patients was under 20 years of age. L a n m a n , 16 in 1929, reported five cases of ovarian tumors in children u n d e r 12 years of age out of a total of 12,260 admissions in ten years to the Children's Hospital, Boston. He observed, as have others, that difficulty was encountered in accurately classifying some of these tumors ; there were two carcinomas, two teratomas, and one dermoid cyst.
356
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JOURNAL
OF P E D I A T R I C S
DIAGNOSIS
Because of the rarity of these tumors the diagnosis is not infrequently missed at an early stage of the disease. This is particularly unfortunate in children, in whom the clinical course of the disease apparently moves to a fatal termination more rapidly than in adults. The importance of considering cancer as a possible diagnosis should be realized when any lesion occurs on the external genitals. Vaginal discharge in a child can be the manifestation of a neoplasm of the cervix or corpus, as well as of a Neisserian infection. Vaginal bleeding should immediately be investigated u n d e r anesthesia, so t h a t vagina, cervix, or corpus can be thoroughly examined. The short history in most eases of ovarian new growths emphasizes the necessity for careful abdominal and rectal examination, also u n d e r anesthesia if necessary, whenever a p a t i e n t complains of abdominal pain or backache. The presence of a pelvic or abdominal tumor calls for immediate surgical investigation. I n the eases of cancer of the genitals observed in children at the Memorial Hospital, there was an average delay of about five months between the onset of the first s y m p t o m and the arrival at a correct diagnosisl ANATOMIC
VARIETIES
In the period from 1930 to 1936, seven cases of cancer of the female genitals in children 15 years of age or younger were observed at the Memorial Hospital. Of these five were ovarian tumors, one was a leiomyosarcoma of the round ligament, and one was a melanoma of the vulva. It will be convenient to discuss the symptoms, the findings, and the treatment under the three separate headings of these type s . Melanoma of the Vulva.--This disease occurred in a child 14 years of age. The first s y m p t o m was the a p p e a r a n c e of a white spot about 13/~ cm. in diameter on the left side of the labium majus, about a year and a half before the patient was admitted to the Memorial Hospital. F o r one year there was no change in this lesion, but it then became bluish in color and enlarged rapidly. The past history was irrelevant, and, except for the lesion on the vulva, the general physical examination was essentially negative. The u p p e r half of the left labium m a j u s was involved by a sessile, ulcerated mass, measuring 6 b y 6 b y 41/2 cm. ( F i g . 1). The remaining skin over the lesion was deep blue in color, and streaks of discoloration extended out f r o m the t u m o r mass into the skin ~of the vulva. There was a firm fixed l y m p h node measuring 2.5 cm. in the left inguinal region. There Was no right inguinal a d e n o p a t h y n o r palpable abdominal masses, X - r a y films of the chest revealed no evidence of metastases. The method o f t r e a t m e n t was excision of the entire left vulva four days a f t e r admission to the hospital and removal of the t u m o r mass. At the same time dissection of tile left groin was carried out.
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The immediate postoperative course was uneventful. For about eight months, the patient was well and showed no evidence of iocal disease. A t this time pigmented lesions appeared on the back and tongue. Several of these were removed at another institution. When seen at the
Fig. L--Melanoma of the vulva in a child aged 14 years. After excision of the entire left vulva and dissection of an inguinal lymph node, the child showed no evidence of disease for a period of about eight months.
s 2.--Pigmented lesions which s h o w n i n F i g . 1, e i g h t m o n t h s a f t e r eralized metastases about ten weeks
appeared on the skin of the back of the patient the excision of the melanoma. She died of genlater.
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Memorial Hospital about this time, the patient showed multiple pigmented lesions of the skin of the back (Fig. 2). The vulva and groins showed no evidence of disease. Rectal examination revealed the presence of a tumor mass about the size of an orange in tile upper left pelvis. X-ray fihns of the chest now showed extensive metastatic disease throughout both lungs. Numerous lesions appeared on the legs, arms, and back, and the patient died about two and a half years after the onset of the first detectable symptom. Leiomyosarcoma.--The only case observed at the Memorial Hospital in this series occurred in all infant aged 16 months. The first indication was the appearance of a lump in the left groin about the size of a marble about four months before the patient was admitted to the Memorial Hospital. The tumor had been removed at another institution one month before the patient had been placed under observation at the Memorial Hospital. Except for the local lesion, the patient was in excellent physical condition. The groin showed considerable induration and thickening. X-ray examination revealed no evidence of pulmonary disease.
F i g . 3 . - - R e c u r r e n c e of a l e l o m y o s a r e o m a in a n i n f a n t e~ged 16 m o n t h s , m o n t h s a f t e r t h e ill'st a p p e a r a n c e of t h e d i s e a s e ,
who
d i e d 32
The treatment consisted of x-ray therapy to which the child responded very well. In less than two months, all evidence of disease had vanished, and the patient remained in good health and free of disease for about eight months, when a recurrent mass was noted in the left groin, extending into the left vulva. X-ray treatment was repeated for about a month, and then radon seeds were implanted in the mass of the left groin and vulva. Again the disease responded to treatment, and in two months there was no evidenee of disease. Nine months later, however, a suspicious area appeared in the left groin (Fig. 3). A course of Coley's toxin was administered, but no improvement was observed from this treatment.
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Films of the chest were repeatedly negative for evidence of metastatic disease, but the local lesion progressed gradually, broke down and ulcerated, and the child died about five months later, thirty-two months a f t e r the first a p p e a r a n c e of the disease. Ovarion Tumors.--Observations at the Memorial Hospital bear out the evidence t h a t these are the most frequent forms of cancer of the genitals in children, while in adult life they f o r m a relatively low pereentage of all eases of cancer of the genital organs. A t the time this s t u d y was made, 5,244~ eases of cancer of the female genitals had been observed at the Memorial Hospital. Of these, 434 cases were malignant ovarian tumors, either p r i m a r y or recurrent. They make up 8.27 per cent of the total. I n our present series of eases in children, five out of seven tumors of the female genitals were ovarian. The average age was 1 3 8 9 years. The oldest child was 15 years of age, a n d the youngest was 12. Histologically, two of these eases were classed as embryonal carcinomas, two as m a l i g n a n t teratomas, and the fifth as a myxoxanthosarcoma. The average period of delay between the onset of the first s y m p t o m and the arrival at a correct diagnosis was about three months.
Fig.
4.--Teratoma
of the ovary months after
r e m o v e d f r o m a c h i l d , a g e d 13 y e a r s . the first appearance of the tumor,
She died nine
I n three of these five eases diagnoses had first been made in other hospitals, and in two of these three eases the tumors had been removed before the girls a p p e a r e d for t r e a t m e n t at the Memorial H o s p i t a l ; the third ease had been inoperable. Of the two remaining eases of ovarian tumors, the diagnosis was made at the Memorial Hospital, where the patients were first treated.
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THE
J O U R N A L OF P E D I A T R I C S
Of all five eases, only one patient had a history of trauma as a possible etiological factor. Three had symptoms of abnormal menses aeeompanying the onset of their illness. F o u r suffered early symptoms of severe pain, loeated, in two instances, in the lower quadrant of the abdomen in whieh the tumor was found, and in another case across the lower q u a d r a n t of the back. In three cases abdominal swelling was an early manifestation of the disease. Nausea and vomiting oeeurred in only one case in the early history of the onset. In most eases there were no significant general findings other than the lesion. All had palpable masses of either the p r i m a r y or the r e c u r r e n t tumor when observed at the Memorial Hospital. Reetal examination often diselosed their loeation. Of the three eases originally diagnosed elsewhere, only two received treatment. They both had inoperable tumors and were given x-ray therapy. I n one ease---a teratoma of the o v a r y - - t h e diameter of the abdomen was reduced by 3 era. in the course of three weeks. In the other ease--an embryonal eareinoma of the o v a r y - - t h e r e was an apparent reduction in the fluid formation, which had prevented the outlining of the tumor mass. The first patient lived about two years after the first objeetive symptom of the disease appeared, or one year after admission to the Memorial Hospital for treatment. The second patient died about six weeks after completion of x-ray therapy. X-ray t h e r a p y was prescribed for the third of these cases originally diagnosed in other hospit a l s - - a r e c u r r e n t embryonal eareinoma when observed at the Memorial H o s p i t a l - - b u t the patient never r e t u r n e d for treatment and was completely lost to follow-up. Of the two patients with ovarian tmnors first diagnosed at the Memorial Hospital, one was a teratoma, and the other a myxoxanthosareoma. The history of the first case needs special mention. About ten years before the patient was admitted to the Memorial Hospital for treatment of the ovarian tumor, she had an amputation of the leg for a huge eavernous angioma. F o r about seven years she had been having x-radiation t h e r a p y at the Memorial tIospital for recurrent tumor growth. W h e n the patient was 13 years of age, she developed the abdominal tumor whieh was treated as an intraabdominal hemangioma because of the coexisting cavernous hemangioma. The regression in the size of the tumor was so slight after completion of radiation therapy that the diagnosis was thought untenable. The abdomen was consequently explored, and a large lobulated tumor measuring 16 by 13 by 7 era. (Fig. 4) was removed and was identified as a malignant teratoid tumor of the ovary with fibrosareomatous and eareinomatous elements. The operation was :followed by x-radiation therapy, to whieh the patient responded very well. Five weeks after the operation there was no loeal evidence of disease; the patient had gained weight and was markedly improved in health. Six weeks later, however, the p a t i e n t beeame very ill. She had
KELLY :
GYNECOLOGIC CANCER
361
moved to the country where treatment was not available, and she died from an apparent recurrence of the tumor, about nine months after its first manifestation. The patient with myxoxanthosareoma was operated on in another hospital and has been well and symptom-free for two years. Thus of the five eases of ovarian tumors, one was lost to follow-up, three died from recurrent growths or generalized metastases after good initial responses to treatment, and one has been well and symptom-free for a period of about two years. TREATMENT
Since no one has the advantage of a wide experience in the treatment of cancer of the genital organs in children, the principles of treatment must be based on the experience gaine~l in the management of the same disease in adults. I t is acknowledged today by all gynecologists, in this country at least, that the best treatment for cancer of the cervix and corpus uteri is based on radiation therapy. The fact of the more rapid growth of tumor tissue in children would aecentuate the importance of instituting p r o m p t and aggressive x-ray and radium t h e r a p y in these cases, rather than resorting to surgery. In the ovarian tumors surgical removal is indicated in operable eases: first, because a fair percentage of ovarian tumors in children are benign, and, second, because cure has resulted from this procedure when the histology has been relatively low in the scale of malignant structure. In highly malignant types of tumors surgery should be p r o m p t l y supplemented by thorough radiation therapy. In inoperable and recurrent cases a fair degree of palliation has frequently been obtained by radiation therapy. E N D R E S U L T S AND PROGNOSIS
Accurate end-result figures in the treatment of cancer cannot be calculated until a given series of patients has been followed for a period of five years. We do not attempt, therefore, to compute an informative figure from the results of our series, because thus f a r no patient has been well and free of disease for that long a time. We may state, however, that the prognosis for gynecologic cancer in children is extremely unfavorable. Of our seven eases, five died in spite of good initial response to treatment, and one who was lost to follow-up without treatment is probably dead. Only one is well and symptom-free two years after treatment. SUMMARY A N D C O N C L U S I O N S
Cancer of the female genitals in children is a rare and usually a rapidly fatal disease. Its presence is to be suspected when vaginal discharge or unusual vaginal bleeding exists. Rectal and abdominal examinations are indicated in all cases of undiagnosed abdominal pain and backache.
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THE JOURNAL OF PEDIATRICS
Any pelvic or abdominal tumor requires immediate surgical investigation. E a r l y diagnosis and prompt and efficient radiation therapy may improve the end results of the occasionally encountered ease of cancer of the vagina, cervix, and corpus. The alert pediatrician will always consider cancer as a possible diagnosis when any lesion occurs on the external genitalia of children. REFERENCES
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. ]6.
Hall, N., and Bagby~ J . W . : J . A . 1VL A. llO: 703, 1938. Morse, A . H . : Am. J. Obst. & Gyncc. 19: 520, 1930. Baldwin, L. G.: Am. J. Obst. & Gynec. 21: 728, 1931. Glass, M.: Am. J. Obst. & Gynec. 26: 104, ]933. Ludwig, D . B . : Am. J. Obst. & @ynec. 31: 536, 1936. Seheffey, L. C, ancl Crawford~ B . L . : Am. J. Obst. & G y~nec. 2~: 118, 1932. Bonner~ A.: Am. J. Obst. & Gynec. 14:]75~ 1927. Gilbert, J . B . : Am. J. 0bst. & Gy~ec. 2~: 402, 1932. Lockhart, t t . : Am. J. 0bst. & Gynee. 30: 76, 1935. Wiel, H . I . : Ball. Jolms Hopkins Itosp. 16: 102, 1905. Downes, W . k . : J.A.M.A. 76: 443, 1921. Iiunt, V. C., and Simon, H . E . : Ann. Surg. 87: 84, 1928. Bland, P. B., and Goldstein, L.: Surg. Gy~ee. & Obst. 61: 250, 1935. Anderson, 1Vf. X., and Sheldon, E . A . : Am. J. Obst. & Gynec. 34: ]19, 1937. Levi, A . A . : New England J. Med. 217: 595, 1935. Lanman, T. tI.: New England J. Med. 201: 555, 1929.
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