Bladder tumors in children

BLADDER BISWAMAY

TUMORS

RAY, M.D.

HARRY

GRABSTALD,

PHILIP

R. EXELBY,

WILLET

IN CHILDREN

M.D. M.D.

F. WHITMORE,

JR., M.D.

From the Urologic Service, and Departments and Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York

of Surgery

ABSTRACT-Our experience with bladder tumors in children is presented and the pertinent literature reviewed. Nonepithelial tumors are more common than epithelial ones, and the most common symptom is bladder outlet obstruction. Papilloma, the common epithelial tumor, usually presents with hematuria and is successfully treated by transurethral methods. Treatment of bladder neurofibroma will depend on the site and size of the tumor and on resultant symptoms and obstruction; small or moderate-size nodules may be amenable to transurethral resection, local excision, or segmental resection, but for di$use involvement of the bladder, total cystectomy may be necessary. Hemangiomas are the most common benign connective tissue tumor, and their common location in the upper part of the bladder usually permits successful treatment by open excision or segmental resection. Rhabdomyosarcoma is the most common bladder tumor in children. On present evidence radical cystectomy is the treatment of choice. The contributions of adjunct radio- and chemotherapy are not well defined, but such treatment is recommended since it has contributed to the control of tumor in nonresectable cases. Four of 8 patients in this series are alive and well five and one-half to seventeen years, 3 having hadradical cystectomy (with radiotherapy in 2 and chemotherapy in 1) and 1 segmental resection with of the bladder has been controlled by segmental resection, radio- and chemotherapy. Leiomyosarcoma but it is logical to believe that radical cystectomy would extend the possibilities of surgical control in some cases; adjunct irradiation and chemotherapy may deserve a place in treatment as well.

Tumors of the urinary bladder are rare in infancy and childhood. During a thirty-year period (1940 to 1969), 16 such tumors were seen at Memorial Sloan-Kettering Cancer Center. Seven of these tumors were benign, 4 were papilloma, 1 neurofibroma, and 2 hemangiomas. Nine children had malignant tumors, 8 were embryonal rhabdomyosarcoma and 1 leiomyosarcoma. These 16 cases are reported here (Table I). Clinical

Aspects

Papilloma Three boys and 1 girl had solitary papillary tumors near a ureteral orifice, varying from 4 mm. to 2.5 cm. in diameter. All had gross hematuria from two to six months prior to treatment. There

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was no hydronephrosis. All patients are free of tumor from twenty to one hundred eight months following transurethral resection and fulguration (Table I). Neuro$broma A thirteen-year-old boy had neurofibroma involving bladder and other pelvic structures. At age nine a neurofibroma of the right submandibular region had been excised. Two months prior to admission to Memorial Hospital, examination revealed a neurofibroma of the right posterior thigh and a mass in the lower part of the abdomen. After radiographic and cystoscopic studies excluded intrinsic bladder involvement, laparotomy elsewhere revealed a bulky pelvic tumor which showed neurofibroma on biopsy.

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Bladder tumors in children

TABLE I.

Diagnosis*

Age at Diagnosis (Years)

Sex

1

P

8

F

Hematuria

2

P

10

M

Hematuria

3

P

12

M

Hematuria

4

P

18

M

Hematuria

5 6 7

N H H

13 7.5 4

M M M

Abdominal mass Hematuria Hematuria

8

ER

3.5

M

Frequency, incontinence, difficulty in voiding, hematuria, urinary retention

9

ER

1.5

F

10

ER

4

M

Frequency, difficulty in voiding, dysuria, passage of tissue per urethra Hematuria

11

ER

M

Hematuria,

12

ER

M

Difficulty in voiding, urinary retention

13

ER

10

M

Difficulty in voiding, urinary retention, hematuria, incontinence

14

ER

11 months

M

Difficulty in voiding, urinary retention

15

ER

‘6

M

Difficulty in voiding, urinary retention

16

LS

M

Dysuria

Patient Number

7

*KEY: P = Papilloma, N = Neurofibroma, disease.

Treatment

Symptoms

H = Hemangioma,

dysuria

Resection and fulguration of the base Resection and fulguration of the base Resection and fulguration of the base Resection and fulguration of the base Radical cystectomy Segmental resection Radiation therapy; segmental resection Segmental resection and suprapubic cystostomy; radical cystectomy and pelvic node dissection; postoperative radio- and chemotherapy Preoperative radiotherapy; anterior exenteration Segmental resection and right ureteroneocystostomy; radio- and chemotherapy Segmental resection; radical cystectomy, pelvic node dissection Suprapubic cystostomy, biopsy; external radiotherapy; insertion of radon seeds; chemotherapy, radical cystourethrectomy, pelvic node dissection, ileal conduit External radiation therapy, radical cystectomy, pelvic node dissection, anterior resection of rectum, cutaneous ureterostomies, postoperative radiotherapy for recurrence Suprapubic cystostomy, electroresection; radical cystectomy and ureterosigmoidostomies; chemotherapy Suprapubic excision; radio- and chemotherapy; nephrostomy

Incomplete excision of tumor by segmental resection, suprapubic cystostomy; chemotherapy; exploratory laparotomy, nonresectable tumor, construction of ileal conduit; radio- and chemotherapy; reexploration for bowel obstruction, no evidence of tumor ER = Embryonal

rhabdomyosarcoma,

Result NED*

9 years

NED 3 years, 4 months NED 1 year, 8 months NED 8 years NED 13 years, 3 months NED 5 years NED 18 years NED 11 years

NED 5 years, 8 months

NED 5 years, 6 months

NED 17 years

Dead in 32 months; metastasis in lungs, liver, brain; no pelvic recurrence

Dead in 20 months; extensive disease in abdomen and pelvis

Dead in 18 months; extensive disease in abdomen and pelvis

Dead in 10 months; pulmonary metastasis, extensive disease in pelvis, abdomen, perineum, and penis NED 4 years, 6 months

LS = Leiomyosarcoma,

NED = No evidence of

The child was referred to Memorial Hospital where the pertinent physical findings included scattered lesions of von Recklinghausen’s neurofibromatosis, a right submandibular scar with underlying thickening, right facial weakness, a long scar in the lower midline, a 14 by 8 cm. neurofibroma on the posterior right upper thigh, a suprapubic mass, and a bulky, smooth, nontender, rubbery tumor filling the entire anterior half of the pelvis on rectal examination. Results of laboratory studies and intravenous pyelograms were normal. Review of the previous bladder biopsies revealed plexiform neuroma. Preliminary cystoscopic examination revealed no intrinsic vesicle lesion, and on September 9, 1958, laparotomy revealed a bulky, nodular tumor with an origin from the superior aspect of the bladder and an apparently separate mass involving the prostate. There were numerous apparent neuromas arising from the lateral sacral sympathetic chains, presacral nerve plexus, and right obturator nerve. Because of the imminence of ureteral and intestinal obstruction and because there seemed no reasonable alternative, radical cystectomy was performed and an ileal conduit constructed. The pathologic report was neurofibromatosis (plexiform neuroma) involving bladder, prostate, and distal ureters without nodal involvement but with numerous independent sites of neurofibroma formation in the perivesical tissues, the presacral plexus, and the lateral sympathetic chains. His postoperative course was uneventful, and he was discharged on the tenth postoperative day. He was readmitted in 1962 for excision of plexiform neuromas of the right thigh and right mandibular region. An intravenous pyelogram at that time showed normal findings. He has remained free of recurrent disease. An intravenous pyelogram on December 14, 1971, thirteen years and three months after cystectomy, revealed normal kidneys and slightly dilated ureters with good drainage.

Hemangioma Two boys, four and seven and one-half years of age at the time of diagnosis of bladder hemangiomas, are surviving five and eighteen years, respectively, after segmental resection of the bladder lesions (Table I). Both have hemangiomas elsewhere. These cases have been reported previously.1*2

Embryonal rhabdomyosarcoma (sarcoma botryoides) Of 8 children (6 reported by Mackenzie, Whitmore and Melamed3), 4 survive and 4 have died

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(Table I). Three boys and 1 girl, one and one-half to five years of age, are alive and apparently free of disease five and one-half to seventeen years after various forms of treatment and are described in some detail. Case 1. A three and one-half-year-old white boy had urinary frequency, dysuria, hematuria, and finally urinary retention. He was seen with a cystostomy tube in place after segmental bladder resection with incomplete removal of the tumor was done elsewhere on July 14, 1961 (Fig. 1). Results of physical examination were normal except for a healing, lower abdominal midline scar and a cystostomy tube. Chest and skeletal x-ray survey gave negative findings. Intravenous pyelogram revealed grade I and II hydroureteronephrosis on the right and left sides, respectively. Cystogram showed elevation of the bladder, right ureteral reflux, and marked irregularity of the left lateral wall extending to the bladder neck. On August 2,1961, the patient underwent radical cystectomy, bilateral pelvic node dissection, and construction of an ileal conduit. The pathologic diagnosis was botryoid embryonal rhabdomyosarcoma involving dome and neck of the bladder and prostate; pelvic lymph nodes were negative for disease. Although there was no gross residual disease after cystectomy both prophylactic radio- and chemotherapy were given postoperatively, utilizing 2,440 rads with a Cobalt-60 unit to the lower half of the abdomen and perineum from August 11, 1961, to September 26, 1961, and a total dose of 1,000 micrograms (75 micrograms per kilogram) of actinomycin D in 4 divided doses October 4 to 11, 1961. Nine years after surgery a routine pyelogram revealed progression of a right hydronephrosis which first appeared five years after cystectomy (Fig. 2). On August 20, 1970, exploration revealed no evidence of recurrent disease. A side-to-side anastomosis of the right ureter to the ileal conduit was done with subsequent stabilization of the right hydronephrosis (Fig. 3).

Case 2. A seventeen-month-old Venezuelan girl developed frequency, dysuria, and strangury in March, 1967. Elsewhere, intravenous pyelogram revealed normal upper tracts, elevation of the bladder floor, and multiple vesical filling defects, and cystoscopy revealed “edematous tumor-like area” in the right trigone and bladder wall. She was treated with antibiotics without benefit and following spontaneous passage of cystic and gelatinous tissue per urethra from which a pathologic diagnosis of sarcoma bot-

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FIGURE 1. (A) Zntravenous pyelogram showing bilateral hydroureteronephrosis, and (B) cystogram strating elevation of bladder jloor and irregular filling defect in both lateral walls.

demon-

FIGURE 2. Intravenous pyelograms. (A) Five months postradical cystectomy showing normal collecting systems bilaterally, and (B) nine years later showing progressive right hydroureteronephrosis.

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FIGURE 3. Side-to-side ureteroileal conduit anastomosis.

ryoides was made, she was placed on catheter drainage and referred to Memorial Hospital. The pertinent physical findings were suprapubic fullness and a soft, movable mass 4 to 5 cm. in diameter apparently arising from the bladder on rectal examination. Intravenous pyelogram on April 27, 1967, revealed right hydroureteronephrosis consistent with ureterovesical junction obstruction and a bladder tumor which had increased in size when compared with previous films. Results of chest and skeletal x-ray survey, bone marrow biopsy, and urine cytology were normal. Preoperatively a total dose of 1,000 rads was delivered to the bladder through an 8 by 10 cm. portal in six days via Cobalt-60 unit. On May 4, 1967, anterior exenteration, bilateral pelvic lymph node dissection, and construction of an ileal conduit were performed. The ovaries were preserved. There was no evidence of extravesical tumor. The pathologic diagnosis was botryoid embryonal rhabdomyosarcoma of the bladder arising from the posterior and right lateral walls, penetrating superficially into muscularis, and partially obstructing the right ureteral orifice. The pelvic lymph nodes were normal. The postoperative course was uneventful. A course of actinomycin D therapy was advised but refused by the child’s parents. An intravenous pyelogram in March, 1969, revealed normal kidneys and pelvicalyceal systems. The child was free of disease in November, 1972.

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Case 3. A four-year-old boy had gross painless hematuria and low-grade fever in September, 1966. Intravenous pyelogram revealed a large filling defect in the right side of the bladder. Cystoscopy revealed a large grape-like tumor covering the right ureteral orifice. On September 16, 1966, the patient underwent partial cystectomy with excision of the distal right ureter and ureteroneocystostomy and was then referred to Memorial Hospital. Pathologic examination revealed embryonal rhabdomyosarcoma. Physical examination showed shotty lymph nodes in both groins and a fixed mass in the right pelvis was noted on rectal examination, Results of chest and skeletal x-ray survey were negative. Intravenous pyelogram on October 13, 1966, revealed grade III right hydronephrosis. Cystogram showed a bladder filling defect. He was treated with radio- and chemotherapy in anticipation of later possible radical cystectomy, receiving 3,450 rads to the pelvis and para-aortic area via Cobalt-60 from October 18, 1966, to November 17, 1966, and chemotherapy with actinomycin D, 10 micrograms per kilogram per day from October 14 to 27, 1966. The urinary symptoms subsided, the lymph nodes in both groins became unpalpable, and the pelvic mass disappeared. Plans for surgery were refused by the child’s mother. In January, 1967, bilateral inguinal nodes were again noted. He received 1,360 micrograms of actinomycin D from November 16, 1966, to

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January 23, 1967. Chest x-ray film on February 3, 1967, revealed left pulmonary metastasis. He was then treated cyclicahy with cyclophosphamide (Cytoxan) and vincristine from February, 1967, to January, 1968. In this interval the left pulmonary metastasis first regressed completely and then recurred. Radiotherapy with Cobalt-60 unit was given from January 10, 1968, to February 13,1968, to the solitary metastatic focus in the left midlung field, delivering 3,500 rads. Chest x-ray film on January 25, 1968, revealed complete disappearance of the left lung lesion. Chest x-ray film and intravenous pyelogram on September 4, 1970, were normal. The child remains free of disease five and one-half years after the initial diagnosis. No biopsy evidence of either local recurrence or of metastases was ever sought. Case 4. A five-year-old boy gave a three-month history of hematuria, dysuria, and diminution in size and force of the urinary stream. Cystoscopy and attempted biopsy were followed by segmental resection of the “lower bladder” elsewhere in November, 1949. Within three months there was recurrence of gross hematuria and pain, followed shortly by incontinence of urine. Physical examination on admission to Memorial Hospital on August 26, 1950, revealed a healthy appearing male child with an 8 cm. in diameter irregular suprapubic mass. Intravenous pyelogram revealed mild dilatation of both ureters. On August 29, 1950, radical cystectomy, bilateral pelvic node dissection, and biIatera1 ureterosigmoidostomy were performed. The bladder was filled with soft gelatinous grape-like tumors. Pelvic lymph nodes were negative for disease. The pathologic diagnosis was embryonal rhabdomyosarcoma. The patient’s postoperative course was completely uneventful, and he has had no recurrence of disease up to the last follow-up in 1967. This particular patient was alluded to in the 1955 report of Dean4 but was overlooked in the 1968 review of Mackenzie, Whitmore, and Melamed. The 4 dead patients (Table I, patients 12-15) were males, ranging from eleven months to ten years of age, with difficulty in voiding progressing to urinary retention. Three had initial surgery elsewhere consisting of some type of excisional therapy via suprapubic cystostomy. Patient 12 had a combination of external and interstitial irradiation, chemotherapy, and radical cystectomy, urethrectomy, and pelvic node dissection with ileal conduit diversion. Patient 13 had radical cystectomy, bilateral pelvic node dissection, resection of a segment of rectum, and diversion by cutaneous ureterostomies. He was

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the only patient referred without cystostomy and even he had open bladder biopsy at the time of cystectomy. Patient 14 had a radical cystectomy, bilateral pelvic node dissection and ureterosigmoid diversion after cystostomy elsewhere. Patient 15 had suprapubic excision at another institution and presented with metastatic disease in lung, abdomen, pelvis, perineum, and penis which was treated with radio- and chemotherapy. All died ten to thirty-two months from the time of diagnosis, all but one had extensive local disease and 2 also had pulmonary metastasis.

Leiomyosarcoma A seven-year-old white boy (previously reported by Mackenzie et aL5) was admitted elsewhere for evaluation of dysuria. Cystoscopy was “negative,” and a meatotomy was performed. Dysuria persisted and an intravenous pyelogram revealed marked deformity of the left side of the bladder; biopsy was reported as negative. On October 10, 1968, he underwent laparotomy which revealed a large retrovesical tumor adherent to bladder wall and peritoneum. The tumor was incompletely removed, a cystostomy performed, and the patient then referred to Memorial Hospital. The submitted pathologic slides showed leiomyosarcoma, grade II. The pertinent physical findings included a suprapubic cystostomy tube and a 4-cm. mass in the suprapubic midline which could also be palpated rectally. Intravenous pyelogram revealed right calyceal blunting and decreased function. Chest x-ray film, skeletal survey, and bone marrow biopsy results were negative. Cystogram showed irregularity of the left bladder wall and left ureteral reflux. The suprapubic tube was removed on November 5, 1968. He received actinomycin D, 20 micrograms per kilogram per day from November 7 to 12, 1968. On December 6, 1968, laparotomy revealed the bladder to be markedly adherent and fixed to the left external iliac vessels, anterior abdominal wall, and the left superior pubic ramus. A nodule in the omentum adherent to a segment of ileum revealed malignant spindle cell tumor similar to the primary tumor. The lesion was considered nonresectable. A segmental resection of small intestine and ileal conduit urinary diversion were performed. Postoperatively he received actinomycin D, totaling 75 micrograms per kiIogram. Combination chemotherapy (actinomycin D, vincristine, cyclophosphamide and daunomycin) was then started and continued cyclically until August, 1969. He also received 6,000 rads

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via Cobalt-60 to the lower abdomen and pelvis from December 16, 1968, to February 14, 1969. An initial 900 rads were administered to the whole abdomen from December 16 to 23, 1968, and subsequently the treatment was limited to the lower portion of the abdomen and pelvis. He was readmitted in September, 1969, for small bowel obstruction. On September 2, 1969, laparotomy revealed distal ileal obstruction secondary to irradiation. There was no gross or biopsy evidence of tumor in the abdomen or pelvis. Segmental resection of ileum was performed and showed radiation enteritis. A second laparotomy was performed on October 1, 1969, for persisting partial intestinal obstruction. Lysis of adhesions and an ileocolic anastomosis were performed bypassing considerable small bowel. The child remains free of disease four and one-half years after initial diagnosis. Comment Papilloma MelicowG in reviewing 914 cases of primary urothelial tumors found only 1 case of papilloma in the first two decades of life. Javadpour and Mostofi’ in reviewing 10,000 cases of epithelial tumors of the bladder found only 40 in the first two decades of life (0.4 per cent), and of these, only 5 were diagnosed as papilloma. Deming8 refers to a case of papilloma in a three-year-old male child reported by Charbon and Lagedenck in 1879,g but challenged the diagnosis since there was rapid recurrence of tumor in the wound and the child died. In our 4 cases the tumor was solitary, results of urine cytology were negative, and transurethral treatment was successful, judged by tumor-free follow-up ranging from twenty months to nine years. In young boys perineal urethrostomy is an important aid in performing resection and was employed in one of our cases. Transitional-cell (epidermoid) carcinoma of the bladder in children is rare, and we have seen none. Neurojibroma Until 1970 about 36 cases of neurofibroma of the bladder had been reported,lO,” approximately 35 per cent occurring in the first 2 decades of life, being associated (75 per cent) with generalized neurofibromatosis, and was twice as common in males as in females.‘O Although these tumors may be asymptomatic and diagnosed incidentally during abdominal or pelvic surgery for some other condition, the majority produce symptoms relating to the size and site of the tumor.

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Development of urinary symptoms (frequency, dysuria, hematuria, urinary retention) in a patient with generalized neurofibromatosis suggests bladder involvement. The bladder may be nodular and palpable suprapubically or rectally. Cystoscopy may reveal solitary or multiple grayish-white discrete nodules or a diffuse swelling merging imperceptibly with the surrounding bladder wall. The mucosa overlying the tumor usually remains intact, but biopsy will confirm the diagnosis. When the tumor is located on the serosal aspect of the bladder, cystoscopy results may be normal except for an impression of extrinsic pressure, biopsy may be negative, and exploration may be necessary for diagnosis. In our case cystoscopy results were negative, but exploration revealed extensive neurofibromatosis involving bladder and prostate. Justification for treatment is based largely on symptoms and/ or signs of obstruction. Small or moderate sized nodules may be amenable to transurethral resection, local excision, or segmental resection, but for diffuse involvement of the bladder, total cystectomy is the treatment of choice. A small symptomless tumor discovered during unrelated abdominal or pelvic surgery may be excised for diagnosis and for elimination of a potential source of trouble. Although malignant change has been reported in 5 to 16 per cent of cases of neurofibromatosis,i2-l4 such change in neurofibroma of the bladder has been described only once.15 There was no evidence of pre-existing neurofibroma in 2 patients with neurogenic sarcoma of the bladder reported by Mintz. l6 The prognosis with vesical neurofibroma is good when adequate therapy is administered before irreversible obstructive damage has occurred, and this is true whether the neurofibromatosis is localized or generalized. Hemangioma Ganem and Ainsworthl’ considered hemangioma to be the most common benign connective tissue tumor arising from the bladder. At least 70 cases were reported up until 1971,18 32 occurring in the first two decades of life, the earliest at five weeks of age. lo Recurrent painless hematuria is one of the most common symptoms. About one third of patients with bladder hemangioma have hemangiomas elsewhere, usually on the skin of the lower portion of the abdomen, external genitalia, and/or thighs. The vesical lesion is solitary and well defined in two thirds of the cases, usually involving the upper half of the bladder; in one-third, multiple lesions occur anywhere in the bladder; in two thirds of cases the tumor involves the muscle; in one-third, it is

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may be of cavernsuperficial. l”*16 Hemangioma ous, plexiform, or capillary type, but cavernous hemangioma is the most common. Both of our cases had hemangiomas elsewhere in the body, mainly on the genitalia and the legs; both had hemangiomas mainly involving the upper half of the bladder; in 1 case the tumor involved muscle, serosa, and peritoneum over the posterior bladder wall. On cystoscopy hemangioma is usually blue or pink in color, covered with intact epithelium, and may be pedunculated or sessile, lobulated or flattened. Whether or not biopsy of the tumor should be done is debatable. Hamsher, Farrar, and Moorels reported 1 patient who exsanguinated following such a procedure. Stanley20 advised biopsy to establish the diagnosis. We feel that if cystoscopy leads to suspicion of hemangioma, biopsy should be deferred until the patient has been prepared for possible laparotomy. Treatment depends on the extent of the lesion. Transurethral surgery is limited to small and superficial lesions. Tumors may be larger than cystoscopy suggests due to an “iceberg” type of involvement of the bladder wall. However, the common location in the upper part of the bladder facilitates open excision or segmental resection. In sufficiently extensive disease a total cystectomy might be indicated, but we are unaware that such has ever been done for hemangioma. Our 2 patients underwent segmental resections, and neither has had recurrence five and eighteen years, respectively, after the surgery.

Rhabdomyosarcoma Rhabdomyosarcoma is the most common bladder tumor in childhood, the majority presenting during the first four years of life. Demine found sarcoma to comprise about 56.9 per cent of all bladder tumors in the first decade of life. Males are more commonly affected than females; Legier21 noted a male predominance of 4 to 1. Eight of 16 cases (50 per cent) in this series had rhabdomyosarcoma, 7 occurring in males, and 5 presenting during the first four years of life. Symptoms of bladder outlet obstruction are almost invariably present, and hematuria is common because the initially intact bladder mucous membrane is disrupted by tumor ulceration and necrosis. In girls there is sometimes protrusion of polypoid tumor through the urethra. In our 8 patients, 7 had difficulty in voiding, 5 urinary retention, 4 hematuria, 2 incontinence, 2 frequency, 2 dysuria, and 1 passage of tissue per urethra. The presence of a suprapubic mass, sometimes mistaken for a distended bladder, is a fairly com-

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mon finding; 5 of our 8 patients had a suprapubic mass and all had a mass on rectal examination. The intravenous urogram often shows unilateral or bilateral hydroureteronephrosis and the cystogram, a filling defect. A voiding cystourethrogram may help define the extent of urethral involvement. All of our 8 patients had slightto-moderate hydronephrosis, 6 bilateral and 2 unilateral. Cystoscopic examination usually reveals a polypoid mass involving the trigone and bladder neck, but no part of the bladder is exempt. If the tumor shows grape-like clusters of neoplastic tissue, the term “botryoid” is applicable. The tumor tissue is grayish-pink or grayish-white and translucent, often with an intact bladder mucous membrane overlying it. Sloughing of the tumor may result in spontaneous passage of mucoid or gelatinous masses, histologic examination of which may provide the diagnosis. Cystoscopy and adequate biopsy will confirm the diagnosis. Superficial biopsy may fail to reveal the true nature of the disease and may show only normal bladder mucosa. In this series 1 out of 8 patients on initial examination had pulmonary metastasis. Skeletal survey was obtained in 6 patients and gave normal findings. Transurethral resection or suprapubic excision of the tumor has invariably been followed by prompt recurrence, including frequent suprapubic sinus recurrences when the bladder has been opened. 22-24 Segmental resection of the bladder with or without adjunct irradiation and/ or chemotherapy has been successful in controlling tumor in a few cases (including 1 case in the present series), but the most common site of tumor occurrence precludes this operation in most cases. Most survivors of bladder rhabdomyosarcoma have had radical cystectomy with or without supplemental radio- and/or chemotherapy. The literature reveals that there are now 26 patients surviving one to twenty-two years following total cystectomy with or without adjunct radio- and/or chemotherapy.3,4p25-3g Four patients in our series are alive and well five and one-half to seventeen years, 3 having had radical cystectomy (with radiotherapy in 2 and chemotherapy in 1) and 1 having had segmental resection with radio- and chemotherapy. Although the best results with treatment have followed radical excision, comparable data utilizing irradiation alone or in combination with chemotherapy are nonexistent. Furthermore, just how radical the excision should be is uncertain. The extent of excision necessary to encompass tumor is difficult to define before or during surgical intervention because of the PO-

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tential for unrecognizable submucosal tumor extensions. However, the incidence of local and of urethral recurrences postcystectomy clearly indicates the potential hazards. In this institution radical cystectomy for vesical rhabdomyosarcoma includes total cystoprostatovesiculectomy and removal of the proximal half of the bulbous urethra in the male and total cystourethrectomy with removal of the uterus and anterior vaginal wall in the female. In both sexes the plane of the dissection is adjacent to the muscular and bony walls of the pelvis, and bilateral pelvic lymph node dissection is included. Although the precise role of adjunct radio- and/or chemotherapy is not well established, the ability of either modality alone to produce objective regressions of nonresectable embryonal rhabdomyosarcoma is well established and implies usefulness in appropriate Long survival following adjunct treatment. 3*5*40-43 radical surgery without adjunctive therapy has been reported.26-30,33j34*3g In this series, patient 10 had residual disease when first seen and later developed pulmonary metastasis but was successfully treated with radio- and chemotherapy and is well five and one-half years after diagnosis. Grosfeld, Clatworthy, and Newton40 recommended radical surgical procedure, postoperative and prolonged repeated regional irradiation, courses of chemotherapy, reporting 12 survivors among 32 cases so treated. Eight of the 12 survivors were treated with sequential chemotherapy utilizing the combination of actinomycin D and vincristine. The site and size of the tumor, if localized in the bladder, do not seem to influence the prognosis, unless the kidneys are irreversibly damaged from obstruction, Depth of muscle invasion has not had apparent influence on the prognosis either.21*22,2g Lymph node metastasis is rare, even when there is deep muscle invasion.22*25*2g,33None of the patients in this series who underwent radical cystectomy and pelvic node dissection had metastasis in the lymph nodes, although pathologic examination revealed superficial muscle invasion in at least two. The commonest cause of treatment failure has been persistent tumor in the pelvis. Death usually follows massive local recurrence with upper urinary tract obstruction and infection, and occasionally distant metastasis. Mostofi and Morse25 noted invariable local recurrence of tumor within four months and death within twenty-four months. Four patients in this series died ten to thirty-two months after the initial diagnosis, all but one with extensive local recurrence and 2

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also had distant metastasis. Our experience has led us to the following conclusions: 1. Rhabdomyosarcoma of the bladder is a potentially curable disease. 2. Radical surgery probably offers the best chance of survival. Whether or not pelvic node dissection is worthwhile is debatable, but we have done it routinely since it adds little or nothing to morbidity. 3. The role of adjunct radio- and chemotherapy has not been clearly established, but we are inclined to advise both although the optimal methods for adjunct treatment remain undefined. 4. In inoperable cases aggressive radio- and chemotherapy will apparently control some tumors. Chemotherapy seems to be more effective when several drugs (actinomycin D, vincristine, cyclophosphamide) are used in combination sequentially for one to two years.

Leiomyosarcoma Leiomyosarcoma of the bladder may occur at any age but is most common in the fifth and sixth decades; approximately 30 per cent occur in the first two decades of life. The tumor is twice as common in males as in females and usually arises outside the trigone.10*44-46 Of 15 reported cases of leiomyosarcoma of the bladder in the first two decades of life, 2 are alive ten years after segmental resection of the bladder, and 1 is alive three years after open fulguration and transurethral resection.3,5*10*45-47 In this series, patient 16 had incomplete removal of the tumor at another institution, and on reexploration was found to have a nonresectable tumor with omental metastasis, but is alive and well four and onehalf years after treatment with external irradiation and with sequential actinomycin D, vincristine, cyclophosphamide, and daunomycin. Leiomyosarcoma usually spreads by direct extension. Distant metastasis occurs late and usually involves lung, liver, and intestine.45’48*4g Although this tumor has been controlled by segmental resection, tumors poorly situated for segmental resection probably should be treated initially by radical cystectomy. For nonresectable or metastatic disease radio- and/or chemotherapy may control some tumors. University of Illinois Hospital, P.O. BOX 6998 Chicago, Illinois 60680 (DR. BAY) References Tumors of Childhood, 1. DARGEON, H. W.: Paul B. Hoeber, Inc., pp. 247, 367.

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2. KUFFER,

F. R., et al.: Khppel-Trenaunay syndrome, visceral angiomatosis and thrombocytopenia, J. Pediatr. Surgery 3: 65 (1968). 3. MACKENZIE, A. R., WHITMORE, W. F., JR., and MELAMED, M. R.: Myosarcoma of the bladder and prostate, Cancer 22: 833 (1968). 4. DEAN, A. L.: Tumors of the urogenital tract in infants and children, Pediatr. Clin. N. Amer. 2: 839 (1955). 5. MACKENZIE, A. R., SHARMA, T. C., WHITMORE, W. F., JR., and MELAMED, M. R.: Nonextirpative treatment of myosarcomas of the bladder and prostate, Cancer 28: 329 (1971). 6. MELICOW, M. M.: Tumors of the urinary bladder: a clinico-pathological analysis of over 2,500 specimens and biopsies, J. Urol. 74: 498 (1955). 7. JAVADPOUR, N., and MOSTOFI, F. K.: Primary epithelial tumors of the bladder in the first two decades of life, ibid. 101:706 (1969). 8. DEMING, C. L.: Primary bladder tumors in the first decade of life. Sure. Gvnecol. Obstet. 39: 432 (1924). 9. CHARBON, M., and LEGEDANCK, M.: Bull. ‘Acad. R. Med. Belg. 20 (1879); cited by Deming.8 10. SARMA, K. P.: Tumors of the Urinary Bladder, London, Appleton-Century-Crofts, 1969, pp. 90-93,95-101, 105111. Neurofibromatosis 11. CHARRON, J. W., and GARIEPY, G.: of bladder: Case report and review of literature, Can. J. Surg. 13: 303 (1970). 12. STOUT, A. P.: Tumors of soft tissues, in Atlas of Tumor Pathology, sec. 2, part 5, Washington, D.C., U.S. Armed Forces Institute of Pathology, 1953, p. 9. 13. CROW, F. W., SCHULL, W. J., and NEEL, J. V.: Clinical, Pathological, and Genetic Study of Multiple Neurofibromatosis, Springfield, Illinois, Charles C Thomas, 1956. (Von Reckling14. HOSOI, K.: Multiple neurofibromatosis hausen’s disease), with special reference to malignant transformation, Arch. Surg. 22: 258 (1931). 15. Ross, J. A.: Case of sarcoma of urinary bladder in Von Recklinghausen’s disease, Brit. J. Urol. 29: 121 (1957). Pedunculated neurofibroma of the blad16. MINTZ, E. R.: der, J. Ural. 43: 268 (1940). Benign neoplasms 17. GANEM, E. J., and AINSWORTH, L. B.: of the urinary bladder in children: Review of the literature and report of a case, ibid. 73: 1032 (1955). Hemangioma of 18. HENDRY, W. F., and VINNICOMBE, J.: bladder in children and young adults. Br. 1. Ural. 43: _ 309 (1971). Con19. HAMSHER, J. B., FAFXAR, T., and MOORE, T. D.: genital vascular tumors and malformations involving urinary tract; diagnosis and surgical management, J. Urol. 80: 299 (1958). Hemangioma-lymphangioma of the 20. STANLEY, K. E.: bladder in a child, ibid. 96: 51 (1966). Botryoid sarcoma and rhabdomyosar21. LEGIER, J. F.: coma of the bladder; Review of the literature and report of 3 cases, ibid. 86: 583 (1961). The manage22. THOMPSON, I. M., and COPPRIDGE, A. J.: ment of bladder tumors in children. A study of sarcoma botryoides, ibid. 82: 590 (1959). Rhabdomyosarcoma causing acute reten23. MINCHIN, E.: tion in infants, Br. Med. J. 2: 94 (1947). 24. BHANSALI, S. K.: Sarcoma botryoides of the bladder in infancy and childhood, J. Urol. 87: 871 (1962). Polypoid rhabdo25. MOSTOFI, F. K., and MORSE, W. H.: myosarcoma (sarcoma botryoides) of bladder in children, ibid. 67: 681 (1952). I

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26. MORSE, W. H., and JARMAN, W. D.: Sarcoma botryoides of the bladder in children. ibid. 70: 900 (1953). Rhabdomyosarcoma 27. SLOTKIN, E. A., and DA&S, R. D.: of the bladder, New York State J. Med. 54: 2837 (1954). 28 FLOCKS, R. H., and CULP, D. A.: Polypoid fibromyxosarcoma of the urinary bladder in a child, J. Urol. 73: 299 (1955). 29. MARSHALL, V. F.: Pelvic exenteration for polypoid myosarcoma (sarcoma botryoides) of the urinary bladder in an infant, Cancer 9: 620 (1956). Sarcoma boiryoides-rhabdomyosar30. SMITH, B. A., JR.: coma of the bladder, J. Urol. 82: 101 (1959). 31. WEAVER, R. G., CARD, R. Y., and RUEB, R. L.: Polypoid rhabdomyosarcoma of the bladder, ibid. 85: 297 (1961). Sarcoma bot32. CLEVELAND, J. C., and FORSYTHE, W. E.: ryoides: Report of a three-year survival, ibid. 89: 683

(1963). 33. WILLIAMS, D. I., and SCHISTAD, G.: Lower urinary tract tumors in children, Br. J. Urol. 36: 51 (1964). 34. JONES, C. B., and OBERMAN, H. A.: Rhabdomyosarcoma of the bladder; occurrence in childhood and in advanced age, J. Urol. 91: 533 (1964). 35. KAFKA, V., KROLUPPER, M., and PALECEK, L.: Rhabdomyosarcoma of the bladder in childhood; report of a successfully treated case, ibid. 96: 210 (1966). Bladder tumors in children, Med. Science 36. PERSKY, L.: 18: 43 (1967). 37. MILLER, H. C., BENJAMIN, J. A., and MCEVOY, R. K.: Sarcoma botryoides: a seven-year survival, J. Urol. 101: 567 (1969). Polypoid rhabdo38. JARMAN, W. D., and KENEALY, J, C.: mvosarcoma of the bladder in children. ibid. 103: 227 (1970). 39. RUSSI, M. F., DALE, R. L., and GOVAN, D. E.: Rhabdomyosarcoma of the bladder and prostate in children: A study of seven patients, Urol. Digest 10: 21 (1971). 40. GROSFELD, J. L., CLATWORTHY, H. W., and NEWTON, W. A.: Combined therapy in childhood rhabdomyosarcoma; an analysis of 42 cases, J. Pediair. Surg. 4: 637 (1969). of the bladder, Br. J. 41. HOLMES, A.: Rhabdomyosarcoma Urol. 41: 604 (1969). Re42. NELSON, A. J., III: Embryonal rhabdomyosarcoma. port of twenty-four cases and study of the effectiveness of radiation therapy upon the primary tumor, Cancer 22: 64 (1968). 43. JAMES, D. H., HUSTU, O., WRENN, E. L., and JOHNSON, W. W.: Childhood malignant tumors, concurrent chemotherapy with dactinomycin and vincristine sulfate, J.A.M.A. 197: 1043 (1966). Leiomvosarcoma of the 44. LEV. M.. and BELL, W. E.: urinary bladder; report of a case, J. Ural. 57: 251 (1947). Leiomyosarcoma of 45. SILBAR, J. D., and SILBAR, S. J.: bladder: Three case reports and a review of literature, ibid. 73: 103 (1955). Leiomyosarcoma of the bladder: Follow46. BROWN, H. E.: up report of two cases with 4 and 10 years’ survival, ibid. 94: 247 (1965). Myosarcoma of the uri47. FLINT,‘L. D., and DICK, V. S.: nary bladder-preliminary report of favorable case, Lahey Clin. Bull. 6: 181 (1969); cited by Mackenzie, Whitmore, and Melamed. 48. RAMEY, W. P., ASHBURN, L. L., GRABSTALD, H., and Myosarcoma of the urinary bladder, J. HAINES, J. S.: Ural. 70: 906 (1953). Myosarcoma of the 49. UEHLING, D., and FRABLE, W. J.: bladder; report of two cases, ibid. 91: 354 (1964).

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