Urinary Bladder Botryoid Rhabdomyosarcoma with Widespread Metastases in an 8-month-old Labrador Cross Dog

INTRODUCTION Tumours of the urinary bladder represent less than 0.5 % of all primary neo-plasms in canine patients. Of these tumours, most are of epithelial origin 6 and most are malignant 16. Tumours of mesen-chymal origin occur uncommonly, with those of smooth muscle origin being the most abundant 3. Within the urinary tract, the bladder is the organ most frequently afflicted with neoplasia. It is thought that the role of the bladder as a storage organ may result in prolonged exposure to carcinogens voided in the urine. Metasta-sis to the bladder is rare, since this organ does not provide the right environment for haematogenous or lymphatic tumour embolisation nor does it lend itself to transcoelomic metastasis 16. Rhabdomyosarcoma is a tumour of striated muscle (skeletal or cardiac) which may also occur in other non-muscle locations 21. It is a rare primary mesenchymal tumour of the urinary bladder 6,16. and occurs here more commonly than in other


INTRODUCTION
Tumours of the urinary bladder represent less than 0.5 % of all primary neoplasms in canine patients.Of these tumours, most are of epithelial origin 6 and most are malignant 16 .Tumours of mesenchymal origin occur uncommonly, with those of smooth muscle origin being the most abundant 3 .Within the urinary tract, the bladder is the organ most frequently afflicted with neoplasia.It is thought that the role of the bladder as a storage organ may result in prolonged exposure to carcinogens voided in the urine.Metastasis to the bladder is rare, since this organ does not provide the right environment for haematogenous or lymphatic tumour embolisation nor does it lend itself to transcoelomic metastasis 16 .
Rhabdomyosarcoma is a tumour of striated muscle (skeletal or cardiac) which may also occur in other non-muscle locations 21 .It is a rare primary mesenchymal tumour of the urinary bladder 6,16 .and occurs here more commonly than in other locations, comprising approximately 2/3 of the reported rhabdomyosarcoma cases in dogs 7 .They occur most commonly at the bladder trigone 9 , although urethral involvement has also been documented 17 .Rhabdomyosarcoma can be classified histologically as pleomorphic, embryonal or alveolar.The embryonal and alveolar forms occur in young patients and are known collectively as juvenile rhabdomyosarcoma, whereas the pleomorphic form occurs mainly in adults 2,10 .Those rhabdomyosarcomas that protrude from the mucous membrane of a hollow organ have been described macroscopically as botryoid (sarcoma botryoides -meaning 'grape-like'), as they often take a lobulated form resembling a bunch of grapes 10 .
Tumours in the bladder occupy space and may cause mucosal ulceration, resulting in signs that mimic cystitis, such as haematuria, dysuria, stranguria, pollakiuria and incontinence.These cases often show a partial response to antibiotic treatment and may be erroneously diagnosed as recurrent cystitis 3,6,16,18 .A delay in diagnosis often occurs due to the lack of specificity of these signs or due to partial response to treatment of their more common causes.Tumours in this location may result in various complications such as obstruction of urethral outflow result-ing in bladder distension, infiltration of the bladder's muscular layer by tumour cells and obstruction of the ureters at the trigone 16 .Obstruction of ureteral urine flow increases ureteral pressure and results in hydroureter and hydronephrosis 3 .Relief of the ureteral obstruction can result in some reversal of renal damage, but chronic obstruction can lead to the obliteration of the entire renal cortex 13 .Rhabdomyosarcoma of the urinary bladder has also been associated with hypertrophic osteopathy (Marie's disease), even without the presence of pulmonary metastasis 4,6 .

CASE HISTORY
An 8-month-old entire male crossbred Labrador presented with stranguria and dysuria of 1 month's duration and anorexia and depression of 2-day duration.The owner reported that the dog would attempt to urinate, which only resulted in urine dripping from the prepuce.On clinical examination he was depressed and slightly underweight.Temperature, pulse and respiration were within normal limits.Multiple hard, mobile subcutaneous masses of 2-3 cm in diameter were palpable over the trunk and hindlimbs, as well as enlarged superficial inguinal lymph nodes.Abdominal palpation revealed a grossly distended urinary bladder occupying most of the caudal abdomen.The kidneys appeared considerably enlarged and even visible as bulges of the abdominal wall when the dog was placed in dorsal recumbency.He was unable to urinate spontaneously and small amounts of urine dripped from the penile urethra when mild pressure was applied to the bladder.He could, however, be easily catheterised.The dog was a unilateral cryptorchid with the retained testicle palpable subcutaneously in the inguinal area.
The dog was admitted and stabilised overnight.Initial therapy included urinary catheterisation to facilitate bladder emptying and intravenous isotonic crystalline fluids (IntraMed Ringer's lactate, Fresenius Kabi) to compensate for the expected post-obstructive diuresis.
Abdominal ultrasound showed gross enlargement of the left kidney, measuring 12.5 × 6.7 cm in sagittal view.The pelvis was dilated and filled with anechoic fluid and a thin rim of renal cortical tissue could be discerned (hydronephrosis) (Figs 1a  and 1b).Blood flow was demonstrated in the cortical tissue using colour Doppler.The bladder was grossly distended and contained a mass measuring 5.1 × 3.2 cm in the trigone area (Fig. 2).Dilated ureters could be seen entering the bladder in this area.The prostate appeared normal, but was surrounded by multiple small nodules (most likely superficial inguinal lymph nodes).The right kidney was also grossly enlarged and hypoechoic due to severe pelvic dilation and hydronephrosis and measured 15 × 9 cm in sagittal view.No remaining cortical tissue could be visualised (Fig. 3).A hypoechoic mass measuring 3 × 3 cm could be seen at the caudal edge of the right liver lobe.(Fig. 4) The sublumbar lymph nodes were enlarged.Ultrasound-guided fine needle aspirates of the trigone mass, the liver nodule and the caudal epigastric and internal iliac lymph nodes revealed anaplastic spindle-shaped cells consistent with a tumour of mesenchymal origin.Results of aspirates of the subcutaneous masses were similar.No specific diagnosis could, however, be made on the basis of cytology.
On the strength of these findings the prognosis was considered poor, and the dog was euthanased.Post mortem examination confirmed the ultrasonographic findings.A yellowish grapelike mass was found in the bladder lumen at the trigone, obliterating the prostate and occluding the ureters.There was severe bilateral hydroureter and hydronephrosis.The right kidney cortex was completely obliterated and the organ reduced to a fluidfilled sac (Figs 6 and 7).The superficial inguinal lymph nodes were enlarged and there were nodules in the mesentery.The liver contained a mass in the right lobe with a necrotic, fluid centre consistent with the ultrasonographic observations (Fig. 4).Tumours were also found in the lungs, mediastinum, abdominal muscles, intercostal muscles, cervical and quadriceps muscle groups and the papillary muscles of the heart.Rhabdomyosarcoma was confirmed by histopathology in all the macroscopic lesions.

DISCUSSION
Rhabdomyosarcoma is a rare tumour most commonly occurring in large-breed dogs under 2 years of age, particularly Saint Bernards 2,6,7,10,12 , although several cases have been reported in Retrievertype dogs 1,2,17 .It is similar to embryonal rhabdomyosarcoma in humans 19 , the most common soft tissue tumour in children under 15 years of age. 10 Whereas rhabdomyosarcoma arising in skeletal muscle metastasises early (to other skeletal muscle sites) 8 , the type occurring in the bladder metastasises more rarely and later in the course of the disease. 6,19etastases have been reported previously in the liver, lungs, mesentery, kidneys, adrenal glands, spleen and regional lymph nodes 2,6,17,19 .There have also been reports of post-operative metastasis within the peritoneal cavity after attempted resection of the primary lesion, most likely as a result of tumour seeding during surgery 6 .The extensive metastases seen in this case, most notably those to various striated muscle groups and the papillary muscles of the heart, sets it apart from previously documented cases.It is difficult to explain the presence of the subcutaneous nodules in this patient.They may represent widespread contemporary neoplastic transformation of subcutaneous pleuripotent mesenchymal stem cells, as opposed to metastatic foci.
The location and macroscopic appearance of the tumour, as well as the patient's clinical picture, are very similar to previously reported cases.The mass in the bladder was most likely the primary lesion.This mass occluded the patient's urethral outflow, resulting in bladder distension and stranguria.The blockage of the ureters resulted in the severe hydronephrosis and hydroureter and the decreased functional renal mass and urinary obstruction   resulted in severe renal and post-renal azotaemia, high normal serum potassium and mild hyperphosphataemia.
The origin of a skeletal muscle tumour within the urinary bladder appears to be linked to the embryology of this organ.In the embryo the urinary bladder is formed when mesodermal folds grow medially to divide the cloaca (endoderm) into the rectum dorsally and the bladder ventrally.Most of the bladder is derived from the ventral portion of the cloaca and is therefore of endodermal origin, with part of the dorsal wall (the area forming the trigone) being formed by mesodermal tissue 14 .It is postulated that tumours develop from pleuripotential mesodermal cells that have the potential for skeletal muscle differentiation.Such cells are believed to reside in this area, particularly around the Mullerian and Wolffian ducts 10,12,19 that are incorporated into the dorsal bladder wall 14 .The fact that leiomyosarcomas and teratomas also arise from this region supports the notion that pleuripotential cells reside at the trigone 8 .
Diagnosis and prognostication was greatly aided in this case by the use of ultrasound.Assessment of the urinary tract by diagnostic ultrasound is convenient as this is a non-invasive modality in which the internal architecture of relatively superficially situated structures can be studied 5,11 .Evaluation is further aided by the presence of urine, which provides a good acoustic window, allowing better assessment of the bladder wall.Masses in the bladder may be confused with those caused by other non-neoplastic conditions such as polypoid cystitis, adherent blood clots or mural haematomas.Thorough examination, together with the use of ultrasound-guided fine needle aspiration and careful consideration of the ultrasonographic characteristics of each condition, can allow a fairly confident diagnosis of neoplasia 11 .As well as its diagnostic uses, ultrasound is a suitable medium for monitoring of treatment or detection of tumour recurrence 22 .
Tumours of the urinary bladder may be treated successfully by partial cystectomy if the tumour can be excised completely along with a 1 to 2 cm border of grossly normal tissue. 18Over 75 % of the bladder can be removed without complications, provided the trigone remains intact. 16The typical location and infiltrative nature of rhabdomyosarcoma at the trigone implies a poor prognosis 12 .A technique involving en-bloc removal of the bladder neck and proximal urethra has recently been described for dogs with invasive tumours causing urinary tract obstruction and although technically challenging, may be indicated in some cases in the future. 15omplete cystectomy with surgical diversion of the ureters into the colon has been described as treatment for tumours with trigone involvement, 18 but the associated complications (including loss of continence) make it an undesirable choice. 16urgical treatment alone is often unrewarding due to recurrence and post-operative metastasis. 7 Chemotherapy is critical to success and remission postoperatively. 17Treatment should follow as soon as possible after surgery to prevent recurrence 20 , especially if the tumour margins were incomplete, and to prevent possible tumour seeding in the abdomen as a result of surgical manipulation of the tumour. 17Chemotherapy protocols such as a combination of vincristine, doxorubicin and cyclophosphamide 20 or doxorubicin with cyclophosphamide have been used.In addition, antibiotic treatment should be initiated if the patient has concurrent cystitis. 17lmost all reported cases of rhabdomyosarcoma have been euthanased at diagnosis, or soon after attempted surgery. 2,17,19For treatment to be successful, the whole tumour must be removed relatively early in the course of the disease. 19here is only 1 report of prolonged remission in a dog with urinary bladder rhabdomyosarcoma.This is thought to have been a slower growing, less infiltrative tumour diagnosed relatively early and treated aggressively with surgery and post-operative chemotherapy 17 .The presence of hydronephrosis and/or hydroureter worsens the prognosis in these patients as this indicates likely trigonal involvement as well as the possibility of compromised renal function. 16In the case reported here the prognosis was deemed to be extremely poor due to the location of the tumour, the severity of the hydronephrosis, the compromised renal function and the extent of metastasis.

Fig. 3 :
Fig. 3: Right parasagittal image of a fluid-filled sac thought to represent the right kidney, suggesting severe hydronephrosis.

Fig. 4 :
Fig. 4: Right parasagittal view of the caudal liver margin showing a 3 cm × 3 cm mass with distal acoustic enhancement.

Fig. 5 :
Fig. 5: Left lateral radiograph of the thorax showing multiple pulmonary nodules of varying sizes.