Clinical communication — Klieniese mededeling

Urinary bladder botryoid rhabdomyosarcoma with widespread metastases inan 8-month-old Labrador cross dog

K Gerbera* and P Reesb

INTRODUCTIONTumours of the urinary bladder repre-

sent less than 0.5 % of all primary neo-plasms in canine patients. Of thesetumours, most are of epithelial origin6 andmost are malignant16. Tumours of mesen-chymal origin occur uncommonly, withthose of smooth muscle origin being themost abundant3. Within the urinary tract,the bladder is the organ most frequentlyafflicted with neoplasia. It is thought thatthe role of the bladder as a storage organmay result in prolonged exposure tocarcinogens voided in the urine. Metasta-sis to the bladder is rare, since this organdoes not provide the right environmentfor haematogenous or lymphatic tumourembolisation nor does it lend itself totranscoelomic metastasis16.

Rhabdomyosarcoma is a tumour ofstriated muscle (skeletal or cardiac) whichmay also occur in other non-muscle loca-tions21. It is a rare primary mesenchymaltumour of the urinary bladder6,16. andoccurs here more commonly than in other

locations, comprising approximately 2/3of the reported rhabdomyosarcoma casesin dogs7. They occur most commonly atthe bladder trigone9, although urethralinvolvement has also been documented17.Rhabdomyosarcoma can be classifiedhistologically as pleomorphic, embryonalor alveolar. The embryonal and alveolarforms occur in young patients and areknown collectively as juvenile rhabdo-myosarcoma, whereas the pleomorphicform occurs mainly in adults2,10. Thoserhabdomyosarcomas that protrude fromthe mucous membrane of a hollow organhave been described macroscopically asbotryoid (sarcoma botryoides – meaning‘grape-like’), as they often take a lobulatedform resembling a bunch of grapes10.

Tumours in the bladder occupy spaceand may cause mucosal ulceration,resulting in signs that mimic cystitis, suchas haematuria, dysuria, stranguria, polla-kiuria and incontinence. These casesoften show a partial response to antibiotictreatment and may be erroneously diag-nosed as recurrent cystitis3,6,16,18. A delay indiagnosis often occurs due to the lack ofspecificity of these signs or due to partialresponse to treatment of their morecommon causes. Tumours in this locationmay result in various complications suchas obstruction of urethral outflow result-

ing in bladder distension, infiltration ofthe bladder’s muscular layer by tumourcells and obstruction of the ureters at thetrigone16. Obstruction of ureteral urineflow increases ureteral pressure andresults in hydroureter and hydrone-phrosis3. Relief of the ureteral obstructioncan result in some reversal of renal dam-age, but chronic obstruction can lead tothe obliteration of the entire renal cortex13.Rhabdomyosarcoma of the urinary bladderhas also been associated with hypertro-phic osteopathy (Marie’s disease), evenwithout the presence of pulmonarymetastasis4,6.

CASE HISTORYAn 8-month-old entire male crossbred

Labrador presented with stranguria anddysuria of 1 month’s duration and ano-rexia and depression of 2-day duration.The owner reported that the dog wouldattempt to urinate, which only resulted inurine dripping from the prepuce. On clin-ical examination he was depressed andslightly underweight. Temperature,pulse and respiration were within normallimits. Multiple hard, mobile subcutane-ous masses of 2–3 cm in diameter werepalpable over the trunk and hindlimbs, aswell as enlarged superficial inguinallymph nodes. Abdominal palpation re-vealed a grossly distended urinary blad-der occupying most of the caudalabdomen. The kidneys appeared consid-erably enlarged and even visible as bulgesof the abdominal wall when the dog wasplaced in dorsal recumbency. He was un-able to urinate spontaneously and smallamounts of urine dripped from the penileurethra when mild pressure was appliedto the bladder. He could, however, be eas-ily catheterised. The dog was a unilateralcryptorchid with the retained testicle pal-pable subcutaneously in the inguinalarea.

Urine obtained by catheterisation wasdark orange in colour. Results of a urinalysiswere as follows: isosthenuria (specificgravity 1.012), pH 6, moderate proteinuria(2+) and severe haematuria. Examinationof the urine sediment, stained initiallywith Sternheimer-Malbin and then withDiffquick, revealed erythrocytes, some

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aPO Box 12064, Die Boord, Stellenbosch, 7613 SouthAfrica.

bSection of Small Animal Medicine, Department ofCompanion Animal Clinical Studies, Private Bag X04,Onderstepoort, 0110 South Africa.

*Author for correspondence.E-mail: kgerbervet@gmail.com

Received: January 2008. Accepted: July 2009.

ABSTRACTAn 8-month-old crossbred Labrador retriever was presented with a history and clinicalsigns suggestive of lower urinary tract obstruction. Laboratory results revealed azotaemiaand hyperphosphataemia. Ultrasonographic evaluation of the urinary tract showed a massat the bladder trigone, hydronephrosis, hyrodureter, and suspected metastases to lymphnodes and the liver. Pulmonary metastasis was identified on thoracic radiographs. A postmortem confirmed metastases to the liver, lungs and regional lymph nodes, as well as to themesenteric lymph nodes, mediastinum, heart, subcutaneous tissue and several musclegroups. A histopathological diagnosis of metastatic botryoid rhabdomyosarcoma (sarcomabotryoides) was made. A review of the literature shows that, although the bladder trigone isa well documented location for this tumour, this case was unique with its widespreadmetastases to previously undocumented organs. The incidence, embryology, ultra-sonographic appearance and treatment of this tumour are discussed.

Keywords: botryoid, hydronephrosis, metastasis, rhabdomyosarcoma, stranguria, ultra-sonography, urinary bladder.

Gerber K, Rees P Urinary bladder botryoid rhabdomyosarcoma with widespreadmetastases in an 8-month-old Labrador cross dog. Journal of the South African VeterinaryAssociation (2009) 80(3): 199–203 (En.). PO Box 12064, Die Boord, Stellenbosch, 7613 SouthAfrica.

leukocytes and several anaplastic spin-dle-shaped cells. No parasites were ob-served on blood smear.

The dog was admitted and stabilisedovernight. Initial therapy included urinarycatheterisation to facilitate bladder emp-tying and intravenous isotonic crystallinefluids (IntraMed Ringer’s lactate, FreseniusKabi) to compensate for the expectedpost-obstructive diuresis.

On day 2, haematology revealed adegenerative left shift neutrophilia with amild thrombocytopaenia. Serum sodiumand calcium were within referenceranges; serum potassium was at the highend of the normal range (4.95 mmol/ ;reference 3.6–5.1 mmol/ ); serum globulinwas mildly elevated (39.9 g/ ; reference20–37 g/ ); serum inorganic phosphatewas mildly elevated (2.37 mmol/ ; refer-ence 0.9–1.6 mmol/ ), and serum urea(44.2 mmol/ ; reference 3.6–8.9 mmol/ )and creatinine (674 µ / ; reference 40–133 µ / ) concentrations were markedlyraised.

Abdominal ultrasound showed grossenlargement of the left kidney, measuring12.5 × 6.7 cm in sagittal view. The pelviswas dilated and filled with anechoic fluidand a thin rim of renal cortical tissue couldbe discerned (hydronephrosis) (Figs 1aand 1b). Blood flow was demonstrated inthe cortical tissue using colour Doppler.The bladder was grossly distended andcontained a mass measuring 5.1 × 3.2 cmin the trigone area (Fig. 2). Dilated ureterscould be seen entering the bladder in thisarea. The prostate appeared normal, butwas surrounded by multiple small nod-ules (most likely superficial inguinallymph nodes). The right kidney was alsogrossly enlarged and hypoechoic due tosevere pelvic dilation and hydronephrosisand measured 15 × 9 cm in sagittal view.No remaining cortical tissue could bevisualised (Fig. 3). A hypoechoic massmeasuring 3 × 3 cm could be seen atthe caudal edge of the right liver lobe.(Fig. 4) The sublumbar lymph nodes wereenlarged. Ultrasound-guided fine needleaspirates of the trigone mass, the livernodule and the caudal epigastric andinternal iliac lymph nodes revealedanaplastic spindle-shaped cells consistentwith a tumour of mesenchymal origin.Results of aspirates of the subcutaneousmasses were similar. No specific diagnosiscould, however, be made on the basis ofcytology.

Thoracic radiographs revealed a diffusenodular lung pattern, suggesting exten-sive pulmonary metastasis (Fig. 5).

On the strength of these findings theprognosis was considered poor, and thedog was euthanased. Post mortem exami-nation confirmed the ultrasonographic

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Fig. 1: Sagittal (a) and transverse (b) views of the left kidney showing severe hydro-nephrosis.

Fig. 2: Sagittal view of the urinary bladder showing a mass at the trigone area.

findings. A yellowish grapelike mass wasfound in the bladder lumen at the trigone,obliterating the prostate and occludingthe ureters. There was severe bilateralhydroureter and hydronephrosis. Theright kidney cortex was completely oblit-erated and the organ reduced to a fluid-filled sac (Figs 6 and 7). The superficialinguinal lymph nodes were enlarged andthere were nodules in the mesentery. Theliver contained a mass in the right lobewith a necrotic, fluid centre consistentwith the ultrasonographic observations(Fig. 4). Tumours were also found in thelungs, mediastinum, abdominal muscles,intercostal muscles, cervical and quadri-ceps muscle groups and the papillarymuscles of the heart. Rhabdomyo-sarcoma was confirmed by histopathol-ogy in all the macroscopic lesions.

DISCUSSIONRhabdomyosarcoma is a rare tumour

most commonly occurring in large-breeddogs under 2 years of age, particularlySaint Bernards2,6,7,10,12, although severalcases have been reported in Retriever-type dogs1,2,17. It is similar to embryonalrhabdomyosarcoma in humans19, themost common soft tissue tumour inchildren under 15 years of age.10 Whereasrhabdomyosarcoma arising in skeletalmuscle metastasises early (to other skeletalmuscle sites)8, the type occurring in thebladder metastasises more rarely andlater in the course of the disease.6,19

Metastases have been reported previouslyin the liver, lungs, mesentery, kidneys,adrenal glands, spleen and regionallymph nodes2,6,17,19. There have also beenreports of post-operative metastasiswithin the peritoneal cavity after at-tempted resection of the primary lesion,most likely as a result of tumour seedingduring surgery6. The extensive meta-stases seen in this case, most notably thoseto various striated muscle groups and thepapillary muscles of the heart, sets it apartfrom previously documented cases. It isdifficult to explain the presence of thesubcutaneous nodules in this patient.They may represent widespread contem-porary neoplastic transformation of sub-cutaneous pleuripotent mesenchymalstem cells, as opposed to metastatic foci.

The location and macroscopic appear-ance of the tumour, as well as the patient’sclinical picture, are very similar to previ-ously reported cases. The mass in thebladder was most likely the primary lesion.This mass occluded the patient’s urethraloutflow, resulting in bladder distensionand stranguria. The blockage of the uretersresulted in the severe hydronephrosisand hydroureter and the decreased func-tional renal mass and urinary obstruction

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

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

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

resulted in severe renal and post-renalazotaemia, high normal serum potassiumand mild hyperphosphataemia.

The origin of a skeletal muscle tumourwithin the urinary bladder appears to belinked to the embryology of this organ. Inthe embryo the urinary bladder is formedwhen mesodermal folds grow medially todivide the cloaca (endoderm) into therectum dorsally and the bladder ventrally.Most of the bladder is derived from theventral portion of the cloaca and is there-fore of endodermal origin, with part ofthe dorsal wall (the area forming thetrigone) being formed by mesodermal

tissue14. It is postulated that these tumoursdevelop from pleuripotential meso-dermal cells that have the potential forskeletal muscle differentiation. Such cellsare believed to reside in this area, particu-larly around the Mullerian and Wolffianducts10,12,19 that are incorporated into thedorsal bladder wall14. The fact that leio-myosarcomas and teratomas also arisefrom this region supports the notion thatpleuripotential cells reside at the trigone8.

Diagnosis and prognostication wasgreatly aided in this case by the use ofultrasound. Assessment of the urinarytract by diagnostic ultrasound is conve-nient as this is a non-invasive modality inwhich the internal architecture of rela-tively superficially situated structures canbe studied5,11. Evaluation is further aidedby the presence of urine, which providesa good acoustic window, allowing betterassessment of the bladder wall. Masses inthe bladder may be confused with thosecaused by other non-neoplastic conditionssuch as polypoid cystitis, adherent bloodclots or mural haematomas. Thoroughexamination, together with the use ofultrasound-guided fine needle aspirationand careful consideration of the ultra-sonographic characteristics of each condi-tion, can allow a fairly confident diagnosisof neoplasia11. As well as its diagnosticuses, ultrasound is a suitable medium formonitoring of treatment or detection oftumour recurrence22.

Tumours of the urinary bladder may betreated successfully by partial cystectomyif the tumour can be excised completelyalong with a 1 to 2 cm border of grossly

normal tissue.18 Over 75 % of the bladdercan be removed without complications,provided the trigone remains intact.16 Thetypical location and infiltrative nature ofrhabdomyosarcoma at the trigone impliesa poor prognosis12. A technique involvingen-bloc removal of the bladder neckand proximal urethra has recently beendescribed for dogs with invasive tumourscausing urinary tract obstruction andalthough technically challenging, may beindicated in some cases in the future.15

Complete cystectomy with surgical diver-sion of the ureters into the colon has beendescribed as treatment for tumours withtrigone involvement,18 but the associatedcomplications (including loss of conti-nence) make it an undesirable choice.16

Surgical treatment alone is often unreward-ing due to recurrence and post-operativemetastasis.7 In general, the more invasivea tumour is, the more likely it is to recurand metastasise.17,16 Chemotherapy iscritical to success and remission post-operatively.17 Treatment should follow assoon as possible after surgery to preventrecurrence20, especially if the tumourmargins were incomplete, and to preventpossible tumour seeding in the abdomenas a result of surgical manipulation of thetumour.17 Chemotherapy protocols suchas a combination of vincristine, doxo-rubicin and cyclophosphamide20 or doxo-rubicin with cyclophosphamide havebeen used. In addition, antibiotic treat-ment should be initiated if the patient hasconcurrent cystitis.17

Almost all reported cases of rhab-domyosarcoma have been euthanasedat diagnosis, or soon after attemptedsurgery.2,17,19 For treatment to be success-ful, the whole tumour must be removedrelatively early in the course of the disease.19

There is only 1 report of prolongedremission in a dog with urinary bladderrhabdomyosarcoma. This is thought tohave been a slower growing, less infiltrativetumour diagnosed relatively early andtreated aggressively with surgery andpost-operative chemotherapy17. The pres-ence of hydronephrosis and/or hydro-ureter worsens the prognosis in thesepatients as this indicates likely trigonal in-volvement as well as the possibility ofcompromised renal function.16 In the casereported here the prognosis was deemedto be extremely poor due to the location ofthe tumour, the severity of the hydro-nephrosis, the compromised renal func-tion and the extent of metastasis.

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