Abstract
Arab Journal of Urology (2013) 11, 159–164 Arab Journal of Urology (Official Journal of the Arab Association of Urology) www.sciencedirect.com ONCOLOGY/RECONSTRUCTION REVIEW Leiomyosarcoma of the urinary bladder: A review and a report of two further cases a b, a Nader Y. Hamadalla , Usama N. Rifat , Khalid C. Safi , c d Mustafa Mohammed , Hussam Abu-Farsakh Jordan Hospital and Medical Center, Amman, Jordan Israa Hospital, Amman, Jordan Royal Alexandra Hospital, Glasgow, UK First Medical Laboratory, Amman, Jordan Received 23 January 2013, Received in revised form 25 February 2013, Accepted 16 March 2013 Available online 6 May 2013 KEYWORDS Abstract Objectives: To review the published cases of leiomyosarcoma of the uri- nary bladder and to report two further cases. Leiomyosarcoma; Methods: The databases Pubmed and Hinari were searched using the keywords Urinary bladder; ‘bladder’, ‘leiomyosarcoma’ and ‘smooth muscle neoplasm’. The 14 articles identi- Outcome; fied were reviewed, and we present a further two cases. Management Results: Of more than 100 cases reported, 77 were reviewed. There is a lack of con- sensus about the standard treatment, and little is known about the natural history and ABBREVIATIONS prognosis of the tumour, due to its very low incidence. These tumours occur in older HPF, high-power adults of either sex and are characterised by an aggressive behaviour. There is usually Corresponding author. Address: Usama Nihad Rifat, FRCSEd, FACS, Urologist and Transplant Surgeon, Emeritus Professor of Surgery (Urology), P.O. Box 941418 Amman, Jordan. Tel.: +962 65300300x1440. E-mail address: usama.rifat@yahoo.com (U.N. Rifat). Peer review under responsibility of Arab Association of Urology. Production and hosting by Elsevier 2090-598X ª 2013 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. http://dx.doi.org/10.1016/j.aju.2013.03.004 160 Hamadalla et al. fields; an unfavourable outcome, with the lungs being the most common site of metastasis. FNCLCC, Fe´ de´ ration The two further cases we report had a different presentation and outcome. Nationale des Centres Conclusions: Because of the limited experience with this rare tumour, there are de Lutte Contre le insufficient data to suggest the optimum management strategy and prognosis. Cancer; ª 2013 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. MSKCC, Memorial Sloan Kettering Can- cer Center Introduction a-adrenergic blocker and 5a-reductase inhibitor for BPH. Urinary cytology was negative for urothelial malignant cells. CT (Fig. 1) showed a large mass at Non-epithelial tumours of the urinary bladder account the right lower wall of the bladder, encroaching upon for <5% of overall bladder malignancies, with leiomy- the bladder neck. No enlarged lymph nodes were de- osarcoma representing 0.1% of bladder cancers. There tected on pelvic and abdominal CT. Bone scanning are >100 cases reported in the medical literature as lei- and chest radiography showed no lesions. Cysto-ure- omyosarcoma, and a total of 192 cases considering all throscopy showed a fungating mass mainly at the right cases of bladder sarcoma. There is no consensus about side of the bladder neck, and the mass was biopsied. the standard treatment, and because of the very low inci- Some histopathological sections showed a spindle-cell dence, little is known about the natural history and tumour with marked atypia (Fig. 2) and pleomorphic prognosis of the tumour. Leiomyosarcomas have a poor cells, with high mitotic count of 20 per 10 high-power prognosis, especially if they are of high-grade and stage fields (HPF) (Fig. 3). There was necrosis, representing [1]. Herein we review previous cases and report two new 20% of the tumour. The tumour reached the surface, cases of bladder leiomyosarcoma. with ulceration, and there was calcification on the sur- face. Immunostaining for actin was positive (Fig. 4A), Methods for desmin showed a few positive cells (Fig. 4B), and for uroplakin and uroplakin III was negative (Fig. 4C The databases of Pubmed and Hinari were searched using the keywords ‘bladder’, ‘leiomyosarcoma’ and ‘smooth muscle neoplasm’. This review includes the 14 articles identified, comprising 77 cases (Table 1 [1–12]). Two new cases are also described below. Case 1 A 71-year-old man presented with haematuria and a burning sensation on micturition, of a few months’ duration. His PSA level was normal. He was taking an Figure 1 CT showing a large mass at the right lower wall of the bladder, encroaching upon the bladder neck. Table 1 Summary of some of the previous reports. Reference No. of cases Year Category of study 1 1 2010 Case report 2 20 2010 Review 3 2 2003 Case reports 4 7 2011 Review 5 1 2011 Case report 6 1 2011 Case report 7 34 2010 Review 8 1 2009 Case report 9 1 2008 Case report 10 7 2008 Review 11 1 2010 Review Figure 2 Microscopic findings of the leiomyosarcoma, showing 12 1 2009 Case report spindle-shaped cells with marked atypia (Haematoxylin and eosin, Present 2 2012 Review ·400). Leiomyosarcoma of the urinary bladder 161 cell tumour involving the urinary bladder wall, bladder neck and prostate, composed of interlacing bundles of spindle cells with markedly pleomorphic nuclei, promi- nent nucleoli and very high mitotic rate (>20/10 HPF). Bizarre giant tumour cells were noted. There were multi- ple foci of tumour necrosis and calcification (<50% of the surface area). The trigone was involved by malignant cells. The rest of the bladder mucosa showed oedema, congestion and chronic inflammation. The right and left seminal vesicles were free of tumour, as was the urethral resection margin, and right and left ureters. Immunohis- tochemical staining showed focal positive staining for S- Figure 3 Microscopic findings of the leiomyosarcoma, showing 100 protein and negative staining for cytokeratin and des- pleomorphic cells with a high mitotic count of 20/10 HPF min. The tumour was classified as high-grade. (Haematoxylin and eosin, ·400). After a team discussion it was decided to treat the pa- and D). The diagnosis was high-grade leiomyosarcoma tient with radiotherapy, followed by chemotherapy. He of the urinary bladder. received 50.4 Gy (28 fractions in two phases) over The patient underwent cystoprostatectomy with an 5.6 weeks. Three months later a positron-emission ileal conduit diversion. There was a mass involving the tomography/CT whole-body scan showed a small nodu- prostate, bladder neck, and anterior and posterior blad- lar focal hypermetabolic lesion in the left upper lobe of der walls, of 8 cm in maximum dimension, with a firm the lung, suggestive of metastatic disease. After a further whitish to yellow cut surface. Focal necrosis was identi- 3 months the chest and abdominal CT showed small fied, with an area of rupture in the anterior wall of nodules in the chest, of uncertain significance, but there 3.5 cm in diameter, with tumour extension. The rest of were no abdominal or pelvic recurrences. the bladder had a granular appearance with oedema A year later the patient presented with a cough, and and haemorrhage. The tumour was close to the seminal chest CT showed bilateral metastatic deposits, including vesicles but not invading them. The urethral margin was the pleura, and in the left superior pulmonary vein free. extending to the left atrium. Further chemotherapy con- Microscopically there was no glandular component. sisted of a combination of ifosfamide and adriamycin, The tumour cells were invading the anterior bladder wall with Mesna, at the usual doses, in the form of three with extravesicular extension into soft tissue, reaching the treatment cycles. He died 2 years after the surgery, from resection margin. Histological sections showed a spindle- pulmonary involvement, with no local recurrence. Figure 4 Immunostaining of the tumour for: (A) actin (positive); (B) desmin (a few positive cells); (C) uroplakin (negative); and (D) uroplakin III (negative). 162 Hamadalla et al. an aggressive behaviour and a very poor prognosis. Case 2 Lee et al. [2] reviewed 20 cases of bladder leiomyosar- coma, focusing on the criteria for distinguishing leiomy- A 31-year-old man presented in July 2011 with dysuria oma from leiomyosarcoma, and the subdivision of the of 3 months’ duration. Ultrasonography showed a latter into low- and high-grade sarcomas, largely based 4 · 4 cm mass at the right posterolateral aspect of the on mitotic activity. Tanguay et al. [3] described two bladder, with pressure on the right ureter causing hydro- cases of an interesting association between cyclophos- nephrosis. CT of the chest, abdomen and pelvis showed phamide exposure and bladder leiomyosarcoma. Lee a well-demarcated enhancing mass of 2.8 · 4 · 3.2 cm at et al. [4] studied seven bladder soft-tissue sarcomas, on the right posterolateral aspect of the bladder, with right the basis of 28 years of experience with these tumours hydronephrosis. Cystoscopy showed no bladder pathol- at one centre in Korea. Because of the rarity of these tu- ogy and an intact urothelium. Because of the technical mours clinical data are limited and the prognosis is often difficulty (unlike in renal cell carcinoma) no attempt considered unpredictable. There is no universal agree- was made to take a percutaneous biopsy and it was ment on the prognostic factors. Yamada et al. [5] re- decided to proceed with surgery. ported one case that showed a rapid progression and a The tumour mass was mobile and extramural, involv- very poor prognosis (for only a month), that was differ- ing the bladder and distal ureter. The patient underwent ent in its clinical course from those reported previously. a right distal ureterectomy, partial cystectomy, and re- They indicated that there is no consensus on the stan- implantation over a JJ stent, and had an uneventful dard treatment for this tumour. Xu et al. [6] reported postoperative course. the case of a 31-year-old woman with a leiomyosarcoma The histopathological assessment showed leiomyo- of 4 cm in diameter on the left wall of the bladder, trea- sarcoma of the bladder wall (4.5 cm, grade II) with an ted by a partial cystectomy. That report indicated that intact overlying urothelium. All the margins were free although bladder leiomyosarcoma has always been con- of tumour, by 0.25 mm. The tumour was positive for sidered a highly aggressive tumour, partial surgery is caldesmon and desmin, and negative for myogenin. now considered a reliable option, as it preserves function There were 22 mitotic figures per 10 HPF, indicating and decreases aggressiveness. a high-grade tumour. No involved lymph nodes were In a comprehensive review, Lindberg et al. [7] as- identified, and the stage was determined as T1bNXM0. sessed 34 well-characterised leiomyosarcomas of the uri- The JJ stent was removed at 4 weeks after surgery nary bladder and compared the prognostic power of the and cystoscopy showed a normal urothelium. The bone Fe´ de´ ration Nationale des Centres de Lutte Contre le scan was free from metastasis. The team decision was to Cancer (FNCLCC) and the National Cancer Institute give adjuvant chemo-radiotherapy for the close margins systems with that of one published grading scheme for (0.25 mm). The patient had concomitant four cycles of this tumour from the Mayo Clinic (all cited in [7]). All ifosfamide/Mesna and doxorubicin monthly. External available slides from 34 tumours were retrieved and beam radiotherapy was given for a total of 50.4 Gy in evaluated. 28 doses. One tumour was well-differentiated, 17 were moder- CT of the chest, abdomen and pelvis at 4 months ately differentiated and 16 were poorly differentiated. after surgery showed no interval changes, and cystos- Mitotic rates were 1–>30/10 HPF (median 12/10 HPF). copy then showed that the bladder was free of tumour. There was an adverse outcome in nine of these 17 pa- The patient is living uneventfully but declined to attend tients. Seven of the eight patients with a clinical for a further follow-up. follow-up of <12 months died from their disease. Over- all, there was an adverse outcome in 16 of 25 (64%) Discussion cases, with metastatic disease in 13 of 25 (52%), with the lungs being the most common site of metastasis The two cases we report had a dissimilar presentation, (62%). the first having severe symptoms like those reported pre- The authors concluded that leiomyosarcoma occurs viously, with haematuria being the prevailing feature. in older adults of either sex and is characterised by an The patient underwent early diagnostic steps followed aggressive behaviour, with an adverse outcome in by radical surgery and adjuvant therapy. The second >60% of cases. Certain advantages of the FNCLCC case presented with minimal symptoms. Imaging system might support its more widespread adoption showed a mass at the right posterolateral aspect of the for future studies. bladder with right hydronephrosis. He had partial sur- Tsujita et al. [8] reported on a 68-year-old man with a gery and adjuvant therapy afterwards. huge bladder diverticulum tumour that infiltrated the Ricciardi et al. [1] reported one case of leiomyosar- mesentery and abdominal wall, with multiple lymph coma of the bladder with an unusual presentation, node swellings in the pelvis. The tumour was partially resembling mostly a pelvic mass. The patient had sur- resected using a transurethral approach, and was histo- gery for a high-grade and high-stage tumour that had Leiomyosarcoma of the urinary bladder 163 logically diagnosed as a malignant neoplasm with osarcoma and osteosarcoma [1]. No specific risk factors marked necrosis. The patient had a partial cystectomy have yet been identified for this tumour. In previous re- with dissection of the mesentery and ileum. The patho- ports, retinoblastoma gene mutations were identified logical examination showed the tumour to be a leiomy- among possible causes in at least nine cases, as was osarcoma with mesenteric infiltration. The patient had a the use of cyclophosphamide. Pelvic radiotherapy for local recurrence with a pulmonary metastasis at 2 weeks other malignancies was also reported as a risk factor after surgery, and died 39 days after the operation. This in the clinical history of some patients. The diagnosis was the third case reported in Japan of a leiomyosar- can be delayed [1] because patients might have no symp- coma in a diverticulum of the urinary bladder. toms until the tumour reaches an advanced stage and Bakaris et al. [9] reported an interesting coexistence becomes locally invasive. The present first case was of two distinct and separate primary tumours of the symptomatic, and he had haematuria that was not taken bladder, i.e. a leiomyosarcoma and a TCC (urothelial seriously before presenting to our centre. According to cancer). CT of the pelvis showed a bladder mass along Rosser et al. [13] the most common clinical presentation the left anterolateral wall. The patient had a transure- is gross haematuria (81%). At 3 months after radical thral resection of the bladder, and the pathological surgery the positron-emission scan showed a left upper examination showed that the mass was leiomyosarcoma. lung lesion, and the patient died 2 years after the initial The patient then had a radical cystectomy with an ileal diagnosis. In the series by Mackenzie et al. [14], pub- conduit diversion. The urinary cystectomy specimen lished in 1968, only 11 patients were alive at 3 years after showed an 11 · 6 · 5 cm solid mass on the left anterolat- surgery. Subsequent series showed that the outcome eral wall and two 1-cm papillary tumours with different reported previously could be better than once thought localisation on the right and left lateral walls of the uri- [6]. The best prognostic factor appears to be the pres- nary bladder. The pathological examination showed ence of tumour-free margins. However, even if the mar- that these masses were high-grade leiomyosarcoma and gins were disease-free, that did not determine a better urothelial cancer. Seven cases of coexisting sarcoma outcome [1]. This concurs with our first case, who had and TCC of the urinary bladder have been reported tumour-free margins but had lung involvement that previously. shortened his survival. The lungs, liver, bone and brain Labanaris et al. [10] examined the records of seven [6] are the most common sites of metastases. The overall patients with bladder leiomyosarcoma. Transurethral recurrence of distant metastases is 50%. resection of the bladder tumour was the initial treatment Because of the very low incidence of this tumour in all patients, with leiomyosarcoma being initially diag- there is no universal consensus on the treatment of these nosed on the basis of an examination of the transure- patients. The treatment should be adapted to each case, thral specimen. A low-grade tumour was evident in and preferably using a multimodal and/or multidisci- one patient only, with the remaining six having a high- plinary approach to the disease. A team of physicians grade tumour. The authors suggested treatment by an experienced in managing soft-tissue sarcomas should aggressive surgical extirpation and, when surgical resec- make the decisions [1]. Minimally invasive approaches, tion is possible, a radical cystectomy with wide margins. such as transurethral resection or laser fulguration, in Nelius et al. [11] described a case of leiomyosarcoma addition to chemotherapy or radiotherapy in adjuvant presenting initially as a UTI with lower abdominal pain. settings, have been used for patients with small lesions. A life-threatening episode of gross haematuria guided Long-term survival rates did not differ significantly them to the final diagnosis and treatment. from patients undergoing more radical surgery [1]. Cumplido et al. [12] reported a new case of bladder Our second patient was treated with a right distal ure- leiomyosarcoma, for which partial surgery of the terectomy, partial cystectomy and re-implantation over primary tumour followed by concomitant chemo-radio- a JJ stent. He had an uneventful postoperative course. therapy was the approach. It was emphasised that Recently, more young patients with small tumours have although bladder leiomyosarcoma is treated basically been treated with partial cystectomy [6]. Our second pa- with radical surgery, partial surgery is currently the tient was tumour-free and living uneventfully at the time usual approach. There is a trend towards less aggressive of this report. surgery, with preservation of function, in tumours of Reports strongly suggest that T1 or T2 Memorial e.g., the head, neck or bladder. Sloan Kettering Cancer Center (MSKCC) stage 1 or 2 Sarcoma is the most frequent mesenchymal malig- small masses (<4 cm) that are not in the neck and tri- nancy of the bladder [1] with leiomyosarcoma as the gone of the bladder might be indications for a partial most common histology, as stated in two retrospective cystectomy of bladder leiomyosarcoma. Besides being reviews of mesenchymal genitourinary tumours. Consid- beneficial, adjuvant chemo-radiotherapy is not essential ering all cases reported to date (192), half were leiomyo- immediately after a partial cystectomy. The overall local sarcomas, 20% rhabdomyosarcomas and the remainder recurrence of bladder leiomyosarcoma is 16%, mostly consisted of other histology, like carcinosarcoma, angi- recurring in the pelvis. Therefore, there should be close 164 Hamadalla et al. [3] Tanguay C, Harvey I, Houde M, Srigley JR, Teˆ tu B. Leiomyo- monitoring with abdominopelvic CT, chest X-ray and sarcoma of urinary bladder following cyclophosphamide therapy. cystoscopy, especially in the first year after surgery, A report of two cases. Mod Pathol 2003;5:512–4. and which might be conducive to the early diagnosis [4] Lee G, Lee SY, Seo S, Jeon S, Lee H, Choi H, et al. Prognostic of tumour recurrence and metastasis. Local recurrences factors and clinical outcomes of urological soft tissue sarcomas. should be treated with systemic chemotherapy and/or Korean J Urol 2011;52:669–73. [5] Yamada T, Nagai S, Kanimoto Y. Rapid progression of a urinary pelvic external beam radiotherapy [6]. Partial rather bladder leiomyosarcoma. Report of a case. Case Reports Urol than radical cystectomy might be a reliable option for 2011;1:532081. a small bladder leiomyosarcoma (<4 cm) of a low [6] Xu YF, Wang GC, Zheng JH, Peng B. Partial cystectomy. Is it a MSKCC stage, because it might offer a similar thera- reliable option for the treatment of bladder leiomyosarcoma? Can peutic efficacy and a better quality of life. The second Urol Assoc J 2011;5:E11–3. [7] Lindberg MR, Fisher C, Thway K, Cao D, Cheville JC, Folpe patient’s tumour was 2.8 · 4 · 3.2 cm, and we think that AL. Leiomyosarcoma of the urinary bladder: a clinicopatholog- our treatment was effective and adequate at the time of ical study of 34 cases. J Clin Pathol 2010;63:708–13. surgery. [8] Tsujita Y, Sumitomo M, Tasaki S, Shirotake S, Hashiguchi Y, In conclusion, we agree with other authors [15] that Asano T. A case of leiomyosarcoma in a huge bladder divertic- because of the limited experience with this rare tumour, ulum. Hinyokika Kiyo 2009;55:761–4. [9] Bakaris S, Resim S, Tasci AI, Demirpolat G. A rare case of there are insufficient data to suggest an optimum man- synchronous leiomyosarcoma and urothelial cancer of the blad- agement strategy and prognosis, and as we are in an der. Can J Urol 2008;15:3920–3. exciting period of discovery about tumours [16] further [10] Labanaris AP, Zugor V, Meyer B, Nu¨ tzel R, Helmus S, Labanaris options might be available in future. PG, et al. Urinary bladder leiomyosarcoma in adults. Int Urol Nephrol 2008;40:311–6. [11] Nelius T, Stevens J, Samathanam C, Filleur S. Leiomyosarcoma of Conflict of interest the urinary bladder presenting as life threatening gross hematuria. Med Oncol 2010;27:562–7. None. [12] Cumplido JD. Toral Pena JC [Bladder leiomyosarcoma. Partial cystectomy and adjuvant treatment]. Arch Esp Urol 2009;62:320–2. 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Journal
Arab Journal of Urology
– Taylor & Francis
Published: Jun 1, 2013
Keywords: Leiomyosarcoma; Urinary bladder; Outcome; Management; HPF, high-power fields; FNCLCC, Fédération Nationale des Centres de Lutte Contre le Cancer; MSKCC, Memorial Sloan Kettering Cancer Center
