A case of high-grade leiomyosarcoma of the bladder with delayed onset and very poor prognosis

Department of Gynecology, Perinatology and Child Health, Sapienza University of Rome, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00195 Rome, Italy.
World Journal of Surgical Oncology (Impact Factor: 1.41). 03/2010; 8(1):16. DOI: 10.1186/1477-7819-8-16
Source: PubMed
ABSTRACT
Mesenchymal tumors represent a small number of bladder cancer cases. Leiomyosarcoma is the most common histology with over 100 cases reported in the whole literature. This tumor is been historically considered as highly aggressive and showing a poor prognosis. Despite very low survival rates showed in older reports, some authors indicate that some patients could have a better outcome. We report a review of the literature and a case of high-grade LMS of the bladder in a 68 years old woman. Diagnosis was delayed and disease was locally advanced. Symptoms and imaging of our case first oriented to a gynecologic condition with an adnexal or uterine origin of the mass, and, a genitourinary origin could be unveiled only intra-operatively.

Full-text

Available from: Enzo Ricciardi
WORLD JOURNAL OF
SURGICAL ONCOLOGY
Ricciardi et al. World Journal of Surgical Oncology 2010, 8:16
http://www.wjso.com/content/8/1/16
Open Access
CASE REPORT
© 2010 Ricciardi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Case report
A case of high-grade leiomyosarcoma of the
bladder with delayed onset and very poor
prognosis
Enzo Ricciardi*, Paolo Maniglio, Mauro Schimberni and Massimo Moscarini
Abstract
Mesenchymal tumors represent a small number of bladder cancer cases. Leiomyosarcoma is the most common
histology with over 100 cases reported in the whole literature. This tumor is been historically considered as highly
aggressive and showing a poor prognosis. Despite very low survival rates showed in older reports, some authors
indicate that some patients could have a better outcome. We report a review of the literature and a case of high-grade
LMS of the bladder in a 68 years old woman. Diagnosis was delayed and disease was locally advanced. Symptoms and
imaging of our case first oriented to a gynecologic condition with an adnexal or uterine origin of the mass, and, a
genitourinary origin could be unveiled only intra-operatively.
Background
Non-epithelial tumors of the urinary bladder account for
less than 5% of the overall bladder malignancies, with
leiomyosarcoma being the 0.1% of bladder cancer [1].
There are over 100 cases reported in the whole medical
literature as leiomyosarcomas, and a total of 192 cases
considering all bladder sarcoma cases [2]. There is a lack
of consensus about a standard treatment, and little is
known about natural history and prognosis of the tumor,
due to a very low incidence.
Cases presented in literature had mostly gross urinary
symptoms, more often with an earlier onset. This may,
eventually, lead to earlier diagnosis, allowing a safer ther-
apeutic approach. The case we report shows an unusual
presentation, differing from the symptoms reported in
literature, resembling mostly a pelvic mass. The patient
underwent, in the early diagnostic steps, a gynecologic
evaluation that addressed to a final multidisciplinary sur-
gical approach to the disease. The high-grade and stage of
the tumor, in association to the fatal outcome of the case,
are expression of the aggressive behavior of the tumor,
showing mostly a very poor prognosis.
Case presentation
We report a case of a 68 years old woman presenting to
the emergency department with macrohematuria and
dysuria. She experienced fever several times, starting two
months before medical examination. Fever was treated
with NSAID. A history of recent pelvic pain was also
reported. Her clinical status was good and no other
symptoms or concurrent illnesses were present at the
time of hospitalization.
She was admitted to Gynecologic service for further
evaluation.
The patient was virgin and in post-menopausal status.
Clinical history was unremarkable; negative either for
previous medical or surgical procedures. Family history
was positive for cancer with one male sibling deceased
from a pancreatic malignancy; the remainder two siblings
had no positive history for malignancies as well as par-
ents and closest relatives. Social history was negative for
use or addiction to drugs, alcohol and exposure to poten-
tial risk factors.
A digital rectal examination had to be performed in
place of the gynecologic bimanual examination. A gross,
firm mass located in the pelvis was found at physical
examination.
Pelvic US, abdominal CT scans, descending pielogra-
phy, cystoscopy and chest RX were performed to both
* Correspondence: e.ricciardi81@gmail.com
1
Department of Gynecology, Perinatology and Child Health. Sapienza
University of Rome. Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00195,
Rome, Italy
Page 1
Ricciardi et al. World Journal of Surgical Oncology 2010, 8:16
http://www.wjso.com/content/8/1/16
Page 2 of 4
assess local disease and evaluate the presence of local and
distant metastases.
Computed tomography imaging confirmed the pres-
ence of a complex mass in the pelvis (13 × 14 cm) show-
ing irregular contours and small areas of calcifications.
Uterus and adnexa could not be clearly recognized, show-
ing as being part of the mass. Iliac vessels and bladder
were displaced. Imaging technique reports stated that no
vessels or bladder invasion was present. A hypoplasia of
the left kidney was also reported. No other metastasis
was reported in the abdomino-pelvic cavity.
Pielography showed a delay in the opacification of the
renal pelvis associated to a dilation of the right ureter that
was compressed and displaced in its pelvic course till
entering the bladder. No opacification of the contra lat-
eral kidney and excretory ways could be obtained.
Cystoscopy showed, eventually, a bleeding lesion onto
the bladder wall that raised suspicion of neoplastic inva-
sion. The lesion appeared more likely as a loss of continu-
ity of the urothelial mucosa; an ulcerating mass was
visualized and eventually described on final report.
Chest RX and bone scan were negative for distant
metastases.
A multidisciplinary board, including a urologist, a radi-
ologist, a radiation oncologist, an oncologist and a gyne-
cologist, evaluated the collected data. It was eventually
decided to surgically extirpate the tumor. A transurethral
biopsy of the vesical wall lesion was not considered since
major suspicion was addressing to uterine or adnexal
neoplasms and the high stage was reasonably an indica-
tion to undergo definitive surgery.
Surgery was eventually performed after pre-operative
routine and evaluation.
A longitudinal abdominal incision was preferred to
access peritoneal cavity. A bulky mass was found in the
pelvis. Uterus and adnexa appeared macroscopically free
from neoplastic invasion. The mass showed a cleavage
with recto-sigmoid tract, iliac vessels and pubic bone,
whether uterus, adnexa, right ureter and left obturator
nerve could not be separated from the tumor. A histolog-
ical intra-operative examination revealed a malignant,
spindled cell neoplasm. Surgery had to include a wide
mass excision, in order to obtain free margins and control
of local disease. Final treatment choice was a pelvic exen-
teration. This decision was made since local disease was
advanced and it was set to obtain specimen's margins dis-
ease-free as a primary target.
An en-bloc resection of the mass, together with uterus,
adnexa, bladder, distal part of right ureter and left obtura-
tor nerve was performed (anterior pelvic exenterantion).
A cutaneous ureterostomy was placed in the site of ure-
teral dissection. The decision to perform this procedure
in place of a standard urinary diversion, as a ileal conduit
or Miami pouch, was made on the evidence of poor prog-
nosis that appeared from surgical exploration and intra-
operative histology that was addressing to a malignant
stromal neoplasm. It seemed to be reasonable to lower
intra- and post-operative morbidity whereas the potential
overall survival of the patient appeared to be prospec-
tively low.
A final histological diagnosis of high-grade leiomyosar-
coma, (Fig. 1), (G3, FNCLCC 1986) pT2b pN0 pM0,
AJCC (2002) Stage III, was made based on immunoreac-
tivity to smooth muscle actin, score 2 (Fig. 2). The speci-
men resulted negative to c-kit and EGFR. Proliferation
index was 90%, evaluated thru MIB-1 (Ki-67) (Fig. 3).
Necrosis was inferior to 50% (score 2) and mitotic index
higher than 20 mitosis per field/10 HPF (score 3). The
tumor presented, macroscopically, as a bulky, brain-like,
white-grayish mass. The tumor contained diverse
necrotic and hemorrhagic areas, and invaded the vesical
wall. The size of the mass was 14 × 11 × 6.5 cm. Histology
confirmed that uterus and adnexa were free from neo-
plastic invasion. Surgical margins resulted negative at the
final examination. LVI was not reported.
Post-operative course was free from complications and
the patient could be discharged from the hospital four-
teen days after surgery.
The patient underwent chemotherapy one month after
surgery, using doxorubicin as a single agent in an adju-
vant setting. She died after the first cycle from a distant
recurrence to the left lung.
Discussion
Sarcoma is the most frequent mesenchymal malignancy
of the bladder with leiomyosarcoma as most common
histology, according to two retrospective reviews of mes-
enchymal genitourinary tumors [3,4]. Considering the
whole of the cases reported in literature (192 in total),
Figure 1 Leiomyosarcoma of the bladder (Hematoxylin and eo-
sin).
Page 2
Ricciardi et al. World Journal of Surgical Oncology 2010, 8:16
http://www.wjso.com/content/8/1/16
Page 3 of 4
50% were leiomyosarcomas, 20% rhabdomyosarcomas
and the remainder consisting of other histologies as car-
cinosarcomas, angiosarcomas and osteosarcomas [2]. No
specific risk factors have been identified yet for this
tumor. Reviewing the literature, retinoblastoma (RB)
gene mutations were identified among possible causes in
at least 9 cases, as well as use of cyclophosphamide [5-8].
Pelvic radiation therapy for other malignancies was also
described in literature as a risk factor present in the clini-
cal history of the patient. According to Rosser et al., the
most common clinical presentation is gross hematuria
(81%), dysuria (19%) and pollakiuria (28%). Our case pre-
sented mostly as a pelvic mass, showing urinary symp-
toms similar to those described by Rosser and coll [9] but
very late in disease course. Diagnosis in our case was
therefore delayed, due on the fact that the patient had no
symptoms until tumor reached an advanced stage and
became locally invasive. The patient, otherwise being
well, did not consider undergoing a medical evaluation,
until the onset of urinary symptoms.
Initial reports for this tumor showed a very aggressive
disease. In a series by Mackenzie et al. published in 1968,
only 11 patients were alive at 3 years from surgery [10].
Further series showed that the outcome shown in previ-
ous series, could be better that once believed. A series at
MD Anderson considered 19 patients with a bladder sar-
coma diagnosis. It showed a 5 years disease-specific sur-
vival of 59%. They also reported lymph-vascular invasion
and node status as significant prognostic markers, claim-
ing a 3.4 median survival for patients with no LVI in front
of a 0.8 median survival when LVI was present. Patho-
logic node status showed a median survival of 7.6 when
negative and 0.3 when positive [11]. Largest series, by
Rosser and coll. (35 patients, with a diagnosis of LMS of
the bladder) showed a 5 years disease-specific survival of
62%, with a 34% recurrence rate at a median follow-up of
38 months, with both local and distant disease sites
affected [9].
However, the best prognostic factor seems to be the
presence of free margins. In our case, we achieved dis-
ease-free margins; still, they did not determine a better
outcome. In addition to margin status, local invasiveness
and size, as well as tumor grade, seem to play an impor-
tant role in determining the final outcome. In our case, as
stated above, LVI was unavailable.
According to one of the greatest series available to date,
overall local recurrence of bladder leiomyosarcomas is
about 16%, with most recurrences occurring in the pelvis.
Overall recurrence of distant metastases is about 53%,
with the most common sites of metastases being the
lungs, liver, bone, and brain [11].
Because of very low incidence, there is no universal
consensus on the treatment of patients affected. Mini-
mally invasive approaches, such as transurethral resec-
tion or laser fulguration, in addition to CTX or RT
adjuvant settings, have been used for patients with small
lesions. Long-term survival rates did not differ signifi-
cantly to cases undergone a more radical surgery. A sole
resection of the mass, even when free margins were
achieved, as in case of partial cystectomy, should be con-
sidered a palliative treatment [12-14]. Main treatment
consists in radical cystectomy (including removal of
uterus, cervix and vaginal cuff in women). The procedure
should include wide margins resection with 2-3 cm depth
free from tumor invasion [15-17,19]. Neoadjuvant and
adjuvant therapies were used in 21% and 16% of patients
at MD Anderson, respectively, and both resulted in a
doubling of disease-specific survival. However, this result
was not statistically significant, reflecting the small num-
bers of patients in each group. Similarly, it is difficult to
evaluate the impact of neoadjuvant and adjuvant chemo-
therapy on quality of life [11].
Figure 2 Leiomyosarcoma of the bladder (Smooth muscle actin).
Figure 3 Leiomyosarcoma of the bladder (Ki67).
Page 3
Ricciardi et al. World Journal of Surgical Oncology 2010, 8:16
http://www.wjso.com/content/8/1/16
Page 4 of 4
A multimodal treatment with CTX settings targeting
mesenchymal cancers (as sarcoma chemotherapy proto-
cols using doxorubicin, ifosfamide, cisplatinum and doc-
etaxel) should be mandatory in the event of metastatic
disease, [11]. With positive margins after surgery, adju-
vant radiotherapy should be advocated for the patient
[18]. Local recurrences should be treated by systemic
CTX and/or external pelvic RT, salvage therapy showed
to be ineffective, with a median survival of 20 months
after surgery [11].
Conclusions
Sarcomas should be considered as a possible histology at
differential diagnosis, even if they are no frequent com-
pared to other tumors. Unfortunately, obtaining a pre-
operative histological diagnosis does not improve the
prognosis. Rare tumors represent a great challenge for
physicians. They require experienced teams and well-
equipped centers for cancer cure. Bladder sarcomas, as
other genito-urinary sarcomas, require close cooperation
between urologist and gynecologic oncologist, as well as
medical and radiation oncologist. A pathologist expert in
mesenchymal tumors is mandatory.
Nowadays, no statistically relevant evidences on thera-
peutic behavior can be found yet in the literature. There-
fore, treatment should be tailored case-by-case,
preferring a multimodal and/or multidisciplinary
approach to the disease. A decision-making team made
by physicians experienced in managing soft tissues sarco-
mas should be also strictly required.
Consent
Written informed consent was obtained from the patient
for publication of this case report and any accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Competing interests
The authors report no conflicts of interest. The authors alone are responsible
for the content and writing of the paper.
Authors' contributions
ER conceived of the study, and participated in its design and coordination and
drafted the manuscript. PM collected clinical data. MS participated in collect-
ing data and read and corrected the manuscript. MM participated in design of
the study and revisions, gave intellectual input and corrected the manuscript.
All authors read and approved the final manuscript.
Acknowledgements
Special thanks goes out to Prof. Andrea Vecchione for providing the histologi-
cal pictures used in these article.
Author Details
Department of Gynecology, Perinatology and Child Health. Sapienza University
of Rome. Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00195, Rome, Italy
References
1. Pedersen-Bjergaard J, Jonsson V, Pedersen M, Hou-Jensen K:
Leiomyosarcoma of the urinary bladder after cyclophosphamide. J Clin
Oncol 1995, 13:532-3.
2. Parekh DJ, Jung C, O'Conner J, Dutta S, Smith ER Jr: Leiomyosarcoma in
urinary bladder after cyclophosphamide therapy for retinoblastoma
and review of bladder sarcomas. Urology 2002, 60:164.
3. Berkmen F, Celebioglu AS: Adult genitourinary sarcomas: a report of
seventeen cases and review of the literature. J Exp Clin Cancer Res 1997,
16:45-48.
4. Dahm P, Gschwend JE: Malignant non-urothelial neoplasms of the
urinary bladder: a review. Eur Urol 2003, 44:672-681.
5. Seo IS, Clark SA, McGovern FD, Clark DL, Johnson EH: Leiomyosarcoma of
the urinary bladder: 13 years after cyclophosphamide therapy for
Hodgkin's disease. Cancer 1985, 55:1597-1603.
6. Rowland RG, Eble JN: Bladder leiomyosarcoma and pelvic fibroblastic
tumor following cyclophosphamide therapy. J Urol 1983, 130:344-346.
7. Venkatraman L, Goepel JR, Steele K, Dobbs SP, Lyness RW, McCluggage
WG: Soft tissue, pelvic, and urinary bladder leiomyosarcoma as second
neoplasm following hereditary retinoblastoma. J Clin Pathol 2003,
56:233-6.
8. Kawamura J, Sakurai M, Tsukamoto K, Tochigi H: Leiomyosarcoma of the
bladder eighteen years after cyclophosphamide therapy for
retinoblastoma. Urol Int 1993, 51:49-53.
9. Rosser CJ, Slaton JW, Izawa JI, Levy LB, Dinney CP: Clinical presentation
and outcome of high-grade urinary bladder leiomyosarcoma in adults.
Urology 2003, 61:1151-5.
10. Mackenzie AR, Whitmore WF Jr, Melamed MR: Myosarcomas of the
bladder and prostate. Cancer 1968, 22:833-44.
11. Spiess PE, Kassouf W, Steinberg JR, Tuziak T, Hernandez M, Tibbs RF,
Czerniak B, Kamat AM, Dinney CP, Grossman HB: Review of the M.D.
Anderson experience in the treatment of bladder sarcoma. Urol Oncol
2007, 25:38-45.
12. De Berardinis E, Giulianelli R, Zarrelli G, De Santis C, Ginepri A, Gentile BC,
Di Silverio F: Leiomyosarcoma of urinary bladder: personal experience
in 3 cases over a 10-year period. Arch Ital Urol Androl 1997, 69:73-80.
13. Strander H, Turesson I, Cavallin-Stahl E: A systematic overview of
radiation therapy effects in soft tissue sarcomas. Acta Oncol (Stockholm,
Sweden) 2003, 42:516-31.
14. Swartz DA, Johnson DE, Ayala AG, Watkins DL: Bladder leiomyosarcoma:
a review of 10 cases with 5-year followup. J Urol 1985, 133:200-2.
15. Martin SA, Sears DL, Sebo TJ, Lohse CM, Cheville JC: Smooth muscle
neoplasms of the urinary bladder: a clinicopathologic comparison of
leiomyoma and leiomyosarcoma. Am J Surg Pathol 2002, 26:292-300.
16. Cody HSIII, Turnbull AD, Fortner JG, Hajdu SI: The continuing challenge of
retroperitoneal sarcomas. Cancer 1981, 47:2147-52.
17. Dotan ZA, Tal R, Golijanin D, Snyder ME, Antonescu C, Brennan MF, Russo
P: Adult genitourinary sarcoma: the 25-year Memorial Sloan-Kettering
experience. J Urol 2006, 176:2033-8.
18. O'Sullivan B, Ward I, Catton C: Recent advances in radiotherapy for soft-
tissue sarcoma. Curr Oncol Rep 2003, 5:274-81.
19. Nelius T, Stevens J, Samathanam C, Filleur S: Leiomyosarcoma of the
urinary bladder presenting as life threatening gross ematuria. Med
Oncol 2009 in press.
doi: 10.1186/1477-7819-8-16
Cite this article as: Ricciardi et al., A case of high-grade leiomyosarcoma of
the bladder with delayed onset and very poor prognosis World Journal of Sur-
gical Oncology 2010, 8:16
Received: 22 December 2009 Accepted: 19 March 2010
Published: 19 March 2010
This article is available from: http://www.wjso.com/content/8/1/16© 2010 Ricciardi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.World Journal of Surgical Oncology 2010, 8:16
Page 4
  • Source
    • "Tumors of a high grade and advanced stage should be treated with radical cystectomy and urinary diversion. Partial cystectomy is reserved for tumors that present at an early stage and a low grade [4,5] . The best prognostic factor is the presence of tumor-free margins. "
    [Show abstract] [Hide abstract] ABSTRACT: A 22-year-old young woman presented with dysuria and lower urinary tract symptoms that had persisted for 6 months. She was diagnosed with a tumor near the bladder neck. Transurethral resection was done under anaesthesia. The histopathological examination with immunohistochemical staining showed the tumor to be a low-grade leiomyosarcoma. Adjuvant chemoradiation was given, and the patient has been doing well for 12 months of follow-up. Nonurothelial tumors of the bladder are rare and consensus is lacking regarding their definitive treatment. Furthermore, little is known about the natural history and prognosis of this type of bladder sarcoma. We present a minimally invasive treatment for this relatively rare tumor in which bladder preservation was achieved with no evidence of local or distant recurrences during the follow-up to date.
    Full-text · Article · Jun 2013 · Korean journal of urology
  • Source
    • "Minimally invasive approaches, such as transurethral resection or laser fulguration, in addition to chemotherapy or radiotherapy in adjuvant settings, have been used for patients with small lesions. Long-term survival rates did not differ significantly from patients undergoing more radical surgery [1]. Our second patient was treated with a right distal ureterectomy , partial cystectomy and re-implantation over a JJ stent. "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives To review the published cases of leiomyosarcoma of the urinary bladder and to report two further cases. Methods The databases Pubmed and Hinari were searched using the keywords ‘bladder’, ‘leiomyosarcoma’ and ‘smooth muscle neoplasm’. The 14 articles identified were reviewed, and we present a further two cases. Results Of more than 100 cases reported, 77 were reviewed. There is a lack of consensus about the standard treatment, and little is known about the natural history and prognosis of the tumour, due to its very low incidence. These tumours occur in older adults of either sex and are characterised by an aggressive behaviour. There is usually an unfavourable outcome, with the lungs being the most common site of metastasis. The two further cases we report had a different presentation and outcome. Conclusions Because of the limited experience with this rare tumour, there are insufficient data to suggest the optimum management strategy and prognosis.
    Full-text · Article · Jun 2013 · Arab Journal of Urology
  • Source
    • "Patients with positive surgical margin could be candidates for adjuvant radiotherapy. Patients with local recurrence or metastatic bladder sarcomas should be treated with systemic chemotherapy (as sarcoma chemotherapy protocol using doxorubicin, ifosfamide, cisplatin, and docetaxel), and/or radiotherapy [4] [5]. Contemporary studies suggest that these tumors may have a better prognosis than once believed and show remarkable 5-year-disease-specific survival rates of 59– 62% [2] [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: The case we report shows rapid progression and a very poor prognosis only for a month that differs from the clinical course reported in the literature. An 83-year-old man was referred to our hospital for macroscopic hematuria. Computed tomography (CT) revealed a large bladder tumor measuring 4 cm × 3 cm and magnetic resonance imaging revealed extravesical invasion and pelvic wall invasion of the tumors. Chest CT and bone scintigraphy revealed no evidence of distant visceral metastases, and a clinical diagnosis of T4N0M0 was made. Transurethral resection of the bladder tumor (TUR-BT) was performed for histopathological diagnosis 18 days after admission, and no further adjuvant treatment was given. At 15 days after TUR-BT, the patient's clinical status worsened with symptoms of exertional dyspnea. CT showed multiple metastatic lesions in the lung, liver, and retroperitoneal lymphadenopathy. The patient died 2 days later and underwent autopsy. A final histopathological diagnosis of leiomyosarcoma was made based on immunohistochemical staining.
    Full-text · Article · Jul 2011
Show more