California Tumor Tissue Registry
Case of the Month - Vol 7(9)
June, 2005
“An 83 y/o Man with Hematuria”
An 83-year-old man presented with a six week history of
hematuria. Upon cystoscopic examination a bladder tumor
was found which was 10 cm in greatest diameter, broadbased, smooth and somewhat lobular. The tumor was located in the left wall and
obstructed the ureter. Imaging studies showed enlarged left iliac nodes. The tumor was
curetted resulting in multiple fragments of friable tissue measuring 8.0 x 6.0 x 1.5 cm in
aggregate and weighing 50 grams.
Approximately two-thirds of the fragments contained an infiltrating high-grade malignant
neoplasm consisting mostly of spindled cells (Fig. 1). There were, however, foci of
delicate lace-like osteoid lined by oval to polygonal cells with scant cytoplasm and large
hyperchromatic nuclei with prominent nucleoli (Fig. 2). Focal cartilaginous differentiation
was also seen (Fig. 3). Other regions showed glandular and squamous differentiation
(Fig. 4). The epithelial component showed immunoreactivity for cytokeratin and EMA,
while the mesenchymal component was diffusely reactive for vimentin, alpha-1antitrypsin and lysozyme. S100, desmin and smooth muscle actin were negative.
Diagnosis: “Carcinosarcoma of the bladder with components of high-grade
papillary urothelial carcinoma and chondroblastic osteosarcoma”
Wafaa Elatre, Fuoad Abdelhalim, Donald Chase
Loma Linda University and Medical Center
Department of Pathology and Human Anatomy
Follow-up: The patient underwent radical resection of the bladder and prostate,
and had an ileo-conduit. Although the surgery was uneventful the post-operative
recovery period was complicated and the patient expired one month after
surgery.
Chondrosarcoma (CS) of the bladder is a rare tumor occurring late in life, usually in the
7th or 8th decade. It has a male preponderance and usually presents with hematuria.
Like uterine CS, it has been linked to previous exposure to cyclophosphamide
chemotherapy, however recurrent urothelial carcinoma is the most common antecedent.
The mass is usually bulky, polypoid and contains both malignant epithelial and
mesenchymal components.
The epithelial component usually consists as a mixture of:
 urothelial carcinoma
 adenocarcinoma
 squamous cell carcinoma, or
 small cell carcinoma
The Mesenchymal components usually includes one or more types of:
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June, 2005
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chondrosarcoma
leiomyosarcoma
malignant fibrous histiocytoma
osteosarcoma, or
rhabdomyosarcoma
Rarely has the tumor shown fatty or neural features.
There is considerable confusion and disagreement as to the nomenclature and
histogenesis of the bladder CS. The terms carcinosarcoma, sarcomatoid urothelial
carcinoma, and malignant mixed mesodermal tumor (MMMT) have been used
interchangeably. The term sarcomatoid urothelial carcinoma generally is used to define
a carcinoma with a prominent spindle cell component which is cytokeratin positive. The
terms CS/MMMT have usually been reserved for tumors with distinct mesenchymal
heterologous elements such as bone (as seen in this case), cartilage, and muscle etc.
The terminology distinction, however, seems irrelevant because currently there is no
clinical significance in splitting. The presentation, treatment, and prognosis are similar.
Most patients die within a few months of presentation.
Grossly, both CS/MMMT and sarcomatoid urothelial carcinoma are seen as bulky
polypoid or nodular tumors within the bladder. Microscopically the malignant epithelial
and stromal components may be sharply demarcated or may gradually merge with each
other.
Treatment of CS/MMMT and sarcomatoid urothelial carcinoma is stage dependant, and
is the main predictor of patient survival irrespective of treatment, histological subtypes,
or gender. Most patients present with a high stage malignancy and the preferred
modalities of treatment include cystectomy or transurethral resection with or without
radiation therapy and chemotherapy. In a large series there seemed no difference
between CS/MMMT and sarcomatoid urothelial carcinoma. 79% of CS patients died at a
mean of 17.2 months (range 1 to 48 months) whereas 81% of patients with sarcomatoid
urothelial carcinoma died at a mean of 9.8 months (range 1 to 73 months).
The differential diagnosis of bladder carcinosarcoma includes urothelial carcinoma with
pseudosarcomatous stroma, carcinoma with osseous or cartilaginous metaplasia, and
primary osteosarcoma or chondrosarcoma of bladder. CS may also simulate
myofibroblastic proliferations such as post-operative spindle cell nodule and
inflammatory pseudotumor.
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Sarcomatoid urothelial carcinoma with osseous metaplasia is the main
differential. In this entity clearly malignant osteoid production is present. The
prognosis is poor with patients dying within 6 months.
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Urothelial Carcinoma with Pseudosarcomatous Stroma: Urothelial carcinoma
may rarely possess a cellular stroma mimicking sarcoma or sarcomatoid
urothelial carcinoma The stroma may be myxoid, containing stellate or
multinucleated cells or consist of short intersecting fascicles of spindle cells.
Cytologic atypia is usually minimal. The stromal cells show immunoreactivity
for actin but are negative for cytokeratin. Squamous cell carcinoma of the
bladder may also have a pseudosarcomatous stroma.
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Primary Osteosarcoma of Urinary Bladder is an extremely rare tumor with
only seven reported cases in the world literature. The majority occur in older
males. They tend to be large, bulky, and deeply infiltrative tumors.
Microscopically, malignant cells are intimately associated with delicate lacelike osteoid.
Urinary carcinosarcoma has shown 40 microsatellite markers from 19 human
chromosomes. In some cases there is an identical LOH on chromosomal arms 9p, 9q,
8p, and 8q, corresponding to relatively early events in bladder carcinogenesis.
Discordant losses between two alleles in the remaining chromosomes, associated with
progression, have been seen in 9 tumors with a trend toward a higher incidence in the
more advanced tumors (N1M1 and N1Mx). E-cadherin has been seen in the
carcinomatous components (5 of 6), whereas most of sarcomatous elements have
displayed absence of the protein product (4 of 6). These results indicate that both the
carcinomatous and sarcomatous components of carcinosarcoma are derived from a
common stem cell. Down regulation of E-cadherin may define one of the pathways
responsible for conversion of epithelial cells to the sarcomatous phenotype.
Suggested Reading:
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Lopez-Beltran A, Pacelli A, Rothenberg HJ, Wollan PC, Zincke H, Blute ML,
Bostwick DG. Carcinosarcoma and sarcomatoid carcinoma of the bladder:
Clinicopathologic study of 41 cases. J Urol 1998; 159:1497-1503.
Lahoti C, Schinella R, Rangwala AF, Lee M, Mizrachi H. Carcinosarcoma of
urinary bladder: report of 5 cases with immunohistologic study. Urology
1994; 43:389.
Torenbeek R, Blomjus CM, de Bruin PC, Newlin DWW, Meijer CJLM.
Sarcomatoid carcinoma of the urinary bladder. Am J Surg Pathol 1994;
18:241.
Bannach B, Grignon DJ, Shum DT. Sarcomatoid transitional cell carcinoma vs
pseudosarcomatous stromal reaction in bladder carcinoma. J Urol Path
1993; 1:105-19.
Young RH, Eble JN. Unusual forms of carcinoma of the urinary bladder. Hum
Pathol 1991; 22:948.
Sigal SH, Tomaszewski JE, Brooks JJ, Wein A, LiVolsi VA. Carcinosarcoma of
bladder following long-term cyclophosphamide therapy. Arch Path Lab Med
1991; 115:1049 Bigotti G, Coli A, Prisco LA, Spina C, Russo F, Castri F,
Massi G.
Rare presentation of carcinosarcoma arising in bladder diverticulum. Dept. of
Pathology, Catholic University of Sacred Heart, Rome, Italy J Exp Clin
Cancer Res. 2001 Jun;20(2):301-4.
Baschinsky DY, Chen JH, Vadmal MS, Lucas JG, Bahnson RR, Niemann TH.
Carcinosarcoma of the urinary bladder--an aggressive tumor with diverse
histogenesis. A clinicopathologic study of 4 cases and review of the
literature. Arch Pathol Lab Med. 2000 Aug;124(8):1172-8.
Gonzalez-Carrero J, Nogueira March JL, Ojea A, Figueiredo L, Jamardo D,
Guate JL, Cunqueiro R. Carcinosarcoma and papillary transitional cell
carcinoma coexisting in the same bladder. Actas Urol Esp. 1990 JulAug;14(4):286-8.
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Li Y, Outman JE, Mathur SC. Carcinosarcoma with a large cell neuroendocrine
epithelial component: first report of an unusual biphasic tumour of the
urinary bladder. J Clin Pathol. 2004 Mar;57(3):318-20.
Zuck erberg LR, Armin AR, Pisharodi L, Young RH. Transitional cell carcinoma of
the urinary bladder with osteoclast-type giant cells: a report of two cases
and review of the literature. Histopath 1990; 17:407.
Young RH, Rosenberg AE. Osteosarcoma of the urinary bladder: Report of a
case and review of literature. Cancer 1987; 59:174-8.
Ro JY, El-Naggar AK, Amin MB, Sahin AA, Ordonez NG, Ayala AG.
Pseudosarcomatous fibromyxoid tumor of the urinary bladder and prostate:
immunohistochemical, ultrastructural, and DNA flow cytometric analyses of
nine cases. Hum Pathol 1993; 24:1203.
Perret L, Chaubert P, Hessler D, Guillou L. Primary heterologous
carcinosarcoma (metaplastic carcinoma) of the urinary bladder: a
clinicopathologic, immunohistochemical, and ultrastructural analysis of eight
cases and a review of the literature. Cancer1998; 15(82)1535-49.
Sarel Halachmi, Angelo M. DeMarzo, Nan-Haw Chow, Naomi Halachmi, Ann E.
Smith, Jurgen F. Linn, Ofer Nativ, Jonathan I. Epstein, Mark P. Schoenberg,
David Sidransky . Genetic Alterations in Urinary Bladder Carcinosarcoma:
Evidence of a Common Clonal Origin. European Urology 2000;37:350-357.
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