Bertaccini_edit.qxp 25/9/08 10:00 am Page 48
Bladder Cancer
Update on Neuroendocrine Carcinomas of the Bladder
a report by
Alessandro Bertaccini
Assistant Professor, Alma Mater Studiorum, University of Bologna
Neuroendocrine (NE) tumours account for approximately 1% of all carcinomas, but in reality they are more frequent since they often co-exist
primary bladder tumours. These carcinomas are rare, with the exception with conventional urothelial carcinomas.
2
It is important to understand
of the histologically distinctive and clinically indolent carcinoids, and they the difference between solid small-cell tumours and tumours with focal
usually present at an advanced stage. The prognosis in patients with NE NE differentiation: the latter have glandular structures with isolated NE
tumours of the bladder remains poor despite an aggressive surgical cells, while pure NE tumours are characterised by the diffuse expression
approach and improvements in systemic multiagent chemotherapy.
1
of NE markers in 50–100% of cells. No definitive predisposing factors are
Better characterisation of clinical outcome and response to therapy of known; however, small-cell carcinomas of the bladder (SCCB) have been
extrapulmonary NE carcinomas is an ongoing effort. seen in smokers, patients affected by long-standing cystitis, those with
bladder lithiasis and those with augmented cystoplasty.
8–10
This neoplasm
NE tumours can arise in almost all epithelium-containing organs and are is strongly predominant in males, and develops between the fifth and
commonly encountered in the respiratory and gastrointestinal tract, skin, ninth decades of life.
breast, nasal cavity and paranasal sinuses, larynx, trachea, thymus gland
and parotid and salivary glands, but they can also be found in organs of The origin of the small cells is still subject to debate. The first theory was
the genito-urinary tract (uterus, cervix, kidney, ureter, bladder and that NE carcinomas of the bladder developed from Kulchitsky cells. Next,
prostate gland).
2,3
it was hypothesised that they originated from the NE amine precursor
uptake and decarboxylation (APUD) system within the transitional
Following the revised World Health Organization (WHO) classification in epithelium or as a result of urothelial mucosal metaplasia.
11
It is now
1999, NE tumours can be classified into four major histological categories: believed that SCCB derives from the totipotent stem cells of the
low-grade malignant ‘typical’ carcinoids, intermediate-grade malignant submucosa of the bladder wall. This explains the frequent association of
‘atypical’ carcinoids, and two high-grade tumours – small-cell lung SCCB with non-small-cell carcinomas (transitional cell carcinomas,
carcinomas (SCLCs) and large-cell NE carcinomas (LCNECs); the latter was adenocarcinomas, carcinosarcomas – with 10 documented cases to
introduced by the group of Travis in 1991 to describe a distinct category of date – squamous cell carcinomas or carcinoid tumours), but it fails
high-grade NE tumours with biologic and light microscopic characteristics.
4
to explain the low incidence of concomitant carcinomas in situ.
NE carcinomas of the bladder are not as well defined histologically as one
might assume; in fact, they appear as pure or composite tumours where SCCB are often of high stage at initial diagnosis, with higher metastatic
the NE component (small-cell or large-cell) is associated with the urothelial potential and poorer prognosis than pure urothelial carcinomas.
cell elements. At present, in contrast to NE carcinomas of other organs, for Prognosis seems to correlate to stage at clinical manifestation. At
tumours arising from the bladder we are not able to grant clinical diagnosis, an estimated 51–100% are T3/T4, and 28–80% have lymph
significance to any correlation between different ratios of NE and non-NE node or distant metastases, most commonly to bone (44%), the liver
components and outcome or response to therapy.
5,6
In the literature, case (33%) or the brain (20%). The five-year overall survival rate is only 8%,
reports and series of variable numbers of patients present conflicting data and the mortality rate reaches 68.7% less than two years after diagnosis,
about treatment and outcomes due to the unknown aetiology and natural with mean survival of nine to 13 months.
8,12,13
history of NE tumours of the urinary bladder.
7
On urine cytology, SCCB present a pattern of isolated single cells,
Small-cell Neuroendocrine Carcinomas hypercellularity, nuclear moulding and nuclear hyperchromatism, with
Pure small-cell urinary carcinomas (SCUCs) are the most common kind of staining for NE markers and a haemorrhagic necrotic background. In this
NE differentiation in the bladder: they account for 0.48–1% of all bladder context, differentiation from lymphomas may be difficult.
14,15
At
histology, SCCB appear to be composed of tumour cells with marked
hypercellularity, necrosis, nuclear chromatin crush artefact and numerous
Alessandro Bertaccini is an Assistant Professor at Alma
Mater Studiorum, University of Bologna. His clinical and
mitoses associated with lymphovascular deposition of basophilic material
research interest is uro-oncology, in particular prostate
around blood vessel walls (Azzopardi phenomenon).
13
Since the
disease. Dr Bertaccini has been Secretary General and
neoplastic cells range from small to intermediate-type cells, some authors
Treasurer of the Italian Society of Urological Oncology since
2003, and is a member of the European Association of propose subdividing this tumour category into small- or oat-cell
Urology (EAU), the Italian Society of Urology (SIU) and
carcinomas and intermediate-type cell carcinomas.
12
A positive expression
the Italian Society of Andrology (SIA). He is the author or
co-author of many scientific publications and book chapters.
of neural markers such as neurone-specific enolase (NSE) can be obtained
in 87% of patients, although this lacks specificity. Chromogranin
E:
alessandro.bertaccini@gmail.com
(positive in around half of cases of SCCB but in only 5% of urothelial
48 © TOUCH BRIEFINGS 2008
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