Eble JN, Sauter G., Epstein JI, Sesterhenn IA - iarc

Small cell carcinoma
F. Algaba
G. Sauter
M.P. Schoenberg
Definition
Small cell carcinoma is a malignant neuroendocrine
neoplasm derived from the
urothelium which histologically mimics its
pulmonary counterpart.
ICD-O code 8041/3
Clinical features
Gross haematuria is the most common
presenting symptom in patients with
small cell carcinoma (SCC) of the bladder.
Other symptoms include dysuria or
localized abdominal/pelvic pain {1531}.
Approximately 56% of patients will present
with metastatic disease at the time of
diagnosis. The most common locations
for disease spread include: regional
lymph nodes, 56%; bone, 44%; liver,
33%; and lung, 20% {2640}. Peripheral
(sensory) neuropathy may also be a clinical
sign of metastatic disease and is
attributed to the paraneoplastic syndrome
associated with tumour production
of antineuronal autoantibodies. The
presence of antiHU autoantibodies (IgG)
is a specific marker of the paraneoplastic
syndrome and should prompt careful
evaluation for SCC (particularly in the
lung) in a patient without a history of cancer
{93}. Electrolyte abnormalities such
as hypercalcemia or hypophosphatemia,
and ectopic secretion of ACTH have also
been reported as part of the paraneoplastic
syndrome associated with primary
SCC of the bladder {2021,2182}.
Localization and macroscopy
Almost all the small cell carcinomas of
the urinary tract arise in the urinary bladder
{2640}. The tumour may appear as a
large solid, isolated, polypoid, nodular
mass with or without ulceration, and may
extensively infiltrate the bladder wall. The
vesical lateral walls and the dome are the
most frequent topographies, in 4.7% they
arise in a diverticulum {100}.
Histopathology
All tumours are invasive at presentation
{2640}. They consist of small, rather uniform
cells, with nuclear molding, scant
cytoplasm and nuclei containing finely
stippled chromatin and inconspicuous
nucleoli. Mitoses are present and may be
frequent. Necrosis is common and there
may be DNA encrustation of blood vessels
walls (Azzopardi phenomenon).
Roughly 50% of cases have areas of
urothelial carcinoma {1934} and exceptionally,
squamous cell carcinoma and/or
adenocarcinoma. This is important,
because the presence of these differentiated
areas does not contradict the diagnosis
of small cell carcinoma.
The neuroendocrine expression of this
tumour is identified by many methods. In
some papers, neuroendocrine granules
are found with electron microscopy or
histochemical methods, but in the majority
of them, the immunohistochemical
method is used. The neuronal-specific
enolase is expressed in 87% of cases,
and Chromogranin A only in a third of
cases {2640}. The diagnosis of small cell
carcinoma can be made on morphologic
grounds alone, even if neuroendocrine
differentiation cannot be demonstrated.
The differential diagnosis is metastasis of
a small cell carcinoma from another site
(very infrequent) {608}, malignant lymphoma,
lymphoepithelioma-like carcinoma,
plasmacytoid carcinoma and a poorly
differentiated urothelial carcinoma.
Histogenesis
In the spite of the low frequency of associated
flat carcinoma "in situ" referred in
the literature (14%) {2640}, the high frequency
of cytokeratin (CAM5.2 in 64%)
expression in the small cell component
supports the hypothesis of urothelial origin
{60}. Other hypotheses are the malignant
transformation of neuroendocrine
cells demonstrated in normal bladder
{60}, and the stem cell theory {254}.
Somatic genetics
Data obtained by comparative genomic
A
B
Fig. 2.68 Neuroendocrine carcinoma of the urinary bladder. A Low power view of a neuroendocrine carcinoma showing both atypical carcinoid and undifferentiated
small cell features. B Well differentiated neuroendocrine carcinoma characterized by cell pleomorphism and high mitotic rate.
Villous adenoma / Small cell carcinoma 135