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

mon in females by 1.4:1 {1845}. The clinical
triad of sustained or paroxysmal
hypertension, intermittent gross hematuria
and "micturition attacks" is the characteristic
feature {1420,1845}. These
attacks consist of bursting headache,
anxiety, tremulousness, pounding sensation,
blurred vision, sweating and even
syncope related to increased levels of
catecholamines or their metabolites
which can be found in serum or urine
{1845}. Some cases have been familial.
Macroscopy
An autopsy study has shown that paraganglia
were present in 52% of cases
{1115}. They were present in any part of
the bladder and at any level of the bladder
wall. Most were in the muscularis
propria and this is where most of the
tumours are located. In 45 cases where
the location was known, we found 38% in
the dome, 20% in the trigone, 18% posterior
wall, 13% anterior wall and the others
in the bladder neck and lateral walls.
Most of these are circumscribed or
multinodular tumours, usually less then
4.0 cm in size. In one study there was an
average diameter of 1.9 cm {1420}.
Histopathology
Microscopically, the cells are arranged in
discrete nests, the "Zellballen" pattern,
separated by a prominent vascular network.
Cells are round with clear,
amphophilic or acidophilic cytoplasm
and ovoid nuclei. Scattered larger or
even bizarre nuclei are often present
{1845}. Mitoses are rare, and usually
absent {1466}. In some cases there may
be striking resemblance to urothelial carcinoma.
In about 10% of the cases, small
neuroblast-like cells are present, usually
immediately beneath the urothelium. By
immunohistochemistry, bladder paragangliomas
react as they do at other
sites – negative for epithelial markers
Fig. 2.72 Paraganglioma of the urinary bladder.
Large paraganglioma adjacent to the wall of the
urinary bladder.
A
B
Fig. 2.71 Paraganglioma. A Paraganglioma with circumscribed growth pattern. B Paraganglioma with dissection
through the muscularis propria. C Paraganglioma with circumscribed growth pattern.
and positive for the neuroendocrine
markers – chromogranin, synaptophysin
and others. Flattened sustentacular cells
can sometimes be highlighted in the
periphery of the cell nests with S-100
protein. Ultrastructural features include
dense core neurosecretory granules,
usually having the typical morphology of
catecholamine–secreting tumours with
eccentric dense cores {948,1280}.
Prognosis and predictive factors
The criteria for diagnosing malignant
paraganglioma are metastasis and/or
"extensive local disease" {1508}. Longterm
follow-up is always indicated
because metastases have been known
to occur many years later {948,1280,
1508}. A recent study found that those
tumours staged as T1 or T2 did not show
any recurrences or metastases while
those that were stage T3 or higher were
at risk for both {429}. A review of 72 AFIP
cases accumulated since the initial 58
cases reported in 1971 {1466} has
C
recently been done (unpublished data).
Twelve of the 72 (16.7%) were judged to
be malignant based upon the presence
of metastasis or extension beyond the
bladder. Four features appear to indicate
an increased potential for malignant
behaviour:
1. Younger age: there were 8 cases in
the second decade of life and 5 of these
were malignant.
2. Hypertension: this was seen in 50%
of malignant cases and 12% of the
benign ones.
3. Micturition attacks: these were also
seen in 50% of malignant cases and
12% of benign ones.
4. Invasive dispersion through the bladder
wall. The malignant tumours usually
demonstrated widespread dispersion
through the bladder wall, sometimes with
fragmentation of muscle fascicles by
tumour nests. This was rarely seen in
those that proved to be benign.
Paraganglioma 137