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

chronically inflamed urothelium and has
nuclear changes clearly ascribable to a
reactive/regenerative process. Cells are
uniformly enlarged with a single prominent
nucleolus and evenly distributed
vesicular chromatin. Mitotic activity may
be brisk but without atypical forms.
Inflammation may be present in the
urothelium or lamina propria {79,424}.
Fig. 2.32 Reactive urothelial atypia due to chronic inflammation.
cystoscopically silent. Primary (de novo)
dysplasia may present with irritative
bladder symptoms with or without hematuria
{423,1849,2947}. A clinical history
of stones, infection, instrumentation or
intravesical therapy is often available in
reactive cases.
Macroscopy
Lesions may be inapparent or associated
with erythema, erosion or, rarely,
ulceration.
Histopathology
Normal urothelium
Normal urothelium is urothelium without
cytologic atypia and overall maintenance
of polarity, or mild architectural alteration
{706}. It is three to six layers thick,
depending on the state of distention, and
is composed of basal cells, intermediate
cells and superficial cells. Minimal
crowding and nuclear overlap without
any cytologic abnormality is within the
range of normal {79,84,706}.
Dysplasia
Lesions show variable often appreciable
loss of polarity with nuclear rounding and
crowding and cytologic atypia that is not
severe enough to merit a diagnosis of
CIS. The cells may have increased cytoplasmic
eosinophilia and the nuclei have
irregular nuclear borders, mildly altered
chromatin distribution, inconspicuous
nucleoli and rare mitoses. Pleomorphism,
prominent nucleoli throughout the urothelium
and upper level mitoses argue for a
CIS diagnosis {79,84,424,706,1851}.
Cytokeratin 20 may be of value in its
recognition {261,1023}.
Reactive atypia
Reactive atypia occurs in acutely or
Urothelial atypia of unknown significance
Atypia of unknown significance is not a
diagnostic entity, but a descriptive category
for cases with inflammation in which
the severity of atypia appears out of proportion
to the extent of inflammation such
that dysplasia cannot be confidently
excluded {424,706}. Alterations vary significantly.
This is not meant to be a "waste
basket" term but should be used for
lesions with atypia that defy categorization
but which the observer feels would
benefit from clinical follow-up {424,706}.
Somatic genetics
Alterations of chromosome 9 and p53
and allelic losses have been demonstrated
{534,1031}.
Prognostic and predictive factors
Dysplasia is most relevant in non-invasive
papillary neoplasms, where its presence
indicates urothelial instability and a
marker for progression or recurrence
(true risk remains to be established)
{71,1361,1802,1866,2450}. It is frequently
present with invasive cancer, whose
attributes determine outcome {1361,
1846}. De novo dysplasia progresses to
bladder neoplasia in 5-19% of cases; in
most cases, however progressive lesions
do not arise from dysplastic regions {79,
423,424,1849,1851,2947}.
112 Tumours of the urinary system