Pathologica 4-07.pdf - Pacini Editore

SLIDE SEMINAR JUNIORES
Urothelial dysplasia. The thickness of the urothelium is usually
normal four to seven layers but may be increased or decreased.
There is loss of clearing of cytoplasm, nucleomegaly,
irregularity of nuclear contours and altered chromatin distribution.
Nucleoli are usually not conspicuous; only a minor degree
of pleomorphism is allowable in dysplasia and the mitotic
activity is variable though usually not in the higher layers.
Loss of polarity is evidenced by crowding and nuclei with the
long axis parallel to the basement membrane 16 . Comparison
with more normal appearing urothelium, if present, may help
in assessing features like nucleomegaly, and loss of clearing
and polarity. The distinction between urothelial dysplasia and
carcinoma in situ is essentially one of morphologic threshold
since nuclear atypia is evident but should not be severe
enough to merit a diagnosis of carcinoma in situ. The lamina
propria is usually unaltered but may contain increased inflammation
and/or neovascularity.
Immunohistochemistry shows abnormal expression of CK20,
Ki-67 and p53 in the majority of the cases, together or individually,
and helps to distinguish reactive atypia from dysplasia
but not dysplasia from CIS 5 . Increased reactivity for
CD44 in all layers of the urothelium is, on the contrary, more
commonly seen in reactive atypia 7 .
Dysplastic lesions are typically seen in bladders with urothelial
neoplasia and are uncommon in patients without it 17 . In
patients with bladder tumors, the presence of dysplasia
places them at higher risk for recurrence and progression 18 .
Urothelial carcinoma in situ. Carcinoma in situ CIS Highgrade
Intraurothelial Neoplasia is histologically characterized
by unequivocal severe cytological atypia, i.e., the type
of atypia usually seen in invasive urothelial carcinoma. The
urothelium may be diminished in thickness or of normal
thickness, while the observation of an increased thickness is
exceedingly rare. Cells have large, irregular, hyperchromatic
nuclei often with one or more large nucleoli. There is alteration
or complete loss of polarity and mitotic activity is
frequently observed 9 2 . The lamina propria is frequently hypervascular
and inflamed reflecting the erythematous appearance
witnessed on cystoscopy. When evaluating the degree
of cytological atypia, it is always important the comparison
with the cells of the surrounding normal urothelium.
CIS may grow in the surrounding normal urothelium as clusters
or isolated single cells pagetoid spread or undermining
or overriding it 19 . The term of clinging CIS is used for cases
where only a few residual cancer cells remain on the surface
9 .
A common feature of CIS is the lack of intercellular cohesion
resulting in extensive denudation. Since denudation may occur
also in association with trauma due to instrumentation or
therapy, deeper sections through the paraffin block may be
helpful in revealing atypical cells diagnostic for CIS. In the
absence of atypical cells, the finding of extensive denudation,
particularly when associated with neovascularity and chronic
inflammation in the lamina propria, must be included in
the report and correlation with urine cytology findings may
be suggested 1 .
Potential mimics of CIS are the truncated papillae that remain
after treatment of papillary carcinoma with Mitomycin
C and thiotepa, particularly when associated with denudation
and inflammation 20 . CIS can be mimicked 21 by infection of
immunocompromised patients with the human polyoma virus
resulting in large homogeneous inclusions in enlarged nuclei
of urothelial cells.
The differentiation of CIS from other flat urothelial lesions
with atypia is based primarily on the cytologic features. Lim-
99
ited studies suggest a potential adjunctive role of immunohistochemistry
7 22-24 . CIS frequently shows diffuse, strong cytoplasmic
reactivity for CK20 and diffuse nuclear reactivity
for p53 throughout the full thickness of the urothelium.
CD44 reactivity is limited to a residual basal cell layer of
normal urothelium when present, but is absent in the neoplastic
cells. A panel consisting of these three antibodies is
important as not all cases of CIS consistently exhibit the
characteristic immunostaining.
CIS with microinvasion. In bladder carcinoma in situ, a
careful search should be made for the presence of invasion.
Microinvasive carcinoma of the urinary bladder is defined by
invasion into the lamina propria to a depth ranging 2-to-5
mm from the basement membrane 25 26 . Microinvasion appears
as direct extension cords tentacular, single cells, or single
cells and clusters of cells. The neoplastic cells may be interspersed
among and masked by chronic inflammation. In
this case immunohistochemistry with antibodies against CEA
or cytokeratins such as AE1-AE3 should be applied to identify
the invading cells 9 . Desmoplasia or retraction artifacts
that may mimic vascular invasion are useful in recognizing
invasion 27 28 .
Some patients who have had prior bladder biopsies or
transurethral resections undergo a repeat resection within
several months for various reasons. The detection of a few
residual tumour cells in bladder specimens with prior biopsy
site changes can be challenging based on histology alone.
Immunohistochemistry for cytokeratins may be used as an
adjunct in this situation. However, when interpreting CK
stains for the detection of residual tumour cells, one should
pay attention to the nature of the cells and not assume all CK
positive cells are neoplastic 2 .
Papillary urothelial neoplasms. The papillary lesions are
here described according to the WHO 2004 classification 1 .
We do not report here the WHO 1973 classification because
it is already well known in the pathology, urology and oncology
communities. There still is debate as to whether the
WHO 2004 system should be the only one to be used and
whether the WHO 1973 system should be abandoned. Current
practice in patient’s management is still based on the old
one.
Urothelial papilloma. Urothelial papilloma without qualifiers
refers to the exophytic variant of papilloma, defined as
a discrete papillary growth with a central fibrovascular core
lined by urothelium of normal thickness and cytology. This is
a rare, benign condition typically occurring as a small, isolated
growth, commonly but not exclusively seen in younger
patients 29 30 .
Inverted urothelial papilloma. Although not strictly speaking
a papillary lesion is classified here because it shares certain
features with exophytic urothelial papilloma. The histology
of inverted papillomas has been well described 31 . Rarely,
cases are hybrid in which significant portions of the lesion resemble
exophytic urothelial papillomas and inverted urothelial
papillomas. These lesions should be classified as papillomas
with both exophytic and inverted features 2 .
When completely excised, inverted papillomas have a very
low risk of recurrence. In a minority of cases, they may be
associated with urothelial carcinoma occurring either concurrently
or subsequently. Rarely, cases of urothelial carcinoma
arising in inverted urothelial papillomas have been described
1 .
Papillary urothelial neoplasm of low malignant potential.
A papillary urothelial lesion with an orderly arrangement of
cells with minimal architectural abnormalities and minimal