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

The clinical significance of glandular differentiation
and mucin positivity in urothelial
carcinoma remains uncertain {1528}.
Nested variant
The nested variant of urothelial carcinoma
is an aggressive neoplasm with less
than 50 reported cases {639,1109,1848,
2562,2896}. There is a marked male predominance
{639}, and 70% of patients
died 4-40 months after diagnosis, in spite
of therapy {1109}. This rare pattern of
urothelial carcinoma was first described
as a tumour with a "deceptively benign"
appearance that closely resembles
Brunn nests infiltrating the lamina propria.
Some nests have small tubular
lumens {2562,2896}. Nuclei generally
show little or no atypia, but invariably the
tumour contains foci of unequivocal
anaplastic cells exhibiting enlarged
nucleoli and coarse nuclear chromatin
{639,1848}. This feature is most apparent
in deeper aspects of the tumour {1848}.
Useful features in recognizing this lesion
as malignant are the tendency for
increasing cellular anaplasia in the deeper
aspects of the lesion, its infiltrative
nature, and the frequent presence of
muscle invasion. The differential diagnosis
of the nested variant of urothelial carcinoma
includes prominent Brunn nests,
cystitis cystica and glandularis, inverted
papilloma, nephrogenic metaplasia, carcinoid
tumour, paraganglionic tissue and
paraganglioma {639,1109,1848,2562,
2896}. The presence of deep invasion is
most useful in distinguishing carcinoma
from benign proliferations, and the
nuclear atypia, which is occasionally
present is also of value. Closely packed
and irregularly distributed small tumour
cells favour carcinoma. Inverted papilloma
lacks a nested architecture.
Nephrogenic metaplasia typically has a
mixed pattern, including tubular, papillary,
and other components, and only
rarely has deep muscle invasion {639}.
The nested variant of carcinoma may
mimic paraganglioma, but the prominent
vascular network of paraganglioma,
which surrounds individual nests, is not
usually present in nested carcinoma.
Microcystic variant
Occasionally urothelial carcinomas show
a striking cystic pattern with cysts ranging
from microscopic up to 1-2 mm in
diameter. The cysts are round to oval,
sometimes elongated and may contain
necrotic material or pale pink secretions.
The cyst lining may be absent, flattened
or urothelial and may show the differentiation
towards mucinous cells. The differential
diagnosis therefore includes
urothelial carcinoma with gland like lumina,
as well as benign processes like cystitis
cystica, cystitis glandularis or even
nephrogenic adenoma. The pattern
should be separated from the nested
variant of urothelial carcinoma with tubular
differentiation. Urothelial carcinoma
A
Fig. 2.10 A,B Nested cell variant of urothelial carcinoma of the urinary bladder.
B
A
Fig. 2.11 A, B Infiltrative urothelial carcinoma. Nested variant.
B
Infiltrating urothelial carcinoma
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