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

A
B
Fig. 1.14 Birt-Hogg-Dubé syndrome (BHD). A Hybrid oncocytic tumour composed of a mixture of clear cells and cells with abundant eosinophilic cytoplasm. B Small
cluster of clear cells is surrounded by normal tubules. These lesions can be found scattered through the renal parenchyma.
presence of pulmonary cysts are recognised
features of BHD syndrome. Multiple
lipomas and mucosal papules have been
described {2361}. A reported association
with colonic neoplasia has not been confirmed
in subsequent studies, there may be
a slight increase in the incidence of other
neoplasia although this remains unclear
{1307}.
Genetics
BHD syndrome is a rare autosomal dominant
condition with incomplete penetrance.
The BHD gene maps to chromosome
17p11.2 {1306,2328}. It codes for a novel
protein called folliculin whose function is
unknown currently {1891}.
Affected family members typically show
frameshift mutations, ie insertions, stop
codons, deletions {1891}. A mutational hot
spot present in more than 40% of families
was identified in a tract of 8 cytosines
{2032}.
LOH analyses and assessment of promoter
methylation indicate that BHD is also
involved in the development of a broad
spectrum of sporadic renal cancers {1308}.
Management
Surveillance for all first-degree relatives of
an affected individual is advocated. Skin
examination to determine diagnosis from
the third decade. For those with skin features
or found to have the characteristic
dermatological features, annual renal MRI
scan would be the investigation of choice to
detect any renal malignancy at as early a
stage as possible and to facilitate minimal
renal surgery where possible to conserve
renal function. In tumour predisposition
syndromes where a second somatic mutation
in the normally functioning wild type
gene will leave no functioning protein in the
cell, repeated examinations involving ionising
radiation may carry a risk of inducing
malignancy.
Constitutional chromosome 3
translocations
Definition
Inherited cancer syndrome caused by constitutional
chromosome 3 locations with different
break points, characterized by an increased
risk of developing renal cell carcinomas (RCC).
MIM No. 144700 {1679}.
Diagnostic criteria
Occurrence of single or multiple, unilateral
or bilateral RCC in a member of a family
with a constitutional chromosome 3 translocation.
The association of RCC with a chromosome
3 translocation alone is not diagnostic
since this genetic alteration is also
observed in sporadic cases.
Pathology
Tumours show histologically the typical features
of clear cell RCC.
Table 1.03
Familial renal cell cancer associated with chromosome 3 constitutional translocation.
From F. van Erp et al. {2695}.
Translocation Number of Generations Mean Reference
RCC cases Involved age
t(3:8)(p14:q24) 10 4 44 Cohen et al. {476}
t(3:6)(p13:q25.1) 1 3 50 Kovacs et al {1371}
t(2:3)(q35:q21) 5 3 47 Koolen et al. {1355}
t(3:6)(q12:q15) 4 4 57.5 Geurts van Kessel
et al. {862}
t(3:4)(p13:p16) 1 3 52 Geurts van Kessel
et al. {862}
t(2:3)(q33:q21) 7 3 n.i. Zajaczek et al.
{2917}
t(1:3)(q32:q13.3) 4 4 66.7 Kanayama et al.
{1265}
Familial renal cell carcinoma
21