CHAPTER X CHAPTER 4 - Cancer et environnement

Tumours containing both germ cell and
sex cord / gonadal stromal elements
T.M. Ulbright
Gonadoblastoma
Definition
A tumour composed of two principal cell
types: large germ cells similar to those of
seminoma and small cells resembling
immature Sertoli and granulosa cells;
elements resembling Leydig or lutein-like
cells may also be present.
ICD-O code 9073/1
Incidence and clinical features
Gonadoblastoma is most commonly
seen in mixed gonadal dysgenesis associated
with ambiguous genitalia and 45,X
karyotype and Y chromosome material
{1389,1390,2266,2350}. The estimated
risk of developing gonadoblastoma in
this setting is 15-25% {2026}. In one
series about 24% of patients with Turner
syndrome had Y chromosome material
{2026} and in another series 12.2%
{930}. In the latter only 7-10% of patients
had gonadoblastoma. Rarely, gonadoblastoma
is found in genotypical and
phenotypical males {413,2350}.
Macroscopy
The gonads contain yellowish to tan nodules
with a gritty cut surface. The
tumours may consist of microscopic foci
or can measure up to 8 cm {2350}.
Histopathology
The lesion consists of immature Sertoli
cells and germ cells which form rounded
or irregularly outlined discrete aggregates.
Most commonly, the Sertoli cells
encircle rounded hyaline nodules and
are intimately associated with basement
membranes surrounding the nests. In the
second growth pattern the Sertoli cells
surround large germ cells or in the third
pattern the germ cells occupy the center
of the nests and the Sertoli cells form a
peripheral ring. Mostly in the post pubertal
patient, the stroma may contain large
polygonal cells indistinguishable from
Leydig cells. Calcifications may be focal,
involving the hyaline bodies or extensive.
About 50% of all patients with gonadoblastoma
irrespective of the underlying
abnormality develop germ cell tumours
mainly seminomas, but in 8%, other
germ cell tumour types. By the age of 40,
25% of patients with mixed gonadal dysgenesis
and Y component have gonadoblastoma
and germ cell tumour {1620}.
Immunoprofile
The germ cells in gonadoblastoma
express the VASA protein {2929}, testis
specific protein Y-encoded (TSPY)
{1448}, and overexpress p53 protein
{1149}. They also have features of
intratubular malignant germ cells
expressing PLAP and c-kit {1248}. The
stromal cells express inhibin and the
Wilms tumour gene (WT-1) {1149}.
Differential diagnosis
Sertoli cell nodules containing germ cells
may be mistaken for gonadoblastoma.
Germ cell-sex cord/stromal tumours
occur rarely in otherwise normal males
{266,2566}. In these tumours the germ
cells are seen within tubules or form
cohesive nests.
Genetics
Germs cells in gonadoblastoma have
been reported to be aneuploid {1248}.
Gonadoblastomas contain evidence of Y-
chromosome material by fluorescence in
situ hybridization {1163}. The Y-chromosome
contains the candidate gene of the
gonadoblastoma locus {2286,2650}.
Interestingly, the seminomas and nonseminomas
originating in dysgenetic
A
B
Fig. 4.82 Gonadoblastoma. A Characteristic nested arrangement. B Gonadoblastoma with seminoma. C This
nest has cylinders of basement membrane, some of which are calcified.
C
Tumours containing both germ cell and sex cord / gonadal stromal tumours 259