Invasive breast carcinoma - IARC

atives intimately admixed. The germ cells
are large and round with clear or slightly
granular cytoplasm and large, ro u n d ,
vesicular nuclei, often with pro m i n e n t
nucleoli, and show mitotic activity, which
may be brisk. Their histological and ultrastructural
appearance and histochemical
reactions are similar to the germ cells of
dysgerminoma or seminoma. The immature
Sertoli or granulosa cells are smaller
and epithelial-like. These cells are round
or oval and contain dark, oval or slightly
elongated carrot-shaped nuclei. They do
not show mitotic activity {2598,2849,
2850}. The sex cord derivatives are
arranged within the cell nests in three
typical patterns as follows:
(1) Forming a coronal pattern along the
periphery of the nests.
(2) Surrounding individual or collections
of germ cells.
(3) Surrounding small round spaces containing
amorphous, hyaline, eosinophilic,
PAS-positive material resembling Call-
Exner bodies.
The connective tissue stroma surrounding
the cellular nests may be scant or
abundant and cellular, resembling ovarian
stroma, or dense and hyalinized. It
may contain luteinized or Leydig-like
cells devoid of Reinke crystals {2598,
2849,2850}.
Three processes, hyalinization, calcification
and overgrowth by a malignant germ
cell element, usually dysgerm i n o m a ,
may alter the basic histological appearance
of gonadoblastoma. The hyalinization
occurs by coalescence of the hyaline
bodies and bands of hyaline material
around the nests with replacement of
the cellular contents. Calcification originates
in the hyaline Call-Exner-like bodies
and is seen histologically in more
than 80% of cases {2598}. It tends to
replace the hyalinized nests form i n g
rounded, calcified concretions. Coalescence
of such concretions may lead
to the calcification of the whole lesion,
and the presence of smooth, rounded,
calcified bodies may be the only evidence
that gonadoblastoma has been
present. The term "burned-out gonadoblastoma"
has been applied to such
lesions {2598,2849,2850}. Gonadoblastoma
is overgrown by dysgerminoma in
approximately 50% of cases, and in an
additional 10% another malignant germ
cell element is present {2598,2846,
2849,2850}. Gonadoblastoma has never
been observed in metastatic lesions or
Fig. 2.111 Dysgerminoma with “burnt out” gonadoblastoma. The typical pattern of a dysgerminoma consists
of aggegates of primitive germ cells separated by fibrous septa infiltrated by lymphocytes. The presence of
“burnt out” gonadoblastoma is indicated by smooth, rounded, calcified bodies.
outside the gonads {2598,2849,2850}.
In most cases the gonad of origin is indeterminate
because it is overgrown by the
tumour. When the nature of the gonad
can be identified, it is usually a streak or
a testis. The contralateral gonad, when
identifiable, may be either a streak or a
testis, and the latter is more likely to harbour
a gonadoblastoma {2598,2849,
2850}. Occasionally, gonadoblastoma
may be found in otherwise norm a l
ovaries {2077,2598,2849,2850}.
Tumour spread and staging
At the time of operation gonadoblastomas
typically are bilateral, although at
times they may be not macroscopically
detectible in the gonad. Those that are
overgrown by dysgerminoma or other
malignant germ cell tumour may be
much larger. If a malignant germ cell
tumour develops, the potential for
metastatic disease exists. Dysgerm i-
nomas typically spread by the lymphatic
route, less frequently by peritoneal dissemination.
There f o re, it is extre m e l y
i m p o rtant not only to remove both
gonads but to perform surgical staging if
at the time of operative consultation a
malignant germ cell tumour is identified.
The typical staging for a dysgerminoma
or other malignant germ cell tumour
includes pelvic and para-aortic lymph
node sampling as well as peritoneal
washings if no ascites is present {2586}.
The operation should include omentectomy,
and multiple peritoneal samplings
are required. For patients with spread of
a malignant germ cell tumour other than
d y s g e rminoma, aggressive cytore d u c-
tion surgery is appropriate {2586}.
Precursor lesions
Gonadoblastoma is almost invariably
associated with an underlying gonadal
disorder. When the disorder is identifiable,
it is usually pure or mixed gonadal
dysgenesis with a Y chromosome being
detected in over 90% of the cases {2598,
2605}.
Prognosis and predictive factors
Clinical criteria
Patients having gonadoblastoma without
dysgerminoma or other germ cell tumour
are treated by surgical excision of the
gonads without additional therapy.
However, if dysgerminoma and/or another
malignant germ cell element is present,
surgical staging and postoperative
combination chemotherapy, the most
popular current regimen being
bleomycin, etoposide and cisplatin
(BEP), are re q u i red. Other re g i m e n s
include etoposide and carboplatin
{2586}. Dysgerminoma is exquisitely
sensitive to chemotherapy, as it was previously
shown to be exquisitely responsive
to radiation therapy.
Mixed germ cell-sex cord-stromal tumours 177