Séances ordinaires

Pour améliorer la qualité de l’exérèse chirurgicale chez 54 patients traités pour cancer différencié de la thyroïde et ayant une maladie persistante ou récidivée, le protocole suivant a été utilisé : -administration thérapeutique de 100 mCi d’iode 131 à j0, -scintigraphie corps entier à j4, -chirurgie radio-guidée à j5, contrôle scintigraphique post-chirurgical à j7. Ce protocole a été associé à une imagerie conventionnelle (échographie cervicale, scanographie cervico-médiastinale).Tous ces patients avaient déjà été opérés (thyroïde, ganglions) et traités par l’iode 131 (1 à 7 traitements). L’apport de la technique a été considéré comme décisif chez 20 patients (dissection difficile dans la sclérose, situations anatomiques particulières des ganglions métastatiques). Chez 26 patients, l’utilisation de la sonde a facilité la détection des formations fixantes, et dans tous les cas a permis de contrôler le caractère complet de l’exérèse chez 46 patients. La disparition des fixations était confirmée en postopératoire par la scintigraphie chez 46 patients. Les 8 échecs se répartissent en échecs de l’exploration chirurgicale (pas de foyer retrouvé chez 4 patients) et échecs liés à une mauvaise interprétation des foyers fixants (2 fixations thymiques, 2 fixations au niveau des glandes salivaires).

Le regroupement des tumeurs neuroendocrines au sein d’une même
entité de recherche se justifie non seulement par l’existence d’une
définition et de propriétés communes à l’ensemble de ces tumeurs,
mais également par leur rareté. Cette revue fait le point des avancées
récentes en matière de classification, détaille la place prise par
la Chromogranine A dans le bilan biologique de ces tumeurs, de la
scintigraphie des récepteurs de la somatostatine dans le bilan d’imagerie.
Elle rappelle la complexité de la prise en charge des patients
porteurs de tumeurs endocrines associées à un syndrome de prédisposition.
Enfin, elle souligne les avancées en matière de définition
des facteurs pronostiques et notamment la place croissante que
prennent les marqueurs de prolifération et d’invasion vasculaire
dans cette classification. Enfin, l’individualisation progressive du
phénotype histologique, clinique, biologique et morphologique des
patients, répondeurs aux différentes thérapeutiques disponibles, est
rappelée.

Classification and treatment of Endocrine Tumors (ET)

Endocrine tumors (ET) are defined by positive immunostaining for
chromogranine A, synaptophysin and less specific markers such as
neuron-specific enolase and N-CAM. This definition includes various
tumors scattered within the body and which share common
characteristics : hormone secretion, association as part of inherited
syndrome, common prognostic parameters and therapeutic management.
Several points challenge the clinical management of these
tumors : confusion regarding previous definition (apudoma, carcinoid…),
their rarity, insufficient knowledge regarding prognostic
parameters of relapse and survival and poor chemosensitivity. ETs
stem from two main embryological tissues : the neuroectoderm
(medullary thyroid carcinoma and pheochromocytoma mainly) and
the endoderm (also called gastro-enteropancreatic (GEP) tumors).
In the latter group, ETs are subdivided into three subgroups with
various behavior regarding biological activity, association as part of
inherited syndrome frequency, prognosis : foregut-derived (head
and neck, thymus, bronchus, pancreas mainly), midgut-derived
(ileum), hindgut-derived (rectum) ET.
Classification aims at recognizing tumors with common clinical
presentation, prognostic or therapeutic behavior. Initial clinical management of these tumors has two main goals, to look for associated
hormone secretions and inherited syndromes, both being dependent
on the primary. The great majority of ETs secrete at least
one hormone with or without clinical consequences. Morbidity induced
hormone secretion (metanephrine, serotonine, insulin, gastrin)
should be early recognized and treated. Also, hormone secretion
may constitute helpful biological markers which high specificity
but various sensitivity. The recommended biological work-up
has been standardized according to the primary (Baudin et al, Ann
Oncol 2001). Of note, secretions in foregut -derived ETs, in contrast
with midgut-derived ETs are characterized by their biological diversity.
Screening for association as part of inherited syndrome is restricted
to neuroectoderm and well-differentiated endoderm-derived
ET. Familial and personal patient history, ET primary and tumor
presentation (multifocality, natural history) are major points to look
for a genetic screening. Main consequences of such a diagnosis are :
early diagnosis of associated tumors, and familial screening with a
various impact on cure rate depending on each syndrome. Main
inherited syndromes to be screened for are : multiple endocrine
neoplasia type 1 and 2, Von-Hippel-Lindau disease, type 1 neurofibromatosis,
mitochondrial complex type II disease. Genes responsible
for these syndromes are known and genotype-phenotype correlations
have been described for some.
ET prognosis mainly depends on pathological differentiation and
tumor stage. Primary impact on prognosis is still questioned, as well
as ET association as part of an inherited syndrome. Hormone secretion
is no more a major prognostic parameter. The best prognostic
approach has been brought by studying lung ETs. Travis demonstrated
that 4 subgroups of lung ETs can be distinguished according
to their survival by taking into account the mitotic count and necrosis.
Typical carcinoid is characterized by a low mitotic count (< 2 /
10 HPF), atypical carcinoid or well differentiated endocrine carcinoma
by mitosis ranging between 2 to 10 / HPF and or punctiforme
necrosis, large cell (poorly differentiated ) endocrine carcinoma by
a high rate of mitosis above 10 / HPF , large necrosis area and lost
of the endocrinoid pathological pattern. For intestinal ETs, the
WHO 2000 classification defines benign or uncertain well differentiated
endocrine tumors depending on size, depth invasion and angioinvasiveness.
For pancreatic ETs, the Ki67 positive percentage
of cells and the mitotic count is taken into account instead of depth
invasion. Patients with locoregional extension or distant metastases
are classified as well differentiated endocrine carcinoma. Poorly
differentiated endocrine carcinoma may be encountered mainly in
pancreatic, colon and rectum ET.
Therapeutic management aims at reducing both hormone secretion
(always first) and tumor burden. The only curative therapy is surgery in patients presenting with localized ET mainly, appendix,
rectum, bronchus and insulinoma. In the majority of metastatic ET
patients treatment remains palliative and should therefore take into
account the natural history of the disease. Poorly differentiated ET
and pancreatic ET are chemosensitive but complete responses are
rare. In no or slowly progressive ET, a wait-and-see policy and/or
locoregional therapeutic approaches should be considered. Protocols
should include patients with morphologically progressive ET.