Background:
Pheochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumors. Nearly 40% of patients with PCC/PGL have germline mutations. Genetic screening algorithims are based on specific clinical features. Phenotype differences from PCC/PGL manifest as different hormonal profile, anatomical localization and risks of recurrence or metastatic disease. According to molecular biology and genetic-based classification PCC/PGL can be divided in three Clusters: Cluster 1a (Krebs Cycle), Cluster 1b (Pseudohypoxic) and Cluster 2 (Kinases signaling).
In order to characterize these groups, we retrospectively reviewed the electronic charts of PCC/PGL patients seen at our hospital (2007 until 2017). We identified 54 PCC/PPGL diagnosed patients. Thirteen (13) had positive genetic testing, one had clinical diagnosis of VHL and two of NF 1 (29.6%).
Sixteen patients were classified in three clusters: Cluster 1a (3 SDHB and 1 SDHD), Cluster 1b (5 VHL), Cluster 2 (2 MEN 2 A, 2 MEN 2 B, 2 NF1 and 1.
|
|
Cluster 1a N: 4 |
Cluster 1b N: 5 |
Cluster 2 N: 7 |
|
Mean age at diagnosis |
44 years old |
24 years old |
32 years old |
|
Male/Female |
3/1 |
1/4 |
5/2 |
|
Clinical Presentation |
Signs and Symptoms |
Signs and Symptoms |
Signs and Symptoms (2), Genetic Predisposition (4), Incidentaloma (1) |
|
Biochemical Phenotype |
Noradrenergic phenotype (3), biochemical silent (1) |
Noradrenergic phenotype (4) |
Adrenergic phenotype (4), biochemical silent (3) |
|
Localization |
Bilateral PCC (1), head and neck PGL (1), abdominal PGL (4) |
Bilateral PCC (4), unilateral PCC (1), abdominal PGL (1) |
Bilateral PCC (3), unilateral PCC (4) |
|
Size tumor range |
4-6 cm |
4-6 cm |
2-4 cm |
|
Recurrence/Metastasis |
2 metastasis |
1 recurrence
|
No |
Conclusions:
Genetic syndromes associated with PCC / PGL are present in a significant proportion of patients. It is essential to carry out the genetic workup and identify particular clinical and biochemical characteristics, risks of recurrence and metastatic disease.