(4.) Cavalli T, Giudici F, Santi R Nesi G, Brandi ML, Tonelli F Ventricular fibrillation resulting from electrolyte imbalance reveals vipoma in MEN1 syndrome
. Fam Cancer 2016; 15: 645-9.
Kovacs et al., "Pituitary tumors in patients with MEN1 syndrome
," Clinics, vol.
Most insulinomas are solitary and sporadic, although about 10% are associated with MEN1 syndrome
. In MEN1 patients, insulinomas are often multiple and other manifestations of this syndrome must be considered, although in our patient, due to normal level of serum prolactin, MEN1 was excluded.
These features are frequently seen not only in von Hippel-Lindau syndrome but also in sporadic pancreatic NETs and in association with MEN1 syndrome
. (95) Differential diagnosis of clear cell pancreatic NETs includes metastatic renal cell carcinomas, especially in the setting of patients with von Hippel-Lindau syndrome.
Instead, hereditary MEN1 gene mutations give rise to MEN1 syndrome
, in which primary tumors occur in two or more endocrine glands.
MEN1 syndrome is usually an autosomal dominant inherited disorder that arises from germline mutation of the MEN1 gene (chromosome 11q13), which encodes menin, a protein required for transcriptional regulation and genomic stability.
It is already thought that loss of PPAR-[gamma] function may lead to the overproduction of lipomas in patients with MEN1 syndrome .
The first reason they gave for this is that hibernomas are not known to occur in MEN1 syndrome, although lipomas and other mesenchymal tumours are.
This case illustrates that hibernomas can be identified in patients with MEN1 syndrome. The incidence of hibernomas in patients with MEN1 syndrome has not been fully established; this might be because these are benign and slowly growing and therefore are less well documented.
In the case of the MEN1 gene, evidence is beginning to accumulate that suggests that its function is likely to be lost in some sporadic cancers of the same tissues affected in the hereditary MEN1 syndrome
. One study showed that ~21% of sporadic parathyroid tumors had MEN1 mutations (5).
While the underlying mechanism of this finding is largely unknown, this phenomenon is attributed to the status of pseudohypoxia resulting in HIF-1[alpha] increase in the setting of VHL disease, (15) since positivity for inhibin has not been observed in other clear cell NETs associated with MEN1 syndrome. (22) Thus, positivity for inhibin is used to suggest the possibility of VHL disease underlying multifocal clear cell NETs.
Of note, clear cell pancreatic NETs can also occur, although less commonly, in patients with MEN1 syndrome (22); therefore, the finding of a clear cell pancreatic NET should not prompt the pathologist to reflexively suggest the patient be examined for VHL, but should also bring MEN1 to consideration in the differential diagnosis.