Tuberous sclerosis complex‐associated nonfunctional pancreatic neuroendocrine tumors: Management and surgical outcomes

Evans, Leah M.; Geenen, Kennedy R.; O’Shea, Aileen; Hedgire, Sandeep; Ferrone, Cristina R.; Thiele, Elizabeth A.

doi:10.1002/ajmg.a.62850

Cited by 9 publications

(14 citation statements)

References 32 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of NETs in the setting of TSC are represented by pNET with an overall prevalence ranging from 1 to 9% [88,[92][93][94][95]. The association between TSC and other NETs in the gastrointestinal tract remains still largely unknown [96].…”

Section: Epidemiology Clinical and Pathological Featuresmentioning

confidence: 99%

“…Functional pNETs are predominantly insulinomas, but rare cases of gastrinomas or glucagonomas were also documented [96,97]. Compared to the general population, pNETs in TSC individuals present an earlier age at onset [88,93] and a major trend to arise as cystic lesions [95,100]. TSC-related pNETs tend to be predominantly solitary and not multifocal [95].…”

Section: Epidemiology Clinical and Pathological Featuresmentioning

confidence: 99%

See 1 more Smart Citation

Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies

Ruggeri

Benevento²,

Cicco³

et al. 2022

J Endocrinol Invest

View full text Add to dashboard Cite

Purpose Neuroendocrine neoplasms can occur as part of inherited disorders, usually in the form of well-differentiated, slow-growing tumors (NET). The main predisposing syndromes include: multiple endocrine neoplasias type 1 (MEN1), associated with a large spectrum of gastroenteropancreatic and thoracic NETs, and type 4 (MEN4), associated with a wide tumour spectrum similar to that of MEN1; von Hippel-Lindau syndrome (VHL), tuberous sclerosis (TSC), and neurofibromatosis 1 (NF-1), associated with pancreatic NETs. In the present review, we propose a reappraisal of the genetic basis and clinical features of gastroenteropancreatic and thoracic NETs in the setting of inherited syndromes with a special focus on molecularly targeted therapies for these lesions. Methods Literature search was systematically performed through online databases, including MEDLINE (via PubMed), and Scopus using multiple keywords' combinations up to June 2022. Results Somatostatin analogues (SSAs) remain the mainstay of systemic treatment for NETs, and radiolabelled SSAs can be used for peptide-receptor radionuclide therapy for somatostatin receptor (SSTR)-positive NETs. Apart of these SSTR-targeted therapies, other targeted agents have been approved for NETs: the mTOR inhibitor everolimus for lung, gastroenteropatic and unknown origin NET, and sunitinib, an antiangiogenic tyrosine kinase inhibitor, for pancreatic NET. Novel targeted therapies with other antiangiogenic agents and immunotherapies have been also under evaluation. Conclusions Major advances in the understanding of genetic and epigenetic mechanisms of NET development in the context of inherited endocrine disorders have led to the recognition of molecular targetable alterations, providing a rationale for the implementation of treatments and development of novel targeted therapies.

show abstract

Section: Epidemiology Clinical and Pathological Featuresmentioning

confidence: 99%

Section: Epidemiology Clinical and Pathological Featuresmentioning

confidence: 99%

Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies

Ruggeri

Benevento²,

Cicco³

et al. 2022

J Endocrinol Invest

View full text Add to dashboard Cite

show abstract

“…It is now widely accepted that PNET is associated with TSC and included in TSC management guidelines [ 4 ]. However, there remains controversy over the frequency of PNET in TSC patients, as most are now identified incidentally; it is believed that less than 10% of TSC patients develop PNET [ 5 , 15 – 19 , 27 ]. One study observed that as low as 0.65% of TSC patients have nonfunctional PNET [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Renal cell carcinoma (RCC) is considered the most common malignancy in TSC patients and presents in 2–5% of cases, usually bilaterally, more often in women, and at a younger age than the general population [ 2 , 5 , 13 , 14 ]. PNET arise in 1–9% of cases and are thought to be associated with TSC2 mutations [ 5 , 15 – 19 ]. Both malignancies are included in the updated TSC surveillance guidelines, though neither contribute to TSC diagnostic criteria [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Malignant tumors in tuberous sclerosis complex: a case report and review of the literature

Liu,

Lele,

Goodenberger

et al. 2024

BMC Med Genomics

View full text Add to dashboard Cite

Background Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations. Case presentation A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5’UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient’s history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified. Conclusions To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.

show abstract

“…[4,5] Although most pNENs are sporadic and likely carry somatic mutations in death domainassociated protein 6 (DAXX) and ATP-dependent heli-case (ATRX), [6] they may develop in patients with hereditary endocrinopathies, including multiple endocrine neoplasia type 1 (MEN1), [7] von Hippel-Lindau (VHL) syndrome, [8] neurofibromatosis type 1 (NF1), [9] and Tuberous Sclerosis Complex (TSC). [10] Evidence for diagnosing, staging, and treating pNENs has emerged over the past few years, particularly in original trials among the Chinese population. Based on this, the Pancreatic Tumor Group of the Oncology Society of the Chinese Medical Association convened a writing committee of multidisciplinary experts to compile Chinese Medical Association Consensus for the Standardized Diagnosis and Management of Pancreatic Neuroendocrine Neoplasms (2022).…”

mentioning

confidence: 99%

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms

Jiao,

Cui,

et al. 2023

Chinese Medical Journal

View full text Add to dashboard Cite

Pancreatic neuroendocrine neoplasms (pNENs) are rare and highly heterogeneous tumors originating from pluripotent stem cells with neuroendocrine differentiation in the pancreas, constituting approximately 3% of all pancreatic tumors. [1] The global incidence of pNENs has been increasing recently, and most cases are sporadic and more common in women. [1,2] Feng Jiao and Jiujie Cui contributed equally to this work.

show abstract

Tuberous sclerosis complex‐associated nonfunctional pancreatic neuroendocrine tumors: Management and surgical outcomes

Cited by 9 publications

References 32 publications

Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies

Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies

Malignant tumors in tuberous sclerosis complex: a case report and review of the literature

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms

Contact Info

Product

Resources

About