Endoscopic ultrasound-guided radiofrequency ablation of pancreatic insulinoma: a state of the art review.

INTRODUCTION: Insulinomas are the most common functional pancreatic neuroendocrine tumors (PNETs) that lead to incapacitating hypoglycemia. Guidelines recommend surgical resection as the mainstay of management. However, surgery is fraught with complications, causing significant peri/post-operative morbidity. Since insulinomas are usually benign, solitary, small (<2 cm), and do not need lymphadenectomy, hence, in this regard, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is now being increasingly performed, to circumvent these adverse events and impairment of pancreatic function. AREAS COVERED: A comprehensive literature search was undertaken across various databases (PubMed/MEDLINE, Embase, Scopus), with no language restriction, for relevant articles (case series, reviews, case reports) pertaining to EUS-RFA for insulinoma and PNETs, till October 2023. In this review, we have explicated the role of EUS-RFA for insulinoma management, detailing thoroughly its mechanism of action, EUS-RFA devices with data on its safety and efficacy, and an algorithmic approach for its management. EXPERT OPINION: EUS-RFA is being advocated as a 'mini-invasive' option with the potential to replace surgery as a first-line approach for benign, sporadic, solitary, and small (<2 cm) insulinomas. Under real-time guidance, EUS-RFA has immense precision, is safe, predictable, with acceptable safety profile. Presently, it is being frequently performed for high-risk or inoperable candidates. Current need-of-the-hour is a randomized controlled trial to substantiate its role in the therapeutic algorithm for insulinoma management.

Multiple Endocrine Neoplasia Type 1 Syndrome Pancreatic Neuroendocrine Tumor Genotype/Phenotype: Is There Any Advance on Predicting or Preventing?

Multiple endocrine neoplasia type 1 syndrome (MEN1) is a disease caused by mutations in the MEN1 tumor suppressor gene leading to hyperparathyroidism, pituitary adenomas, and entero-pancreatic neuroendocrine tumors. Pancreatic neuroendocrine tumors (PNETs) are a major cause of mortality in patients with MEN1. Identification of consistent genotype-phenotype correlations has remained elusive, but MEN1 mutations in exons 2, 9, and 10 may be associated with metastatic PNETs; patients with these mutations may benefit from more intensive surveillance and aggressive treatment. In addition, epigenetic differences between MEN1-associated PNETs and sporadic PNETs are beginning to emerge, but further investigation is required to establish clear phenotypic associations.

Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies.

Background: Splanchnic vein thrombosis due to co-existing metastatic pancreatic neuroendocrine tumour (pNET) and JAK2V617F mutation is a rare condition. Case report: Here we present a case of a young woman with complete remission of a non-functioning grade 2 pNET with unresectable liver metastases, coexisting with JAK2V617F mutation. Splenectomy and distal pancreatectomy were performed. Neither surgical removal, nor radiofrequency ablation of the liver metastases was possible. Therefore, somatostatin analogue (SSA) and enoxaparine were started. Peptide receptor radionuclide therapy (PRRT) was given in 3 cycles 6-8 weeks apart. Genetic testing revealed no multiple endocrine neoplasia type 1 (MEN-1) gene mutations. After shared decision making with the patient, she gave birth to two healthy children, currently 2 and 4 years old. On pregnancy confirmation, SSA treatment was interrupted and resumed after each delivery. Ten years after the diagnosis of pNET, no tumour is detectable by MRI or somatostatin receptor scintigraphy. PRRT followed by continuous SSA therapy, interrupted only during pregnancies, resulted in complete remission and enabled the patient to complete two successful pregnancies.

[Enucleation of pancreatic tumors: a multiple-center study]. / Enukleatsiya opukholei podzheludochnoi zhelezy (mnogotsentrovoe issledovanie).

OBJECTIVE: To evaluate the immediate results of enucleation of pancreatic neuroendocrine tumors (pNETs). MATERIAL AND METHODS: The results of enucleation of pancreatic neuroendocrine tumors (pNETs) were analyzed in 95 patients between 2016 and 2021. Functioning tumors (mean size 16.8 mm) were found in 70 patients, non-functioning (mean size 25 mm) - in 25 patients. Intraparenchymal tumors were found in 48 people, extraorganic lesion - in 47 patients. RESULTS: There were 262 patients with pNETs who underwent various surgeries between 2016 and 2021. Various resections were performed in 167 (63.8%) cases, enucleations - in 95 (36.2%) patients. Traditional surgical approach was used in 65 patients. Pancreatic fistula occurred in 21 patients (type B - 17, type C - 4), while arrosive bleeding occurred in 6 patients with unfavorable outcomes in 2 cases. Minimally invasive surgeries were performed in 30 patients. Eight patients with intraparenchymal tumors required conversion to open surgery. Type B pancreatic fistula occurred in 5 patients that led to arrosive bleeding in 2 cases (hemostasis was provided by endovascular method). Comparison of intraparenchymal and extraorgan tumors regarding the incidence of pancreatic fistula revealed odds ratio 5.26 (95% CI 1.5355; 18.0323, p=0.0041). Postoperative mortality was 2.1%. CONCLUSION: Enucleation is advisable for highly differentiated pancreatic neuroendocrine tumors up to 2 cm. Minimally invasive enucleation is indicated for extraorgan tumors. Intraparenchymal tumors significantly increase the risk of postoperative complications.

Tumor-to-tumor metastasis of colon cancer metastasizing to a pancreatic neuroendocrine tumor associated with von Hippel-Lindau disease: a case report.

Von Hippel-Lindau disease (VHL) is frequently associated with pancreatic neuroendocrine tumors (PNETs). Here, we report a case of tumor-to-tumor metastasis in a VHL patient in whom colon cancer metastasized to the interior of a PNET. A 65-year-old man had undergone bilateral adrenalectomy for pheochromocytomas in both adrenal glands in his 50 s. Genetic screening was performed considering his family history of pheochromocytoma, and he was diagnosed with VHL. PNET was detected, for which the patient was regularly monitored by follow-up imaging. One year ago, the patient underwent right hemicolectomy to remove a tumor in the ascending colon (pT3N0M0, pStage IIA). He was admitted to our department for detailed examination because the pancreatic tumor had grown, and thus, pancreaticoduodenectomy was performed. Diagnostic imaging and histological findings indicated tumor-to-tumor metastasis, in which the patient's previous colon cancer had metastasized to and proliferated within the PNET. Colon cancer metastasizing to a PNET is extraordinarily rare and has never been reported in the literature. Thus, practitioners should be vigilant for tumor-to-tumor metastasis when performing imaging surveillance of PNETs.

FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease-Associated Tumors.

On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET. For VHL disease-associated RCC, ORR was 49% [95% confidence interval (CI), 36-62], median duration of response (DoR) was not reached, 56% of responders had DoR ≥12 months, and median time to response was 8 months. Twenty-four patients had measurable CNS hemangioblastomas with an ORR of 63% (95% CI, 41-81), and 12 patients had measurable pNET with an ORR of 83% (95% CI, 52-98). For these tumors, median DoR was not reached, with 73% and 50% of patients having response durations ≥12 months for CNS hemangioblastomas and pNET, respectively. The most common adverse reactions, including laboratory abnormalities, reported in ≥20% were anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Belzutifan can render some hormonal contraceptives ineffective and can cause embryo-fetal harm during pregnancy. This article summarizes the data and the FDA thought process supporting traditional approval of belzutifan for this indication.

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

We aimed to further characterize pancreatic involvement in tuberous sclerosis complex (TSC), with a focus on management of TSC-associated nonfunctional pancreatic neuroendocrine tumors (PNETs). This was a retrospective chart review of a large cohort of TSC patients. A total of 637 patients with a confirmed diagnosis of TSC were seen at the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital. Of the 637 total patients with a confirmed diagnosis of TSC, 28 patients were found to have varying pancreatic findings ranging from simple-appearing cysts to well-differentiated PNETs. Thirteen of the 28 patients had PNET confirmed on pathology; 10 of these tumors were resected at Massachusetts General Hospital. None of the patients had serious perioperative or postoperative complications; only one of the patients had a recurrence following resection. As roughly 4.4% of our TSC patient population had pancreatic involvement, surveillance abdominal imaging should include evaluation of the pancreas instead of limiting to a renal protocol. Additionally, given the low risk of complications and recurrence combined with documented risk of metastasis in TSC-associated PNET, TSC patients with pancreatic lesions suspicious for PNETs should be considered as surgical candidates.

Primitive Neuroectodermal Tumor in a Child with Human Immunodeficiency Virus Infection: A Rare Association.

Children with human immunodeficiency virus (HIV) infection are reported to have various malignancies, most common being Non-Hodgkin lymphoma. Despite higher risk of malignancies, brain tumors are infrequently described in these children. We report Primitive Neuroectodermal tumor (PNET) in a young boy with HIV infection. PNET has never been described in association with HIV infection. Though a causative association cannot be established, it does emphasize that with longer survivals on effective antiretroviral therapy, we may see a wide range of malignancies more frequently.

Large Epileptogenic Type IIIb Dysplasia: A Radiological and Anatomopathological Challenge.

BACKGROUND: Type IIIb dysplasia is a subtype of focal cortical dysplasia associated with a tumor, most frequently with gangliogliomas then with dysembryoplastic neuroepithelial tumors (DNETs). Their preoperative diagnosis often remains equivocal since specific features are missing. The functional results (i.e., seizure free) is good with 81%-87% of Engel Ia at 5-year follow-up. CASE DESCRIPTION: A 4-year-old boy presented with a 1-year history of severe, invalidating, drug-resistant epilepsy. Imaging workup demonstrated a huge left limbic lesion, of which diagnosis remained speculative. Because of worsening neurological status, resective surgery was recommended after multidisciplinary discussion. The resection was performed through left transtemporal approach under neuronavigation (C.R.). Postoperative magnetic resonance imaging assessed uncomplicated near-total resection. Histopathological analysis showed combined features of a DNET of nonspecific type and a focal cortical dysplasia. CONCLUSION: We describe a rare condition of type IIIb dysplasia combining a focal cortical dysplasia with a DNET. Preoperative diagnosis of the lesion was of utmost difficultly, thereby rendering mandatory a thorough histopathological examination of resected specimen in the vast majority of cases. Increased recognition of the condition brings up the hypothesis of a genetic continuum or linkage between the 2 conditions. Functional results on seizure activity after ablative surgery are good and maximal safe resection should be the goal.

An Eight-Year-Old Girl Presents With Two Weeks of Vision Loss and Nightly Headaches.

Intraocular medulloepithelioma is a rare congenital tumor that arises from the nonpigmented epithelium of the ciliary body. It is the second most common primary intraocular neoplasm during the first decade of life. It may present with an iris mass or cyst (56%), glaucoma (48%), cataract (26%), leukocoria (18%), decrease in vision (41%), or pain (30%). Here, the authors present a case of a medulloepithelioma investigated with multimodal imaging, including the first characterization with intraoperative optic coherence tomography. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:314-317.].

Refractory LCH With Secondary Intracranial PNET: A Case Report and Review of Literature.

The occurrence of second malignant neoplasms in patients with Langerhans cell histiocytosis is infrequent but has been reported. Here we report the case of a child with refractory Langerhans cell histiocytosis who was treated with cladribine and later developed a secondary intracranial primitive neuroectodermal tumor. The possible association of cladribine with second neoplasm is further discussed.

Lumbosacral Epidural Primitive Neuroectodermal Tumor (PNET): Case Report and Literature Review.

The primitive neuroectodermal tumors (PNETs) of the spine are rare. They are usually intramedullary and reported in children. We herein report an epidural PNET of lumbosacral area presenting with the cauda equina syndrome in an adult. A 38-year-old woman presented to our emergency room with acute onset lower extremity weakness and urinary incontinence. Emergent magnetic resonance imaging revealed a mass lesion isointense on T1-weighted and heterogeneously hyperintense in T2-weighted images in the epidural lumbosacral area. The patient underwent emergent laminectomy of L1-L3 and total resection of the lesion. The patient"s neurological examination improved dramatically after the surgery and after 6-month of follow-up, she was neurologically intact. The histopathological and immunohistochemical evaluations revealed PNET. Epidural PNET of the spinal column, although rare, can present with an acute neurological deficit. Surgery remains the treatment of choice and immunohistochemistry is required for confirming the diagnosis.

Renal Ewing's sarcoma/primitive neuroectodermal tumor: a case report and literature review.

Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) in the kidney is a rare but high-grade malignant tumor that affects predominantly elder children and adolescents. Patients mostly present with nonspecific symptoms such as abdominal pain and gross hematuria. Since EWS/PNET has a rapid clinical progression with early metastasis and death, it is essential to make an accurate and early diagnosis. Once diagnosed, multimodality treatment, including radical surgery combined with adjuvant chemotherapy, and radiotherapy if necessary, is recommended. Unfortunately, there are no characteristic signsthat have been described in ultrasonography or any other imaging modalities so far. The diagnosis of EWS/PNET is now based on a classical histological and immunohistochemical investigation complemented by a demonstration of specific chromosomal changes. Strong immunoreactivity to CD99 is ubiquitous, and t(11;22) translocation is seen in approximately 90% of EWS/PNET. Herein, we report a patient with such condition. The patient was a young woman, and she presented with sudden right flank pain clinically. Ultrasonography revealed a large heterogeneous mass in the lower pole of her right kidney. The tumor compressed the renal pelvis and led to upper pole caliectasis. Color Doppler demonstrated blood flow with a pulsatile arterialized waveform within the mass. The patient received radical nephrectomy with right renal vein and vena cava thrombectomy. A search for other sites of tumor involvement yielded negative results. And six cycles of chemotherapy were sequentially performed. The diagnosis of EWS/PNET was confirmed based on primitive small round cell histology and characteristic immunohistochemical results. She was still alive with no evidence of recurrence five years after initial diagnosis. We would like to point out that ultrasound is still a useful method for initial assessment, and ultrasound-guided fine needle aspiration may play an important role in determining preoperative diagnosis.

Rare Ileal Ewing Sarcoma/Primitive Neuroectodermal Tumor on 18F-FDG PET/CT.

A 24-year-old woman who had melena, dizziness, and fatigue and looked pale for 2 months was confirmed to have a microcytic hypochromic anemia in the local hospital. It was further revealed that the patient had splenomegaly and a small intestinal lump, and she was then referred to our hospital. The enhanced CT showed an ileal lesion with enhancement, which showed an increased F-FDG activity in further PET/CT scanning. Lymphoma was therefore suspected, and an uncomplicated surgical resection of the ileal lesion was then performed. Nevertheless, the histopathologic and immunohistochemical examination was finally proved to be a rare ileal Ewing sarcoma/primitive neuroectodermal tumor.

Pediatric Basal Ganglia Region Tumors: Clinical and Radiologic Features Correlated with Histopathologic Findings.

PURPOSE: To summarize the clinical and radiologic features of pediatric basal ganglia region tumors (PBGRT) in correlation with their histopathologic findings to reduce inappropriate surgery and identify tumors that can benefit from maximal safe resection. METHODS: The records of 35 children with PBGRT treated in our hospital from December 2011 to December 2015 were analyzed retrospectively. The clinical and radiologic features of these tumors were summarized and correlated with their histopathologic diagnosis. RESULTS: Our series included 15 astrocytomas and 11 germ cell tumors (GCTs). Basal ganglia astrocytomas were characterized by various clinical presentations and an ill-circumscribed mass with the involvement of surrounding structures on neuroimaging and mostly occurred in the first decade of life (n = 10; 66.7%). Basal ganglia GCT mostly occurred in the second decade of life (n = 8; 72.7%) with hemiparesis as the most common symptom (n = 9; 81.8%). The tumors were located predominantly in the caput of caudate nucleus (n = 8; 72.7%) with hemiatrophy as the typical sign (n = 8; 72.7%). Occasionally, other tumors also could occur in this region, including primitive neuroectodermal tumor (n = 1), atypical teratoid/rhabdoid tumor (n = 1), anaplastic ependymoma (n = 1), lymphoma (n = 1), extraventricular neurocytoma (n = 1), gangliogliomas (n = 2), oligodendroglioma (n = 1), and dysembryoplastic neuroepithelial tumor (n = 1). CONCLUSIONS: Astrocytoma and GCT are the most common PBGRTs. Low-grade astrocytomas could benefit from maximal surgical resection, whereas GCTs merit neoadjuvant chemoradiation therapy followed by second-look surgery. We advocate routine testing of tumor markers and analysis of their clinical and radiologic features to optimize the therapeutic strategy.

Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

Background: Medulloblastoma is the most common malignant childhood brain tumor, although long-term risks for chronic neurologic health and psychosocial functioning in aging adult survivors are incompletely characterized. Methods: The Childhood Cancer Survivor Study (CCSS) includes 380 five-year survivors of medulloblastoma/primitive neuroectodermal tumor (PNET; median age at follow-up: 30 y, interquartile range 24-36) and sibling comparison (n = 4031). Cumulative incidence of neurologic health conditions was reported. Cox regression models provided hazard ratios (HRs) and 95% CIs. Cross-sectional outcomes were assessed using generalized linear models. Results: Compared with siblings, survivors were at increased risk of late-onset hearing loss (HR: 36.0, 95% CI: 23.6-54.9), stroke (HR: 33.9, 95% CI: 17.8-64.7), seizure (HR: 12.8, 95% CI: 9.0-18.1), poor balance (HR: 10.4, 95% CI: 6.7-15.9), tinnitus (HR: 4.8, 95% CI: 3.5-6.8), and cataracts (HR: 31.8, 95% CI: 16.7-60.5). Temporal/frontal lobe radiotherapy of 50 Gy or more increased risk for hearing loss (HR: 1.9, 95% CI: 1.1-1.3), seizure (HR: 2.1, 95% CI: 1.1-3.9), stroke (HR: 3.5, 95% CI: 1.3-9.1), and tinnitus (HR: 2.0, 95% CI: 1.0-3.9). Survivors were less likely than siblings to earn a college degree (relative risk [RR]: 0.49, 95% CI: 0.39-0.60), marry (RR: 0.35, 95% CI: 0.29-0.42), and live independently (RR: 0.58, 95% CI: 0.52-0.66). Conclusions: Adult survivors of childhood medulloblastoma/PNET demonstrate pronounced risk for hearing impairment, stroke, lower educational attainment, and social independence. Interventions to support survivors should be a high priority.

Primary Leptomeningeal PNETs Mimicking TB Meningitis: A Case Report and Literature Review.

Primitive neuroectodermal tumors (PNETs) are easily detected, and the diagnosis made by neuroradiologic imaging. Leptomeningeal seeding is a common complication and carries a poor prognosis. Primary leptomeningeal PNETs are rarer and difficult to diagnose on magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF) studies. We encountered a rare case of primary leptomeningeal primitive neuroectodermal tumor without intracranial mass lesion which was diagnosed by spinal lesion biopsy. This 25-year-old woman presented with worsening headaches and progressive visual impairment.The initial diagnosis was tubercle bacillus (TB) meningitis, and the final diagnosis of primary leptomeningeal PNET was made by spinal biopsy. We present this illustrative case, review previous cases in the literature, and suggest that diagnosis is considered in mildly affected patients with similar symptoms.

A Rare Initial Presentation of Primary Diffuse Leptomeningeal PNET in a 10-Year-Old-Male.

Primary leptomeningeal primitive neuroectodermal tumors (PNETs) are extremely rare childhood central nervous system malignancies harboring a very poor prognosis. There is no consensus treatment for these tumors to date. We report a case of a 10-year-old male who presented with mental status change, hydrocephalus, intracranial and spinal diffuse leptomeningeal enhancement without a primary mass upon cranial imaging and a negative initial biopsy until five months into his presentation. He responded significantly well to initial chemotherapy and radiotherapy.

Adult supratentorial primitive neuroectodermal tumour presenting as intracranial haemorrhage: Case report.

Primitive neuroectodermal tumours (PNET) are highly malignant tumours with an aggressive clinical behaviour. Commonly seen in children, they are uncommon in the adult population, and rare in the supratentorial location. Adult supratentorial PNETs (ST-PNET) typically present with symptoms relating to raised intracranial pressure, seizures, or focal neurological deficits. Presentation with intracranial haemorrhage has been reported only twice before in the literature, one of which was fatal. We report the case of intracranial haemorrhage secondary to ST-PNET in a young adult and her immediate management.