scholarly journals Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops

2019 ◽  
pp. 145749691987448 ◽  
Author(s):  
J. Eriksson ◽  
O. Norlén ◽  
M. Ögren ◽  
H. Garmo ◽  
C. Ihre-Lundgren ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Metastatic Disease ◽  
High Rate ◽  
Primary Tumors ◽  
The People ◽  
Swedish Cancer Registry ◽  
The Mean ◽  
Small Intestinal ◽  
Diagnostic Modalities

Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of “carcinoid tumor” were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.

scholarly journals Genetic characterization of a case of sellar metastasis from bronchial carcinoid neuroendocrine tumor

2020 ◽  
Vol 11 ◽  
pp. 303
Author(s):  
. Hong Christopher S ◽  
Adam J. Kundishora ◽  
Aladine A. Elsamadicy ◽  
Andrew B. Koo ◽  
Jason M. Beckta ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Pituitary Tumors ◽  
Metastatic Tumor ◽  
Mass Effect ◽  
Endoscopic Endonasal ◽  
Primary Tumors ◽  
Visual Deficits ◽  
History Of

Background: Metastasis to the pituitary gland from neuroendocrine tumors is a rare occurrence that may originate from primary tumors the lung, gastrointestinal tract, thyroid, and pancreas, among others. Patients may present with signs of endocrine dysfunction secondary to pituitary involvement, as well as mass effect-related symptoms including headaches and visual deficits. Despite a small but accumulating body of literature describing the clinical and histopathological correlates for pituitary metastases from neuroendocrine tumors, the genetic basis underlying this presentation remains poorly characterized. Case Description: We report the case of a 68-year-old with a history of lung carcinoid tumor who developed a suprasellar lesion, causing mild visual deficits but otherwise without clinical or biochemical endocrine abnormalities. She underwent endoscopic endonasal resection of her tumor with final pathology confirming metastasis from her original neuroendocrine tumor. Whole-exome sequencing was performed on the resected sellar tumor and matching blood, revealing increased genomic instability and key mutations in PTCH1 and BCOR that have been previously implicated in both systemic neuroendocrine and primary pituitary tumors with potentially actionable therapeutic targets. Conclusion: This is the first genomic characterization of a metastatic tumor to the sella and reports potential genetic insight, implicating PTCH1 and BCOR mutations, into the pathophysiology of sellar metastasis from primary systemic tumors.

scholarly journals Sexual dimorphism in small-intestinal neuroendocrine tumors: lower prevalence of mesenteric disease in premenopausal women

2022 ◽  
Author(s):  
Anela Blažević ◽  
Anand M Iyer ◽  
Marie-Louise F van Velthuysen ◽  
Johannes Hofland ◽  
Lindsey Oudijk ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Sexual Dimorphism ◽  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Estrogen Receptor Alpha ◽  
Premenopausal Women ◽  
Primary Tumors ◽  
Tertiary Center ◽  
Male Patients ◽  
Small Intestinal

Abstract Context Small intestinal neuroendocrine tumors (SI-NETs) have a modest but significantly higher prevalence and worse prognosis in male patients. Objective This work aims to increase understanding of this sexual dimorphism in SI-NETs. Patients and Methods Retrospectively, SI-NET patients treated in a single tertiary center were included and analyzed for disease characteristics. Estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR) and androgen receptor (AR) mRNA expression was assessed in primary tumors and healthy intestine. Estrogen receptor alpha (ERα) and AR protein expression was analyzed by immunohistochemistry in primary tumors and mesenteric metastases. Results Of the 559 patients, 47% were female. Mesenteric metastasis/fibrosis was more prevalent in men (71/46%) than women (58/37%, P=0.001 and P = 0.027). In women, prevalence of mesenteric metastases increased gradually with age from 41.1% in women <50 years to 71.7% in women >70 years. Increased expression of ESR1 and AR mRNA was observed in primary tumors compared to healthy intestine (both P < 0.001). ERα staining was observed in tumor cells and stroma with a strong correlation between tumor cells of primary tumors and mesenteric metastases (rho=0.831, P=0.02), but not in stroma (rho=-0.037, P=0.91). AR expression was only found in stroma. Conclusion Sexual dimorphism in SI-NETs was most pronounced in mesenteric disease and the risk of mesenteric metastasis in women increased around menopause. The combination of increased ERα and AR expression in the SI-NET microenvironment suggests a modulating role of sex steroids in the development of the characteristic SI-NET mesenteric metastasis and associated fibrosis.

Loss of Expression of DNA Mismatch Repair Proteins Is Rare in Pancreatic and Small Intestinal Neuroendocrine Tumors

2011 ◽  
Vol 135 (12) ◽  
pp. 1539-1544 ◽  
Author(s):  
Thomas Arnason ◽  
Heidi L Sapp ◽  
Daniel Rayson ◽  
Penelope J Barnes ◽  
Magdalena Drewniak ◽  
...  
Keyword(s):  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Neuroendocrine Tumors ◽  
Dna Mismatch Repair ◽  
High Rate ◽  
Dna Mismatch ◽  
Small Intestinal ◽  
Msi Analysis ◽  
Mmr Proteins

Context.—Two recent studies have identified a high rate of microsatellite instability (MSI) in pancreatic neuroendocrine tumors (pNETs). Microsatellite instability is rare in small intestinal neuroendocrine tumors (NETs). It is unclear why there is discordance in the frequency of MSI in the 2 studies of pNETs and why this mechanism is comparatively rare in small intestinal tumors. Loss of expression of DNA mismatch repair (MMR) proteins, which is known to correlate strongly with MSI, is not well studied in pancreatic or small intestinal NETs. Objective.—To determine if there is loss of expression of MMR protein expression in pancreatic or small intestinal NETs. Design.—Sixty-nine patients (31 male, 38 female; mean age, 59.2 years) were identified who had a resection for a primary pancreatic (n  =  35) or primary small intestinal (n  =  34) NET during an 18-year period. Immunohistochemical stains for MLH1, MSH2, MSH6, and PMS2 were applied to archived tissue from all cases. All pNETs with adequate tissue (n  =  32) were also assessed by MSI analysis. Results.—There was preserved expression of MLH1, MSH2, MSH6, and PMS2 in all 35 pNETs. Of 32 pNETs tested by polymerase chain reaction, 28 were microsatellite stable and DNA did not amplify in 4. In 34 small intestinal NETs, 2 cases had indeterminate MLH1 and 1 case had indeterminate PMS2 expression. The remainder had intact MMR protein expression. Conclusion.—Defects in DNA MMR proteins are rare in pancreatic and small intestinal NETs, raising doubt that MSI plays a significant role in the pathogenesis of these tumors.

scholarly journals Validation of a Cytotechnologist Manual Counting Service for the Ki67 Index in Neuroendocrine Tumors of the Pancreas and Gastrointestinal Tract

2018 ◽  
Vol 142 (3) ◽  
pp. 402-407 ◽  
Author(s):  
Jennielee Cottenden ◽  
Emily R. Filter ◽  
Jon Cottreau ◽  
David Moore ◽  
Martin Bullock ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Gold Standard ◽  
Pancreatic Neuroendocrine Tumor ◽  
Tumor Grade ◽  
High Rate ◽  
Ki67 Index ◽  
Perfect Agreement ◽  
Manual Count ◽  
Manual Counting ◽  
The Mean

Context.— Pathologists routinely assess Ki67 immunohistochemistry to grade gastrointestinal and pancreatic neuroendocrine tumors. Unfortunately, manual counts of the Ki67 index are very time consuming and eyeball estimation has been criticized as unreliable. Manual Ki67 counts performed by cytotechnologists could potentially save pathologist time and improve accuracy. Objective.— To assess the concordance between manual Ki67 index counts performed by cytotechnologists versus eyeball estimates and manual Ki67 counts by pathologists. Design.— One Ki67 immunohistochemical stain was retrieved from each of 18 archived gastrointestinal or pancreatic neuroendocrine tumor resections. We compared pathologists' Ki67 eyeball estimates on glass slides and printed color images with manual counts performed by 3 cytotechnologists and gold standard manual Ki67 index counts by 3 pathologists. Results.— Tumor grade agreement between pathologist image eyeball estimate and gold standard pathologist manual count was fair (κ = 0.31; 95% CI, 0.030–0.60). In 9 of 20 cases (45%), the mean pathologist eyeball estimate was 1 grade higher than the mean pathologist manual count. There was almost perfect agreement in classifying tumor grade between the mean cytotechnologist manual count and the mean pathologist manual count (κ = 0.910; 95% CI, 0.697–1.00). In 20 cases, there was only 1 grade disagreement between the 2 methods. Eyeball estimation by pathologists required less than 1 minute, whereas manual counts by pathologists required a mean of 17 minutes per case. Conclusions.— Eyeball estimation of the Ki67 index has a high rate of tumor grade misclassification compared with manual counting. Cytotechnologist manual counts are accurate and save pathologist time.

scholarly journals Metastatic Pheochromocytoma/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to SDHB Mutations

2011 ◽  
Vol 29 (31) ◽  
pp. 4137-4142 ◽  
Author(s):  
Kathryn S. King ◽  
Tamara Prodanov ◽  
Vitaly Kantorovich ◽  
Tito Fojo ◽  
Jacqueline K. Hewitt ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Tumor Development ◽  
Gene Mutations ◽  
National Institutes Of Health ◽  
High Rate ◽  
Adrenal Tumors ◽  
Primary Tumors ◽  
Tumor In Childhood

Purpose To present data on the high rate of SDHB mutations in patients with metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began in childhood or adolescence. Patients and Methods From 2000 to 2010, 263 patients with pheochromocytoma/paraganglioma were evaluated through the National Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were found to have metastatic disease; of these 125 patients, 32 patients presented with a tumor before 20 years of age. An additional 17 patients presented with a tumor before 20 years of age but demonstrated no development of metastatic disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was performed on patients without previously identified genetic mutations. Results Of the 32 patients who presented with metastatic disease and had their primary tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL mutations in two patients (6.3%), and an absence of a known mutation in four patients (12.5%). The majority of these 32 patients (78.1%) presented with primary tumors in an extra-adrenal location. Conclusion The majority of patients with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB mutations. Except for primary tumors located in the head and neck where SDHD genetic testing is advised, we recommend that patients who present with metastatic pheochromocytoma/paraganglioma with primary tumor development in childhood or adolescence undergo SDHB genetic testing before they undergo testing for other gene mutations, unless clinical presentation or family history suggests a different mutation.

scholarly journals Double contrast-enhanced ultrasonography of a small intestinal neuroendocrine tumor: a case report of a recommendable imaging modality

2020 ◽  
Vol 3 (2) ◽  
pp. 147-152
Author(s):  
Jie-ying Zhao ◽  
Hua Zhuang ◽  
Yuan Luo ◽  
Ming-gang Su ◽  
Mo-li Xiong ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Imaging Modality ◽  
Intestinal Tumors ◽  
Double Contrast ◽  
Diagnostic Challenge ◽  
Contrast Enhanced ◽  
Contrast Enhanced Ultrasonography ◽  
Small Intestinal

Abstract A 57-year-old male presenting with spontaneously relieved abdominal cramp and distension was admitted to the West China Hospital. The diagnosis remained unclear after colonoscopy and computed tomography. Double contrast-enhanced ultrasonography was then performed and a neoplasm in the small intestine was suspected, supported by a thin-section computed tomography and positron emission tomography/computed tomography. This was confirmed pathologically after surgery to be a small intestinal G1 neuroendocrine tumor. Surgery was performed to remove approximately 25 cm of small bowel and a 3-cm solid mass located in the mesentery. The patient had a complete recovery and was tumor-free at the final follow-up. Small intestinal tumors including neuroendocrine tumors have always posed a diagnostic challenge. This case indicated that double contrast-enhanced ultrasonography is feasible in detection of small intestinal neuroendocrine tumors, and it may be an advisable approach assisting diagnosis of small intestinal tumors.

scholarly journals Searching for primaries in patients with neuroendocrine tumors (NET) of unknown primary and clinically suspected NET: Evaluation of Ga-68 DOTATOC PET/CT and In-111 DTPA octreotide SPECT/CT

2014 ◽  
Vol 48 (4) ◽  
pp. 339-347 ◽  
Author(s):  
Nils Friedemann Schreiter ◽  
Ann-Mirja Bartels ◽  
Vera Froeling ◽  
Ingo Steffen ◽  
Ulrich-Frank Pape ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Clinical Efficacy ◽  
Unknown Primary ◽  
Primary Tumors ◽  
Pet Ct ◽  
Clinical Verification

Abstract Background. To evaluate the clinical efficacy of In-111 DTPA octreotide SPECT/CT and Ga-68 DOTATOC PET/CT for detection of primary tumors in patients with either neuroendocrine tumor of unknown primary (NETUP) or clinically suspected primary NET (SNET). Patients and methods. A total of 123 patients were included from 2006 to 2009, 52 received Ga-68 DOTATOC PET/CT (NETUP, 33; SNET, 19) and 71 underwent In-111 DTPA octreotide SPECT/CT (50; 21). The standard of reference included histopathology or clinical verification based on follow-up examinations. Results. In the NETUP group Ga-68 DOTATOC detected primaries in 15 patients (45.5%) and In-111 DTPA octreotide in 4 patients (8%) (p < 0.001); in the SNET group, only 2 primaries could be detected, all by Ga-68 DOTATOC. In patients with NETUP, primary tumors could be found significantly more often than in patients with SNET (p = 0.01). Out of these 21 patients 14 patients were operated. Conclusion. Ga-68 DOTATOC PET/CT is preferable to In-111 DTPA octreotide SPECT/CT when searching for primary NETs in patients with NETUP but should be used with caution in patients with SNET.

Dosimetric analyses of intra-arterial versus standard intravenous administration of 177Lu-DOTATATE in patients of well differentiated neuroendocrine tumor with liver-dominant metastatic disease

2021 ◽  
pp. 20210403
Author(s):  
Parul Thakral ◽  
Ishita Sen ◽  
Subha Shankar Das ◽  
Divya Manda ◽  
Virupakshappa CB ◽  
...  
Keyword(s):  
Single Dose ◽  
Neuroendocrine Tumor ◽  
Metastatic Disease ◽  
Intravenous Administration ◽  
Radionuclide Therapy ◽  
Organs At Risk ◽  
Hepatic Metastases ◽  
Whole Body ◽  
Intravenous Route ◽  
The Mean

Objective: The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of 177Lu-DOTATATE. Methods: 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of 177Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of 177 Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post 177Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software. Results: The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2–251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12–55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group. Conclusion: IA administration of 177Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT. Advances in knowledge: Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with 177Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.

The Role of Wireless Capsule Endoscopy (WCE) in the Detection of Occult Primary Neuroendocrine Tumors

2017 ◽  
Vol 26 (2) ◽  
pp. 151-156
Author(s):  
Manuele Furnari ◽  
Andrea Buda ◽  
Gabriele Delconte ◽  
Davide Citterio ◽  
Theodor Voiosu ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Capsule Endoscopy ◽  
Primary Tumor ◽  
Diagnostic Yield ◽  
Somatostatin Receptor ◽  
Tertiary Care ◽  
Wireless Capsule Endoscopy ◽  
First Line ◽  
Wireless Capsule

Background & Aims: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumor in patients showing liver NET metastases when first-line investigations are inconclusive.Method: Twenty-four patients with histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration.Results: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded.Conclusions: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.Abbreviations: DBE: double balloon enteroscopy; GEP-NET: gastro-entero-pancreatic neuroendocrine tumor; GI: gastrointestinal; ENETS: European Neuroendocrine Tumor Society; NET: neuroendocrine tumor; SSRS: somatostatin receptor scintigraphy; WCE: wireless capsule endoscopy.

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