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Rossi, R.E.; Corti, F.; Pusceddu, S.; Milione, M.; Coppa, J.; Masoni, B.; Oldani, S.; Sabella, G.; Cafaro, P.; Repici, A. Epidemiology-Clinical Presentation of Occult Primary Neuroendocrine Neoplasms. Encyclopedia. Available online: https://encyclopedia.pub/entry/49005 (accessed on 21 December 2024).
Rossi RE, Corti F, Pusceddu S, Milione M, Coppa J, Masoni B, et al. Epidemiology-Clinical Presentation of Occult Primary Neuroendocrine Neoplasms. Encyclopedia. Available at: https://encyclopedia.pub/entry/49005. Accessed December 21, 2024.
Rossi, Roberta Elisa, Francesca Corti, Sara Pusceddu, Massimo Milione, Jorgelina Coppa, Benedetta Masoni, Simone Oldani, Giovanna Sabella, Pietro Cafaro, Alessandro Repici. "Epidemiology-Clinical Presentation of Occult Primary Neuroendocrine Neoplasms" Encyclopedia, https://encyclopedia.pub/entry/49005 (accessed December 21, 2024).
Rossi, R.E., Corti, F., Pusceddu, S., Milione, M., Coppa, J., Masoni, B., Oldani, S., Sabella, G., Cafaro, P., & Repici, A. (2023, September 11). Epidemiology-Clinical Presentation of Occult Primary Neuroendocrine Neoplasms. In Encyclopedia. https://encyclopedia.pub/entry/49005
Rossi, Roberta Elisa, et al. "Epidemiology-Clinical Presentation of Occult Primary Neuroendocrine Neoplasms." Encyclopedia. Web. 11 September, 2023.
Epidemiology-Clinical Presentation of Occult Primary Neuroendocrine Neoplasms
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This entry is adapted from the peer-reviewed paper 10.3390/jcm12175537

Neuroendocrine neoplasms (NENs) are rare tumors that originate in diffuse neuroendocrine cells, potentially affecting any organ. NENs encompass a large and heterogenous group of neoplasms characterized by different biological behavior, depending on the clinical and histopathological features and primary site. NENs are classified into well-differentiated G1–G3 NENs and poorly differentiated G3 neuroendocrine carcinomas (NECs), based on their morphological features and proliferation rate. Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel

neuroendocrine neoplasms unknown primary tumor diagnosis ultrasound endoscopy capsule endoscopy

1. Epidemiology

Neuroendocrine neoplasms (NENs) represent around 0.5% of all newly diagnosed neoplasms [1]. In recent decades, the incidence of NENs has hugely increased, likely due to improvements in diagnostic techniques and increased disease awareness [2], being approximately 5.86/100,000 per year [3]. The most frequent primary sites are represented by the gastrointestinal/pancreatic tract (62–67%) and lung (22–27%). In well-differentiated tumors, the majority of metastatic sites are found within the liver only [1].
Approximately 11% to 14% of subjects with NENs present metastatic lesions with a UPO, being the majority of UPO-NENs found in the small bowel [4], particularly for well-differentiated forms, followed by the pancreas. Conversely, in poorly differentiated forms, the primary site is generally located in the lung [5]. In 2020, Abdel-Rahman et al. [6] conducted a real-world, population-based study to evaluate the actual incidence and outcome of UPO-NENs. Out of a total of 51,415 recorded cases with NENs, a total of 3550 cases (7%) were diagnosed with UPO-NENs. The authors observed first that the diagnosis of UPO-NENs has increased across the past 4 decades; furthermore, they reported that metastatic small-intestinal NENs appear to have a better prognosis when compared with metastatic UPO-NENs (for both carcinoid tumors and neuroendocrine carcinomas).

2. Clinical Presentation

In the neuroendocrine setting, the majority of symptoms are non-specific and tend to overlap with more common, often gastro-intestinal (GI), conditions, leading to a significant delay in diagnosis. This assumption is particularly true for those cases in which the primary lesion is undetectable thorough conventional imaging techniques [computed tomography (CT) scan, magnetic resonance imaging (MRI)], and the diagnosis of NENs may be, therefore, mistakenly shelved in favor of other endocrine or GI disorders contributing to the aforementioned diagnostic delay.
Clinical features may be related to the tumor’s hormonal production (functioning NENs), to the site of the primary tumor or to its metastases (mostly hepatic). Functioning NENs can be responsible for many renowned clinical syndromes (as depicted in Table 1), while non-functioning forms’ presentation is often connected to their mass effect.
Table 1. Functioning neuroendocrine neoplasms and their associated clinical syndromes.
Insulinoma Whipple’s triad
  • Hypoglycemia (<50 mg/dL)
  • Hypoglycemic symptoms (dizziness, sweating, confusion, increased HF)
  • Symptoms’ resolution with glucose ingestion
Gastrinoma Zollinger Ellison Syndrome
  • Peptic ulcer disease
  • Diarrhea
  • Gastro-esophageal reflux disease
  • Weight loss
VIP-oma Verner Morrison Syndrome
  • Watery diarrhea
  • Dehydration
  • Hyperkalemia
Glucagonoma
  • Diarrhea
  • Glucose intolerance/diabetes
  • Necrolytic migratory erythema
  • Weight loss and steathorrhoea
  • Anemia
Somatostatinoma
  • Diarrhea
  • Weight loss
  • Diabetes
  • Gallstones
Midgut/small-intestine NENs (SI-NENs), generally represent the majority of UPO-NENs, which account for 12–22% of all patients diagnosed with NENs [7].
In this scenario, frequent local symptoms include: bowel obstruction or perforation (as a matter of fact, small-bowel NENs are often identified during emergency abdominal surgery), obscure intestinal bleeding without any significative endoscopic finding, unexplained anemia from chronic blood loss or, rarely, obstructive manifestations from vascular compression. Likewise, occult bronchial NENs can be responsible for hemoptysis, dyspnea or recurrent infections due to bronchial obstruction.
The presence of liver metastases can be symptomatic itself by causing abdominal pain (due to liver-capsule stretching or bleeding) or mixed hyperbilirubinemia (as a result of both obstruction and hepatic failure) up to obstructive jaundice. In addition, liver metastases—whether detectable through conventional imaging or not [8]—can be responsible for the development of carcinoid syndrome (CS), a clinical syndrome characterized by flushing, diarrhea and bronchospasm as leading symptoms that can lead to life-threatening complications, such as carcinoid heart disease. The prevalence of CS in patients with NENs has grown significantly in the past decade together with the well-known increase in NENs’ incidence: a large American study showed an increase in its incidence from 11% to 19% during the decade 2000–2011 and its association mainly to midgut NENs (40%); moreover, the presence of CS seemed to be linked to a shorter overall survival [9]. In the setting of UPO-NENs, CS can represent the first or the only clinical manifestation (especially if the primary tumor has a small size), but, again, its symptoms can be mistaken for other conditions (including anxiety, irritable bowel syndrome, menopause, allergic asthma) and the presence of liver metastases frequently ends up being an incidental finding. It is, indeed, a common experience that the diagnosis of NENs is generally delayed and patients with small-bowel NENs are often erroneously diagnosed with irritable bowel syndrome or inflammatory bowel disease due to the non-specific clinical presentation.

3. Diagnostic Work-Up

Localization of midgut tumors might be challenging due to their usually small size. Early localization of the primary site is a fundamental prerequisite for improving the patient’s management and prolonging survival [10], especially for patients with well-differentiated NENs.
A continuum of investigations to identify the primary tumor is warranted. A multimodal imaging approach, including CT, MRI, positron emission tomography (PET) and somatostatin receptor scintigraphy (SRS) together with endoscopy, is often necessary for detecting the primary tumor [11][12]. In addition to conventional upper and lower GI endoscopy, more sophisticated techniques, including CT enterography, CT angiography, video capsule endoscopy or double-balloon enteroscopy and endoscopic ultrasonography, may all be combined to shed light on challenging cases [12][13]. In selected cases, whenever all the available diagnostic tools have failed, surgical exploration may be warranted. In this setting, an open exploration is considered to be superior to laparoscopy when the primary site cannot be identified but the data are limited [13][14]. However, despite surgical exploration, the primary site is not found in approximately 13% of the cases [12].
The presence of a functional syndrome might be of help to identify the site of the primary lesion in UPO-NENs. In fact, CS is typically secondary to an NEN located in the small bowel and, in this setting, 5-hydroxyindoleacetic acid (5-HIAA) urine levels should be determined, being the specific biomarker for CS [15]. On the other hand, when a functioning NEN as a gastrinoma is suspected, the primary lesion is generally small in size, difficult to be detected and often located at an anatomic region known as the gastrinoma triangle [16]. In the presence of paraneoplastic syndrome, including ectopic ACTH syndrome, a primary tumor located in the lung, the thyroid (medullary carcinoma) or associated with a gastrinoma should be suspected [17]. However, specific biomarkers for UPO-NENs are still lacking.
In clinical practice, the first sign of a neoplastic process secondary to a UPO-NEN is the detection of liver metastases via conventional radiology (i.e., CT scan). Additional work-up, such as upper and lower GI endoscopy, chest CT and MRI of the abdomen, should be required. Conventional radiology might fail to detect the primary tumor in the pancreas or small bowel when the lesions are small or the tests are performed using a suboptimal protocol [18].

3.1. Pathology

In patients with UPOs, immunohistochemical markers are useful for cell-type determination and pathologic diagnosis.
UPO-NENs are most often well-differentiated grade 1 or 2 tumors which commonly originate from the intestinal or pancreatic system (approximately 60–65% of cases) or lungs (approximately 20–25%) [1][19]. Liver metastases dominate in the clinical setting, and these lesions are usually reachable using a core-needle biopsy (CNB), as current guidelines strongly recommend; however, occasionally, focal liver resections might be necessary to obtain sufficient material [20]. 
Morphological, immunohistochemical and molecular analyses are equally essential in the assessment of NENs. NENs may exhibit variable growth patterns and cellular characteristics easily identifiable on routine hematoxylin–eosin staining alone [21][22]. For instance, while metastatic NENs with a primary tumor located in the stomach and duodenum may demonstrate a glandular-like pattern, and SI-NENs often exhibit an organoid or nested growth pattern; in contrast, pancreatic and rectal NENs may present with a ribbon-like or trabecular architecture. To identify the actual origin of a UPO-NEN, a wide variety of immunohistochemical markers may be assessed. These include classic markers such as Chromogranin A (CgA) and Synaptophysin (SYP) or INSM1 [23] to confirm the neuroendocrine differentiation [24][25]. CDX2 is a transcription factor, a useful marker of intestinal NENs and, because of its association with GI differentiation, it is also found in gastrin-positive pancreatic NENs and colorectal adenocarcinoma [26][27]. In the setting of WDNENs, Thyroid Transcription Factor1 (TTF1) positivity may suggest a bronchial primary in 43% of the cases. However, it is not specific in poorly differentiated lung neuroendocrine carcinomas (PDNECs), as it is also present in 50% of small-cell tumors at other sites [26][28][29]. Islet-1 (ISL1) can be used as a marker for pancreatic origin [30][31]. Serotonin, associated with CDX2 and SATB2, has utility in identifying EC tumors originating in the ileum or appendix [32][33]. Colorectal NENs may present with positive staining for glucagon-like peptide 1, CDX2 and SATB2 [31][34]. Pheochromocytomas and abdominal paragangliomas stain positive for neuroendocrine markers CgA, SYP, ISL1, INSM1 and, often, GATA3; subsets of cases may display an intricate network of supporting sustentacular cells which are highlighted by an S100 or SOX10 stain [35]. Paranuclear dot-like staining for CgA, CK20 and Neurofilament (NF), and polyomavirus stain, may also help in the identification of neuroendocrine skin lesions such as Merkel cell carcinomas (MCCs) [36][37]. Therefore, to successfully identify UPO-NENs, a combined assessment using clues from clinical history, radiology, morphology and immunohistochemistry is recommended, rather than blind trust in a single marker [7][38]. The interaction between physicians and pathologists is, therefore, fundamental.

3.2. Functional Imaging

Somatostatin receptor scintigraphy (SRS) has been extensively used for the initial staging of disease and to evaluate somatostatin receptor (SSTRs) status; furthermore, it has been explored to detect occult primary sites in patients with metastatic gastro-entero-pancreatic (GEP) NENs with a detection rate of 39%. However, 68GaDOTANOC positron emission tomography (PET)/CT has proved to be more accurate and generally represents the functional imaging of choice, being able to also detect very small lesions [39]. According to previous experiences, Ga-68-DOTANOC PET/CT helped in the detection of undiagnosed primary sites in patients with metastatic NENs in a percentage ranging from 45.5% [40] to 59% of the patients [41][42].
A recent meta-analysis [43], including 10 studies of a total of 484 patients with UPO-NENs, demonstrated the high diagnostic sensitivity of 68Ga-DOTA-SSTR for UPO-NENs. 68Ga-DOTA-SSTR PET/CT was highly effective in locating the primary and metastatic sites of UPO-NENs, with a pooled detection rate of 61%.
Fluorodeoxyglucose PET may be employed for the detection of occult primary sites in case of high-grade histology (G3 NEN), whereas F-DOPA and MIBG imaging may be employed in selected cases, especially when paraganglioma/pheochromocytoma are suspected.

References

  1. Taal, B.G.; Visser, O. Epidemiology of Neuroendocrine Tumours. Neuroendocrinology 2004, 80, 3–7.
  2. Yao, J.C.; Hassan, M.; Phan, A.; Dagohoy, C.; Leary, C.; Abdalla, J.E.M.K.; Fleming, J.B.; Vauthey, J.-N.; Rashid, A.; Evans, D.B. One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J. Clin. Oncol. 2008, 26, 3063–3072.
  3. Rindi, G.; Bordi, C.; Rappel, S.; La Rosa, S.; Stolte, M.; Solcia, E. Gastric carcinoids and neuroendocrine carcinomas: Path-ogenesis, pathology, and behavior. World J. Surg. 1996, 20, 168–172.
  4. Pavel, M.; O’Toole, D.; Costa, F.; Capdevila, J.; Gross, D.; Kianmanesh, R.; Krenning, E.; Knigge, U.; Salazar, R.; Pape, U.-F.; et al. ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site. Neuroendocrinology 2016, 103, 172–185.
  5. Dasari, A.; Shen, C.; Halperin, D.; Zhao, B.; Zhou, S.; Xu, Y.; Shih, T.; Yao, J.C. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States. JAMA Oncol. 2017, 3, 1335.
  6. Abdel-Rahman, O. A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Unknown Primary. Neuroendocrinology 2021, 111, 876–882.
  7. Berner, A.M. Nostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site. Neuroendocrinology 2020, 110, 563–573.
  8. Datta, S.; Williams, N.; Suortamo, S.; Mahmood, A.; Oliver, C.; Hedley, N.; Ray, P. Carcinoid syndrome from small bowel endocrine carcinoma in the absence of hepatic metastasis. Age Ageing 2011, 40, 760–762.
  9. Halperin, D.M.; Shen, C.; Dasari, A.; Xu, Y.; Chu, Y.; Zhou, S.; Shih, Y.-C.T.; Yao, J.C. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: A population-based study. Lancet Oncol. 2017, 18, 525–534.
  10. Stoyianni, A.; Pentheroudakis, G.; Pavlidis, N. Neuroendocrine carcinoma of unknown primary: A systematic review of the literature and a comparative study with other neuroendocrine tumors. Cancer Treat. Rev. 2011, 37, 358–365.
  11. Ramage, J.K.; Ahmed, A.; Ardill, J.; Bax, N.; Breen, D.J.; Caplin, M.E.; Corrie, P.; Davar, J.; Davies, A.H.; Lewington, V.; et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012, 61, 6–32.
  12. Alexandraki, K.; Angelousi, A.; Boutzios, G.; Kyriakopoulos, G.; Rontogianni, D.; Kaltsas, G. Management of neuroendocrine tumors of unknown primary. Rev. Endocr. Metab. Disord. 2017, 18, 423–431.
  13. Wang, S.C.; Parekh, J.R.; Zuraek, M.B.; Venook, A.P.; Bergsland, E.K.; Warren, R.S.; Nakakura, E.K. Identification of Unknown Primary Tumors in Patients with Neuroendocrine Liver Metastases. Arch. Surg. 2010, 145, 276–280.
  14. Massimino, K.P.; Han, E.; Pommier, S.J.; Pommier, R.F. Laparoscopic surgical exploration is an effective strategy for locating occult primary neuroendocrine tumors. Am. J. Surg. 2012, 203, 628–631.
  15. Spada, F.; Rossi, R.E.; Kara, E.; Laffi, A.; Massironi, S.; Rubino, M.; Grimaldi, F.; Bhoori, S.; Fazio, N. Carcinoid Syndrome and Hyperinsulinemic Hypoglycemia Associated with Neuroendocrine Neoplasms: A Critical Review on Clinical and Pharmacological Management. Pharmaceuticals 2021, 14, 539.
  16. Rossi, R.E.; Elvevi, A.; Citterio, D.; Coppa, J.; Invernizzi, P.; Mazzaferro, V.; Massironi, S. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J. Gastroenterol. 2021, 27, 5890–5907.
  17. Wu, Y.; Xiong, G.; Zhang, H.; Wang, M.; Zhu, F.; Qin, R. Adrenocorticotropic Hormone-Producing Pancreatic Neuroendocrine Neoplasms: A Systematic Review. Endocr. Pract. 2021, 27, 152–157.
  18. Bergsland, E.K.; Nakakura, E.K. Neuroendocrine Tumors of Unknown Primary: Is the Primary Site Really Not Known? JAMA Surg. 2014, 149, 889.
  19. Catena, L.; Bichisao, E.; Milione, M.; Valente, M.; Platania, M.; Pusceddu, S.; Ducceschi, M.; Zilembo, N.; Formisano, B.; Bajetta, E. Neuroendocrine tumors of unknown primary site: Gold dust or misdiagnosed neoplasms? Tumori J. 2011, 97, 564–567.
  20. Pavel, M.; Baudin, E.; Couvelard, A.; Krenning, E.; Öberg, K.; Steinmüller, T.; Anlauf, M.; Wiedenmann, B.; Salazar, R. ENETS Consensus Guidelines for the Management of Patients with Liver and Other Distant Metastases from Neuroendocrine Neoplasms of Foregut, Midgut, Hindgut, and Unknown Primary. Neuroendocrinology 2012, 95, 157–176.
  21. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours. Digestive System Tumours, 5th ed.; WHO Classification of Tumours Editorial Board: Geneva, Switzerland, 2021.
  22. WHO Classification of Tumours of Endocrine Organs. World Health Organization Classification of Tumours, 4th ed.; WHO Classification of Tumours Editorial Board: Geneva, Switzerland, 2017.
  23. Lilo, M.T.; Chen, Y.; LeBlanc, R.E. INSM1 Is More Sensitive and Interpretable than Conventional Immunohistochemical Stains Used to Diagnose Merkel Cell Carcinoma. Am. J. Surg. Pathol. 2018, 42, 1541–1548.
  24. Oien, K.A. Pathologic Evaluation of Unknown Primary Cancer. Semin. Oncol. 2009, 36, 8–37.
  25. Kriegsmann, K.; Zgorzelski, C.; Muley, T.; Christopoulos, P.; Thomas, M.; Winter, H.; Eichhorn, M.; Eichhorn, F.; von Winterfeld, M.; Herpel, E.; et al. Role of Synaptophysin, Chromogranin and CD56 in adenocarcinoma and squamous cell carcinoma of the lung lacking morphological features of neuroendocrine differentiation: A retrospective large-scale study on 1170 tissue samples. BMC Cancer 2021, 21, 486.
  26. Lin, X.; Saad, R.S.; Luckasevic, T.M.; Silverman, J.F.; Liu, Y. Diagnostic Value of CDX-2 and TTF-1 Expressions in Separating Metastatic Neuroendocrine Neoplasms of Unknown Origin. Appl. Immunohistochem. Mol. Morphol. 2007, 15, 407–414.
  27. Silberg, D.G.; Swain, G.P.; Suh, E.R.; Traber, P.G. Cdx1 and Cdx2 expression during intestinal development. Gastroenterology 2000, 119, 961–971.
  28. Jagirdar, J. Application of Immunohistochemistry to the Diagnosis of Primary and Metastatic Carcinoma to the Lung. Arch. Pathol. Lab. Med. 2008, 132, 384–396.
  29. Lazzaro, D.; Price, M.; Felice, M.D.; Lauro, R.D. The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development 1991, 113, 1093–1104.
  30. Koo, J.; Mertens, R.B.; Mirocha, J.M.; Wang, H.L.; Dhall, D. Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin. Mod. Pathol. 2012, 25, 893–901.
  31. Koo, J.; Zhou, X.; Moschiano, E.; De Peralta-Venturina, M.; Mertens, R.B.; Dhall, D. The Immunohistochemical Expression of Islet 1 and PAX8 by Rectal Neuroendocrine Tumors Should Be Taken into Account in the Differential Diagnosis of Metastatic Neuroendocrine Tumors of Unknown Primary Origin. Endocr. Pathol. 2013, 24, 184–190.
  32. Solcia, E.; Vanoli, A. Histogenesis and Natural History of Gut Neuroendocrine Tumors: Present Status. Endocr. Pathol. 2014, 25, 165–170.
  33. Bellizzi, A.M. SATB2 in neuroendocrine neoplasms: Strong expression is restricted to well-differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas. Histopathology 2020, 76, 251–264.
  34. Kim, J.Y.; Kim, K.-S.; Kim, K.-J.; Park, I.J.; Lee, J.L.; Myung, S.-J.; Park, Y.; Park, Y.S.; Yu, C.S.; Kim, J.C.; et al. Non-L-cell Immunophenotype and Large Tumor Size in Rectal Neuroendocrine Tumors Are Associated With Aggressive Clinical Behavior and Worse Prognosis. Am. J. Surg. Pathol. 2015, 39, 632–643.
  35. Juhlin, C.C. Challenges in Paragangliomas and Pheochromocytomas: From Histology to Molecular Immunohistochemistry. Endocr. Pathol. 2021, 32, 228–244.
  36. Shuda, M.; Arora, R.; Kwun, H.J.; Feng, H.; Sarid, R.; Fernández-Figueras, M.-T.; Tolstov, Y.; Gjoerup, O.; Mansukhani, M.M.; Swerdlow, S.H.; et al. Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int. J. Cancer 2009, 125, 1243–1249.
  37. Kuhajda, F.P.; Olson, J.L.; Mann, R.B. Merkel cell (small cell) carcinoma of the skin: Immunohistochemical and ultrastructural demonstration of distinctive perinuclear cytokeratin aggregates and a possible association with B cell neoplasms. Histochem. J. 1986, 18, 239–244.
  38. Juhlin, C.C.; Zedenius, J.; Höög, A. Metastatic Neuroendocrine Neoplasms of Unknown Primary: Clues from Pathology Workup. Cancers 2022, 14, 2210.
  39. Pellegrino, F.; Granata, V.; Fusco, R.; Grassi, F.; Tafuto, S.; Perrucci, L.; Tralli, G.; Scaglione, M. Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists. Tomography 2023, 9, 217–246.
  40. Schreiter, N.F.; Bartels, A.-M.; Froeling, V.; Steffen, I.; Pape, U.-F.; Beck, A.; Hamm, B.; Brenner, W.; Röttgen, R. 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. Radiol. Oncol. 2014, 48, 339–347.
  41. Prasad, V.; Ambrosini, V.; Hommann, M.; Hoersch, D.; Fanti, S.; Baum, R.P. Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT. Eur. J. Nucl. Med. Mol. Imaging 2010, 37, 67–77.
  42. Pruthi, A.; Pankaj, P.; Verma, R.; Jain, A.; Belho, E.S.; Mahajan, H. Ga-68 DOTANOC PET/CT imaging in detection of primary site in patients with metastatic neuroendocrine tumours of unknown origin and its impact on clinical decision making: Experience from a tertiary care centre in India. J. Gastrointest. Oncol. 2016, 7, 449–461.
  43. Ma, H.; Kan, Y.; Yang, J. Clinical value of 68Ga-DOTA-SSTR PET/CT in the diagnosis and detection of neuroendocrine tumors of unknown primary origin: A systematic review and meta-analysis. Acta Radiol. 2021, 62, 1217–1228.
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Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Roberta Elisa Rossi
,
Francesca Corti
,
Sara Pusceddu
,
Massimo Milione
,
Jorgelina Coppa
,
Benedetta Masoni
,
Simone Oldani
,
Giovanna Sabella
,
Pietro Cafaro
,
Alessandro Repici
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Update Date: 11 Sep 2023
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