Carcinoids are infrequent neoplasms arising from neuroendocrine cells. Due to blurred symptoms and the presence of equivocal diagnostic findings, these tumors are sometimes misdiagnosed. Therefore, increased rates of false neuroendocrine tumors represent an emerging problem in clinical practice. Our aim is to alert clinicians on this matter by supplying them with useful warnings.
Methods
In the specialized neuroendocrine tumor study Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a neuroendocrine tumor have been recognized as having false neuroendocrine tumors. The related clinical and instrumental findings leading to a previous wrong neuroendocrine tumor diagnosis are reported.
Results
From July 2006 to December 2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the remaining 80 cases a correct Net diagnosis was carried out. Watchful differential diagnoses and skill appraisal of laboratory investigations resulted in: chronic atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases), estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome (1), and sarcoidosis (1).
Conclusions
Neuroendocrine tumors are still relatively known clinical entities. To discriminate false neuroendocrine tumors from neuroendocrine tumors requires a good expertise and a large daily practice with the disease. Good knowledge and skillfulness in identifying biochemical alterations and false radiological positive results could avoid both patient inconvenience and very expensive workup. The importance of a multidisciplinary approach in specialized centers is emphasized.
SolciaE., KloppelG., SobinL.H.: Hystologic typing of endocrine tumours. In: World Health Organization International Histological Classification of Tumors, 2nd Edition, Berlin, Springer, 2000.
3.
Toth-FejelS., PommierR.F.: Relationship among delay of diagnosis, extent of disease, and survival in patients with abdominal carcinoid tumors. Am J Surg, 187: 575–579, 2004.
4.
KrenningE.P., BakkerW.H., BreemanW.A., KoperJ.W., KooijP.P., AusemaL., LamerisJ.S., ReubiJ.C., LambertsS.W.: Localisation of endocrine-related tumors with radioiodinated analog of somatostatin. Lancet, 1: 242–244, 1989.
5.
FerrariL., SeregniE., BajettaE., MartinettiA., BombardieriE.: The biological characteristics of chromogranin A and its role as circulating marker in neuroendocrine tumors. Anticancer Res, 19: 3415–3427, 1999.
BajettaE., BichisaoE., ArtaleS., CelioL., FerrariL., Di BartolomeoM., ZilemboN., StaniS.C., BuzzoniR.: New clinical trials for the treatment of neuroendocrine tumors. Q J Nucl Med, 44: 96–101, 2000.
12.
ChitiA., FantiS., SavelliG., RomeoA., BellanovaB., RodariM., van GraafeilandB.J., MonettiN., BombardieriE.: Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours. Eur J Nucl Med, 25: 1396–1403, 1998.
13.
ModlinI., KiddM., LatichI., ZikusokaM.N., ShapiroM.D.: Current status of gastrointestinal carcinoids. Gastroenterology, 128: 1717–1751, 2005.
14.
ErikssonB., ObergK.: Peptide hormones as tumor markers in neuroendocrine gastrointestinal tumours. Acta Oncologica, 30: 477–483, 1991.
15.
GoebelS.U., SerranoJ., YuF., GibrilF., VenzonD.J., JensenR.T.: Prospective study of the value of chromogranin A or serum gastrin levels in the assessment of the presence, extent or growth of gastrinomas. Cancer, 85: 1470–1483, 1999.
16.
StivanelloM., BerrutiA., TortaM., TermineA., TampelliniM., GorzegnoG., AngeliA., DogliottiL.: Circulating chromogranin A in the assessment of patients with neuroendocrine tumors. A single institution experience. Ann Oncol, 12: 73–77, 2001.
17.
NobelsF.R., KwekkeboomD.J., BouillonR., LambertsW.J.: Chromogranin A: its clinical value as marker of neuroendocrine tumours. Eur J Clin Inv, 28: 431–440, 1998.
18.
GiustiM., SidotiM., AugeriC., RabittiC., MinutoF.: Effect of short-term treatment with low dosages of the protonpump inhibitor omeprazole on serum chromogranin A levels in man. Eur J Endocrin, 150: 299–303, 2004.
19.
StridsbergM., ErikssonB., ObergK., JansonE.T.: A comparison between three commercial kits for chromogranin A measurements. J Endocrinol, 177: 337–341, 2003.
20.
FerrariL., SeregniE., LucignaniG., BajettaE., MartinettiA., AlibertiG., PallottiF., ProcopioG., Della TorreS., LukschR., BombardieriE.: Accuracy and clinical correlates of two different methods for chromogranin A assay in neuroendocrine tumors. Int J Biol Markers, 19: 295–304, 2004.
21.
LeonA., TortaM., DittadiR., Degli UmbertiE., AmbrosioM.R., Delle FaveG., De BraudF., TomasettiP., GionM., DogliottiL.: A comparison of circulating chromograin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study. Int J Biol Markers, 20: 156–168, 2005.
22.
PeracchiM., GebbiaC., BasilicoG., QuatriniM., TarantinoC., VescarelliC., MassironiS., ConteD.: Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids. Eur J Endocrin, 152: 443–448, 2005.
23.
SolciaE., FioccaR., VillaniL., LuinettiO., CapellaC.: Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and histogenesis. Am J Surg Pathol, 19: 1–7, 1995.
24.
BordiC., D'AddaT., AzzoniC., PilatoF.P., CaruanaP.: Hypergastrinemia and gastric enterochromaffin-like-cells. Am J Surg Pathol, 19: 8–19, 1995.
25.
ModlinI.M., LyeK.D., KiddM.: A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem?Am J Gastroenterol, 99: 23–32, 2004.
26.
BordiC., D'AddaT., AzzoniC., FerraroG.: Pathogenesis of ECL cell tumors in humans. Yale J Biol Med, 71: 273–284, 1998.
27.
BajettaE., FerrariL., MartinettiA., CelioL., ProcopioG., ArtaleS., ZilemboN., Di BartolomeoM., SeregniE., BombardieriE.: Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer, 86: 858–865, 1999.
28.
TomassettiP., MiglioriM., SimoniP., CasadeiR., De IasioR., CorinaldesiR., GulloL.: Diagnostic value of plasma chromogranin A in neuroendocrine tumours. Eur J Gastroenterol Hepatol, 13: 55–58, 2001.
29.
PanzutoF., SeveriC., CannizzaroR., FalconiM., AngelettiS., PasqualiA., CorletoV.D., AnnibaleB., BonadonnaA., PederzoliP., Delle FaveG.: Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors. J Endocrinol Invest, 27: 6–11, 2004.
30.
CampanaD., NoriF., PiscitelliL., Morselli-LabateA.M., PezzilliR., CorinaldesiR., TomassettiP.: Chromogranin A: is it a useful marker of neuroendocrine tumors?J Clin Oncol, 25: 1967–1973, 2007.
31.
SeregniE., FerrariL., BajettaE., MartinettiA., BombardieriE.: Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Oncol, 12: 69–72, 2001.
32.
RamageJ.K., DaviesA.H., ArdillJ., BaxN., CaplinM., GrossmanA., HawkinsR., McNicolA.M., ReedN., SuttonR., ThakkerR., AylwinS., BreenD., BrittonK., BuchananK., CorrieP., GillamsA., LewingtonV., McCanceD., MeeranK., WatkinsonA., UKNETwork for Neuroendocrine Tumours: Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut, 54: 1–16, 2005.
33.
SogaJ., YakuwaY., OsakaM.: Carcinoid syndrome: a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res, 18: 133–141, 1999.
34.
ChitiA., BrigantiV., FantiS., MonettiN., MasiR., BombardieriE.: Results and potential of somatostatin receptor imaging in gastroenteropancreatic tumours. Q J Nucl Med, 44: 42–49, 2000.
35.
KrenningE.P., BakkerW.H., KooijP.P., BreemanW.A., OeiH.Y., de JongM., ReubiJ.C., VisserT.J., BrunsC., KwekkeboomD.J., ReijsA.E.M., van HagenP.M., KoperJ.W., LambertsS.W.J.: Somatostatin receptor scintigraphy with indium-111-DPTA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med, 33: 652–658, 1992.
36.
GibrilF., ReynoldsJ.C., ChenC.C., YuF., GoebelS.U., SerranoJ., DoppmanJ.L., JensenR.T.: Specificity of somatostatin receptor scintigraphy: a prospective study and effects of false positive localizations on management in patients with gastrinomas. J Nucl Med, 40: 539–553, 1999.
ReubiJ.C., LaisseJ., WaserB., HorisbergerU., ShaerJ.C.: Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann N Y Acad Sci, 733: 122–137, 1994.
39.
VanhagenP.M., MarkusseH.M., LambertsS.W., KwekkeboomD.J., ReubiJ.C., KrenningE.P.: Somatostatin receptor imaging. The presence of somatostatin receptors in rheumatoid arthritis. Arthritis Rheum, 37: 1521–1527, 1994.
