Skip to main content
SpringerLink
Log in

An Analysis of Rare Carcinoid Tumors: Clarifying These Clinical Conundrums

  • Original Scientific Reports
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Carcinoid tumors are distinct neuroendocrine neoplasms with characteristic histological, clinical, and biological properties. Though commonly associated with the gastrointestinal tract and bronchopulmonary system, a substantial number of these tumors originate in less common anatomical sites and can range from indolent, unrecognized entities to highly active, metastatic secretory tumors. Their presentation within unfamiliar locations often results in clinical confusion, and they persist as unrecognized lesions, subjecting patients to delayed, inappropriate, or ineffective treatment. The authors reviewed 13,715 carcinoid tumors identified by three consecutive registries of the National Cancer Institute (NCI) from 1950 to 1999, focusing on the anatomic sites accounting for less than one percent of all carcinoids. In addition, data from the world’s literature published on carcinoid tumors within these particular anatomic locations were then analyzed with respect to incidence, clinical presentation, symptoms, diagnostic evaluation, microscopic and immunohistochemical findings, treatment strategies, and prognosis. The primary organs in which carcinoids are most commonly mistaken for some of the more conspicuous endemic tumors include the esophagus, pancreas, liver, biliary tract, gallbladder, and Meckel’s diverticulum, as well as within the pelvic and otolaryngeal organs and the breast. In general, the highest proportion of “rare” carcinoids was identified in the gastrointestinal (GI) tract, with the ovary as the single most affected extra-GI site. Tumors with the worst prognosis were those that involved the pancreas (37.5%: 5-year survival) and those in the cervix (12-33%: 3-year survival). While gastrointestinal carcinoids have become a more recognized entity and thus more amenable to identification, similar lesions are often not considered in other sites and have often either been overlooked or misdiagnosed. Widespread reports of their occurrence in rare locations warrants attention. The diminution of the likelihood of inadvertently neglecting these often benign, indolent neoplasms that are well known to metastasize if unaddressed would represent an important advance. Familiarity with such unusual sites of origin will facilitate appropriate recognition and characterization of such tumors, allowing for timely intervention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References

  1. O Lubarsch (1888) ArticleTitleUeber den primaren Krebs des Ileum, nebst Bemerkungen uber das gleichzeitige Vorkommen von Krebs und Tuberkolose Virchows Arch. Pathol. Anat. Physiol. Klin. Med. 111 280–317

    Google Scholar 

  2. A Gosset P Masson (1914) ArticleTitleTumeurs endocrines de l’appendice Presse Med. 25 237–239

    Google Scholar 

  3. B Pernow J. Waldenstrom (1954) ArticleTitleParoxysmal flushing and other symptoms caused by 5-hydroxytryptamine and histamine in patients with malignant tumors Lancet 2 951

    Google Scholar 

  4. IM Modlin K Lye M Kidd (2003) Carcinoid tumors Endocrine Surgery Marcel Dekker New York 611–639

    Google Scholar 

  5. M Pilichowska N Kimura A Ouchi et al. (1999) ArticleTitlePrimary hepatic carcinoid and neuroendocrine carcinoma: clinicopathological and immunohistochemical study of five cases Pathol Int. 49 318–324

    Google Scholar 

  6. MG Arrigoni LB Woolner PE Beraatz (1972) ArticleTitleAtypical carcinoid of the lung J. Thorac. Cardiovasc. Surg. 49 413–421

    Google Scholar 

  7. CA Maurer C Glaser JC Reubi et al. (1997) ArticleTitleCarcinoid of the pancreas Digestion 58 410–414

    Google Scholar 

  8. R Delcore SR Friesen (1994) ArticleTitleGastrointestinal neuroendocrine tumors J Am. Coll. Surg. 178 187–211

    Google Scholar 

  9. S Andreola L Lombardi RA Audisio et al. (1990) ArticleTitleA clinicopathologic study of primary hepatic carcinoid tumors Cancer 65 1211–1218

    Google Scholar 

  10. IM Modlin KD Lye M Kidd (2003) ArticleTitleA 5-decade analysis of 13,715 carcinoid tumors Cancer 97 934–959 Occurrence Handle10.1002/cncr.11105 Occurrence Handle12569593

    Article  PubMed  Google Scholar 

  11. M Froudarakis P Fournel G Burgard et al. (1996) ArticleTitleBronchial carcinoids A review of 22 cases. Oncology 51 153–158

    Google Scholar 

  12. Surveillance, Epidemiology, and End Results (SEER) Program. Public-use data (1973-1999), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch (released April 2002, based on the November 2001 submission). Bethesda, MD: National Cancer Institute, 2002

  13. IM Modlin K Lye M Kidd (2004) ArticleTitleA 50-year analysis of 562 gastric carcinoids: small tumor or larger problem? Am J. Gastroenterol. 99 23–32

    Google Scholar 

  14. JD Godwin (1975) ArticleTitleCarcinoid tumors: an analysis of 2837 cases Cancer 36 560–569 Occurrence Handle1157019

    PubMed  Google Scholar 

  15. S Brenner H Heimlich M Widman (1969) ArticleTitleCarcinoid of esophagus N. Y. state J. Med. 69 1337–1339

    Google Scholar 

  16. K Broicher HA Hienz (1974) ArticleTitleKarzinoid-Syndrom bei im Osophagus lokalisiertem Primartumor Z Gastroenterol 12 IssueIDSuppl 0 377–384

    Google Scholar 

  17. GM Lindberg KH Molberg MF Vuitch et al. (1997) ArticleTitleAtypical carcinoid of the esophagus: a case report and review of the literature Cancer 79 1476–1481

    Google Scholar 

  18. AR Ready JO Soul J Newman et al. (1989) ArticleTitleMalignant carcinoid tumour of the oesophagus Thorax 44 594–596

    Google Scholar 

  19. M Griffin EC Sweeney (1987) ArticleTitleThe relationship of endocrine cells, dysplasia and carcinoembryonic antigen in Barrett’s mucosa to adenocarcinoma of the oesophagus Histopathology 11 53–62

    Google Scholar 

  20. “Rationale of staging in cancer of the esophagus” In: Delarue, N, Wilkins, EW, Wong, J (1988) International Trends in General Thoracic Surgery: Esophageal Cancer, vol 4, C. V. Mosby, St. Louis

  21. Z Pataky L Nagy E Popik (1959) ArticleTitleUber einen vom Pankreaskopf hervorgehenden primarin Argentaffintumorbefall Zbl. Allg. Pathol. 99 442–444

    Google Scholar 

  22. CA Maurer HU Baer TH Dyong et al. (1996) ArticleTitleCarcinoid of the pancreas: clinical characteristics and morphological features Eur. J. Cancer 32A 1109–1116

    Google Scholar 

  23. RC Semelka CM Custodio N Cem Balci et al. (2000) ArticleTitleNeuroendocrine tumors of the pancreas: spectrum of appearances on MRI J. Magn. Reson. Imaging 11 141–148 Occurrence Handle10.1002/(SICI)1522-2586(200001)11:1<51::AID-JMRI7>3.0.CO;2-L Occurrence Handle1:STN:280:DC%2BD3c7nvVartw%3D%3D Occurrence Handle10713946

    Article  CAS  PubMed  Google Scholar 

  24. B Skogseid D Grama J Rastad et al. (1995) ArticleTitleOperative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1 J. Intern. Med. 238 281–288

    Google Scholar 

  25. HA Edmondson (1958) Tumor of the liver and intrahepatic bile duct Atlas of Tumor Pathology, section 7, fascicle 25 Armed Forces Institute of Pathology Washington, DC 105–109

    Google Scholar 

  26. T Asakawa T Tomioka K Abe (1999) ArticleTitlePrimary hepatic carcinoid tumor J. Gastroenterol. 34 123–127

    Google Scholar 

  27. DC Mehta RR Warner I Parnes et al. (1996) ArticleTitleAn 18-year follow-up of primary hepatic carcinoid with carcinoid syndrome J. Clin. Gastroenterol. 23 60–62

    Google Scholar 

  28. B Eriksson M Bergstrom A Sundin et al. (2002) ArticleTitleThe role of PET in localization of neuroendocrine and adrenocortical tumors Ann. N. Y. Acad. Sci. 970 159–169

    Google Scholar 

  29. Y Iimuro Y Deguchi Y Ueda et al. (2002) ArticleTitlePrimary hepatic carcinoid tumor with metachronous lymph node metastasis after long-term follow up J. Gastroenterol. Hepatol. 17 1119–1124

    Google Scholar 

  30. ET Janson K Oberg (1993) ArticleTitleLong-term management of the carcinoid syndrome: treatment with octreotide alone and in combination with a-interferon Acta Oncol. 32 225–229

    Google Scholar 

  31. AJ Davies (1959) ArticleTitleCarcinoid tumors (argentaffinomata) Ann. R. Coll. Surg. 25 277–292

    Google Scholar 

  32. RS Chamberlin LH Blumgart (1999) ArticleTitleCarcinoid tumors of the extrahepatic bile duct: a rare cause of malignant biliary obstruction Cancer 86 1959–1965 Occurrence Handle10.1002/(SICI)1097-0142(19991115)86:10<1959::AID-CNCR12>3.3.CO;2-8 Occurrence Handle1:STN:280:DC%2BD3c%2FktVWisg%3D%3D Occurrence Handle10570419

    Article  CAS  PubMed  Google Scholar 

  33. A Maitra JE Krueger M Tascilar et al. (2002) ArticleTitleCarcinoid tumors of the extrahepatic bile ducts: a study of seven cases Am. J. Surg. Pathol. 24 1501–1510

    Google Scholar 

  34. PD Hardt WE Doppl HU Klor et al. (1998) ArticleTitleA rare combination of pheochromocytoma and somatostatin-rich neuroendocrine tumor of Vater’s papilla (carcinoid) in a patient with von Recklinghausen neurofibromatosis Z. Gastroenterolo. 36 233–238

    Google Scholar 

  35. HR Makhlouf AP Burke LH Sobin (1999) ArticleTitleCarcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors Cancer 85 1241–-1249

    Google Scholar 

  36. E Hatzitheokiltos MW Buchler H Friess et al. (1994) ArticleTitleCarcinoid of the ampulla of Vater: clinical characteristics and morphologic features Cancer 73 1580–1588

    Google Scholar 

  37. AC Ross JB Hurley WB Hay et al. (1999) ArticleTitleCarcinoids of the common bile duct: a case report and literature review Can. J. Surg. 42 59–63

    Google Scholar 

  38. W. Joel (1929) ArticleTitleKarzinoidtumor der Gallenblase Zentralbl. Allg. Pathol. 46 14

    Google Scholar 

  39. T Nishigami M Yamada K Nakasho et al. (1996) ArticleTitleCarcinoid tumor of the gall bladder Int. Med. 35 953–956

    Google Scholar 

  40. Y Mizukami T Nagashima K Ikuta et al. (1998) ArticleTitleAdvanced endocrine cell carcinoma of the gallbladder: a patient with 12-year survival Hepatogastroenterology 45 1462–1467

    Google Scholar 

  41. T Kaiho T Tanaka S Tsuchiya et al. (1999) ArticleTitleA case of classical carcinoid tumor of the gallbladder: review of the Japanese published works Hepatogastroenterology 46 2189–2195

    Google Scholar 

  42. PA Sinkre L Murakata L Rabin et al. (2001) ArticleTitleClear cell carcinoid tumor of the gallbladder: another distinctive manifestation of von Hippel-Lindau disease Am. J. Surg. Pathol. 25 1334–1339

    Google Scholar 

  43. K Z’graggen S Birrer CA Maurer et al. (1998) ArticleTitleIncidence of port site recurrence after laparoscopic cholecystectomy for preoperatively unsuspected gallbladder carcinoma Surgery 124 831–838 Occurrence Handle10.1067/msy.1998.90364 Occurrence Handle1:STN:280:DyaK1M%2FktVOhuw%3D%3D Occurrence Handle9823395

    Article  CAS  PubMed  Google Scholar 

  44. P. Thorek (1963) Meckel’s diverticulum. Anatomy in Surgery Lippincott Philidelphia 394

    Google Scholar 

  45. JF Meckel (1809) ArticleTitleUber die Divertikel am Damkanal Arch. Physiol. Halle 9 421–453

    Google Scholar 

  46. C Nies A Zielke C Hasse et al. (1992) ArticleTitleCarcinoid tumors of Meckel’s diverticula. Report of two cases and review of the literature Dis. Colon Rectum 35 589–596

    Google Scholar 

  47. KO Shebani WW Souba DM Finkelstein et al. (1999) ArticleTitlePrognosis and survival in patients with gastrointestinal tract carcinoid tumors Ann. Surg. 229 815–821 Occurrence Handle10.1097/00000658-199906000-00008 Occurrence Handle1:STN:280:DyaK1M3ptVGlsQ%3D%3D Occurrence Handle10363895

    Article  CAS  PubMed  Google Scholar 

  48. DJ Anderson (2000) ArticleTitleCarcinoid tumor in Meckel’s diverticulum: laparascopic treatment and review of the literature J. Am. Osteopath. Assoc. 100 432–434

    Google Scholar 

  49. J Driessens A Clay L Adenis et al. (1964) ArticleTitleTumeur cervico-uterine et syndrome biologique de carcinoidose Arch. Anat. Pathol. 12 200–203

    Google Scholar 

  50. S Starzynski M Kubicka-Pertkiewicz (1978) ArticleTitleCarcinoid of the uterine corpus Patol. Pol. 29 237–240

    Google Scholar 

  51. K Hirahatake H Hareyama R Kure et al. (1990) ArticleTitleCytologic and hormonal findings in a carcinoid tumor of the uterine cervix Acta Cytol. 34 119–124

    Google Scholar 

  52. R Chetty SP Clark PS Bhathal (1993) ArticleTitleCarcinoid tumour of the uterine corpus Virchows Arch. A Pathol. Anat. Histopathol. 422 93–95

    Google Scholar 

  53. J Albores-Saavedra HA Rodriguez-Martinez O Larraza-Hernandez (1979) ArticleTitleCarcinoid tumors of the cervix Pathol. Annu. 14 IssueIDPt 1 273–291

    Google Scholar 

  54. DW Hsu SC Hooi ET Hedley-Whyte et al. (1991) ArticleTitleCoexpression of galanin and adrenocorticotropic hormone in human pituitary and pituitary adenomas Am. J. Pathol. 138 897–909

    Google Scholar 

  55. CA Koch N Azumi MA Furlong et al. (1999) ArticleTitleCarcinoid syndrome caused by an atypical carcinoid of the uterine cervix J. Clin. Endocrinol. Metab. 84 4209–4213

    Google Scholar 

  56. EG Silva MM Kott NG Ordonez (1984) ArticleTitleEndocrine carcinoma intermediate cell type of the uterine cervix Cancer 54 1705–1713

    Google Scholar 

  57. KP Davis LK Hartmann GL Keeney et al. (1996) ArticleTitlePrimary ovarian carcinoid tumors Gynecol. Oncol. 61 259–265

    Google Scholar 

  58. SJ Robboy HJ Norris RE Scully (1975) ArticleTitleInsular carcinoid primary in the ovary. A clinicopathologic analysis of 48 cases Cancer 36 404–418

    Google Scholar 

  59. D Vergani L Massironi F Lombardi et al. (1998) ArticleTitleCarcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure Heart 80 623–626

    Google Scholar 

  60. HB Simon JR McDonald OS Culp (1954) ArticleTitleArgentaffin tumor (carcinoid) occurring in a benign cystic teratoma of the testicle Am. J. Clin. Pathol. 72 892–894

    Google Scholar 

  61. A Zavala-Pompa JY Ro A el-Naggar et al. (1993) ArticleTitlePrimary carcinoid tumor of testis. Immunohistochemical, ultrastructural, and DNA flow cytometric study of three cases with a review of the literature Cancer 72 1726–1732

    Google Scholar 

  62. T Hayashi S Iida J Taguchi et al. (2001) ArticleTitlePrimary carcinoid of the testis associated with carcinoid syndrome Int. J. Urol. 8 522–524

    Google Scholar 

  63. CC Berdjis FK Mostofi (1977) ArticleTitleCarcinoid tumors of the testis J. Urol. 118 777–782

    Google Scholar 

  64. GF Murphy BZ Pilch GR Dickersin et al. (1980) ArticleTitleCarcinoid tumor of the middle ear Am. J. Clin. Pathol. 73 816–823

    Google Scholar 

  65. JH Krouse JB Nadol SuffixJr ML Goodman (1990) ArticleTitleCarcinoid tumors of the middle ear Ann. Otal. Rhinol. Laryngol. 99 IssueID7 Pt 1 547–552

    Google Scholar 

  66. KR Torske LD Thompson (2002) ArticleTitleAdenoma versus carcinoid tumor of the middle ear: a study of 48 cases and review of the literature Mod. Pathol. 15 543–555

    Google Scholar 

  67. G Menezes P Wakely SuffixJr. (2001) ArticleTitleAspiration cytopathology of middle-ear neuroendocrine carcinoma Diagn. Cytopathol. 25 168–171

    Google Scholar 

  68. NC Goldman CI Hood GT Singleton (1969) ArticleTitleCarcinoid of the larynx Arch. Otolaryngol. 90 64–67

    Google Scholar 

  69. JC Cuzzourt JC Pezold CW Dunn (2002) ArticleTitleTypical carcinoid tumor of the larynx occurring with otalgia: a case report Ear Nose Throat J 81 40–43

    Google Scholar 

  70. R Dieler J Dammrich (1995) ArticleTitleImmunohistochemical and fine structural characterization of primary carcinoid tumors of the larynx Eur. Arch. Otorhinolaryngol. 252 229–235

    Google Scholar 

  71. E Duvall A Johnston K McLay et al. (1983) ArticleTitleCarcinoid tumour of the larynx. A report of two cases J. Laryngol Otol 97 IssueID11 1073–1080

    Google Scholar 

  72. AL Cubilla JM Woodruff (1977) ArticleTitlePrimary carcinoid tumor of the breast: a report of eight patients Am. J. Surg. Pathol. 1 283–292

    Google Scholar 

  73. B Meunier J Le Cloirec L Dazord et al. (1995) ArticleTitlePerioperative localization of a carcinoid tumour of the breast using indium-111 pentetreotide and a nuclear surgical probe Eur. J. Nucl. Med. 22 281–283

    Google Scholar 

  74. R Giacchi M Sebastiani F Lungarotti (1986) ArticleTitleThe so-called “carcinoid” tumors of the breast Ital. J. Surg. Sci. 16 249–253

    Google Scholar 

  75. KA Hussein DS Sanders PE Preece et al. (1989) ArticleTitleArgyrophil carcinoma of the breast: a cytologic, histochemical, and ultrastructural study of a case Diagn. Cytopathol. 5 217–220

    Google Scholar 

  76. M Papotti F Tanda G Bussolati et al. (1993) ArticleTitleArgyrophilic neuroendocrine carcinoma of the male breast Ultrastruct. Pathol. 17 115–121

    Google Scholar 

  77. M Imamura H Yamauchi T Namiki (1995) ArticleTitleResected case of carcinoid tumor of the liver metastatic from the breast J. Gastroenterol. 30 398–402

    Google Scholar 

  78. M Kurosumi C Nomoto K Suemasu et al. (1989) ArticleTitleArgyrophilic carcinoma “carcinoid tumor” of the breast: case report with electron microscopic and immunohistochemical investigations Jpn. J. Clin. Oncol. 19 397–401

    Google Scholar 

  79. LK Jablon RG Somers PY Kim (1998) ArticleTitleCarcinoid tumor of the breast: treatment with breast conservation in three patients Ann. Surg. Oncol. 5 261–264

    Google Scholar 

  80. HH Hartgrink MB Lagaay PJ Spaander et al. (1995) ArticleTitleA series of carcinoid tumours of the breast Eur. J. Surg. Oncol. 21 609–612

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastric Pathobiology Research Group, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208062, New Haven, Connecticut 06520-8062, USA

    Irvin M. Modlin M.D., Ph.D., Michael D. Shapiro B.S. & Mark Kidd Ph.D.

Authors
  1. Irvin M. Modlin M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael D. Shapiro B.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark Kidd Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irvin M. Modlin M.D., Ph.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Modlin, I.M., Shapiro, M.D. & Kidd, M. An Analysis of Rare Carcinoid Tumors: Clarifying These Clinical Conundrums. World J. Surg. 29, 92–101 (2005). https://doi.org/10.1007/s00268-004-7443-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-004-7443-z

Keywords

Search

Navigation