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Primäre neuroendokrine Karzinome der Leber

Vom Karzinoidtumor bis zum kleinzelligen Leberkarzinom: Fallberichte und Literaturübersicht

Primary neuroendocrine carcinoma of the liver

From carcinoid tumor to small-cell hepatic carcinoma: case reports and review of the literature

  • Schwerpunkt: Leberpathologie
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Zusammenfassung

Primäre neuroendokrine Karzinome der Leber sind seltene Neoplasien. Das Spektrum reicht von hoch differenzierten primär hepatischen Karzinoidtumoren (PHCT) bis zu undifferenzierten primären hepatischen kleinzelligen Karzinomen (PHSCC). Unsere erste Patientin mit einem PHCT beobachten wir bereits über einen Zeitraum von 32 Jahren. Während dieser Zeit kam es 4-mal zu einem Rezidiv und zu hämatogenen Metastasen mit gleich bleibendem histologischen und immunhistochemischen Muster. Unsere zweite Patientin erkrankte an einem kleinzelligen Karzinom der Leber ohne hepatozelluläre oder cholangiozelluläre Differenzierungsmerkmale. Es bestanden keine Risikofaktoren für ein hepatozelluläres Karzinom. Selbst eine extensive prä- und postoperative Diagnostik konnte keinen extrahepatischen Primärherd identifizieren. Immunhistochemisch erwies sich der Tumor als negativ für Hepar-1, AFP, TTF1, CDX2, exprimierte punktförmig die Keratine 8, 18 und 20, weiterhin CD56. Nach der Diagnose eines neuroendokrinen PHSCC wurde der Tumor ohne nachweisbare tumorreduktive Wirkung neoadjuvant chemotherapiert und anschließend komplett exstirpiert. 18 Monate nach der Operation ist die Patientin beschwerdefrei ohne Anhalt für ein Rezidiv oder Metastasen.

PHCT und PHSCC müssen klar von hepatozellulären und cholangiozellulären Karzinomen unterschieden werden. Auch der Ausschluss eines extrahepatischen Primärherds ist essenziell und erfordert eine sorgfältige synoptische Analyse der klinischen, radiologischen und pathologischen Befunde. Die chirurgische Entfernung ist Therapie der Wahl.

Abstract

Primary hepatic neuroendocrine tumors are rare neoplasms. While primary hepatic carcinoid tumors (PHCT) are well-differentiated tumors, primary hepatic small-cell carcinomas (PHSCC) represent the poorly differentiated end of the spectrum of neuroendocrine carcinomas. The first patient, suffering from PHCT, has had a follow-up for 32 years and is still alive. Within this time, the tumor relapsed 4 times with unchanged histology and immunohistochemistry features. The second patient suffered from small-cell carcinoma of the liver. There were no risk factors for a hepatocellular carcinoma. An extensive preoperative and postoperative diagnostic investigation could rule out an extrahepatic primary site. Immunohistochemically the tumor was negative for Hepar-1, AFP, TTF1 and CDX2 but reacted positively with CD56 and sporadically with the keratins 8, 18 and 20. A neuroendocrine PHSCC was diagnosed. After neoadjuvant cytostatic treatment the carcinoma was completely extirpated and 18 months after treatment the patient is healthy.

PHCT and PHSCC have to be clearly separated from hepatocellular and cholangiocellular carcinomas. Exclusion of an extrahepatic primary site requires an accurate and synoptic analysis of clinical, radiologic and pathologic findings. Surgical resection is the treatment of choice.

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Literatur

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

    Article  PubMed  CAS  Google Scholar 

  2. Aoki K, Sakamoto M, Mukai K et al. (1992) Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic inclusions comprising of aggregates of keratin. Jpn J Clin Oncol 22: 54–59

    PubMed  CAS  Google Scholar 

  3. Arnold JC, O’Grady JG, Bird GL et al. (1989) Liver transplantation for primary and secondary hepatic apudomas. Br J Surg 76: 248–249

    Article  PubMed  CAS  Google Scholar 

  4. Asakawa T, Tomioka T, Abe K et al. (1999) Primary hepatic carcinoid tumor. J Gastroenterol 34: 123–127

    Article  PubMed  CAS  Google Scholar 

  5. Ayub A, Zafar M, Abdulkareem A et al. (1993) Primary hepatic vipoma. Am J Gastroenterol 88: 958–961

    PubMed  CAS  Google Scholar 

  6. Bastaki W, Mothaffer F, Varro J et al. (2005) Primary hepatic carcinoid tumor. Med Princ Pract 14: 288–291

    Article  PubMed  CAS  Google Scholar 

  7. Craig JR, Peters RL, Edmondson HA (1989) Tumors of the liver and intrahepatic bile ducts. Atlas of tumor pathology. Armed Forces Institute of Pathology, Washington/DC, pp 102–103

  8. Diaz R, Aparicio J, Pous S et al. (2003) Primary hepatic gastrinoma. Dig Dis Sci 48: 1665–1667

    Article  PubMed  Google Scholar 

  9. Edmondson HA (1958) Carcinoid tumor. Atlas of tumor pathology. Armed Forces Institute of Pathology, Washington DC, pp 105–111

  10. Fenwick SW, Wyatt JI, Toogood GJ, Lodge JP (2004) Hepatic resection and transplantation for primary carcinoid tumors of the liver. Ann Surg 239: 210–219

    Article  PubMed  Google Scholar 

  11. Ferrero A, Gallino C, D’Aloisio G et al. (1999) Primary neuroendocrine carcinoma of the liver: difficult diagnosis of a rare neoplasm. Acta Chir Belg 99: 299–302

    PubMed  CAS  Google Scholar 

  12. Fujino K, Koito K, Sano S et al. (1998) A primary hepatic carcinoid tumor: evaluation by computed tomography and magnetic resonance imaging. Radiat Med 16: 371–373

    PubMed  CAS  Google Scholar 

  13. Fukunaga M (1998) Neuroendocrine carcinoma of the liver: an autopsy case. Pathol Int 48: 481–485

    PubMed  CAS  Google Scholar 

  14. Furrer J, Hattenschwiler A, Komminoth P et al. (2001) Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver. J Clin Endocrinol Metab 86: 2227–2230

    Article  PubMed  CAS  Google Scholar 

  15. Gutgemann I, Standop J, Fischer HP (in press) Primary intrahepatic malignant mesothelioma of epithelioid type. Virchows Arch: Epub ahead of print

  16. Hirata M, Ishida H, Konno K et al. (2002) Primary carcinoid tumor of the liver: report of two cases with an emphasis on US findings. Abdom Imaging 27: 325–328

    PubMed  CAS  Google Scholar 

  17. Hirohashi S, Ishak KG, Kojiro M et al. (2000) Hepatocellular carcinoma. In: Hamilton SR, Aaltonen LA (eds) Pathology and genetics of tumors of the digestive systeme. WHO Classification of Tumors. IARC Press, Lyon, pp 158–172

  18. Hsueh C, Tan XD, Gonzalez-Crussi F (1993) Primary hepatic neuroendocrine carcinoma in a child. Morphologic, immunocytochemical, and molecular biologic studies. Cancer 71: 2660–2665

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Inoue Y, Nakamura H, Mizumoto S et al. (1993) Primary hepatic carcinoid with production of gastrin: a case report. Radiat Med 11: 102–106

    PubMed  CAS  Google Scholar 

  21. Ishak KG, Goodman ZD, Stocker JT (2001) Tumors of the liver and intrahepatic bile ducts. In: Atlas of tumor Pathology. Armed Forces Institute of Pathology, Washington/DC

  22. Ishida M, Seki K, Tatsuzawa A et al. (2003) Primary hepatic neuroendocrine carcinoma coexisting with hepatocellular carcinoma in hepatitis C liver cirrhosis: report of a case. Surg Today 33: 214–218

    Article  PubMed  Google Scholar 

  23. Ito H, Masuda H, Tahara E, Wittekind C (1989) Karzinoid-Tumor der Leber. Dtsch Med Wochenschr 114: 623–627

    Article  PubMed  CAS  Google Scholar 

  24. Iwao M, Nakamuta M, Enjoji M et al. (2001) Primary hepatic carcinoid tumor: case report and review of 53 cases. Med Sci Monit 7: 746–750

    PubMed  CAS  Google Scholar 

  25. Kaya G, Pasche C, Osterheld MC et al. (2001) Primary neuroendocrine carcinoma of the liver: an autopsy case. Pathol Int 51: 874–878

    Article  PubMed  CAS  Google Scholar 

  26. Kehagias D, Moulopoulos L, Smirniotis V et al. (1999) Imaging findings in primary carcinoid tumour of the liver with gastrin production. Br J Radiol 72: 207–209

    PubMed  CAS  Google Scholar 

  27. Kim SR, Imoto S, Maekawa Y et al. (2002) CEA producing primary hepatic carcinoid. Hepatol Res 22: 313–321

    Article  PubMed  Google Scholar 

  28. Knox CD, Anderson CD, Lamps LW et al. (2003) Long-term survival after resection for primary hepatic carcinoid tumor. Ann Surg Oncol 10: 1171–1175

    Article  PubMed  Google Scholar 

  29. Kohashi T, Itamoto T, Katayama K et al. (2005) Primary hepatic carcinoid tumor (a case report). Hepatogastroenterology 52: 1218–1220

    PubMed  Google Scholar 

  30. Komatsuda T, Ishida H, Furukawa K et al. (2005) Primary carcinoid tumor of the liver: report of a case with an emphasis on contrast-enhanced ultrasonographic findings. J Clin Ultrasound 33: 302–304

    Article  PubMed  Google Scholar 

  31. Krishnamurthy SC, Dutta V, Pai SA et al. (1996) Primary carcinoid tumor of the liver: report of four resected cases including one with gastrin production. J Surg Oncol 62: 218–221

    Article  PubMed  CAS  Google Scholar 

  32. Larriva-Sahd J, Angeles-Angeles A, Hernandez-Pando R et al. (1992) Ultrastructural and immunocytochemical study of a primary gastrinoma of the liver. Ultrastruct Pathol 16: 667–672

    Article  PubMed  CAS  Google Scholar 

  33. Maire F, Couvelard A, Vullierme MP et al. (2005) Primary endocrine tumours of the liver. Br J Surg 92: 1255–1260

    Article  PubMed  CAS  Google Scholar 

  34. Mehta DC, Warner RR, Parnes I, Weiss M (1996) An 18-year follow-up of primary hepatic carcinoid with carcinoid syndrome. J Clin Gastroenterol 23: 60–62

    Article  PubMed  CAS  Google Scholar 

  35. Miura K, Shirasawa H (1988) Primary carcinoid tumor of the liver. Am J Clin Pathol 89: 561–564

    PubMed  CAS  Google Scholar 

  36. Mizuno Y, Ohkohchi N, Fujimori K et al. (2000) Primary hepatic carcinoid tumor: a case report. Hepatogastroenterology 47: 528–530

    PubMed  CAS  Google Scholar 

  37. Nemes B, Podder H, Jaray J et al. (1999) Primary hepatic carcinoid in a renal transplant patient. Pathol Oncol Res 5: 67–69

    Article  PubMed  CAS  Google Scholar 

  38. Nishimori H, Tsuji K, Miyamoto N et al. (2005) Recurrence of primary hepatic carcinoid tumor in the remnant liver 13 yr after resection. Int J Gastrointest Cancer 35: 147–151

    Article  PubMed  Google Scholar 

  39. Norton JA, Doherty GM, Fraker DL et al. (1998) Surgical treatment of localized gastrinoma within the liver: a prospective study. Surgery 124: 1145–1152

    Article  PubMed  CAS  Google Scholar 

  40. Oh YH, Kang GH, Kim OJ (1998) Primary hepatic carcinoid tumor with a paranuclear clear zone: a case report. J Korean Med Sci 13: 317–320

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  42. Ruckert RI, Ruckert JC, Dorffel Y et al. (1999) Primary hepatic neuroendocrine tumor: successful hepatectomy in two cases and review of the literature. Digestion 60: 110–116

    Article  PubMed  CAS  Google Scholar 

  43. Rugge M, Sonego F, Militello C et al. (1992) Primary carcinoid tumor of the cystic and common bile ducts. Am J Surg Pathol 16: 802–807

    Article  PubMed  CAS  Google Scholar 

  44. Ryu SH, Han SY, Suh SH et al. (2005) [A case of primary small cell carcinoma of the liver]. Korean J Hepatol 11: 289–292

    PubMed  Google Scholar 

  45. Sano K, Kosuge T, Yamamoto J et al. (1999) Primary hepatic carcinoid tumors confirmed with long-term follow-up after resection. Hepatogastroenterology 46: 2547–2550

    PubMed  CAS  Google Scholar 

  46. Shih WJ, Samayoa L, Shih GL, Milan P (2005) Primary hepatic carcinoid tumor presenting as a large multicystic lesion of the liver and on Tc-99m RBC abdominal imaging showing photopenic areas. Clin Nucl Med 30: 530–531

    Article  PubMed  Google Scholar 

  47. Sioutos N, Virta S, Kessimian N (1991) Primary hepatic carcinoid tumor. An electron microscopic and immunohistochemical study. Am J Clin Pathol 95: 172–175

    PubMed  CAS  Google Scholar 

  48. Staren ED, Gould VE, Warren WH et al. (1988) Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation. Surgery 104: 1080–1089

    PubMed  CAS  Google Scholar 

  49. Staren ED, Lott S, Saavedra VM et al. (1992) Neuroendocrine carcinomas of the stomach: a clinicopathologic evaluation. Surgery 112: 1039–1046; discussion 1046–1047

    PubMed  CAS  Google Scholar 

  50. Takayasu K, Muramatsu Y, Sakamoto M et al. (1992) Findings in primary hepatic carcinoid tumor: US, CT, MRI, and angiography. J Comput Assist Tomogr 16: 99–102

    Article  PubMed  CAS  Google Scholar 

  51. Tanaka M, Shibui S, Nomura K, Nakanishi Y (1999) Brain metastases from adenoendocrine carcinoma of the common bile duct: a case report. Jpn J Clin Oncol 29: 252–255

    Article  PubMed  CAS  Google Scholar 

  52. Tohyama T, Matsui K, Kitagawa K (2005) Primary hepatic carcinoid tumor with carcinoid syndrome and carcinoid heart disease: a case report of a patient on long-term follow-up. Intern Med 44: 958–962

    Article  PubMed  Google Scholar 

  53. Tsuchimochi S, Nakajo M, Inoue H et al. (1995) Primary hepatic neuroendocrine carcinoma with multiple metastases: a case report. Radiat Med 13: 183–185

    PubMed  CAS  Google Scholar 

  54. Ulusan S, Kizilkilic O, Yildirim T et al. (2005) Primary hepatic carcinoid tumor: dynamic CT findings. Abdom Imaging 30: 281–285

    Article  PubMed  CAS  Google Scholar 

  55. Warner TF, Seo IS, Madura JA et al. (1980) Pancreatic-polypeptide-producing apudoma of the liver. Cancer 46: 1146–1151

    Article  PubMed  CAS  Google Scholar 

  56. Xi YP, Yu JY (1986) Primary neuroendocrine carcinoma of the liver. Ultrastruct Pathol 10: 331–336

    Article  PubMed  CAS  Google Scholar 

  57. Yamashita Y, Takahashi M, Tsuji A et al. (1986) Primary carcinoid tumor of the liver: a case report. J Comput Tomogr 10: 313–317

    Article  PubMed  CAS  Google Scholar 

  58. Yang L, Li S, Hatch H et al. (2002) In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci U S A 99: 8078–8083

    Article  PubMed  CAS  Google Scholar 

  59. Yang YY, Lin HC, Hou MC et al. (2003) Good response to hepatic arterial chemoembolization in a patient with primary neuroendocrine tumor of the liver. J Chin Med Assoc 66: 247–251

    PubMed  Google Scholar 

  60. Yasoshima H, Uematsu K, Sakurai K et al. (1993) Primary hepatic carcinoid tumor. Acta Pathol Jpn 43: 783–789

    PubMed  CAS  Google Scholar 

  61. Zanconati F, Falconieri G, Lamovec J, Zidar A (1996) Small cell carcinoma of the liver: a hitherto unreported variant of hepatocellular carcinoma. Histopathology 29: 449–453

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinik Bonn, Bonn, Deutschland

    Z. Balta, R. Büttner & H.-P. Fischer

  2. Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Bonn, Deutschland

    T. Sauerbruch

  3. Chirurgische Universitätsklinik, Universitätsklinikum Bonn, Bonn, Deutschland

    A. Hirner

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Balta, Z., Sauerbruch, T., Hirner, A. et al. Primäre neuroendokrine Karzinome der Leber. Pathologe 29, 53–60 (2008). https://doi.org/10.1007/s00292-007-0957-z

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