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Kleinzelliges Lungenkarzinom

Pathologie und Molekularpathologie

Small cell lung cancer

Pathology and molecular pathology

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Zusammenfassung

Kleinzellige Lungenkarzinome werden in der aktuellen WHO-Klassifikation mit dem Subtyp des kombinierten kleinzelligen Karzinoms als eigenständige Tumorentität geführt. Ihr mikroskopisches Bild wird von kleinen, nacktkernig erscheinenden Tumorzellen mit häufig hypodiploiden Zellkernen geprägt. Zur sicheren histologischen Diagnose, insbesondere zur differenzialdiagnostischen Abgrenzung gegenüber pulmonalen Lymphominfiltraten, werden ergänzende immunhistochemische Untersuchungen empfohlen. Die dargestellte Kernklassifikation der Lungenkarzinome soll helfen „atypische“ kleinzellige Karzinome semiquantitativ zu erfassen. Genetisch sind kleinzellige Karzinome insbesondere durch vielfältige chromosomale Deletionen mit Verlust ganzer Chromosomen oder Chromosomenarme gekennzeichnet, was mit einer Inaktivierung zahlreicher Tumorsuppressorgene einhergeht. Während die ausgedehnten DNA-Verluste eine hohe Sensibilität dieser Tumoren gegenüber Chemo- und Radiotherapie erklären, korreliert die große chromosomale Instabilität kleinzelliger Lungenkarzinome mit der Entwicklung von Therapieresistenzen.

Abstract

In the current WHO classification, together with the subtype of combined small cell lung cancer, small cell lung cancers (SCLC) are listed as a special tumour entity. Their microscopic appearance is characterised by small tumour cells with scant cytoplasm and frequently hypodiploid nuclei. For the precise histological diagnosis of SCLC, especially for the diagnostic differentiation from pulmonary NHL infiltrates, additional immunohistochemical investigations are recommended. The presented core classification of lung cancer is intended to facilitate the semi-quantitative registration of “atypical” SCLC. Genetically SCLC is especially characterised by manifold chromosomal deletions with losses of whole chromosomes or chromosome arms, associated with the inactivation of numerous tumour suppressor genes. Whereas the extensive DNA losses may explain the marked sensitivity of SCLC to anti-neoplastic chemotherapy or radiotherapy, its considerable chromosomal instability is correlated with the development of resistance to therapy.

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Literatur

  1. Borges M, Linnoila RI, van de Velde HJ et al. (1997) An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature 386(6627): 852–855

    Article  PubMed  CAS  Google Scholar 

  2. Bhattacharjee A, Richards WG, Staunton J et al. (2001) Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98(24): 13790–13795

    Article  PubMed  CAS  Google Scholar 

  3. Chen Y, Knösel T, Kristiansen G et al. (2003) Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. J Pathol 200(5): 640–646

    Article  PubMed  CAS  Google Scholar 

  4. Chen Y, Petersen S, Pacyna-Gengelbach M et al. (2003) Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer. Oncology 64(4): 450–458

    Article  PubMed  CAS  Google Scholar 

  5. Chen Y, Hühn D, Knösel T et al. (2005) Downregulation of connexin 26 in human lung cancer is related to promoter methylation. Int J Cancer 113(1): 14–21

    Article  PubMed  CAS  Google Scholar 

  6. Chen Y, Pacyna-Gengelbach M, Ye F et al. (2007). Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer. J Pathol 211(4): 431–438

    Article  PubMed  CAS  Google Scholar 

  7. Chen Y, Pacyna-Gengelbach M, Deutschmann N et al. (2007) Homeobox gene HOP has a potential tumor suppressive activity in human lung cancer. Int J Cancer 121(5): 1021–1027

    Article  PubMed  CAS  Google Scholar 

  8. Colby TV, Koss MN, Travis WD (1995) Atlas of Tumor Pathology; Tumors of the lower respiratory tract. AFIP, New York

  9. Corrin B, Nicholson AG (2006) Pathology of the lungs. Churchill Livingstone, London

  10. Crivellari G, Monfardini S, Stragliotto S et al. (2007) Increasing chemotherapy in small cell lung cancer: From dose intensity and density to megadoses. Oncologist 12: 78–89

    Article  CAS  Google Scholar 

  11. Cuttitta F, Carney DN, Mulshine J et al. (1985) Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316(6031): 823–826

    Article  PubMed  CAS  Google Scholar 

  12. Forgacs E, Zöchbauer-Müller S, Oláh E, Minna JD (2001) Molecular genetic abnormalities in the pathogenesis of human lung cancer. Pathol Oncol Res 7(1): 6–13

    Article  PubMed  CAS  Google Scholar 

  13. Fukasawa M, Kimura M, Morita S et al. (2006) Microarray analysis of promoter methylation in lung cancers. J Hum Genet 51(4): 368–374

    Article  PubMed  CAS  Google Scholar 

  14. Garber ME, Troyanskaya OG, Schluens K et al. (2001) Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 98(24): 13784–13789

    Article  PubMed  CAS  Google Scholar 

  15. Goeze A, Schlüns K, Wolf G et al. (2002) Chromosomal imbalances of primary and metastatic lung adenocarcinomas. J Pathol 196(1): 8–16

    Article  PubMed  Google Scholar 

  16. Gómez-Martín C, Rubio-Viqueira B, Hidalgo M (2005) Current status of mammalian target of rapamycin inhibitors in lung cancer. Clin Lung Cancer Suppl 1: S13–S18

    Article  Google Scholar 

  17. Hatcher J, Dover DC (2003) Trends in histopathology of lung cancer in Alberta. Can J Public Health 94(4): 292–296

    PubMed  Google Scholar 

  18. Hohla F, Schally AV, Kanashiro CA et al. (2007) Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt. Proc Natl Acad Sci USA 104(47): 18671–18676

    Article  PubMed  CAS  Google Scholar 

  19. Jackman DM, Johnson BE (2005) Small-cell lung cancer. Lancet 366(9494): 1385–1396

    Article  PubMed  CAS  Google Scholar 

  20. Janssen – Heijnen ML, Coebergh JW (2003) The changing epidemiology of lung cancer in Europe. Lung Cancer 41: 245–258

    Article  Google Scholar 

  21. Junker K, Müller KM (1989) Metastasierungsmuster beim Bronchialkarzinom. Z Herz Thorax Gefäßchir 3: 189–194

    Google Scholar 

  22. Junker K, Krapp D, Müller KM (1995) Kleinzelliges Bronchialkarzinom nach Chemotherapie – morphologische Befunde. Pathologe 16: 217–222

    Article  PubMed  CAS  Google Scholar 

  23. Junker K, Gumprich T, Müller KM (1997) Diskontinuierliche Lymphknotenmetastaen („skipping“) bei bösartigen Lungentumoren. Chirurg 68: 596–600

    Article  PubMed  CAS  Google Scholar 

  24. Junker K, Wiethege T, Müller KM (2000) Pathology of small cell lung cancer. J Cancer Res Clin Oncol 126: 361–368

    Article  PubMed  CAS  Google Scholar 

  25. Junker K, Langner K, Klinke F et al. (2001) Grading of tumor regression in non-small cell lung cancer: Morphology and prognosis. Chest 120: 1584–1591

    Article  PubMed  CAS  Google Scholar 

  26. Junker K (2004) Therapieinduzierte morphologische Veränderungen bösartiger Lungentumoren. Pathologe 25: 475–480

    Article  PubMed  CAS  Google Scholar 

  27. Junker K (2006) Aktuelle morphologische Diagnostik bösartiger Lungentumoren. Pathologe 27: 90–98

    Article  PubMed  CAS  Google Scholar 

  28. Langner K, Müller KM, Junker K (2000) Differenzierungswandel kleinzelliger Lungenkarzinome nach Chemotherapie. Pathologe 21: 358–363

    Article  PubMed  CAS  Google Scholar 

  29. Lerman MI, Minna JD (2000) The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res 60(21): 6116–6133

    PubMed  CAS  Google Scholar 

  30. Leslie KO, Wick MR (2005) Practical pulmonary pathology – a diagnostic approach. Churchill Livingstone, Philadelphia Edinburgh London

  31. Mergenthaler HG, Beinert T, Possinger K (1998) Paraneoplastische Syndrome. Internist (Berl) 39(1): 67–81

    Google Scholar 

  32. Metzgeroth G, Mautz C, Kuhn C et al. (2007) Reliable identification of small cell lung cancer in cytological specimens by immunocytology. Onkologie 30(6): 311–315

    Article  PubMed  Google Scholar 

  33. Müller KM, Junker K, Stief A (1993) Wert und Bedeutung pathologisch-anatomischer Befunde für die Thoraxchirurgie. In: Vogt-Mogkopf I, Drings P (Hrsg) Thoraxchirurgie – Stand und Ausblick. Steinkopff, Darmstadt S 23–36

  34. Osada H, Tatematsu Y, Yatabe Y et al. (2005) ASH1 gene is a specific therapeutic target for lung cancers with neuroendocrine features. Cancer Res 65(23): 10680–10685

    Article  PubMed  CAS  Google Scholar 

  35. Petersen I, Langreck H, Wolf G et al. (1997) Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p. Br J Cancer 75(1): 79–86

    PubMed  CAS  Google Scholar 

  36. Petersen I, Hidalgo A, Petersen S et al. (2000) Chromosomal imbalances in brain metastases of solid tumors. Brain Pathol 10(3): 395–401

    PubMed  CAS  Google Scholar 

  37. Petersen I, Petersen S (2001) Towards a genetic-based classification of human lung cancer. Anal Cell Pathol 22(3): 111–121

    PubMed  CAS  Google Scholar 

  38. Petersen I, Amin Kotb WFM, Friedrich KH et al. (2009) Core classification of lung cancer: correlating nuclear size and mitoses with ploidy and clinicopathological parameters. Lung Cancer (accepted)

  39. Petersen S, Wolf G, Bockmühl U et al. (1998) Allelic loss on chromosome 10q in human lung cancer: association with tumour progression and metastatic phenotype. Br J Cancer 77(2): 270–276

    PubMed  CAS  Google Scholar 

  40. Petersen S, Rudolf J, Bockmühl U et al. (1998) Distinct regions of allelic imbalance on chromosome 10q22-q26 in squamous cell carcinomas of the lung. Oncogene 17(4): 449–454

    Article  PubMed  CAS  Google Scholar 

  41. Petersen S, Rudolf J, Bockmühl U et al. (2000) Analysis of the DMBT1 gene in carcinomas of the respiratory tract. Int J Cancer 88(1): 71–76

    Article  PubMed  CAS  Google Scholar 

  42. Petersen S, Aninat-Meyer M, Schlüns K et al. (2000) Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung. Br J Cancer 82(1): 65–73

    Article  PubMed  CAS  Google Scholar 

  43. Ried T, Petersen I, Holtgreve-Grez H et al. (1994) Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization. Cancer Res 54(7): 1801–1806

    PubMed  CAS  Google Scholar 

  44. Rehfeld N, Geddert H, Atamna A et al. (2006) Coexpression of fragile histidine triad and c-kit is relevant for prediction of survival in patients with small cell lung cancer. Cancer Epidemiol Biomarkers Prev 15(11): 2232–2238

    Article  PubMed  CAS  Google Scholar 

  45. Righi L, Volante M, Rapa I et al. (2007) Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data. Virchows Arch 451(1): S51–S59

    Article  PubMed  Google Scholar 

  46. Sato M, Shames DS, Gazdar AF, Minna JD (2007) A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol 2(4): 327–343

    PubMed  Google Scholar 

  47. Schwendel A, Langreck H, Reichel M et al. (1997) Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations. Int J Cancer 74(1): 86–93

    Article  PubMed  CAS  Google Scholar 

  48. Stahel RA, Ginsberg R, Havemann K (1989) Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer 5: 119–126

    Article  Google Scholar 

  49. Sugita M, Geraci M, Gao B et al. (2002) Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res 62(14): 3971–3979

    PubMed  CAS  Google Scholar 

  50. Taniwaki M, Daigo Y, Ishikawa N et al. (2006) Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer. Int J Oncol 29(3): 567–575

    PubMed  CAS  Google Scholar 

  51. Thomas M, Rübe C, Semik M et al. (1999) Impact of preoperative bimodality induction including twice-daily radiation on tumor regresssion and survival in stage III non-small cell lung cancer. J Clin Oncol 17: 1185–1193

    PubMed  CAS  Google Scholar 

  52. Travis WD, Brambilla E, Müller-Hermeling K, Harris CC (2004) Tumours of the lung, pleura, thymus and heart. IARCPress, Lyon

  53. Wang XY, Dakir el H, Naizhen X et al. (2007) Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary epithelium. Lab Invest 87(6): 527–539

    Article  PubMed  CAS  Google Scholar 

  54. Whang-Peng J, Kao-Shan CS, Lee EC et al. (1982) Specific chromosome defect associated with human small-cell lung cancer deletion 3p(14–23). Science 215(4529): 181–182

    Article  PubMed  CAS  Google Scholar 

  55. WHO (1999) Histological typing of lung and pleural tumours. Springer, Berlin Heidelberg New York

  56. Yoshimi I, Ohshima A, Ajiki W et al. (2003) A comparison of trends in the incidence rate of lung cancer by histological type in the Osaka cancer registry, Japan, and in the surveillance, epidemiology and end results program, USA. Jpn J Clin Oncol 33: 98–194

    Article  PubMed  Google Scholar 

  57. Zabarovsky ER, Lerman MI, Minna JD (2002) Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers. Oncogene 21(45): 6915–6935

    Article  PubMed  CAS  Google Scholar 

  58. Zelen M (1973) Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 4: 31–42

    CAS  Google Scholar 

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  1. Zentrum für Pathologie, Klinikum Bremen-Mitte, St.-Jürgen-Straße 1, 28177, Bremen, Deutschland

    K. Junker

  2. Institut für Pathologie, Universitätsklinikum Jena, Jena, Deutschland

    I. Petersen

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  1. K. Junker
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  2. I. Petersen
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Correspondence to K. Junker.

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Dieser Beitrag ist in gering abweichender Form bereits in der Ausgabe 8/2008 der Zeitschrift „Der Onkologe“ erschienen.

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Junker, K., Petersen, I. Kleinzelliges Lungenkarzinom. Pathologe 30, 131–140 (2009). https://doi.org/10.1007/s00292-008-1115-y

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