Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-ndmmz Total loading time: 0 Render date: 2024-05-01T11:38:12.467Z Has data issue: false hasContentIssue false

Chapter 29 - Large cell carcinoma and adenosquamous carcinoma of the lung

Published online by Cambridge University Press:  05 June 2014

By
Sylvie Lantuejoul ,
Michèle Fior-Gozlan ,
Gilbert R. Ferretti  and
Denis Moro-Sibilot
Edited by
Philip Hasleton  and
Douglas B. Flieder
Philip Hasleton
Affiliation:
University of Manchester
Douglas B. Flieder
Affiliation:
Fox Chase Cancer Center, Philadelphia
Get access

Summary

Large cell carcinoma

Large cell carcinoma (LCC) is a “waste basket” histological group of non-small cell lung carcinomas (NSCLC). Prior to the 1999 World Health Organization (WHO) classification, these carcinomas were variously termed large cell anaplastic carcinoma or large cell undifferentiated carcinoma. In the current WHO classification, LCC is clearly defined as a malignant epithelial tumor composed of large cells lacking light microscopic or histochemical evidence of squamous, glandular or small cell differentiation. Nevertheless, this subgroup includes three distinctive histological entities, namely large cell neuroendocrine carcinoma (LCNEC), basaloid carcinoma and lymphoepithelioma-like carcinoma (LELC). In addition, two other morphological variants, namely clear cell and rhabdoid, warrant discussion (Table 1).

Large cell carcinomas are poorly differentiated tumors diagnosed in the absence of glandular or squamous features. This small group represents no more than 10% of lung cancers. However, if classified on the basis of either electron microscopy or molecular findings, this category would account for a far smaller percentage of lung carcinomas. LCNEC and basaloid carcinoma may be the most common LCC, with each accounting for 3 to 5% of lung carcinomas. Lymphoepithelioma-like carcinoma accounts for 1% of lung tumors in China, but even fewer in Western countries.

Type
Chapter
Information
Spencer's Pathology of the Lung , pp. 1114 - 1126
Publisher: Cambridge University Press
Print publication year: 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Travis, WD, Colby, TV, Corrin, B, Shimosato, Y, Brambilla, E.Histological Typing of Lung and Pleural Tumours, 3rd ed. Berlin: Springer-Verlag, 1999.CrossRefGoogle Scholar
Travis, WD, Brambilla, E, Muller-Hermelink, HK, Harris, CC.Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC, 2004.Google Scholar
Travis, WD, Linnoila, RI, Tsokos, MG, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991;15:529–53.CrossRefGoogle ScholarPubMed
Brambilla, E, Moro, D, Veale, D, et al. Basal cell (basaloid) carcinoma of the lung: a new morphologic and phenotypic entity with separate prognostic significance. Hum Pathol 1992;23:993–1003.CrossRefGoogle ScholarPubMed
Travis, WD, Travis, LB, Devesa, SS.Lung cancer. Cancer 1995;75(1 Suppl):191–202.3.0.CO;2-Y>CrossRefGoogle ScholarPubMed
Nacht, M, Dracheva, T, Gao, Y, et al. Molecular characteristics of non-small cell lung cancer. Proc Natl Acad Sci USA 2001;98:15203–8.CrossRefGoogle ScholarPubMed
Virtanen, C, Ishikawa, Y, Honjoh, D, et al. Integrated classification of lung tumors and cell lines by expression profiling. Proc Natl Acad Sci USA 2002;99:12357–62.CrossRefGoogle ScholarPubMed
Bhattacharjee, A, Richards, WG, Staunton, J, et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 2001;98:13790–5.CrossRefGoogle ScholarPubMed
Garber, ME, Troyanskaya, OG, Schluens, K, et al. Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 2001;98:13784–9.CrossRefGoogle ScholarPubMed
Iyoda, A, Hiroshima, K, Toyozaki, T, et al. Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology. Cancer 2001;91:1992–2000.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Moro-Sibilot, D, Lantuejoul, S, Diab, S, et al. Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis. Eur Respir J 2008;31:854–9.CrossRefGoogle ScholarPubMed
Ho, JC, Wong, MP, Lam, WK.Lymphoepithelioma-like carcinoma of the lung. Respirology 2006;11:539–45.CrossRefGoogle ScholarPubMed
Geisinger, KR, Stanley, MW, Raab, SS, Silverman, JF, Abati, A.Modern Cytopathology. New York: Churchill Livingstone, 2003.Google Scholar
Jerome, Marson V, Mazieres, J, Groussard, O, et al. Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade. Histopathology 2004;45:125–34.CrossRefGoogle Scholar
Kargi, A, Gurel, D, Tuna, B.The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas. Appl Immunohistochem Mol Morphol 2007;15:415–20.CrossRefGoogle ScholarPubMed
Boucher, LD, Yoneda, K.The expression of trophoblastic cell markers by lung carcinomas. Hum Pathol 1995;26:1201–6.CrossRefGoogle ScholarPubMed
Hammar, SP, Bolen, JW, Bockus, D, Remington, F, Friedman, S.Ultrastructural and immunohistochemical features of common lung tumors: an overview. Ultrastruct Pathol 1985;9:283–318.CrossRefGoogle ScholarPubMed
Hammar, S.Adenocarcinoma and large cell undifferentiated carcinoma of the lung. Ultrastruct Pathol 1987;11:263–91.CrossRefGoogle ScholarPubMed
Delmonte, VC, Alberti, O, Saldiva, PH.Large cell carcinoma of the lung. Ultrastructural and immunohistochemical features. Chest 1986;90:524–7.CrossRefGoogle ScholarPubMed
Ninomiya, H, Nomura, K, Satoh, Y, et al. Genetic instability in lung cancer: concurrent analysis of chromosomal, mini- and microsatellite instability and loss of heterozygosity. Br J Cancer 2006;94:1485–91.CrossRefGoogle ScholarPubMed
Johansson, M, Dietrich, C, Mandahl, N, et al. Karyotypic characterization of bronchial large cell carcinomas. Int J Cancer 1994;57:463–7.CrossRefGoogle ScholarPubMed
Ohtsuka, K, Ohnishi, H, Fujiwara, M, et al. Abnormalities of epidermal growth factor receptor in lung squamous-cell carcinomas, adenosquamous carcinomas, and large-cell carcinomas: tyrosine kinase domain mutations are not rare in tumors with an adenocarcinoma component. Cancer 2007;109:741–50.CrossRefGoogle Scholar
Zhu, CQ, da Cunha, Santos G, Ding, K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008;26:4268–75.CrossRefGoogle ScholarPubMed
Ishida, T, Kaneko, S, Tateishi, M, et al. Large cell carcinoma of the lung. Prognostic implications of histopathologic and immunohistochemical subtyping. Am J Clin Pathol 1990;93:176–82.CrossRefGoogle ScholarPubMed
Downey, RJ, Asakura, S, Deschamps, C, Colby, TV.Large cell carcinoma of the lung: results of resection for a cure. J Thorac Cardiovasc Surg 1999;117:599–604.CrossRefGoogle Scholar
Wertzel, H, Grahmann, PR, Bansbach, S, Lange, W, Hasse, J, Bohm, N.Results after surgery in undifferentiated large cell carcinoma of the lung: the role of neuroendocrine expression. Eur J Cardiothorac Surg 1997;12:698–702.CrossRefGoogle ScholarPubMed
Martini, N, Rusch, VW, Bains, MS, et al. Factors influencing ten-year survival in resected stages I to IIIa non-small cell lung cancer. J Thorac Cardiovasc Surg 1999;117:32–6; discussion 7–8.CrossRefGoogle ScholarPubMed
Moro, D, Brichon, PY, Brambilla, E, et al. Basaloid bronchial carcinoma. A histologic group with a poor prognosis. Cancer 1994;73:2734–9.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Sturm, N, Lantuejoul, S, Laverriere, MH, et al. Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung. Hum Pathol 2001;32:918–25.CrossRefGoogle ScholarPubMed
Kim, DJ, Kim, KD, Shin, DH, Ro, JY, Chung, KY.Basaloid carcinoma of the lung: a really dismal histologic variant?Ann Thorac Surg 2003;76:1833–7.CrossRefGoogle ScholarPubMed
Chen, FF, Yan, JJ, Lai, WW, Jin, YT, Su, IJ.Epstein-Barr virus-associated nonsmall cell lung carcinoma: undifferentiated “lymphoepithelioma-like” carcinoma as a distinct entity with better prognosis. Cancer 1998;82:2334–42.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Curcio, LD, Cohen, JS, Grannis, FW Jr, et al. Primary lymphoepithelioma-like carcinoma of the lung in a child. Report of an Epstein-Barr virus-related neoplasm. Chest 1997;111:250–1.CrossRefGoogle Scholar
Weiss, LM, Movahed, LA, Butler, AE, et al. Analysis of lymphoepithelioma and lymphoepithelioma-like carcinomas for Epstein-Barr viral genomes by in situ hybridization. Am J Surg Pathol 1989;13:625–31.CrossRefGoogle ScholarPubMed
Castro, CY, Ostrowski, ML, Barrios, R, et al. Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. Hum Pathol 2001;32:863–72.CrossRefGoogle ScholarPubMed
Chang, YL, Wu, CT, Shih, JY, Lee, YC.New aspects in clinicopathologic and oncogene studies of 23 pulmonary lymphoepithelioma-like carcinomas. Am J Surg Pathol 2002;26:715–23.CrossRefGoogle ScholarPubMed
Huang, CJ, Chan, KY, Lee, MY, et al. Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma. Br J Radiol 2007;80:803–6.CrossRefGoogle ScholarPubMed
Chan, JK, Hui, PK, Tsang, WY, et al. Primary lymphoepithelioma-like carcinoma of the lung. A clinicopathologic study of 11 cases. Cancer 1995;76:413–22.3.0.CO;2-X>CrossRefGoogle Scholar
Han, AJ, Xiong, M, Zong, YS.Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the lung in southern China. Am J Clin Pathol 2000;114:220–6.CrossRefGoogle ScholarPubMed
Chow, LT, Chow, WH, Tsui, WM, Chan, SK, Lee, JC.Fine-needle aspiration cytologic diagnosis of lymphoepithelioma-like carcinoma of the lung. Report of two cases with immunohistochemical study. Am J Clin Pathol 1995;103:35–40.CrossRefGoogle ScholarPubMed
Kobayashi, M, Ito, M, Sano, K, Honda, T, Nakayama, J.Pulmonary lymphoepithelioma-like carcinoma: predominant infiltration of tumor-associated cytotoxic T lymphocytes might represent the enhanced tumor immunity. Intern Med 2004;43:323–6.CrossRefGoogle ScholarPubMed
Kasai, K, Kon, S, Sato, N, et al. Case report of lymphoepithelioma-like carcinoma of the lung – lymphoid population consisting of cytotoxic T cells in resting state. Pathol Res Pract 1999;195:773–9.CrossRefGoogle ScholarPubMed
Han, AJ, Xiong, M, Gu, YY, Lin, SX, Xiong, M.Lymphoepithelioma-like carcinoma of the lung with a better prognosis. A clinicopathologic study of 32 cases. Am J Clin Pathol 2001;115:841–50.CrossRefGoogle ScholarPubMed
Tam, IY, Chung, LP, Suen, WS, et al. Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res 2006;12:1647–53.CrossRefGoogle ScholarPubMed
Matsui, K, Kitagawa, M, Wakaki, K, Masuda, S.Lung carcinoma mimicking malignant lymphoma: report of three cases. Acta Pathol Jpn 1993;43:608–14.Google ScholarPubMed
Katzenstein, AL, Prioleau, PG, Askin, FB.The histologic spectrum and significance of clear-cell change in lung carcinoma. Cancer 1980;45:943–7.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Inase, N, Takayama, S, Nakayama, M, Miura, H, Kimula, Y.Pulmonary clear cell carcinoma. J Surg Oncol 1991;48:145–7.CrossRefGoogle ScholarPubMed
McNamee, CJ, Simpson, RH, Pagliero, KM, Meyns, B, Hamilton-Wood, C.Primary clear-cell carcinoma of the lung. Respir Med 1993;87:471–3.CrossRefGoogle ScholarPubMed
Garzon, JC, Lai, FM, Mok, TS, et al. Clear cell carcinoma of the lung revisited. J Thorac Cardiovasc Surg 2005;130:1198–9.CrossRefGoogle ScholarPubMed
Parham, DM, Weeks, DA, Beckwith, JB.The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. Am J Surg Pathol 1994;18:1010–29.CrossRefGoogle ScholarPubMed
Chetty, R, Bhana, B, Batitang, S, Govender, D.Lung carcinomas composed of rhabdoid cells. Eur J Surg Oncol 1997;23:432–4.CrossRefGoogle ScholarPubMed
Attems, JH, Lintner, F.Pseudomesotheliomatous adenocarcinoma of the lung with rhabdoid features. Pathol Res Pract 2001;197:841–6.CrossRefGoogle ScholarPubMed
Miyagi, J, Tsuhako, K, Kinjo, T, et al. Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma. Histopathology 2000;37:37–44.CrossRefGoogle ScholarPubMed
Hammar, S, Troncoso, P, Yowell, R, Mackay, B.Use of electron microscopy in the diagnosis of uncommon lung tumors. Ultrastruct Pathol 1993;17:319–51.CrossRefGoogle Scholar
Ordonez, NG.Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases. Mod Pathol 2006;19:373–83.CrossRefGoogle ScholarPubMed
Izquierdo-Garcia, FM, Moreno-Mata, N, Herranz-Aladro, ML, Canizares, MA, Alvarez-Fernandez, E.Lung carcinoma with rhabdoid component. A series of seven cases associated with uncommon types of non-small cell lung carcinomas and alveolar entrapment. Histol Histopathol 2010;25:1287–95.Google ScholarPubMed
Tamboli, P, Toprani, TH, Amin, MB, et al. Carcinoma of lung with rhabdoid features. Hum Pathol 2004;35:8–13.CrossRefGoogle ScholarPubMed
Cavazza, A, Colby, TV, Tsokos, M, Rush, W, Travis, WD.Lung tumors with a rhabdoid phenotype. Am J Clin Pathol 1996;105:182–8.CrossRefGoogle ScholarPubMed
Shimazaki, H, Aida, S, Sato, M, Deguchi, H, Ozeki, Y, Tamai, S.Lung carcinoma with rhabdoid cells: a clinicopathological study and survival analysis of 14 cases. Histopathology 2001;38:425–34.CrossRefGoogle ScholarPubMed
Hiroshima, K, Shibuya, K, Shimamura, F, et al. Pulmonary large cell carcinoma with rhabdoid phenotype. Ultrastruct Pathol 2003;27:55–9.CrossRefGoogle ScholarPubMed
Takamori, S, Noguchi, M, Morinaga, S, et al. Clinicopathologic characteristics of adenosquamous carcinoma of the lung. Cancer 1991;67:649–54.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Naunheim, KS, Taylor, JR, Skosey, C, et al. Adenosquamous lung carcinoma: clinical characteristics, treatment, and prognosis. Ann Thorac Surg 1987;44:462–6.CrossRefGoogle Scholar
Ichinose, Y, Hara, N, Takamori, S, et al. DNA ploidy pattern of each carcinomatous component in adenosquamous lung carcinoma. Ann Thorac Surg 1993;55:593–6.CrossRefGoogle ScholarPubMed
Steele, VE, Nettesheim, P.Unstable cellular differentiation in adenosquamous cell carcinoma. J Natl Cancer Inst 1981;67:149–54.Google ScholarPubMed
Ishida, T, Kaneko, S, Yokoyama, H, et al. Adenosquamous carcinoma of the lung. Clinicopathologic and immunohistochemical features. Am J Clin Pathol 1992;97:678–85.CrossRefGoogle ScholarPubMed
Sridhar, KS, Raub, WA Jr, Duncan, RC, Hilsenbeck, S.The increasing recognition of adenosquamous lung carcinoma (1977–1986). Am J Clin Oncol 1992;15:356–62.CrossRefGoogle Scholar
Fitzgibbons, PL, Kern, WH.Adenosquamous carcinoma of the lung: a clinical and pathologic study of seven cases. Hum Pathol 1985;16:463–6.CrossRefGoogle ScholarPubMed
Nakagawa, K, Yasumitu, T, Fukuhara, K, Shiono, H, Kikui, M.Poor prognosis after lung resection for patients with adenosquamous carcinoma of the lung. Ann Thorac Surg 2003;75:1740–4.CrossRefGoogle ScholarPubMed
Shimizu, J, Oda, M, Hayashi, Y, Nonomura, A, Watanabe, Y.A clinicopathologic study of resected cases of adenosquamous carcinoma of the lung. Chest 1996;109:989–94.CrossRefGoogle ScholarPubMed
Shelton, DA, Rana, DN, Holbrook, M, Taylor, P, Bailey, S. Adenosquamous carcinoma of the lung diagnosed by cytology?: A diagnostic dilemma. Diagn Cytopathol 2011 Mar 17. [Epub ahead of print].
Kang, SM, Kang, HJ, Shin, JH, et al. Identical epidermal growth factor receptor mutations in adenocarcinomatous and squamous cell carcinomatous components of adenosquamous carcinoma of the lung. Cancer 2007;109:581–7.CrossRefGoogle ScholarPubMed
Jia, XL, Chen, G.EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung. Lung cancer 2011;74:396–400.CrossRefGoogle ScholarPubMed
Toyooka, S, Yatabe, Y, Tokumo, M, et al. Mutations of epidermal growth factor receptor and K-ras genes in adenosquamous carcinoma of the lung. Int J Cancer 2006;118:1588–90.CrossRefGoogle ScholarPubMed
Tochigi, N, Dacic, S, Nikiforova, M, Cieply, KM, Yousem, SA.Adenosquamous carcinoma of the lung: a microdissection study of KRAS and EGFR mutational and amplification status in a western patient population. Am J Clin Pathol 2011;135:783–9.CrossRefGoogle Scholar
Rossi, G, Sartori, G, Cavazza, A, Tamberi, S.Mucoepidermoid carcinoma of the lung, response to EGFR inhibitors, EGFR and K-RAS mutations, and differential diagnosis. Lung Cancer 2009;63:159–60.CrossRefGoogle ScholarPubMed
Shilo, K, Foss, RD, Franks, TJ, DePeralta-Venturina, M, Travis, WD.Pulmonary mucoepidermoid carcinoma with prominent tumor-associated lymphoid proliferation. Am J Surg Pathol 2005;29:407–11.CrossRefGoogle ScholarPubMed
Filosso, PL, Ruffini, E, Asioli, S, et al. Adenosquamous lung carcinomas: A histologic subtype with poor prognosis. Lung cancer 2011;74:25–9.CrossRefGoogle ScholarPubMed
Niho, S, Yokose, T, Kodama, T, Nishiwaki, Y, Mukai, K.Clonal analysis of adenosquamous carcinoma of the lung. Jpn J Cancer Res 1999;90:1244–7.CrossRefGoogle ScholarPubMed
Kanazawa, H, Ebina, M, Ino-Oka, N, et al. Transition from squamous cell carcinoma to adenocarcinoma in adenosquamous carcinoma of the lung. Am J Pathol 2000;156:1289–98.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×