Abstract
Over the past decade, the diagnosis, treatment and management of lung cancer has evolved substantially, in large part to the development of novel chemotherapeutic agents and targeted therapy in particular. As such, accurate classification of lung carcinomas from a histologic standpoint has become increasingly critical for appropriate patient management. Much of the focus of lung cancer pathology in the past decade has concentrated on adenocarcinoma. As such, the aim of this chapter will primarily focus on the evolution of this cancer subtype and review the recently published adenocarcinoma classification prepared jointly by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society. Squamous cell carcinoma will also be discussed, particularly in regard to accurate discrimination from adenocarcinoma. The role of the pathologist in molecular testing will be reviewed, particularly as it relates to specimens obtained from radiologic procedures. Finally, given that the scope of this publication is radiation oncology, the histologic changes and evaluation of tumors which have undergone radiation and/or neo-adjuvant therapy will be discussed.
Keywords
- Epidermal Growth Factor Receptor
- Epidermal Growth Factor Receptor Mutation
- Molecular Testing
- Mucinous Carcinoma
- Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Amin MB, Tamboli P et al (2002) Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol 26(3):358–364
Beasley MB, Brambilla E et al (2005) The 2004 World Health Organization classification of lung tumors. Semin Roentgenol 40(2):90–97
Borczuk AC (2009) Micropapillary histology: a frequent morphology of mutation-associated lung adenocarcinoma? Am J Clin Pathol 131(5):615–617
Borczuk AC, Qian F et al (2009) Invasive size is an independent predictor of survival in pulmonary adenocarcinoma. Am J Surg Pathol 33(3):462–469
Brownlee NA, Mott RT et al (2005) Mucinous (colloid) adenocarcinoma of the lung. Arch Pathol Lab Med 129(1):121–122
Camilo R, Capelozzi VL et al (2006) Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. Hum Pathol 37(5):542–546
Cohen MH, Gootenberg J et al (2007) FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist 12(6):713–718
Copin MC, Buisine MP et al (2001) Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas. Hum Pathol 32(3):274–281
Dacic S (2008) EGFR assays in lung cancer. Adv Anat Pathol 15(4):241–247
Dacic S, Shuai Y et al (2010) Clinicopathological predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas. Mod Pathol 23(2):159–168
Douillard JY, Shepherd FA et al (2010) Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol 28(5):744–752
Finberg KE, Sequist LV et al (2007) Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. J Mol Diagn 9(3):320–326
Gillespie JW, Best CJ et al (2002) Evaluation of non-formalin tissue fixation for molecular profiling studies. Am J Pathol 160(2):449–457
Hata A, Katakami N et al (2010) Frequency of EGFR and KRAS mutations in Japanese patients with lung adenocarcinoma with features of the mucinous subtype of bronchioloalveolar carcinoma. J Thorac Oncol 5(8):1197–1200
Hoshi R, Tsuzuku M et al (2004) Micropapillary clusters in early-stage lung adenocarcinomas: a distinct cytologic sign of significantly poor prognosis. Cancer 102(2):81–86
Inamura K, Satoh Y et al (2005) Pulmonary adenocarcinomas with enteric differentiation: histologic and immunohistochemical characteristics compared with metastatic colorectal cancers and usual pulmonary adenocarcinomas. Am J Surg Pathol 29(5):660–665
Junker K, Thomas M et al (1997a) Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment. J Cancer Res Clin Oncol 123(9):469–477
Junker K, Thomas M et al (1997b) [Regression grading of neoadjuvant non-small-cell lung carcinoma treatment]. Pathologe 18(2):131–140
Junker K, Langner K et al (2001) Grading of tumor regression in non-small cell lung cancer : morphology and prognosis. Chest 120(5):1584–1591
Kamiya K, Hayashi Y et al (2008) Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma. Mod Pathol 21(8):992–1001
Kargi A, Gurel D et al (2007) The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas. Appl Immunohistochem Mol Morphol 15(4):415–420
Kawakami T, Nabeshima K et al (2007) Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors. Mod Pathol 20(5):514–521
Kuroda N, Hamaguchi N et al (2006) Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases. APMIS 114(5):381–385
Lim E, Goldstraw P et al (2008) Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 2007. J Thorac Oncol 3(10):1194–1201
Liu-Jarin X, Stoopler MB et al (2003) Histologic assessment of non-small cell lung carcinoma after neoadjuvant therapy. Mod Pathol 16(11):1102–1108
Loo PS, Thomas SC et al (2010) Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol 5(4):442–447
Maemondo M, Inoue A et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388
Makimoto Y, Nabeshima K et al (2005) Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (</=20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi’s type C tumours). Histopathology 46(6):677–684
Mitsudomi T, Kosaka T et al (2005) Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 23(11):2513–2520
Mitsudomi T, Morita S et al (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11(2):121–128
Miyoshi T, Satoh Y et al (2003) Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct pathologic marker for a significantly poor prognosis. Am J Surg Pathol 27(1):101–109
Mok TS, Wu YL et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957
Nicholson AG, Gonzalez D et al (2010) Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis. J Thorac Oncol 5(4):436–441
Noguchi M, Morikawa A et al (1995) Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer 75(12):2844–2852
Pirker R, Herth FJ et al (2010) Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop. J Thorac Oncol 5(10):1706–1713
Rekhtman N, Brandt SM et al (2011) Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing. J Thorac Oncol 6(3):451–458
Rodig SJ, Mino-Kenudson M et al (2009) Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res 15(16):5216–5223
Rossi G, Murer B et al (2004) Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Am J Surg Pathol 28(4):442–452
Sakurai H, Dobashi Y et al (2004a) Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diameter: a prognostic assessment. Ann Thorac Surg 78(5):1728–1733
Sakurai H, Maeshima A et al (2004b) Grade of stromal invasion in small adenocarcinoma of the lung: histopathological minimal invasion and prognosis. Am J Surg Pathol 28(2):198–206
Sartori G, Cavazza A et al (2009) EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 131(4):478–489
Scagliotti GV, Parikh P et al (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26(21):3543–3551
Scagliotti G, Hanna N et al (2009a) The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist 14(3):253–263
Scagliotti GV, Park K et al (2009b) Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaive patients with advanced non-small cell lung cancer: a risk-benefit analysis of a large phase III study. Eur J Cancer 45(13):2298–2303
Soda M, Choi YL et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566
Srinivasan M, Sedmak D et al (2002) Effect of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol 161(6):1961–1971
Suzuki K, Asamura H et al (2002) “Early” peripheral lung cancer: prognostic significance of ground glass opacity on thin-section computed tomographic scan. Ann Thorac Surg 74(5):1635–1639
Terry J, Leung S et al (2010) Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J Surg Pathol 34(12):1805–1811
Travis WD, Brambilla E et al (2004) Pathology and genetics: tumours of the lung, pleura, thymus and heart. IARC, Lyon
Travis WD, Brambilla E et al (2011) International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6(2):244–285
Wu M, Wang B et al (2003) p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. Am J Clin Pathol 119(5):696–702
Yim J, Zhu LC et al (2007) Histologic features are important prognostic indicators in early stages lung adenocarcinomas. Mod Pathol 20(2):233–241
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Beasley, M.B. (2011). Pathology of Lung Cancer. In: Jeremic, B. (eds) Advances in Radiation Oncology in Lung Cancer. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2011_304
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DOI: https://doi.org/10.1007/174_2011_304
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