Pathology of lung malignancies
- Henry D Tazelaar, MD
Henry D Tazelaar, MD
- Mayo Clinic Arizona
- Professor of Pathology
- Mayo Clinic College of Medicine
- Section Editors
- Andrew Nicholson, MD
Andrew Nicholson, MD
- Section Editor — Pulmonary Pathology
- Professor of Respiratory Pathology
- Imperial College School of Medicine, London
- James R Jett, MD
James R Jett, MD
- Section Editor — Lung Cancer
- Professor of Medicine
- National Jewish Health
- Rogerio C Lilenbaum, MD, FACP
Rogerio C Lilenbaum, MD, FACP
- Section Editor — Lung Cancer
- Yale Cancer Center
Lung cancer is the most common cancer worldwide, with about 1.8 million new cases and 1.6 million deaths in 2012 . (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer".)
The pathologic features of the major lung malignancies will be reviewed here. Clinical features, diagnosis, and management of patients with the different lung malignancies are discussed in the appropriate topic reviews. (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer" and "Overview of the initial evaluation, treatment and prognosis of lung cancer".)
Classification of lung carcinomas by histopathologic subtype provides important information about prognosis and is necessary for optimal treatment of advanced disease. (See "Overview of the treatment of advanced non-small cell lung cancer".)
Traditionally, the classification of lung carcinoma has been based solely on evaluation of routinely stained biopsies or cytologic preparations. Increasingly, however, ancillary tests such as immunohistochemistry are being used to aid pathologists in diagnosis of subtypes. The classification scheme for lung carcinoma is therefore in a state of flux with the 2004 World Health Organization (WHO) providing the framework for classification, but the tools used to arrive at the diagnosis now supersede what that classification scheme endorsed.
The 2004 World Health Organization (WHO) schema of lung tumors has been the foundation for lung cancer classification (table 1) . This incorporated a number of developments, including recognition of lung carcinoma heterogeneity, the introduction of diagnostic immunohistochemical staining (IHC) techniques for the routine diagnosis of some neuroendocrine tumors, and the recognition of newly described entities such as fetal adenocarcinoma, cystic mucinous tumors, and large cell neuroendocrine carcinoma.
- Brambilla E, Travis WD. Lung cancer. In: World Cancer Report, Stewart BW, Wild CP (Eds), World Health Organization, Lyon 2014.
- Pathology and genetics of tumours of the lung, pleura, thymus and heart. In: World Health Organization classification of tumours, Travis, WD, Brambilla, E, Muller-Hermlink, HK, Harris, CC (Eds), IARC Press, Lyon 2004.
- Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6:244.
- Travis WD, Rekhtman N, Riley GJ, et al. Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. J Thorac Oncol 2010; 5:411.
- Nicholson AG, Gonzalez D, Shah P, et al. 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 2010; 5:436.
- Loo PS, Thomas SC, Nicolson MC, et al. Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol 2010; 5:442.
- Janssen-Heijnen ML, Coebergh JW, Klinkhamer PJ, et al. Is there a common etiology for the rising incidence of and decreasing survival with adenocarcinoma of the lung? Epidemiology 2001; 12:256.
- Kish JK, Ro JY, Ayala AG, McMurtrey MJ. Primary mucinous adenocarcinoma of the lung with signet-ring cells: a histochemical comparison with signet-ring cell carcinomas of other sites. Hum Pathol 1989; 20:1097.
- Moran CA. Mucin-rich tumors of the lung. Adv Anat Pathol 1995; 2:299.
- Ou SH, Ziogas A, Zell JA. Primary signet-ring carcinoma (SRC) of the lung: a population-based epidemiologic study of 262 cases with comparison to adenocarcinoma of the lung. J Thorac Oncol 2010; 5:420.
- Miyoshi T, Satoh Y, Okumura S, et al. Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct pathologic marker for a significantly poor prognosis. Am J Surg Pathol 2003; 27:101.
- Silver SA, Askin FB. True papillary carcinoma of the lung: a distinct clinicopathologic entity. Am J Surg Pathol 1997; 21:43.
- Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol 2002; 26:358.
- Nitadori J, Bograd AJ, Kadota K, et al. Impact of Micropapillary Histologic Subtype in Selecting Limited Resection vs Lobectomy for Lung Adenocarcinoma of 2cm or Smaller. J Natl Cancer Inst 2013.
- Nakatani Y, Dickersin GR, Mark EJ. Pulmonary endodermal tumor resembling fetal lung: a clinicopathologic study of five cases with immunohistochemical and ultrastructural characterization. Hum Pathol 1990; 21:1097.
- Yousem SA, Wick MR, Randhawa P, Manivel JC. Pulmonary blastoma. An immunohistochemical analysis with comparison with fetal lung in its pseudoglandular stage. Am J Clin Pathol 1990; 93:167.
- Roggli VL, Vollmer RT, Greenberg SD, et al. Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases. Hum Pathol 1985; 16:569.
- Cooke DT, Nguyen DV, Yang Y, et al. Survival comparison of adenosquamous, squamous cell, and adenocarcinoma of the lung after lobectomy. Ann Thorac Surg 2010; 90:943.
- Filosso PL, Ruffini E, Asioli S, et al. Adenosquamous lung carcinomas: a histologic subtype with poor prognosis. Lung Cancer 2011; 74:25.
- Dulmet-Brender E, Jaubert F, Huchon G. Exophytic endobronchial epidermoid carcinoma. Cancer 1986; 57:1358.
- Yendamuri S, Caty L, Pine M, et al. Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis. Surgery 2012; 152:397.
- Travis, WD.. The concept of pulmonary neuroendocrine tumours.. In: Pathology & Genetics: Tumours of the Lung, Pleura, Thymus, and Heart., Travis, WD, Brambilla, E, Muller-Hermelink, HK, Harris, CC. (Eds), IARC Press, Lyon 2004. p.19.
- Hirsch FR, Matthews MJ, Aisner S, et al. Histopathologic classification of small cell lung cancer. Changing concepts and terminology. Cancer 1988; 62:973.
- Bepler G, Neumann K, Holle R, et al. Clinical relevance of histologic subtyping in small cell lung cancer. Cancer 1989; 64:74.
- Aisner SC, Finkelstein DM, Ettinger DS, et al. The clinical significance of variant-morphology small-cell carcinoma of the lung. J Clin Oncol 1990; 8:402.
- Davies SJ, Gosney JR, Hansell DM, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under-recognised spectrum of disease. Thorax 2007; 62:248.
- Armas OA, White DA, Erlandson RA, Rosai J. Diffuse idiopathic pulmonary neuroendocrine cell proliferation presenting as interstitial lung disease. Am J Surg Pathol 1995; 19:963.
- Aguayo SM, Miller YE, Waldron JA Jr, et al. Brief report: idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells and airways disease. N Engl J Med 1992; 327:1285.
- Aubry MC, Thomas CF Jr, Jett JR, et al. Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients. Chest 2007; 131:1635.
- Gosney JR. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia as a precursor to pulmonary neuroendocrine tumors. Chest 2004; 125:108S.
- Bonikos DS, Archibald R, Bensch KG. On the origin of the so-called tumorlets of the lung. Hum Pathol 1976; 7:461.
- D'Agati VD, Perzin KH. Carcinoid tumorlets of the lung with metastasis to a peribronchial lymph node. Report of a case and review of the literature. Cancer 1985; 55:2472.
- Darvishian F, Ginsberg MS, Klimstra DS, Brogi E. Carcinoid tumorlets simulate pulmonary metastases in women with breast cancer. Hum Pathol 2006; 37:839.
- el-Naggar AK, Ballance W, Karim FW, et al. Typical and atypical bronchopulmonary carcinoids. A clinicopathologic and flow cytometric study. Am J Clin Pathol 1991; 95:828.
- 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.
- González-Aragoneses F, Moreno-Mata N, Cebollero-Presmanes M, et al. Prognostic significance of synaptophysin in stage I of squamous carcinoma and adenocarcinoma of the lung. Cancer 2007; 110:1776.
- Schleusener JT, Tazelaar HD, Jung SH, et al. Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma. Cancer 1996; 77:1284.
- CLASSIFICATION SCHEMES
- 2004 WHO classification of adenocarcinoma
- 2011 IASLC/ATS/ERS classification of adenocarcinoma
- ADENOSQUAMOUS CARCINOMA
- SQUAMOUS CELL CARCINOMA
- LARGE CELL CARCINOMA
- SARCOMATOID CARCINOMA
- Pleomorphic carcinoma
- Spindle cell carcinoma
- Giant cell carcinoma
- Pulmonary blastoma
- NEUROENDOCRINE TUMORS
- Small cell carcinoma
- Non-small cell neuroendocrine tumors
- - DIPNECH and carcinoid tumorlets
- - Typical carcinoid tumors
- - Atypical carcinoid tumors
- - Large cell neuroendocrine carcinoma
- - NSCLC with neuroendocrine differentiation