Pathology of lung malignancies
- Henry D Tazelaar, MD
Henry D Tazelaar, MD
- Mayo Clinic Arizona
- Professor of Pathology
- Mayo Clinic College of Medicine
- Chair of the Department of Laboratory Medicine and Pathology
- Mayo Clinic Arizona
- 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. (See "Overview of the treatment of advanced non-small cell lung cancer".)
Rationale for 2015 WHO classification — The 2015 World Health Organization (WHO) classification of lung tumors should be the foundation for lung cancer classification (table 1) [1,2]. In contrast to previous classification systems, the 2015 WHO classification relies to a greater extent on immunohistochemical characterization in addition to light microscopy, allowing for subtyping that more judiciously guides treatment strategy and predicts clinical course. In addition, it provides standardized criteria and terminology for lung cancer diagnosis on small biopsies and cytology, which is critical, given that the majority of patients with lung cancer present with high-stage disease and are not surgical candidates. Finally, it provides guidance for doing molecular testing on many carcinoma types, particularly adenocarcinomas, recognizing the therapeutic importance of targetable genetic alterations. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer".)
Changes from the 2004 WHO classification for adenocarcinomas and biopsies are based on the 2011 multidisciplinary expert panel recommendations, representing the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) [3,4]. The rationale for the changes introduced by the 2015 WHO classification is based upon several observations:
- Brambilla E, Travis WD. Lung cancer. In: World Cancer Report, Stewart BW, Wild CP (Eds), World Health Organization, Lyon 2014.
- Travis WD, Brambilla EW, Burke AP, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus, and Heart, IARC Press, Lyon 2015.
- 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.
- 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, 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.
- Kadota K, Yeh YC, Sima CS, et al. The cribriform pattern identifies a subset of acinar predominant tumors with poor prognosis in patients with stage I lung adenocarcinoma: a conceptual proposal to classify cribriform predominant tumors as a distinct histologic subtype. Mod Pathol 2014; 27:690.
- Tsao MS, Marguet S, Le Teuff G, et al. Subtype Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant Chemotherapy in Patients Undergoing Complete Resection. J Clin Oncol 2015; 33:3439.
- Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol 2015; 10:1243.
- Travis WD, Brambilla E, Burke AP, et al. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol 2015; 10:1240.
- Brownlee NA, Mott RT, Mahar A, Roggli VL. Mucinous (colloid) adenocarcinoma of the lung. Arch Pathol Lab Med 2005; 129:121.
- 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; 105:1212.
- 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.
- Funai K, Yokose T, Ishii G, et al. Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol 2003; 27:978.
- Dulmet-Brender E, Jaubert F, Huchon G. Exophytic endobronchial epidermoid carcinoma. Cancer 1986; 57:1358.
- Clinical Lung Cancer Genome Project (CLCGP), Network Genomic Medicine (NGM). A genomics-based classification of human lung tumors. Sci Transl Med 2013; 5:209ra153.
- 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.
- 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.
- 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.
- Davies SJ, Gosney JR, Hansell DM, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under-recognised spectrum of disease. Thorax 2007; 62:248.
- Nassar AA, Jaroszewski DE, Helmers RA, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a systematic overview. Am J Respir Crit Care Med 2011; 184:8.
- CLASSIFICATION SCHEMES
- Rationale for 2015 WHO classification
- Comparison of the 2015 and 2004 WHO 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
- Large cell neuroendocrine carcinoma
- Carcinoid tumors
- - Typical carcinoid tumors
- - Atypical carcinoid tumors
- DIFFERENTIAL DIAGNOSIS