Lung cancer classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kim-Son H. Nguyen M.D. Cafer Zorkun, M.D., Ph.D. [2] Rim Halaby, M.D. [3] Dildar Hussain, MBBS [4]

Overview

Primary lung cancers may be classified into small cell lung cancer (~15%) and non small cell lung cancer (~85%). Non small cell lung cancer are a heterogeneous group of lung cancers that are often grouped together because they share similar clinical features (e.g. prognosis and management). The 2015 WHO histological classification of tumors of the lung categorized lung tumors into malignant epithelial tumors, benign epithelial tumors, lymphoproliferative tumors, miscellaneous tumors, and metastatic tumors.

Classification

Primary lung cancers may be classified into two main categories:

• Small cell lung cancer (~15%)
• Non small cell lung cancer (~85%).

Lung Cancer

Small cell lung cancer (~15%)

Non small cell lung cancer (~85%) Squamous cell carcinoma (25% of lung cancers) Adenocarcinoma (40% of lung cancers). Large cell carcinoma (10% of lung cancers) Other non-small cell lung carcinomas: Adenosquamous carcinoma Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements Carcinoid tumor Lung carcinoma of salivary gland type Unclassified carcinoma

WHO Histological Classification of Tumors of the Lung

The World Health Organization (WHO) classifies tumors of the lungs as follows:

WHO Classification of Lung Tumors
Histological type	Subtype
Epithelial tumors
Adenocarcinoma	Lepidic adenocarcinoma Acinar adenocarcinoma Papillary adenocarcinoma Micropapillary adenocarcinoma Solid adenocarcinoma Invasive mucinous adenocarcinoma Mixed invasive mucinous Nonmucinous adenocarcinoma Colloid adenocarcinoma Fetal adenocarcinoma Enteric adenocarcinoma Minimally invasive adenocarcinoma Nonmucinous Mucinous Pre-invasive lesions Atypical adenomatous hyperplasia Adenocarcinoma in situ Nonmucinous Mucinous
Squamous cell carcinoma	Keratinizing squamous cell carcinoma Nonkeratinizing squamous cell carcinoma Basaloid squamous cell carcinoma Pre-invasive lesion Squamous cell carcinoma in situ
Neuroendocrine tumors
Small cell carcinoma	Combined small cell carcinoma
Large cell neuroendocrine carcinoma	Combined large cell neuroendocrine carcinoma
Carcinoid tumors	Typical carcinoid tumor Atypical carcinoid tumor
Pre-invasive lesion	Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Large cell carcinoma	N/A
Adenosquamous carcinoma	N/A
Sarcomatoid carcinomas	Pleomorphic carcinoma Spindle cell carcinoma Giant cell carcinoma Carcinosarcoma Pulmonary blastoma
Other and Unclassified carcinomas	Lymphoepithelioma-like carcinoma NUT carcinoma
Salivary gland-type tumors	Mucoepidermoid carcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Pleomorphic adenoma
Papillomas	Squamous cell papilloma Exophytic Inverted Glandular papilloma Mixed squamous and glandular papilloma
Adenomas	Sclerosing pneumocytoma Alveolar adenoma Papillary adenoma Mucinous cystadenoma Mucous gland adenoma
Mesenchymal tumors
Pulmonary hamartoma	N/A
Chondroma	N/A
PEComatous tumors	Lymphangioleiomyomatosis PEComa (benign) Clear cell tumor PEComa (malignant)
Congenital peribronchial myofibroblastic tumor	N/A
Diffuse pulmonary lymphangiomatosis	N/A
Inflammatory myofibroblastic tumor	N/A
Epithelioid hemangioendothelioma	N/A
Pleuropulmonary blastoma	N/A
Synovial sarcoma	N/A
Pulmonary artery intimal sarcoma	N/A
Pulmonary myxoid sarcoma with EWSR1–CREB1 translocation	N/A
Myoepithelial tumors	Myoepithelioma Myoepithelial carcinoma
Lymphohistiocytic tumors
Extranodal marginal zone lymphomas of mucosa-associated Lymphoid tissue (MALT lymphoma)	N/A
Diffuse large cell lymphoma	N/A
Lymphomatoid granulomatosis	N/A
Intravascular large B cell lymphoma	N/A
Pulmonary Langerhans cell histiocytosis	N/A
Erdheim-Chester disease	N/A
Tumors of ectopic origin
Germ cell tumors	Mature teratoma Immature teratoma
Intrapulmonary thymoma	N/A
Melanoma	N/A
Meningioma, NOS	N/A

Classification of Lung Cancer among Nonsmoking Individuals:

• Adenocarcinoma is the most common histologic subtype in nonsmoking individuals, accounting for approximately 60%–80% of cases.
• Squamous cell carcinoma represents about 17% of lung cancers in nonsmokers.
• Small cell lung cancer is uncommon in nonsmoking individuals, comprising fewer than 10% of cases.
• Lung cancers in nonsmoking individuals more frequently contain actionable oncogenic alterations.

• EGFR mutations and ALK rearrangements are particularly enriched in tumors from nonsmoking individuals.

References

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