Etiology

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Kleincellige en niet-kleincellige longkanker: diagnose, behandeling en opvolgingPublished by: KCELast published: 2013Cancer du poumon à petites cellules et non à petites cellules : diagnostic, traitement et suiviPublished by: KCELast published: 2013

Tobacco exposure continues to be the most important cause of lung cancer, and in the US and Europe up to 90% of lung cancer is directly attributable to smoking.[11] Tobacco smoke contains multiple carcinogens including polynuclear aromatic hydrocarbons, aromatic amines, N-nitrosamines, and other organic and inorganic compounds.[12] However, because it is such a common tumor the absolute number of patients who develop lung cancer who have never smoked is high.

Lung cancer has also been linked to radon gas, a radioactive decay product of uranium.[13][14]​​ Radon can percolate into homes from the ground underlying the homes. Radon itself is not dangerous; however, radon decays into progeny that emit alpha-particles, and these can damage DNA, leading to lung cancer induction.[12] Less commonly, occupational factors, notably exposure to asbestos, play a significant part in the etiology, and air pollution has been shown to confer some risk.[15][16]​​[17]

Pathophysiology

There are three major types of non-small cell lung cancer (NSCLC).

  • Squamous cell carcinoma: commonly involves the central airways and is thought to metastasize later in the disease course than adenocarcinoma; constitutes approximately 25% of lung cancers.[18]

  • Adenocarcinoma: tends to be located peripherally in the lung; adenocarcinoma is the most common NSCLC histology, and frequency is rising; comprises approximately 39% of lung cancers.[18][19] 

  • Large cell carcinoma: undifferentiated tumors without histologic features typical of a squamous cell or adenocarcinoma and tend to arise centrally; accounts for about 8% of lung cancers.[18]

Sarcomatoid carcinoma represents a rare subset of poorly differentiated NSCLC.[20] In a proportion of cases of NSCLC it is not possible to further classify the tumor.

The classification of adenocarcinoma clarifies the terminology for premalignant and early invasive lesions.[21] Atypical adenomatous hyperplasia (AAH) is a premalignant lesion that typically measures less than 5 mm in diameter and may appear as a pure ground-glass nodule (pGGN) on computed tomography (CT) or may not be apparent on CT. AAH is a relatively common incidental finding, present in the lung tissue adjacent to resected adenocarcinomas in up to 23% of cases. A proportion of AAH lesions may evolve (often slowly) into adenocarcinoma in situ (AIS) and AIS may progress to become invasive adenocarcinoma. AIS is a preinvasive lesion that may measure up to 30 mm in diameter and typically appears as pGGN on CT. The first stage of AIS becoming invasive adenocarcinoma is termed minimally invasive adenocarcinoma (MIA). MIA is defined as a lesion of AIS within which there is an area of invasive adenocarcinoma that measures 5 mm in diameter or less. MIA may correlate with an appearance on CT scans as a ground-glass opacity within which there is a solid area measuring less than 5 mm.

Bronchioloalveolar carcinoma (BAC) is an obsolete term but roughly corresponds to adenocarcinoma with lepidic pattern, characterized by the growth of tumor cells along the surface of alveolar walls - so-called lepidic pattern. The CT correlate is either a subsolid nodule or consolidation. AIS and MIA when presenting as subsolid nodules on CT have an excellent prognosis with few deaths due to lung cancer on long-term follow-up.[22][23][24]​ Lesions that show tissue invasion but also a component of lepidic spread should not be called BAC but instead are considered to be adenocarcinomas (with a lepidic component). Multifocal lesions showing a lepidic growth pattern may occur. Some of these patients will have multiple synchronous AIS and, usually, at least one associated adenocarcinoma.[25] Some cases show mucinous adenocarcinoma (previously known as mucinous BAC) and may mimic pneumonic consolidation rather than present as a typical solitary pulmonary nodule or subsolid nodule.[21][25]

Classification

The 2021 World Health Organization classification of lung tumors[2]

Epithelial tumors

  • Papillomas

    • Squamous cell papilloma, not otherwise specified (NOS)

    • Squamous cell papilloma, inverted

    • Glandular papilloma

    • Mixed squamous cell and glandular papilloma

  • Adenomas

    • Sclerosing pneumocytoma

    • Alveolar adenoma

    • Papillary adenoma

    • Bronchiolar adenoma/ciliated muconodular papillary tumor

    • Mucinous cystadenoma

    • Mucous gland adenoma

  • Precursor glandular lesions

    • Atypical adenomatous hyperplasia

    • Adenocarcinoma in situ

      • Adenocarcinoma in situ, nonmucinous

      • Adenocarcinoma in situ, mucinous

  • Adenocarcinomas

    • Minimally invasive adenocarcinoma

      • Minimally invasive adenocarcinoma, nonmucinous

      • Minimally invasive adenocarcinoma, mucinous

    • Invasive nonmucinous adenocarcinoma

      • Lepidic adenocarcinoma

      • Acinar adenocarcinoma

      • Papillary adenocarcinoma

      • Micropapillary adenocarcinoma

      • Solid adenocarcinoma

    • Invasive mucinous adenocarcinoma

      • Mixed invasive mucinous and nonmucinous adenocarcinoma

    • Colloid adenocarcinoma

    • Fetal adenocarcinoma

    • Adenocarcinoma, enteric type

    • Adenocarcinoma, NOS

  • Squamous precursor lesions

    • Squamous cell carcinoma in situ

    • Mild squamous dysplasia

    • Moderate squamous dysplasia

    • Severe squamous dysplasia

  • Squamous cell carcinomas

    • Squamous cell carcinoma, NOS

      • Squamous cell carcinoma, keratinizing

      • Squamous cell carcinoma, nonkeratinizing

      • Basaloid squamous cell carcinoma

    • Lymphoepithelial carcinoma

  • Large cell carcinomas

    • Large cell carcinoma

  • Adenosquamous carcinomas

    • Adenosquamous carcinoma

  • Sarcomatoid carcinomas

    • Pleomorphic carcinoma

      • Giant cell carcinoma

      • Spindle cell carcinoma

    • Pulmonary blastoma

    • Carcinosarcoma

  • Other epithelial tumors

    • NUT carcinoma

    • Thoracic SMARCA4-deficient undifferentiated tumor

  • Salivary gland-type tumors

    • Pleomorphic adenoma

    • Adenoid cystic carcinoma

    • Epithelial-myoepithelial carcinoma

    • Mucoepidermoid carcinoma

    • Hyalinizing clear cell carcinoma

    • Myoepithelioma

    • Myoepithelial carcinoma

Lung neuroendocrine neoplasms

  • Precursor lesion

    • Diffuse idiopathic neuroendocrine cell hyperplasia

  • Neuroendocrine tumors

    • Carcinoid tumor, NOS/neuroendocrine tumor, NOS

      • Typical carcinoid/neuroendocrine tumor, grade 1

      • Atypical carcinoid/neuroendocrine tumor, grade 2

  • Neuroendocrine carcinomas

    • Small cell carcinoma

      • Combined small cell carcinoma

    • Large cell neuroendocrine carcinoma

      • Combined large cell neuroendocrine carcinoma

Tumors of ectopic tissues

  • Melanoma

  • Meningioma

Mesenchymal tumors specific to the lung

  • Pulmonary hamartoma

  • Chondroma

  • Diffuse lymphangiomatosis

  • Pleuropulmonary blastoma

  • Intimal sarcoma

  • Congenital peribronchial myofibroblastic tumor

  • Pulmonary myxoid sarcoma with EWSR1-CREB1 fusion

  • PEComatous tumors

    • Lymphangioleiomyomatosis

    • PEComa, benign

    • PEComa, malignant

Hematolymphoid tumors

  • MALT lymphoma

  • Diffuse large B-cell lymphoma, NOS

  • Lymphomatoid granulomatosis, NOS

    • Lymphomatoid granulomatosis, grade 1

    • Lymphomatoid granulomatosis, grade 2

    • Lymphomatoid granulomatosis, grade 3

  • Intravascular large B-cell lymphoma

  • Langerhans cell histiocytosis

  • Erdheim-Chester disease

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