Lung cancer

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Lung cancer (primary lung cancer), or frequently if somewhat incorrectly known as bronchogenic carcinoma, is a broad term referring to the main histological subtypes of primary lung malignancies that are mainly linked with inhaled carcinogens, with cigarette smoke being a key culprit.

This article will broadly discuss all the histological subtypes as a group, focussing on their common aspects and for further details please refer to the specific articles on each subtype described below.

Epidemiology

Lung cancer is a leading type of cancer, equal in prevalence to breast cancer ¹³. It is the leading cause of cancer mortality worldwide; accounting for ~20% of all cancer deaths ¹.

Risk factors

The major risk factor is cigarette smoking which is implicated in 90% of cases and increase the risk of lung cancer, which can be divided by histological subtype ¹⁰:

squamous cell lung cancer: 11x (men), 15x (women)
small cell lung cancer: 10x (men), 25x (women)
large cell lung cancer: 7x (men), 8x (women)
lung adenocarcinoma: 4x (men and women)

Other risk factors:

asbestos: 5x increased risk
occupational exposure: uranium, radon, arsenic, chromium
diffuse lung fibrosis: 10x increased risk
chronic obstructive pulmonary disease

Associations

Various paraneoplastic syndromes can arise in the setting of lung cancer:

endocrine/metabolic
- SIADH causing hyponatraemia: small-cell subtype
- ACTH secretion (Cushing syndrome): carcinoid and small-cell subtypes
- carcinoid syndrome
- gynaecomastia
- adrenal insufficiency (Addison disease): from bilateral metastases ⁷
- hyperparathyroidism: NSCLC can produce parathyroid hormone (extremely rare) ⁸
- hypocalcaemia: occurs in the setting of skeletal metastases; especially associated with NSCLC ⁶
- PTH-related peptide (PTHrp) causing hypercalcaemia: squamous cell carcinoma
neurological
- polyneuropathy
- myelopathy
- limbic encephalitis: particularly associated with SCLC ⁹
- cerebellar degeneration
- Lambert-Eaton myasthenia syndrome
other
- finger clubbing
- hypertrophic pulmonary osteoarthropathy (HPOA): squamous cell carcinoma subtype
- nephrotic syndrome
- polymyositis ³
- dermatomyositis ³
- eosinophilia
- acanthosis nigricans
- thrombophlebitis: adenocarcinoma subtype

Clinical presentation

Patients with lung cancer may be asymptomatic in up to 50% of cases. Cough and dyspnoea are rather non-specific symptoms that are common amongst those with lung cancer.

Central tumours may result in haemoptysis and peripheral lesions with pleuritic chest pain.

Pneumonia, pleural effusion, wheeze, lymphadenopathy are not uncommon. Other symptoms may be secondary to metastases (bone, contralateral lung, brain, adrenal glands, and liver, in frequency order for NSCLC ¹²) or paraneoplastic syndromes.

Pathology

The term bronchogenic carcinoma is somewhat loosely used to refer to primary malignancies of the lung that are associated with inhaled carcinogens ¹ and includes four main histological subtypes. These are broadly divided into non-small cell carcinoma and small cell carcinoma as they differ clinically regarding presentation, treatment, and prognosis:

non-small cell lung cancer (NSCLC) (80%)
- adenocarcinoma (35%)
  - most common cell type overall
  - most common in women
  - most common cell type in non-smokers but still most patients are smokers
  - peripheral
- squamous cell carcinoma (30%)
  - strongly associated with smoking
  - most common carcinoma to cavitate
  - poor prognosis
- large-cell carcinoma (15%)
  - peripherally located
  - very large, usually >4 cm
small cell lung cancer (SCLC) (20%)
- almost always in smokers
- metastasises early
- most common primary lung malignancy to cause paraneoplastic syndromes and SVC obstruction
- worst prognosis

Other malignant pulmonary neoplasms include lymphoma and sarcoma (rare).

Each subtype has different radiographic appearances, demographics, and prognoses:

Markers

Several antibodies or markers from tissue samples may be useful in the diagnosis and prognostication of disease. These include

programmed death-ligand 1 (PD-L1)-targeted monoclonal antibodies
thyroid transcription factor 1 (TTF-1): expressed in most lung cancer except squamous cell cancer

Genetics

ROS1 mutation: 1-2% of NSCLC ¹⁵; more common in females ¹⁴
ALK mutation: 2-5% of NSCLC; more common in males, younger, light/never smokers, and more likely to be adenocarcinoma presenting with advanced disease ¹⁶ (see: main article)

Staging

according to the IASLC (International Association for the Study of Lung Cancer) 8th edition lung cancer staging system
previously small cell and non-small cell lung ~~cancer staging~~
~~small cell~~cancers were staged differently, but since 2013 all lung ~~cancer staging~~cancers are staged the same way

Treatment and prognosis

Treatment and prognosis vary not only with stage but also with cell type. In general, surgery, chemotherapy, and radiotherapy are offered according to the stage, resectability, operability, and functional status. Targeted treatments depend on molecular testing, e.g. ALK mutated lung cancers can be treated with ALK-inhibitors (e.g. crizotinib) ¹⁶.

Non-small cell carcinoma

treatment
- operable disease (stage I to IIIA): surgery
- unresectable disease: neoadjuvant chemotherapy, radiotherapy
- advanced disease: palliative combined chemotherapy
prognosis (5-year survival rates):
- local (stage I): 55-67%
- locally advanced (stages II-IIIA): 23-40%
- advanced (stages IIIB and IV): 1-3%

Small-cell carcinoma

treatment
- limited disease: chemoradiotherapy
- extensive disease: palliative combined chemotherapy
prognosis: poor
- limited: 5-year survival rate 15-25%
- extensive: 2-year survival 20% (with palliative combined chemotherapy and supportive care)

~~-<li><a href="/articles/lung-cancer-staging-iaslc-8th-edition">non-small cell lung cancer staging</a></li>~~
~~-<li><a href="/articles/small-cell-lung-cancer-staging-superseded-3">small cell lung cancer staging</a></li>~~
+<li>according to the <a title="Lung cancer staging" href="/articles/lung-cancer-staging-iaslc-8th-edition">IASLC (International Association for the Study of Lung Cancer) 8th edition lung cancer staging system</a>
+</li>
+<li>previously small cell and non-small cell lung cancers were staged differently, but since 2013 all lung cancers are staged the same way</li>

References changed:

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1. Rosado-de-christenson ML, Templeton PA, Moran CA. Bronchogenic carcinoma: radiologic-pathologic correlation. Radiographics. 1994;14 (2): 429-46. <a href="http://radiographics.rsna.org/content/14/2/429.abstract">Radiographics (abstract)</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/8190965">Pubmed citation</a><div class="ref_v2"></div>
2. Fauci AS, Braunwald E, Kasper DL et-al. Harrison's Principles of Internal Medicine. McGraw-Hill Professional. (2008) ISBN:0071466339. <a href="http://books.google.com/books?vid=ISBN0071466339">Read it at Google Books</a> - <a href="http://www.amazon.com/gp/product/0071466339?ie=UTF8&tag=radiopaediaor-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=0071466339">Find it at Amazon</a><div class="ref_v2"></div>
3. Kubo M, Ihn H, Yamane K et-al. Serum KL-6 in adult patients with polymyositis and dermatomyositis. Rheumatology (Oxford). 2000;39 (6): 632-6. <a href="http://dx.doi.org/10.1093/rheumatology/39.6.632">doi:10.1093/rheumatology/39.6.632</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/10888708">Pubmed citation</a><div class="ref_v2"></div>
4. Talley NJ, O'Connor S. Clinical examination, a systematic guide to physical diagnosis. Churchill Livingstone. (2006) ISBN:0729537625. <a href="http://books.google.com/books?vid=ISBN0729537625">Read it at Google Books</a> - <a href="http://www.amazon.com/gp/product/0729537625?ie=UTF8&tag=radiopaediaor-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=0729537625">Find it at Amazon</a><div class="ref_v2"></div>
5. Webb WR, Higgins CB. Thoracic Imaging. Lippincott Williams & Wilkins. (2010) ISBN:1605479764. <a href="http://books.google.com/books?vid=ISBN1605479764">Read it at Google Books</a> - <a href="http://www.amazon.com/gp/product/1605479764">Find it at Amazon</a><span class="ref_v3"></span>
6. Body JJ, Bone HG, de Boer RH et-al. Hypocalcaemia in patients with metastatic bone disease treated with denosumab. Eur. J. Cancer. 2015;51 (13): 1812-21. <a href="http://dx.doi.org/10.1016/j.ejca.2015.05.016">doi:10.1016/j.ejca.2015.05.016</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/26093811">Pubmed citation</a><span class="auto"></span>
7. Carvalho F, Louro F, Zakout R. Adrenal Insufficiency in Metastatic Lung Cancer. World Journal of Oncology. 11;6 (3): . <a href="http://www.wjon.org/index.php/wjon/article/view/890/659">World Journal of Oncology (full text)</a><span class="auto"></span>
8. Suliburk JW, Perrier ND. Primary hyperparathyroidism. Oncologist. 2007;12 (6): 644-53. <a href="http://dx.doi.org/10.1634/theoncologist.12-6-644">doi:10.1634/theoncologist.12-6-644</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/17602056">Pubmed citation</a><span class="auto"></span>
9. Alamowitch S, Graus F, Uchuya M et-al. Limbic encephalitis and small cell lung cancer. Clinical and immunological features. Brain. 1997;120 ( Pt 6): 923-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9217677">Pubmed citation</a><span class="auto"></span>
10. Khuder S. Lung Cancer. 2001;31 (2-3): . <a href="http://dx.doi.org/10.1016/S0169-5002(00)00181-1">doi:10.1016/S0169-5002(00)00181-1</a><span class="auto"></span>
11.Blake Eric Christianson, Supriya Gupta, Shikhar G Vyas et-al. A diagnostic challenge: An incidental lung nodule in a 48-year-old nonsmoker. (2018) Lung India. 35 (3): 251. <a href="https://doi.org/10.4103/lungindia.lungindia_212_17">doi:10.4103/lungindia.lungindia_212_17</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/29697085">Pubmed</a> <span class="ref_v4"></span>
12. Tamura T, Kurishima K, Nakazawa K et-al. Specific organ metastases and survival in metastatic non-small-cell lung cancer. (2015) Molecular and clinical oncology. 3 (1): 217-221. <a href="https://doi.org/10.3892/mco.2014.410">doi:10.3892/mco.2014.410</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/25469298">Pubmed</a> <span class="ref_v4"></span>
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