the vast majority of primary lung cancers are carcinomas which are divided into:
non small cell carcinoma (NSCLC) - accounts for 80%
small cell carcinoma (SMLC) “oat cell” - accounts for 17%
other primary lung cancers include:
carcinoid - accounts for < 1%
sarcoma - accounts for 0.1%
mesothelioma
> 85% of lung cancers occur in smokers
smokers have a 13% lifetime risk of lung cancer but this is doubled if they have a c.9976T BRCA2 gene mutation
lung cancers in never smokers is increasing (see below)
overall 5 year survival for lung cancer even with Rx is poor at ~14%
LungVax lung cancer vaccine targeting neoantigens on lung cancer cells developed in 2024 and will be trialed
non small cell carcinoma (NSCLC)
accounts for 80%
tends to be Rx surgically
~50% are squamous cell and the other 50% are adenocarcinomas
some may metastasise to the brain in which case Ix workup of this possibility usually entails:
CT brain with iv contrast
plus MRI scan if either:
CT findings may represent other pathology such as infarcts instead of tumour
when surgical resection is being considered and thus there is need to exclude other metastases to brain or meninges
small cell carcinoma (SMLC) "oat cell"
accounts for 17%
tends to respond better to chemoRx and radioRx
most grow in the larger airways and grow rapidly and contain dense neurosecretory granules which may result in a variety of paraneoplastic neuroendocrine features including:
ectopic secretion of ACTH in 5% ⇒ hypokalaemic nephropathy
atrial natriuretic factor
Eaton-Lambert reverse myasthenic syndrome 5-6%
Subacute cerebellar degeneration
Subacute sensory neuropathy - it seems to be related to the loss of the dorsal root ganglia with early involvement of major fibers responsible for detecting vibration and position.
Limbic encephalopathy via Anti-Hu, Anti-Yo antibodies and characterized by rapid onset of depression, seizures, irritability, and short-term memory loss
lung cancer occurring in never smokers (LCINS) is increasing, more common in women and in Asian populations, and is a distinct biological and clinical entity attributed to either1):
passive smoking
second-hand smoke increases lung cancer risk in never smokers by approximately 20–25%
indirect tobacco exposure may act synergistically with other biological processes, such as APOBEC-related mutagenesis
genetic factors
first-degree family history of lung cancer
variants in EGFR, TP53, ATM, and members of the APOBEC3 family
certain mutations, such as EGFR p.Thr790Met (T790M), confer a particularly high lifetime risk and may lead to the development of multifocal lung lesions at younger ages
population-specific genetic factors, such as the APOBEC3A/B germline deletion, significantly increase the risk of certain lung cancers in some ethnic groups
clonal hematopoiesis of indeterminate potential (CHIP) represents another emerging risk factor.
CHIP involves somatic mutations in hematopoietic stem cells, commonly affecting genes such as DNMT3A, TET2, and ASXL1.
Individuals with high variant allele fractions may experience a higher risk of solid tumors, including lung cancer, independent of smoking status
may promote tumorigenesis through chronic inflammation, including elevated interleukin-1β (IL-1β) signaling
radon gas - 50% increased risk if levels exceed EPA recommended levels as they do in Cornwall, UK and in 1 of 15 homes in the US
air pollution
ultrafine particulate matter - an increase in air concentration of only 1% leads to 14% increase in cancer
high PM2.5 exposure correlates with a greater mutation burden, TP53 mutations, telomere shortening, and inflammatory activation within the lung microenvironment
mesothelioma (asbestos exposure) - 2-3% of all male deaths from lung cancer
perhaps ultra-processed food diets
a 2025 study showed those in the highest quarter of energy-adjusted UPF consumption were 41% more likely to be diagnosed with lung cancer than those in the lowest quarter 2)