Primary lung cancer refers to uncontrolled growth of any component of the lung. In 2023 the WHO stated that lung cancer is the most common cause of cancer-related deaths in men and women globally and that 85% of lung cancer cases are related to smoking.

This article gives an overview of the histological subtypes focussing on their common aspects; for more information please refer to the articles on each subtype described below. 

Terminology

Bronchogenic carcinoma is a term that is frequently used as a synonym for lung cancer but is inaccurate because lung cancers can arise any lung component, not just the airways ¹⁷.

Epidemiology

Lung cancer is a leading type of cancer, roughly 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 tobacco smoking, implicated in 85% of cases. This increases the risk of lung cancer depending on 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

• air pollution

Associations

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

• endocrine/metabolic

  • SIADH causing hyponatremia: small-cell subtype

  • ACTH secretion (Cushing syndrome): carcinoid and small-cell subtypes

  • carcinoid syndrome

  • gynecomastia

  • adrenal insufficiency (Addison disease): from bilateral metastases ⁷

  • hyperparathyroidism: NSCLC can produce parathyroid hormone (extremely rare) ⁸

  • hypocalcemia: occurs in the setting of skeletal metastases; especially associated with NSCLC ⁶

  • PTH-related peptide (PTHrp) causing hypercalcemia: 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): non-small cell ¹⁸

  • 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 dyspnea are rather non-specific symptoms that are common amongst those with lung cancer.

Central tumors may result in hemoptysis 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

  • metastasizes 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:

• squamous-cell carcinoma of the lung

• adenocarcinoma of the lung

• large cell carcinoma of the lung

• small cell carcinoma of the lung

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) 8^th edition lung cancer staging system

• previously small cell and non-small cell lung cancers were staged differently, but since 2013 all lung 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)

Differential diagnosis

• fibrosing mediastinitis

• pulmonary tuberculosis

• venous collateral pathways - venous varices

See also

• CT guided thoracic biopsy

• lung cancer staging