Lung Tumours: Classification and Metastasis

• Lung cancer is the biggest cancer killer in the UK, causing approximately 36,000 deaths per year.

Lung Tumours Classification and Metastasis

• Lung tumours are classified as either benign or malignant, and as either primary or secondary.
• Pulmonary hamartoma/chondroma are benign primary lung tumours.
• Pulmonary carcinoid (indolent low-grade malignant), bronchogenic carcinoma, malignant mesothelioma, malignant lymphoma and certain mesenchymal sarcomas are malignant primary lung tumours.
• Metastases to the lung are as common, or more, than primary malignant instances.
• Metastatic tumours in the lungs are often multiple and bilateral.
• Haematogenous spread can cause cannonball tumours from sarcomas, melanomas, malignant testicular germ cell tumours, and carcinomas like renal cell carcinoma.
• Lymphatic spread can result in a diffuse pattern of involvement, such as lymphangitis carcinomatosa from breast carcinoma.
• Malignant pleural effusions can also occur.
• Common primary sites of cancer that frequently metastasise to the lungs are the colorectum, kidney, pancreas and breast, as well as other lung cancers.
• Rarer primary origins of metastasis to the lungs include: choriocarcinoma, Ewing's sarcoma, malignant melanoma, osteogenic sarcoma, testicular germ cell tumours, thyroid carcinoma and pancreatic carcinoma

Pulmonary Chondroma/Hamartoma

• Hamartoma is a benign neoplasm composed of tissue elements normally found at the site, but growing in a haphazard mass
• Hamartomas involve disordered proliferation of mature cartilage, fat, smooth muscle, and entrapped respiratory epithelial lined clefts.
• Hamartomas are more common in males.
• Hamartomas are usually solitary and central/peripheral.

Classification of Primary Lung Carcinomas

• Histology is used to classify these.
• Squamous cell carcinoma accounts for 20-30% of cases.
• Adenocarcinoma accounts for 30-40% of cases.
• Large cell carcinoma (undifferentiated) accounts for 10-15% of cases.
• The above three are sometimes grouped together as "non-small cell carcinoma".
• Small cell carcinoma accounts for 15-20% of cases.
• Squamous cell carcinoma are characterized by keratin pearls and intercellular bridges.
• Adenocarcinomas are characterized by gland formation and moderate differentiation.
• Large cell carcinomas are anaplastic or poorly differentiated with high grade.
• Small cell carcinomas are very malignant tumours with high proliferation fraction, increased apoptosis, and neuroendocrine differentiation.

Pathogenesis

• Cigarette smoking and bronchial epithelium injury may cause metaplasia: a change from respiratory ciliated bronchial epithelium lining to abnormal squamous epithelium.
• Dysplastic change can progress to carcinoma, often centrally situated, close to the lung hilum.
• Adenocarcinomas often develop more peripherally, associated with fibrous scarring; the precursor lesion is atypical adenomatous hyperplasia.
• Central (hilar) tumours are most often squamous cell carcinoma.
• Peripheral tumours are most often adenocarcinoma.

Anatomical Relations and Local Effects

• The hilum contains bronchi, pulmonary A&V, Bronchial A& V, Nerves and Lymphatics
• Mass effect of tumours can obstruct a bronchus
• Local effects include Ulceration, invasion of local anatomical structures.
• SVC Obstruction is a local effect, identifiable via fixed elevated JVP
• Collapse of lung distal to tumour causes atelectasis and infection.
• Ulceration of pulmonary artery or veins/branches can result in haemoptysis.
• Injury to the recurrent laryngeal nerve causes hoarseness.
• Injury to the Phrenic nerve causes elevation of hemidiaphragm
• Pericardium can lead to malignant pericardial effusion; atrial fibrillation and other arrythmias
• The Pleura, carina, oesophagus and vertebra can also be affected.

Pancoast Tumour

• Pancoast tumours compress the superior vena cava, leading to elevated jugular venous pressure (JVP).
• Compression/infiltration of the sympathetic/stellate ganglion can cause Horner's syndrome, that involves miosis, ptosis and anhidrosis.

TNM Staging System

• The TNM system is adopted for most malignant tumours

• Staging is informed by clinical examination and radiological and pathological investigations.

• T refers to the primary tumour.

  • TX: Tumour cannot be assessed, or malignant cells are present in sputum or bronchial washings but not visualised.
  • T0: No evidence of primary tumour.
  • Tis: Carcinoma in situ.
  • T1: Tumour 30mm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal that the lobar bronchus.
  • T2: Tumours more than 30 mm but not more than 50 mm in greatest dimension; or tumours with specific features.
  • T3: Tumour more than 50 mm but not more than 70 mm in greatest dimension, or one that directly invades certain structures.
  • T4: Tumour over 70 mm or directly invades certain structures or separate tumour nodules in a different ipsilateral lobe.

• N refers to regional lymph nodes.

  • NX: Regional lymph nodes cannot be assessed.
  • N0: No regional node involvement.
  • N1: Metastasis in ipsilateral peribronchial/hilar nodes and/or intrapulmonary nodes.
  • N2: Metastasis in ipsilateral mediastinal and/or subcarinal node(s).
  • N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral/contralateral scalene/supraclavicular nodes.

• M refers to distant metastasis.

  • M1: Distant metastasis.
  • M1a: Separate tumour nodule(s) in a contralateral lobe; tumour with pleural nodules/pericardial effusion.
  • M1b: Single extrathoracic metastasis in a single organ and involvement of a single distant lymph node.
  • M1c: Multiple extrathoracic metastases in several organs.

• Stage IV Metastatic Lung Carcinoma has conventional treatments

• Lung cancer is able to spread to bones, brain, liver, lung and pleural cavity.

Clinical effects of malignant Lung Tumours

• Persistent Cough
• Haemoptysis
• Dyspnoea
• Chest Pain
• Finger clubbing
• Weight loss/cachexia
• Fatigue

Paraneoplastic Syndromes

• These syndromes are not explained by local effect/metastases but from secretion of hormones, peptides, cytokines and/or immune reactivity.
• These occur in about 10% of patients with malignancy.
• Small cell lung cancer, breast cancer, gynaecological or haematological tumours are commonly associated with paraneoplastic syndromes.
• Eaton-Lambert syndrome, Cushing's syndrome, Hypertrophic osteoarthropathy and SIADH are examples.
• Approximately 5%-10% of Cushing's syndrome cases are paraneoplastic, of which 50%-60% are lung tumours.
• Hypertrophic Osteoarthropathy manifests as painful swelling of joints and finger-clubbing.
• 1%-2% of cancer patients are affected by SIADH (Syndrome of Inappropriate Antidiuretic Hormone)
• 10% to 45% small cell lung cancer patients develop SIADH.
• Hypercalcaemia is common in up to 30% of patients with malignancy, and severe cases are associated with severe neurocognitive dysfunction, volume depletion and renal insufficiency/failure.

Malignant Mesothelioma

• This is a malignant tumour arising from mesothelial lining cells of the pleura.
• It is strongly associated with exposure to asbestos and may see calcified pleural plaques on CXR or CT.
• The majority of cases arise in Shipyard workers, electricians, and plumbers.
• Such cases are notified to the Coroner and a Coroner's autopsy required.

Lung Cancer Treatments

• Conventional treatments for cancer and non-small cell lung carcinoma include surgery, radiotherapy and chemotherapy
• Small cell carcinoma are not treated by Surgery and is commonly treated with chemotherapy.
• Overall prognosis is poor and driven development and adoption of innovative targeted treatments have improved care.

Classification of lung tumors as benign or malignant, primary or secondary. Metastatic tumors in the lungs are often multiple and bilateral. Haematogenous and Lymphatic spread are discussed.