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PA25.6 | Tumours of the Lung & Pleura — SDL Guide (Part 3)

Spread, Metastasis, and TNM Staging

Diagram showing local, lymphatic, and haematogenous spread of lung cancer with Pancoast tumour features and TNM staging summary. — **Panel A:** Central lung tumour, bronchial obstruction, lung collapse, pneumonia, abscess, superior vena cava, SVC obstruction, pericardium, malignant pericardial effusion, oesophagus, dysphagia, left recurrent laryngeal nerve, hoarseness, hilar nodes, mediastinal nodes, supraclavicular Virchow node, Brain, Adrenal glands, Liver, Bone, BAL + bone mnemonic. **Panel B:** Apical Pancoast tumour, lung apex, clavicle, brachial plexus C8-T2, sympathetic chain, arm pain, Horner syndrome, ptosis, miosis, anhidrosis. **Panel C:** T tumour size and local invasion, N0 no nodes, N1 ipsilateral hilar nodes, N2 ipsilateral mediastinal nodes, N3 contralateral mediastinal or supraclavicular nodes, M distant metastasis. **Panel D:** Stage I-II potentially resectable, Stage IIIA marginal resectability with multimodality therapy, Stage IIIB-IV unresectable with systemic therapy, SCLC limited versus extensive staging.

Local spread:
• Bronchial obstruction → collapse, pneumonia, abscess.
• Hilar/mediastinal spread → superior vena cava (SVC) obstruction (SVCO): facial oedema, plethora, distended neck veins; most often SCLC or central SCC.
• Apical (Pancoast/superior sulcus) tumour → invades brachial plexus (C8-T2) causing arm pain + Horner syndrome (ptosis, miosis, anhidrosis) from sympathetic chain compression.
• Pericardial involvement → malignant pericardial effusion/tamponade.
• Left recurrent laryngeal nerve → hoarseness.
• Oesophagus → dysphagia.

Lymphatic spread: Hilar nodes → mediastinal nodes → supraclavicular (Virchow) nodes.

Haematogenous metastases — the "BAL" mnemonic: Brain, Adrenal, Liver, bone (also — adrenal metastases are almost always bilateral and cortex-derived; rarely cause Addison's clinically).

TNM Staging (8th edition, IASLC):
• T = tumour size and extent of local invasion.
• N = nodal involvement (N0 = none; N1 = ipsilateral hilar; N2 = ipsilateral mediastinal; N3 = contralateral or supraclavicular).
• M = distant metastasis.
• Stage I–II: potentially resectable.
• Stage IIIA: marginal resectability (multimodality).
• Stage IIIB–IV: unresectable (systemic therapy).
• SCLC uses a simpler limited vs extensive staging because surgery is not relevant.

Schematic lung cancer spread diagram showing local invasion to the SVC and brachial plexus, lymphatic spread with N1 to N3 nodal staging, and blood-borne metastases to brain, adrenal, liver, and bone. — **Panel A:** Right upper lobe apical tumour, trachea, main bronchi, lungs, mediastinum, superior vena cava, cervical sympathetic chain, brachial plexus, N1 ipsilateral hilar/peribronchial/intrapulmonary nodes, N2 ipsilateral mediastinal/subcarinal nodes, N3 contralateral mediastinal/hilar and supraclavicular/scalene nodes, local extension arrows, lymphatic spread arrows, haematogenous spread arrows.. **Panel B:** Pancoast tumour at lung apex, first rib, subclavian vessels, cervical sympathetic chain, stellate ganglion region, lower brachial plexus C8-T1, Horner syndrome callout, medial arm pain callout.. **Panel C:** Blood vessel/systemic circulation, brain metastasis, adrenal metastasis, liver metastasis, vertebral/bone metastasis, red dashed haematogenous spread arrows..

SELF-CHECK

A 62-year-old male with a right upper lobe mass develops ptosis and miosis of the right eye, along with pain radiating down the inner aspect of the right arm. Which of the following BEST explains these findings?

A. Haematogenous metastasis to the brain causing a third-nerve palsy

B. Apical tumour invading the cervical sympathetic chain and brachial plexus

C. SVC obstruction reducing venous return from the orbit

D. Paraneoplastic antibodies targeting the autonomic nervous system

Reveal Answer

Answer: B. Apical tumour invading the cervical sympathetic chain and brachial plexus

Pancoast (superior sulcus) tumour at the apex invades the first rib and adjoining structures. Compression of the cervical sympathetic chain (T1 sympathetic fibres) causes ipsilateral Horner syndrome (ptosis, miosis, anhidrosis). Simultaneous invasion of the lower brachial plexus (C8–T1) causes medial arm and ulnar distribution pain. This is a classical presentation of a Pancoast tumour — most often SCC or adenocarcinoma.

Paraneoplastic Syndromes — Linked to Tumour Subtype

Table-style diagram mapping each paraneoplastic syndrome to its tumour subtype, mechanism, and key clinical feature — SCLC syndromes (SIADH, ectopic ACTH, LEMS) on one side, SCC hypercalcaemia on the other, with hormone/antibody labelled in each row — click to enlarge

Paraneoplastic syndromes arise from tumour secretion of biologically active peptides, hormones, or induction of immune cross-reactivity — NOT from direct tumour infiltration or metastasis. Recognising them is clinically important: they may antedate the tumour diagnosis.

Syndrome	Mechanism	Tumour subtype
SIADH (hyponatraemia)	Ectopic ADH (AVP) secretion	SCLC (most common cause of SIADH in cancer)
Ectopic ACTH syndrome (Cushing's)	Ectopic ACTH or CRH secretion	SCLC — rapid-onset Cushing's, hypokalaemic alkalosis
Lambert-Eaton myasthenic syndrome (LEMS)	Anti-VGCC antibodies (autoimmune)	SCLC — proximal limb weakness, preserved reflexes that improve with repetitive stimulation
Hypercalcaemia	Ectopic PTHrP	Squamous cell carcinoma
Hypertrophic pulmonary osteoarthropathy (HPOA)	Periosteal proliferation; VEGF?	NSCLC (all subtypes, especially adenocarcinoma) — clubbing + periosteal pain + X-ray periostitis
Carcinoid syndrome	Serotonin	Carcinoid tumour (not lung carcinoma) — flushing, diarrhoea

Key exam differentiator: SIADH + ectopic ACTH + LEMS → SCLC. Hypercalcaemia → SCC.

A side-by-side table infographic compares SCLC paraneoplastic syndromes SIADH, ectopic ACTH, and LEMS with SCC-associated PTHrP hypercalcaemia. — **Panel A:** Small-cell lung carcinoma; SIADH; ectopic ADH; dilutional hyponatraemia; ectopic ACTH; adrenal cortisol response; Lambert-Eaton myasthenic syndrome; anti-VGCC antibody; neuromuscular junction; proximal weakness improves with repeated use.. **Panel B:** Squamous cell carcinoma; PTHrP secretion; hypercalcaemia; increased serum Ca2+; bone and blood calcium icons; clinical features of hypercalcaemia..

SELF-CHECK

A patient with lung cancer develops proximal muscle weakness that paradoxically IMPROVES with repeated use. Serum sodium is 128 mEq/L. Which tumour type and mechanism BEST explains the combined picture?

A. Squamous cell carcinoma secreting PTHrP

B. Adenocarcinoma with ALK rearrangement causing neuropathy

C. Small-cell carcinoma causing LEMS (anti-VGCC) and SIADH (ectopic ADH)

D. Large cell carcinoma with hypercalcaemia and myopathy

Reveal Answer

Answer: C. Small-cell carcinoma causing LEMS (anti-VGCC) and SIADH (ectopic ADH)

Lambert-Eaton myasthenic syndrome (LEMS) causes proximal weakness that characteristically improves with repetitive stimulation (unlike true myasthenia gravis), because brief repeated activity transiently increases calcium influx through the partially blocked VGCC. SIADH from ectopic ADH secretion causes hyponatraemia. Both are classic paraneoplastic syndromes of SCLC. PTHrP-mediated hypercalcaemia is the hallmark of SCC, not SCLC.

Malignant Mesothelioma — Pleural Tumour

Diagram of malignant pleural mesothelioma showing asbestos-related latency, sheath-like pleural tumour encasing the lung, gross progression, and histological subtypes. — **Panel A:** Pleural tumour rind, shrunken lung, obliterated pleural space, haemorrhagic exudative pleural effusion, chest wall invasion, mediastinal invasion, diaphragmatic invasion, parietal pleura, visceral pleura.. **Panel B:** Asbestos exposure, amphibole fibres: crocidolite blue asbestos and amosite brown asbestos, chrysotile white asbestos, inhaled fibres reaching pleura, latency 25-45 years, BAP1 susceptibility, no smoking co-exposure required.. **Panel C:** Early pleural plaques or nodules, progressive pleural thickening, diffuse sheath-like encasement of lung, loss of discrete mass pattern.. **Panel D:** Epithelioid type approximately 60 percent with tubulo-papillary or sheet-like cells, sarcomatoid type approximately 20 percent with spindle cells, biphasic type approximately 20 percent with mixed pattern..

Malignant mesothelioma is a primary pleural malignancy arising from mesothelial cells lining the pleura (less commonly the peritoneum or pericardium).

Aetiology — asbestos is the dominant cause:
• ~80% of cases are attributable to asbestos exposure.
• Latency is characteristically long: 25–45 years after first exposure — important medico-legal and epidemiological point.
• Asbestos fibre type matters: amphibole fibres (crocidolite = blue asbestos; amosite = brown) carry far higher mesothelioma risk than chrysotile (white asbestos) due to their needle-like shape and lung-persistent biopersistence.
• Mesothelioma from asbestos does NOT require cigarette smoking co-exposure (unlike asbestos-associated lung carcinoma).
• BAP1 germline mutation increases susceptibility.

Gross pathology: Mesothelioma does not form a discrete mass. Instead:
• Starts as small pleural plaques or nodules.
• Progresses to a thick, sheath-like rind of tumour that encases the lung entirely — the lung shrinks within a cage of tumour.
• Obliterates the pleural space; massive exudative pleural effusion (haemorrhagic).
• Invades chest wall, mediastinum, diaphragm — direct invasion rather than haematogenous spread.

Histological types:
• Epithelioid (~60%) — tubulo-papillary or sheet-like; best prognosis among the three.
• Sarcomatoid (~20%) — spindle cells; worst prognosis.
• Biphasic (~20%) — mixed; intermediate prognosis.

Diagram of malignant mesothelioma forming a thick pleural rind around a shrunken entrapped lung with obliterated pleural space and chest wall invasion. — **Panel A:** Thick pleural rind, malignant mesothelioma, shrunken entrapped lung, obliterated pleural space, chest wall invasion, ribs, intercostal muscles, diaphragm, mediastinum. **Panel B:** Normal lung, visceral pleura, parietal pleura, narrow pleural space, chest wall, rib. **Panel C:** Tumor rind bridging pleural layers, obliterated pleural cavity, invaded parietal pleura, chest wall soft tissue invasion, compressed lung surface.