Lung and gastric cancer
Lung, oesophageal and gastric cancer: types, spread and markers (FCPS Part 1)
Lung cancer types, oesophageal squamous versus adenocarcinoma, gastric cancer, MALT lymphoma, gastric NETs and GIST for FCPS Part 1. Cell of origin, site and risk factor explain nearly every exam question on these cancers.
Lung cancer: causes
- Leading cause of cancer death. Smoking causes 85–90%; the main carcinogens in smoke are polycyclic aromatic hydrocarbons (benzo[a]pyrene) and tobacco nitrosamines. Asbestos multiplies the smoking risk. Other causes: radon, arsenic, chromium, nickel, air pollution, pulmonary fibrosis.
- Nickel refining raises the risk of nasal sinus and lung carcinoma. TP53 is the gene most often mutated across lung and other common cancers.
Lung cancer: types
| Type | Share and site | Cell and histology | Typical associations |
|---|---|---|---|
| Adenocarcinoma | Commonest overall (about 40%), peripheral; commonest in non-smokers and women | Glandular, mucin; EGFR, ALK, ROS1, KRAS mutations | Scar carcinoma, clubbing and hypertrophic osteoarthropathy |
| Squamous cell | 25–30%, central | Keratin pearls, intercellular bridges; may cavitate | Strongly smoking-related; hypercalcaemia from PTHrP |
| Small cell | About 15%, central | Small moulded cells with scant cytoplasm (oat cells), chromogranin, synaptophysin; from Kulchitsky (neuroendocrine) cells | SIADH, ectopic ACTH, Lambert–Eaton; early spread so treated by chemotherapy, rarely surgery |
| Large cell | 5–10%, peripheral | Undifferentiated | Poor prognosis |
| Carcinoid | 1–2%, central bronchus | Low-grade neuroendocrine (Kulchitsky) | Younger non-smokers, haemoptysis; carcinoid syndrome is rare and, unlike midgut NETs, does not need liver metastases (lung venous blood bypasses the liver) |
- Adenocarcinoma in situ shows the stepwise origin of peripheral adenocarcinoma. A persistent ground-glass or part-solid nodule that slowly grows, resected to show atypical columnar cells spreading along intact alveolar walls (lepidic growth) with no stromal, vascular or pleural invasion, is adenocarcinoma in situ (3 cm or less). Once stromal invasion appears it becomes minimally invasive, then invasive adenocarcinoma. A ground-glass nodule that persists for months must not be dismissed as inflammation.
- Large sheets of clear cells in a lung metastasis suggest a renal cell carcinoma primary.
Lung cancer: local effects and spread
- Pancoast tumour at the apex: Horner syndrome (sympathetic chain), shoulder and arm pain, T1 root damage with small hand muscle wasting.
- Superior vena cava obstruction (facial swelling, distended neck veins), commonest with small cell. Left recurrent laryngeal nerve palsy causes hoarseness; phrenic palsy raises a hemidiaphragm.
- A tumour blocking a bronchus stops ventilation of that segment; the alveolar capillaries there then carry unoxygenated blood (shunt) and hypoxic vasoconstriction reduces flow to them.
- Metastases: brain, bone, liver and adrenal glands (the endocrine gland most often involved).
- Paraneoplastic: SIADH and ACTH (small cell), PTHrP (squamous), clubbing, Lambert–Eaton, dermatomyositis, Trousseau syndrome.
- Work-up: CT chest and abdomen, PET-CT, bronchoscopy or CT-guided biopsy, EBUS for mediastinal nodes, molecular testing and PD-L1. Non-small cell: lobectomy if early and fit; chemoradiotherapy, targeted therapy, immunotherapy. Small cell: chemotherapy and radiotherapy.
- Mesothelioma: asbestos, latency of decades, pleural thickening and effusion, poor prognosis.
Oesophageal cancer
| Feature | Squamous cell carcinoma | Adenocarcinoma |
|---|---|---|
| Site | Upper and middle third | Lower third and gastro-oesophageal junction |
| Risk factors | Smoking, alcohol, very hot drinks, nitrosamines, areca nut, achalasia, Plummer–Vinson, caustic stricture, tylosis | Barrett oesophagus (from GORD), obesity, smoking, male sex |
| Geography | Commonest worldwide, including Pakistan, Iran and China | Commonest in Western countries |
- Why it spreads early and leaks: the oesophagus has no serosa, only adventitia. Nothing holds tumour back from the trachea, bronchi and aorta, and anastomoses lack the strong serosal layer that helps bowel anastomoses seal, so they leak more readily. Its longitudinal submucosal lymphatics produce skip lesions, so margins must be generous.
- Presentation: progressive dysphagia (solids then liquids), weight loss, odynophagia, hoarseness, cough from a tracheo-oesophageal fistula. New dysphagia means urgent endoscopy with biopsy; barium shows an irregular "apple-core" stricture.
- Staging: CT, endoscopic ultrasound (T and N), PET-CT. Treatment: neoadjuvant chemotherapy or chemoradiotherapy then oesophagectomy (Ivor Lewis, transhiatal, McKeown); definitive chemoradiotherapy for squamous; palliation with a self-expanding metal stent.
- Barrett is metaplasia of squamous to intestinal-type columnar epithelium with goblet cells; it is the predisposing condition for adenocarcinoma.
Gastric adenocarcinoma
- More than 90% of gastric cancers. Risk: *H. pylori* (commonest), smoked, salted and pickled foods (nitrosamines), smoking, pernicious anaemia (atrophic gastritis), gastric remnant, blood group A, CDH1 (E-cadherin) mutation, adenomatous polyps.
| Lauren type | Histology | Associations |
|---|---|---|
| Intestinal | Gland-forming | *H. pylori*, atrophy, intestinal metaplasia; older men; antrum and lesser curve |
| Diffuse | Signet ring cells, poorly cohesive, E-cadherin loss | Younger; linitis plastica ("leather bottle" stomach) |
- Spread signs: Virchow node (left supraclavicular, Troisier sign), Sister Mary Joseph nodule (umbilicus), Krukenberg tumour (ovarian deposits of signet ring cells), Blumer shelf on rectal examination, ascites, acanthosis nigricans.
- Alarm features for urgent endoscopy: dysphagia, weight loss, mass, persistent vomiting, bleeding or iron deficiency, age over 55 with new dyspepsia.
- Staging adds staging laparoscopy for peritoneal disease. Treatment: perioperative chemotherapy (FLOT) and gastrectomy with D2 lymphadenectomy; trastuzumab if HER2 positive.
- After gastrectomy: dumping (early osmotic; late reactive hypoglycaemia), B12 deficiency (lifelong injections after total gastrectomy), iron deficiency, osteoporosis.
Other gastric tumours
| Tumour | Origin and mechanism | Treatment point |
|---|---|---|
| MALT lymphoma | Low-grade B-cell lymphoma driven by chronic *H. pylori* antigen stimulation | Early low-grade disease: H. pylori eradication first; many regress |
| Type 1 gastric neuroendocrine tumour | Pernicious anaemia or atrophic gastritis: no acid, so antral G cells secrete large amounts of gastrin, which drives ECL cell hyperplasia and multiple small body polyps | Usually indolent; endoscopic removal; surveillance also for adenocarcinoma |
| GIST | Interstitial cells of Cajal; CD117 (c-KIT) and DOG1 positive; commonest in stomach | Resection; imatinib for high-risk or metastatic disease |
Remember Two gastric tumours can be treated by attacking their cause: eradicate H. pylori for MALT lymphoma, and remember that gastrin drives the NETs of pernicious anaemia.
Exam trap Small cell carcinoma has usually spread at diagnosis, so surgery is rarely the answer; chemotherapy is.
Exam trap Signet ring cells mean diffuse gastric cancer and also explain the Krukenberg ovarian tumour.
How FCPS asks about this
- Nickel refinery worker: nasal sinus and lung carcinoma.
- Central tumour of small moulded chromogranin-positive cells: small cell carcinoma from Kulchitsky cells; SIADH, ACTH, Lambert–Eaton.
- Hypercalcaemia in lung cancer: squamous cell carcinoma secreting PTHrP; commonest type overall and in non-smokers is adenocarcinoma.
- Lepidic growth along alveolar walls without invasion: adenocarcinoma in situ.
- Why oesophageal cancer invades the mediastinum and anastomoses leak: no serosa.
- Low-grade gastric MALT lymphoma: H. pylori eradication; multiple gastric NETs in pernicious anaemia are gastrin-driven ECL hyperplasia.
- Predisposing condition for oesophageal adenocarcinoma: Barrett oesophagus in the lower third.
Test yourself on this topic
5 of the 48 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 68-year-old smoker has progressive dysphagia, first to solids and now to liquids, with weight loss over 3 months. What is the first investigation?
Answer: Upper GI endoscopy with biopsy
Progressive dysphagia (solids then liquids) with weight loss in an older patient is oesophageal carcinoma until proven otherwise—an urgent cancer referral. Upper GI endoscopy with biopsy is the first investigation; staging follows with CT chest/abdomen, PET-CT and endoscopic ultrasound. Squamous cell carcinoma (upper and middle third; smoking, alcohol, hot beverages, achalasia, Plummer-Vinson) predominates in South Asia; adenocarcinoma (lower third; GORD, Barrett's, obesity) predominates in the West. Delaying with a PPI trial is unsafe.
Oesophageal cancer
- Progressive dysphagia + weight loss → urgent endoscopy
- Squamous: upper/middle; smoking, alcohol, hot drinks
- Adenocarcinoma: lower; Barrett's, GORD, obesity
- Stage: CT, PET, EUS
Remember Old, thin and cannot swallow: scope now.
Why the other options are wrong
- Barium meal only Endoscopy allows biopsy.
- Oesophageal manometry For motility disorders after excluding obstruction.
- Chest X-ray only Insufficient.
- Trial of PPI and review in 3 months Delays diagnosis.
A 60-year-old smoker with a peripheral lung carcinoma has painful swollen wrists and ankles and finger clubbing. X-ray shows new periosteal bone along the distal radius and tibia. Which of the following is the diagnosis?
Answer: Hypertrophic pulmonary osteoarthropathy
Hypertrophic pulmonary osteoarthropathy combines clubbing, painful swelling of wrists and ankles, and periostitis with new bone formation along the distal long bones. It is most often caused by lung cancer, especially non-small cell types. One theory is that megakaryocytes and platelet clumps bypass the lung capillaries and lodge in distal vessels, releasing growth factors such as VEGF and PDGF. It may improve after the tumour is removed.
HPOA
- Clubbing plus painful joints
- Periosteal new bone in long bones
- Usually lung cancer
- May resolve after resection
Remember Clubbing with painful ankles in a smoker: HPOA.
Exam trap Small cell carcinoma rarely causes clubbing or HPOA; think non-small cell first.
Why the other options are wrong
- Multiple osteolytic bone metastases Metastases cause lytic destruction, not smooth periosteal new bone.
- Seropositive rheumatoid arthritis Causes erosions, not periosteal new bone and clubbing.
- Paraneoplastic dermatomyositis Causes proximal muscle weakness and skin rash.
- Polyarticular tophaceous gout Causes punched-out erosions and tophi.
A 28-year-old non-smoker with three pneumonias in one lobe has a smooth, cherry-red mass blocking a lobar bronchus. What is the likely tumour?
Answer: Typical bronchial carcinoid
Typical carcinoid is a low-grade neuroendocrine tumour that usually grows as a smooth, very vascular polypoid mass in a central bronchus of a young adult, often a non-smoker. It obstructs the bronchus, causing recurrent pneumonia in the same lobe, and bleeds easily, causing haemoptysis. Carcinoid syndrome is rare unless there are liver metastases. Surgical resection is usually curative.
Bronchial carcinoid
- Young non-smoker
- Smooth cherry-red bronchial mass
- Recurrent pneumonia, haemoptysis
- Low-grade neuroendocrine tumour
Remember Same-lobe pneumonia in a young adult: look for an obstructing tumour.
Exam trap These tumours are very vascular and can bleed heavily at biopsy.
Why the other options are wrong
- Small cell carcinoma Occurs in older smokers and grows rapidly.
- Squamous cell carcinoma Occurs in older smokers; often cavitating.
- Pulmonary hamartoma Usually a peripheral coin lesion with popcorn calcification.
- Bronchial adenocarcinoma Usually peripheral in older adults.
A routine chest X-ray of a 50-year-old man shows a 2 cm well-defined peripheral coin lesion that has not changed in size for 3 years. CT shows popcorn calcification and fat within it. What is the most likely diagnosis?
Answer: Pulmonary hamartoma
Pulmonary hamartoma is the commonest benign lung tumour. It is a disorganised mixture of cartilage, fat, smooth muscle and respiratory epithelium, usually forming a well-defined peripheral coin lesion. Fat within the nodule on CT is almost diagnostic, and 'popcorn' calcification of the cartilage is typical. Stability for two years or more also favours a benign lesion. Tuberculomas may calcify but do not contain fat.
Pulmonary hamartoma
- Commonest benign lung tumour
- Cartilage, fat, muscle, epithelium
- CT: fat and popcorn calcification
- Stable over two years or more
Remember Fat in a coin lesion: hamartoma.
Exam trap Calcification alone does not prove a nodule is benign; the pattern of calcification matters.
Why the other options are wrong
- Bronchial carcinoid Usually central and vascular, causing obstruction.
- Tuberculoma Can calcify, but does not contain fat.
- Solitary metastasis Usually multiple and growing.
- Peripheral adenocarcinoma Grows over time and rarely contains fat.
Several young members of a family have diffuse (signet-ring) gastric cancer. Which inherited mutation is most likely?
Answer: CDH1 (E-cadherin)
Hereditary diffuse gastric cancer is autosomal dominant, caused by germline CDH1 mutations; loss of E-cadherin lets cells grow singly as signet-ring cells infiltrating the wall (linitis plastica). Lifetime risk is high, so prophylactic total gastrectomy is offered. Women carriers also have a raised risk of lobular breast cancer, which also lacks E-cadherin.
Hereditary diffuse gastric cancer
- Gene: CDH1 (E-cadherin)
- Signet-ring cells, linitis plastica
- Prophylactic total gastrectomy
- Also lobular breast cancer
Remember No E-cadherin: cells scatter as signet rings.
Exam trap Lobular breast cancer also lacks E-cadherin.
Why the other options are wrong
- APC (adenomatous polyposis) Familial adenomatous polyposis.
- BRCA2 Breast, ovarian, prostate cancers.
- TP53 (p53) Li–Fraumeni syndrome.
- MLH1 (mismatch repair) Lynch syndrome (intestinal-type gastric cancer can occur).
Where this sits in the CPSP syllabus
- Surgery & Allied, Paper 2: Oncology, Lung, oesophagus and stomach cancer