• Accounts for ~15% of cases
• Central, arises from neuroendocrine Kulchitsky cells
• Highly aggressive, rapid doubling time, early widespread metastases:
o Brain (common cause of paraneoplastic encephalopathy)
o Liver
o Bone
o Adrenal glands
• Paraneoplastic syndromes:
o SIADH → hyponatraemia (euvolaemic)
o Ectopic ACTH → Cushing's syndrome
o Lambert-Eaton myasthenic syndrome → proximal muscle weakness improves with use
• Treatment: usually chemotherapy ± radiotherapy, surgery rare due to early spread
• ~85% of lung cancers; subtypes:
• Central, often cavitating
• Strong smoking association
• Produces PTHrP → hypercalcaemia
• Can cause obstructive pneumonia
• Peripheral, subpleural
• Most common type in non-smokers and women
• May present as solitary pulmonary nodule
• May arise in scarred lung ("scar carcinoma")
• Poorly differentiated, can be central or peripheral
• Rapid growth, early metastasis
• Associated with poor prognosis
Diagnostic Pathway
• Initial: CXR (e.g., hilar mass, effusion, collapse)
• CT thorax and upper abdomen: staging, operability
• PET-CT: identifies occult metastases
• Tissue diagnosis:
o Bronchoscopy ± endobronchial ultrasound (EBUS) for central lesions/lymph nodes
o CT-guided percutaneous biopsy for peripheral lesions
• Features:
o Iron deficiency anaemia (occult bleeding)
o Weight loss
o Mass in right iliac fossa
• More common in Lynch syndrome (HNPCC)
• Features:
o Change in bowel habit (often alternating diarrhoea and constipation)
o Obstructive symptoms (colicky pain, distension)
o Fresh rectal bleeding
• Apple-core lesion on barium enema (historical)
• Features:
o Tenesmus (feeling of incomplete emptying)
o Urgency
o Rectal bleeding
• Digital rectal exam important
Molecular subtypes
• Microsatellite instability (MSI): seen in Lynch syndrome
• Chromosomal instability (APC pathway): sporadic majority
Types
• Invasive ductal carcinoma (~80%): most common type, firm ("stellate" on imaging)
• Invasive lobular carcinoma:
o Tends to be bilateral and multicentric
o "Single-file" cells histologically
Molecular subtypes
• Triple negative (ER-, PR-, HER2-):
o More aggressive, higher risk of early recurrence
o Common in BRCA1 mutation carriers
• HER2-positive:
o Targeted therapy: trastuzumab (Herceptin)
o Requires cardiac monitoring (risk of cardiomyopathy)
Risk factors
• Nulliparity
• Late first pregnancy
• Early menarche, late menopause
• Hormone replacement therapy
Screening
• Mammography screening (UK): age 50–70, every 3 years
Features
• Age-related, very common in elderly men
• Arises from peripheral zone → often asymptomatic early
• PSA:
o Typically >4 ng/mL (age-adjusted cut-offs used)
o Can also rise with prostatitis and BPH
• Metastases:
o Bone metastases → osteoblastic/sclerotic lesions
o Features: back pain, pathological fractures, raised ALP, hypercalcaemia (rare)
Diagnosis
• Digital rectal exam: hard, irregular prostate
• Transrectal ultrasound-guided biopsy for histology
• MRI for staging (locoregional spread)
Features
• Often late presentation with vague symptoms:
o Abdominal distension ("bloating")
o Early satiety
o Pelvic/abdominal pain
o Urinary urgency
• CA-125:
o Elevated in ~80%, but non-specific
o Also rises with benign conditions (e.g., endometriosis, menstruation, liver disease)
Types
• High-grade serous carcinoma: most common and aggressive
• Mucinous, endometrioid, clear cell: less common
Risk factors
• BRCA1/2 mutations (lifetime risk up to 40% in BRCA1)
• Nulliparity, infertility
• Early menarche, late menopause
Protective factors
• Pregnancy, breastfeeding
• Oral contraceptive pill
• Lynch syndrome: think right-sided colon cancer and associated endometrial cancer
• BRCA1: more often triple negative breast cancer, higher ovarian risk
• Prostate cancer metastases: sclerotic vs lytic bone metastases (breast can be mixed, myeloma purely lytic)
• CA-125: not a screening tool but useful in monitoring treatment response
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Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
