Benign and malignant tumours
Neoplasia: benign and malignant tumours, oncogenes, carcinogens, spread and imaging
Neoplasia for FCPS Part 1: benign versus malignant, named tumours, oncogenes, carcinogens, spread, paraneoplastic syndromes, markers and imaging. It explains why each tumour behaves and looks as it does.
One of the most tested topics in past papers
What makes a growth a neoplasm
- A neoplasm is clonal growth that persists after the stimulus stops. Endometrial hyperplasia from unopposed oestrogen regresses when the drug is stopped; a carcinoma keeps growing whatever is done to the hormones. That autonomy defines neoplasia (atypical hyperplasia can still progress).
- Metastasis is the only absolute proof of malignancy. Others: invasion, anaplasia (pleomorphism, high nuclear to cytoplasmic ratio, hyperchromasia, atypical mitoses), rapid growth.
- Benign capsule: an expanding benign tumour compresses surrounding stroma into a fibrous rim, so a fibroadenoma shells out cleanly. Some benign tumours (haemangioma) lack a capsule; a sarcoma's pseudocapsule contains tumour cells, so shelling it out leaves disease.
- Grade = differentiation; stage = extent of spread (TNM), the stronger predictor.
- Hamartoma: disorganised native tissue (pulmonary hamartoma with fat and popcorn calcification). Choristoma: normal tissue in the wrong place.
- Locally malignant tumours invade but rarely metastasise: basal cell carcinoma, ameloblastoma (multilocular soap-bubble lucency of the posterior mandible), desmoid, giant cell tumour of bone.
Named tumours CPSP likes
| Tumour | Key fact |
|---|---|
| Capillary haemangioma | Child's face; thin-walled anastomosing capillaries lined by single endothelium; benign, often regresses |
| Warthin tumour | Benign parotid tumour of older male smokers, may be bilateral; oncocytic epithelium with lymphoid stroma |
| Fibroadenoma | Young woman, firm, very mobile breast mouse |
| Lipoma | Uniform fat (about −100 HU) with thin septa; a retroperitoneal fatty mass is liposarcoma until proven otherwise |
| Schwannoma | Encapsulated, beside a nerve; compact Antoni A and loose myxoid Antoni B areas (very bright on T2) |
| Angiomyolipoma | Fat-containing renal mass; bilateral and multiple in tuberous sclerosis (epilepsy, angiofibromas) |
| Oncocytoma | Renal mass with central scar; granular pink cells packed with mitochondria |
| Mature cystic teratoma | Ovarian dermoid with hair, sebum, teeth; commonest ovarian germ cell tumour |
| Serous cystadenocarcinoma | Commonest malignant epithelial ovarian tumour; psammoma bodies; CA-125 |
| Brenner tumour | Ovarian nests of transitional cells with coffee-bean grooved nuclei in fibrous stroma |
| GIST | Spindle cell tumour of gut wall from interstitial cells of Cajal; CD117 (KIT) positive; treated with imatinib |
| Linitis plastica | Diffuse signet-ring gastric carcinoma: thick rigid leather-bottle stomach (CDH1) |
| Medulloblastoma | Child, midline cerebellar tumour filling the 4th ventricle; small round blue cells with Homer Wright rosettes; CSF seeding |
| Hodgkin lymphoma | Reed–Sternberg binucleate owl-eye cells, CD15 and CD30 positive, in reactive lymphocytes and eosinophils |
| Spermatocytic tumour | Man over 60; small, medium and large cells; no lymphocytes; markers normal; rarely metastasises |
| Seminoma | Commonest tumour in an undescended (intra-abdominal) testis; orchidopexy lowers but does not remove the risk; most radiosensitive tumour |
| Acute promyelocytic leukaemia | t(15;17) PML–RARA; Auer rods (faggot cells), DIC; treated with ATRA |
| Polycythaemia vera | JAK2 V617F; itching after hot baths, high Hb, splenomegaly |
- Raised AFP with "pure seminoma" on histology means unsampled non-seminomatous elements (yolk sac); treat as non-seminoma (exclude liver disease first).
Genes
| Class | Examples |
|---|---|
| Proto-oncogenes (gain of function, one allele) | KRAS (pancreas, colon), MYC (Burkitt t(8;14)), N-myc amplification (neuroblastoma: small round blue cells secreting catecholamines), RET (MEN 2), HER2, EGFR, KIT (GIST), BCL-2 (t(14;18)) |
| Tumour suppressors (both alleles lost) | TP53, RB (retinoblastoma, the classic of Knudson's two-hit hypothesis: inherited cases are born with one hit, so bilateral and early), APC, VHL, BRCA1/2, PTEN, CDH1 |
| DNA mismatch repair | Lynch syndrome: colon, endometrium; microsatellite instability |
- Familial cancer syndromes from a germline tumour suppressor mutation are autosomal dominant in inheritance even though both alleles must be lost in the cell: familial adenomatous polyposis (APC), Li–Fraumeni, retinoblastoma, BRCA, VHL.
- Chromosomal instability pathway of colorectal cancer: APC loss, then KRAS, then p53 (adenoma–carcinoma sequence). Microsatellite instability pathway: mismatch repair loss.
- Bcl-2 is anti-apoptotic; tumours escape apoptosis. Telomerase allows endless division.
- Viruses: DNA viruses insert oncogenes (HPV E6 degrades p53, E7 binds RB; EBV; HBV); RNA viruses such as HTLV-1 use reverse transcription.
Carcinogens and premalignant lesions
- Initiator: permanent DNA mutation. Promoter: makes initiated cells proliferate without mutating DNA (phorbol esters, oestrogen). Order matters: promoter before initiator gives no tumours.
| Agent | Cancer |
|---|---|
| Asbestos | Mesothelioma, lung carcinoma |
| Aromatic amines (aniline dyes, rubber), smoking | Urothelial bladder carcinoma (painless haematuria in a factory worker) |
| Radon decay products (uranium mines) | Lung, multiplied by smoking |
| Vinyl chloride | Hepatic angiosarcoma |
| Aflatoxin B1; HBV, HCV | Hepatocellular carcinoma |
| Areca nut, gutka | Oral submucous fibrosis, oral squamous carcinoma |
| Schistosoma haematobium | Squamous carcinoma of bladder |
| Clonorchis sinensis | Cholangiocarcinoma (East Asia) |
| Cranial irradiation | Meningioma (commonest), later gliomas, sarcomas |
| UV light | Basal cell, squamous cell, melanoma (also dysplastic naevi, fair skin, family history) |
- Premalignant: actinic keratosis (commonest on sun-exposed skin of the elderly); leukoplakia (commonest oral premalignant lesion) and erythroplakia (less common, most likely malignant); oral submucous fibrosis; long-standing extensive ulcerative colitis (flat dysplasia); Barrett oesophagus; gallbladder polyp over 10 mm (stones shadow and move; polyps do not).
- CIN 3 (carcinoma in situ) on cervical biopsy: full-thickness dysplasia, high N:C ratio, hyperchromatic irregular nuclei, intact basement membrane.
- Epidemiology: in high-income countries endometrial is the commonest gynaecological cancer; cervical leads in low-income countries.
- Dermatomyositis in an adult warrants screening for underlying malignancy (ovary, lung, gut).
Invasion and spread
- Invasion needs loss of E-cadherin and type IV collagenases that break the basement membrane.
| Route | Typical tumours | Notes |
|---|---|---|
| Lymphatic | Carcinomas first | Sentinel node subcapsular sinus |
| Haematogenous | Sarcomas; RCC, HCC, follicular thyroid | Colon to liver via portal vein |
| Transcoelomic | Ovarian carcinoma | Omentum, Krukenberg, pouch of Douglas |
| Implantation | Mesothelioma | Along biopsy tracks |
- Liver is the commonest site of metastasis because of its dual blood supply and fenestrated sinusoids with no basement membrane; in cirrhosis, metastases are rarer and HCC commoner.
- Brain metastases sit at the grey–white junction, where arterioles narrow abruptly and trap tumour emboli.
- Uveal (choroidal) melanoma spreads only by blood, to the liver, because the eye's interior has no lymphatics.
- Bone: red-marrow sites; complete loss of T1 marrow fat in a collapsed vertebra favours malignancy. Prostate gives osteoblastic deposits.
- Malignant pleural effusion: exudate from leaky tumour vessels plus blocked pleural lymphatic drainage.
- Colorectal presentation: right-sided tumours (wide lumen, liquid stool) bleed occultly, giving iron deficiency anaemia; left-sided tumours obstruct (change in bowel habit, narrow stools, colic).
- Small bowel lymphoma infiltrates the wall without provoking fibrosis and destroys the muscle and nerve plexus, so the lumen widens (aneurysmal dilatation) rather than obstructs.
Paraneoplastic syndromes
| Syndrome | Tumour |
|---|---|
| SIADH, ectopic ACTH, Lambert–Eaton | Small cell lung carcinoma |
| PTHrP hypercalcaemia | Squamous lung carcinoma |
| Polycythaemia (EPO) | Renal cell carcinoma, HCC |
| Migratory thrombophlebitis | Pancreatic adenocarcinoma |
| Acanthosis nigricans | Gastric adenocarcinoma |
| Carcinoid syndrome | Midgut NET with liver metastases |
Markers
| Marker | Use |
|---|---|
| AFP | HCC screening and monitoring in cirrhosis (with ultrasound), yolk sac tumour |
| hCG | Choriocarcinoma; mildly raised in some seminomas |
| CA-125; CA 19-9; CEA | Serous ovarian; pancreas; colorectal |
| PSA; PSMA | Prostate; Ga-68 PSMA PET finds nodal recurrence in normal-sized nodes |
- Stains: cytokeratin (carcinoma), desmin (muscle), GFAP (glia), chromogranin (neuroendocrine), CD117 (GIST), CD15/CD30 (Hodgkin).
Imaging behaviour
| Appearance | Mechanism |
|---|---|
| Narrow transition zone, sclerotic rim | Slow growth bone can wall off |
| Permeative, moth-eaten bone | Rapid infiltration (Ewing, lymphoma) |
| Codman triangle, sunburst | Periosteum lifted faster than it ossifies (osteosarcoma) |
| Rings and arcs of calcification, endosteal scalloping | Calcified cartilage matrix (enchondroma, chondrosarcoma) |
| Expansile lytic lesion with fluid–fluid levels | Aneurysmal bone cyst (blood-filled spaces) |
| Thick irregular ring enhancement | Leaky vessels around necrosis (glioblastoma) |
| Very bright on T2 | Myxoid stroma (Antoni B, pleomorphic adenoma) |
| Calcification with encasement of the aorta | Neuroblastoma (Wilms rarely calcifies and displaces vessels, with a claw sign) |
- One volume doubling increases diameter by only 26%; a nodule stable for two years is benign.
- Oxygen fixes radiation DNA damage, so hypoxic tumours resist radiotherapy. Most radiosensitive: seminoma, dysgerminoma, lymphoma.
Remember Carcinomas travel by lymphatics, sarcomas by blood, ovarian cancer across the peritoneum.
Exam trap Grade describes how the cells look; stage describes how far the tumour has spread, and stage predicts outcome better.
Exam trap Inherited cancer syndromes caused by tumour suppressor genes are autosomal dominant, although each cell needs two hits.
How FCPS asks about this
- Characteristic feature of malignancy: metastasis; neoplasia is growth that persists without the stimulus.
- Classic two-hit tumour: retinoblastoma; FAP is autosomal dominant with a germline APC mutation.
- Spindle cell gastric tumour, CD117 positive: GIST from interstitial cells of Cajal, treated with imatinib.
- Paraneoplastic syndrome of small cell lung cancer: SIADH with hyponatraemia.
- Commonest brain tumour after cranial irradiation: meningioma.
- Why uveal melanoma spreads to liver without nodes: the eye's interior has no lymphatics.
- Most radiosensitive tumour: seminoma.
Test yourself on this topic
5 of the 446 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 60-year-old smoker has facial swelling worse on bending, distended neck veins and dilated veins over the upper chest from a large right paratracheal mass. Biopsy shows small cells with scant cytoplasm and nuclear moulding. Why did this tumour obstruct the superior vena cava?
Answer: Central growth compressing the SVC
Small cell carcinoma usually arises centrally near the hilum and spreads early to bulky mediastinal nodes. The thin-walled, low-pressure superior vena cava is easily compressed and invaded by this central mass, and thrombosis may add to the obstruction. Venous blood from the head and arms then returns through collateral channels such as the azygos and chest wall veins. Lung cancer, especially small cell, and lymphoma are the commonest causes.
SVC obstruction
- Central tumour or bulky nodes
- Thin-walled SVC compressed
- Collateral chest wall veins
- Small cell cancer, lymphoma
Remember Central chest tumours squash the low-pressure SVC.
Exam trap Get tissue before steroids if lymphoma is possible.
Why the other options are wrong
- Haematogenous spread to the SVC wall SVC obstruction is due to local compression and invasion, not blood-borne deposits.
- Paraneoplastic venous thrombosis only Thrombosis may contribute but is not the main cause here.
- Spasm of the venous wall Venous spasm is not a cause.
- Peripheral tumour invading the pleura Pleural invasion does not compress the SVC.
At curettage of an expansile lytic lesion in the proximal tibial metaphysis of a 14-year-old girl, the cavity contains many blood-filled spaces separated by septa containing fibroblasts, giant cells and woven bone. Which lesion is most likely?
Answer: Aneurysmal bone cyst
An aneurysmal bone cyst is a benign, expansile lesion made of blood-filled spaces separated by septa containing fibroblasts, osteoclast-like giant cells and woven bone. Primary lesions carry rearrangements of the USP6 gene, showing they are true neoplasms. On MRI, blood products of different ages settle within the cysts, producing multiple fluid-fluid levels. Secondary aneurysmal change can occur in other lesions, such as giant cell tumour or telangiectatic osteosarcoma, which must be excluded.
Aneurysmal bone cyst
- Expansile, blood-filled spaces
- Septa with giant cells, woven bone
- Primary: USP6 rearrangement
- Exclude telangiectatic osteosarcoma
Remember Blood-filled spaces in an expanded metaphysis: aneurysmal bone cyst.
Exam trap Blood-filled spaces can also occur in telangiectatic osteosarcoma; look for atypical cells.
Why the other options are wrong
- Simple bone cyst Usually a single fluid-filled cavity with a thin lining.
- Osteoid osteoma A small nidus of osteoid with dense sclerosis.
- Enchondroma Lobules of hyaline cartilage.
- Fibrous dysplasia Curved trabeculae of woven bone in fibrous stroma.
A 50-year-old man has a soft, mobile, lobulated 6 cm lump in the subcutaneous tissue of his shoulder. Excision shows mature adipocytes of uniform size with a few thin fibrous septa, no atypical cells and a thin capsule. What is the diagnosis?
Answer: Simple lipoma
A lipoma is the commonest benign soft-tissue tumour, made of mature fat cells, usually encapsulated and subcutaneous on the trunk, shoulders and neck. Histologically it is indistinguishable from normal fat apart from the capsule, and a few thin septa are acceptable. Atypical stromal cells in thick septa, large size and deep location suggest a well-differentiated liposarcoma. Haemangiomas contain vessels, and epidermoid cysts contain keratin.
Lipoma vs liposarcoma
- Lipoma: pure fat attenuation
- Lipoma: thin septa only
- Liposarcoma: thick septa, nodules
- Deep, large: be suspicious
Remember All fat and thin septa: lipoma.
Exam trap Retroperitoneal fatty masses should be treated as liposarcoma until proven otherwise.
Why the other options are wrong
- Well-differentiated liposarcoma Would show atypical hyperchromatic stromal cells in thickened septa.
- Haemangioma Made of blood vessels, not mature fat.
- Epidermoid cyst A keratin-filled cyst lined by squamous epithelium.
- Neurofibroma A spindle-cell nerve sheath tumour.
A 32-year-old man has had an empty right hemiscrotum since birth and now has a 7 cm firm mass in the right iliac fossa near the deep inguinal ring. Which tumour is most likely?
Answer: Seminoma in an undescended testis
An undescended testis carries a several-fold higher risk of germ cell tumour, and the commonest type is seminoma. A homogeneous mass along the path of descent in a man with an empty hemiscrotum strongly suggests this. The contralateral, normally descended testis also has a slightly raised risk, suggesting an underlying developmental defect. Orchidopexy in infancy lowers but does not abolish the risk and allows the testis to be examined.
Undescended testis
- Raised risk of germ cell tumour
- Commonest: seminoma
- Mass along path of descent
- Other testis slightly at risk
Remember Empty scrotum plus pelvic mass: seminoma of an undescended testis.
Exam trap Orchidopexy reduces but does not remove the cancer risk.
Why the other options are wrong
- Lymphoma of the caecum Possible in this region but the empty scrotum points to the testis.
- Appendiceal mucocele A cystic lesion of the appendix, not a solid firm mass.
- Retroperitoneal liposarcoma Rare, and the empty scrotum points elsewhere.
- Wilms tumour in an ectopic kidney Wilms tumour is a childhood tumour.
A 50-year-old woman has a 3 cm autonomously functioning thyroid nodule: TSH is low, free T4 raised, and the nodule takes up iodine while the rest of the gland is suppressed. What does this mean for the nodule?
Answer: Malignancy is very unlikely
A hot nodule that takes up iodine or tracer and suppresses the rest of the gland is an autonomously functioning (toxic) adenoma. Hyperfunctioning nodules are almost always benign, so fine-needle aspiration is usually not needed. Most thyroid cancers are 'cold', taking up less iodine than normal tissue. A cyst would also be cold.
Hot thyroid nodule
- Autonomous toxic adenoma
- Rest of gland suppressed
- Malignancy very unlikely
- Cancers are usually cold
Remember Hot nodules are almost never cancer.
Exam trap Most cold nodules are benign too, but they need further assessment.
Why the other options are wrong
- It is probably papillary carcinoma Papillary carcinoma is usually a cold nodule.
- It is probably medullary carcinoma Medullary carcinoma arises from C cells, which do not trap iodine.
- Urgent surgery is needed Hot nodules are treated for hyperthyroidism, not as cancer.
- It is a thyroid cyst A cyst does not concentrate iodine.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: General pathology and genetics, Neoplasia: features, spread and imaging-relevant behaviour