Pathology chapters
Dysplasia, neoplasia and benign vs malignant tumours
What a neoplasm is, how dysplasia and carcinoma in situ come before invasive cancer, how tumours are named, and the features that separate benign from malignant tumours (differentiation, anaplasia, growth rate, invasion and metastasis).
- A neoplasm is an abnormal mass of tissue whose growth is excessive, uncoordinated and persists after the stimulus stops; it is clonal and driven by genetic changes.
- Dysplasia is disordered growth (pleomorphism, hyperchromasia, loss of polarity) in epithelium; full-thickness dysplasia with an intact basement membrane is carcinoma in situ, and breaching the basement membrane makes it invasive.
- Benign tumours are well differentiated, slow-growing, often encapsulated and never metastasise; malignant tumours show anaplasia, faster growth, local invasion and metastasis (the most reliable sign of malignancy).
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Definitions
Neoplasia means "new growth". A neoplasm (tumour) is an abnormal mass of tissue whose growth is excessive and uncoordinated with normal tissue and continues after the stimulus that started it has gone.
Key points:
- Neoplasms arise from genetic changes (mutations) passed to daughter cells, so they are clonal (monoclonal).
- They are autonomous, although many still need a blood supply and some depend on hormones (breast, prostate).
- Oncology is the study of tumours; cancer is the common term for malignant tumours.
Every tumour has two parts: the parenchyma (the neoplastic cells, which decide its behaviour and name) and the stroma (connective tissue and vessels). Abundant collagenous stroma gives a hard, desmoplastic (scirrhous) tumour, as in some breast cancers.
Hyperplasia vs neoplasia
| Hyperplasia | Neoplasia |
|---|---|
| Response to a stimulus | Autonomous |
| Stops when the stimulus is removed | Persists |
| Polyclonal | Monoclonal |
| Normal cells | Genetically abnormal cells |
Dysplasia
Dysplasia is disordered growth, mostly in epithelium, with loss of uniformity of cells and of their arrangement. Features:
- Pleomorphism (variation in size and shape of cells and nuclei).
- Hyperchromatic (dark-staining) nuclei; high nuclear-to-cytoplasmic ratio.
- Mitoses more numerous and found above the basal layer.
- Loss of polarity (architectural disorder).
Grading: mild, moderate, severe (for the cervix, CIN 1, 2, 3; now low-grade and high-grade lesions).
- Mild dysplasia may regress if the cause is removed.
- Carcinoma in situ: dysplasia through the full thickness of the epithelium, with the basement membrane intact. It is pre-invasive and cannot metastasise.
- Invasive carcinoma: cells breach the basement membrane.
Dysplasia is not cancer, but severe dysplasia often comes before it. Carcinoma in situ = full thickness, basement membrane intact.
Dysplasia often appears in metaplastic epithelium (Barrett oesophagus, the cervical transformation zone), but metaplasia and dysplasia are different things: metaplasia is one normal cell type replacing another.
Nomenclature
| Tissue of origin | Benign | Malignant |
|---|---|---|
| Surface epithelium (squamous) | Squamous papilloma | Squamous cell carcinoma |
| Glandular epithelium | Adenoma | Adenocarcinoma |
| Fibrous tissue | Fibroma | Fibrosarcoma |
| Fat | Lipoma | Liposarcoma |
| Smooth muscle | Leiomyoma (fibroid) | Leiomyosarcoma |
| Skeletal muscle | Rhabdomyoma | Rhabdomyosarcoma |
| Bone | Osteoma | Osteosarcoma |
| Cartilage | Chondroma | Chondrosarcoma |
| Blood vessels | Haemangioma | Angiosarcoma |
| Haematopoietic cells | (none) | Leukaemia, lymphoma |
| Melanocytes | Naevus | Melanoma |
| Germ cells | Mature teratoma | Immature teratoma, seminoma, choriocarcinoma |
Rules: benign tumours end in -oma; malignant epithelial tumours are carcinomas; malignant mesenchymal tumours are sarcomas.
Misnomers: lymphoma, melanoma, seminoma, mesothelioma and hepatoma (hepatocellular carcinoma) are all malignant despite the "-oma".
Special terms
- Mixed tumour: more than one cell type from one germ layer (pleomorphic adenoma of the salivary gland: epithelium and myxoid stroma).
- Teratoma: from totipotent germ cells; contains tissues from all three germ layers (skin, hair, teeth, cartilage, gut). Mature cystic teratoma (dermoid cyst) of the ovary is benign; most testicular teratomas in adults behave as malignant.
- Hamartoma: a disorganised mass of tissue native to the site (for example, a lung hamartoma of cartilage and bronchial epithelium). Many are now known to be clonal.
- Choristoma (heterotopia): normal tissue in an abnormal site (pancreatic tissue in the stomach wall or in a Meckel diverticulum).
- Blastomas: tumours of embryonic tissue in children (neuroblastoma, retinoblastoma, nephroblastoma = Wilms tumour).
Benign vs malignant
| Feature | Benign | Malignant |
|---|---|---|
| Differentiation | Well differentiated; resembles the tissue of origin | Ranges from well differentiated to anaplastic |
| Rate of growth | Usually slow; mitoses few and normal | Usually faster; mitoses many, abnormal (atypical) mitoses |
| Local invasion | Expansile; often encapsulated; does not invade | Infiltrative; invades and destroys surrounding tissue; no true capsule |
| Metastasis | Absent | Frequently present |
| Necrosis and haemorrhage | Uncommon | Common (outgrows blood supply) |
| Effect on the patient | Usually harmless, but can harm by site (brain), pressure, hormone excess or bleeding | Can kill |
Metastasis is the most reliable feature of malignancy; invasion is the next most reliable. Benign tumours never metastasise.
Some benign tumours are dangerous because of site (a meningioma compressing the brain) or hormones (an insulinoma causing hypoglycaemia). Some malignant tumours rarely metastasise: basal cell carcinoma and most gliomas invade locally but seldom spread.
Differentiation and anaplasia
Differentiation is how closely tumour cells resemble the normal cells they came from, in structure and function. Anaplasia is lack of differentiation: a hallmark of malignant cells.
Features of anaplasia:
- Pleomorphism, sometimes with tumour giant cells.
- Abnormal nuclear morphology: hyperchromasia, high N:C ratio (up to 1:1, normally 1:4 to 1:6), coarse chromatin, large nucleoli.
- Many and atypical mitoses (tripolar or quadripolar spindles).
- Loss of polarity.
- Areas of necrosis.
Well-differentiated tumours can keep normal functions (keratin pearls in squamous cell carcinoma; hormones from endocrine tumours); anaplastic tumours may produce unexpected products (ectopic hormones).
Expect: the definition of a neoplasm, hyperplasia vs neoplasia, features of dysplasia and carcinoma in situ, nomenclature (carcinoma vs sarcoma) and misnomers, hamartoma vs choristoma, teratoma, benign vs malignant features, the most reliable sign of malignancy, and the features of anaplasia.
Quick revision
- Neoplasm: autonomous, clonal growth that persists after the stimulus.
- Dysplasia: pleomorphism, hyperchromasia, high N:C, loss of polarity.
- Carcinoma in situ: full thickness, basement membrane intact.
- Carcinoma (epithelial), sarcoma (mesenchymal); misnomers: lymphoma, melanoma, seminoma, mesothelioma, hepatoma.
- Hamartoma: native tissue, disorganised. Choristoma: normal tissue, wrong place. Teratoma: three germ layers.
- Malignancy: metastasis (most reliable), invasion, anaplasia.
Written by The House Job from standard pathology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
What is a neoplasm?
An abnormal mass of tissue that grows excessively and without co-ordination with normal tissue, and keeps growing after the stimulus that started it has gone.
What is the difference between a hamartoma and a choristoma?
A hamartoma is a disorganised overgrowth of tissue native to that site; a choristoma is normal tissue found in an abnormal place.
What is the most reliable feature of malignancy?
Metastasis, followed by invasion of surrounding tissue.
What is anaplasia?
Lack of differentiation of tumour cells, shown by pleomorphism, large dark nuclei, a high nuclear-to-cytoplasmic ratio, abnormal mitoses and loss of polarity.