Learn — Neoplasia: tumours, carcinogenesis, spread & tumour markers

2 notes · 2 questions on the topic

Neoplasia — benign versus malignant, nomenclature and spread

A neoplasm is an abnormal mass of tissue whose growth exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the stimulus that evoked it has stopped (Willis) — a clone of cells that has escaped the controls on division. The paper asks its nomenclature, the features that separate benign from malignant, the routes of spread and the difference between grading and staging, and the nurse asks the same questions in another form: is the lump dangerous, where might it have gone, and what does the stage mean for the plan.

Every tumour has a parenchyma (the neoplastic cells, which name it) and a stroma (the supporting connective tissue and vessels); benign tumours take the suffix -oma on their tissue of origin — adenoma (gland), papilloma (surface epithelium), fibroma, lipoma, chondroma, osteoma, leiomyoma (smooth muscle, the uterine fibroid), haemangioma; malignant epithelial tumours are carcinomas (adenocarcinoma from glands, squamous cell carcinoma from squamous epithelium, transitional cell carcinoma from the urothelium) and malignant mesenchymal tumours are sarcomas (osteosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma).
The exceptions the examiner loves: lymphoma, melanoma, seminoma, mesothelioma, hepatoma, glioma and myeloma are all malignant despite the -oma; a teratoma has tissues of all three germ layers and is usually benign in the ovary (the dermoid cyst with hair and teeth) and malignant in the testis; a hamartoma is a disorganised overgrowth of the tissue's own components, a choristoma is normal tissue in the wrong place, and a mixed tumour such as the pleomorphic adenoma of the parotid has more than one parenchymal element.
Differentiation is how far the tumour resembles its parent tissue; anaplasia is its loss — pleomorphism of cells and nuclei, large hyperchromatic nuclei with a high nuclear-to-cytoplasmic ratio, prominent nucleoli, many and abnormal mitoses, loss of polarity and tumour giant cells; dysplasia is disordered growth short of cancer (as in the cervix) and carcinoma in situ is a full-thickness malignant change that has not yet crossed the basement membrane.
Benign versus malignant: slow, expansile growth with a capsule against rapid, infiltrative growth without one; well-differentiated cells against anaplastic; rare mitoses against many; local effects only (pressure, obstruction, hormone secretion) against destruction, cachexia and paraneoplastic effects; rare recurrence after excision against frequent; and no metastasis against metastasis — the one feature that settles the question, since a benign tumour never metastasises and a malignant one, given time, will.
Spread: direct invasion of surrounding tissue; lymphatic spread, the route of carcinomas, to the regional nodes in order (the sentinel node is the first) and then beyond; haematogenous spread, the route of sarcomas and of the carcinomas that invade veins (renal cell, hepatocellular, follicular thyroid, choriocarcinoma), to the lung, liver, bone and brain; transcoelomic spread across the peritoneum or pleura (the ovarian carcinoma seeding the peritoneum, the gastric carcinoma reaching the ovaries as a Krukenberg tumour); implantation along a needle track or at surgery; and spread along the cerebrospinal fluid.
Grading scores differentiation on the slide (grade I well differentiated to grade IV anaplastic — the Gleason score in prostate, the Bloom-Richardson grade in breast); staging measures the extent of spread in the patient by the TNM system — T for the size and local extent of the primary (T1 to T4), N for regional nodes (N0 to N3), M for distant metastasis (M0 or M1) — grouped into stages I to IV; staging predicts survival and decides treatment better than grading, which is why the CT scan and the sentinel node matter more than the histology grade.
Precancerous conditions the nurse screens for: leukoplakia and erythroplakia of the mouth in tobacco chewers, cervical intraepithelial neoplasia on the Pap smear, Barrett's oesophagus, chronic atrophic gastritis, ulcerative colitis of long standing, familial adenomatous polyposis, actinic keratosis, chronic non-healing ulcers and burn scars (Marjolin's ulcer), and undescended testis; the warning signs to teach spell CAUTION — a change in bowel or bladder habit, a sore that does not heal, unusual bleeding or discharge, a thickening or lump, indigestion or difficulty swallowing, an obvious change in a wart or mole, and a nagging cough or hoarseness.

Carcinogenesis — carcinogens, oncogenes, staging and tumour markers

Carcinogenesis is the multistep process — initiation by a mutation, promotion by stimuli that drive the mutated cell to divide, and progression to invasion and metastasis — by which chemical, physical and biological carcinogens acting on oncogenes, tumour-suppressor genes and DNA-repair genes turn a normal cell into a cancer over years. The paper asks the carcinogens with the cancers they cause, the named genes and their tumours, the staging systems by organ, and the tumour markers with their tumours, and the nurse uses the list twice — in prevention and screening, and in reading the marker that says whether the treatment is working.

Chemical carcinogens by cancer: tobacco smoke (polycyclic hydrocarbons and nitrosamines — lung, larynx, mouth, oesophagus, bladder, pancreas), betel quid and areca nut (oral cancer, India's commonest in men), aflatoxin B1 from Aspergillus on stored groundnuts and grain (hepatocellular carcinoma, with hepatitis B), asbestos (mesothelioma and bronchogenic carcinoma, multiplied by smoking), benzene (leukaemia), aniline dyes and beta-naphthylamine (bladder), vinyl chloride (angiosarcoma of the liver), arsenic (skin, lung), nickel and chromium (lung), alkylating chemotherapy drugs (leukaemia) and the oestrogens (endometrial and breast carcinoma).
Physical and biological carcinogens: ultraviolet light (basal cell and squamous cell carcinoma and melanoma of the skin), ionising radiation (leukaemia, thyroid, breast, bone — the survivors of Hiroshima and Chernobyl); the oncogenic viruses — human papillomavirus types 16 and 18 (cervical, anal and oropharyngeal carcinoma), hepatitis B and C (hepatocellular carcinoma), Epstein-Barr virus (Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma), human T-cell leukaemia virus 1 (adult T-cell leukaemia), human herpesvirus 8 (Kaposi's sarcoma), and the bacterium and parasites — Helicobacter pylori (gastric carcinoma and MALT lymphoma), Schistosoma haematobium (squamous carcinoma of the bladder) and the liver flukes (cholangiocarcinoma).
The genes: proto-oncogenes that become oncogenes by gain of function — RAS (many carcinomas), MYC (Burkitt's), HER2/neu (a fifth of breast cancers, targeted by trastuzumab), BCR-ABL from the Philadelphia chromosome t(9;22) (chronic myeloid leukaemia, targeted by imatinib), RET (medullary thyroid carcinoma); tumour-suppressor genes lost by two hits (Knudson) — p53, the guardian of the genome mutated in half of all cancers and inherited in Li-Fraumeni syndrome, RB (retinoblastoma and osteosarcoma), APC (familial adenomatous polyposis), BRCA1 and BRCA2 (hereditary breast and ovarian cancer), NF1, VHL and WT1; the DNA mismatch-repair genes (hereditary non-polyposis colorectal cancer) and xeroderma pigmentosum; and the anti-apoptotic BCL2 of follicular lymphoma.
Staging systems by organ: TNM from the Union for International Cancer Control for most solid tumours, Dukes' A to D for colorectal carcinoma, Ann Arbor I to IV with A or B for the presence of fever, night sweats and weight loss in lymphoma, FIGO for cervical, endometrial and ovarian carcinoma, Breslow thickness and Clark level for melanoma, and Gleason score 2 to 10 for the grade of prostate cancer; carcinoma in situ is stage 0, and the stage at diagnosis is the strongest predictor of survival in every one of them.
Tumour markers by tumour: alpha-fetoprotein (hepatocellular carcinoma and yolk-sac and non-seminomatous germ-cell tumours — and, in pregnancy, neural tube defects), carcinoembryonic antigen (colorectal, also pancreatic and breast, and raised in smokers), CA-125 (ovary), CA 19-9 (pancreas), CA 15-3 (breast), prostate-specific antigen (prostate, above 4 ng/mL), human chorionic gonadotropin (choriocarcinoma, hydatidiform mole, germ-cell tumours), calcitonin (medullary thyroid carcinoma), thyroglobulin (papillary and follicular thyroid after thyroidectomy), 5-hydroxyindoleacetic acid in urine (carcinoid), vanillylmandelic acid and catecholamines (phaeochromocytoma and neuroblastoma), Bence Jones protein and the M band (myeloma), lactate dehydrogenase (lymphoma and germ-cell tumours) and alkaline phosphatase (bone and liver metastases).
Markers are for monitoring and prognosis far more than for diagnosis: a marker that falls after treatment and rises again on follow-up signals recurrence months before the scan, but most markers are raised by benign disease too, so none — with the partial exception of PSA — is a screening test; immunohistochemistry on the tissue (oestrogen and progesterone receptors and HER2 in breast) is the marker that chooses the drug.
Paraneoplastic syndromes are the tumour's remote effects through hormones and antibodies: hypercalcaemia from parathyroid-hormone-related peptide in squamous carcinoma of the lung, Cushing's syndrome and the syndrome of inappropriate antidiuretic hormone from small cell carcinoma, polycythaemia from erythropoietin in renal cell carcinoma, the Lambert-Eaton myasthenic syndrome, hypertrophic osteoarthropathy and clubbing, migratory thrombophlebitis (Trousseau's sign of pancreatic cancer), disseminated intravascular coagulation, and the cachexia of tumour necrosis factor that no diet reverses.

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