Laryngeal Cancer

28/05/2013 by admin | Oncology

Paraneoplastic syndromes and hormone producing cancers:

  1. When cancers release biologically active substances which cause ‘additional’ diseases these are termed paraneoplastic syndromes.
  2. Most common are:
    1. o Tumour-induced hypercalcaemia
    2. o SIADH
    3. o Cushing’s syndrome from ectopic ACTH release
    4. o Hypoglycaemia associated to the production of insulin-like growth factor (IGF-1)
  3. Pathogenesis:
    1. o Not really known – variety of mechanisms including
    2. o Increased amounts of normal proteins being released
    3. o Cytokine production
    4. o Autoantibody production (typically resulting in neurological disorders)
    5. o Abnormal metabolism of steroids/enzymes/fetal proteins…
  4. Hypercalcaemia:
    1. o Tumour-induced hypercalcaemia (TIH):
    2. Associated with production of parathyroid hormone-related protein (PTHrP) – which may activate the PTH receptor
    3. Solid tumours causing ectopic PTH-like secretion are those of SCC (=lung, GU, gynae)
    4. Differentials: hypercalcaemia from bony mets (=lung, breast, prostate, thyroid, renal cell primaries) – develop in 10-20% of patients with disseminated malignancy.
    5. Bony mets cause hypercalcaemia due to release of TNF, various prostaglandins and other paracrine agents that activate local osteoclasts
    6. MM and T-cell HTLV-associated lymphoma are most common haematological malignancies associated with TIH the latter being the result of production of Vit D within the tumour.
    7. Tx:
    8. Correct volume depletion that all hypercalcaemic individuals have (due to Ca induced diabetes insipidus)
    9. Bisphosphonates have revolutionised management of TIH, but PTHrP induced hypercalacemia is often refractory. Bisphosphonates inhibit osteoclast function, reduce levels of calcium, slow development of bone mets, and reduce associated symptoms.
    10. Steroids are used for steroid responsive tumours (=MM and lymphoma)
  5. Cushing’s syndrome:
    1. o Small cell lung cancer (SCLS) produce ectopic ACTH.
    2. o Only 2-3% of patients will produce enough to have actual Cushing’s syndrome.
    3. o When the syndrome is acute and prominent – it is typically associated with hirsutism, acne, hypokalaemia.
  6. SIADH:
    1. o Excessive vasopressin = hyponatriemia, renal sodium loss, hypervolaemia, and inappropriately high urine osmolality
    2. o Symptoms related to hyponatraemia may occur: tiredness, mental clouding, delerium, coma.
    3. o Mechanism:
    4. o Reflex release by CNS/tumours/drugs/co-existing lung disease
    5. o Ectopic release by the tumour, as in SCLC and more rarely tumours of the duodenum, pancreas, thymus, and lymphomas.
    6. o A precursor molecule is split to release ADH and neurophysin.
    7. o Underlying disease should be treated aggressively. Fluid restrict. Demeclocycline can be used to induce nephrogenic diabetes insipidus
  1. Cachexia and hypoglycaemia:
    1. o Weight loss and malaise in cancer are related to tumour burden, but also to release of cytokines (=TNF and cachexin)
    2. o Can be combated with: thalidomide, a TNF-a antagonist and progesterones.
    3. o Hypoglycaemia in cancer occurs through 3 pathways:
    4. o Massive size of slow growing tumour
    5. o IGF typically from hepatic or adrenal carcinomas
    6. o Insulin secretion by insulinomas (with the rare but classic p/c = hypoglycaemia, relentless weight gain and neuropsychiatric sequelae).
  2. Dermatological:
    1. o Many dermatological paraneoplastic syndormes associated to stomach or other intra-abdominal malignancies:
    2. o Trousseau’s sign of superficial migratory thrombophlebitis
    3. o The sign of Leser-Trelat (=prominent seborrhoeic keratosis)
    4. o Acanthosis nigricans: hyperpigmented velvety plaques found in the axillae and flexural areas
    5. o Dermatomyositis: >50yo, 50% of cases are linked to occult malignancy
    6. o Pemphigus related to malignancy
    7. o Gynaecomastia is associated with the production of beta-hCG by hepatomas or germ cell tumours.
  3. Presentations and likely paraneoplastic causes:
    1. o Confusion/dementia: low Na (= SIADH), high Ca (= ectopic PTH), hyperviscosity (= MM/Waldenstrom’s), cerebral cortex autoantibodies
    2. o Anaemia: anaemia of chronic disease (cytokine mediated), autoimmune haemolytic anaemia (= lymphoma), microangiopathic haemolytic anaemia (=mucin-producing cancers), aplasia (=thymic tumour)
    3. o Polycythaemia: renal cancer, cerebellar haemangioblastoma
    4. o Cachexia: TNF-a (high cachexin)
    5. o Anorexia: secondary to metabolic disturbances (=SIADH, high Ca)
    6. o Nephrotic syndrome: GN (=due to tumour Ag-Ab complex deposition), minimal change GN (=Hodgkin’s disease), membranous GN (=many cancers), membranoproliferative GN (=Non-Hodgkin’s lymphoma)
    7. o DVT
    8. o Peripheral neuropathy
    9. o Cerebellar syndromes: due to autoantibodies
    10. o Muscle weakness: cachexia (=high TNF-a), polymyositis/dermatomyositis, low K (=due to ectopic ACTH production), high Ca (due to ectopic PTH production), Eaton-Lambert syndrome, GBS
    11. o Ectopic ACTH syndromes: Slow growing tumours (=’full blown’ Cushing’s syndrome), rapidly growing tumours (=metabolic affects = low K, weakness)
    12. o Spinal cord syndromes: myelitis in thoracic region (leads to rapid paralysis and death), ALS (=motor neurone disease). 5-10% are cancer related.
    13. o Hypertrophic pulmonary osteoarthropathy: painful wrists and ankles – clubbing, distal long bone periosteal reaction.


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