LinkedIn emplea cookies para mejorar la funcionalidad y el rendimiento de nuestro sitio web, así como para ofrecer publicidad relevante. Si continúas navegando por ese sitio web, aceptas el uso de cookies. Consulta nuestras Condiciones de uso y nuestra Política de privacidad para más información.
LinkedIn emplea cookies para mejorar la funcionalidad y el rendimiento de nuestro sitio web, así como para ofrecer publicidad relevante. Si continúas navegando por ese sitio web, aceptas el uso de cookies. Consulta nuestra Política de privacidad y nuestras Condiciones de uso para más información.
Paraneoplastic opsoclonus: Paraneoplastic opsoclonus–myoclonus (POM) is an extremely rare syndrome seen in young children with neuroblastoma (dancing eyes syndrome) and adults with breast cancer and SCLC. It is characterised by opsoclonus, a disorder of saccadic eye movements causing continuous involuntary arrhythmic multidirectional high amplitude saccades. This may occur in isolation but more commonly is associated with action myoclonus affecting the whole body, including the diaphragm and palate. Some patients also have cerebellar ataxia. This syndrome is associated with cancer in about 20% of adults—it can also be seen in viral infections, drug overdose, and as part of a postinfectious encephalitis. As with other PND affecting the CNS, the standard investigations are usually normal or non-specifically normal. Several autoantibodies have been described in POM, particularly anti-Ri antibodies (breast, SCLC) and anti-neurofilament antibodies in children with neuroblastoma. (http://jnnp.bmj.com/content/75/suppl_2/ii43.full)
Stauffer syndrome: paraneoplastic syndrome in RCC: liver dysfunction without hepatic metastasis or jaundice. Resolves after RCC treated. Tumor induced osteomalacie: hypophosphatemia due to tumor production of fibroblast growth factor 23 usually by benign connective tissue tumor, but has been reported with osteosarcoma
Sir Charles Gairdner Hospital
Paraneoplastic syndrome is a disease or a
symptom that is a consequence of cancer, but
not due to the presence of local cancer cells.
Paraneoplastic syndrome is mediated
Cross reacting antibodies
Production of physiologically active factors
Interference with normal metabolic pathways
Syndrome of inappropriate ADH (secretion)
1. insertion of aquaporin-2 in apical membrane in distal tubule: increased water absorption
2. Increases urea reabsorption in collecting ducts.
SCC of head and neck
plasma hypo-osmolality (plasma Osm< Urine Osm)
urine Na concentration > 20 mmol/l
Treat underlying cause
Carefull administration of hypertonic Saline
Demeclocyclin (tetracyclin which induces DI)
1. Islet cell malignancies: usually after hepatic metastases
2. Insufficient gluconeogenesis due to near complete
replacement of hepatic parenchyma by tumor
3. Secretion of Insulin-like Growth Factor II (IGF-II). Seen in
febrosarcoma, haemangiofibropericytoma, hepatoma)
Diagnosis: fasting hypoglycemia
Plasma insulin/pro-insulin/peptide C during hypoglycemia
Most common metabolic emergency in cancer.
10-20 % of cancer patients.
1. parathyroid hormone related protein (PTHrP)
SCC, breast, renal, melanoma, prostate cancer.
Binds and activates PTH receptor causing
Osteoclast differentation: bone resorption
Symptoms of hyperparathyroidism, but low PTH, low calcitriol
Increases Ca absorption in GIT
Lymphoma: hypercalciuria, low PTH, high Calcitriol.
Bone metastasis: uncoupling of bone resorption and formation, no direct effect
of metastasis. MM: IL-6, RANKL, osteoprotegerin, IL-3
Treatment of hypercalcemia
Volume expansion + natriuresis
Loop diuretics once euvolemic
inhibition of osteoclast activity
Zoledronate more potent than pamidronate and less side effects.
Additive effect with bisphosphonates
Inhibits osteoclastic bone resorption, promotes excretion of calcium
Decrease GI absorption by decreasing calcitriol production
Anti tumour effects
New: PTHrH antibodies,
Endocrine: Carcinoid syndrome
Humoral factors producing neuro-endocrine tumours 80 % from small
bowel. But gastric, bronchial also possible.
> 40 secretory products identified, most important:
Serotonin, histamine, tachykinin, kallikrein, prostaglandins
Liver metabolises most, so carcinoid syndrome seen most often when
liver metastases have developed.
Episodes of flushing: hypotension and tachycardia (histamine and
Cutaneous venous teleangiectasia
Secretory diarrhoea (serotonin)
Cardiac valvular lesions (serotonin)
HIAA in 24 hr urine.
MRI for tumour localisation
Somatostatin receptor scintigraphy (ostreoscan)
Removal of tumour (difficult as most have extensive disease)
Diarrhoea: octreotide, cypraheptadine, cholestyramine
Flushing: antihistamine, octreotide,
Interferon alfa (IFNa)
Neurological (from up to date overview summary)
Antibodies against antigens on cancer cells cross reacts to antigens on cells of nervous system
Paraneoplastic syndrome can proceed cancer diagnosis
Almost all cancers can cause neurological paraneoplastic syndrome (except for brain cancer)
Patients suspected of having paraneoplastic neurological syndrome should have serum tested for
Presence of antibodies don’t distinguish between paraneoplastic and non-paraneoplastic cause of a syndrome
Low levels of antibodies may be seen in patients with cancer without paraneoplastic syndrome
Well characterized antibodies don’t occurr in normal individuals: search for cancer in mandatory
The same antibodies may be associated with different syndromes and one syndrome may be associated with
Neuroimaging studies, LP’s, Electrophysiological studies can be useful
Two general approaches for treatment:
Remove the antigen and treat the cancer
Suppression of immune response.
Lambert Eaton Myasthenic Syndrome
Antibodies against voltage gated Calcium channels: causing
interference with normal Calcium flux required for release of
Acteylcholine at neuromuscular endplate
SCLC, Hodgkin lymphoma, Thymoma
Slowly progressive symmetrical proximal muscle weakness of lower
Autonomic dysfunction (dry mouth)
No extra ocular muscle weakness, or upper limb weakness
Reduced deep tendon reflexes
Recovery of strength or reflexes after short vigorous exercise
Anti Hu: SCLC
Anti Mg2: germ cell testis
Anti NMDA: teratoma
Anti VGKC: thymus
Indistinguishable from HSS encephalitis
Subacute onset of seizures, short term memory loss, confusion
and psychiatric symptoms.
CSF: lymphocytosis, raised protein, normal glucose,
increased igG (auto antibodies)
Treatment: removal of tumour, immunological treatment
Subacute cerebellar degeneration
Multiple different auto-antibodies identified that cross react to Cerebellar Purkinje cells
T-cell immune response
Associated with SCLC, breast cancer, ovarian/uterus/ cancer, Hodgkins lymphoma
Rarely no cancer involved
signs similar to peripheral vestibular problem
Severe cerebellar symptoms
aggressive search for cancer.
Removal of uterus, adnex and ovaries if no tumour found (in postmenopausal women
Immunological treatment is usually unsatisfactory.
Thickened darker skin in
neck, armpits, skin folds or
prostate, breast or ovarian
Fades when cancer
Dermatology: Leser Trelat sign
Explosive onset of
Often associated with
Acute febrile neutrophilic
Associated with leukemia
Acute tender red nodules or
Fever, arthralgia, oral lesions,
Almost all organs can be
Neutrophil mediated, with role
for TNF, G-CSF
Prednison extremely effective,
most immunosuppressive drugs