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Paraneoplastic Syndrome

Paraneoplastic Syndrome

PARANEOPLASTIC

Ingrid Dravecká I.Department of Internal medicine University Hospital, Košice

 Neoplastic cells can produce a variety of products that can stimulate o Hormonal o Hematologic o Dermatologic o Neurologic responses

Paraneoplastic syndrome

 Disorders that acompany benign or malignant tumors  Not directly related to mass effects or  Every type of tumor has potential to produce , induce and immunological responses Paraneoplastic syndrome

 More common than generally appreciated  Occurs in 7-15% of patients with  Atypical „clinical manifestation“ of cancer  Presenting sign of an unknown neoplasma  Precedes the diagnosis of  The first sign of recurence

Paraneoplastic syndrome

 dysfunction is not caused by invasion of (i.e. not neoplastic) → paraneoplastic  systemic or organic-specific effects  such as small cell of the lung are more likely to cause paraneoplastic than others  symptoms develop rapidly over days, weeks or months

Autoimune hypothesis

 most paraneoplastic disorders are autoimmunity diseases  certain protein antigens are sometime expressed in a cancer  generate an  tumor cells express „onconeural“ antigens that are identical to molecules normally expressed by neurons  that react with both the tumor and other tissue

Hormonal hypothesis

 synthesis and secretion of peptide proteins (hormons)

Treatment

 to identify the tumor and to treat it effectively  stop progressing of symptoms  immune supression (plasma exchange, i.v. immunoglobulin)

Distribution

 Cutaneous system  Neurological system  Haematological system  Gastrointestinal system  Common and metabolic

ENDOCRINE SYSTEM

 Ectopic production (by neoplastic cells) and expression of hormones  Aberrant expression  Clinical or biochemical evidence of abnormal endocrine function in the absence of metastatic tumor spread to the respective endocrine gland  Defective feedback control

Hypercalcemia caused by ectopic production of PTHrP - etiology

 Common finding in patients with cancer of the lung, head, neck, skin, breast, ...  Ectopic secretion of parathormon related peptide (PTHrP)  Elevated PTH-like activity (functionally similar but immunologically different)  Bone can produce PTHrP o Cellular proliferation and differentiation in other tissues o Local osteolysis

Syndrome of a inappropriate antidiuretic hormone secretion (SIADH)

 hyponatremia with plasma hypoosmolality and innapropriate concentrate urine  absent cardial, renal, adrenal and thyroid disorders  small cell carcinoma of the lung  elevated level of ADH as possible marker of response to therapy Syndrome of a inappropriate antidiuretic hormone secretion (SIADH)

Laboratory:  hyponatremia (< 120 mmol/l)  elevated levels of ADH Clinical manifestation  mental status changes, confusion, lethargy, Humoral hypercalcemia of malignancy

Clinical manifestation  fatigue, mental status change, weakness  abdominal pain, constipation  nausea, vomiting, anorexia, polyuria  ecg: prolongation of PR and QRS intervals, shortening of QT interval, bradycardia

Ectopic Cushing´s syndrome (ECS)

 uncontrolled secretion of ACTH from non-pituitary tissue  manifestation of hypercorticolism  12% !!! of all cases of Cushing´s syndrome (50% - lungs tumors)  aberrant processing of POMC Ectopic Cushing´s syndrome (ECS)

Clinical manifestation  ECS secondary to small cell carcinoma rarely shows all the clasic signs of Cushing syndrome  proximal myopathy, moon faciei, hypokalemia, hyperglycemia  ECS secondary to bronchial carcinoma is presented as hypertension and hypokalemia Ectopic secretion of gonadotropin

 leydig cell  low to normal testosteron  excessive estrogen production  supression of FSH  testicular atrophy  gynecomastia syndrome

 skin rash  impaired glucose tolerance  weight loss,

 GhRH syndrome  acromegaly

 Pseudofeochromocytoma  Hypertension, hyperglycemia

 ectopic production of IGF-II  Inhib. of glycogenolysis, gluconeogenesis

CUTANEOUS PARANEOPLASTIC SYNDROMES

Clubbing and hypertrophic

osteoarthropathy  digital clubbing – broadening and thickening of the distal phalanges of the fingers or toes, convexity of the nails  symetrical painfull arthropathy  squamous cell and adenocarcinoma of lung

Pruritus

 associated with Hodgkin , other lymphomas  adenocarcinomas of various organs  dissappears with eradication of the tumor and reappears with reccurence of the disease

Erythromelalgia

 recurrent burning pain, redness and warmth of the extremities  concomitant Raynaud´s phenomenon  myeloproliferative disorders

Palmar

 commonly associated with hyperestrogenic states, liver disease, hyperthyroidism, rheumatoid arthritis  18.5% patients with malignant brain tumors  correlation between intensity of the erythema and vascularity of the  other tumors: lung cancers, Hodgkin´s disease, gastric adenocarcinoma

Erythroderma or exfoliative dermatitis

 diffuse erythema involving at least 90% of the body  lymphoproliferative disorders, cancer of cervix, lungs..  skin changes precede the diagnosis of malignancy by several years

Necrolytic migratory erythema or glucagonoma syndrome  pruritic and painful mucocutaneous eruption presenting with the weight loss, anemia, diabetes  lesions fluctuate and migrate on the body surface  it is characteristic of glucagon secreting alpha cell pancreatic carcinoma  high glucagon levels Raynaud´s syndrome

 acral ulcerations or digital ischemia, manifesting as blanching and or cyanosis of distal fingers after exposure to cold  cancers of all types

Dermatomyositis with or without

 15-30% of  scaly of erythematous eruption affecting photoexposed areas of the face, neck

Paraneoplastic

 B-cell lymphoproliferative disorders  mucosal erosions and eruptions

Acquired ichthyosis  lymphoproliferative disorders, solid tumors  lower portion of the legs as large, adherent, scaly lesions with pretibial accentuation

Acanthosis nigricans

 common marker for hyperinsulinism and resistance  asymptomatic hyperpigmented patches on the neck, axxile, antecubital and popliteal fossae  paraneoplastic form: sudden onset, rapid and extensive spread  develops concomitantly with malignancy

Hypertrichosis lanuginosa acquista

 sudden appearance of lanugo hair diffusely on the face, trunk and extremities  women between 40-70 years

NERVOUS SYSTEM

 variety of central and peripheral nervous system syndromes  any cancer has the potential to cause a paraneoplastic syndrome that will affect the nervous system  severe nervous system disability  spinal fluid often contains an excess of white cells and immunoglobulines

NERVOUS SYSTEM

Dementia

Limbic encephalopathy  the progressive change of personality to

Cellebelar degeneration

NERVOUS SYSTEM

Carcinoma associated retinopathy

Amyotrophic lateral sclerosis

Sensory neuropathy

Sensorimotor polyneuropathy

Myasthenia gravis

 autoimmunity disease – antibodies against ACCH receptors  muscle weakness, fatigue, double vision, drop of eyelashes, malfunction of eye muscles

Dermatomyositis  muscle weakness, fatigue, pain – pelvic and arm muscles, joint disability, dysphagi 

HAEMATOLOGICAL SYSTEM

Erythrocytosis

 increased production of erythropoetine  , liver cancer  Thrombocytosis  IL-6 produced by tumor

HAEMATOLOGICAL SYSTEM

Phlebothrombosis  Trousseau´s syndrome (adenocarcinoma of pancreas + )  pulmonary embolism  Intravascular coagulation  release and consuption of procoagulation factors

GASTROINTESTINAL SYSTEM

 Enteropathies  Hepatopathies  Anorexia, cachexy

Thanks for your attention

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