Para Neoplastic Syndromes in bronchogenic carcinoma
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Paraneoplastic syndromes
in bronchogenic
carcinoma
ByGroup 1 A students
Fifth year Alexandria faculty of medecine
2008-2009
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Definition
• Paraneoplastic syndromes• Clinical effects produced by a tumour
that cannot be explained by the local or distant spread of the tumor or by hormones native to the tissue of origin of the tumor
• They are triggered by the immune system's response to cancer cells, or by remote effects of tumor-derived factors.
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Importance
• Paraneoplastic syndromes are common in patients with lung cancer and may be the presenting finding or first sign of recurrence.
• They may mimic metastatic disease and, unless detected, lead to inappropriate palliative rather than curative treatment.
• They may represent significant clinical problems and may even be lethal.
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Local Effects A single tumor mass may:
*destroy a vital structure ; *obstruct or perforate a hollow organ
(esophagus); *ulcerate a natural surface (mucosa); *undergo necrosis and predispose to
infection; *cause bleeding (melena, hematuria),
hemorrhage, thrombosis, infarction;*invade adjacent structures (e.g. the superior
vena caval syndrome)
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Superior Vena Cava Syndrome
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Systemic effects:• Anemia may be caused by:
*blood loss , or under production, *malnutrition, chronic infection, etc
• Decreased resistance to infections - * Weak immune responsiveness:* cytotoxic drugs, radiation therapy,
* tumor products , tumor- cell invasion of bone marrow and lymphoid spaces.
• Weight loss and cachexia• Fever :caused by pyrogenic cytokines produced
by tumours (IL-1, TNF alpha…. etc)
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Classification
• Paraneoplastic syndromes can be divided into 4 main categories: Endocrine, neurological, mucocutaneous and hematological paraneoplastic syndromes, as well as others that may not fit into any of the above categories.
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Endocrinal syndromes
• Some tumors not originating in endocrine glands may produce ectopic hormones inappropriate for the tissue of origin causing multiple endocrinal syndromes such as:
• Cushing syndrome
• SIADH
• Hypercalcemia
• Carcinoid syndrome
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Ectopic ACTH Syndrome Adrenocorticotrophin (ACTH) stimulates cortisol
secretion
mostly associated with cancer of the Lung (Small Cell Lung Cancer), Pancreas and Thymus.
Excess ACTH Excess CORTISOL ==> Cushing’s (1) overproduction of cortisol (2) muscle wasting (3) hypokalaemia with metabolic alkalosis (4) “Moon” face and abdominal striae
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SIADH
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Neurologic syndromes
• Lung cancer is one of the most common cancers associated with paraneoplastic neurological disorders.
• 1% of cancer patients develop a neurologic PNS
• Most are due to autoimmune phenomena
• Ag expressed by tumour cells cause immune response and Ab cross-reacts with normal neuronal antigens
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Neurologic syndromes:
• These paraneoplastic disorders affect the central or peripheral nervous system and they are degenerative.
• Symptoms of paraneoplastic neurological disorders may include ataxia , dizziness, nystagmus , difficulty swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, sensory loss in the limbs.
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Neurological syndromes:
• Lambert-Eaton myasthenic syndrome
• Paraneoplastic cerebellar degeneration
• Encephalomyelitis
• Limbic encephalitis
• Brainstem encephalitis
• Opsoclonus (involving eye movement)
• Encephalitis
• Polymyositis
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Lambert-Eaton myasthenic syndrome (LEMS)
• Lambert-Eaton myasthenic syndrome is a condition in which weakness results from an abnormality of acetylcholine release at the neuromuscular junction. It results from an autoimmune attack against voltage-gated calcium channels on the presynaptic motor nerve terminal
• Cancer is present when the weakness begins or is later found in 40% of patients with LEMS. This is usually a small cell lung cancer (SCLC), although LEMS has also been associated with non-SCLC and other malignancies
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Lambert-Eaton myasthenic syndrome
• The typical patient with LEMS presents with slowly progressive proximal leg weakness. – Weak muscles may ache and are occasionally
tender. – Oropharyngeal and ocular muscles may be
mildly affected. – Respiratory muscles are not usually affected,
but cases with severe respiratory compromise have been reported.
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Lambert-Eaton myasthenic syndrome
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:Mucocutaneous
• Acanthosis nigricans
• Dermatomyositis
• Leser-Trélat sign
• Necrolytic migratory erythema
• Sweet's syndrome
• Florid cutaneous papillomatosis
• Pyoderma gangrenosum
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Hematological
• Granulocytosis
• Polycythemia
• Trousseau sign
• Nonbacterial thrombotic endocarditis
• Anemia
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Others
• Membranous glomerulonephritis
• Tumor induced osteomalacia
• Hypertrophic osteoarthropathy
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Isolated clubbing also occurs in chronic obstructive lung disease and congenital cyanotic heart disease
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Other syndromesOther syndromes Hormone Tumour type Dermatomyositis None Carcinoma of lung, ovary, breast Hypertrophic osteo-arthropathy None Bronchogenic carcinoma (Finger clubbing) Myasthenia gravis None Thymoma Autoimmune haemolytic anemia None Chronic lymphocytic leukemia Renal dysfunction None Multiple myeloma, colon cancer Disseminated intravascular coagulation (DIC) None Several Advanced cancers
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