Lecture 40 - Para Neoplastic Syndromes

Paraneoplastic Syndromes Segun Mojiminiyi

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 • Appear in 10% to 15% of patients with  cancer • May be the first manifestation of an occult  tumor

Paraneoplastic Syndromes • Paraneoplastic syndromes are  important for three reasons: • 1) they may represent the earliest  manifestation of an occult tumor • 2) they may represent significant clinical  problems and may even be lethal • 3) they may mimic metastatic disease  and therefore confound treatment

 

 

Things You Must Know • Understand the effect of tumour on the  host (patient) • Understand the concept of  paraneoplastic syndromes • Know the tumours that are associated  with paraneoplastic syndromes

 

 

Effects of Tumor on Host Local Effects A single tumor mass may: *destroy a vital structure (e.g. pituitary); *obstruct or perforate a hollow organ (bowel); *ulcerate a natural surface (mucosa, epidermis); *undergo necrosis and predispose to infection; *cause bleeding (melena, hematuria), hemorrhage, thrombosis, infarction; *invade adjacent structures (e.g. the superior vena caval syndrome)

Superior Vena Cava Syndrome

Main Paraneoplastic Syndromes Hypercalcemia Hypoglycemia Cushing’s Syndrome Hypertrophic osteopathy SIADH secretion Myopathies Renal disorders Anaemia Thrombocytopenia Polycythemia DIC Neurological disorders

Effects of Tumor on Host Systemic Effects : - Anemia may be caused by: *blood loss,or under-production, *malnutrition, chronic infection, etc - Decreased resistance to infections decreased resistance to opportunistic infections: * Weak immune responsiveness: - cytotoxic drugs, radiation therapy, - tumor products, - tumor- cell invasion of bone marrow and lymphoid spaces.

Other Effects of Tumor on Host Systemic Effects : - Weight loss and cachexia Cachexia : a state of extreme wasting, malnutrition, malaise, and weakness. TNFa (“cachectin”) which depresses appetite is most probably responsible Many factors contribute : *loss of appetite; *malabsorption; *increased catabolism; *chronic infection.

Paraneoplastic syndromes Fever • Fever – hypothalamus is the thermostat for the body – resetting the thermostat allows for higher body temperature – Caused by pyrogenic cytokines produced by tumours (IL1, TNF alpha…. etc) –– although any tumour can cause fevers, most common in • leukemias, lymphomas, Renal cell carcinoma, osteogenic sarcoma, Primary liver cell cancer – usually the result of tissue necrosis and infection - in a patient with known cancer, you must rule out infection as this is the most common reason for fever

Hypercalcaemia of Malignancy: Not always paraneoplastic for example… Local osteolytic hypercalcemia - Not paraneoplastic invasion of bone or bone marrow – Not Paraneoplastic What is Paraneoplastic?

Secretion of factors that mediate bone resorption : Prostaglandins: PGE1, PGE2 Osteoclast Activating Factor examples lymphoma, multiple myeloma

Paraneoplastic Hypercalcaemia: Secretion of Hormones that Raise Serum Calcium: PTH Parathyroid hormone-related peptide (PTHrP) Calcitriol Tumor-derived growth factors

Hypoglycemia Seen in Fibrosarcoma, Hepatocellular carcinoma

Mechanisms of hypoglycemia:  secretion of insulin-like substances  accelerated use of glucose by the tumor  failure of gluconeogenesis or glycogenolysis  increased peripheral glucose utilization

Hormone Production and Paraneoplastic Syndromes • Some tumors not originating in endocrine glands may produce ectopic hormones inappropriate for the tissue of origin.

Ectopic Production Of Hormones By Non-Endocrine Tumours Ectopic ADH Production Usually by caused by Small Cell Lung Cancer. ==> Syndrome of inappropriate ADH secretion (SIADH): low plasma osmolality with inappropriately high urine osmolality. hyponatraemia, dilution effect resulting in low plasma urea, creatinine Protein etc,

Hyperparathyroidism Ectopic production of PTH Production of a PTH-like substance (PTH-related peptide, PTHrP) Tumours that produce PTH: renal cortical carcinoma and bronchial squamous cell carcinoma.

Ectopic ACTH Syndrome Adrenocorticotrophin secretion

(ACTH)

stimulates

cortisol

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

Smoking is main cause of Small Cell Lung Cancer

Neurologic Paraneoplastic Syndromes • 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

Paraneoplastic Syndromes Neuromyopathies • Myasthenia Gravis: – Block in neuromuscular transmission caused by antibodies against tumour cells that crossreact with neuronal cells or by “toxins”

• Tumours: – Thymoma – Bronchogenic carcinoma

Isolated clubbing also occurs in chronic obstructive lung disease and congenital cyanotic heart disease

Summary Slides Paraneoplastic Syndromes can be endocrine or non-endocrine

Some Endocrine Paraneoplastic Syndromes Endocrine Syndromes                      Hormone                        Cushing's syndrome                         ACTH                                                                   Dilutional hyponatraemia               ADH                                                  Gynecomastia                                  HCG                                                  Hypercalcemia                               PTH­like                                                                 Hypoglycemia                              Insulin­like                         Carcinoid syndrome                     Serotonin                            Polycythemia                               Erythropoietin                  

Tumour Type    Oat (small)­cell carcinoma of     lung, thymoma, pancreatic     carcinoma  Oat­cell carcinoma of lung,    intracranial tumors  Oat­cell carcinoma of lung,     liver tumors    Squamous cell carcinoma of     lung, breast carcinoma, renal     carcinoma    Fibrosarcoma, other sarcomas  Pancreatic carcinoma,   liver carcinomas 

Other syndromes – Non Endocrine Other syndromes          Dermatomyositis                            Hypertrophic osteo­arthropathy   (Finger clubbing)    Myasthenia gravis                          Autoimmune haemolytic anemia     Renal dysfunction                           Disseminated intravascular  coagulation (DIC)                       

Hormone  

Tumour type 

None                      Carcinoma of lung, ovary, breast  None                       Bronchogenic carcinoma  None                      Thymoma  None                      Chronic lymphocytic leukemia  None                      Multiple myeloma, colon cancer  None                      Several Advanced cancers