Medicine Delta 7 Oncology 4 Paraneoplastic Syndromes PDF

(L4) paraneoplastic syndromes  LECTURE 04 PARANEOPLASTIC SYNDROMES DEFINITION  Disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion by the primar...

(L4) paraneoplastic syndromes  LECTURE 04 PARANEOPLASTIC SYNDROMES DEFINITION  Disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion by the primary tumor or its metastases.  So, atypical clinical manifestations in a patient with cancer should prompt consideration of a paraneoplastic syndrome. PATHOGENESIS  Paraneoplastic syndrome is mediated through: ① Cross reacting antibodies ② Production of physiologically active factors ③ Interference with normal metabolic pathways ④ Idiopathic TYPES ① Endocrinal paraneoplastic syndromes ② Hematologic paraneoplastic syndromes ③ Neurological paraneoplastic syndromes ④ Dermatological paraneoplastic syndromes Dr.Noaman Page 1  Medicine - Delta Semester (7) Paraneoplastic syndromes Endocrinal paraneoplastic syndromes OVERVIEW  Result from production of hormones or peptides that lead to metabolic derangements.  Thus, successful treatment of the underlying tumor often improves these conditions  The development of these disorders does not necessarily correlate with cancer stage or prognosis Common syndromes ① Cushing Syndrome ② Hypercalcemia ③ Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) ④ Hypoglycemia 1 Cushing Syndrome 1 Ectopic Hormone  Adrenocorticotropic hormone (ACTH) ① Muscle weakness ② Peripheral oedema 2 Clinical presentation ③ HTN ④ Weight gain and centripetal fat distribution ① Lung  Small cell  Adenocarcinoma  Bronchial  Squamous 3 Typical Tumor Type  Carcinoid ② Thymus ③ Pancreatic islet ④ Medullary thyroid carcinoma 4 Treatment  Treatment of the cause Dr.Noaman Page 2  Medicine - Delta Semester (7) Paraneoplastic syndromes 2 Hypercalcemia of malignancy 1 Ectopic Hormone  Parathyroid hormone-related protein (PTHrP) ① Altered mental status ⑤ Hypertonia ② Weakness ⑥ Renal failure 2 Clinical presentation ③ Ataxia ⑦ HTN ④ Lethargy ⑧ Bradycardia ① Squamous cell (head and neck, lung, skin) ② Breast 3 Typical Tumor Type ③ Genitourinary ④ Gastrointestinal ① Saline hydration ② Forced diuresis with furosemide or other loop diuretics 4 Treatment ③ Bisphosphonates (iv) can reduce serum calcium within 1 to 2 days and suppress calcium release for several weeks 3 SIADH 1 Ectopic Hormone  Vasopressin ① Gait disturbance ⑦ Anorexia, ② Falls ⑧ Confusion ③ Headache 2 Clinical presentation ⑨ Lethargy ④ Nausea ⑩ Seizures ⑤ Fatigue ⑪ Coma ⑥ Cramps ① Lung (squamous, small cell) ② Gastrointestinal 3 Typical Tumor Type ③ Genitourinary ④ Ovary ① Treatment of the cause 4 Treatment ② Fluid restriction ③ Hypertonic saline Dr.Noaman Page 3  Medicine - Delta Semester (7) Paraneoplastic syndromes Hematologic paraneoplastic syndromes OVERVIEW  The paraneoplastic hematologic syndromes in patients with solid tumors are less well characterized than the endocrine syndromes because the ectopic hormone(s) or cytokines responsible have not been identified in most of these tumors.  The severity of the paraneoplastic syndromes parallels the course of the cancer. Common syndromes Syndrome Proteins Typically Associated cancers ① Renal cancers Erythrocytosis Erythropoietin ② Hepatocarcinoma ③ Cerebellar hemangioblastomas ① Lung cancer G-CSF ② Gastrointestinal cancer Granulocytosis GM-CSF ③ Ovarian cancer IL-6 ④ Genitourinary cancer ⑤ Hodgkin's disease ① Lung cancer ② Gastrointestinal cancer Thrombocytosis IL-6 ③ Breast cancer ④ Ovarian cancer ⑤ Lymphoma ① Lymphoma, Leukemia Eosinophilia IL-5 ② Lung cancer ① Lung cancer ② Pancreatic cancer ③ Gastrointestinal cancer Thrombophlebitis Unknown ④ Breast cancer ⑤ Genitourinary cancer ⑥ Ovarian cancer, Prostate cancer ⑦ Lymphoma Dr.Noaman Page 4  Medicine - Delta Semester (7) Paraneoplastic syndromes ERYTHROCYTOSIS 1 Overview  Ectopic production of erythropoietin by cancer cells causes most paraneoplastic erythrocytosis.  The ectopically produced erythropoietin stimulates the production of red blood cells in the bone marrow and raises the hematocrit.  Most patients with erythrocytosis have an elevated hematocrit (>52% in men; >48% in women) that is detected on a routine blood count.  In most cases the erythrocytosis is asymptomatic. 2 Diagnosis  Patients with erythrocytosis due to a renal cell cancer, hepatoma, or CNS cancer should have measurement of red cell mass.  If the red cell mass is elevated, the serum erythropoietin level should then be measured.  Patients with an appropriate cancer, elevated erythropoietin levels, and no other explanation for erythrocytosis have to be diagnosed as the paraneoplastic syndrome. 3 Treatment ① Successful resection of the cancer usually resolves the erythrocytosis. ② If the tumor cannot be resected or treated effectively with radiation therapy or chemotherapy, phlebotomy may control any symptoms related to erythrocytosis. GRANULOCYTOSIS  Patients with granulocytosis are nearly all asymptomatic.  Patients with advanced-stage disease are more likely to have granulocytosis than those with early-stage disease.  The granulocytosis resolves when the underlying cancer is successfully treated. Dr.Noaman Page 5  Medicine - Delta Semester (7) Paraneoplastic syndromes THROMBOCYTOSIS  Patients with thrombocytosis are nearly all asymptomatic.  Thrombocytosis is not clearly linked to thrombosis in patients with cancer.  Patients with thrombocytosis are more likely to have advanced-stage disease and have a poorer prognosis than patients without thrombocytosis.  Paraneoplastic thrombocytosis does not require treatment. THROMBOPHLEBITIS 1 Overview  Deep venous thrombosis and pulmonary embolism are the most common thrombotic conditions in patients with cancer.  Migratory or recurrent thrombophlebitis may be the initial manifestation of cancer.  The coexistence of peripheral venous thrombosis with visceral carcinoma, particularly pancreatic cancer, is called Trousseau's syndrome. 2 Clinical picture  Patients with cancer who develop deep venous thrombosis usually develop: ① Swelling or pain in the leg ② Physical examination reveals tenderness, warmth, and redness.  Patients who present with pulmonary embolism develop: ① Dyspnea, chest pain, and syncope ② Physical examination shows tachycardia, cyanosis, and hypotension 3 Treatment  LMWH for at least 5 days then either continue or shift to oral anticoagulants Dr.Noaman Page 6  Medicine - Delta Semester (7) Paraneoplastic syndromes Note  Hypercalcemia is most often encountered with squamous cell neoplasms  The hematologic syndromes with adenocarcinomas  The remaining syndromes are much more common with small-cell neoplasms Neurological paraneoplastic syndromes MECHANISM  In response to a developing cancer, a patient produces tumor-directed antibodies known as onconeural antibodies.  These onconeural antibodies and associated onconeural antigen-specific T lymphocytes inadvertently attack components of the nervous system  Paraneoplastic syndrome may proceed the onset of cancer  All cancers can produce neurological paraneoplastic syndrome (except brain cancer) TREATMENT ① Remove the antigen and treat cancer ② Suppression of the immune response Common paraneoplastic neurologic diseases ① Paraneoplastic encephalomyelitiss ± sensory neuronopathy (PEM/PSN) ② Limbic encephalitis (LE) ③ Brainstem encephalitis (BE) 1 Brain and retina ④ Paraneoplastic encephalomyelitis with rigidity ⑤ Paraneoplastic cerebellar degeneration (PCD) ⑥ Paraneoplastic opsoclonus–myoclonus (POM) ⑦ Paraneoplastic retinal degeneration Dr.Noaman Page 7  Medicine - Delta Semester (7) Paraneoplastic syndromes Spinal cord ① Myelitis 2 Dorsal root ganglia ② Motor neurone syndromes Anterior horn cells ① Sensory neuropathy (axonal or demyelinating) 3 Peripheral nerve ② Sensorimotor neuropathy (axonal or demyelinating) ③ Motor neuronopathy Neuromuscular 4 ① Myasthenia gravis junction ① Polymyositis/dermatomyositis (PM/DM) 5 Muscle ② Acute necrotising myopathy Dr.Noaman Page 8  Medicine - Delta Semester (7) Paraneoplastic syndromes Dermatologic & rheumatologic paraneoplastic s. overview  Many of the dermatologic and rheumatologic paraneoplastic syndromes are conditions that occur most commonly without an associated malignancy  Management of dermatologic and rheumatologic paraneoplastic syndromes consists of cancer-directed therapy plus standard treatments of the non-paraneoplastic counterparts of these syndromes  Development of these disorders often precedes a diagnosis of cancer or recurrence of a previously treated malignancy Common syndromes 1 Acanthosis Nigricans  Skin condition that causes a dark discoloration in body folds and creases.  It typically affects: the armpits, groin and neck 2 Dermatomyositis  Disease that causes muscle weakness and skin rash.  Symptoms include: ① Red or purple rash on sun exposed skin and eyelids ② Calcium deposits under the skin ③ Muscle weakness ④ Trouble talking or swallowing Dr.Noaman Page 9  Medicine - Delta Semester (7) Paraneoplastic syndromes 3 Hypertrophic Osteoarthropathy ① Digital clubbing ② Increased periosteal activity of the tubular bones ③ Arthralgias ④ joint effusion 4 Leukocytoclastic Vasculitis  Inflammation in small blood vessels that leads to tissue destruction. Dr.Noaman Page 10  Medicine - Delta Semester (7) Paraneoplastic syndromes 5 Paraneoplastic Pemphigus  Fatal paraneoplastic mucocutaneous blistering disease 6 Sweet Syndrome ① Painful, edematous, and erythematous papules, plaques, or nodules on the skin. ② Fever and leukocytosis. ③ In addition, involvement of the eyes, musculoskeletal system, and internal organs may occur. Dr.Noaman Page 11