Paraneoplastic syndrome

Paraneoplastic syndrome
Classification and external resources
Specialty	Oncology
DiseasesDB	2064
eMedicine	med/1747
Patient UK	Paraneoplastic syndrome
MeSH	D010257

A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of cancer in the body but that, unlike mass effect, is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor.

Paraneoplastic syndromes are typical among middle-aged to older patients, and they most commonly present with cancers of the lung, breast, ovaries or lymphatic system (a lymphoma). Sometimes, the symptoms of paraneoplastic syndromes show before the diagnosis of a malignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens (e.g., neuronal proteins), triggering an anti-tumor immune response which may be partially or, rarely, completely effective in suppressing tumor growth and symptoms. Patients then come to clinical attention when this tumor immune response breaks immune tolerance and begins to attack the normal tissue expressing that (e.g., neuronal) protein.

The abbreviation PNS is sometimes used for paraneoplastic syndrome, although it is used more often to refer to the peripheral nervous system.

Classification

Paraneoplastic syndromes can be divided into four main categories: endocrine, neurological, mucocutaneous and hematological paraneoplastic syndromes, as well as others that may not fit into any of the above categories:

Syndrome class	Syndrome	Main causal cancers	Causal mechanism
Endocrine
	Cushing syndrome	small-cell lung cancer Pancreatic carcinoma Neural tumors Thymoma	Ectopic ACTH and ACTH-like substance
	SIADH	small-cell lung cancer CNS malignancies	antidiuretic hormone
	Hypercalcemia	Lung cancer (typically squamous cell) Breast carcinoma Renal carcinoma Multiple myeloma (may occur independent of osteolytic lesions) Adult T cell leukemia/lymphoma Ovarian carcinoma	PTHrP (Parathyroid hormone-related protein), TGF-α, TNF, IL-1
	Hypoglycemia	Fibrosarcoma Other mesenchymal sarcomas Insulinoma Hepatocellular carcinoma	Insulin or insulin-like substance or "big" IGF-II
	Carcinoid syndrome	Bronchial adenoma (carcinoid type) Pancreatic carcinoma Gastric carcinoma	Serotonin, bradykinin
	Polycythemia		See hematological paraneoplastic syndromes
	Hyperaldosteronism	Adrenal adenoma / Conn's syndrome Non-Hodgkin's lymphoma ovarian carcinoma pulmonary	Aldosterone
Neurological	Lambert-Eaton myasthenic syndrome (LEMS)	Small-cell lung cancer	Immunologic
	Paraneoplastic cerebellar degeneration	lung cancer ovarian cancer breast carcinoma Hodgkin's lymphoma
	Encephalomyelitis		inflammation of the brain and spinal cord
	Limbic encephalitis	small-cell lung carcinoma
	Brainstem encephalitis
	Opsoclonus myoclonus ataxia syndrome	breast carcinoma ovarian carcinoma small-cell lung carcinoma neuroblastoma (in children)	Autoimmune reaction against the RNA-binding protein Nova-1
	Anti-NMDA receptor encephalitis	Teratoma	Autoimmune reaction against NMDA-receptor subunits
	Polymyositis	Non-Hodgkin lymphoma lung cancer bladder cancer
Mucocutaneous	Acanthosis nigricans	Gastric carcinoma Lung carcinoma Uterine carcinoma	Immunologic Secretion of EGF
	Dermatomyositis	Bronchogenic carcinoma Breast carcinoma ovarian cancer pancreatic cancer stomach cancer colorectal cancer Non-Hodgkin lymphoma	Immunologic
	Leser-Trélat sign
	Necrolytic migratory erythema	Glucagonoma
	Sweet's syndrome
	Florid cutaneous papillomatosis
	Pyoderma gangrenosum
	Acquired generalized hypertrichosis
Hematological	Granulocytosis		G-CSF
	Polycythemia	Renal carcinoma Cerebellar hemangioma Hepatocellular carcinoma	Erythropoietin
	Trousseau sign	Pancreatic carcinoma Bronchogenic carcinoma	Mucins that activate clotting, others
	Nonbacterial thrombotic endocarditis	Advanced cancers	Hypercoagulability
	Anemia	Thymic neoplasms	Unknown
Others	Membranous glomerulonephritis	Various	Tumor antigens Immune complexes
	Tumor-induced osteomalacia	Hemangiopericytoma Phosphaturic mesenchymal tumor	FGF-23 (Fibroblast growth factor-23)
	Stauffer syndrome	renal cell carcinoma
	Neoplastic fever

Neurological

A particularly devastating form of paraneoplastic syndromes is a group of disorders classified as paraneoplastic neurological disorders (PNDs). These paraneoplastic disorders affect the central or peripheral nervous system; some are degenerative, though others (such as LEMS) may improve with treatment of the condition or the tumor. Symptoms of paraneoplastic neurological disorders may include ataxia (difficulty with walking and balance), dizziness, nystagmus (rapid uncontrolled eye movements), 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.

The most common cancers associated with paraneoplastic neurological disorders are breast, ovarian and lung cancer, but many other cancers can produce paraneoplastic symptoms as well.

Treatment options include:

1. Therapies to eliminate the underlying cancer such as chemotherapy, radiation and surgery, and
2. Therapies to reduce or slow neurological degeneration. Rapid diagnosis and treatment are critical for the patient to have the best chance of recovery. Since these disorders are relatively rare, few doctors have seen or treated PNDs. Therefore, it is important that PND patients consult with a specialist with experience in diagnosing and treating paraneoplastic neurological disorders.