Paraneoplastic Syndromes 

  • Author: Luigi Santacroce, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Feb 21, 2010
 

Background

The first report of a paraneoplastic syndrome dates back to the 19th century. The description of the relationship between neurological disorders and systemic tumors has been attributed to a French physician, M. Auchè, who described peripheral nervous system involvement in cancer patients in 1890.[1]

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease.

In a broad sense, these syndromes are collections of symptoms that result from substances produced by the tumor, and they occur remotely from the tumor itself. The symptoms may be endocrine,[2] neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature.

Although fever is the most common presentation, several clinical pictures may be observed, each of which specifically simulates more common benign conditions. These syndromes vary from dermatomyositis-polymyositis to Cushing syndrome[3] to the malignant carcinoid syndrome. A large number of cancer patients show CNS involvement.[4]

Paraneoplastic syndromes may be the first or most prominent manifestation. When a patient without a known cancer presents with one of the “typical” paraneoplastic syndromes, a diagnosis of cancer should be considered and investigated.

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Pathophysiology

The pathophysiology of paraneoplastic syndromes is complex and intriguing. When a tumor arises, the body may produce antibodies to fight it by binding to and destroying tumor cells. Unfortunately, in some cases, these antibodies cross-react with normal tissues and destroy them, which may result in a paraneoplastic disorder.[5] For example, antibodies or T cells directed against the tumor may mistakenly attack normal nerve cells. The detection of paraneoplastic anti-neural antibody was first reported in 1965.[6]

In other cases, paraneoplastic syndromes result from the production and release of physiologically active substances by the tumor. Tumors may produce hormones, hormone precursors, a variety of enzymes, or cytokines. Several cancers produce proteins that are physiologically expressed in utero by embryonic and fetal cells but not expressed by normal adult cells. These substances may serve as tumor markers (eg, carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP], carbohydrate antigen 19-9 [CA 19-9]). More rarely, the tumor may interfere with normal metabolic pathways or steroid metabolism. Finally, some paraneoplastic syndromes are idiopathic.

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Epidemiology

Frequency

International

The reported frequency of paraneoplastic syndromes ranges from 10-15% to 2-20% of malignancies, However, these could be underestimates. Neurological paraneoplastic syndromes are estimated to occur in fewer than 1% of patients with cancer.

Mortality/Morbidity

The true incidence of deaths and complications related to paraneoplastic syndromes is unknown.

Race

No race predilection is reported.

Sex

No sex predilection is known.

Age

People of all ages may be affected by cancers and their related paraneoplastic syndromes.

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Contributor Information and Disclosures
Author

Luigi Santacroce, MD  Assistant Professor, Medical School, State University at Bari, Italy

Disclosure: Nothing to disclose.

Coauthor(s)

Laura Diomede  University of Bari School of Medicine, Italy

Disclosure: Nothing to disclose.

Silvia Gagliardi, MD  Consulting Staff, Department of Surgery, Medical Center Vita, Italy

Disclosure: Nothing to disclose.

Lodovico Balducci, MD  Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Perry, MD, MS, MACP  Nellie B Smith Chair of Oncology Emeritus, Professor, Department of Internal Medicine, Division of Hematology and Oncology, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Benjamin Movsas, MD  Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

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