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Paraneoplastic Syndromes Clinical Presentation

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News Reference Education Log In Register 3/2/14, 3:52 PM History Paraneoplastic syndromes most commonly occur in

History

Paraneoplastic syndromes most commonly occur in patients not known to have cancer, as well as in those with active cancer and those in remission after treatment. A complete history and physical examination findings can suggest neoplasia. Persons with a family history of malignancies (eg, breast, [7, 8] colon) may be at increased risk and should be screened for cancer. Nonspecific syndromes can precede the clinical manifestations of the tumor, and this occurrence is a negative prognostic factor.

Because of their complexity and variety, the clinical presentations of these syndromes may vary greatly. Usually, paraneoplastic syndromes are divided into the following categories: (1) miscellaneous (nonspecific), (2) rheumatologic, (3) renal, (4) gastrointestinal, (5) hematologic, (6) cutaneous, (7) endocrine, and (8) neuromuscular.

Miscellaneous (nonspecific) Fever , dysgeusia, anorexia, and cachexia are included in this category. Fever, dysgeusia, anorexia, and cachexia are included in this category.

anorexia, and cachexia are included in this category. Fever is frequently associated with lymphomas , [

Fever is frequently associated with lymphomas , [ 9 ] acute leukemias , sarcomas, renal cell carcinomas (Grawitz tumors), and lymphomas, [9] acute leukemias, sarcomas, renal cell carcinomas (Grawitz tumors), and digestive malignancies (including the liver).

Rheumatologic Paraneoplastic arthropathies arise as rheumatic polyarthritis [ 1 0 ] or polymyalgia , particularly in patients with myelomas; lymphomas; acute leukemia; [10] or polymyalgia, particularly in patients with myelomas; lymphomas; acute leukemia; malignant histiocytosis; and tumors of the colon, pancreas, prostate, and CNS. Hypertrophic osteoarthropathy may be observed in patients with lung cancers, pleural mesothelioma, or phrenic neurilemmoma. Scleroderma may precede direct evidence of tumor

. Scleroderma may precede direct evidence of tumor The widespread form is typical of malignancies of
. Scleroderma may precede direct evidence of tumor The widespread form is typical of malignancies of
. Scleroderma may precede direct evidence of tumor The widespread form is typical of malignancies of

The widespread form is typical of malignancies of the breast , uterus , and lung (both alveolar and bronchial forms). breast, uterus, and lung (both alveolar and bronchial forms).

Renaluterus , and lung (both alveolar and bronchial forms). The localized form is characteristic of carcinoids

The localized form is characteristic of carcinoids and of lung tumors (bronchoalveolar forms). Systemic lupus erythematosus (SLE) may develop in patients with lymphomas or cancers of the lung, Systemic lupus erythematosus (SLE) may develop in patients with lymphomas or cancers of the lung, breast, or gonads. Secondary amyloidosis of the connective tissues is a rare presentation in patients with myeloma, renal carcinoma, and lymphomas.

Hypokalemic nephropathy, which is characterized by urinary potassium leakage of more than 20

Hypokalemic nephropathy, which is characterized by urinary potassium leakage of more than 20

mEq per 24 hours, may develop in patients with tumors that secrete adrenocorticotropic hormone (ACTH)

mEq per 24 hours, may develop in patients with tumors that secrete adrenocorticotropic hormone (ACTH) or ACTH-like substances. It occurs in 50% of individuals with ACTH-secreting tumors of the lung (ie, small cell lung cancer [11] ). Hypokalemia, hyponatremia or hypernatremia, hyperphosphatemia, and alkalosis or acidosis may

result from other types of tumors that produce ACTH, antidiuretic hormone (ADH), or gut hormones

result from other types of tumors that produce ACTH, antidiuretic hormone (ADH), or gut hormones (see Endocrine and neuromuscular, below). Nephrotic syndrome is observed, although infrequently, in patients who have Hodgkin lymphoma

(HL); non-Hodgkin lymphoma (NHL); leukemias; melanomas ; or malignancies of lung , thyroid , colon

(HL); non-Hodgkin lymphoma (NHL); leukemias; melanomas; or malignancies of lung, thyroid, colon, breast, ovary, or pancreatic head. Secondary amyloidosis of the kidneys, heart, or CNS may rarely be a presenting feature in patients with myeloma, renal carcinoma, or lymphomas. The clinical picture of secondary amyloidosis is related to renal and cardiac injuries.

Gastrointestinal Watery diarrhea [ 1 2 ] a ccompanied by an electrolyte imbalance leads to asthenia, confusion, a [12] accompanied by an electrolyte imbalance leads to asthenia, confusion, and exhaustion. These problems are typical of patients with proctosigmoid tumors (both benign and malignant) and of medullary thyroid carcinomas (MTCs) that produce several prostaglandins (PGs; especially PG E2

that produce several prostaglandins (PGs; especially PG E2 http://emedicine.medscape.com/article/280744-clinical Page
that produce several prostaglandins (PGs; especially PG E2 http://emedicine.medscape.com/article/280744-clinical Page

Paraneoplastic Syndromes Clinical Presentation

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Syndromes Clinical Presentation 3/2/14, 3:52 PM and F2) that lead to malabsorption and, consequently,

and F2) that lead to malabsorption and, consequently, unavailability of nutrients. These alterations also can be observed in patients with melanomas, myelomas, ovarian tumors, pineal body tumors, and lung metastases.

Hematologicovarian tumors, pineal body tumors, and lung metastases. Symptoms related to erythrocytosis or anemia, [ 1

Symptoms related to erythrocytosis or anemia, [ 1 2 ] thrombocytosis , disseminated intravascular coagulation
Symptoms related to erythrocytosis or anemia, [ 1 2 ] thrombocytosis , disseminated intravascular coagulation
Symptoms related to erythrocytosis or anemia, [ 1 2 ] thrombocytosis , disseminated intravascular coagulation
Symptoms related to erythrocytosis or anemia, [ 1 2 ] thrombocytosis , disseminated intravascular coagulation

Symptoms related to erythrocytosis or anemia, [12] thrombocytosis, disseminated intravascular coagulation (DIC), and leukemoid reactions may result from many types of cancers. In some cases, symptoms result from migrating vascular thrombosis (ie, Trousseau syndrome) [13] occurring in at least 2 sites. Leukemoid reactions, characterized by the presence of immature WBCs in the bloodstream, are usually accompanied by hypereosinophilia and itching. These reactions are typically observed in patients with lymphomas or cancers of the lung, breast, or stomach. Cryoglobulinemia may occur in patients with lung cancer or pleural mesothelioma.

of the lung, breast, or stomach. Cryoglobulinemia may occur in patients with lung cancer or pleural
of the lung, breast, or stomach. Cryoglobulinemia may occur in patients with lung cancer or pleural
of the lung, breast, or stomach. Cryoglobulinemia may occur in patients with lung cancer or pleural

Cutaneous [ 1 4 ] Itching is the most frequent cutaneous manifestation in patients with s [14] Itching is the most frequent cutaneous manifestation in patients with cancer. Herpes zoster, ichthyosis, [15] flushes, alopecia, or hypertrichosis also may be observed. Acanthosis nigricans and dermic melanosis are characterized by a blackish pigmentation of the skin and usually occur in patients with metastatic melanomas or pancreatic tumors.

Endocrine Endocrine symptoms related to paraneoplastic syndromes usually resemble the more common endocrine disorders (eg, Cushing syndrome ) . Neuromuscular symptoms may mimic common neurological conditions (eg, dementia ). Cushing Cushing syndrome). Neuromuscular symptoms may mimic common neurological conditions (eg, dementia). Cushing syndrome, accompanied by hypokalemia, very high plasma ACTH levels, and increased serum and urine cortisol concentrations, is the most common example of an endocrine disorder linked to a malignancy. [16, 17, 3, 18] This is related to the ectopic production of ACTH or ACTH-like molecules from many tumors (eg, small cell cancer of the lung).

Neuromuscular Neuromuscular disorders related to cancers are now included among the paraneoplastic syndromes. Such disorders affect 6% of all patients with cancer and are prevalent in ovarian and pulmonary cancers. Examples include the following:from many tumors (eg, small cell cancer of the lung). Myasthenia gravi s [ 1 9

and pulmonary cancers. Examples include the following: Myasthenia gravi s [ 1 9 ] is the
and pulmonary cancers. Examples include the following: Myasthenia gravi s [ 1 9 ] is the
and pulmonary cancers. Examples include the following: Myasthenia gravi s [ 1 9 ] is the
and pulmonary cancers. Examples include the following: Myasthenia gravi s [ 1 9 ] is the
and pulmonary cancers. Examples include the following: Myasthenia gravi s [ 1 9 ] is the
and pulmonary cancers. Examples include the following: Myasthenia gravi s [ 1 9 ] is the

Myasthenia gravi s [ 1 9 ] is the most common paraneoplastic syndrome in patients Myasthenia gravis [19] is the most common paraneoplastic syndrome in patients with thymoma, [20] a malignancy arising from epithelial cells of the thymus. Indeed, thymoma is the underlying cause in approximately 10% to 15% of cases of myasthenia gravis. [21] Rarely, hypogammaglobulinemia and pure red cell aplasia occur as paraneoplastic syndromes in patients with thymoma. [20]

Lambert-Eaton myasthenic syndrome (LEMS), which manifests as asthenia of the scapular and pelvic girdles and Lambert-Eaton myasthenic syndrome (LEMS), which manifests as asthenia of the scapular and pelvic girdles and a reduction of tendon reflexes. LEMS sometimes can be accompanied by xerostomia, sexual impotence, myopathy, and peripheral neuropathy. It is associated with cancer 40-70% of the time, most commonly small cell lung cancer (SCLC). It seems to result from interference with the release of acetylcholine due to immunologic attack against the presynaptic voltage-gated calcium channel.

Opsoclonus-myoclonus syndrome [ 2 2 ] usually affects children younger than 4 years. It is associated e [22] usually affects children younger than 4 years. It is associated with hypotonia, ataxia, and irritability. One in two patients has neuroblastoma.

Paraneoplastic limbic encephalitis [ 2 3 ] is characterized by depression, seizures, irritability, and short-term memory loss. The [23] is characterized by depression, seizures, irritability, and short-term memory loss. The neurologic symptoms develop rapidly and can resesmble dementia. Paraneoplastic limbic encephalitis is most commonly associated with SCLC. [24]

Paraneoplastic encephalomyelitis is characterized by a complex of symptoms derived from brainstem encephalitis, limbic encephalitis, cerebellar degeneration, myelitis, and autonomic dysfunction. Such neurologic deficits and signs seem to be related to an inflammatory process involving multiple areas of the nervous system.is most commonly associated with SCLC. [ 2 4 ] Paraneoplastic cerebellar degeneration causes gait

Paraneoplastic cerebellar degeneration causes gait difficulties, dizziness, nausea, and diplopia, followed by ataxia, dysarthria, and dysphagia. Paraneoplastic cerebellar degeneration is frequently associated with Hodgkin lymphoma, [ 2 5 ] b reast cancer, [ 2 6 ] S CLC, and ovarian [25] breast cancer, [26] SCLC, and ovarian cancer; it may occur in association with prostate carcinoma. [27]

Paraneoplastic sensory neuropathy affects lower and upper extremities and is characterized by progressive sensory loss, either symmetric or asymmetric. It seems to be related to the loss of the dorsal root ganglia with early involvement of major fibers responsible for detecting vibration and position.occur in association with prostate carcinoma. [ 2 7 ] http://emedicine.medscape.com/article/280744-clinical Page

Paraneoplastic Syndromes Clinical Presentation

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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 Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape 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

Disclosure: Nothing to disclose.

Chief Editor Jules E Harris, MD Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Disclosure: Nothing to disclose.

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Paraneoplastic Syndromes Clinical Presentation

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