What is paraneoplastic syndrome?

From the Guidelines

Paraneoplastic syndrome is a group of symptoms that occur in some cancer patients when substances released by cancer cells disrupt the normal function of surrounding tissues and organs, and early recognition is crucial to prevent increased morbidity and mortality. These syndromes develop as a remote effect of cancer, meaning they occur in parts of the body not directly affected by the tumor or its metastases. The symptoms arise when the immune system, responding to cancer cells, mistakenly attacks healthy cells in the body. Common manifestations include:

• Neurological disorders (such as cerebellar degeneration or Lambert-Eaton myasthenic syndrome)
• Endocrine abnormalities (like Cushing syndrome or hypercalcemia)
• Hematological problems (such as anemia or blood clotting disorders)
• Dermatological conditions (like dermatomyositis)
• Rheumatological issues. Treatment primarily focuses on addressing the underlying cancer through surgery, chemotherapy, radiation, or immunotherapy, as eliminating the cancer often resolves the paraneoplastic symptoms 1. However, specific treatments for symptom management may include corticosteroids, immunosuppressants, intravenous immunoglobulin, or plasmapheresis depending on the particular syndrome.

Key Considerations

• Prompt recognition and treatment of paraneoplastic syndromes is important for patients with lung cancer, as delayed diagnosis may lead to increased complications that limit or delay cancer treatment 1.
• Paraneoplastic syndromes can be categorized as being either hormonally based or immunologically based 1.
• Early recognition of paraneoplastic syndromes is crucial as they sometimes appear before the cancer is diagnosed, potentially allowing for earlier cancer detection and treatment.

Management

• The goal of treatment is to recognize and diagnose paraneoplastic syndromes during the initial evaluation so that treatment of the underlying condition can be initiated, thereby permitting more-effective cancer treatment with less risk 1.
• Consensus statements and guidelines are available to guide the management of hypercortisolism in paraneoplastic Cushing syndrome in patients with lung cancer, including the use of metyrapone, ketoconazole, etomidate, mitotane, and mifepristone to decrease circulating glucocorticoids 1.

From the Research

Definition and Overview of Paraneoplastic Syndrome

• Paraneoplastic syndromes are disorders that arise from tumor secretion of hormones, peptides, or cytokines or from immune cross-reactivity between malignant and normal tissues 2.
• These syndromes can affect diverse organ systems, including the endocrine, neurologic, dermatologic, rheumatologic, and hematologic systems 2.
• Paraneoplastic syndromes may occur concurrently with tumor diagnosis, before tumor is diagnosed, and even after tumors have been resected 3.

Causes and Classification of Paraneoplastic Syndrome

• Paraneoplastic syndromes are largely due to two main causes: those due to tumor secretions of hormones, functionally active peptides, enzymes, cytokines, or to tumors operating through auto-immune/immunological mechanisms with cross-reacting antibodies between neoplastic and normal tissues 3.
• Classification schemes vary, but most currently place paraneoplastic syndromes in one of five groups: endocrine, neurological, musculocutaneous, hematological, and other 3.

Diagnosis and Treatment of Paraneoplastic Syndrome

• Diagnosing paraneoplastic syndromes is challenging, requiring exclusion of other differential diagnoses 4.
• New diagnostic criteria classify paraneoplastic neurological syndromes into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence 4.
• Treatments include addressing the underlying malignancy, immunosuppression (for neurologic, dermatologic, and rheumatologic paraneoplastic syndromes), and correction of electrolyte and hormonal derangements (for endocrine paraneoplastic syndromes) 2.
• Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins, with second-line immunosuppressants like rituximab or cyclophosphamide used if initial treatments fail 4.

Paraneoplastic Syndromes as Biomarkers for Early Cancer Detection

• Paraneoplastic antigens can be used as biomarkers for early detection of ovarian cancer, with subclinical levels of paraneoplastic autoantibodies potentially exploited to screen asymptomatic high-risk patients 5.
• The presence of onconeural antibodies in patient sera can provide diagnostic utility for earlier therapeutic intervention, improving overall survival in ovarian cancer patients 5.