II. Epidemiology
- Paraneoplastic Syndromes affect 1 to 8% of cancer patients
III. Mechanism
- Neoplasms secrete biologically active substances (e.g. Hormones, peptides, Cytokines)
- May have direct effects (e.g. endocrine) or stimulate an immune-mediated response
- Released substances may affect multiple organ systems
- Endocrine
- Neurologic
- Dermatologic
- Rheumatologic
- Hematologic
- Associated neoplasms (most common)
- Small Cell Lung Cancer
- Breast Cancer
- Gynecologic neoplasms (e.g. Ovarian Neoplasms)
- Hematologic malignancies (e.g. Leukemia)
IV. Precautions
- Early cause identification may significantly impact morbidity and mortality
- Reduce high symptom burden associated with Paraneoplastic Syndrome
- Counter Electrolyte and hormonal effects
- Early diagnosis of associated malignancy (paraneoplastic symptoms are often the cancer presentation)
V. Types: Endocrine
-
Syndrome Inappropriate ADH Secretion (SIADH)
- Presents with symptoms related to isovolemic hyposmolar Hyponatremia
- Multiple associated cancers
-
Hypercalcemia of Malignancy
- Presents with Altered Mental Status, Ataxia, hypertonia, Vomiting, Renal Failure
- Multiple associated cancers
-
Cushing Syndrome
- Presents with Muscle Weakness, Peripheral Edema, weight gain, Hypertension
- Associated with Lung Cancer (50-60% of cases)
- Also associated with thymoma, Medullary Thyroid Cancer, Pancreatic Cancer, adrenal cancer, Ovarian Cancer
-
Hypoglycemia
- Associated with Lung Cancer (including Mesothelioma), Sarcomas and gastrointestinal tumors
- IGF2 or Insulin secretion by Non-Islet cell tumors (NICTH)
- More commonly occurs with primary islet cell tumors (Insulinomas)
VI. Types: Neurologic
- Limbic Encephalitis
- Presents with mood changes, Hallucinations, Memory Loss and Seizures
- Various associated antibodies
- Anti-Hu (Small Cell Lung Cancer)
- Anti-Ma2 (Testicular Cancer - germ cell)
- Anti-CRMP5
- Anti-NMDA (see NMDA Encephalitis, associated with ovarian malignancies)
- Associated with Small Cell Lung Cancer (40-50%), testicular germ cell cancer (20%) or Breast Cancer (8%)
- Other associated cancers include thymoma, Teratoma, Hodgkin Lymphoma
- Paraneoplastic Cerebellar Degeneration
- Presents with Ataxia, Diplopia, Dysphagia and Dysarthria
- Associated with Small Cell Lung Cancer, gynecologic cancer, Hodgkin Lymphoma, Breast Cancer
-
Lambert-Eaton Myasthenic Syndrome (LEMS)
- Presents with proximal leg weakness, diaphragmatic weakness and bulbar symptoms (speach, swallow)
- Associated with Small Cell Lung Cancer, Prostate Cancer, Cervical Cancer, Lymphomas
-
Myasthenia Gravis
- Presents with presents with ocular, bulbar and limb fatigable weakness and diaphragmatic weakness
- Associated with thymoma (15% of Myasthenia Gravis patients)
-
Autonomic Neuropathy
- Presents with Orthostatic Hypotension, gastrointestinal symptoms
- Associated with Small Cell Lung Cancers and thymomas
- Peripheral Sensory Neuropathy
- Presents with initial arm>leg Paresthesias, followed by Ataxia
- Associated with Small Cell Lung Cancer (70-80% of cases)
- Also associated with Breast Cancer, Ovarian Cancer, Sarcomas, Hodgkin Lymphoma
VII. Types: Dermatologic and Rheumatologic
-
Acanthosis Nigricans
- Associated with abdominal adenocarcinomas (esp. Gastric Cancer)
-
Dermatomyositis
- Presents with heliotrope rash, Gottron Papules, and erythematous rash face/neck/trunk
- Associated with Ovarian Cancer, Breast Cancer, Prostate Cancer, Lung Cancer, Colorectal Cancer
- Also associated with nasopharyngeal cancers and Non-Hodgkin Lymphoma
-
Erythroderma
- Presents with a diffuse erythematous, exfoliating rash
- Associated with CLL, Cutaneous T-Cell Lymphoma, myeloproliferative disorders and GI cancers
-
Hypertrophic Osteoarthropathy
- Presents with Digital Clubbing, bone thickening of wrists and ankles, large joint effusions
- Associated with intrathoracic tumors, lung metastases, Rhabdomyosarcoma, nasopharyngeal cancers
-
Leukocytoclastic Vasculitis
- Presents with digital erosions and Cyanosis, leg palpable Purpura, Renal Insufficiency, Peripheral Neuropathy
- Associated with Leukemia, Lymphoma, Myelodysplastic Syndrome, Multiple Myeloma
- Also associated with Colon Cancer, Lung Cancer, urologic cancer and Rhabdomyosarcoma
- Paraneoplastic Pemphigus (PNP)
-
Polymyalgia Rheumatica
- Presents with proximal Muscle pain, stiffness
- Associated with Leukemia, Lymphoma, Myelodysplastic Syndrome
- Also associated with Colon Cancer, Lung Cancer, Renal Cancer, Prostate Cancer, Breast Cancer
-
Sweet Syndrome
- Presents with tender erythematous Papules, Nodules, and Plaques on face, upper trunk, arms
- Associated with Leukemia (esp. AML), Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Multiple Myeloma
- Also associated with Breast Cancer, GI/GU/Gyn cancers, Melanoma, Testicular Cancer
VIII. Types: Hematologic
-
Eosinophilia
- Presents with respiratory symptoms (e.g. Dyspnea, Wheezing)
- Associated with Lymphoma, Leukemia (CML, ALL), Lung Cancer, Thyroid Cancer, GI cancer, Renal Cancer, Breast Cancer
- Granulocytosis
- Typically asymptomatic
- Associated with Hodgkin Lymphoma, GI/GU cancer, Lung Cancer, Breast Cancer, brain cancer
- Pure Red Cell Aplasia
-
Thrombocytosis
- Typically asymptomatic
- Associated with head and neck cancers, Glioblastoma and Lymphoma
- Also associated with GI/Gyn cancers, Lung Cancer, Breast Cancer, Renal Cell Cancer, Prostate Cancer
IX. Resources
- Paraneoplastic Syndromes (StatPearls)