Paraneoplastic Syndrome

See Also

Cancer Complication

Epidemiology

Paraneoplastic Syndromes affect 1 to 8% of cancer patients

Mechanism

Neoplasms secrete biologically active substances (e.g. Hormones, peptides, Cytokines)
1. May have direct effects (e.g. endocrine) or stimulate an immune-mediated response
Released substances may affect multiple organ systems
1. Endocrine
2. Neurologic
3. Dermatologic
4. Rheumatologic
5. Hematologic
Associated neoplasms (most common)
1. Small Cell Lung Cancer
2. Breast Cancer
3. Gynecologic neoplasms (e.g. Ovarian Neoplasms)
4. Hematologic malignancies (e.g. Leukemia)

Precautions

Early cause identification may significantly impact morbidity and mortality
1. Reduce high symptom burden associated with Paraneoplastic Syndrome
2. Counter Electrolyte and hormonal effects
3. Early diagnosis of associated malignancy (paraneoplastic symptoms are often the cancer presentation)

Types
Endocrine

Syndrome Inappropriate ADH Secretion (SIADH)
1. Presents with symptoms related to isovolemic hyposmolar Hyponatremia
2. Multiple associated cancers
Hypercalcemia of Malignancy
1. Presents with Altered Mental Status, Ataxia, hypertonia, Vomiting, Renal Failure
2. Multiple associated cancers
Cushing Syndrome
1. Presents with Muscle Weakness, Peripheral Edema, weight gain, Hypertension
2. Associated with Lung Cancer (50-60% of cases)
3. Also associated with thymoma, Medullary Thyroid Cancer, Pancreatic Cancer, adrenal cancer, Ovarian Cancer
Hypoglycemia
1. Associated with Lung Cancer (including Mesothelioma), Sarcomas and gastrointestinal tumors
2. IGF2 or Insulin secretion by Non-Islet cell tumors (NICTH)
3. More commonly occurs with primary islet cell tumors (Insulinomas)

Types
Neurologic

Limbic Encephalitis
1. Presents with mood changes, Hallucinations, Memory Loss and Seizures
2. Various associated antibodies
  1. Anti-Hu (Small Cell Lung Cancer)
  2. Anti-Ma2 (Testicular Cancer - germ cell)
  3. Anti-CRMP5
  4. Anti-NMDA (see NMDA Encephalitis, associated with ovarian malignancies)
3. Associated with Small Cell Lung Cancer (40-50%), testicular germ cell cancer (20%) or Breast Cancer (8%)
4. Other associated cancers include thymoma, Teratoma, Hodgkin Lymphoma
Paraneoplastic Cerebellar Degeneration
1. Presents with Ataxia, Diplopia, Dysphagia and Dysarthria
2. Associated with Small Cell Lung Cancer, gynecologic cancer, Hodgkin Lymphoma, Breast Cancer
Lambert-Eaton Myasthenic Syndrome (LEMS)
1. Presents with proximal leg weakness, diaphragmatic weakness and bulbar symptoms (speach, swallow)
2. Associated with Small Cell Lung Cancer, Prostate Cancer, Cervical Cancer, Lymphomas
Myasthenia Gravis
1. Presents with presents with ocular, bulbar and limb fatigable weakness and diaphragmatic weakness
2. Associated with thymoma (15% of Myasthenia Gravis patients)
Autonomic Neuropathy
1. Presents with Orthostatic Hypotension, gastrointestinal symptoms
2. Associated with Small Cell Lung Cancers and thymomas
Peripheral Sensory Neuropathy
1. Presents with initial arm>leg Paresthesias, followed by Ataxia
2. Associated with Small Cell Lung Cancer (70-80% of cases)
3. Also associated with Breast Cancer, Ovarian Cancer, Sarcomas, Hodgkin Lymphoma

Types
Dermatologic and Rheumatologic

Acanthosis Nigricans
1. Associated with abdominal adenocarcinomas (esp. Gastric Cancer)
Dermatomyositis
1. Presents with heliotrope rash, Gottron Papules, and erythematous rash face/neck/trunk
2. Associated with Ovarian Cancer, Breast Cancer, Prostate Cancer, Lung Cancer, Colorectal Cancer
3. Also associated with nasopharyngeal cancers and Non-Hodgkin Lymphoma
Erythroderma
1. Presents with a diffuse erythematous, exfoliating rash
2. Associated with CLL, Cutaneous T-Cell Lymphoma, myeloproliferative disorders and GI cancers
Hypertrophic Osteoarthropathy
1. Presents with Digital Clubbing, bone thickening of wrists and ankles, large joint effusions
2. Associated with intrathoracic tumors, lung metastases, Rhabdomyosarcoma, nasopharyngeal cancers
Leukocytoclastic Vasculitis
1. Presents with digital erosions and Cyanosis, leg palpable Purpura, Renal Insufficiency, Peripheral Neuropathy
2. Associated with Leukemia, Lymphoma, Myelodysplastic Syndrome, Multiple Myeloma
3. Also associated with Colon Cancer, Lung Cancer, urologic cancer and Rhabdomyosarcoma
Paraneoplastic Pemphigus (PNP)
1. Presents with severe mucosal erosions and skin bullae/erosions (esp. on palms/soles)
2. Associated with Non-Hodkin Lymphoma, CLL, Leukemia, thymoma, Castleman disease, Sarcoma
Polymyalgia Rheumatica
1. Presents with proximal Muscle pain, stiffness
2. Associated with Leukemia, Lymphoma, Myelodysplastic Syndrome
3. Also associated with Colon Cancer, Lung Cancer, Renal Cancer, Prostate Cancer, Breast Cancer
Sweet Syndrome
1. Presents with tender erythematous Papules, Nodules, and Plaques on face, upper trunk, arms
2. Associated with Leukemia (esp. AML), Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Multiple Myeloma
3. Also associated with Breast Cancer, GI/GU/Gyn cancers, Melanoma, Testicular Cancer

Types
Hematologic

Eosinophilia
1. Presents with respiratory symptoms (e.g. Dyspnea, Wheezing)
2. Associated with Lymphoma, Leukemia (CML, ALL), Lung Cancer, Thyroid Cancer, GI cancer, Renal Cancer, Breast Cancer
Granulocytosis
1. Typically asymptomatic
2. Associated with Hodgkin Lymphoma, GI/GU cancer, Lung Cancer, Breast Cancer, brain cancer
Pure Red Cell Aplasia
1. Presents with Dyspnea, pallor, Syncope, Fatigue
2. Associated with thymoma (most common), Leukemia, Lymphoma, Myelodysplastic Syndrome
Thrombocytosis
1. Typically asymptomatic
2. Associated with head and neck cancers, Glioblastoma and Lymphoma
3. Also associated with GI/Gyn cancers, Lung Cancer, Breast Cancer, Renal Cell Cancer, Prostate Cancer

Resources

Paraneoplastic Syndromes (StatPearls)
1. https://www.ncbi.nlm.nih.gov/books/NBK507890/

References