Paraneoplastic Syndrome

Original Editors -Brittany Chorley &Seth Chorleyfrom Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Seth Chorley, Brittany Chorley, Lucinda hampton, Admin, Kim Jackson, Priya Gulla, Elaine Lonnemann, WikiSysop, Rujuta Naik, 127.0.0.1, Vidya Acharya, Claire Knott, Wendy Walker, Mariam Hashem and Adam Vallely Farrell

Introduction

Paraneoplastic syndrome

Paraneoplastic syndromes (PNS) occur due to the systemic effect of a malignancy and occur remotely to the primary malignancy. Symptoms are brought about by cytokines, hormones or immune cross-reactivity. These syndromes can cause a manifold of symptoms and can affect numerous systems. PNS can occur concurrently with tumour diagnosis before a tumour is diagnosed and even after tumours have been resected. The symptoms typically present in the middle-aged to older population. Also, it is common in individuals with lung, ovarian, lymphatic, or breast cancer. The most common cancer associated with paraneoplastic syndrome is small-cell cancer of the lungs.

There is no cure for paraneoplastic syndromes and the treatment does not stop neurological damage.

Aetiology

PNS are largely due to two main causes:

1. Those due to tumour secretions of hormones, functionally active peptides, enzymes cytokines
2. Those due to tumours operating through auto-immune/immunological mechanisms with cross-reacting antibodies between neoplastic and normal tissues. Nb Remission of symptoms often follows resection of humoral secretory tumours but not always of tumours due to immunological mechanisms.

Types of Paraneoplastic Syndrome

The Paraneoplastic Syndromes are classified based on the organ systems involved or on the etiological groups and are as follows :

• Lambert-Eaton Myasthenic Syndrome
• Stiff-Person Syndrome
• Encephalomyelitis
• Myasthenia Gravis
• Cerebellar Degeneration
• Limbic or Brainstem Encephalitis
• Neuromyotonia
• Opsoclonus
• Sensory Neuropathy

Epidemiology

PNS occur in up to 15% of patients with cancer. Neurological manifestation in the form of neuropathies is common. Males and females are affected equally.

Clinical Presentation

PNS can affect multiple systems and have various presentations. Symptoms usually start before a tumour is found, slowly developing over a few days or weeks. Some of the more common symptoms include - Difficulty walking or swallowing; Loss of muscle tone; Loss of fine motor coordination; Slurred speech; Memory loss; Vision problems; Sleep disturbances; Dementia; Seizures; Sensory loss in the limbs; Vertigo or dizziness.

Examples are given below based on the organ system involved.

1. Paraneoplastic neurological syndromes: encephalitis (paraneoplastic rhombencephalitis, limbic encephalitis); Lambert-Eaton myasthenic syndrome; Optic neuropathy; Cerebellar degeneration.
2. Endocrine eg Cushing syndrome; Syndrome of inappropriate antidiuretic hormone secretion (SIADH); Hypercalcemia
3. Rheumatological eg Paraneoplastic polyarthritis; Polymyalgia rheumatica; Multicentric reticulohistiocytosis; Hypertrophic osteoarthropathy
4. Paraneoplastic haematologic syndromes: Good syndrome; Polycythaemia
5. Dermatological eg Acanthosis nigricans; Paraneoplastic pemphigus; Sweet syndrome; Leukocytoclastic vasculitis; Dermatomyositis
6. Renal eg Electrolyte imbalance (hypokalemia, hypo or hypernatremia, hyperphosphatemia) causing nephropathy and acid-base disturbance due to ectopic hormones produced by tumour cells such as ACTH and ADH. Nephrotic syndrome can also be one of the manifestations of paraneoplastic syndrome.
7. Miscellaneous eg Fever, cachexia, anorexia, dysgeusia

Management

Management of the patients is based on the type, severity, and location of the paraneoplastic syndrome. First, therapeutic options are to treat underlying malignancy with chemotherapy, radiation, or surgery.

• Other therapeutic options are immunosuppression with corticosteroids or other immunosuppressive drugs, intravenous immunoglobulins, plasma exchange, or plasmapheresis.

Diagnostic Tests/Lab Tests/Lab Values

First, a healthcare provider will perform a clinical exam that would include a general physical and neurological screening.

1. Neurological screening: reflexes, sensation, myotomes, balance, and coordination.
2. Laboratory tests that could be utilized to diagnose paraneoplastic syndrome include: Blood tests, Spinal tap
3. Imaging tests that could be utilized to diagnose paraneoplastic syndrome include: CT Scan; MRI; PET Scan; and PET-CT, which may enhance the detection rate of small cancers

If the physicians cannot find a malignant tumour, the syndrome may be the cause of a tumour that is too small to locate. In this instance, the physician will continue to have follow-up imaging conducted every three to six months for several years unless the cause is identified. 

Physical Therapy Management

People with paraneoplastic syndrome can have difficulty with walking, balance, coordination, muscle tone, sensory of where the body is in space, and vertigo.

• All of these symptoms the physical therapist can treat with traditional therapy.
• Precautions must be taken into account for the cancer or neoplasm that is involved.

Conclusion

The diagnosis and management of paraneoplastic syndromes is difficult.

• In most cases, there is an underlying malignancy responsible.
• Due to the numerous causes, the condition is best managed by an interprofessional team (including a pathologist, oncologist, radiologist, haematologist, nurse specialist, and internist).
• Once the cause is discovered, it needs to be treated.

The management of the patients is based on the type, severity, and location of the paraneoplastic syndrome.

• First, therapeutic options are to treat underlying malignancy with chemotherapy, radiation, or surgery.
• Other therapeutic options are immunosuppression with corticosteroids or other immunosuppressive drugs, intravenous immunoglobulins, plasma exchange, or plasmapheresis.