From the Guidelines
Paraneoplastic syndromes are a group of rare disorders that are triggered by an abnormal immune response to a cancer, and early recognition is crucial as they often precede cancer diagnosis by months. The most recent and highest quality study on this topic is from 2021, which highlights the importance of considering paraneoplastic syndromes in patients with small cell lung cancer (SCLC) 1. Some notable examples of paraneoplastic syndromes include:
- Lambert-Eaton myasthenic syndrome (LEMS), which is characterized by proximal leg weakness caused by antibodies directed against the voltage-gated calcium channels, and is often associated with SCLC 2, 1
- Paraneoplastic encephalomyelitis and sensory neuropathy, which are caused by the production of an antibody (antiHu) that cross-reacts with both small cell carcinoma antigens and human neuronal RNA-binding proteins, resulting in multiple neurologic deficits 1
- Anti-Yo syndrome, which is associated with ovarian and breast cancers, and is characterized by brain stem abnormalities and cerebellar degeneration 3 Treatment of paraneoplastic syndromes typically involves addressing both the underlying malignancy and immunosuppression to manage the autoimmune component, and may include medications such as 3,4-diaminopyridine, prednisone, and intravenous immunoglobulin (IVIG), as well as chemotherapy and tumor resection 2, 3, 1. It is essential to consider obtaining a comprehensive paraneoplastic antibody panel if a neurologic paraneoplastic syndrome is suspected, as recommended by the NCCN SCLC Panel 1. In terms of specific case studies, a notable example is a 67-year-old male who presented with progressive muscle weakness and was diagnosed with LEMS, later found to have SCLC, and was treated with 3,4-diaminopyridine, prednisone, and concurrent chemotherapy with cisplatin and etoposide. Another example is a 58-year-old female with anti-NMDA receptor encephalitis, ultimately diagnosed with ovarian teratoma, who was treated with tumor resection, followed by IVIG and rituximab. A third example is a 72-year-old with dermatomyositis, later diagnosed with colorectal adenocarcinoma, who was treated with surgical resection of the tumor and prednisone. These cases highlight the importance of early recognition and treatment of paraneoplastic syndromes to improve patient outcomes.
From the Research
Paraneoplastic Syndromes
- Paraneoplastic syndromes are conditions that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases 4
- These syndromes can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau's syndrome) 4
Types of Paraneoplastic Syndromes
- Humoral hypercalcemia of malignancy in squamous cell carcinoma 4
- Syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer 4
- Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors 5
- Cachexia, hypercalcemia, and hyponatremia are common paraneoplastic syndromes associated with lung cancer 6
Diagnosis and Treatment
- Diagnosing paraneoplastic syndromes is challenging, requiring exclusion of other differential diagnoses 5
- New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence 5
- Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement 4, 6
- Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins, with second-line immunosuppressants like rituximab or cyclophosphamide used if initial treatments fail 5