Paraneoplastic syndromes can commonly occur due to lung cancer, especially small cell lung cancer. Frequently paraneoplastic syndromes can precede the diagnosis of the neoplasm or present with limited stage disease. However, these syndromes can also occur at the time of recurrence or metastasis of disease. This review focuses on the epidemiology, pathogenesis, clinical features, and current management of the most common paraneoplastic syndromes encountered in patients with small cell lung cancer. Manifestations of paraneoplastic syndromes in small cell lung cancer include endocrine syndromes with secretion of excess hormones, and neurologic syndromes due to the production of antibodies causing an autoimmune condition. Recent advances have allowed for greater understanding of these syndromes and for the development of improved diagnostic as well as therapeutic tools. Awareness of paraneoplastic syndromes in small cell lung cancer can lead to an earlier diagnosis and recognition of both the condition and in some cases the disease potentially improving the overall survival and prognosis for patients. Further research examining effective methods to improve recovery from neurologic deficits in patients with a paraneoplastic neurologic illness is warranted.

• Paraneoplastic syndrome
• paraneoplastic endocrine syndromes
• paraneoplastic neurologic syndromes
• small cell lung cancer (SCLC)

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently recommended by international guidelines as first-line treatment in patients with advanced EGFR-mutant non-small-cell lung cancer. With the availability of drugs, more and more patients choose EGFR-TKI treatment. However, pharmaceutical drugs used in clinical practice have side effects, such as diarrhea, paronychia, and hepatotoxicity. Mental or conscious disturbance has never been reported before. In our clinical center, we found that several patients with advanced lung adenocarcinoma developed a mental disorder or conscious disturbance after EGFR-TKI treatment. This situation has not previously been reported. We conducted a retrospective study of patients with advanced lung adenocarcinoma treated with EGFR-TKI who showed a mental disorder or conscious disturbance. We reported five cases of lung adenocarcinoma who developed a mental disorder or conscious disturbance after treatment with EGFR-TKI. The main clinical symptoms of these patients were sluggishness, memory deterioration, cognitive disorder, and even hallucination. Brain magnetic resonance imaging showed increased ischemic foci and lacunar infarction, worse encephalatrophy, and demyelination after EGFR-TKI therapy. These psychiatric symptoms did not improve but worsened after taking antipsychotic drugs, suggesting that they were irreversible. The neuropsychiatric symptoms in EGFR-TKI treatment must be considered, and the underlying reason warrants further study.

• advanced lung adenocarcinoma
• conscious disturbance
• epidermal growth factor receptor-tyrosine kinase inhibitor
• mental disorder

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. 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. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

• Paraneoplastic syndrome
• Small cell lung cancer
• Non-small cell lung cancer
• Symptom
• Diagnosis
• Treatment
• Endocrine
• Neurologic
• Hematologic
• Trousseau’s syndrome