Paraneoplastic neurologic syndromes in lung cancer

Introduction Paraneoplastic neurologic syndromes (PNS) arise out of misguided autoimmune reactions against neoplastic antigens that are ectopically expressed by cells of the nervous system, neuromuscular junction or muscle. We aimed to provide a descriptive overview of certain clinico-pathologic and radiologic patterns, with which PNS in thoracic malignancies are associated.

Methods We systematically searched for patients with PNS and lung cancer at the University Hospital of Leipzig and the Regional Cancer Registry of Saxony, Germany, between 2001 and 2018. We collected comprehensive data on laboratory, histologic, neurologic, radiologic, nuclear medical, pulmonary and oncologic characteristics.

Results Out of 7,120 lung cancer patients, we identified nine with PNS (0.13 %). Of these, 67 % (6/9) were diagnosed with small cell lung cancer (SCLC), of which 67 % (4/6) exclusively presented with thoracic lymph node enlargement, without any evidence of a primary tumor. In addition, we found six PNS patients due to extrathoracic malignancies. The most prevalent autoantibodies found in PNS patients due to lung cancer were directed against Hu and voltage-gated calcium channels (VGCC), which were present in three SCLC patients, respectively. The median time between the establishment of PNS and lung cancer diagnosis were 0.5 months. Among PNS, limbic encephalitis was diagnosed in 44 % (4/9) of lung cancer patients. Quality of neurologic symptoms varied along with the presence of paraneoplastic autoantibodies, brain imaging characteristics (MRI, PET/CT) and cerebrospinal fluid pleocytosis: Motoric impairment occured in 67 % (6/9), epileptic seizures in 44 % (4/9), and both altered mental status and dizziness in 33 % (3/9). Survival differed considerably (range: 1 to 106 months). Notably, three SCLC patients presented with concomitant autoantibodies against Hu and VGCC, Hu and CV2 as well as striated muscle antigen and VGCC, while they survived 16, 26 and 106 months, respectively.

Conclusions SCLC was the predominant thoracic malignancy associated with PNS, while PNS in lung cancer appeared to be a rarity. SCLC and PNS almost exclusively presented with thoracic lymph node enlargement. Symptoms’ severity did not correlate with tumor stage. Clinical presentation suggestive of PNS should warrant a reasonable work-up for malignancy.