Paraneoplastic neurologic syndrome in advanced lung cancer with mixed adenocarcinoma and squamous features: a diagnostic challenge—a case report

Abstract

BACKGROUND: Paraneoplastic neurologic syndromes (PNS) are rare immune-mediated disorders that may precede the diagnosis of an underlying malignancy, including non-small cell lung cancer (NSCLC). Tumor heterogeneity in NSCLC, particularly in rare subtypes such as adenosquamous carcinoma, may result in variable histologic findings across different biopsy sites, posing significant diagnostic challenges. CASE PRESENTATION: We report a case of a 45-year-old Tanzanian male, a never-smoker, who presented with progressive neurologic symptoms, including ageusia, dystonia, paresthesia, and ataxia, without respiratory complaints. Brain Magnetic resonance imaging (MRI) demonstrated diffuse cerebral microhemorrhages, and extensive autoimmune and neuronal antibody testing was negative. He received intravenous methylprednisolone followed by an oral prednisolone taper with transient stabilization. Positron emission tomography-computed tomography (PET-CT) revealed an ill-defined FDG-avid right lower lobe lesion and vertebral metastases. Biopsy of a T10 vertebral lesion confirmed metastatic lung adenocarcinoma (TTF-1 positive), and the disease was staged as stage IV (cTxNxM1b). The patient was treated with carboplatin and pemetrexed, with partial neurologic improvement. During disease progression, repeat bronchoscopy biopsy revealed tumor cells with squamous features (p63 positive, patchy TTF-1 expression), raising the possibility of mixed histology (adenosquamous). However, histologic transformation cannot be completely excluded due to a lack of molecular analysis. His condition deteriorated rapidly, and he died from complications of advanced metastatic disease with progressive neurologic involvement. CONCLUSION: This case highlights the diagnostic challenges of antibody-negative paraneoplastic neurologic syndromes. The study underscores the important role of PET-CT in identifying occult malignancy and the role of repeat biopsy in progressive disease. Discordant histologic findings should be interpreted cautiously, as they may reflect tumor heterogeneity or possible adenosquamous carcinoma rather than true histologic evolution. Limited molecular testing, and sampling constraints remain important challenges, particularly in resource-limited settings.