etoposide

Coronary Thrombosis Detected by Intravascular Ultrasound During Bleomycin, Etoposide, and Cisplatin Chemotherapy.

Omiya Jo J, Miura Mizuki M, Watanabe Yusuke Y, Kozuma Ken K

Case Report: Cholestatic liver injury during atezolizumab therapy in EGFR-mutant combined small cell lung cancer with possible underlying primary biliary cholangitis.

Zhu Yingqiong Y, Xiong Jin J, Tan Chuan C, Tan Benxu B et al.

Combined small cell lung cancer (C-SCLC) may coexist with EGFR driver mutations. For extensive-stage disease, PD-L1 inhibitor plus platinum-etoposide is first-line. Immune checkpoint inhibitor (ICI)-associated cholangiopathy is a rare immune-related adverse event hard to distinguish from pre-existing autoimmune biliary disease such as primary biliary cholangitis (PBC) when baseline serology and histology are unavailable. A 68-year-old male former smoker presented with an incidentally detected right upper lobe mass. CT-guided percutaneous biopsy showed C-SCLC with a small adenocarcinoma component, neuroendocrine marker positivity, and loss of Rb, and next-generation sequencing revealed an EGFR exon 21 L858R mutation (mutant allele frequency 60.78%). The disease was classified as extensive-stage C-SCLC. First-line etoposide, carboplatin, and atezolizumab (four cycles) achieved partial response; alkaline phosphatase rose from mildly elevated baseline (156 U/L) to 532 U/L and gamma-glutamyl transferase from 87 to 317 U/L, with mild transaminase elevation and normal total bilirubin, a cholestatic pattern (CTCAE v5.0 grade 2). AMA-M2 was positive, raising the possibility of a previously unrecognized PBC background. Imaging showed no biliary dilatation, steatosis, or advanced fibrosis, but magnetic resonance cholangiopancreatography, liver biopsy, and pre-treatment autoantibody testing were not performed. Atezolizumab was stopped and ursodeoxycholic acid continued without high-dose corticosteroids. The cholestatic enzymes fell thereafter, but neither an underlying PBC nor a contribution from superimposed ICI-related biliary injury could be established. Consolidative thoracic radiotherapy and concurrent maintenance with furmonertinib and oral etoposide followed. At the last follow-up on July 28, 2026, partial response was maintained. This patient with EGFR-mutant C-SCLC was managed with SCLC-directed chemo-immunotherapy then maintenance with EGFR tyrosine kinase inhibitor after cholestatic liver injury. AMA-M2 positivity with pre-existing cholestatic abnormalities raises the possibility of an underlying PBC, but without pre-treatment serology, magnetic resonance cholangiopancreatography, or liver biopsy, neither a definite PBC background nor a definite ICI-related cholangiopathy could be established. Cholestatic liver injury during immunotherapy warrants evaluation for autoimmune biliary disease and drug-related biliary injury.

Cervical lymph node metastasis of neuroendocrine carcinoma of unknown primary origin: a rare case report and review of the literature.

Methnani Alia A, Jeridi Lina L, Amri Ameni A, Houcine Yoldez Y et al.

Cervical lymph node metastases from a neuroendocrine carcinoma (NEC) of unknown primary origin represent an exceptionally rare clinical entity, accounting for only 3%-5% of all carcinomas of unknown primary origin. Due to their aggressive biological behavior and the absence of standardized clinical guidelines, they pose significant diagnostic and therapeutic dilemmas. A 28-year-old male with unremarkable medical, family, and social histories presented with a rapidly growing, painless, right-sided neck swelling of 8 months' duration. Fine-needle aspiration cytology was inconclusive. A diagnostic adenectomy suggested a poorly differentiated neuroendocrine neoplasm. Extensive whole-body imaging, including a CT scan, an OctreoScan, and subsequent upper and lower gastrointestinal endoscopies, failed to reveal a primary source. The patient underwent a right-sided radical neck dissection due to extensive local infiltration, followed by adjuvant chemotherapy consisting of cisplatin and etoposide. At the 12-month follow-up, the patient remains in complete clinical and radiological remission. High-grade (grade III) cervical NECs require systematic exclusion of primary tumors, particularly from the bronchopulmonary tract, gastrointestinal tract, and thyroid gland. Immunohistochemical profiling is paramount; our case demonstrated positivity for synaptophysin, chromogranin, and CD56, with a Ki-67 index of 40%. Management must be aggressive and multidisciplinary, combining radical surgical clearance with platinum-based systemic chemotherapy to optimize locoregional control. Cervical high-grade NEC of unknown primary origin requires an exhaustive diagnostic workup and immunohistochemical evaluation. Early management via radical surgical resection and adjuvant systemic chemotherapy offers favorable locoregional control and survival outcomes.

Neurological syndrome with CSF anti-Hu positivity during serplulimab therapy in extensive-stage small-cell lung cancer: a case report.

Wang Linjing L, Zhao Yanan Y, Fan Bo B, Sang Shang S et al.

Immune checkpoint inhibitors (ICIs) have improved outcomes in extensive-stage small-cell lung cancer (ES-SCLC), but neurological immune-related adverse events (n-irAEs) can be severe and disabling. Small-cell lung cancer (SCLC) is also strongly associated with anti-Hu-associated paraneoplastic neurological syndromes (PNSs). Neurological syndromes emerging or worsening after ICI exposure may therefore represent post-ICI PNS, in which paraneoplastic autoimmunity and ICI-related neurotoxicity overlap clinically. A 52-year-old woman with stage IV ES-SCLC received four cycles of serplulimab plus etoposide and carboplatin, followed by five cycles of serplulimab maintenance. During maintenance therapy, she developed anorexia, weight loss, and alternating constipation and diarrhea, followed by progressive memory impairment, somnolence, cognitive dysfunction, and gait instability. Cerebrospinal fluid (CSF) examination showed mild mononuclear pleocytosis, and CSF anti-Hu antibody was detected by a cell-based assay at a titer of 1:100; no residual specimen was available for independent confirmatory testing. Brain magnetic resonance imaging (MRI) demonstrated newly developed bilateral paramedian thalamic abnormalities, whereas diffusion-weighted imaging and apparent diffusion coefficient mapping showed no evidence of acute cerebral infarction. The neurological presentation was classified as an intermediate-risk phenotype under the 2021 PNS-Care criteria. If the reported CSF anti-Hu result is accepted, the recalculated PNS-Care score would be 9, corresponding to the definite PNS category, although interpretation is limited by the absence of orthogonal antibody confirmation. Serplulimab was permanently discontinued, and corticosteroids plus intravenous immunoglobulin (IVIG), followed by individualized IVIG maintenance, resulted in substantial but incomplete neurological recovery. MoCA, MMSE, and mRS improved from 11/30, 12/30, and 3 to 24/30, 22/30, and 2, respectively, although residual cognitive impairment persisted. Separately, a complete response was first documented on July 20, 2021, and radiological CR remained confirmed through May 2023, with no subsequently documented clinical tumor progression before death in January 2025. In 2024, intestinal pseudo-obstruction required segmental colectomy, and histopathology demonstrated lymphocytic inflammation surrounding the myenteric plexus. This case illustrates the diagnostic overlap between paraneoplastic neurological autoimmunity and ICI-related neurological toxicity in a patient with CSF anti-Hu positivity. The later gastrointestinal episode raised the possibility of enteric nervous system involvement, but its etiology remained uncertain.