Probable Early‐Stage Anti‐Amphiphysin–Related Paraneoplastic Cerebellar Degeneration Associated With Undiagnosed Lung Squamous Cell Carcinoma: An Autopsy Case and Literature Review

ABSTRACT

We report an autopsy case of a man in his early 80s who was found deceased, submerged in a bathtub at home. He had no history of regular medical care or smoking. One month before death, he experienced vomiting, malaise, and reduced appetite; however, due to limited clinical information, it was unclear whether he exhibited symptoms suggestive of cerebellar dysfunction. The autopsy showed fibrinous pericarditis resulted from left atrial metastasis from lung squamous cell carcinoma (LSCC) originating in the left lower lobe, which was determined to be the cause of death. Neuropathological examination exhibited no gross abnormalities in the cerebrum or brainstem; however, mild atrophy of the cerebellar vermis, extending from the lobulus centralis to the culmen, was observed. Histologically, focal loss of Purkinje cells accompanied by gliosis was noted, predominantly affecting the superficial layers of the superior vermis and simple lobule, while other cerebellar regions were largely preserved. Mild‐to‐moderate CD8‐positive T‐lymphocyte‐predominant perivascular infiltration was present in the cerebellar white matter and leptomeninges, whereas no significant inflammation was detected in the cerebrum or brainstem. No abnormal protein aggregates (phosphorylated tau, α‐synuclein, polyglutamine, or p62) were identified in the cerebellum. Postmortem serum testing revealed the presence of anti‐amphiphysin antibodies. Collectively, although the clinical manifestations were unclear and a definitive diagnosis remains difficult, these findings support a pathological diagnosis of paraneoplastic cerebellar degeneration (PCD) associated with previously undiagnosed LSCC. Although autopsy data are limited, the preferential involvement of the superficial superior vermis may represent an early‐stage pattern of PCD. This case highlights the importance of autopsy with detailed neuropathological examination in patients with malignancy, even when cerebellar symptoms are mild or absent and imaging or gross abnormalities are lacking. To our knowledge, this is the first reported autopsy case of anti‐amphiphysin antibody–associated PCD in association with LSCC.