Discussion:
Paraneoplastic syndromes are rare in ACC, with occasional reports of hypoglycaemia(3), Cushing syndrome and polycythaemia(4). To the best of our knowledge, paraneoplastic neurologic syndromes (PNS) has never been reported in ACC. Malignancies usually reported with PNS include lung cancers, breast cancer, teratomas, lymphomas, neuroendocrine tumours and malignant thymomas. Paraneoplastic encephalitis is one of the PNS that is usually associated with tumors of neuroendocrine origin and has a debilitating course(5). Though the exact mechanism of immune-tolerance breakdown that leads to paraneoplastic encephalitis is not known, cross reaction between tumor antigen and neural antigens is the most plausible explanation(2). Interestingly ACC despite not being of direct neuroendocrine origin, is positive for neuroendocrine markers like synaptophysin and NSE(6). This raises the possibility that some unknown neuroendocrine antigens could also be expressed over the ACC cells, that cross-reacts with neural antigens leading to autoimmune encephalitis.
For diagnostic certainty of PNS, updated PNS-Cares score was proposed in 2021 (Table-1), with the known limitation that it will be false negative if the cross-reactant antigen is a novel one(7). The index patient will be “possible PNS” as per the score, but it is fairly possible that the clinical syndrome in him could be due to some novel antigen not detected by the current antibody panel.
In addition to CSF auto-antibody panel, MRI is an important modality to diagnose autoimmune encephalitis, but findings can be normal or non-specific in a sizable number of cases(8). Multiple studies have reported increased sensitivity of FDG-PET over MRI in assessment of autoimmune encephalitis (9) (10) (11). As paraneoplastic encephalitis is a form of autoimmune encephalitis the patterns of involvement in imaging is often similar. Common patterns reported in FDG-PET are mesial temporal hypermetabolism, bilateral occipital lobes hypometabolism with hypermetabolism of the frontal-temporal lobe, and basal ganglia (11) (12). Though mesial temporal hypermetabolism is the most common pattern in PET, index patient had hypermetabolism of the frontal lobe and basal ganglia with nonspecific findings on MRI of same time point.
First-line therapy of paraneoplastic encephalitis begin with high-dose methylprednisolone, IVIG and plasmapheresis given individually or in combination(13). Cases refractory to initial therapy are treated with, second-line drugs like cyclophosphamide and/or rituximab(14). To conclude, paraneoplastic encephalitis should be kept as a rare differential of an unexplained encephalitis in a case of adrenocortical carcinoma. Exploration of the inciting antibody will give more information on the exact antigen and the pathogenesis of this clinically interesting process.
Conflict of Interest statement: The authors declare no conflict of interest.
Acknowledgement: We sincerely acknowledge the family of the patient for giving us the consent to publish the case
Funding: None