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