Paraneoplastic Syndromes in Children with Hodgkin Lymphoma

Abstract

Paraneoplastic syndromes (PNS) refer to a phenomenon whereby certain malignancies manifest as symptoms not directly related to the tumor itself. PNS has been described in association with Hodgkin lymphoma (HL) in adults and children and may affect a number of organ systems. The pathophysiology is variable and in many cases is not well understood. Specific paraneoplastic antibodies have been isolated in some syndromes, though are not required for the diagnosis. The two best described for HL are the anti-Tr and anti-mGluR5 antibodies identified in some cases of limbic encephalitis and cerebellar degeneration respectively. A high index of suspicion for underlying malignancy is necessary when recognizing these clinical syndromes to avoid a diagnostic delay. Successful treatment of the HL often reverses the manifestations of PNS although organ function at diagnosis may limit therapeutic options. Some patients suffer devastating complications of their PNS.

Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease

“…However, the underlying molecular mechanisms leading to both anti-mGluR5 encephalitis and classical Hodgkin lymphoma were poorly understood. This study contributes to the understanding and may have clinical implications: Detection of paraneoplastic neurological disease preceding classical Hodgkin's lymphoma can be challenging [21]. However, early diagnosis of an Ophelia syndrome is paramount both for the treatment of anti-mGluR5 encephalitis and the earliest possible recognition of a subsequent classical Hodgkin lymphoma.…”

“…One of the latter was first described as "Ophelia syndrome" by Ian Carr (1982) [14,[18][19][20]. It primarily and exceedingly affects children and young adults, who develop severe psychosis with extensive hallucinations, behavioral changes, cognitive dysfunction, seizures, movement disorders, and sleep disturbance [10,18,21,22]. Lancaster et al (2011) described pathogenic autoantibodies in Ophelia syndrome that target the metabotropic glutamate receptor 5 (mGluR5) and cause a decrease in mGluR5 density on neurons [19].…”