Paraneoplastic disorders are a relatively rare condition where substances secreted by both benign and malignant tumours can have affects on different bodily systems often far removed from the anatomical location of the causative tumour.1
Paraneoplastic tumours can affect a wide range of systems including the endocrine, renal, haematological, gastrointestinal and, as in this case, the neurological systems and in many cases the paraneoplastic signs and symptoms can present before the initial primary tumour has been identified.2
This patient presented with a progressive neurological disorder which at the onset was felt to be paraneoplastic in origin. This led to an extensive search for a primary causative tumour, which for 3 years was negative. It was not until a mass appeared in the gluteal region that the tumour was identified and treated and the patient's condition stabilised.3
There are now internationally accepted diagnostic criteria for paraneoplastic syndromes which have been summarised in .4
This divides presentations into classical and non-classical forms.3 4
The list of classical syndromes includes encephalomyelitis, limbic encephalitis, subacute cerebellar degeneration, opsoclonus-myoclonus, stiff person syndrome, subacute sensory neuronopathy, chronic gastrointestinal pseudo-obstruction, Lambert-Eaton myasthenic syndrome and dermatomyositis.3 4
In our case the patient had cerebellar dysfunction with dysarthria, impaired coordination, nystagmus and a loss of smooth pursuit eye movements.3 5 6
Over and above this, however, he had spasticity and dystonic posturing, supporting a diagnosis of paraneoplastic cerebellar degeneration with additional dystonic features. We did not consider any definite evidence of a brain stem encephalitic process. He therefore does not fall into the classical category. The spasticity has some hallmarks of stiff person syndrome, again a classical paraneoplastic disorder, but antiglutamic acid decarboxylase (GAD) antibodies were negative. In paraneoplastic stiff person syndrome there is axial rigidity and intermittent painful spasms.3
There is a strong correlation with encephalomyelitis and autoantibodies against GAD are positive in 50–90% of cases.3
Our patient, therefore, was non-classical. Finally, the fact that there was a confirmed tumour and positive serology for the onconeural antibody anti-Hu makes the diagnosis of paraneoplastic syndrome with an associated movement disorder definite.
Figure 1 Flow chart of diagnostic evidence of paraneoplastic neurological syndromes.4
Paraneoplastic movement disorders have been widely reported in the literature, however overall they are relatively rare conditions, affecting fewer than 1/10 000 cancer patients.1
The vast majority of anti-Hu positive paraneoplastic tumours are small cell lung cancers. Extensive imaging using both CT and MRI scanning failed to show any evidence of this in our patient, however, he did have a malignant fibrous histiocytoma removed which was anti-Hu positive. To our knowledge only three similar cases have been reported in the literature. In 1992 Reinecke et al7
described a patient with a paraparesis due to a malignant fibrous histiocytoma previously known as a pleomorphic sarcoma. There was no evidence of metastases and the presumption was that the paraparesis was paraneoplastic in nature.7
In 2004 Zámecník et al8
reported a the case of a 77-year-old woman with opsoclonus-myoclonus. Her symptoms deteriorated rapidly and she entered a coma and died several months later.8
At autopsy a pleomorphic sarcoma in the retroperitoneum was found with no evidence of metastatic spread.8
Microscopic examination of the cerebellum showed atrophy of the granular layer accompanied by severe patchy loss of Purkinje cells, and neuronal loss in the cerebellar nuclei with distinct peridental demyelination and astrogliosis.8
Unfortunately, the investigating pathologist was unable to confirm the presence of any known onconeural antibodies in the CSF or serum, but the autoimmune nature of the disease was confirmed by the presence of oligoclonal bands in CSF and the immunohistochemical detection of immunoglobulin G deposits on membranes of Purkinje cells, neurons of cerebellar granular layer and in the cerebellar nuclei.8
Also in 2004 Corato et al9
reported a case of paraneoplastic brainstem encephalitis in a patient with a malignant fibrous histiocytoma with atypical antineuronal antibodies. In this case, a 74-year-old man presented with a 2-month history of myoclonus affecting the upper extremities and with increased tendon reflexes on the right.9
An abdominal CT revealed a retroperitoneal mass with multiple hepatic and lymphatic formations with biopsies of the lateral aortic lymph node confirming the presence of a malignant fibrous histiocytoma which was shown to be producing atypical antineuronal antibodies by a combination of immunohistochemical and western blot analysis.9
In conclusion, this is the first case of a paraneoplastic syndrome due to a malignant fibrous histiocytoma with confirmed pathological evidence and a positive onconeural antibody serology for anti-Hu. It highlights the importance of looking for unusual and unexpected primary tumours in paraneoplastic syndrome. The time-scale from initial presentation until a confirmed diagnosis was over 3 years. Clinicians should be aware of this and if they suspect paraneoplastic syndrome, screening using standard imaging techniques may be required. The identification of the primary tumour is essential as the best way to treat paraneoplastic disorders is to remove the source of the problem by excising the causative tumour.1
- While the majority of paraneoplastic tumours are small cell lung cancers, other less common tumours such as malignant fibrous histiocytomas should be considered.
- The time course from initial presentation to the identification of the primary causative tumour can be quite long, which can present a challenge in terms of patient management.
- Identification and removal of the causative tumour is essential as it is the only proven method of arresting paraneoplastic neurodegeneration.
- Paraneoplastic disorders can lead to severe physical disability often with preserved higher cortical functions, meaning that a holistic approach to patient care is necessary, with adequate home support and a community care package being essential.
- When screening for possible underlying neoplasia, one needs to consider sites other than simply the thorax, abdomen and pelvis.