Paraneoplastic neurological syndrome
associated with a pulmonary
adenocarcinoma: a case report
1
2
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2
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3
Chaves M , Abido FC , Verardino GC , Pinheiro C , Lopes-Pontes E , Fainstein L , Carneiro SC
1,4
1. Sector of Dermatology-HUPE/UERJ and Post-Graduation Course, School of Medical Sciences, Universidade do Estado do Rio de Janeiro,Brazil
2. Department of Internal Medicine 9th Infirmary - Santa Casa da Misericórdia do Rio de Janeiro General Hospital
3. Sector of Thoracic Surgery - Bonsucesso General Hospital-Ministry of Health, Brazil
4. Sector of Dermatology-HUCFF/UFRJ and Post-Graduation Course, School of Medicine, Universidade Federal do Rio de Janeiro, Brazil
Introduction
Case Report
Paraneoplastic neurological syndromes (PNS) can be defined as remote effects
of cancer that are not caused by the tumor and its metastasis, or by infection,
ischemia or metabolic disruptions. PNS are rare, affecting less than 1/10,000
patients with cancer. In most patients, the neurological disorder develops before
the cancer becomes clinically. PNS are caused by autoimmune processes
triggered by cancer and directed against antigens common to both cancer and
the nervous system, designated as onconeural antigens. Due to their high
specificity (> 90%), the best way to diagnose a neurological disorder as
paraneoplastic is to identify one of the well-characterized anti-onconeural
protein antibodies in the patient's serum. In addition, as these antibodies are
associated with a restricted range of cancers, they can guide the search for the
underlying tumor at a stage when it is frequently not clinically overt. This is a
critical point as, to date, the best way to stabilize PNS is to treat the cancer as
soon as possible.
A 79-year-old male was admitted to this hospital because of a history of
dysesthesia involving both legs, which onset was subacute and the clinical
course, progressive. The patient described the pain as a uncomfortable
sensation of burning induced by tactile stimuli. Approximately 1-year before the
admission, the onset of intermitent cough, occasionally productive of whitish
mucus, associated with a non-quantified weight-loss was related. After
excluding primary neurological diseases, a thoracic CT scan showed a spiciform lung mass, in the left lower lobe (Figure 1). The patient was submitted to a
lobectomy and the histopathology of the lung mass revealed an adenocarcinoma
(Figure 2). Soon after the neurological symptoms have progressively improved.
Most frequently paraneoplastic neurological syndromes
and associated antibodies
Paraneoplastic
neurological
syndromes
Discussion
Although capable of producing diverse clinical presentations, most often the
remote effect of cancer takes the form of a predominantly distal, symmetrical
sensory neuropathy. All these symptoms may occur months or even years before
a malignant tumor is found and the tumor is most often lung cancer. Most or all
PNC are immune-mediated and the best way to diagnose them is to identify one of
the anti-onconeural antibodies in the patient's serum. Each of this antibodies is
associated with a narrow spectrum of clinical syndromes and a restrict subgroup
of cancers. ANNA-3 and anti-Hu antibody is related to lung cancer, causing
sensory neuropathy as PNS (Tab 1). In most patients, the tumor is found months
or even a few years after the development of the neurological disorder. Two
treatment approaches have been used: removal of the source of the antigen by
treating the tumor or suppression of the immune response.
Frequency of
Most frequently
paraneoplastic origin associated tumors
Subacute cerebellar
ataxia
50%
Ovary, breast
SCLC
Hodgkin's disease
Others
Opsomyoclonus
20%
Sensory neuronopathy
20%
Neuroblastoma
Breast, lung
SCLC
Limbic encephalitis
20%
SCLC
Testicular
SCLC
Encephalomyelitis
10%
SCLC Others
Retinopathy
NA
Stiff-person syndrome
Chronic gastrointestinal
pseudoobstruction
20%
NA
SCLC
Melanoma
Breast
SCLC
Most frequently associated
paraneoplastic antibodies
Yo-Ab (PCA1-Ab)
Hu-Ab (ANNA1-Ab)
CV2-Ab (CRMP5-Ab)
Tr-Ab
Ma-Ab (Ta-Ab)
Hu-Ab (ANNA1-Ab)
Ri-Ab (ANNA2-Ab)
Hu-Ab (ANNA1-Ab)
CV2-Ab (CRMP5-Ab)
Hu-Ab (ANNA1-Ab)
CV2-Ab (CRMP5-Ab)
Ma2-Ab (Ta-Ab)
Amphiphysin-Ab
Hu-Ab (ANNA1-Ab)
CV2-Ab (CRMP5-Ab)
Amphiphysin-Ab
Ma2-Ab (Ta-Ab)
Recoverin-Ab
CV2-Ab (CRMP5-Ab)
Rod-bipolar-cell-Ab
Amphiphysin-Ab
Hu-Ab (ANNA1-Ab)
CV2-Ab (CRMP5-Ab)
Adapted from Orphanet J Rare Dis 2007;2:22.
Figure 1: CT scan showed a spici-form lung mass
Figure 2: Lung mass after surgical excision
Conclusions
Although this patient had not dosed the auto-antibodies described above, his
neurological syndrome turned out to be secondary to an pulmonary
adenocarcinoma, a description almost identical to literature reports.
References
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neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135-40.
3. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet Journal of Rare Diseases 2007;2:22.
4. Linke R, Schroeder M, Helmberger T, Voltz R. Antibody-positive paraneoplastic neurologic syndromes: value of CT and PET for tumor diagnosis. Neurology 2004;63:282-6.