An interesting and rare association of paraneoplastic myelopathy with Hurthle cell neoplasm
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.237028
Source of Support: None, Conflict of Interest: None
Paraneoplastic neurological syndromes can be the presenting feature or may antedate the diagnosis of cancer. Antibodies can be against the cell surface or synaptic proteins. Myelopathy as a paraneoplastic manifestation is rarely encountered in clinical practice. It is most commonly seen in the setting of lung and breast cancers. Aquaporin-4 has recently been found as a potential triggering antigen for paraneoplastic neurological syndromes. Various tumors including breast, lung, and esophageal cancers are reported in the literature in the context of neuromyelitis optica. We report an interesting and a rare association of a patient with rapidly progressive myelopathy with negative aquaporin-4 antibodies who was found to have Hurthle cell adenoma of the thyroid gland.
A 55-year old gentleman presented with fever followed by paraparesis. Fever was of moderate grade (102°F) and lasted for approximately 5 days. On the third day of his illness, he developed progressive weakness of the left lower limb followed by weakness of the right lower limb and inability to stand on his own. This was accompanied by a decreased perception of hot and cold sensation below the umbilicus along with an inability to pass urine. There was no history of headache, seizures, or altered sensorium. On examination, higher mental functions and cranial nerves were normal. Fundus examination did not reveal any disc edema or pallor. Power was 5/5 in the upper limbs. Tone was decreased in both the lower limbs. Hip flexion and extension were 2/5 on the right side and 1/5 on the left side; hip adduction and abduction were 4/5 bilaterally. Knee flexion, extension, and ankle dorsiflexion were 4+/5 on the right side and 4/5 on the left side. Plantar flexion was 5/5 on both sides. Knee and ankle reflexes were absent bilaterally and the reflexes were 2+ in the upper limbs. Plantar response was bilaterally extensor. Sensory examination revealed a sensory level at T10 with touch and pain sensation decreased below the umbilicus. Vibration and joint position sensation were absent at bilateral great toes.
Clinically, a possibility of myelopathy at T10 level was considered. However, MRI of the dorsal spine did not reveal any abnormality. During his hospital stay, weakness in the lower limbs increased and the patient became paraplegic. MRI of the brain and whole spine were repeated and were found to be normal [Figure 1]. He was further worked up on the lines of MR negative myelopathy.
His routine investigations were well within normal limits except for mildly raised transaminase values. Cerebrospinal fluid (CSF) examination done at presentation showed a total leucocytic count (TLC) of 320 cells/mm 3, mainly composed of lymphocytes, a protein level of 74 mg/dl, and a sugar level of 62 mg/dl, with the random blood sugar being 96 mg/dl. The CSF was negative for malignant cytology. This test was repeated thrice. CSF venereal disease research laboratory (VDRL) test was negative. CSF repeated 10 days later showed no white blood cells, the protein level being 54 mg/dl, and the sugar level being 50 mg/dl. Nerve conduction studies showed reduced tibial and peroneal compound muscle action potential (CMAP) bilaterally with normal distal latency and conduction velocity and absent sural sensory nerve action potentials (SNAPs).
He was started on methylprednisolone pulse for 5 days with no significant response. The work-up for other causes of noncompressive myelopathy including viral markers, antinuclear antibody (ANA), anti-cholinesterase (ACE) levels, vitamin B12, VDRL test, and serum protein electrophoresis revealed no abnormality. Test for aquaporin-4 antibodies, to rule out neuromyelitis optica, was negative. He was detected to be hypothyroid in the hospital (thyroid stimulating hormone [TSH], 30.28 μIU/ml, thyroxine [T4], 2.44 μg/dl, and T3, 0.629 ng/ml). A possibility of paraneoplastic myelopathy was also considered. Contrast enhanced computed tomographic scan (CECT) chest and abdomen did not reveal any abnormality. Whole body fludeoxyglucose positron emission tomography (FDG-PET) scan showed a FDG avid lesion (maximum standardised uptake value [SUV max], 24.2) in the right lobe of thyroid gland of size 1.5 × 1.8 cm. Ultrasound-guided fine needle aspiration cytology (FNAC) of the lesion was suggestive of Hurthle cell neoplasm. Paraneoplastic antibodies were found to be negative in the serum.
The option of intravenous immunoglobulin/plasma exchange/cyclophosphamide was discussed with the patient but he opted for the monthly pulses of cyclophosphamide because of affordability issues. Ear nose throat (ENT) consultation was taken and total thyroidectomy was done 3 weeks after the presentation. Histopathological examination of the thyroid gland revealed Hurthle cell adenoma [Figure 2]. Three months after the surgery and immunomodulation, he showed a significant improvement. His power in the lower limbs improved to grade 4/5. However, he still needed a stick for support to walk because of sensory ataxia.
MRI can be normal in approximately 20% of cases clinically diagnosed as having a myelopathy,, which means that it is not uncommon for a physician to encounter a normal MRI in a patient who suffers from myelopathy. Causes for MRI negative myelopathy can be many, ranging from connective tissue disorders to sarcoidosis, to toxins and paraneoplastic syndromes. Our index case probably fits into a possible paraneoplastic syndrome, according to the diagnostic criteria because of negative onconeural antibodies.
Spinal cord involvement in the paraneoplastic syndromes can be in the form of acute necrotizing myelopathy, stiff person syndrome, or as motor neuron disease. Most common tumors associated with it are small cell lung cancer; breast, ovarian, and gastrointestinal cancers; or, lymphomas.
Hurthle cell neoplasm is a rare thyroid cancer presumed to be of follicular cell origin. It accounts for 3–7% of differentiated thyroid carcinomas. The mean age of presentation in a study of 28 patients was 49.3 years. Most patients were euthyroid in this study but our patient was hypothyroid. Paraneoplastic syndromes associated with Hurthle cell neoplasm are also rare. We could find only a few case reports referring to the paraneoplastic manifestations of Hurthle cell neoplasm., In the first study, a 53-year old female patient, diagnosed as having a neuromyelitis optica (NMO) spectrum disorder clinically, was aquaporin-4 positive, and was found to have Hurthle cell carcinoma of thyroid; and, in another study, a 67-year old lady presented with mononeuritis multiplex and was found to have diffuse toxic goitre and Hurthle cell carcinoma., The pathogenesis may be due to some hitherto unidentified antibody because of the rarity of Hurthle cell neoplasm presenting as paraneoplastic syndrome. There are only a few reported cases of paraneoplastic myelopathy associated with thyroid cancer., Flanagan et al., reported 31 patients of paraneoplastic myelopathy; only two had thyroid cancer (thyroid papillary carcinoma and thyroid chondrosarcoma). Classically, contrast-enhancing tract-specific MRI signal abnormalities in the spinal cord, which are longitudinally extensive, are described in paraneoplastic myelopathy; however, MRI can be normal in 50% of the cases. Treatment consists of managing the primary malignancy and/or immunomodulation, although there are no randomized controlled trials to support these modlities of management.
To conclude, we report an uncommon association of possible paraneoplastic myelopathy with a rare thyroid neoplasm. This report emphasizes that, for a patient presenting with MRI-negative myelopathy, a work-up to determine the presence of a tumor should always be done.
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[Figure 1], [Figure 2]