A rare case of long-term paraesthesia diagnosed as a paraneoplastic syndrome by anti-SOX1 antibody determination

Abstract

Paraneoplastic syndromes (PS) are a rare presentation of cancer, most commonly associated with small cell lung cancer (SCLC), breast cancer and haematologic malignancies. The diagnosis of PS is challenging because it could affect multiple organ systems and it may present before the tumour is visible by imaging. We report a malignant tumour diagnosed in a male patient who referred long-term paraesthesia and proximal muscle strength loss. After ruling out common causes of polyneuropathy, the anti-SOX1 antibody gave light to the diagnosis. A pulmonary opacity in the upper right lobe was observed in the chest X-ray and a pulmonary tumour was later confirmed by CT scan. The biopsy of the cervical lymphadenopathy determined an SCLC, which caused a PS called Lambert-Eaton myasthenic syndrome (LEMS). Our case raises awareness of a rare PS presentation, which can be diagnosed by specific antibodies, allowing early diagnosis and treatment of lung cancer.

Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome

“…Among the 110 anti-SOX1-abspositive patients with identified cancer, LEMS (30.0%, n= 33) was the most common PNS, 6,11,12,[40][41][42][43] followed by PCD (18.2%, n=20), 12,16,25,40,44 PLE (18.2%, n=20), 6,12,17,40,45 and neuropathy (8.2%, n=9) (Table 3). 6,[41][42][43]46 As the most frequent symptom in patients with anti-SOX1 abs, 30.0% of the patients in our review had LEMS and anti-SOX1 abs alone. In the literature there are reports of 64% of patients with both LEMS and SCLC presenting with anti-SOX1 abs, 7 compared with 22-36.5% of patients with SCLC alone.…”

“…In addition, attention still needs to be paid to the case reports of only anti-SOX1 abs being present in patients with a relatively short follow-up period, which may lead to statistical errors. 17,41…”

“…The follow-up time ranged from 15 days to 29 months. 17,20,41,46,47,[58][59][60]66 The neurological symptoms did not improve in 10 patients. 25,42,44,46,47,51,61,65 Among the other patients with or without treatment, 14 died during a follow-up of up to 30.75 months, 40,43,45,[52][53][54][55][56][57] all of whom were SCLC patients.…”

“…The neurological dysfunction associated with anti-SOX1 abs may involve multiple levels of the neuraxis, including the limbic system, cerebellum, peripheral nervous system, and neuromuscular junction. Among the 110 anti-SOX1-abs-positive patients with identified cancer, LEMS (30.0%, n =33) was the most common PNS, 6 11 12 40 41 42 43 followed by PCD (18.2%, n =20), 12 16 25 40 44 PLE (18.2%, n =20), 6 12 17 40 45 and neuropathy (8.2%, n =9) ( Table 3 ). 6 41 42 43 46 …”

“…The presence of anti-SOX1 abs is a potential predictor of underlying SCLC, and SCLC represented the predominant cancer (85.2%, 414 of the 486 cancer patients) ( Table 3 ). 6 7 11 12 15 16 21 40 41 42 43 44 45 46 47 48 49 51 52 53 54 55 56 57 58 59 60 61 The underlying pathogenic mechanism may be due to the immunoreactivity of SCLC patients against epitopes of the conserved high-mobility group box; 14 apart from preventing neural differentiation in progenitor cells and being mainly expressed in the developing nervous system and down-regulated in adults, SOX1 proteins also affect the airway epithelial differentiation and are highly immunogenic. 14 18 …”