Letter to the Editor
Myasthenia gravis in association with extrathymic neoplasia
Miastenia gravis y asociación con neoplasias extratímicas
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Roche, J.L. Capablo, J.R. Ara" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J.C." "apellidos" => "Roche" "email" => array:1 [ 0 => "jcrochebueno@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.L." "apellidos" => "Capablo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J.R." "apellidos" => "Ara" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Neurología, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sección de Neurología, Hospital San Jorge, Huesca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Miastenia gravis y asociación con neoplasias extratímicas" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Myasthenia gravis (MG) is considered a paraneoplastic phenomenon and it is associated with thymoma in 15% of all thymoma patients. However, its association with other extrathymic malignancies remains a matter of debate that has not been completely investigated.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In an MG prevalence study carried out in our setting,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> we found that 3 out of 29 patients (10%) had presented extrathymic malignancies previous to or at the time of diagnosis with MG. These 3 cases were a man with history of non-Hodgkin lymphoma, a man diagnosed with gastric adenocarcinoma when admitted due to MG symptom onset, and a woman with history of breast cancer.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of our study is to review and discuss the association of MG with other extrathymic malignancies and present 3 new cases evaluated in our hospital.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 1.</span> Male patient 62 years of age who had presented generalised adenopathy 15 years previously. Imaging tests showed bilateral axillary adenopathies, retroperitoneal adenopathies, and adenopathies on the right paratracheal lymph nodes. Results from the anatomical pathology study of adenopathies and of the spine were compatible with follicular mixed small-cleaved and large-cell lymphoma. Since the patient was clinically and radiologically stable, no treatment had been started at that date. Regarding neurological follow-up, the patient presented fluctuating diplopia in the past year that responded well to treatment with pyridostigmine (240<span class="elsevierStyleHsp" style=""></span>mg/day). A few months later, the patient's condition worsened and he presented total ptosis and difficulty chewing. Doctors then started treatment with low doses of prednisone (10<span class="elsevierStyleHsp" style=""></span>mg/day), with good tolerability and efficacy. Diagnosis of MG was based on the electrophysiological study, which revealed a pathological decrement of more than 10% to low-frequency repetitive facial nerve stimulation. No presence of thymoma has been confirmed by any of the imaging tests requested during follow-up. Although no antibodies were detected initially, subsequent measurement of anti-AChR antibodies showed high levels in blood, with a titre of 3.98<span class="elsevierStyleHsp" style=""></span>nmol/L (normal level<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.20<span class="elsevierStyleHsp" style=""></span>nmol/L).</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 2.</span> A 72-year-old man was admitted to the emergency department due to progressive loss of limb and neck strength with no bulbar or ocular symptoms. He did not present wasting syndrome or pain. Treatment with IV immunoglobulins and pyridostigmine was started and the patient regained walking ability. Results for anti-AChR antibodies were positive (14.50<span class="elsevierStyleHsp" style=""></span>nmol/L). During his hospital stay, he presented upper gastrointestinal bleeding. Gastroscopy showed an ulcer affecting the lesser curvature. Anatomical pathology study of the ulcer was compatible with intestinal-type gastric adenocarcinoma. Subtotal gastrectomy was performed surgically. After 12 months of follow-up in which the patient tolerated treatment with capecitabine and pyridostigmine, imaging tests showed multiple liver nodules compatible with tumour implants. The patient died 3 years later.</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 3.</span> A 70-year-old woman presenting ocular MG. She had undergone surgical treatment for breast cancer more than 10 years before. Results for anti-AChR antibodies were positive (4.01<span class="elsevierStyleHsp" style=""></span>nmol/L).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Although the association between MG and thymoma is widely recognised, the relationship between MG and other neoplasms remains unclear. Different studies suggest an increase in risk of cancer among MG patients which ranges from 1.7% to 15.4%. In contrast, this risk is estimated at 2.78% for the general population.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The variability among studies may be due to the heterogeneity of samples and follow-up times for MG patients.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,6</span></a> The study with the largest sample size to date, 2614 MG patients, showed an increased risk of extrathymic neoplasm incidence of 1.38 compared to a control cohort during a follow-up period of 8 years. Incidence in the general population is 4.82 new cases of extrathymic neoplasms per 1000 inhabitants per year.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">This increased tendency to present cancer, found in many other autoimmune diseases,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–10</span></a> is due to an immune dysregulation that elicits both the autoimmune cascade and limits the defensive response to cancer cells. Studies do not show a temporal association between cancer and MG, or associations with any specific tumour type. This cannot therefore be regarded as a paraneoplastic phenomenon, unlike the case of small cell lung cancer in Eaton-Lambert syndrome.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,11</span></a> Liu et al. reported that although MG patients presented a higher risk of presenting extrathymic malignancies, they showed no specific susceptibility to certain malignancies.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> That team showed that the most frequent extrathymic malignancy was breast cancer, which is also true in the general population. Rather than being a direct relationship, the association consists of an increased risk of neoplasms at different locations, even with wide time intervals, as we observed in cases 1 and 3.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Of the different extrathymic malignancies in MG patients, we can categorise haematological malignancies as especially frequent.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–15</span></a> Causes may be secondary to immune-suppressing treatments or, as some studies highlight, due to an intrinsic involvement of lymphocytes which undergo chronic stimulation, a process that in turn increases the probability of mutations.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Finally, we should highlight that no cases of MG associated with simultaneous gastric cancer have been reported to date.</p><p id="par0050" class="elsevierStylePara elsevierViewall">We should not forget this increased risk, especially among the subgroup of older patients who present more severe clinical manifestations or thymoma, or those on immunomodulatory treatment.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,17</span></a> Therefore we suggest using cancer screening methods in MG patients, bearing in mind those already used in the general population. Doctors must ensure that they are performed correctly and watch closely for any warning symptoms.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, our data suggest that extrathymic malignancies may be associated with MG. Whether or not co-presence of MG and other extrathymic malignancies represents a real association has yet to be confirmed. Meanwhile, we should consider whether it is necessary to review cancer screening methods, especially in the case of patients with generalised late-onset MG who are treated with immunomodulatory drugs.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Roche JC, Capablo JL, Ara JR. Miastenia gravis y asociación con neoplasias extratímicas. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 16 | 0 | 16 |
| 2024 October | 150 | 11 | 161 |
| 2024 September | 147 | 4 | 151 |
| 2024 August | 132 | 6 | 138 |
| 2024 July | 168 | 12 | 180 |
| 2024 June | 137 | 13 | 150 |
| 2024 May | 181 | 13 | 194 |
| 2024 April | 135 | 22 | 157 |
| 2024 March | 186 | 5 | 191 |
| 2024 February | 185 | 11 | 196 |
| 2024 January | 237 | 12 | 249 |
| 2023 December | 133 | 10 | 143 |
| 2023 November | 201 | 29 | 230 |
| 2023 October | 189 | 6 | 195 |
| 2023 September | 143 | 13 | 156 |
| 2023 August | 83 | 5 | 88 |
| 2023 July | 107 | 16 | 123 |
| 2023 June | 92 | 4 | 96 |
| 2023 May | 136 | 17 | 153 |
| 2023 April | 118 | 4 | 122 |
| 2023 March | 121 | 7 | 128 |
| 2023 February | 84 | 10 | 94 |
| 2023 January | 96 | 10 | 106 |
| 2022 December | 66 | 6 | 72 |
| 2022 November | 107 | 13 | 120 |
| 2022 October | 72 | 17 | 89 |
| 2022 September | 58 | 6 | 64 |
| 2022 August | 75 | 13 | 88 |
| 2022 July | 49 | 11 | 60 |
| 2022 June | 56 | 9 | 65 |
| 2022 May | 60 | 6 | 66 |
| 2022 April | 80 | 11 | 91 |
| 2022 March | 110 | 18 | 128 |
| 2022 February | 115 | 9 | 124 |
| 2022 January | 100 | 5 | 105 |
| 2021 December | 83 | 9 | 92 |
| 2021 November | 86 | 8 | 94 |
| 2021 October | 100 | 12 | 112 |
| 2021 September | 82 | 12 | 94 |
| 2021 August | 93 | 10 | 103 |
| 2021 July | 77 | 12 | 89 |
| 2021 June | 61 | 15 | 76 |
| 2021 May | 96 | 17 | 113 |
| 2021 April | 138 | 24 | 162 |
| 2021 March | 89 | 8 | 97 |
| 2021 February | 50 | 11 | 61 |
| 2021 January | 71 | 15 | 86 |
| 2020 December | 71 | 16 | 87 |
| 2020 November | 68 | 13 | 81 |
| 2020 October | 61 | 10 | 71 |
| 2020 September | 62 | 7 | 69 |
| 2020 August | 67 | 8 | 75 |
| 2020 July | 75 | 10 | 85 |
| 2020 June | 40 | 12 | 52 |
| 2020 May | 40 | 18 | 58 |
| 2020 April | 30 | 8 | 38 |
| 2020 March | 65 | 10 | 75 |
| 2020 February | 69 | 6 | 75 |
| 2020 January | 77 | 22 | 99 |
| 2019 December | 53 | 19 | 72 |
| 2019 November | 69 | 20 | 89 |
| 2019 October | 55 | 6 | 61 |
| 2019 September | 60 | 15 | 75 |
| 2019 August | 48 | 17 | 65 |
| 2019 July | 53 | 22 | 75 |
| 2019 June | 107 | 20 | 127 |
| 2019 May | 240 | 40 | 280 |
| 2019 April | 102 | 39 | 141 |
| 2019 March | 41 | 12 | 53 |
| 2019 February | 38 | 11 | 49 |
| 2019 January | 23 | 14 | 37 |
| 2018 December | 21 | 3 | 24 |
| 2018 November | 19 | 20 | 39 |
| 2018 October | 38 | 7 | 45 |
| 2018 September | 32 | 11 | 43 |
| 2018 August | 9 | 5 | 14 |
| 2018 July | 5 | 8 | 13 |
| 2018 June | 15 | 4 | 19 |
| 2018 May | 10 | 16 | 26 |
| 2018 April | 6 | 3 | 9 |
| 2018 March | 21 | 1 | 22 |
| 2018 February | 3 | 3 | 6 |
| 2018 January | 13 | 5 | 18 |
| 2017 December | 7 | 3 | 10 |
| 2017 November | 18 | 3 | 21 |
| 2017 October | 19 | 5 | 24 |
| 2017 September | 15 | 8 | 23 |
| 2017 August | 24 | 3 | 27 |
| 2017 July | 20 | 1 | 21 |
| 2017 June | 19 | 8 | 27 |
| 2017 May | 22 | 7 | 29 |
| 2017 April | 18 | 4 | 22 |
| 2017 March | 19 | 37 | 56 |
| 2017 February | 12 | 3 | 15 |
| 2017 January | 14 | 6 | 20 |
| 2016 December | 23 | 1 | 24 |
| 2016 November | 33 | 5 | 38 |
| 2016 October | 37 | 8 | 45 |
| 2016 September | 41 | 24 | 65 |
| 2016 August | 21 | 5 | 26 |
| 2016 July | 28 | 3 | 31 |
| 2016 June | 26 | 9 | 35 |
| 2016 May | 21 | 7 | 28 |
| 2016 April | 14 | 26 | 40 |
| 2016 March | 32 | 17 | 49 |
| 2016 February | 28 | 10 | 38 |
| 2016 January | 14 | 10 | 24 |
| 2015 December | 15 | 7 | 22 |
| 2015 November | 15 | 10 | 25 |
| 2015 October | 28 | 14 | 42 |
| 2015 September | 28 | 41 | 69 |
| 2015 August | 21 | 5 | 26 |
| 2015 July | 16 | 6 | 22 |
| 2015 June | 27 | 2 | 29 |
| 2015 May | 19 | 8 | 27 |
| 2015 April | 22 | 8 | 30 |
| 2015 March | 24 | 21 | 45 |
| 2015 February | 33 | 18 | 51 |
| 2015 January | 41 | 13 | 54 |
| 2014 December | 50 | 16 | 66 |
| 2014 November | 37 | 17 | 54 |
| 2014 October | 91 | 38 | 129 |
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