Cancer Frequency in <scp>MuSK</scp> Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology

Falso, Silvia; Gessi, Marco; Marini, Sofia; Benvenuto, Roberta; Sabatelli, Eleonora; D'Amati, Antonio; Marini, Martina; Evoli, Amelia; Iorio, Raffaele

doi:10.1002/ana.27033

Annals of Neurology

2024

DOI: 10.1002/ana.27033

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Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology

Silvia Falso,

Marco Gessi,

Sofia Marini

et al.

Abstract: Cancer frequency in muscle‐specific kinase myasthenia gravis (MuSK‐MG) has not yet been explored and the mechanisms leading to the formation of MuSK IgG remain elusive. We aimed to explore cancer frequency in MuSK‐MG patients and to assess MuSK expression in cancer cells from 2 tumors occurred in this cohort. Immunohistochemistry on tumor specimens revealed the expression of MuSK in the cancer cells from primary mediastinal B cell lymphoma and endometrial carcinoma. Twenty‐one males and 73 females were enrolle… Show more

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2024

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Cited by 2 publications

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Falso,

Iorio

2024

Annals of Neurology

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The recent article described by Falso et al 1 suggested the potential association between muscle-specific kinase (MuSK) myasthenia gravis (MuSK-MG) and paraneoplastic etiology. The Japan MG Registry (JAMG-R) study group also pays special attention to the association between MG and cancer, because of the cancer risk conferred by long-term immunosuppression therapy.In our recent study on the clinical features and outcomes of MuSK-MG, we analyzed 51 MuSK-MG patients (3.0% of the total study population: males:females = 5:46) selected from among 1,710 consecutive patients who were followed at 13 hospitals participating in the JAMG-R between April and October 2021. 2 Onset age and disease duration were 38.0 years and 13.5 years, respectively. All 51 patients had the generalized form of MG with bulbar involvement in 50 and myasthenic crisis in 8 patients. Twenty-six patients had refractory MG. Although MuSK-MG is less frequent in Asians than Caucasians, the clinical characteristics are similar among different ethnic populations.Of the 51 patients with MuSK-MG, only 1 (2.0%) had cancer, a 48-year-old woman who developed stage II breast cancer 17 years after MuSK-MG diagnosis. In contrast, the cancer frequencies were 8.5% (119/1,402 patients) and 3.9% (10/257) for patients with acetylcholine receptor-MG and seronegative MG, respectively. It is noteworthy that cancer, other than invasive thymoma recurrence, was found in 42 (10.7%) of 393 patients with thymoma-associated MG. Therefore, the JAMG-R investigation demonstrated that patients with MuSK-MG had lower cancer frequency than other MG subtypes. However, because an Italian cohort reported a higher cancer frequency of 13.8% among MuSK-MG patients, 1 additional analysis among MG sunsets is warranted.We must also consider the neurologic autoimmunity induced by immune checkpoint inhibitors (ICI). Although classical paraneoplastic neurological syndrome is known to precede the discovery of cancer, neurological syndromes triggered by ICI develop after cancer diagnosis, usually shortly after ICI initiation. 3 Recently, the indication for ICI administration has been expanded to include small-cell lung cancer. The Japanese Adverse Event Drug Report database revealed that ICI users included a significantly disproportionately large number of patients with Lambert-Eaton myasthenic syndrome, all of whom had been diagnosed with small-cell lung cancer. 4 This result suggests that ICI administration can accelerate the development of paraneoplastic neurological syndrome. Many researchers have described cases of ICI-triggered MG, but only rarely in MuSK-MG patients. 5 If a strong correlation exists between MuSK-MGand cancer, we can expect to experience ICI-induced MuSK-MG more frequently.

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Reply to “MuSK‐Myasthenia Gravis and Cancer”

Falso,

Iorio

2024

Annals of Neurology

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MuSK‐Myasthenia Gravis and Cancer

Suzuki,

Utsugisawa

2024

Annals of Neurology

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Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology

Cited by 2 publications

References 15 publications

Reply to “MuSK‐Myasthenia Gravis and Cancer”

Reply to “MuSK‐Myasthenia Gravis and Cancer”

MuSK‐Myasthenia Gravis and Cancer

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