Mutated DMPK RNA binds to MBNL1, causing ClC-1 pre-mRNA to be spliced into the fetal form instead of the adult form. Functional loss of the chloride channel causes myotonia. Histology
In DM1, there can be increased central nuclei, angular fibers, fiber atrophy, and pyknotic clumps. There can be selective atrophy of type 1 muscle fibers. Muscle fibers show signs of degeneration and regeneration. There is modest fibrosis of the endomysium.In DM2, there can be variation in the sizes of muscle fibers, although often there are no abnormalities. There is selective atrophy of type 2 muscle fibers. Again, there are central nuclei and nuclear clumps. Diagnosis
The diagnosis of DM1 and DM2 can be difficult due to the large number of neuromuscular disorders, most of which are very rare. One study found that diagnosis is made an average of seven years after symptom onset for DM1, and fourteen years for DM2.As a result, people with multiple symptoms that may be explained by a complex disorder such as DM1 or DM2 will generally be referred by their primary care physician to a neurologist for diagnosis. Depending on the presentation of symptoms, people may be referred to a number of medical specialists including cardiologists, ophthalmologists, endocrinologists, and rheumatologists. In addition, the clinical presentation is obscured by the degree of severity or the presence of unusual phenotypes. Though there is presently no cure for DM and management is currently symptom-based, a precise diagnosis is still necessary to anticipate multiple other problems that may develop over time (e.g. cataracts).
having an elevated number of mutations).Therapeutic approaches combining multiple immune checkpoint inhibitors or one immune checkpoint inhibitors and a cytotoxic agent are undergoing clinical trials as of 2018. Howerver, the KEYNOTE-598 phase III trial has reported in 2021 that adding ipilimumab to pembrolizumab for NSCLC patients with PD-L1 tumor proportion score ≥50% does not confer any efficacy benefit, but may introduce greater toxicity. The potential role of anti-PD-1 agents as neoadjuvant therapy in resectable NSCLCs is also being investigated. Epidemiology
As for other lung cancer subtypes, lung adenocarcinoma incidence is strongly associated with smoking. Incidence of pulmonary adenocarcinoma has been increasing in many developed Western nations in the past few decades, with a share reaching 43.3% of all lung cancers in the US as of 2012, thus replacing squamous cell lung carcinoma as the most common type of lung cancer. This can be largely attributed to the decreasing smoking rates, which favors the adenocarcinoma histology. Indeed, although smoking is still its strongest risk factor, lung adenocarcinoma is by far the most common among lifelong non-smokers (<100 cigarettes in a lifetime). == References ==