Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Locomotive syndrome: Prevalence,surgical outcomes,and physical performance of patients treated to correct adult spinal deformity

BackgroundLocomotive syndrome (LS) was proposed by the Japanese Orthopedic Association and refers to a scenario in which imminent future nursing care services will be required by elderly adults to manage the functional deterioration of their locomotive organs. It is a social imperative to clarify the risk factors and treatment strategy for LS. However, the relationship between LS and adult spinal deformity (ASD) in those who are treated with spinal corrective surgery remains largely unknown.MethodsForty consecutive patients who had ASD and underwent spinal surgery for their disorder were included in this study. Locomotive dysfunction was evaluated using the 25-item Geriatric Locomotive Function Scale-25 (GLFS-25) questionnaire and physical performance tests including the one-legged standing test, the two-step test, the stand-up test, the handgrip strength, and gait speed test which were measured preoperatively, 6 months after surgery, and 1 year after surgery.ResultsOf the patients with ASD treated surgically, 95% of them had LS preoperatively and LS prevalence decreased significantly 1 year after surgery by 67.5% compared with the preoperative rate. Among physical performance tests, the walking stride and one-legged standing test improved significantly after spinal corrective surgery. The GLFS-25 items for the domains of pain, mobility, and domestic life improved overall postoperatively, whereas items in the self-care domain did not and the item for difficulty in putting on and taking off trousers and pants worsened.ConclusionsSpinal corrective surgery significantly improved physical performance tests as well as the frequency and severity of LS in patients with ASD. However, some GLFS-25 items can worsen after surgery and require attention.     

Legionella longbeachae pneumonia: A case report and literature review in Japan

Herein, we report the case of a 74-year-old man diagnosed with Legionella pneumonia detected by Loop-Mediated Isothermal Amplification (LAMP) method, which was suspected to have been transmitted from the potting soil. Legionella longbeachae was identified in the sputum culture. The patient was intubated and maintained on mechanical ventilation. Antimicrobial therapy with azithromycin was also administered. His symptoms were resolved and he was discharged after 26 days of hospitalization. Legionella longbeachae pneumonia rarely occurs in Japan, and published literature of Legionella longbeachae pneumonia cases in Japan was reviewed. Patients with severe pneumonia exposed to potting soils, but with negative urinary antigen test results, should be examined by LAMP method.     

Vocal cord inflammatory myofibroblastic tumor with mucoid deposits harboring TIMP3–ALK fusion: A potential diagnostic pitfall

A 35‐year‐old Japanese man who had experienced hoarseness for 10 years presented with a vocal cord lesion. A gross examination revealed a left vocal cord polyp occupying two‐thirds of the vocal space. The endoscopically resected lesion contained scattered atypical fibroblastic, stellate, or ganglion‐like cells with mucoid stroma. Vacuolated cells were also seen. Lymphoplasmacytic infiltrate was largely undetectable. A vocal cord polyp was first suspected, but well‐differentiated liposarcoma and inflammatory myofibroblastic tumor (IMT) were included in the differential diagnoses. The tumor cells were positive for anaplastic lymphoma kinase (ALK), calponin, and vimentin, and negative for other smooth muscle markers by immunohistochemistry. Structures resembling myofibroblasts were not observed by electron microscopy, which confirmed abundant rough endoplasmic reticulum in the tumor cells and accumulated lipid droplets in some tumor cells. ALK gene rearrangement was detected by fluorescence in situ hybridization, and TIMP3–ALK fusion was confirmed by 5′ rapid ampli?cation of cDNA ends. We diagnosed the lesion as an IMT, and an ALK‐rearranged stellate cell tumor may be postulated. This is the first report of a fusion partner gene of ALK in a case of laryngeal IMT.     

Frequent mutations of genes encoding vacuolar H+‐ATPase components in granular cell tumors

Granular cell tumors (GCTs) are rare mesenchymal tumors that exhibit a characteristic morphology and a finely granular cytoplasm. The genetic alterations responsible for GCT tumorigenesis had been unknown until recently, when loss‐of‐function mutations of ATP6AP1 and ATP6AP2 were described. Thus, we performed whole‐exome sequencing, RNA sequencing, and targeted sequencing of 51 GCT samples. From these genomic analyses, we identified mutations in genes encoding vacuolar H⁺‐ATPase (V‐ATPase) components, including ATP6AP1 and ATP6AP2, in 33 (65%) GCTs. ATP6AP1 and ATP6AP2 mutations were found in 23 (45%) and 2 (4%) samples, respectively, and all were truncating or splice site mutations. In addition, seven other genes encoding V‐ATPase components were also mutated, and three mutations in ATP6V0C occurred on the same amino acid (isoleucine 136). These V‐ATPase component gene mutations were mutually exclusive, with one exception. These results suggest that V‐ATPase function is impaired in GCTs not only by loss‐of‐function mutations of ATP6AP1 and ATP6AP2 but also through mutations of other subunits. Our findings provide additional support for the hypothesis that V‐ATPase dysfunction promotes GCT tumorigenesis.