No abstract

Multicentric carpo-tarsal osteolysis syndrome (MCTO) is a rare skeletal disorder commonly caused by MAF bZIP transcription factor B (MAFB) mutation. Clinically, it is characterized by aggressive osteolysis, which mainly affects the carpal tarsal bones, and is frequently associated with progressive nephropathy. Since the painful swelling and motion limitation on the wrists and/or ankles of MCTO mimics those of juvenile idiopathic arthritis (JIA), very often, MCTO is misdiagnosed as JIA. Here, we report two MCTO patients initially diagnosed with JIA but showed no response to treatment: P1, with a medical history of more than 10 years, was presented with a typical triad of arthritis-osteolysis-nephropathy; while P2 showed oligoarthritis. Gene tests were then taken and revealed a novel mutation, p.P63Q, and a previously reported conversion, p.S54L, in the MAFB gene. We also summarized the clinical and genetic features of a cohort containing 49 genetically confirmed MCTO patients. All 51 gene-confirmed MCTO cases (49 identified from the literature plus two patients identified herein) developed the disease during childhood. The median delay in diagnosis was 3.83 years (0–35 years). All cases presented bony lesions, and two-thirds had secondary renal lesions (32/48; three unknown), half of which (16/32) progressed into renal failure. Almost two-thirds (34/51), 75% (38/51), and 71% (36/51) of patients had no record of eye problems, facial abnormalities, and other manifestations. Most were misdiagnosed as JIA but didn't respond to treatment. Based on our experience, we suggest that clinicians should comprehensively evaluate the involvement of multiple systems in JIA patients, especially the kidney and eyes. And for JIA patients who underwent more than 3-month treatment with Bio-DMARD, genetic tests are recommended when they show little/no clinical and imaging changes, their high disease activity remains, and their disease activity remission is <50%, especially when combined with a triad of arthritis-osteolysis-nephropathy.

The prevalence and clinical relevance of pathogenic germline variants in MMR genes have not been investigated in large series of breast cancers. In this study, we screened the germline variants in MMR genes in 8085 consecutive Chinese breast cancer patients, and investigated the MMR/PD-L1 protein expression and tumor mutation burden (TMB) of breast tumors from MMR variant carriers. We found that 15 of 8085 patients (0.19%) carried a pathogenic germline variant in MMR genes. Compared with non-carriers, MMR variant carriers might have worse recurrence-free survival (unadjusted hazard ratios [HR] = 2.70, 95% CI: 1.12–6.49, P = 0.027) and distant recurrence-free survival (unadjusted HR = 3.24, 95% CI: 1.45–7.22, P = 0.004). More importantly, some of the breast cancers from MMR carriers displayed MMR protein loss (5/13), TMB-high (2/10), and PD-L1 positive expression (9/13). This study showed that MMR variant carriers were rare in breast cancer. They might have worse survival and part of them might benefit from immunotherapy.

Background Studies suggested that myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are an isolated group of diseases that are different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The proportion of individuals with MOGAD is higher among children. However, limited data are available on autoimmune antibodies and neuroimaging features in children with MOGAD. Methods This study retrospectively reviewed 42 children with MOGAD. The clinical, neuroradiological, and cerebrospinal fluid data were compared according to courses and radiological results. Results Of the 42 patients, 28 suffered a monophasic course and 14 had a relapsing course. During the follow-up magnetic resonance imaging (MRI), 21 patients had a well-resolved brain condition and another 21 patients showed slight improvement with marked residuals. Most patients with relapse had cortical lesions and a leukodystrophy-like MRI pattern (all p < 0.05). Children with poor radiological outcomes have confluent and hazy lesions that involve both cortexes, white matter lesion of >2 cm, and a leukodystrophy-like pattern, as well as cerebral lesions with T1 hypointensity or enhancement and spinal lesions (all p < 0.05). The multivariable logistic regression analysis used the aforementioned differential features and showed cerebral enhancement and a leukodystrophy-like pattern as the most effective variations associated with poor radiological outcomes of MOGAD with an area under the curve of 0.875. Conclusion MOGAD in children have some radiological features suggestive of clinical courses and radiological outcomes. A good understanding of these differential features can help to give early warnings of disease recurrence or poor radiological improvement and develop subsequent therapeutic strategies.

Background: Rathke's cleft cysts (RCCs) were diagnosed mostly by shape, signal intensity and enhancement characteristics on MR images. Objectives: To identify the diagnosis of RCC by an improved understanding about the cyst's localization in reference to the pituitary gland. Patients and Methods:We retrospectively evaluated 124 patients with pituitary cystic lesions, verified surgically and histologically. The patients were divided into RCC and cystic pituitary adenoma (CPA) groups. The cysts in both groups were observed and compared, focusing on the shape and size, as well as clinical and MRI features, especially localization. Receiver-operating-characteristic (ROC) curve was performed with the clinical and MRI findings between the groups. Results: The RCC group included 90 patients (33 men) with a mean age of 40.9 years, while the CPA group included 34 patients (12 men) with a mean age of 43.5 years. On MRI, the RCCs were mostly located without shift of the pituitary stalk on the coronal view, with the superior margin of the cyst lying behind or across the junction point of the pituitary stalk on the sagittal view. The ROC curve was performed, and the following two variables exhibited good performances in diagnosing RCCs: the coronal localization (sensitivity, 91.1%; specificity, 79.4%; AUC = 0.853, 95% confidence interval: 0.778 -0.910, P < 0.0001), and the sagittal localization (sensitivity, 88.9%; specificity, 91.2%; AUC = 0.889, 95% confidence interval: 0.821 -0.939, P < 0.0001). Conclusion: Cyst localization, observed easily on MRI, can be used as an effective parameter for diagnosing RCC and distinguishing it from a CPA.