We describe the second reported case of multicentric osteosarcoma associated with Rothmund-Thomson syndrome (RTS), a rare hereditary cancer-prone genodermatosis characterized by typical cutaneous lesions and other non-dermatological pathological manifestations, particularly skeletal changes. A high incidence of malignant disorders has been found in RTS patients. This could be explained by the diminished capacity of DNA-repair demonstrated in the fibroblasts of RTS patients following exposure to oncogenic stimuli. The severe cutaneous lesions and the benign bone lesions found in RTS may be considered a predisposing factor to the particularly frequent skin carcinoma and osteogenic sarcoma encountered in these cancer-prone patients. A brief review of the literature is given, with a discussion of the association between these two rare conditions.

In infrahepatic interruption of the inferior vena cava (IVC), continuation is usually through the azygos or hemiazygos systems (Chuang et al, 1974; Smathers et al, 1982; Mayo et al, 1983). Recently, Bercoff et al (1985) described the first case of portal continuation. We observed such an anomaly in a patient who had a single left-sided IVC with hemiazygos-azygos continuation, and a shunt between the portal and hepatic systems. To our knowledge nosuch complex anomaly has yet been reported.

We report the case of a patient in whom brain MR imaging was requested for initial symptoms of intracranial hypertension. The presence of multiple intracranial hemorrhagic lesions suggested brain metastases. Body screening showed periosteal osteosarcoma of the left fibula with no lung metastases, but with a patent foramen ovale which probably allowed neoplastic cells to reach the brain without being filtered through the lungs. The conclusion of this study was that a left-right cardiac communication is to be considered in cases of isolated brain metastases from osteosarcoma.

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BackgroundANCA-associated vasculitis (AAV) carries excessive morbidity and mortality owing to the delay in diagnosis and limited prognostication. Identifying clinically useful biomarkers of disease activity that facilitate accurate prognostication would help personalize management decisions. Biomarkers used in day-to-day practice include PR3- or MPO-ANCA, CRP, and ESR, but these poorly predict future disease activity. Few studies have examined a limited number of circulating proteins as biomarkers, including BCA-1, MMP-3, TIMP-1[1-4]. We previously leveraged a high-throughput, unbiased approach to investigate 92 potential biomarkers for disease prognostication in AAV patients and identified 5 potential biomarkers.ObjectivesTo further investigate the association of 5 novel protein biomarkers with AAV disease activity.MethodsSerum samples from patients in the Mass General Brigham (MGB) AAV cohort were retrieved from the MGB Biobank following IRB approval. We chose a random 78 subjects who had AAV. We classified disease activity as “Active” or “Remission” at sample collection. The O-link high-throughput proteomic assay was used to measure the levels of 5 proteins of interest (MCP3, TNFSF-14, OSM, Flt3L, and SCF). For analysis, protein levels were first normalized. We compared protein levels in active disease vs remission. ESR, CRP, white blood cell (WBC) count and platelet levels were extracted for comparison. Using the mean value of each potential biomarker in the cohort as cut-off values, we determined the odds ratio (OR) and the area under the receiver operating curve (AUC) of the association of elevated biomarkers with active disease.ResultsOf n=78, the mean age was 57.3 +/- 17.6, 55% were female, and 28% had active disease at sample collection. When examining the outcome of active disease vs remission, abnormal levels of OSM, TNF-SF-14, Flt3L, and SCF differentiated disease states: OR of 5.10 (p=0.005), 3.71 (p=0.017), 0.13 (p=0.001), and 0.34 (p=0.040), respectively. AUC analysis indicated that TNF-SF-14 (0.731, CI 0.601-0.862), OSM (0.745, CI 0.622-0.867), and Flt3L (0.757, CI 0.644-0.871) were more strongly associated with active disease than other biomarkers, including WBC (0.703, CI 0.566-0.840), platelets (0.680, CI 0.551-0.809), CRP (0.549, CI 0.376-0.721), and ESR (0.547, CI 0.372-0.722).ConclusionUsing a high-throughput, unbiased proteomics approach, we further investigated 5 novel candidate markers differentiating active AAV disease from remission. These proteins likely reflect different states of immune activation during active disease and outperform conventional inflammatory markers (e.g., CRP, ESR) as well as WBC and platelets. Our study has certain limitations, including sample size, a cross-sectional study design, and requires validation across diverse, longitudinal cohorts. The potential for biomarkers that accurately identify those individuals in remission compared to active disease may facilitate tailored, personalized therapeutic intervention, which avoids unnecessary exposure to the toxic side effects of immunomodulatory agents.Table 1.Biomarker mean levels and characteristics for active disease.BiomarkerMean level Active vs. RemissionOdds Ratio (mean cutoff, CI, p-value)AUC (CI)OSM7.39 ± 0.83 vs. 6.60 ± 1.01, p=0.0025.1 (≥ 6.96, 1.64-15.85, p=0.005)0.745 (0.622-0.867)TNF-SF-147.59 ± 0.90 vs. 6.85 ± 0.91, p=0.0013.71 (≥ 7.07, 1.26-10.93, p=0.017)0.731 (0.601-0.862)Flt3L9.28 ± 0.48 vs. 9.74 ± 0.49, p=0.0010.13 (≥ 9.64, 0.04-0.43, p=0.001)0.757 (0.644-0.871)MCP-33.51 ± 0.78 vs. 2.99 ± 0.73, p=0.0081.24 (≥ 3.18, 0.46-.3.36, p=0.666)0.628 (0.485-0.771)SCF9.73 ± 0.74 vs. 10.19 ± 0.38, p=0.0010.34 (≥ 10.13, 0.12-0.95, p=0.04)0.700 (0.570-0.830)Figure 1.Area under the receiving operating curves for active disease.References[1]Monach, et al. ACR Open Rheum 2022; 4:168.[2]Berti, et al. J Autoimmun 2019; 105:102302.[3]Monach, et al. Ann Rheum Dis 2013; 72:1342.[4]Monach, et al. Arthritis Rheum 2011; 63:3988.Acknowledgements:NIL.Disclosure of InterestsNone Declared.