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Background: The large-scale proteomic platform known as the SomaScan® assay is capable of simultaneously measuring thousands of proteins in patient specimens through next-generation aptamer-based multiplexed technology. While previous studies have utilized patient peripheral blood to suggest serum biomarkers of prognostic or diagnostic value in osteosarcoma (OSA), the most common primary pediatric bone cancer, they have ultimately been limited in the robustness of their analyses. We propose utilizing this aptamer-based technology to describe the systemic proteomic milieu in patients diagnosed with this disease. Methods: To determine novel biomarkers associated with overall survival in OSA, we deployed the SomaLogic SomaScan® 7k assay to investigate the plasma proteomic profile of naive primary, recurrent, and metastatic OSA patients. Following identification of differentially expressed proteins (DEPs) between 2-year deceased and survivor cohorts, publicly available databases including Survival Genie, TIGER, and KM Plotter Immunotherapy, among others, were utilized to investigate the significance of our proteomic findings. Results: Apo-transcobalamin-II (APO-TCN2) was identified as the most DEP between 2-year deceased and survivor cohorts (Log2 fold change = 6.8, P-value = 0.0017). Survival analysis using the Survival Genie web-based platform indicated that increased intratumoral TCN2 expression was associated with better overall survival in both OSA (TARGET-OS) and sarcoma (TCGA-SARC) datasets. Cell-cell communication analysis using the TIGER database suggested that TCN2+ Myeloid cells likely interact with marginal zone and immunoglobinproducing B lymphocytes expressing the TCN2 receptor (CD320) to promote their proliferation and survival in both non-small cell lung cancer and melanoma tumors. Analysis of publicly available OSA scRNA-sequencing datasets identified similar populations in naive primary tumors. Furthermore, circulating APO-TCN2 levels in OSA were then associated with a plasma proteomic profile likely necessary for robust B lymphocyte proliferation, infiltration, and formation of intratumoral tertiary lymphoid structures for improved anti-tumor immunity. Conclusions: Overall, APO-TCN2, a circulatory protein previously described in various lymphoproliferative disorders, was associated with 2-year survival status in patients diagnosed with OSA. The relevance of this protein and apparent immunological function (anti-tumor B lymphocyte responses) was suggested using publicly available solid tumor RNA-sequencing datasets. Further studies characterizing the biological function of APO-TCN2 and its relevance in these diseases is warranted. [ABSTRACT FROM AUTHOR]

Background: Indeterminate thyroid cytopathology diagnoses represent differing degrees of risk that are corroborated by follow‐up studies. However, traditional cytologic–histologic correlation may overestimate the risk of malignancy (ROM) because only a subset of cases undergo resection. Alternatively, some molecular tests provide probability of malignancy data to calculate the molecular‐derived risk of malignancy (MDROM) and the positive call rate (PCR). The authors investigated MDROMs and PCRs of indeterminate diagnoses for individual cytopathologists as quality metrics. Methods: This study was approved by the Department of Pathology Quality Improvement Program. Thyroid cytopathology diagnoses and ThyroSeq v3 results were retrieved for each cytopathologist for a 2‐year period with at least 3 years of follow‐up for the atypia of undetermined significance (AUS), follicular neoplasia (FN), and follicular neoplasia, oncocytic‐type (ONC) cytopathologic diagnoses. MDROMs and PCRs were compared with reference ROMs and cytologic–histologic correlation outcomes. Results: The overall MDROMs (and ranges for cytopathologists) for the AUS, FN, and ONC categories were 13.4% (range, 5.8%–20.8%), 28.1% (range, 22.1%–36.7%), and 27.0% (range, 19.5%–41.5%), respectively, and most individual cytopathologists' MDROMs were within reference ROM ranges. However, PCRs more effectively parsed the differences in cytopathologists' ROM performance. Although the overall PCRs were not significantly different across cytopathologists (p =.06), the AUS PCRs were quite different (p =.002). By cytologic–histologic correlation, six of 55 resected cases (10.9%) were falsely negative, and there were no false‐positive cases. Conclusions: MDROMs and PCRs evaluate concordance with reference ROMs and with one another and provide individual feedback, which potentially facilitates quality improvement. Cytopathologists' molecular‐derived risk of malignancy and positive call rates provide insights regarding their practice patterns when compared with reference ranges stated in the Bethesda System for Reporting Thyroid Cytopathology. This feedback is a useful tool from which systems improvement may be developed. [ABSTRACT FROM AUTHOR]

Due to the histological appearance, immunohistochemical phenotype and protracted clinical course of the current case, even without neoadjuvant chemotherapy, we propose that the I PHF1::NUTM2B i gene fusion should be added to the growing list of genetic alterations found in low-grade endometrial stromal sarcoma. The patient is a female in her 80s who, 18 years prior, and at a different institution, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a uterine low-grade endometrial stromal sarcoma with areas of smooth muscle differentiation. I Sir i : Low-grade endometrial stromal sarcoma is a rare mesenchymal tumour of the uterus, which resembles proliferative-phase endometrial stroma. [Extracted from the article]