Primary Bone Lymphoma: A Case Series and Review of Literature

Primary bone lymphoma (PBL) is a subtype of lymphoma that exclusively affects skeletal tissue. Despite the relatively common involvement of skeletal structures as a manifestation of non-Hodgkin’s lymphoma (NHL), primary and exclusive involvement of the skeletal system is rare. The prevalence of PBL is estimated to be 3–7% amongst primary bone tumors and less than 2% amongst all lymphomas in adults. However, the definition of primary bone lymphoma has been inconsistent over time. Within our institution, we identified four cases of primary bone lymphoma based on diagnostic criteria formed from the general consensus of multiple organizations, including the World Health Organization (WHO) and International Extranodal Lymphoma Study Group (IELSG). Here, we discuss the distinct characteristics amongst these cases in addition to performing a systematic review of current literature regarding this lymphoproliferative entity

A Rare Case of Chondroblastoma from Neolithic Crete of the 7th Millennium BCE

Abstract. Chondroblastoma is a rare primary bone tumor affecting young people comprising <1% of all primary bone tumors (Chen and Di Francesco 2017), first described in the early 20th century (Codman 1931; Jaffe 1942). Recently, the discovery of the first formal Early Neolithic burial ground at Aposelemis site of Herakleion in Crete, Greece, provided a unique opportunity for the retrieval of bioanthropological data from human skeletons. This paper reports the finding of a benign-appearing bone lesion in the distal humerus of a younger individual from this site. The clinicopathological findings of this individual (ca. 35–38 years old) with a small lytic, epiphyseal lesion surrounded by sclerosis suggest a diagnostic assessment of chondroblastoma. This report summarizes the findings and discusses the differential diagnoses in this unique case primarily based on inspectional and radiographic features, lacking the ability of cell and molecular histological investigations through laboratory medicine to narrow down the differential diagnosis of the bone tumor. In a retrospective review, it considers the plausibility of impairing elbow, wrist, and hand arthrokinematic abilities given the cadre of unexampled effects in modern medicine of the persisting and surgically untreated pathology, inclusive of the potential of metastatic complications that would have affected this individual. We deem this to represent the earliest documented case of chondroblastoma in the palaeopathology records of the Aegean region.Résumé. Le chondroblastome est une tumeur osseuse primaire rare, décrite pour la première fois au début du xxe siècle (Codman 1931 ; Jaffe 1942), affectant les jeunes et représentant moins de 1 % des tumeurs osseuses primaires (Chen et Di Francesco 2017). La découverte récente du premier cimetière officiel du Néolithique ancien sur le site d’Aposelemis à Héraklion, en Crète (Grèce), a fourni une occasion unique de récupérer des données bioanthropologiques à partir des squelettes humains. Cet article rapporte la découverte d’une lésion osseuse d’apparence bénigne au niveau de l’extrémité distale de l’humérus chez un jeune individu provenant de ce site. Les résultats clinico-pathologiques de cet individu (environ 35-38 ans) présentant une petite lésion lytique épiphysaire entourée de sclérose suggèrent une évaluation diagnostique de chondroblastome. Ce rapport résume les résultats et discute des diagnostics différentiels de ce cas unique en se basant principalement sur les caractéristiques d'inspection et de radiographie, sans que les investigations histologiques cellulaires et moléculaires effectuées en laboratoire ne permettent de réduire le diagnostic différentiel de la tumeur osseuse. Dans une étude rétrospective, il examine la plausibilité de la détérioration des capacités arthrocinématiques du coude, du poignet et de la main compte tenu des effets inédits en médecine moderne de la pathologie persistante et non traitée chirurgicalement, y compris le potentiel de complications métastatiques qui auraient affecté cet individu. Nous considérons qu’il représente le premier cas documenté de chondroblastome dans les archives de paléopathologie de la région égéenne

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations

Acknowledgements: This work was supported by funding from Helsinn Healthcare (to R.S. and M.L.) and grants from the National Institutes of Health to E.d.S. (U54 D020355) and the MSKCC (Cancer Center Support grant P30 CA008748 and Summer Research Experiences Supervised by Faculty Mentors grant 5R25CA020449).Funder: Helsinn Healthcare, SARET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations.

RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations

Acknowledgements: This work was supported by funding from Helsinn Healthcare (to R.S. and M.L.) and grants from the National Institutes of Health to E.d.S. (U54 D020355) and the MSKCC (Cancer Center Support grant P30 CA008748 and Summer Research Experiences Supervised by Faculty Mentors grant 5R25CA020449).Funder: Helsinn Healthcare, SARET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations

Acknowledgements: This work was supported by funding from Helsinn Healthcare (to R.S. and M.L.) and grants from the National Institutes of Health to E.d.S. (U54 D020355) and the MSKCC (Cancer Center Support grant P30 CA008748 and Summer Research Experiences Supervised by Faculty Mentors grant 5R25CA020449).Funder: Helsinn Healthcare, SAAbstractRET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers.</jats:p