RESUMEN
In patients presenting with symptomatic bone metastases, the usual primary malignancies are breast, prostate, thyroid, lung and kidney. Pancreatic cancers are an uncommon cause of bone metastasis and, when they are, it is typically to the axial skeleton. We present the case of a 77-year-old woman who presented to our emergency department with right arm pain. Investigation demonstrated a metastatic lesion with impending pathological fracture. Further investigation found a necrotic pancreatic mass in the tail of the pancreas. Histopathology from the humeral metastasis was consistent with metastatic adenosquamous carcinoma of pancreatic origin. The humerus metastasis was successfully managed with an intramedullary nail. This case highlights an unusual presentation of pancreatic adenocarcinoma with humeral bone metastasis.
RESUMEN
PI3KC2α is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover a role for PI3KC2α in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular system) that results in dysregulated platelet adhesion under haemodynamic shear stress. Structural alterations in the platelet internal membrane lead to enhanced membrane tether formation that is associated with accelerated, yet highly unstable, thrombus formation in vitro and in vivo. Notably, agonist-induced 3-phosphorylated phosphoinositide production and cellular activation are normal in PI3KC2α-deficient platelets. These findings demonstrate an important role for PI3KC2α in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling. These studies provide a link between the open canalicular system and platelet adhesive function that has relevance to the primary haemostatic and prothrombotic function of platelets.