Bilateral Diffuse Pseudoangiomatous Stromal Hyperplasia Necessitating Mastectomy.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign breast lesion often diagnosed incidentally and frequently mistaken for fibroadenoma given similar radiographic appearance. Histopathology classically reveals diffuse, dense fibrous stromal background with a complex network of spindle cells forming slit-like spaces, giving it the appearance of angiomatous proliferation. Surgical excision is generally not necessary. Here we present two unusual cases of PASH: an adolescent patient with bilateral rapid onset of symptoms, and a premenopausal patient with bilateral, diffuse, recurrent PASH. Both required mastectomy. We aim to highlight the variable nature of presentation and briefly review current management options.

Systems Pharmacology Modeling Identifies a Novel Treatment Strategy for Bortezomib-Induced Neuropathic Pain.

Chemotherapy-induced peripheral neurotoxicity is a common dose-limiting side effect of several cancer chemotherapeutic agents, and no effective therapies exist. Here we constructed a systems pharmacology model of intracellular signaling in peripheral neurons to identify novel drug targets for preventing peripheral neuropathy associated with proteasome inhibitors. Model predictions suggested the combinatorial inhibition of TNFα, NMDA receptors, and reactive oxygen species should prevent proteasome inhibitor-induced neuronal apoptosis. Dexanabinol, an inhibitor of all three targets, partially restored bortezomib-induced reduction of proximal action potential amplitude and distal nerve conduction velocity in vitro and prevented bortezomib-induced mechanical allodynia and thermal hyperalgesia in rats, including a partial recovery of intraepidermal nerve fiber density. Dexanabinol failed to restore bortezomib-induced decreases in electrophysiological endpoints in rats, and it did not compromise bortezomib anti-cancer effects in U266 multiple myeloma cells and a murine xenograft model. Owing to its favorable safety profile in humans and preclinical efficacy, dexanabinol might represent a treatment option for bortezomib-induced neuropathic pain.