Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin.

Fewer than half of patients with systemic sclerosis demonstrate modified Rodnan skin score improvement during mycophenolate mofetil (MMF) treatment. To understand the molecular basis for this observation, we extended our prior studies and characterized molecular and cellular changes in skin biopsies from subjects with systemic sclerosis treated with MMF. Eleven subjects completed ≥24 months of MMF therapy. Two distinct skin gene expression trajectories were observed across six of these subjects. Three of the six subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in CCL2 mRNA expression in skin and reduced numbers of macrophages and myeloid dendritic cells in skin biopsies. MMF cessation at 24 months resulted in an increased inflammatory score, increased CCL2 mRNA and protein levels, modified Rodnan skin score rebound, and increased numbers of skin myeloid cells in these subjects. In contrast, three other subjects remained on MMF >24 months and showed a persistent decrease in inflammatory score, decreasing or stable modified Rodnan skin score, CCL2 mRNA reductions, sera CCL2 protein levels trending downward, reduction in monocyte migration, and no increase in skin myeloid cell numbers. These data summarize molecular changes during MMF therapy that suggest reduction of innate immune cell numbers, possibly by attenuating expression of chemokines, including CCL2.

Multiple hepatocellular adenomas presenting in a male 8 years post-pancreaticoduodenectomy for islet cell tumor of the pancreas.

We report the case of a 29-year-old male who presented with vague right upper quadrant pain, 8 years following a pancreaticoduodenectomy for a symptomatic pancreatic islet cell tumor. Subsequent imaging revealed multiple lesions in the right lobe of the liver. A diagnosis of metastatic disease could not be out ruled and hence a formal resection was performed. A formal retrospective review of case notes, preoperative imaging, operative notes, subsequent histology as well as a review of the current literature using the Medline, CINAHL, and EMBASE databases was performed. Histologic analysis showed these lesions to be hepatocellular adenomas. We highlight in this case the importance of preoperative imaging and workup, discuss hepatocellular adenomas in males and hypothesize as to the underlying pathophysiology in this particular case based on the available evidence.