Prostatic adenocarcinoma oncocytic variant:Case report and literature review

The oncocytic variant of prostatic adenocarcinoma is exceptionally rare with only 4 cases reported in the English literature.Little is known about the clinical behavior of this variant of prostatic adenocarcinoma,because of the exceptionally low number of reported cases.The 2016 World Health Organization Classification of Tumors of Prostate does not recognize the oncocytic variant,again likely related to the exceptional paucity of reported cases.Here,we report the fifth case of the oncocytic variant of acinar type prostatic adenocarcinoma in an asymptomatic 64-year-old Caucasian American male with elevated serum prostate specific antigen(7.33 ng/m L;normal range 0-4.00 ng/mL) during routine blood screening for diabetes mellitus.At subsequent transrectal prostate biopsy,the right side of prostate was infiltrated by adenocarcinoma with tumor cells forming variably differentiated glands,including some poorly differentiated.Tumor cell nuclear:cytoplasmic ratio was low,with small to intermediate sized vesicular nuclei and only rare discernable small nucleoli.Cellular cytoplasm was characteristically granular pink with sharply defined cell membranes.Positive AMACR(P504S) epithelial immunohistochemical staining and absence of staining for prostatic basal cells confirmed the tumor to be primary prostatic adenocarcinoma.AMACR immunohistochemical staining was also helpful with accurate grading of the tumor due to the difficulty of differentiating tumor cells from residual prostate myocytes at routine hematoxylin and eosin(HE) staining.This new case adds to the exceptionally small number of previously reported cases of the oncocytic variant of primary prostatic adenocarcinoma.It also highlights the difficulty associated with Gleason scoring of the oncocytic variant by routine HE evaluation and the usefulness of AMACR(P504S) immunostaining for accurate grading of prostatic adenocarcinoma in the oncocytic variant.

Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

The application of extracellular vesicles,particularly exosomes(EXs),is rapidly expanding in the field of medicine,owing to their remarkable properties as natural carriers of biological cargo.This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues(NAF-EXs)for personalized medicine,which can be derived at the time of diagnosis by endoscopic ultrasound.Herein,we show that exosomes(EXs)derived from NAFs demonstrate differential bio-physical characteristics,efficient cellular internalization,drug loading efficiency,pancreatic tumor targeting and delivery of payloads.NAF-derived EXs(NAF-EXs)were used for loading ormeloxifene(ORM),a potent anti-cancer and desmoplasia inhibitor as a model drug.We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype,which may be due to regulation of Ca^(2+) influx in fibroblast cells.NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition(EMT)and repressed tumor growth in xenograft mouse model.In conclusion,our data suggests preferential tropism of NAF-EXs for PDAC tumors,thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs.Additionally,it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.