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Purpose: Tumor hypoxia is associated with poor response to radiation (RT). We previously discovered a novel mechanism of metformin: enhancing tumor RT response by decreasing tumor hypoxia. We hypothesized that metformin would decrease tumor hypoxia and improve cervical cancer response to RT. Patients and Methods: A window-of-opportunity, phase II randomized trial was performed in stage IB–IVA cervical cancer. Patients underwent screening positron emission tomography (PET) imaging with hypoxia tracer fluoroazomycin arabinoside (FAZA). Only patients with FAZA uptake (hypoxic tumor) were included and randomized 2:1 to receive metformin in combination with chemoRT or chemoRT alone. A second FAZA-PET/CT scan was performed after 1 week of metformin or no intervention (control). The primary endpoint was a change in fractional hypoxic volume (FHV) between FAZA-PET scans, compared using the Wilcoxon signed-rank test. The study was closed early due to FAZA availability and the COVID-19 pandemic. Results: Of the 20 consented patients, 6 were excluded due to no FAZA uptake and 1 withdrew. FHV of 10 patients in the metformin arm decreased by an average of 10.2% (44.4%–34.2%) ± SD 16.9% after 1 week of metformin, compared with an average increase of 4.7% (29.1%–33.8%) ± 11.5% for the 3 controls (P = 0.027). Those with FHV reduction after metformin had significantly lower MATE2 expression. With a median follow-up of 2.8 years, the 2-year disease-free survival was 67% for the metformin arm versus 33% for controls (P = 0.09). Conclusions: Metformin decreased cervical tumor hypoxia in this trial that selected for patients with hypoxic tumor. See related commentary by Lyng et al., p. 5233

Extracellular Vesicles (EVs) are a collection of vesicles released from cells that play an important role in intercellular communication. Microbial infections are known as one of the major problems in the medical field. Considering the increasing resistance of strains to routine drug treatments, the need for new therapies seems to be more than ever. Recent studies have shown that the EVs released from immune cells during microbial infections had anti-microbial effects or were able to induce neighbouring cells to display anti-microbial effects. This mini-review aimed to explore the latest studies on immune cell-derived EVs in viral, bacterial, fungal, and parasitic infections. Review of the literature demonstrated that specific cargos in EVs were involved in the fight against pathogenic infections. Additionally, the transport of appropriate bioactive molecules including miRNAs, mRNAs, and proteins via EVs could mediate the anti-microbial process. Thus, it could be a proof-of-principle that therapeutic approaches based on EVs derived from immune cells could offer a promising path forward, which is still in early stages and needs further assessments.

Alpha-inhibin expression has been reported in pheochromocytomas and paragangliomas (PPGLs). We analyzed alpha-inhibin immunohistochemistry in 77 PPGLs (37 pheochromocytomas [PCCs] and 40 paragangliomas) and correlated the results with catecholamine profile, tumor size, Ki-67 labeling index, succinate dehydrogenase B subunit and carbonic anhydrase IX (CAIX) staining, and genetic pathogenesis. PPGLs were classified as pseudohypoxic cluster 1 disease with documented VHL mutation or SDHx mutation or biochemical phenotype, whereas NF1-driven and RET-driven PPGLs and those with a mature secretory (adrenergic or mixed adrenergic and noradrenergic) phenotype were classified as cluster 2 disease. The Cancer Genome Atlas data on INHA expression in PPGLs was examined. Alpha-inhibin was positive in 43 PPGLs (56%). Ki-67 labeling indices were 8.07% and 4.43% in inhibin-positive and inhibin-negative PPGLs, respectively (P

A 63 year-old postmenopausal woman presented to her family physician with a tender palpable mass in the right lower quadrant in November 2019. She noticed that this pain was reproducible with pressure on the right hip. Her medical history was significant for hypothyroidism, tubular adenomas, and

The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.

Pituitary neuroendocrine tumors (PitNETs) : nomenclature evolution, not clinical revolution

Adrenocortical tumors range from primary bilateral micronodular or macronodular forms of adrenocortical disease to conventional adrenocortical adenomas and carcinomas. Accurate classification of these neoplasms is critical given the varied pathogenesis, clinical behavior, and outcome of these different lesions. Confirmation of adrenocortical origin, diagnosing malignancy, providing relevant prognostic information in adrenocortical carcinoma, and correlation of laboratory results with clinicopathologic findings are among the important responsibilities of pathologists who evaluate these lesions. This article focuses on a practical approach to the evaluation of adrenocortical tumors with an emphasis on clinical and imaging findings, morphologic characteristics, and multifactorial diagnostic schemes and algorithms.

Plasma cell tumors are characterized by a monoclonal proliferation of immunoglobulin-secreting plasma cells. Dural infiltration of plasma cells without involvement of the parenchyma, leptomeninges or skull is a rare event. We present a 34-year-old man presenting with hallucination and amnesia. Magnetic resonance imaging revealed a left fronto-temporal mass with a dural tail mimicking meningioma. The mass was excised and histopathological examination revealed sheet of mature plasma cells. The cells were immunoreactive for kappa light chain, MUM1, CD38, and negative for epithelial membrane antigen. There was no recurrence after postoperative radiotherapy. Intracranial involvement from plasmacytoma should be considered in a case of solitary dural mass.