Immunoglobulin G4-Associated Rosai-Dorfman Disease: Report of 3 Cases.

Rosai-Dorfman disease is characterized by dilated lymph node sinuses filled with lymphocytes, plasma cells, and histiocytes. Many of these histiocytes classically exhibit emperipolesis of lymphocytes and plasma cells. Abundant immunoglobulin G4+ plasma cells occur in some cases, and a potential relationship with immunoglobulin G4-related disease has been suggested. Here, we report 3 cases of immunoglobulin G4-associated Rosai-Dorfman disease. Immunoglobulin G4-related disease was suspected based on immunoglobulin G4+ plasma cell infiltration, but the final diagnosis was immunoglobulin G4-associated Rosai-Dorfman disease. At present, the evidence does not support a link between immunoglobulin G4-associated Rosai-Dorfman disease and immunoglobulin G4-related disease, and one condition should not be considered part of the spectrum of the other. We believe it is of paramount importance to increase the awareness of immunoglobulin G4-associated Rosai-Dorfman disease for pathologists who interpret the biopsies and clinicians who integrate the diagnosis and treat such patients to not overdiagnose immunoglobulin G4-related disease.

Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells.

O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation.

Acroangiodermatitis of the hand secondary to a dysfunctional arteriovenous fistula.

Acroangiodermatitis (AAD) is often seen in association with various vascular anomalies such as venous insufficiency, vascular syndromes, and conditions associated with thrombosis. This is the first case reported in the literature associated with arteriovenous fistula stenosis in a patient with chronic kidney disease on hemodialysis. This case is being described for its rarity and to familiarize the clinicians with this unusual complication, especially, to prevent them from thinking of this condition as an infectious complication. It is essential to recognize the uniqueness of the pathophysiology of this disease and to do a clear distinction with that of a venous ulcer. With this work we also aim to help health practitioners with proper management of the condition. As we've seen, surgical treatment in appropriately selected cases corrects the reflux of the venous system and successfully improves the appearance of the verrucous lesion. Our patient was successfully treated by correcting the arteriovenous fistula stenosis with near-complete subsidence of the verrucous lesion within days of the procedure. Acroangiodermatitis management must be conducted with a multidisciplinary approach (dermatology, vascular surgery, and internal medicine). It is essential the comprehensive management of these patients, to ensure prompt recovery and avoid chronic effects, as well as to guarantee the quality of life in the future.