Salivary gland tumors (SGTs) comprise a group of rare neoplasms. Locally aggressive, recurrent and/or metastatic SGTs are notorious for their resistance to systemic therapy, making the need for carefully designed, prospective and randomized trials with useful predictive markers mandatory to define new effective therapeutic protocols. Histone Deacetylases (HDACs), are thought to play a crucial role in carcinogenesis. They affect the DNA structure, being also able to regulate its transcription, repair, and replication. This study aimed to evaluate—to our knowledge for the first time—the HDAC-1, -2, -4 and -6 immunohistochemical expression in SGTs and their potential use as prognostic biomarkers. Medical records and archival histopathological material of 58 (36 benign and 22 malignant) SGT patients were included in this study. The H-score was statistically correlated with the clinicopathological characteristics for all cases and patients’ survival rate in malignant SGTs. HDAC-2 positivity was significantly associated with more prolonged overall survival (OS) of patients with malignant SGTs (p = 0.028), while HDAC-2 positivity and no HDAC-6 expression were associated with prolonged OS of patients with HG malignant SGT (p = 0.003 and p = 0.043, respectively). Additionally, a high HDAC-2 H-score was significantly associated with longer OS for HG malignant SGT patients (p = 0.027). In our study, HDAC-2 expression is a marker for good prognosis, whereas HDAC-6 expression indicated poor prognosis; thus, an inhibitor of HDAC-6 may be used to improve patients’ survival.

Background Immune checkpoint inhibitors (ICPIs) have changed the way advanced malignancies are currently confronted, improving cancer patients’ outcomes but also generating distinct immune-related (ir) adverse events. ICPIs-induced colitis is a common complication showing different clinical and histological manifestations. In the literature review, 14 cases with ICPIs related colon granulomas have been reported in 5 studies with either limited or unavailable information regarding histology. Granulomatous reactions can be mistakenly perceived as disease recurrence or progression. Better understanding and identification of this infrequent histological display can help to avoid misdiagnosis and mismanagement. Case presentation A 63-year-old female patient with metastatic melanoma was admitted to the hospital with symptoms of nausea, persistent diarrhea and shivering fever under consecutive treatments with ICPIs, initially pembrolizumab and subsequently ipilimumab. Sigmoidoscopy was performed revealing mucosal edema, hyperemia and erosions of the rectum and sigmoid colon. Histological evaluation of sigmoid colon mucosa biopsies revealed an unusual colitis pattern characterized by multiple intracryptal granulomas attributed to ICPIs therapy. Steroids were administered and the patient recovered. ICPIs treatment was discontinued. The patient was subsequently treated with chemotherapy but follow up radiology showed disease progression. A re-challenge with another ICPI regimen was decided and the patient is currently under immunotherapy with stable disease regarding melanoma status and without any sign of colitis recurrence. Conclusions The present report provides detailed histological description of a distinctive ICPIs-induced granulomatous colitis and highlights the need for awareness of the distinct adverse events and reaction patterns in the context of immunotherapy.

Background: The absence of efficient inhibitors for diabetic kidney disease (DKD) progression reflects the gaps in our understanding of DKD molecular pathogenesis. Methods: A comprehensive proteomic analysis was performed on the glomeruli and kidney cortex of diabetic mice with the subsequent validation of findings in human biopsies and omics datasets, aiming to better understand the underlying molecular biology of early DKD development and progression. Results: LC–MS/MS was employed to analyze the kidney proteome of 2 DKD models: Ins2Akita (early and late DKD) and db/db mice (late DKD). The abundance of detected proteins was defined. Pathway analysis of differentially expressed proteins in the early and late DKD versus the respective controls predicted dysregulation in DKD hallmarks (peroxisomal lipid metabolism and β-oxidation), supporting the functional relevance of the findings. Comparing the observed protein changes in early and late DKD, the consistent upregulation of 21 and downregulation of 18 proteins was detected. Among these were downregulated peroxisomal and upregulated mitochondrial proteins. Tissue sections from 16 DKD patients were analyzed by IHC confirming our results. Conclusion: Our study shows an extensive differential expression of peroxisomal proteins in the early stages of DKD that persists regardless of the disease severity, providing new perspectives and potential markers of diabetic kidney dysfunction.

Salivary gland carcinomas (SGCs) represent a group of rare tumors, with complete surgical resection being the main treatment option. Therapeutic armory for cases of locally aggressive, recurrent, and/or metastatic SGCs, though, remains poor since they exhibit high rates of resistance to systematic therapy. Angiogenesis is considered one of the contemporary hallmarks of cancer and anti-angiogenic factors have already been approved for the treatment of several cancer types. This review aims to summarize, in a histotype-specific manner, the most current available data on the angiogenic factors implicated in SGC angiogenesis, in order to highlight the differences between the most common SGC histotypes and the factors that may have a potential role as therapeutic targets.