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Angiosarcoma (AS) is an aggressive malignant tumour of endothelial origin, most frequently compelling the skin. The kidney is a rare site of primary occurrence of AS with a quite challenging diagnosis and poor prognosis, mainly due to its raw metastasising power. We described our first case of AS treatment. A comprehensive literature review in this field is also carried out.

Abstract Exosomes are well established effectors of cell–cell communication. Their role on maturation of embryonic cells located in hippocampus, seat of memory, is unknown. Here we show that ceramide facilitates release of exosomes from HN9.10e cells extending information for cell differentiation to neighboring cells. We found only 38 miRNAs differentially expressed in exosomes derived from ceramide-treated cells in comparison with control cells (including 10 up-regulated and 28 down-regulated). Some overexpressed miRNAs (mmu-let-7f-1-3p, mmu-let-7a-1-3p, mmu-let-7b-3p, mmu-let-7b-5p, mmu-miR-330-3p) regulate genes encoding for protein involved in biological, homeostatic, biosynthetic and small molecule metabolic processes, embryo development and cell differentiation, all phenomena relevant for HN9.10e cell differentiation. Notably, the overexpressed mmu-let-7b-5p miRNA appears to be important for our study based on its ability to regulate thirty-five gene targets involved in many processes including sphingolipid metabolism, sphingolipid-related stimulation of cellular functions and neuronal development. Furthermore, we showed that by incubating embryonic cells with exosomes released under ceramide treatment, some cells acquired an astrocytic phenotype and others a neuronal phenotype. We anticipate our study to be a start point for innovative therapeutic strategies to regulate the release of exosomes useful to stimulate delayed brain development in the newborn and to improve the cognitive decline in neurodegenerative disorders.

Abstract Background The Primary Breast Lymphomas (PBL) represent 0,38-0,70% of all non-Hodgkin lymphomas (NHL), 1,7-2,2% of all extranodal NHL and only 0,04-0,5% of all breast cancer. Most frequent PBLs are the diffuse large B cell lymphomas; in any case-reports MALT lymphomas lack or are a rare occurrence. Their incidence is growing. From 1880 (first breast resection for "lymphadenoid sarcoma" carried out by Gross) to the recent past the gold standard treatment for such diseases was surgery. At present such role has lost some of its importance, and it is matter of debate. Methods Twenty-three women affected by PBL underwent surgery. Average age was 63 years (range: 39-83). Seven suffered of hypothyroidism secondary to autoimmune thyroiditis. Fourteen patients underwent mastectomy, nine patients received quadrantectomy (average neoplasm diameter: 1,85 cm, range: 1,1-2,6 cm). In 10 cases axillary dissection was carried out. Pathologic examination revealed 16 diffuse large B cell lymphomas and 7 MALT lymphomas. Results Seven patients in the mastectomy group had a recurrence (50%), and all of them with diffuse large B cell lymphomas at stage II. Two of these had not received chemotherapy. No patient undergoing quadrantectomy had recurrence. In the mastectomy group disease free survival (DFS) at 5 and 10 years was 57 and 50%. Overall survival (OS) at 5 and 10 years was 71.4% and 57.1% respectively. All recurrences were systemic. DFS and OS at 5 and 10 years was 100% in the quadrantectomy group. In the patients with recurrence mortality was 85.7%. For stage IE DFS and OS at 5 and 10 years were 100%. For stage II DFS at 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62.5% respectively. For MALT lymphomas DFS and OS at 5 and 10 years were 100%. For diffuse large B cell lymphomas DFS at 5 and 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62,5% respectively. Conclusions The role of surgery in this disease should be limited to get a definitive diagnosis while for the staging and the treatment CT scan and chemio/radioterapy are repectively mandatory. MALT PBLs have a definitely better prognosis compared to large B cell lymphomas. The surgical treatment must always be oncologically radical (R0); mastectomy must not be carried out as a rule, but only when tissue sparing procedures are not feasible. Axillary dissection must always be performed for staging purposes, so avoiding the risk of under-staging II o IE, due to the possibility of clinically silent axillary node involvement.

Background: Urine cytology is useful to diagnose urinary neoplasms, whereas its role in the study of microhematuria is debatable. Usually, standard urinalysis (dipstick test and sediment examination with bright field microscope) detects the presence of microhematuria, but only urinalysis with phase-contrast microscopy (PCM) (dipstick test and sediment examination with PCM) allows the observation of red blood cell (RBC) morphology and identify their source. Usually glomerular diseases show RBCs with morphological alterations in high percentages, whereas on urologic bleeding, RBCs are rather homogeneous without morphological alterations. Aims: We compare, for the first time, RBC morphology observed in urine cytology and in urinalysis with PCM, to verify whether urinary cytology allows the recognition of the source of bleeding. Methods and Material: A total of 60 patients who had performed both urine cytology and urinalysis with PCM for microhematuria, detected with standard urinalysis, were investigated. Urine cytology showed RBCs and were negative for neoplastic cells or for inflammatory events. Urine samples were processed with the automated method ThinPrep®. RBCs with abnormal and variable shapes were defined as deformed. RBCs of the same spherical shape were defined as non-deformed. Results: Fifty-six urine cytology with RBCs deformed were confirmed in 55 urinalysis with PCM. One case showed RBCs non deformed in urine cytology and in urine sediment. Overall, agreement, between RBC morphology in urine cytology and urinalysis with PCM, was found in 56/60 cases (93%). Conclusions: Therefore, since sediment examination with PCM is available in only few laboratories, we propose that cytopathologist always reports, in urine cytology, any morphological abnormalities of RBCs in order to provide information of the hematuria origin and correctly refer the patient to a nephrologist rather than a urologist.

Introduction: Cholesterol crystals and granulomas in tubular lumen and interstitium of the kidney are infrequent findings during nephrotic syndrome (NS) and are poorly described. We attempt to discuss cholesterol crystals in NS as a form of crystallopathy. Case Presentation: Three cases of 207 (1.5%) performed kidney biopsies, between 2001 and 2019, in patients with NS, showed cholesterol crystals deposition in tubules, interstitium and even cholesterol granulomas with some degree of interstitial mononuclear inflammation with giant cells, interstitial fibrosis and variable tubular atrophy. Oil Red O staining revealed lipid laden macrophages in interstitium and lipid droplets in tubular epithelium. Two patients had membranous glomerulonephritis (MGN) and one membranoproliferative glomerulonephritis (MPGN). The proteinuria ranged from 6.08 to 12.57 g/24 hours, lasting from 1 to 22 months. All had hypertension, high values of serum cholesterol and triglycerides. Conclusion: Clinically significant deposition of cholesterol crystals in kidney is mainly in atheroembolic renal disease, however deposition of cholesterol crystals during NS is rare and it is not considered a form of crystallopathy. Cholesterol crystals do not seem to be correlated with degree of proteinuria, persistence of NS or type of glomerulonephritis, but it is correlated with amount of serum cholesterol which is strongly associated with the severity of NS. Therefore we propose it as tubular crystallopathy, in the setting of NS associated hypercholesterolemia which may cause chronic kidney disease (CKD).

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1), and its ligand PDL-1, are finding increasing application in the treatment of malignant neoplasms. The widespread clinical use of these drugs, however, resulted in the discovery of side effects. The occurrence of celiac disease (CD) after ICIs therapy has been reported in the literature, but its incidence remains unknown and the role of ICIs in its onset is not yet clear. In this review, we examine the published data on this topic in order to better understand and define this entity from a histological point of view. We performed an electronic literature search to identify original reports in which CD or pathological CD-like conditions were documented histologically in patients treated with ICIs. We identified ten papers. A total of twenty-five patients were included in these publications, eleven of them receiving a serologic and histological diagnosis of CD, and four a histological diagnosis of CD-like conditions, in which pathogenesis appears to be multifactorial. ICIs can cause a CD-like enteropathy and biopsies with clinical integration are crucial to diagnose this condition. CD rarely has been observed during treatment with ICIs and its morphological aspects are similar to ICIs-CD enteropathy. Moreover, the onset of ICIs-CD may have a distinct immune mechanism compared to classical CD. Thus, the pathologists must make a histological diagnosis of CD with caution and only in adequate clinical and serological context.

Background: Urine cytology is useful to diagnose urinary neoplasms, whereas its role in the study of microhematuria is debatable. Usually, standard urinalysis (dipstick test and sediment examination with bright field microscope) detects the presence of microhematuria, but only urinalysis with phase-contrast microscopy (PCM) (dipstick test and sediment examination with PCM) allows the observation of red blood cell (RBC) morphology and identify their source. Usually glomerular diseases show RBCs with morphological alterations in high percentages, whereas on urologic bleeding, RBCs are rather homogeneous without morphological alterations. Aims: We compare, for the first time, RBC morphology observed in urine cytology and in urinalysis with PCM, to verify whether urinary cytology allows the recognition of the source of bleeding. Methods and Material: A total of 60 patients who had performed both urine cytology and urinalysis with PCM for microhematuria, detected with standard urinalysis, were investigated. Urine cytology showed RBCs and were negative for neoplastic cells or for inflammatory events. Urine samples were processed with the automated method ThinPrep®. RBCs with abnormal and variable shapes were defined as deformed. RBCs of the same spherical shape were defined as non-deformed. Results: Fifty-six urine cytology with RBCs deformed were confirmed in 55 urinalysis with PCM. One case showed RBCs non deformed in urine cytology and in urine sediment. Overall, agreement, between RBC morphology in urine cytology and urinalysis with PCM, was found in 56/60 cases (93%). Conclusions: Therefore, since sediment examination with PCM is available in only few laboratories, we propose that cytopathologist always reports, in urine cytology, any morphological abnormalities of RBCs in order to provide information of the hematuria origin and correctly refer the patient to a nephrologist rather than a urologist. [ABSTRACT FROM AUTHOR]