Areas Of Necrosis Research Articles

Chemo-Enzymatic Synthesis and Biological Assessment of p-Coumarate Fatty Esters: New Antifungal Agents for Potential Plant Protection.

One trend in agriculture is the replacement of classical pesticides with more ecofriendly solutions, such as elicitation, which is a promising approach consisting of stimulating the natural immune system of a plant to improve its resistance to pathogens. In this fashion, a library of p-coumaric-based compounds were synthesized in accordance with as many principles of green chemistry as possible. Then, these molecules were tested for (1) the direct inhibition of mycelium growth of two pathogens, Botrytis cinerea and Sclerotinia sclerotiorum, and (2) plasma membrane destabilization in Arabidopsis and rapeseed. Finally, the protective effect was evaluated on an Arabidopsis/B. cinerea pathosystem. Total inhibition of the growth of both fungi could be achieved, and significant ion leakage was observed using dihydroxylated fatty p-coumarate esters. A direct effect on plants was also recorded as a ca. three-fold reduction in the necrosis area.

Clear Cell Renal Cell Carcinoma With Syncytial-Type Multinucleated Giant Tumor Cells: A Clinicopathologic Study of 14 Cases.

The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered.

An Unusual Presentation of Huge Gastric Cystic Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors (GISTs), nonepithelial, mesenchymal tumors arising from the interstitial cells of Cajal. The diagnostic tool for the GISTs is tyrosine kinase growth factor receptor (c-KIT / CD117) expression. They most commonly occur in the the stomach. Here we reported a rare case of GIST, presenting as a large cystic mass connected to the main tumor with a peduncle. A 44-year-old female patient presented to the emergency department with abdominal pain and intestinal obstruction. Emergency laparatomy revealed a cystic mass of approximately 25 cm in diameter. The pathological diagnosis was gastrointestinal stromal tumor with cystic degenaration. Tumor contained areas of necrosis, high mitotic index, c-KIT positive and was large in diameter. Cystic GISTs have poor prognostic factors and patients should be followed closely in the postoperative period.

The success of volumetric means ADC in predicting MGMT promoter hypermethylation in glioblastomas

Aims: This study aimed to investigate the relationship between volumetric mean ADC values and MGMT promoter hypermethylation status in glioblastoma (GB) patients segmented into perilesional edema area, solid tumor area, and necrosis area.
 Methods: The 212 GB patients in the University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF-PDGM) dataset were retrieved from the Cancer Imaging Archive (TCIA). The mean volumetric ADC value was calculated in patients with shared segmentation data in the UCSF-PDGM dataset. The difference in mean volumetric ADC value was investigated in patients divided into groups based on MGMT promoter hypermethylation (MGMT+/ MGMT-).
 Results: Of the patients in our study, 125 (59.0%) were male. The median age of the patients was 62 years (26-94). MGMT promoter hypermethylation was observed in 152 (71.7%) patients. Mean Survival was calculated as 574.14±345.57 days in the MGMT+ group and 484.68±301.71 days in MGMT- group. According to volumetric mean ADC values, a difference was observed in the solid tumor and perilesional edema areas according to MGMT promoter hypermethylation (p1.14 in ADC measurements from the edema area with 72% sensitivity and 90% specificity. MGMT+ group could be determined with a sensitivity of 88% and specificity of 69% with a cut-off value of >1.01 in ADC measurements from the solid tumor area.
 Conclusion: Volumetric ADC measurements from the perilesional edema and solid tumor areas revealed higher ADC values in the MGMT+ group.

EXPERIMENTAL STUDY OF THE USE OF COHERENT RADIATION TO DETERMINE THE BOWELS VIABILITY

Aim of the study – to investigate the effectiveness of using coherent radiation to determinethe viability of intestines in an experiment.Materials and methods. 30 non-linear white rats were used. In 10 animals, the smallintestine (SmlI) with the mesentery was ligated. In 10 animals, the colon with themesentery was ligated. After 12 hours, the width of the scattering zone (WSZ) of laserbeams was measured (in millimeters) on the walls of the intestines in the afferent (Af),efferent (Ef) and ligature (Lig) areas and taken for histological examination. The data of10 healthy animals served as a control. Laser LEDs with wavelengths of λ=0.63 μm andλ=0.5 μm were used.The results. Histological studies revealed morphological abnormalities in the Af withoutnecrosis, minor changes in the Ef and necrosis of the Lig. The ratio of the parametersof WSZ at wavelengths: λ=0.63/λ=0.5 μm in the control on SmlI = 1.01±0.08, on LrgI= 1.04±0.07 (р>0.05), on Lig SmlI = 0.79±0.05, LrgI = 0.82±0.03 (p>0.05), control –p<0.05. On Ef SmlI = 0.93±0.06, LrgI = 0.97±0.07 (p>0.05), control – p>0.05, Lig –p<0.05. On Af SmlI = 0.64±0.03, LrgI = 0.62±0.02 (р>0.05), control – p<0.01, Af andEf – p<0.05.Conclusions. 1. WSZ by the walls of SmlI and LrgI of laser beams with wavelengthsλ=0.63 μm and λ=0.5 μm increases statistically significantly in areas of intestineswith necrosis caused by ligation of the intestine and its mesentery. 2. In the areas ofthe intestines with morphological changes without the development of necrosis, WSZincreases, but, partly, without significant differences. 3. The ratio of the WSZ indicatorsof a laser beam with a wavelength of λ=0.63 μm to that with a wavelength of λ=0.5 μm is statistically significantly different in areas of intestines without impaired viability,with morphological changes without signs of necrosis, and with necrosis. 4. Ratioindicators greater than 0.9 indicate the absence of viability violations, parameters within0.9-0.65 indicate morphological changes without necrosis, and indicator parameterslower than 0.65 indicate intestinal necrosis.

First Report of Xanthomonas hydrangeae Causing Leaf Spot on Oakleaf Hydrangea (Hydrangea quercifolia) in Tuscany (Italy).

Hydrangeas (Hydrangea L.) are popular ornamental plants used in urban landscapes and gardens worldwide for the beauty of their large flowers. In June 2022, dark brown/purple and irregular water-soaked spots coalescing into large areas of necrosis were observed on the leaves of potted Hydrangea quercifolia Bartr. plants growing in two ornamentals nurseries in Pistoia, Tuscany, Italy. Isolations, using two symptomatic plants/nursery, were performed by excising small portions of leaf tissue from the margin of the lesions, and macerating them in 100 μl of sterile distilled water (SDW). After 15 min of incubation, a loopful of the resulting suspension was streaked on yeast extract-dextrose-CaCO3 agar (YDCA) amended with 60 mg L-1 cycloheximide. Mucoid, convex and yellow colonies appeared on YDCA after incubation at 28°C for 48h. After colony purification on yeast extract-nutrient-agar (YNA), two isolates from each nursery were subject to amplification and sequence analysis of the 16S rRNA using universal primers FD1/RD1, for genus identification (Vauterin et al. 2000; Weisburg et al. 1991). All 16S rRNA sequences (OP441051) were identical and BLASTn searches indicated that the isolates belong to the genus Xanthomonas [99.9% nucleotide identity with X. hydrangeae strain LMG 31885 (LR990741.1) and 99.8% with strain LMG 31884T (NR_181958.1)]. For classification at species level, fragments of the housekeeping genes gyrB, rpoD, dnaK, and fyuA, were amplified according to Young et al. (2008). Both strands were sequenced and the consensus sequences aligned using MUSCLE as implemented in MEGA X (Kumar et al. 2018). Homologous sequences were once again identical between the isolates. A neighbor joining phylogenetic analysis of the concatenated fragments, was carried out, using the Tuscan isolate HyQ-Tu1, the type/pathotype strains of the seven pathovars of X.hortorum, proposed by Morinière et al. (2020), the four X.hydrangeae strains characterized by Dia et al. (2021) and the type strain of X.populi as the outgroup. The analysis indicated that HyQ-Tu1 isolate clusters within the X. hydrangeae branch of the recently described X. hortorum - X. hydrangeae species complex (Morinière et al. 2020; Dia et al. 2021; 2022). In agreement with this result, isolates tested positive to the LAMP assay specific for members of the complex's clade C (X. hydrangeae) (Dia et al. 2022). Based on molecular evidence, the isolates were identified as X. hydrangeae (Dia et al. 2021; Oren and Garrity, 2022). Three healthy H. quercifolia potted plants were inoculated by rubbing a 10 µl droplet of a bacterial suspension of X. hydrangeae HyQ-Tu1 adjusted to an OD600 of 0.3 (approx. 108 CFU/ml) in SDW on the adaxial surface of two leaves per plant. Two control leaves/plant were inoculated with SDW. Each inoculated leaf was enclosed for 24h in a polyethylene bag and all plants were maintained in a greenhouse at 28°C. Nine days post inoculation (DPI), leaf spots similar to those observed on naturally infected plants started to become evident on the bacteria-inoculated leaves while control leaves remained asymptomatic throughout the trial (21 DPI). Koch's postulates were fulfilled by re-isolating the bacterium from the symptomatic tissues, obtaining a positive amplification with the clade C-specific LAMP assay (Dia et al. 2022), and confirming that the gyrB sequence was 100% identical to that of X. hydrangeae HyQ-Tu1. Housekeeping gene sequences were submitted to GenBank (OP456006-9). Members of the X. hortorum - X. hydrangeae species complex have been reported to affect H. quercifolia in the USA (Uddin et al. 1996) and H. quercifolia and H. arborescens L. in Belgium (Cottyn et al. 2021). To the best of our knowledge, this is the first documentation of X. hydrangeae causing disease on H. quercifolia in Italy. Further work is required to verify the presence of the bacterium in other European countries and to assess the economic impact that it causes within and outside nurseries.

Finite Element Method (FEM) Modeling of Laser-Tissue Interaction during Hair Removal

In this study, a comprehensive and realistic model of laser light interaction with skin and hair was constructed. The model was applied to study the characteristics of laser-tissue interaction for the deeply penetrating Nd:YAG laser. Three types of finite element method (FEM) models were developed. In the first model, the hair shaft grew straight out of the follicle; in the second model, it grew at a variable angle; and in the third model, an array of hair was considered. The transport equation and heat diffusion equation were solved with the mesh-based Monte Carlo method and partial differential equations, respectively. The results of the simulations indicated that the area of necrosis increased with increasing fluence; cooling had a limited effect on the extent of necrosis, particularly at a fluence of 80 J/cm2. The thermal damage to hair follicles on the periphery of an irradiated array of hair may be insufficient for achieving necrosis. The pulse itself and the short cooling-down period after the pulse contributed the most to the final thermal damage to the hair follicle. The FEM modeling of laser-tissue interaction has proven to be a useful tool for studying the influence of different therapeutic parameters on the resulting hair and skin damage.

Comparison of the cardioprotective effects of St. Thomas and del Nido cardioplegia

Objectives: This study aimed to histopathologically examine the cardioprotective effects of St. Thomas and del Nido (DN) cardioplegia. Materials and methods: A total of 18 rabbits aged 23 weeks and weighing 2000 g were included in the experimental animal study. The animals were randomized to three groups, with six rabbits in each group. The first group was determined as the control group and no cardioprotective agent was given after ligation of the aorta. The rabbits in the second group received DN cardioplegia solution, and those in the third group received the St. Thomas cardioplegia solution. The groups were histopathologically graded and evaluated with six different scores. Results: There were statistically significant differences between St. Thomas, DN, and control groups with hematoxylin and eosin, caspase 3 and connexin 43 staining at 30, 60, and 90 min (p<0.05). However, the St. Thomas, DN, and control groups showed equal score 2- and score 3-weighted, score 3-weighted, and score 3-weighted distributions with connexin 43 at 90 min, respectively; there was no statistically significant difference between the groups (p=0.144). Conclusion: The most adverse tissue damage observed were localized hemorrhage and localized necrosis areas at the end of 90 min of cellular damage. Both cardioplegia applications significantly reduced tissue loss compared to the control group. However, we believe that DN cardioplegia has a longer application time and has better protection.

Cutaneous Malignant Melanoma with Testicular Metastases in a Wild Rabbit (Oryctolagus cuniculus).

Melanocytic skin tumours have been rarely described in pet rabbits, and exposure to UV light in sparsely haired areas has been hypothesised to play a cancerogenic role. Here, we describe a case of cutaneous malignant melanoma arising from the skin of the scrotum in an 8-year-old male wild rabbit, with testicular metastases as an unusual metastatic site for melanoma reported in humans to date. The tumour was nearly 5 cm in size, firm, and highly pigmented, with multifocal superficial ulcerations and large areas of intratumoural necrosis. The adjacent testis was 1.5 cm, multinodular, and black, obscuring tissue morphology. Histologically, the dermis was expanded by an infiltrative, densely cellular neoplasm composed of nests and sheets of polygonal to spindle neoplastic melanocytes, supported by scant fibrovascular stroma. Neoplastic cells showed intermediate N/C ratio, moderate basophilic cytoplasm, often obscured by abundant brownish granular pigment, and eccentric nuclei with prominent nucleoli. Cellular pleomorphism and nuclear atypia were severe, and high mitotic activity was observed. Diffuse dermal lymphovascular invasion was also observed. The testis was delimited by a thin tunica albuginea, and the parenchyma was largely obscured in its morphology by densely packed neoplastic cells. Seminiferous tubules, lined with a thin basement membrane and containing neoplastic and scattered spermatogenic cells, were occasionally observed. Neoplastic cells within the skin and the testis were positive for HMB-45, Melan-A, and S-100. The growing popularity of rabbits as pets allows for a greater ability to accumulate data on the spontaneous occurrence of tumours in these animals. Furthermore, descriptions of the biological aspects of spontaneously occurring tumours may serve to improve current knowledge in animal species and humans in which the same neoplasm may occur.

HIGH-DIMENSIONAL HISTOPATHOLOGIC EVALUATION OF THE HYPOXIC MICROENVIRONMENT IN GLIOBLASTOMA

Abstract Rapidly growing solid tumors such as glioblastoma (GBM) are characteristically hypoxic, displaying large areas of necrosis surrounded by hyperproliferative pseudopalisading cells. Intra-tumoral hypoxia develops over time in the three-dimensional space and the degree of tissue oxygenation is a dynamic process that varies continuously. Combined with the extensive inter- and intra-tumoral heterogeneity associated with GBM at the bulk and single cell level, hypoxia contributes to a gradient of molecular alterations that are specific to the different cell populations that make up the bulk of the tumor and reside in specific niches. To date, high dimensional histopathologic analyses of the hypoxic regions within GBM tissue have not been performed. Here, we took a combined spatial and single-cell proteomic profiling approach to investigate the histopathologic features of hypoxia by leveraging a unique clinical study where the exogenous hypoxia marker pimonidazole (PIMO) is administered to patients with GBM prior to surgery. Tissue specimens were subjected to imaging mass cytometry and serial immunohistochemistry using a panel of 27 markers associated with cellular hallmarks of hypoxia, metabolism, proliferation, stemness, angiogenesis, and immune cell types. We took high-resolution imaging and statistical approaches to explore the interplay of the different markers within hypoxic regions of primary and recurrent GBMs, in addition to IDH-mutant gliomas. Our findings elucidate the expression pattern of key biological markers relative to one another, altered composition of different cell types, along with differential proliferative, transcriptional, and translational activation states associated with each cell type within the hypoxic regions of GBM.

Comparative study of the hypoglycemic and cardioprotective effects of glucagon-like peptide-1 receptors agonist exenatide, insulin and their combined use in myocardial ischemia/reperfusion injury in rats with experimental type 2 diabetes

Introduction. Insulin therapy used during acute myocardial infarction (AMI) is associated with a high risk of hypoglycemia and high glycemic variability. Therefore, the search for optimal therapeutic approaches which affect both cardioprotection and glycemic correction is relevant. It is known that agonists of glucagon-like peptide-1 (aGLP1) exhibit a protective effect on the myocardium and are involved in the normalization of carbohydrate metabolism. The combined use of аGLP1 exenatide and insulin can be more effective and safe but not insufficiently studied.The aim of this study was the comparative investigation of the effect of exenatide, insulin, and their combination on the volume of myocardial damage and the level of glycemia in the myocardial ischemia/reperfusion (I/RP) model in rats with experimental diabetes mellitus (DM2).Materials and methods. Neonatal streptozotocin diabetes was modeled in male Wistar rats on the 4th–5th day of life. At the age of 3 months, I/RP was fulfilled in animals with confirmed hyperglycemia. Experimental groups were formed depending on the time of therapy with insulin, exenatide, or their combination; before or after ischemia. Ischemia lasted for 40 min, while reperfusion was 120 min. The size of the myocardium necrosis zone and the changes in glycemia level and its variability were determined.Results. Insulin reduced glycemia, but it increased glycemic variability by 60 % and caused hypoglycemia in 32–37 % of animals. Exenatide reduced blood glucose concentration to the level of fasting glycemia and glycemic variability by 1.5–2 times compared with insulin. Exenatide given before ischemia reduced the area of necrosis by 2.2 times. The combined use of insulin and exenatide was accompanied by the absence of hypoglycemia and a decrease in the necrosis zone by 3.2 times compared to the control.Conclusion. The combined use of aGLP1exenatide and insulin in experimental conditions of I/RP+DM2 is the most effective and safe. This makes promising their joint use in patients with DM2, both at high risk of AMI and those undergoing AMI.

The effect of Callina papaya (Carica papaya L. var. Callina) leaves extract on histopathology of kidney and liver in cigarette smoke-exposed rats (Rattus norvegicus Berkenhout, 1769)

Cigarette smoke is a source of free radicals that can cause oxidative stress that damages organ systems in the body. The study aimed to determine the protective effect of Callina papaya leaves ethanol extract on the histopathology of the kidneys and liver in cigarette smoke exposed rats. The study used 25 male rats divided into five groups, consisting of control (distilled water), negative control (exposed to cigarette smoke/ECS), P1 (ECS and given 100 mg/kg body weight (BW) extract), P2 (ECS and given 200 mg/Kg BW extract), and P3 (ECS and given 300 mg/kg BW extract) for 21 days. On the 22nd day, rats were sacrificed to take kidneys and liver for histopathological preparation. Observation parameters consists of organ index, and histopathology structure. All data were then analyzed using one-way ANOVA with Duncan's pos hoc test (P<0.05). The results showed no significant differences in organ index, glomerular number, and liver central vein area (P>0.05). Inflammation area, necrosis cells number, diameter, and area of glomerulus in kidney at doses of 200 mg/Kg BW and 300 mg/Kg BW showed improvement compared to other treatments (P>0.05). Hepatocyte area, sinusoid diameter, inflammatory area, number of hydropic degeneration cells, and number of necrosis cells in the liver also showed improvement at doses of 200 mg/kg BW and 300 mg/kg BW compared to other treatments (P>0.05). The conclusion shows that the Callina papaya leaves ethanol extract can protect against kidney and liver damage in rats exposed to cigarette smoke.

Geraniol suppresses tumour growth and enhances chemosensitivity of 5-fluorouracil on breast carcinoma in mice: involvement of miR-21/PTEN signalling.

Breast cancer is the most diagnosed cancer in females worldwide. Phytochemicals are among the recent compelling approaches showing anticancer activity. Geraniol is a monoterpenoid showing anti-tumoral potential in cell lines. However, its exact mechanism in breast cancer has not been elucidated. In addition, the possible chemosenstizing effect of geraniol when combined with chemotherapeutic drugs in breast carcinoma has not been previously addressed. Therefore, the aim of the current work is to investigate the potential therapeutic as well as chemosensitizing effects of geraniol on breast carcinoma induced in mice through examination of tumour biomarkers and histopathology profile. Results showed a prominent suppression of tumour growth following geraniol treatment. This was accompanied with miR-21 downregulation that subsequently upregulated PTEN and suppressed mTOR levels. Geraniol was also able to activate apoptosis and inhibit autophagy. Histopathological examination revealed high necrosis areas separating malignant cells in the geraniol-treated group. Combined geraniol and 5-fluorouracil treatment induced more than 82% inhibition of tumour rate, surpassing the effect of each drug alone. It can be concluded that geraniol could represent a promising avenue for breast cancer treatment as well as a potential sensitizing agent when combined with chemotherapeutic drugs.

BI02 Disseminated toxoplasmosis presenting as panniculitis in an immunocompromised patient

Abstract Inflammatory dermatoses and inflammatory reaction patterns to underlying systemic disease are relatively uncommon in immunosuppressed organ transplant recipients (OTRs) and infection should always be suspected as a possible cause. We present an OTR with biopsy-proven panniculitis resulting from disseminated toxoplasmosis, only identified after extensive histological analysis. A 45-year-old Nigerian woman who was profoundly immunocompromised through a combination of a kidney transplant 12 months earlier, hyposplenism due to sickle cell anaemia and a CD4+ count 74 × 106 cells L–1 (> 455 × 106 L–1) presented with a 3-month history of > 20 painful, red–purple and hyperpigmented subcutaneous nodules and plaques up to 2 cm in diameter limited to her legs, associated with fatigue and weight loss. She only had childhood contact with cats. There was no lymphoedema or lymphadenopathy, and she was HIV negative. Urgent skin biopsy excluded Kaposi sarcoma and demonstrated a lobular, necrotizing panniculitis, a mixed inflammatory cell infiltrate and evidence of vasculitis. The cause was unclear; cultures for mycobacterial, fungal and bacterial infections were negative. However, on rereview of histology, within areas of inflammation and necrosis in the subcutaneous fat, there were a few scattered structures (10–30 μm in diameter) consisting of small basophilic periodic acid–Schiff-positive ‘dots’ within bright eosinophilic cytoplasm, raising the possibility of toxoplasmosis. Toxoplasma immuno­staining was positive. Further tertiary review of histology and immunostaining by the Hospital for Tropical Diseases agreed that there was no other causative organism and the panniculitis and vasculitis were consistent with active toxoplasmosis. The diagnosis of toxoplasma reactivation was supported by positive toxoplasma IgG on pretransplant bloods. Magnetic resonance imaging of the head was consistent with cerebral toxoplasmosis. She received treatment with clindamycin, pyrimethamine and folinic acid and, thereafter, long-term cotrimoxazole prophylaxis. Cutaneous toxoplasmosis is rare, with only three reported cases over the last 10 years. Historically, a wide spectrum of clinical morphologies has been described, including maculopapular rashes, nodules, ulcers, dermatomyositis and even mimicry of varicella and graft-versus-host disease. Most cases affect immunocompromised patients. In our patient, this was the result of reactivation of latent infection, which is more common in West Africa, coinciding with profound immunosuppression. In our case, a diagnosis was only made after extensive histological review. Given the varied morphologies of clinical presentations, it is possible that this condition may be easily missed, with potentially serious consequences. In summary, we highlight the importance of maintaining a high index of suspicion for infection and the need for careful clinicopathological correlation in OTRs presenting with apparently atypical inflammatory skin lesions.

Primary epithelioid hemangioendotheliomas and angiosarcomas of the pleura: a clinicopathological and immunohistochemical analysis of 13 cases

Thirteen cases of primary epithelioid hemangioendotheliomas (EHE) and epithelioid angiosarcomas (EA) of the pleura are presented. The patients were 7 men and 6 women between the ages of 34 and 65 years (mean: 47 years). The patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Diagnostic imaging revealed the presence of either diffuse pleural thickening or pleural nodules involving the serosal surfaces. Open surgical biopsies were obtained in all cases. Histologically, eight tumors were characterized by the presence of a cellular proliferation composed of medium-sized epithelioid cells embedded in a myxohyaline stroma and a variable spindle cell component. Cellular atypia was mild to moderate and mitotic activity ranged from 1 to 2 per 2mm2. Immunohistochemical stains for vascular markers, including CAMTA1 were positive, confirming a diagnosis of EHE. Five cases of epithelioid angiosarcomas were characterized by a neoplastic cellular proliferation admixed with areas of necrosis and hemorrhage and characterized by medium-sized epithelioid to spindle-shaped cells with eosinophilic cytoplasm, round to oval nuclei and prominent nucleoli. In addition, marked cytologic atypia and a mitotic activity ranging from 3 to 5 per 2mm2 were identified. Immunohistochemical studies demonstrated positive staining for vascular markers; however, CAMTA1 was negative. Clinical follow-up obtained in eleven cases showed that all patients had died within 30 months post diagnosis. The current study highlights that even though it may be important to histologically separate EHE from EA for academic purposes, primary pleural origin of these tumors appears to portent an aggressive clinical behavior.

Revolutionizing RCC Immunotherapy to Unlock Predictive Biomarkers

Revolutionizing RCC Immunotherapy to Unlock Predictive Biomarkers

Chromophobe-like carcinoma of the thymus: A clinicopathological and immunohistochemical correlation of 5 cases

Five cases of primary thymic carcinoma with distinct histopathological features resembling chromophobe carcinomas are presented. The patients were four men and one woman ranging in age between 43 and 72 years. Clinically, the patients presented with non-specific symptoms of dyspnea and chest pain. Diagnostic imaging revealed the presence of anterior mediastinal masses. All patients underwent complete surgical resection of their tumors via thoracotomy. Grossly, the tumors measured between 4.0 and 5.5 cm in greatest diameter and were ill-defined neoplasms with infiltrative borders; they were light brown in color and had a lobulated surface. Areas of hemorrhage and necrosis were not identified. Histologically, all tumors shared similar histopathological features, mainly the presence of infiltrative tumor islands separated by a fibrocollagenous stroma. At higher magnification, the neoplastic cellular proliferation was composed of medium-sized, round to polygonal cells with eosinophilic or granular cytoplasm and a clear perinuclear cytoplasmic halo, which imparted a chromophobe-like appearance. Nuclear atypia and mitotic activity were identified. Histochemical stains for colloidal iron were negative while immunohistochemical stains for pancytokeratin, cytokeratin 5/6, and p40 were positive in all cases, supporting squamous differentiation in these tumors. Clinical follow-up information was obtained in three patients all of whom died between 3 and 5 years after initial diagnosis, while two patients were lost to follow-up. The cellular characteristics of these tumors represent an unusual variant of thymic carcinoma that may pose a diagnostic challenge in small biopsies and that could be easily confused with other primary or metastatic tumors.

ORAL MYIASIS APPEARING AS A CRATERIFORM ULCER IN THE UPPER LIP

Oral myiasis is uncommon and can clinically appear as an exophytic, ulcerated, and destructive lesion. This study aimed to present a case of oral myiasis, appearing as a crateriform ulcer. A 46-year-old male was referred for evaluation of a painful lesion in the upper lip. Oral examination showed the presence of an extensive crateriform ulcer in the upper lip's mucosal surface. Several larvae could be observed inside the ulcer, and clinical diagnosis was oral myiasis. The patient was submitted to surgical debridement of the ulcer, associated with surgical removal of the larvae and some fragments of the oral mucosa in close contact with the ulcerated areas. Hematoxylin and eosin stained histological slides showed the presence of an inflammed oral mucosa associated with areas of necrosis and the presence of larvae, confirming the diagnosis of oral myiasis. The patient remains in clinical follow-up. Oral myiasis is uncommon and can clinically appear as an exophytic, ulcerated, and destructive lesion. This study aimed to present a case of oral myiasis, appearing as a crateriform ulcer. A 46-year-old male was referred for evaluation of a painful lesion in the upper lip. Oral examination showed the presence of an extensive crateriform ulcer in the upper lip's mucosal surface. Several larvae could be observed inside the ulcer, and clinical diagnosis was oral myiasis. The patient was submitted to surgical debridement of the ulcer, associated with surgical removal of the larvae and some fragments of the oral mucosa in close contact with the ulcerated areas. Hematoxylin and eosin stained histological slides showed the presence of an inflammed oral mucosa associated with areas of necrosis and the presence of larvae, confirming the diagnosis of oral myiasis. The patient remains in clinical follow-up.

#4967 GASDERMIN D IS REQUIRED FOR CONTROL OF NECROPTOTIC CELL DEATH IN AKI

Abstract Background and Aims Contradicting previous reasoning, it is now established that necrotic rather than apoptotic cell death pathophysiologically drives acute tubular necrosis during AKI. Whereas involvement of necroptosis and ferroptosis has been demonstrated by various groups, the role of pyroptosis, a highly immunogenic form of cell death requiring proteolytic activation of gasdermin protein family members, remains uncertain upon AKI. Thus, we aimed to investigate the role of pyroptosis and its mechanism of action in AKI. Method We set to detect gasdermin D (GSDMD) expression in murine renal samples after ischemia/reperfusion injury (AKI) by immunohistochemistry. Furthermore, we investigated GSDMD-deficient mice in IRI and cisplatin-induced AKI. To conclude on mechanisms, we isolated fresh murine renal tubules and measured LDH release over time. We generated MLKL/GSDMDdko mice to investigate the interplay of these caspase-dependent forms of regulated necrosis in AKI. Results After IRI, we detected a specific GSDMD signal in areas surrounding necrotic tubules, whereas no such signal could be detected within necrotic areas. Whereas interference with other forms of regulated necrosis leads to reduced injury, GSDMD-deficient mice demonstrated higher levels of serum creatinine and urea as well as more severe tubular injury compared to wildtypes. In line with the findings of immunohistochemistry, we only found GSDMD protein expression in whole kidney lysates but not isolated renal tubules; and no difference in spontaneous cell death propagation was detectable. Co-deletion of MLKL (effector protein of necroptosis) reversed the sensitization to AKI by GSDMD-deficiency. These results could be reproduced in cisplatin-induced AKI. Conclusion Here, we found an unexpected protective role for GSDMD, the effector protein of pyroptosis, in two different models of AKI. Mechanistically, our studies indicate the effect of GSDMD to function outside the tubular compartment, specifically surrounding areas of tubular necrosis. These infiltrating innate immune cells appear to interfere with tubular necroptosis in a non-cell autonomous manner. Alongside with these mechanistic insights, our data urge caution when inhibition of pyroptosis is therapeutically considered.

MUCORMYCOSIS IN A PEDIATRIC PATIENT WITH ACUTE LYMPHOID LEUKEMIA POST-HSCT: A CASE REPORT

Fungal osteomyelitis is a life-threatening and seldom seen opportunistic infection considered to be an aggressive infection that needs to be addressed promptly to prevent fatal consequences. An 8-year-old male patient at D+242 post-HSCT for ALL, presented an ulcerated lesion with necrotic bed in the hard palate. The incisional biopsy showed acute inflammation with hemorrhage and necrosis with hyphal fungal structures identified on HE staining, with irregular, tortuous thick hyphae morphology, predominant ramifications, and right angles. Additional stains proved to be positive for fungi on the Grocott and negative for BAAR on the Ziehl-Neelsen stain. A surgical debridement approach was performed, leading to a 3.0cm cavity, communicating with the nasal fossa. A prosthetic device was made to occlude the bone defect caused by surgery. The patient is continuing follow-up and should go through another debridement procedure in a new extensive area of necrosis in the maxillary sinus. Fungal osteomyelitis is a life-threatening and seldom seen opportunistic infection considered to be an aggressive infection that needs to be addressed promptly to prevent fatal consequences. An 8-year-old male patient at D+242 post-HSCT for ALL, presented an ulcerated lesion with necrotic bed in the hard palate. The incisional biopsy showed acute inflammation with hemorrhage and necrosis with hyphal fungal structures identified on HE staining, with irregular, tortuous thick hyphae morphology, predominant ramifications, and right angles. Additional stains proved to be positive for fungi on the Grocott and negative for BAAR on the Ziehl-Neelsen stain. A surgical debridement approach was performed, leading to a 3.0cm cavity, communicating with the nasal fossa. A prosthetic device was made to occlude the bone defect caused by surgery. The patient is continuing follow-up and should go through another debridement procedure in a new extensive area of necrosis in the maxillary sinus.