CD34 Immunoreactivity Research Articles

Differential pericyte marker expression in craniofacial benign and malignant vascular tumors.

Vascular anomalies and tumors are common in the head, neck, and craniofacial areas and are associated with abnormalities in the angiomatous architecture. However, the etiology and molecular basis for the pathogenesis of most vascular lesions are still unknown. Pericytes are mural cells that surround endothelial cells. Besides angiogenesis and other physiological functions, pericytes play an important role in vascularized tissue repair and as resident mesenchymal stem/progenitor cells. Perivascular cells demonstrate a distinct immunohistochemical profile, including expression of alpha-smooth muscle actin (α-SMA), CD146, CD105, and PDGFRβ, without endothelial differentiation (absence of CD31 and CD34 immunoreactivity). These pericyte markers have been shown to be expressed in soft tissue hemangiomas. However, they have not been fully examined in intraosseous hemangiomas. In this study, we compared mesenchymal stem cell (MSC)expression of CD146 and α-SMA markers inpericytes from hemangiomas from different tissues and malignant vascular tumors. The results demonstrated an increased expression of pericyte markers in perivascular cells of benign hemangiomas, especially intraosseous hemangiomas and a significantly reduced expression of pericyte markers in malignant angiosarcomas. The evidence provides insight into the function of pericytes in vascular tumors and suggests their role in vascular tumor disease types.

Vasculature in the mouse colon and spatial relationships with the enteric nervous system, glia, and immune cells.

The distribution, morphology, and innervation of vasculature in different mouse colonic segments and layers, as well as spatial relationships of the vasculature with the enteric plexuses, glia, and macrophages are far from being complete. The vessels in the adult mouse colon were stained by the cardiovascular perfusion of wheat germ agglutinin (WGA)-Alexa Fluor 448 and by CD31 immunoreactivity. Nerve fibers, enteric glia, and macrophages were immunostained in the WGA-perfused colon. The blood vessels entered from the mesentery to the submucosa and branched into the capillary networks in the mucosa and muscularis externa. The capillary net formed anastomosed rings at the orifices of mucosa crypts, and the capillary rings surrounded the crypts individually in the proximal colon and more than two crypts in the distal colon. Microvessels in the muscularis externa with myenteric plexus were less dense than in the mucosa and formed loops. In the circular smooth muscle layer, microvessels were distributed in the proximal, but not the distal colon. Capillaries did not enter the enteric ganglia. There were no significant differences in microvascular volume per tissue volume between the proximal and distal colon either in the mucosa or muscularis externa containing the myenteric plexus. PGP9.5-, tyrosine hydroxylase-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers were distributed along the vessels in the submucosa. In the mucosa, PGP9.5-, CGRP-, and vasoactive intestinal peptide (VIP)-immunoreactive nerves terminated close to the capillary rings, while cells and processes labeled by S100B and glial fibrillary acidic protein were distributed mainly in the lamina propria and lower portion of the mucosa. Dense Iba1 immunoreactive macrophages were closely adjacent to the mucosal capillary rings. There were a few macrophages, but no glia in apposition to microvessels in the submucosa and muscularis externa. In conclusion, in the mouse colon, (1) the differences in vasculature between the proximal and distal colon were associated with the morphology, but not the microvascular amount per tissue volume in the mucosa and muscle layers; (2) the colonic mucosa contained significantly more microvessels than the muscularis externa; and (3) there were more CGRP and VIP nerve fibers found close to microvessels in the mucosa and submucosa than in the muscle layers.

Bioresorbable Poly (L-Lactic Acid) Flow Diverter Versus Cobalt-Chromium Flow Diverter: In Vitro and In Vivo Analysis.

Permanent metallic flow diverter (FD) implantation for treatment of intracranial aneurysms requires antiplatelet therapy for an unclear duration and restricts postprocedural endovascular access. Bioresorbable FDs are being developed as a solution to these issues, but the biological reactions and phenomena induced by bioresorbable FDs have not been compared with those of metallic FDs. We have developed a bioresorbable poly (L-lactic acid) FD (PLLA-FD) and compared it with an FD composed of cobalt-chromium and platinum-tungsten (CoCr-FD). FD mechanical performance and in vitro degradation of the PLLA-FD were evaluated. For in vivo testing in a rabbit aneurysm model, FDs were implanted at the aneurysm site and the abdominal aorta in the PLLA-FD group (n=21) and CoCr-FD group (n=15). Aneurysm occlusion rate, branch patency, and thrombus formation within the FD were evaluated at 3, 6, and 12 months. Local inflammation and neointima structure were also evaluated. Mean strut, porosity, and pore density for the PLLA-FD were 41.7 μm, 60%, and 20 pores per mm2, respectively. The proportion of aneurysms exhibiting a neck remnant or complete occlusion did not significantly differ between the groups; however, the complete occlusion rate was significantly higher in the PLLA-FD group (48% versus 13%; P=0.0399). Branch occlusion and thrombus formation within the FD were not observed in either group. In the PLLA-FD group, CD68 immunoreactivity was significantly higher, but neointimal thickness decreased over time and did not significantly differ from that of the CoCr-FD at 12 months. Collagen fibers significantly predominated over elastic fibers in the neointima in the PLLA-FD group. The opposite was observed in the CoCr-FD group. The PLLA-FD was as effective as the CoCr-FD in this study and is feasible for aneurysm treatment. No morphological or pathological problems were observed with PLLA-FD over a 1-year period.

A rare metastatic mesenteric malignant PEComa with TSC2 mutation treated with palliative surgical resection and nab-sirolimus: a case report

BackgroundMalignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas.Case presentationHere, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient’s excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease.ConclusionsThis report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.

The Distribution of Foxp3 and CD68 in Preeclamptic and Healthy Placentas: A Histomorphological Evaluation.

Preeclampsia is a complication of pregnancy that affects 3-5% of pregnancies and is one of the major causes of maternal/neonatal mortality and morbidities worldwide. We aimed to investigate the distribution of Foxp3+ regulatory T-cells and CD68+ Hofbauer cells in the placenta of preeclamptic and healthy pregnant women with a special focus on correlating these findings with placental histology. Decidua and chorionic villi of the placenta obtained from healthy and preeclamptic pregnancies were evaluated in full-thickness sections. Sections were stained with hematoxylin and eosin and Masson's trichrome and immunostained for Foxp3 and CD68 for histological analyses. The total histomorphological score for placentas was found to be higher in preeclamptic placentas than that in the controls. The CD68 immunoreactivity was higher in the chorionic villi of preeclamptic placentas than that in the controls. The immunoreactivity of Foxp3 was found widely distributed within the decidua in both the groups and did not differ significantly. Interestingly, Foxp3 immunoreactivity in the chorionic villi was found mainly in the villous core and, to a lesser extent, in the syncytiotrophoblasts. We found no significant relation between Foxp3 expressions and morphological changes observed in preeclamptic placentas. Although extensive research is being carried out regarding the pathophysiology of preeclampsia, the findings are still controversial.

CD99 and NKX2.2 positive neuroblastoma diagnosed on cytology: A potential diagnostic pitfall and necessity of pathological evaluation of the primary site.

Immunohistochemistry plays a vital role in the diagnosis of small round cell tumors. CD99 immunonegativity is one of the features, which helps in distinguishing neuroblastoma from other small round cell tumors. NKX2.2 is a specific marker of Ewing sarcoma, which is a differential for poorly differentiated neuroblastoma. Here, we present a case of metastatic neuroblastoma showing immunoreactivity for both CD99 and NKX2.2 on cytology of the metastatic site causing diagnostic dilemma. Biopsy study of the adrenal lesion revealed presence of differentiating cells and neuropil, highlighting the importance of evaluation of the primary site and limitation of cytology.

Solitary extramedullary plasmacytoma of the gingiva—A case report with literature review

Abstract Extramedullary solitary plasmacytoma (EMP) is a plasma cell neoplasm involving the soft tissues without the involvement of the bone marrow. In this case report, we present an isolated soft tissue growth on the lingual gingiva of the left mandibular canine-premolar region diagnosed as EMP based on clinical, histological, and laboratory results. Orthopantomogram and occlusal radiographs showed no osteolytic lesions. Hematoxylin and Eosin staining showed sheets of inflammatory cells, predominantly atypical plasma cells with varying degrees of differentiation showing features of pleomorphism, and multinucleated giant cells with intervening collagen fibers. Positive immunoreactivity for CD56, CD138, and kappa light chain restriction were observed. Serum protein electrophoresis demonstrated an increase in IgA levels and immunofixation electrophoresis confirmed the presence of the M band in the IgG and kappa lanes, indicating monoclonal gammopathies. Based on the above findings, the case was diagnosed as EMP; the consultant pathologist, however, recommended excluding multiple myeloma.

CD44 Expression in Oral Lichen Planus and Related Lesions-An Immunohistochemical Study.

Cluster of differentiation 44 (CD44) is a cell surface adhesion protein involved in the progression and metastasis of oral squamous cell carcinoma. The current study aims to evaluate the expression of CD44 in oral lichen planus and related lesions and thereby assess the relative risk of malignant transformation of these lesions. Formalin-fixed paraffin-embedded tissue blocks of 10 oral lichen planus (Group 1), 10 oral lichenoid lesions (Group 2), 8 with oral lichen planus with dysplasia (Group 3), and 5 with lichenoid dysplasia (Group 4) were included in the study. Immunostaining was done for the tissue sections using CD44 mouse monoclonal antibody. Staining density, staining intensity, and immunoreactive scores of CD44 were evaluated in all four groups. Statistical analysis was done by Statistical Package for the Social Sciences® software and the Kruskal-Wallis test was used. CD44 staining pattern of lichenoid dysplasia and lichen planus with dysplasia changed from membranous to cytoplasmic. The membranous CD44 immunoreactivity was mild with a score of 2.25 for Group 3 and 1.6 for Group 4 whereas moderate for other groups with a P-value of 0.009. The cytoplasmic immunoreactivity was significantly high in Group 3 (5.3 ± 2.6) followed by Group 4 (3.2 ± 1.2), Group 2 (1 ± 1.8), and Group 1 (0.7 ± 1.3) with a P-value of 0.001. The CD44 membranous immunoreactivity scores were low while the cytoplasmic immunoreactivity was high in oral lichen planus with dysplasia and oral lichenoid dysplasia when compared to oral lichen planus and oral lichenoid lesions. CD44 immunostaining pattern can help in assessing the malignant transformation of oral lichen planus or lichenoid lesions.

Neuroinflammation and microglial activation as target for therapeutic strategy: in vitro and in vivo models of study

AbstractBackgroundAlzheimer's disease (AD) is characterized by the extracellular accumulation of senile plaques composed of beta‐amyloid (Aβ) and the intracellular deposition of neurofibrillary tangles composed of hyperphosphorylated tau (Tp). Aβ oligomers (AβO) induce damage beginning with loss of synapses, followed by neurite network disorganization and neuronal death. Neuroinflammation plays an essential role in the disease. In AD patient brains, reactive microglia are closely colocalized with amyloid plaques, indicating their close link. Aβ‐activated microglia produce neurotoxic cytokines/chemokines which subsequently cause neuronal dysfunction and death.MethodUsing rat primary cultures of cortical neurons and microglial cells, generating a solution of AβO/protofibrils, playing with the concentration and time of exposure, we were able to mimic the early effects (acute neuronal loss) and the neuroinflammatory response.ResultAt the beginning of the exposure, we observed a Aβ phagocytosis, followed by a strong increase of TREM2/OX41 marker associated with cytokines release and CD206 (M2 marker) decrease over the time.In addition, microglial activation was deeply studied in the hippocampus of aged mice infused with the AβO/protofibril preparation. We observed progressive Tp accumulation associated with neurodegeneration and progressive activation of microglial cells (transition from a phagocytosis stage to a pro‐inflammatory stage with over‐expression of IBA1, CD68 immunoreactivity and production of pro‐inflammatory cytokines).ConclusionIn this work, we proposed vitro/vivo models showing differential and consecutive microglial responses to Aβ. These models are useful for targeting microglial in the pre‐disease period (in vitro) and for modulating the microglial response in the brain once the disease process is underway, and hold promise as a disease‐modifying treatment strategy.

Molecular and immunohistochemical comparison between primary gastrointestinal mucosal melanomas and atypical gastrointestinal stromal tumors.

It is sometimes challenging to differentiate between gastrointestinal (GI) mucosal melanoma and gastrointestinal stromal tumors (GISTs) because they share some similarities in histological and molecular features. In this study, we investigated their clinicopathological and molecular features. Four primary GI mucosal melanomas and 4 atypical GISTs resected from 2017 to 2019 were included. Electronic medical records and histology slides were reviewed and, if needed, immunohistochemical stainings were additionally done. Somatic mutations were analyzed using whole exome sequencing (WES) with tumors and matched normal tissues. By immunohistochemistry, GISTs were positive for CD117 (4 of 4), DOG1 (4 of 4), and CD34 (2 of 4). In contrast, melanomas were positive for CD117 (2 of 4), HMB-45 (4 of 4), Melan-A (4 of 4), and S100 protein (3 of 4). Using WES, the KIT mutation was detected in 2 of 4 GISTs and 1 of 4 melanomas, all of which showed strong CD117 immunoreactivity. PDGFRA mutation was detected in 2 of 4 GISTs but 0 of 4 melanomas. TP53, NF1, RB1, TERT, and KMT2D mutations were detected in 1 of 4 melanomas but 0 of 4 GISTs. A patient with KIT-mutated melanoma was treated with Gleevec and has remained disease-free for 1 year. GISTs and GI melanomas have a wide histopathological spectrum. Appropriate ancillary studies can be helpful for proper diagnosis and optimal treatment.

Hepatocyte paraffin-1, CD10, and CD34 immunostaining as a diagnostic aid in cytologic diagnosis of hepatic cancer.

Cytomorphological distinction between hepatocellular carcinoma and metastatic tumors to the liver may be difficult, especially when these have poor differentiation. The present study was done to assess the diagnostic utility of hepatocyte paraffin-1 (HepPar-1), CD10, and CD34 in differentiating hepatocellular carcinoma from metastatic carcinoma. Ultrasound-guided fine-needle aspiration was performed on 50 patients with space-occupying lesions of liver suspicious for malignancy on clinical/radiologic findings. The cytological assessment was done on smears stained with May-Grünwald-Giemsa and hematoxylin and eosin. Cell blocks were prepared, and immunostaining for HepPar-1, CD10, and CD34 was done. In these 50 patients, hepatocellular carcinoma was diagnosed in 7 and metastatic tumors in 43 cases. The sensitivity of smears in diagnosing hepatocellular carcinoma was 100% and the specificity was 95.3%, while the sensitivity and specificity of cell block were 100%. A canalicular pattern of CD10 immunoreactivity had a 100% positive predictive value for diagnosing hepatocellular carcinoma. CD10 had a sensitivity of 57.1% and 41.9% in identification of HCC and metastatic tumors, respectively. For the diagnosis of hepatocellular carcinoma, the sensitivity of CD34 was 85.7% and the specificity of sinusoidal pattern of immunoreactivity was 100%. The sensitivity and specificity of granular cytoplasmic staining pattern of HepPar-1 were 100% in hepatocellular carcinoma. The staining patterns of HepPar-1, CD10, and CD34 are highly specific in distinguishing hepatocellular carcinoma from metastasis. These three immunomarkers should be included in the immunocytochemical panel for differentiating hepatocellular carcinoma from metastatic carcinoma to the liver.

Relationship Between Immunohistochemical CD3, CD4, CD5, CD8, and PD1 Staining and Histopathological Diagnosis of Cervical Lesions in Patients With Abnormal Colposcopic Findings.

This study aimed to analyse the relationship between clinicopathological factors in cervical intraepithelial lesions and abnormal colposcopic findings. Thirty high-grade squamous intraepithelial lesion (HSIL) and thirty low-grade squamous intraepithelial lesion (LSIL) patients who underwent biopsy due to abnormal colposcopic findings were included in the study. The immunoreactivity of CD3, CD4, CD5, CD8, and PD-1 was analysed immunohistochemically in tumor-infiltrating lymphocytes (TILs) and stromal lymphocytes. In TILs, CD3, CD4, CD5, CD8, and PD-1 were highly stained in 20/30 (66.6%), 16/30 (53.3%), 15/30 (50.0%), 24/30 (80.0%), and 13/30 (43.3%) of the cases for the HSIL group, while 7/30 (23.3%), 4/30 (13.3%), 5/30 (16.6%), 9/30 (30.0%), and 5/30 (16.6%) were in the LSIL group, respectively. CD3, CD4, CD5, CD8, and PD-1 immunostainings for TILs were higher in the HSIL group (p=0.001, p=0.001, p=0.006, p˂0.001, p=0.024, respectively). Only PD-1 was significantly higher in lymphocytes in the stroma (p=0.001). CD3, CD4, and CD8 also show a positive correlation with the Ki-67 proliferation index. CD3, CD4, CD5, and CD8 may contribute to PD-1-mediated tumour control. Immunohistochemical staining plays a key role in evaluating the tumour microenvironment.

Determination of Microvessel Density by CD34 Immunoreactivity in Female Breast Cancer and its Relation with Grading and Staging

Background: Angiogenesis is a basic process that enables neoplasm to thrive. Microvessel density (MVD) evaluation is an accepted parameter for assessing the angiogenesis process within a tumour. The research was focused to evaluate angiogenesis by using CD34 immunomarker in invasive breast cancer and to correlate the microvessel density with grades and stages. Objective: To determine microvessel density by CD34 immunoreactivity in female breast cancer and its relation with grading and staging. Methods: This cross-sectional descriptive type of study was conducted in the Department of Pathology, Rajshahi Medical College. Forty-five untreated cases of breast cancer were included in this study between the period of July 2019 to June 2021 and paraffin embedded sections were obtained from representative mastectomy specimen. The sections were stained with hematoxylin and eosin stain followed by evaluation of angiogenesis by using CD34 antibody. Results: In this study, most of the patients (71.1%) belonged to age < 50 years where the mean age was found 47.5 + 12.4 years. In 45 cases, tumour sizes ranged from 1-8 cm. 86.7% (39 cases) ranges from 0-5 cm, where only (6 cases) 13.3% were more than 5 cm. About 30 cases (66.7%) lymph nodes were positive for metastasis. According to histopathological grade 51.1% belonged to grade III followed by 28.9% grade II and 20% grade I. Histological stage showed most of the cases was stage II (48.9 %) followed by stage I (26.7 %) then stage III (24.4 %). Upon statistical analysis, a significant relation was obtained between MVD with increasing histologic grades and stages. Conclusion: As a new prognostic marker it would be of great value in diagnosis and in identifying patients at high risk of tumor recurrence more accurately. By this way breast cancer patients might be benefited from adjuvant therapies.

S1990 Colonic Lymphangiomatosis

Introduction: Colonic Lymphangiomatosis Case Description/Methods: A 73-year-old male with history of diabetes mellitus and chronic kidney disease underwent CT abdomen and pelvis with IV contrast (for the evaluation of hematuria and renal cyst), which showed incidental finding of free intraperitoneal air. The patient had a history of recent colonoscopy which showed a large concentration of ‘polyps’ in the sigmoid, not amenable for endoscopic removal. Subsequently the patient developed abdominal pain and nausea, and labs showed worsening leukocytosis 17K/uL. Repeat computed tomography (CT) abdomen revealed moderate free intraperitoneal air and innumerable colonic mucosal cysts of the very redundant sigmoid colon in the right upper quadrant. The patient underwent exploratory laparotomy, and although no perforation was seen, the sigmoid colon exhibited soft-tissue fullness, prompting partial sigmoid colectomy with primary anastomosis. The resected specimen showed large contiguous well circumscribed and simple cystic structures (up to 3 cm size) giving a sessile “polypoid” appearance of the mucosa ( Figure a). Histologic sections demonstrated overlying unremarkable colonic mucosal surface without epithelial dysplasia or serrated neoplasia, large cystic spaces extending into the submucosa, focally separated by thin fibrous septae (Figure b). The contiguous cystic spaces within the muscularis propria were noted to be lined by a bland and attenuated cell layer, showing immunoreactivity for CD31, CD34 and D2-40 (podoplanin – an immunostain defining lymphatic space endothelium) (Figure c); compatible with dilated lymphatic spaces and consistent with colonic lymphangiomatosis (CL). Discussion: CL should be considered as a differential in patients with multiple aggregated mucosal lesions that appear as polyps on endoscopy. Speculation on etiology has ranged from developmental (failure to establish connections to lymphatic drainage sites), or seen secondarily after trauma, prior surgeries, radiation, lymphatic obstruction possibly secondary to adjacent mass lesion, or previous inflammatory processes. Free intraperitoneal air may suggest impending clinical decline in such patients. Surgical resection is the treatment of choice in symptomatic patients.Figure 1.: (a) Gross image of the sigmoid colon, bottom aspect showing partial deroofing of the mucosa of a simple cystic cavity (b) Hematoxylin and Eosin (H&E) stain 40X (c) D2-40 positivity (brown membranous and cytoplasmic staining) 100X.

High expression of CD8 in the tumor microenvironment is associated with PD-1 expression and patient survival in high-grade serous ovarian cancer.

Objective:The current study assesses programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and associates our results with neoadjuvant chemotherapy history and disease prognosis.Materials and Methods:We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher’s Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1.Results:Univariate analysis demonstrated that optimal debulking (p<0.001), early International Federation of Gynecology and Obstetrics stage (p=0.046), and higher scores of stromal CD8+ TIL expression (p=0.028) in tumor cells were all substantially correlated with longer disease-free survival (DFS), whereas the remaining variables analyzed, including PD-1 positivity, stromal CD3+, and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs, were not correlated with DFS. Also, univariate analysis revealed that optimal debulking (p=0.010), and higher scores of stromal CD8+ TIL expression (p=0.021) in tumor cells were all substantially correlated with longer overall survival (OS).Conclusion:Higher scores of stromal CD8+ TILs are substantially correlated with DFS and OS in univariate analyses, whereas scores of stromal CD3+ and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs are not correlated with DFS and OS in both univariate and multivariate analyses. Also, we found a significant association between PD-1 positivity and the scores of stromal CD3+ TILs and intraepithelial CD8+ TILs. However, no remarkable relationship was revealed between PD-1 positivity and the survival of HGSOC cases.

Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion.

Simple SummaryLittle is known about the functions and intracellular mechanisms of the endothelial cells in liver grafts. In particular, we still know little about the effect of the most recent machine perfusion techniques currently applied to improve liver transplant outcomes. In this study we analyzed different endothelial markers of both immunohistochemical and gene expression in two different biopsies (for each donor). We observed a severe depression of endothelial trophism in liver grafts, which is restored after reperfusion. This is interesting for further studies on liver grafts, especially considering that the execution of HOPE seems to improve this functional recovery. We propose that our results may help improve the knowledge on graft tissues in order to customize the perfusion techniques prior to transplant and, therefore, improve liver transplant outcomes.The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy (at the stage of organ allocation) and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period (p < 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p < 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions.

Immunohistochemical analysis of CD31 expression in myocardial tissues from autopsies of patients with ischemic heart disease

CD31, a transmembrane protein expressed on endothelial and hematopoietic cells, plays important roles in leukocyte trafficking, mechanotransduction, angiogenesis, vascular permeability, and regulation of cellular responsiveness. CD31 immunoreactivity is employed as a sensitive and specific endothelial marker in diagnostic pathology. In this study, CD31 expression in myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were examined by immunohistochemical staining. We examined 24 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained within 48 h postmortem from the autopsies of patients who were diagnosed with ischemic heart disease. CD31 expression was observed in vascular endothelial and endocardial cells. In necrotic myocardium, diffusion of CD31 antigen was observed. Elevated CD31 expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, fibrotic myocardial foci did not show upregulated CD31 expression. The same CD31 expression characteristics as those observed in the human samples were observed in the mouse model. CD31 immunostaining as an endothelial and microvasculature marker may be a useful complement to conventional staining techniques currently used in the diagnosis of ischemic heart disease, and may allow the timing and process of myocardial remodeling to be analyzed in detail.

THE EFFECT OF DEXAMETHASONE ON HEMATOLOGIC PROFILES, HEMOSPORIDIAN INFECTION, AND SPLENIC HISTOLOGY IN HOUSE FINCHES (HAEMORHOUS MEXICANUS).

Research on host response to infectious disease often involves pharmacological induction of immunosuppression, frequently through administration of dexamethasone. Reports on the effect of dexamethasone in birds are largely restricted to poultry and pigeons. This study describes changes in white blood cell (WBC) differentials, hemoparasite counts, splenic histology, and splenic CD3 immunoreactivity in House Finches (Haemorhous mexicanus). Experimental group birds (n=9) were treated with a daily intramuscular injection of 25 µg of dexamethasone for 8 d; a control group (n=9) received daily saline solution. Smears were made with blood collected immediately before the first dose (day 0) and on d 4, 8, and 9, and stained with modified Wright. The WBC differential counts were performed by three blinded observers, parasite counts by two blinded observers, and histology by one blinded observer. Dexamethasone-treated birds experienced relative heterophilia and lymphopenia on d 4 (P=0.008); heterophilia was also present at d 8 (P=0.018). Hemosporidian counts were significantly increased in dexamethasone-treated birds on d 4 and 8 (P=0.048 and P=0.031, respectively). In contrast with control birds, all dexamethasone-treated birds lacked histologically apparent splenic lymphoid follicles (P<0.001). No significant difference was observed in splenic CD3 immunoreactivity between groups. Our results indicate that dexamethasone has an effect on the hematologic profile of House Finches and suggest that it may be a useful method to induce immunosuppression in this species.

Superficial myofibroblastoma of the lower female genital tract: A clinicopathological analysis of 15 cases

ObjectiveTo describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female genital tract. MethodsThe clinicopathological data and immunohistochemical findings were retrospectively analyzed in 15 cases of superficial myofibroblastoma. Meanwhile, a systematic literature review was conducted. ResultsThe age of patients ranged from 34 to 73 years (median, 49 years). Most patients presented with nodular or polypoid masses ranging in size from 0.4 cm to 6.5 cm. Twelve tumors were located in the vagina, two in the vulva, and one in the cervix. Microscopically, the tumor was located in the subepithelial tissue, with a clear boundary and without capsule on the surface. The tumor cells were spindle, oval, stellate or wavy, and arranged in various architectural patterns of reticular, fascicular, wavy and disorderly patterns. There were no obvious cellular atypia and mitotic figures. Thin collagen fibers and thin-walled vessels could be observed in all cases. Most cases were diffusely and strongly reactive to Vimentin (12/12), Desmin (14/15), ER (15/15) and PR (13/14). Variable immunoreactivity for CD34 (8/15), Caldesmon (2/8), SMA (4/14) and CD99 (4/5) were observed. The tumors showed a low Ki67 proliferative index (≤5 %). Follow-up information was available in 10 patients and there was no evidence of recurrence or metastasis. ConclusionsSuperficial myofibroblastoma is a rare benign tumor that originates from the hormone-sensitive, subepithelial mesenchymal tissue of the lower female genital tract, and should be differentiated from other mesenchymal tumors.

Thyroid angiosarcoma: A case report and review of literature.

Thyroid angiosarcoma is a very aggressive and rare malignancy that is mostly seen in elderly of Alpine regions, related to high prevalence of iodine deficient goiter. The major diagnostic challenge is to distinguish between this entity and anaplastic carcinoma and to specify whether it is a primary or metastatic angiosarcoma. The objective of this work is to clarify this distinction through our case report and a revue of literature. We report the case of a 55 years-old female patient, with no medical history, admitted to the General Surgery Department of Ibn Sina Hospital in Rabat for the management of a cervical mass classified sonographically TI-RADS 6. It was also noted a lesion of the skin next to the thyroid lodge. The patient underwent total thyroidectomy with simple post-operative course. A third tumor location was discovered in the stomach during Oesophago-Gastro-Duodenoscopy (OGD). Microscopically, the thyroid, cutaneous and gastric tumors showed rows of oval to spindle-shaped cells, with marked cytonuclear atypia and high mitotic activity. The stroma was richly vascularized and fibro-inflammatory. Immunohistochemical studies demonstrated that the tumor cells showed positive staining for cytokeratin (AE1/AE3), CK7, ERG and CD31, while they exhibited no immunoreactivity for CK20, thyroglobulin or CD34. The first diagnostic challenge is to rule out anaplastic carcinoma. Using and the classification proposed by Cutlan et al. and a large immunohistochemical panel the diagnosis of epithelioid angiosarcoma was retained. Based on epidemiological and clinical criteria, the primary site in our case was more likely to be cutaneous. In summary, thyroid angiosarcoma is an uncommon thyroid neoplasm which poses a problem of differential diagnosis with anaplastic carcinoma and metastatic angiosarcoma. The use of a large panel of antibodies as well as the epidemiological and clinical data can solves the problem in the most difficult cases. • Thyroid angiosarcoma is a very rare malignancy that is mostly seen in elderly of Alpine regions, related to high prevalence of iodine deficient goiter. • It is a very aggressive tumor that can rapidly spread to the cervical lymph nodes, lungs, and brain or can metastasize to the duodenum, small bowel and large bowel. • Metastatic disease is associated with poor prognosis and limits the mean survival time to a few months after diagnosis and surgical treatment. • The first diagnostic challenge is to rule out an angiomatoid anaplastic carcinoma, using a large panel of antibodies. • The second challenge is to specify whether it is a primary or metastatic angiosarcoma especially when other sites are involved, based on clinical and epidemiological criteria.