The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis.

Sequence studies of the entire exome and transcriptome of lymphoma tissues have identified MYD88 and PIM1 as involved in the development and oncogenic signaling. We aimed to determine the frequency of MYD88 and PIM1 mutations, as well as their expressions in conjunction with the clinicopathological parameters identified in mature large B-cell non-Hodgkin lymphomas. The ten-year retrospective study included 50 cases of mature large B-cell lymphoma, diagnosed at the Pathology Department of the Emergency County Hospital of Constanta and Sacele County Hospital of Brasov. They were statistically analyzed by demographic, clinicopathological, and morphogenetic characteristics. We used a real-time polymerase chain reaction technique to identify PIM1 and MYD88 mutations as well as an immunohistochemical technique to evaluate the expressions of the 2 genes. Patients with lymphoma in the small bowel, spleen, brain, and testis had a low-performance status Eastern Cooperative Oncology Group (P = .001). The Eastern Cooperative Oncology Group performance status represented an independent risk factor predicting mortality (HR = 9.372, P < .001). An increased lactate dehydrogenase value was associated with a low survival (P = .002). The international prognostic index score represents a negative risk factor in terms of patient survival (HR = 4.654, P < .001). In cases of diffuse large B-cell lymphoma (DLBCL), immunopositivity of MYD88 is associated with non-germinal center B-cell origin (P < .001). The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.

The Predictive Role of the Histopathological Scoring System in Adipose Tumors-Lipoma, Atypical Lipomatous Tumor, and Liposarcoma.

Lipomatous tumors are the most frequent soft tissue neoplasms. Sometimes their differential diagnosis is difficult to perform only by microscopic analysis. This study aims to create a histopathological scoring system and highlight the impact of intratumoral microvascular density. This study was conducted over 10 years. We analyzed the main pathogenic pathways (MDM2 and CDK4), as well as the tumor microvascularization (CD31 and CD34) by immunohistochemical tests. We also analyzed the status of the MDM2 gene by CISH. These data, together with the clinical and histopathological information, were statistically analyzed by appropriate tests. We identified 112 eligible cases, with most of the patients being in their sixth decade of life, with a slight predominance of the female sex. We found important associations like tumor location linked to nuclear pleomorphism severity and microvascularization density correlated with atypia severity. Also, we observed that a maximum diameter of a tumor of at least 69 mm is associated with the presence of tumor necrosis. The score designed in this study shows an increased sensitivity and specificity for the diagnosis of lipomas (100%, respectively, 97%), atypical lipomatous tumors (93.8%, respectively, 82.3%), and liposarcomas (100%, respectively, 90.5%). This present study enhances the present data by bringing to attention the histopathological score with a role in differential diagnosis, as well as in the prediction of immunohistochemical and genetic tests. Also, we highlighted the importance of microvascular density, especially in the diagnosis of liposarcomas.

Clinicopathological Outlines of Post-COVID-19 Pulmonary Fibrosis Compared with Idiopathic Pulmonary Fibrosis.

This review brings together the current knowledge regarding the risk factors and the clinical, radiologic, and histological features of both post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF), describing the similarities and the disparities between these two diseases, using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists, and researchers make an accurate diagnosis, which can help identify the group of patients selected for anti-fibrotic therapies and future therapeutic perspectives.

PD-L1, CD4+, and CD8+ Tumor-Infiltrating Lymphocytes (TILs) Expression Profiles in Melanoma Tumor Microenvironment Cells.

(1) Background: Because melanoma is an aggressive tumor with an unfavorable prognosis, we aimed to characterize the PD-L1 expression in melanomas in association with T cell infiltrates because PD-1/PD-L1 blockade represents the target in treating melanoma strategy. (2) Methods: The immunohistochemical manual quantitative methods of PD-L1, CD4, and CD8 TILs were performed in melanoma tumor microenvironment cells. (3) Results: Most of the PD-L1 positive, expressing tumors, have a moderate score of CD4+ TILs and CD8+TILs (5-50% of tumor area) in tumoral melanoma environment cells. The PD-L1 expression in TILs was correlated with different degrees of lymphocytic infiltration described by the Clark system (X2 = 8.383, p = 0.020). PD-L1 expression was observed often in melanoma cases, with more than 2-4 mm of Breslow tumor thickness being the associated parameters (X2 = 9.933, p = 0.014). (4) Conclusions: PD-L1 expression represents a predictive biomarker with very good accuracy for discriminating the presence or absence of malign tumoral melanoma cells. PD-L1 expression was an independent predictor of good prognosis in patients with melanomas.

Morphopathological features induced by SARS-CoV-2 infection - a series of 57 autopsies.

BACKGROUND: COVID-19 is a systemic disease with multiorgan damage, which requires a better understanding and deepening of histopathogenesis in order to improve treatment. Autopsy remains a gold standard to establish certain diagnoses and to integrate the morphological spectrum of lung lesions, explaining the cause of death, into a clinical context. METHODS AND RESULTS: The study included 57 autopsies performed during 2020-2021 associated with SARS-CoV-2 infection. Among the autopsies we performed, diffuse alveolar damage (DAD) was the most common pulmonary morphological change, 31.8% of them with acute or exudative phase and 33.3% with proliferative phase of DAD. Acute fibrous organizing pneumonia or organizing pneumonia with fibrous remodeling processes and pulmonary fibrosis were rarely observed. The most unfavorable outcome and death associated with SARS-CoV-2 infection was frequent in older men, with a high rate of comorbidities. Microscopically, SARS-CoV-2 presents many common aspects with MERS-CoV and SARS-CoV-1, such as alveolar hyaline membrane, desquamated alveolar cells, alveolar edema and alveolar and interstitial lymphocyte and monocytes infiltration. CONCLUSIONS: Our study includes a large number of autopsies on patients with SARS-CoV-2 infection performed in Romania. COVID 19 associated pneumonia combines classical aspects of alveolar and interstitial pneumonia with some peculiarities. Autopsies are of major importance in understanding SARS-CoV-2 infection.

Umbilical Cord Teratoma - A Short Case Report.

Background: Teratomas can occur in the umbilical cord, and may or may not be associated with other congenital abnormalities. Case report: This 35-year-old primigravida gave birth 37-38 weeks to a 3290-g normal female. The umbilical cord, at 10 cm from the abdominal insertion, had an 8 cm mature teratoma. Work-up revealed no other abnormalities. Discussion: Mature teratomas may occur in the umbilical cord, and may or may not have additional clinical sequalae.

Implications of Cellular Immaturity in Necrosis and Microvascularization in Glioblastomas IDH-Wild-Type.

Necrosis and increased microvascular density in glioblastoma IDH-wild-type are the consequence of both hypoxia and cellular immaturity. Our study aimed to identify the main clinical-imaging and morphogenetic risk factors associated with tumor necrosis and microvascular in the prognosis of patient survival. We performed a retrospective study (10 years) in which we identified 39 cases. We used IDH1, Ki-67 and Nestin immunomarkers, as well as CDKN2A by FISH. The data were analyzed using SPSS Statistics. The clinical characterization identified only age over 50 years as a risk factor (HR = 3.127). The presence of the tumor residue, as well as the absence of any therapeutic element from the trimodal treatment, were predictive factors of mortality (HR = 1.024, respectively HR = 7.460). Cellular immaturity quantified by Nestin was associated with reduced overall survival (p = 0.007). Increased microvascular density was associated with an increased proliferative index (p = 0.009) as well as alterations of the CDKN2A gene (p < 0.001). CDKN2A deletions and cellular immaturity were associated with an increased percentage of necrosis (p < 0.001, respectively, p = 0.017). The main risk factors involved in the unfavorable prognosis are moderate and increased Nestin immunointensity, as well as the association of increased microvascular density with age over 50 years. Necrosis was not a risk factor.

Hypoxia-Inducible Factors and Diabetic Kidney Disease-How Deep Can We Go?

Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.

Characterization of the Tumor Microenvironment and the Biological Processes with a Role in Prostatic Tumorigenesis.

Prostate intratumoral heterogeneity, driven by epithelial−mesenchymal plasticity, contributes to the limited treatment response, and it is therefore necessary to use the biomarkers to improve patient prognostic survival. We aimed to characterize the tumor microenvironment (T lymphocyte infiltration, intratumoral CD34, and KI-67 expressions) by immunohistochemistry methods and to study the biological mechanisms (cell cycle, cell proliferation by adhesion glycoproteins, cell apoptosis) involved in the evolution of the prostate tumor process by flow-cytometry techniques. Our results showed that proliferative activity (S-phase) revealed statistically significant lower values of prostate adenocarcinoma (PCa) and benign prostatic hyperplasia (BPH) reported at non-malignant adjacent cell samples (PCa 4.32 ± 4.91; BPH 2.35 ± 1.37 vs. C 10.23 ± 0.43, p < 0.01). Furthermore, 68% of BPH cases and 88% of patients with PCa had aneuploidy. Statistically increased values of cell proliferation (CD34+ CD61+) were observed in prostate adenocarcinoma and hyperplasia cases reported to non-malignant adjacent cell samples (PCa 28.79 ± 10.14; BPH 40.65 ± 11.88 vs. C 16.15 ± 2.58, p < 0.05). The CD42b+ cell population with a role in cell adhesion, and metastasis had a significantly increased value in PCa cases (38.39 ± 11.23) reported to controls (C 26.24 ± 0.62, p < 0.01). The intratumoral expression of CD34 showed a significantly increased pattern of PCa tissue samples reported to controls (PCa 26.12 ± 6.84 vs. C 1.50 ± 0.70, p < 0.01). Flow cytometric analysis of the cell cycle, apoptosis, and adhesion glycoproteins with a critical role in tumoral cell proliferation, T cell infiltrations, Ki-67, and CD 34 expressions by IHC methods are recommended as techniques for the efficient means of measurement for adenocarcinoma and hyperplasia prostate tissue samples and should be explored in the future.

Surfactant proteins analysis in perinatal deceased preterm twins among the Romanian population.

The molecular basis of the evaluation of children suspected of having disorders of surfactant proteins is still under discussion. In this study, we aimed to describe the morphological characteristics and to evaluate the immunohistochemical expression of surfactant proteins (surfactant protein A [SPA], surfactant protein B, and pro-surfactant protein C) in the preterm twins that deceased due to unexplained respiratory distress syndrome (n = 12). Results showed statistically significant positive correlations between surfactant protein B expressions and pulmonary hemorrhage (ρ = 0.678; P < .05), SPA levels, and Apgar score (ρ = 0.605; P < .05) and also expressions of SPA and bronchopneumonia (ρ = 0.695; P < .05). The fetuses and neonates of the same gestational age showed differences among surfactant proteins regarding the immunostaining expression. Our data evidence a marked interindividual variability in the expression of all 3 surfactant proteins among the cases analyzed (n = 12), suggesting the intervention of some individual and epigenetic factors during gestation that might influence surfactant protein production and consequently survival rate.

A Case of Giant Mesenchymal Uterine Tumor: Lipoleiomyoma.

BACKGROUND Uterine lipoleiomyoma is a rare benign tumor composed of varying proportions of smooth muscle fibers and mature adipocytes, without identification of hemorrhage, necrosis, or cyto-architectural atypia. It is part of the leiomyomas category, with an incidence of 0.03-0.2%. The pathogenesis of this lesional category is still unclear, but there are several theories that could explain the occurrence. Magnetic resonance imaging is the most useful diagnostic imaging method. There are a number of pathologies whose exclusion is necessary, with the differential diagnosis being made mainly based on microscopic examination and completed with immunohistochemical tests. Their treatment, when necessary, is surgical, with an excellent post-therapeutic evolution and prognosis. CASE REPORT We present the case of an elderly, postmenopausal patient who presented with abdominal pain, abnormal vaginal bleeding, and pollakiuria. The associated pathologies of the patient correspond to those mentioned in the literature, the particularities of the case being given by the large size of the tumor and the association with 2 other typical leiomyomas. Immunohistochemical markers used to exclude other diagnoses (desmin, h-caldesmon, S100, calretinin, MDM2, CD34) confirmed the diagnosis of uterine lipoleiomyoma. Because the patient was symptomatic and a large nodular mass was identified by ultrasound, surgical treatment was performed. CONCLUSIONS Although it is a benign lesion with an excellent prognosis, the pathogenetic mechanisms are not fully known. Theories of pathogenesis range from misplacing embryonic adipocytes to connective tissue fatty degeneration, and further studies are needed to establish the origin of this lesion.

Assessment of programmed death-ligand 1 receptor immunohistochemical expression and its association with tumor-infiltrating lymphocytes and p53 status in triple-negative breast cancer.

Breast cancer (BC) is the second most frequent type of cancer for both sexes combined, after lung cancer. Triple-negative BC (TNBC) molecular subtype is characterized by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) immunoexpression or amplification and represent 10-20% of all BC cases. The issue of the present study was to analyze the associations between programmed death-ligand 1 (PD-L1) immunoexpression and distribution of stromal tumor-infiltrating lymphocytes (stTILs) combined with clinico-morphological features of patients with TNBC. Secondly, our research evaluated PD-L1 immunoexpression as a prognostic factor and its correlation with p53 immunoexpression. Thirty cases with primary TNBC without prior neoadjuvant therapy were included in this research. stTILs were identified in all cases, most of them with low distribution (66.7%). A positive immunoreaction for PD-L1 was observed in 40% of cases. The PD-L1 immunoexpression was statistically significant associated with age, pathological tumor size, lymphovascular invasion, stTILs level, the presence of cluster of differentiation 8-positive (CD8+) TILs and p53 immunoexpression. In the present study, a positive PD-L1 immunoexpression was associated with a worse distant metastasis free survival (DMFS). We also found not only that high stTILs level were associated with a better DMFS but also that there was a statistically significant association between stTILs level and PD-L1 immunoexpression. Our results bring new insights to the fine connections between tumor microenvironment and molecular changes of TNBC. It helps us to better understand these aggressive tumors to identify the more useful biomarkers for predicting the response to adjuvant therapy and can represent a method for selecting the most suitable patients for immunotherapy.

Morphological characteristics of a mucinous adenocarcinoma of the prostate: differential diagnosis considerations.

Mucoid adenocarcinoma of the prostate is a very rare variant, account less than 1% of prostatic adenocarcinomas. In this respect, the most common histopathological type of prostate cancer is acinar adenocarcinoma. Diagnosis of this variant is very important due to peculiarities: aggressive biologic behavior, poor response to radiotherapy. Although these tumors are not as hormonally responsive as acinar adenocarcinomas, some of them respond to androgen withdrawal. Before making a diagnosis of primary mucinous adenocarcinoma, is necessary to exclude an extraprostatic malignant neoplasia, especially from the bladder or bowel. We present the case of a male patient who suffered a transurethral prostatic resection surgery. Histopathological examination revealed malignant tumor cells floating in a pool of mucus or even acini mixed with signet ring cells. A particular aspect is that floating mucus cells have a non-papillary pattern similar to colloid carcinoma of the breast. The use of monoclonal antibody revealed positive immunoreaction of malignant cells for prostatic specific markers and excluded neoplastic invasion of the bladder or bowel carcinoma.

Atypical adenomatous hyperplasia of the prostate mimicking adenocarcinoma lesion: case report and literature review.

The diagnosis of prostate cancer is challenging because of the existence of lesions that mimic adenocarcinoma. Such a lesion is atypical adenomatous hyperplasia (AAH) or adenosis, which represents a proliferation of crowded, small to medium glands with basal cell layer invariably present, but often inconspicuous on routine stains. The importance of the lesion lies in the potential for being misdiagnosed as low-grade adenocarcinoma (Gleason 1 or 2). We present the case of a male patient, who suffered a transurethral prostatic resection surgery. Histopathological examination showed benign prostatic hyperplasia with a focus of crowded glands with a nodular appearance. The presence of basal cell was assessed using high molecular-weight cytokeratin (HMWCK), clone 34ßE12 and p63 immunostaining, which revealed discontinuous positive immunostaining. In adenocarcinomas, the basal cell layer is absent. This case highlights the usefulness of 34ßE12 antibodies, avoiding a false positive diagnosis of cancer, with negative consequences on the patient's psychological condition and treatment costs. We recommended the follow-up of the patient.