Immunohistochemical and Morphometric Analysis of Lung Tissue in Fatal COVID-19.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage.

Preoperative MRI accuracy after neoadjuvant chemoradiation for locally advanced rectal cancer.

Background and aims: To evaluate the performance of magnetic resonance imaging (MRI) in restaging locally advanced rectal cancers (LARC) after neoadjuvant chemoradiotherapy (nCRT), with pathologic correlation. Methods: 80 patients with LARC treated with neoadjuvant therapy, with restaging MRI and surgery, were enrolled and prospectively reviewed. The diagnostic accuracy of the restaging MRI was assessed for tumor (ymrT), nodal status (ymrN), circumferential resection margin (ymrCRM), extramural vascular invasion (ymrEMVI) and tumoral deposits (ymrN1c) by calculating the sensitivity (Se), specificity (Sp), negative predictive values (NPV) and positive predictive values (PPV). Response to treatment was classified as good response (complete/near complete) vs. poor response (poor/partial response). The agreement between the tumor regression grade at MRI (mrTRG) and pathology (pTRG) was reported, as well the performance of mrTRG to identify good responders. The correlation between restaging MRI and histopathology was assessed by Spearman correlation coefficient. Results: The MRI accuracy ranged between 63.8% and 92.5% for T stage and was 81.3% for N stage. All MRI parameters evaluated at restaging were statistically significant correlated with histopathology evaluation, but EMVI. There was moderate correlation for N and N1c and a positive strong correlation for T, CRM and TRG (Spearman correlation coefficient of 0.390 for mrN1c-pN1c, 0.428 for mrN-pN, 0.522 for mrCRM-pCRM, 0.550 for mrT-pT and 0.731 for mrTRG-pTRG). Diagnostic accuracy of anal sphincter invasion was 91.3%, with a negative predictive value (NPV) of 100%. Accuracy rate varied between 70% for partial response to 93.75% for complete response after nCRT. Conclusions: MR imaging had good accuracy in restaging LARCs after nCRT. Our results showed high MRI accuracy in detecting anal sphincter involvement for low rectal tumors, with high NPV to exclude tumoral invasion. Restaging MRI predicted well the tumor regression grade, with good diagnostic performance in differentiating good responders from poor/partial responders. The accuracy was high for detecting complete response.

Identification of Histopathological Biomarkers in Fatal Cases of Coronavirus Disease: A Study on Lung Tissue.

We aimed to evaluate the primary lung postmortem macro- and microscopic biomarkers and factors associated with diffuse alveolar damage in patients with fatal coronavirus (COVID-19). We retrospectively analyzed lung tissue collected from autopsies performed in Cluj-Napoca, Romania, between April 2020 and April 2021 on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examined 79 patients with confirmed SARS-CoV-2 infection, ages 34 to 96 years, split into two groups using the cut-off value of 70 years. Arterial hypertension (38%) and type 2 diabetes mellitus (19%) were the most common comorbidities with similar distribution between groups (p-values > 0.14). Macroscopically, bloody exudate was more frequently observed among patients < 70 years (33/36 vs. 29/43, p-value = 0.0091). Diffuse alveolar damage (53.1%) was similarly observed among the evaluated groups (p-value = 0.1354). Histopathological biomarkers of alveolar edema in 83.5% of patients, interstitial pneumonia in 74.7%, and microthrombi in 39.2% of cases were most frequently observed. Half of the evaluated lungs had an Ashcroft score of up to 2 and an alveolar air capacity of up to 12.5%. Bronchopneumonia (11/43 vs. 3/36, p-value = 0.0456) and interstitial edema (9/43 vs. 2/36, p-value = 0.0493) were significantly more frequent in older patients. Age (median: 67.5 vs. 77 years, p-value = 0.023) and infection with the beta variant of the virus (p-value = 0.0071) proved to be significant factors associated with diffuse alveolar damage.

Morphological aspects of basal cell carcinoma vascularization.

Basal cell carcinoma (BCC) is a malignant skin cancer which commonly exhibits aberrant blood flow because of angiogenesis. Its invasiveness and lack of metastatic potential may be explained by the typical pattern of vascularization seen in BCCs, where blood vessels are absent in the tumor islands and prominent in the tumor's periphery. From clinical point of view, high-frequency ultrasound (HFUS) is a useful tool for the evaluation of the lateral and depth extension of these tumors; furthermore, by employing color Doppler, important data regarding the vascularization degree of BCCs is provided. Knowingly, the sonographic vascular pattern of cutaneous tumors can aid in improving diagnosis and treatment by differentiating between benign and malignant lesions, between various types of cutaneous malignancies and also between various types of BCC (e.g., low risk versus high risk). Our aim was to perform a review integrating all currently known vascular properties of BCC as a tumor entity.

Thyroid carcinoma associated with other primary neoplasms, a single center study.

Background and aims: Thyroid carcinoma is the most frequent endocrine malignancy. It develops following a complex interaction of environmental and genetic factors. Its incidence is on the rise mostly due to the frequent diagnosis of microcarcinomas (tumor <1 cm). In most cases, it has very good prognosis and survival rates. The incidence of a second primary malignancy in thyroid cancer patients is higher than in the general population. In this article, we focus on the role of BRAF V600E mutation in the development of other primary neoplasms associated with thyroid carcinoma. Methods: This study was conducted in the department of Nuclear Medicine and Genetics of the "Prof. Dr. Ion Chiricuța" Institute of Oncology of Cluj-Napoca. We evaluated patients with thyroid carcinoma, who were diagnosed and treated for other malignancies such as breast, colorectal, lung cancer and malignant melanoma. In addition, we tested for the BRAF V600E mutation using paraffin samples of patients. Results: We identified 17 patients that had thyroid carcinoma associated with other primary malignancies. Two of the patients included in the study had three associated primary cancers. The time interval between the diagnoses of two primary neoplasms in the same patient was 6.15 years, with a standard deviation (SD) of 5.39 years. The most common primary tumor associated with thyroid carcinoma in this study was breast cancer. We applied genetic testing for the BRAF V600E mutation in 12 patients. The BRAF V600E mutation positivity rate was 26.9% and most of the cancer associations were metachronous (occurring at least 6 months after thyroid cancer). Conclusions: The BRAF V600E mutation is an important prognostic factor in the neoplasms included in this study, but its presence is not a predictive factor for the appearance of a metachronous or synchronous associated primary neoplasm to thyroid cancer.

The Evaluation of the Four-Chamber Cardiac Dissection Method of the Fetal Heart as an Alternative to Conventional Inflow-Outflow Dissection in Small Gestational-Age Fetuses.

The examination of very small fetal hearts requires special equipment and a specialist that are not available in many general pathology laboratories. Compared to conventional examination, the four-chamber cardiac dissection (4CCD) method can be performed by any pathologist using instruments generally available in pathology services. The aim of this study is to evaluate the efficiency of the 4CCD method in the examination of small fetal hearts using post-mortem magnetic resonance imaging (pm-MRI) at 7T as the standard. Twelve fetuses with gestational ages between 13 and 19 weeks have been included in this study. All fetuses underwent pm-MRI examination prior to pathologic examination. The 4CCD method was used for the cardiac examination in all cases following the same guidelines for cardiac sectioning. The 4CCD was able to identify all cardiac anatomic structures as compared to pm-MRI at 7T, demonstrating a sensibility of 95.8% (95% CI, 94.5-95.8) and specificity of 100% (95% CI, 32.3-100). The overall accuracy in identifying cardiac anatomic structures was 95.8% (95% CI, 93.4-95.8). Additionally, the 4CCD method was able to detect cardiac anomalies with an overall diagnostic accuracy of 91% (95% CI, 85.8-94.2), sensibility of 67.6% (95% CI, 54.5-75.3), and specificity of 97% (95% CI, 93.7-99) as compared to pm-MRI at 7T. The four-chamber view dissection method can be considered as an alternative to the conventional inflow-outflow dissection method in selected cases.

Antibody-functionalized theranostic protein nanoparticles for the synergistic deep red fluorescence imaging and multimodal therapy of ovarian cancer.

Among women, ovarian cancer is the fifth most frequent type of cancer, and despite benefiting from current standard treatment plans, 90% of patients relapse in the subsequent 18 months and, eventually, perish. As a result, via embracing nanotechnological advancements in the field of medical science, researchers working in the areas of cancer therapy and imaging are looking for the next breakthrough treatment strategy to ensure lower cancer recurrence rates and improved outcomes for patients. Herein, we design a novel phototheranostic agent with optical features in the biological window of the electromagnetic spectrum via encapsulating a newly synthesized phthalocyanine dye within biocompatible protein nanoparticles, allowing the targeted fluorescence imaging and synergistic dual therapy of ovarian cancer. The nanosized agent displays great biocompatibility and enhanced aqueous biostability and photothermal activity, as well as high reactive-oxygen-species generation efficiency. To achieve the active targeting of the desired malignant tissue and suppress the rapid clearance of the photosensitive agent from the peritoneal cavity, the nanoparticles are biofunctionalized with an anti-folate receptor antibody. A2780 ovarian cancer cells are employed to confirm the improved targeting capabilities and the in vitro cytotoxic efficiency of the theranostic nanoparticles after exposure to a 660 nm LED lamp; upon measurement via MTT and flow cytometry assays, a significant 95% decrease in the total number of viable cells is seen. Additionally, the therapeutic performance of our newly designed nanoparticles was evaluated in vivo, via real-time thermal monitoring and histopathological assays, upon the irradiation of tumour-bearing mice with a 660 nm LED lamp (0.05 W cm-2). Foremost, separately from steady-state fluorescence imaging, we found that, via utilizing FLIM investigations, the differences in fluorescence lifetimes of antibody biofunctionalized and non-functionalized nanoparticles can be correlated to different intracellular localization and internalization pathways of the fluorescent agent, which is relevant for the development of a cutting-edge method for the detection of cancer cells that overexpress folate receptors at their surfaces.

Age-Related Changes of the Pineal Gland in Humans: A Digital Anatomo-Histological Morphometric Study on Autopsy Cases with Comparison to Predigital-Era Studies.

Background and objectives: The pineal gland is a photoneuroendocrine organ in the midline of the brain, responsible primarily for melatonin synthesis. It is composed mainly of pinealocytes and glial tissue. This study examined human postmortem pineal glands to microscopically assess age-related changes using digital techniques, and offers a perspective on evolutionary tendencies compared to the past. Materials and Methods: A retrospective autopsy study has been performed on 72 pediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with glial fibrillary acidic protein (GFAP). Slides were assessed under polarized light and digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. Results: Thirty-three females and 39 males were included in the study, grouped under three age groups: 0-25, 46-65, and 66-96 years of age. The peak gland volume was found within the 46-65 age group, the overall mean volume was 519 mm3, the main architectural types were lobular and insular, and the mean percentage of pineal calcification was 15% of the gland, peaking within the 66-96 age group, with a predominantly globular shape. Glial cysts were found in 20.8% of cases. The intensity of GFAP stain was maximal in the pediatric age group, but the extent of glial tissue was much larger in elderly patients. Discussion: The degenerative process of the pineal gland can be quantified by measuring normal parenchyma, calcifications, glial tissue, and glial cysts. Morphometric differences have been observed and compared to a similar studies performed in the published literature. The current study, unfortunately, lacks a 26-45 age group. Digital techniques seemed to offer a more exact analysis, but returned similar results to studies performed over 40 years ago, therefore offering important information on evolutionary tendencies. Conclusions: Increase in glial tissue, calcifications, and glial cysts have a defining role as age-related changes in the pineal gland.

Particular Morphological Features in the Diagnosis of Pediatric Helicobacter pylori Gastritis: A Morphometry-Based Study.

BACKGROUND: Current pediatric guidelines recommend the use of the Updated Sydney Classification for gastritis to assess histological changes caused by Helicobacter pylori (H. pylori) infection. The purpose of this study was to investigate the morphometric alterations of the antral mucosa in relation to pediatric H. pylori infection. METHODS: A total of 65 cases were considered eligible. Apart from scoring the biopsies according to the recommendations, foveolar hyperplasia (FH) was assessed. The following measurements were performed on digital slides: total mucosal thickness, foveolar and glandular length, number of glandular cross sections per 40X field, glandular diameter, and distance between glands. RESULTS: The thickness of the antral mucosa increased along with the bacterial density and the intensity of inflammation in H. pylori-infected children (p < 0.05). FH was significantly associated with the presence of H. pylori (p < 0.001) and also exhibited a greater length of the foveolar and glandular structures and an increased glandular diameter (p < 0.05), but without influencing the thickness of the mucosa. CONCLUSIONS: Our results reinforce the fact that FH is not only an important histologic characteristic of gastropathy, but is also a significant change observed in H. pylori infection in children and may be considered for reporting when evaluating pediatric gastric biopsies.

Human Chorionic Gonadotropin Improves the Proliferation and Regenerative Potential of Bone Marrow Adherent Stem Cells and the Immune Tolerance of Fetal Microchimeric Stem Cells In Vitro.

Nongonadal tissues express luteinizing hormone-chorionic gonadotropin receptors (LHCG-R) which are essential for their growth during fetal development. Adult mesenchymal stem/stromal cells (MSCs) have been shown to express functional LHCG-R outside pregnancy conditions, making them susceptible to hCG stimulation. In the present study we tested the effect of hCG treatment on bone marrow (BM) derived adherent stem cells in vitro, isolated from a parous women, mother of male sons, in order to evaluate its effect on maternal MSCs and in the same time on fetal microchimeric stem cells (FMSCs), to better understand the outcomes of this safe and affordable treatment on cell proliferation and expression of pluripotency genes. Our study highlights the beneficial effects of hCG exposure on gene regulation in bone marrow adherent stem cells through the upregulation of pluripotency genes and selection of more primitive mesenchymal stem cells with a better differentiation potential. Validation of these effects on MSCs and FMSCs long after parturition in vivo represents a close perspective as it could set the premises of a new mobilization strategy for the stem cell transplantation procedures in the clinical setting.

Isolation and Characterization of a Fetal-Maternal Microchimeric Stem Cell Population in Maternal Hair Follicles Long after Parturition.

Fetal-maternal microchimerism describes the acquisition of fetal stem cells (FSC) by the mother during pregnancy and their long-term persistence after parturition. FSC may engraft in a variety of maternal tissues especially if there is organ/tissue injury, but their role and mechanism of persistence still remains elusive. Clinical applications due to their pluripotency, immunomodulatory effects and accessibility make them good candidates for ex-vivo manipulation and autologous therapies. The hair follicles contain a distinctive niche for pluripotent stem cells (PSC). To date, there is no published evidence of fetal microchimerism in the hair follicle. In our study, follicular unit extraction (FUE) technique allowed easy stem cell cultures to be obtained while simple hair follicle removal by pull-out technique failed to generate stem cells in culture. We identified microchimeric fetal stem cells within the primitive population of maternal stem cells isolated from the hair follicles with typical mesenchymal phenotype, expression of PSC genes and differentiation potential towards osteocytes, adypocites and chondrocytes. This is the first study to isolate fetal microchimeric stem cells in adult human hair long after parturition. We presume a sanctuary partition mechanism with PSC of the mother deposited during early embryogenesis could explain their long-term persistence.

The role of medical registries, potential applications and limitations.

Medical registries provide highly reliable data, challenged hierarchically only by randomized controlled trials. Although registries have been used in several fields of medicine for more than a century and a half, their key role is frequently overlooked and poorly recognized. Medical registries have evolved from calculating basic epidemiological data (incidence, prevalence, mortality) to diverse applications in disease prevention, early diagnosis and screening programs, treatment response, health care planning, decision making and disease control programs. Implementing, maintaining and running a medical registry requires substantial effort. Developing the registry represents a complex task and is one of the major barriers in widespread use of registries. Medical registries have potential to evolve to a next generation by taking benefit from recent semantic web technology developments. This paper is aimed at providing a summary of the basic information available on medical registries and to highlight the progress and potential applications in this field.

Expression of toll-like receptors in ovarian cancer.

PURPOSE: Ovarian cancer continues to be the most lethal gynecologic malignancy, with a complex tumor microenvironment (TME). We investigated the immunohistochemical (IHC) expression of toll like receptors (TLRs) 4,5,7 and 9 together with CD68 and CD 163 as markers for tumor-associated macrophages (TAM) in relation to clinicopathological data. METHODS: Data from 102 patients with serous ovarian cancer treated between 2006 and 2011 was retrospectively reviewed. A TLR IHC score was developed and CD68, CD163 density scores were calculated as the mean number of positive cells from three 0.5 mm2 areas. RESULTS: Advanced-stage disease (FIGO IIIC-IV) was present in 65.7% of cases. A TLR4 score above median was associated with peritoneal carcinomatosis (odds ratio/OR) 3.02, p=0.019) or ascites (OR 2.5, p=0.041). In FIGO stage IIIC-IV patients with a platinum-free interval (PFI) >12 months had, in comparison with patients with PFI ≤12 months, a higher CD68 density score (191.9 ± 95.2 vs. 152.7 ± 69.4, p=0.066) and a lower CD163 density score (106.7 ± 73.3 vs. 154.5 ± 73.9, p=0.011). In early-stage ovarian cancer patients, TLR9 positivity was associated with a higher overall survival than in patients with absent expression (110.2 vs. 22 months, p<0.001), while advanced-stage patients with TLR7 positivity had a lower overall survival than patients with negative TLR7 (38.3 vs. 66.2 months, p=0.01). CONCLUSIONS: Our data shows that TLRs and TAM are important prognostic markers and future studies are needed to better comprehend the immune response in ovarian cancer.

Endobronchial ultrasound - one year of experience in clinical practice.

BACKGROUND AND AIM: Endobronchial ultrasound (EBUS) is a recent minimally invasive, safe examination method for the mediastinum, with a good diagnostic precision. This method makes possible real time examination with transbronchial fine needle aspiration, diagnostic transbronchial needle aspiration (TBNA) and staging of non-small pulmonary tumors, as well as diagnosis of mediastinal and hilar adenopathies of various causes. METHODS: We present the experience of the Bronchoscopy Department of the Pulmonology Clinic of Cluj-Napoca with EBUS-TBNA as a tool for the diagnosis and staging of tumors in contact with the bronchial wall and mediastinal and hilar adenopathies of unknown etiology. During the period August 2014 - January 2016 we examined 152 patients with no direct or indirect signs of lung tumor in traditional bronchoscopy. Rapid on site evaluation (ROSE) was available for all patients. RESULTS: Our study is a retrospective study of 152 EBUS-TBNA examinations. The average age of our patients was 54.43 years and 64% came from urban and 36% from rural background. EBUS-TBNA brought the final histological confirmation (tumors, sarcoidosis, limphoma) in 82.8% of the cases. A tumor confirmation was obtained in 95% of the patients who were suspected of having tumor. For a better understanding of the importance of this method in the daily clinical practice we present a case of peripheral pulmonary neoplasm with mediastinal and hilar adenopathies, where the contribution of EBUS-TBNA to a rapid diagnosis was essential. CONCLUSION: By the introduction of this method in our country one year ago, we can diagnose patients with lung and mediastinal tumors, which cannot be diagnosed by traditional bronchoscopy. This brings a valuable contribution to the improvement of lung cancer staging and diagnostic.

The use of EBUS-TBNA and ROSE in the diagnosis of lung cancer.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method for diagnosing and staging of lung cancer. EBUS-TBNA obtained small specimens. Rapid on-site examination (ROSE) is a rapid, real-time examination method. The aim of our study is to evaluate the impact of ROSE on adequate specimen sampling, rapid results and high diagnostic rate. We present the experience of the Department of Bronchology, "Leon Daniello" Clinic of Pulmonology, Cluj-Napoca, Romania, with EBUS-TBNA as a tool for diagnostic of adenopathies of unknown etiology. We evaluated the diagnostic capacity of ROSE for malignant tumors, by considering the histopathological examination as the diagnostic "gold standard". In our retrospective and descriptive study, we analyze the data of 147 EBUS-TBNA examinations with ROSE and histopathological exam, performed for diagnostic purposes for hilar and mediastinal adenopathies of unknown origin. The age of the patients varied from 21 to 80 years, with an average age of 54.36 years. There were 98 male patients, representing 66.66% of the group. From the total of 90 cases of malignancy, 72 (80%) cases were identified as a primary lung tumor, 13 (14.44%) cases were identified as lymphoma, and five cases as malignant tumor of extrapulmonary origin. The sensitivity of the ROSE is 85.71%. By the introduction of this method, EBUS-TBNA with ROSE, in our country, we can diagnose patients with lung and mediastinal tumors, which cannot be diagnosed by traditional bronchoscopy. This brings a valuable contribution to the improvement of lung cancer diagnostic.

Non-Hodgkin lymphoma in Romania: a single-centre experience.

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.

Endobronchial ultrasound EBUS--a new method for the diagnosis and staging of lung cancer.

In this paper we present a new method, endobronchial ultrasound (EBUS), which appeared recently among the tools of the pulmonologist for the diagnosis and staging of lung cancer. Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) provides the opportunity for obtaining tissue samples required for the histologic and cytologic diagnosis of lung cancer. The advantages of EBUS have to be made popular as it is a minimally invasive method, safe, simple, fast, also with a superior cost/benefit ratio compared to any previously used methods.

The role of microRNAs in the pathogenesis of HIV-related lymphomas.

The incidence of HIV-related lymphomas (HRLs) is increased by 60-100 times in patients with HIV. When compared to the general population, patients with HRLs often present with extranodal lymphoid proliferation, most frequently of the gastrointestinal tract, central nervous system, liver and bone marrow. MicroRNAs (miRs) are non-coding double-stranded RNA molecules of 18-25 nucleotides that regulate post-translational gene expression by inhibiting translation or promoting degradation of messenger RNA complementary sequences. Before their discovery, tumorigenesis was thought to have been caused by the alteration of protein-coding oncogenes and tumor-suppressor genes, but once identified in B-cell chronic lymphocytic leukemia, miRs function as either oncogenes or tumor-suppressor genes was confirmed in different types of malignancies. Since miRs are clearly involved in tumorigenesis in many cancers, their role in HRLs is now receiving attention. A few studies have been conducted thus far in some HRLs on the involvement of miR in the pathogenesis of lymphoid malignancies. Since B-cell lymphomas arise from various stages of B-cell development in both HIV-infected and HIV-naïve patients, investigators have tried to determine the different miR signatures in B-cell development. As classic immunohistochemistry staining is sometimes not enough for the differential diagnosis of HRLs, in the present review, we have described the potential use of miRs in the prognosis and diagnosis of these diseases.

Castleman Disease. A Report of Six Cases.

BACKGROUND AND AIMS: Castleman's disease is a rare disorder situated at the boundary between reactive and neoplastic conditions. The pathogenesis is a subject of debate and the limited number of cases renders the study of the disease difficult. In our paper we present a series of six cases of Castleman disease with emphasis on the clinical presentation, pathology examination and the use of immunohistochemistry in the final diagnosis of the cases. PATIENTS AND METHOD: The classification of the disease was based on clinical, imaging and pathological assessment. Specimens were obtained by surgical excision and were routinely processed for the pathology examination. RESULTS: All cases were unicentric disease. Two cases were locally extensive. The clinical symptoms were related mostly to compression effects. Five case were of the hyaline-vascular type and one was included in the plasma cell variant. One case showed angiomyoid differentiation. CONCLUSIONS: We strongly believe that by understanding the pathogenesis of the precursor lesions we will gain better understanding of the pathways that lead to neoplasia and that Castleman disesase is a very interesting "natural experiment" illustrating the progression from chronic antigen stimulation to reactive lymphoid hyperplasia and finally to overt lymphoid neoplasia.