Prognostic significance of E-Cadherin and B-Catenin in non-muscle invasive bladder cancer.

Non muscle invasive bladder cancer (NMIBC) has unpredictable outcomes with a variable risk of recurrence and progression. Many clinic-pathological prognostic factors have been identified but remain insufficient, raising the need to investigate new biomarkers. The aim of our study was to assess the prognostic value of the immunohistochemical (IHC) markers E-Cadherin and B-Catenin in NMIBC. All cases of NMIBC were collected between 2008 and 2013. IHC analysis was performed using E-Cadherin and B-Catenin. Reduced or loss of E-Cadherin expression was assessed as abnormal. Only cases with B-Catenin intense membranous staining were considered normal. A correlation was found between abnormal E-Cadherin expression and stage (p = 0.001), grade (p = 0.0000000), recurrence (p = 0.0000000), progression (p = 0.01), recurrence-free survival (p = 0.00000001), and progression-free survival (p = 0.01). A statistically significant association was found between B-Catenin and stage (p = 0. 05), grade (p = 0.02), and recurrence (p = 0.02). The abnormal expression of these markers could help to identify a high-risk subgroup of NMIBC that might benefit from either more accurate follow-up or more aggressive treatment.

Prognostic significance of tumor suppressor protein p53 in prostate cancer.

INTRODUCTION: The p53 gene mutation is one of the most common genetic alterations in many cancers. In prostate cancer (PCa), it has been associated with a poor prognosis, tumor progression and aggressiveness. P53 mutation induces an abnormal protein expression in related tissues. AIM: This study aimed to assess p53 expression using immunohistochemistry in PCa and to discuss its prognostic value. METHODS: We have retrospectively collected all cases of PCa diagnosed in our pathology department between 2012 and 2022. An automatized immunohistochemical analysis was performed using monoclonal p53 antibody. For each case, we assessed the proportion of positive cells and the intensity of staining. P53 expression was considered abnormal when it was totally negative or overexpressed (>=50% of positive cells). RESULTS: Twenty-four cases have been selected. Abnormal p53 expression was found in 42% of cases (P53 was overexpressed in 6cases and totally negative in 4 cases). Mean age of patients with p53 abnormal expression was 70years old. Patients with p53 abnormal expression had Gleason score >7 in 5 cases, ISUP grade >2 in 3 cases, peri-neural invasion in 8cases, capsule invasion in 9cases. All patients with p53 overexpression developed androgen resistance (p<0.01). CONCLUSION: An aberrant expression profile of the p53 protein was observed in 42% of cases, and a statistically significant association was found with androgen resistance. Our results suggest a potential prognostic role of p53 in PCa.

Immunochemistry-based quantification of tumor-infiltrating lymphocytes and immunoscore as prognostic biomarkers in bladder cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and the derived immunoscore (IS) have gained considerable attention over the last decade as prognostic markers in many solid cancers. However, in bladder cancer (BC), their prognostic value is not clearly established. METHODS: The present study aimed to quantify the TILs rates in BC, assess the derived immunoscore, and investigate their prognostic value. An immunochemistry-based quantification of the different subtypes of TILS was performed on paraffin-embedded blocks from patients with invasive urothelial carcinoma of the bladder. We have assessed the rates of TILs, respectively, on peri-tumoral (PT) and intra-tumoral (IT) areas and calculated for each case the corresponding IS which is the index: CD8+/CD3+ TILs. The IS was then classified as low (I0, I1) or high (I2, I3, I4). We included 30 cases in the analysis. RESULTS: The median age of patients was 65 years with a sex ratio of 9. TILs densities and distribution were significantly variable between IT and PT areas CD3+ (p = 0.03) and CD8+ (p = 0.004) with the highest rates on the PT areas. In univariate analysis, a low density of CD8+ TILs was significantly associated with an advanced age (p = 0.05), with the presence of lympho-vascular invasion (p = 0.02) and with the absence of specific histological subtype (p = 0.05). A low immunoscore was significantly associated with the presence of lympho-vascular invasion (p = 0.004). No significant association was found between TILs subpopulations, the IS, and the other clinicopathological and survival data. The overall survival (OS) and disease-free survival (DFS) medians were slightly superior in highly T (CD3+/CD8+)-cell infiltrated tumors as well as tumors with a high IS densities. However, the univariate analysis showed that TILs and immunoscore did not impact overall survival (OS) and disease-free survival (DFS). CONCLUSION: TILs and immunoscore might be effective prognostic tools in BC. However, standardized quantification methods and further investigation on larger samples are highly recommended to definitively attest the prognostic value of TILs and IS in BC.

Immunohistochemical analysis of myeloperoxidase expression in cutaneous leucocytoclastic vasculitis.

Myeloperoxidase (MPO) is a pro-oxidant enzyme mainly found in the azurophilic granules of neutrophils. It not only displays a key role in the intracellular microbial killing process but also contributes to the extracellular clearance of several pathogens. This study aimed to detect MPO in cutaneous leukocytoclastic vasculitis (LCV) using immunohistochemistry. We retrospectively collected 22 confirmed cases of skin LCV diagnosed in our pathology department over 11 years (2012-2023). Immunohistochemistry was performed using anti-myeloperoxidase antibody (Leica clone 59A5) on the LeicaBond MAX automated system, following manufacturer's instructions. Two pathologists assessed immunohistochemical staining, scoring intensity as weak (+), moderate (++), or strong (+++). Patients' mean age was 56.9 years, with a male-to-female ratio of 1.18. Pathologically, vasculitis involved small blood vessels in all cases. Immunohistochemical analysis showed granular positive MPO staining in 59.1% of cases. Staining intensity was weak in 46.15%, moderate in 46.15%, and strong in 7.69%. Staining was patchy in 84.62% and diffuse in 15.38% of cases. MPO expression, detected in 59.1% of cutaneous LCV tissues, exhibited a patchy and peri-vascular distribution. It holds potential as a diagnostic marker for patients with early or minor histological changes.

Correction to "Adsorption of Methyl Orange from an Aqueous Solution onto a BPPO-Based Anion Exchange Membrane".

[This corrects the article DOI: 10.1021/acsomega.2c03148.].

Reclassification of papillary thyroid microcarcinoma (pMCT) according to the "Porto proposal" criteria.

INTRODUCTION: pMCT is defined as a variant of papillary carcinoma that measures≤1 cm in diameter and which is characterized by an excellent prognosis. Recently, a proposal has been advanced to use the designation of papillary mirotumour (pMT) for pMCTs with no risk factors . AIM: In this study, we aimed to reclassify pMCTs according to the Porto proposal(Pp) criteria. METHODS: We have retrospectively collected cases of pMCT diagnosed in our pathology department over a period of 10years(2012-2022). Clinical and pathological parameters have been retrieved from the patient's medical records and pathological reports. We have evaluated all cases following the criteria of Pp. Cases that fulfilled all the criteria have been reclassified as pMT. We have briefly compared the clinical outcomes in both groups. RESULTS: 29 cases of pMCT was found. Mean age of patients was 46,6 years-old (17-67) with a female predominance (sex ratio=0,45). 23 cases of pMCT were incidentally discovered. The tumor was located in the right thyroid lobe in 15cases. The mean size of the tumor was 5,2mm. Multifocality was observed in 5 cases. A total of 17 cases could be classified as pMT according to the Pp. Only one patient developed pulmonary metastasis and local recurrence; however it was related to the papillary carcinoma firstly diagnosed in his contralateral lobe. Clinical outcome was also good in the group of papillary microcarcinoma (pMC) with no recurrence or distant metastasis. CONCLUSION: According to the Pp,>50% of pMCT could be reclassified as pMT which could reduce the psychological impact and overtreatment. Further studies with large sample size and molecular analysis are however needed in order to definitively validate and generalize the use of Porto proposal.

Bone metastatic carcinoma coexisting with plasma cell myeloma: a case report.

OBJECTIVE: Multiple myeloma is a clonal plasma cell proliferation often causing bone lytic lesions. It is sometimes challenging to differentiate these lytic lesions associated with multiple myeloma from bone destruction due to a metastasis. Although coexistence of solid tumors and plasma cell myeloma in one patient has been described, synchronous skeletal metastases from both neoplasms occurring in the same bone lesion is exceptional. Indeed, only one case has been reported in the literature. CASE PRESENTATION: Herein, we report a case involving a 68-year-old Caucasian male patient admitted to our department for coronavirus disease 2019 infection with incidental finding of multiple lytic bone lesions during hospitalization. Laboratory tests revealed an increased immunoglobulin G kappa M protein and high levels of carbohydrate antigen 19-9. Bone marrow aspiration showed increased atypical plasma cells consistent with multiple myeloma. Percutaneous image-guided biopsy of one of the osteolytic lesions was performed. Pathological examination identified both plasma cell neoplasm and poorly differentiated metastatic carcinoma within the same bone lytic lesions. CONCLUSION: The present case raises awareness among clinicians and pathologists that clinical and radiologic suspicion of multiple myeloma may be within the spectrum of second primary malignancies.

Adsorption of Methyl Orange from an Aqueous Solution onto a BPPO-Based Anion Exchange Membrane.

In this research, the development of a novel brominated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO)-based homogeneous anion exchange membrane (AEM) via the solution casting method was reported. Fourier transform infrared spectroscopy was used to confirm the successful development of the BPPO-based AEM. The prepared AEM showed excellent thermal stability. It exhibited an ion exchange capacity of 2.66 mg/g, a water uptake (W R) of 68%, and a linear swelling ratio of 31%. Methyl orange (MO), an anionic dye, was used as a model pollutant to evaluate the ion exchange ability of the membrane. The adsorption capacity of MO increased with the increase in contact time, membrane dosage (adsorbent), temperature, and pH while declined with the increase in initial concentration of MO in an aqueous solution and molarity of NaCl. Adsorption isotherm study showed that adsorption of MO was fitted well to the Freundlich adsorption isotherm because the value of the correlation coefficient (R 2 = 0.974) was close to unity. Adsorption kinetics study showed that adsorption of MO fitted well to the pseudo-second-order kinetic model. Adsorption thermodynamics evaluation represented that adsorption of MO was an endothermic (ΔH° = 18.72 kJ/mol) and spontaneous process. The AEM presented a maximum adsorption capacity of 18 mg/g. Moreover, the regeneration of the prepared membrane confirmed its ability to be utilized for three consecutive cycles. The developed BPPO-based AEM was an outstanding candidate for adsorption of MO from an aqueous solution.

Cyclin D1: potential utility as marker for Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disorder of unknown etiopathogenesis. Diagnosis is based on the identification of CD1a positive histiocytic infiltrate. Activation of the mitogen-activated-protein-kinase (MAPK) is constantly observed in LCH and therefore downstream markers such as cyclin D1 may be a useful marker for LCH. The aim of this study was to investigate the expression of cyclin D1 in LCH. We assessed the immunohistochemical expression of cyclin D1 (clone SP4-R) in series of 16 cases of confirmed LCH. Expression of Cyclin D1 was scored as weak, moderate, and strong nuclear staining and results were interpreted by two pathologists. The percentage of positivity was assessed. The mean age of patients was 13.7 years old with a male to female ratio of 1:3. The most common involved site was bone (n = 9; 56,3%), followed by lymph node (n = 5; 31,2%) and skin (n = 2; 12,5%). All cases showed nuclear staining for cyclin D1 with variable intensity. It was assessed moderate in 43,8% (n = 7) and strong in 56,2% (n = 9). The percentage of positive cells was >50% in 13 cases and <50% in 3 cases. Our results have shown that all cases of Langerhans cell histiocytosis from various sites express cyclin D1. This finding may be attributed to MAPK pathway activation that has been described in LCH. Otherwise, cyclin D1 is not significantly expressed in reactive Langerhans cell proliferations. Therefore, cyclin D1 immunohistochemistry may be useful as a diagnostic marker and in excluding non-neoplastic mimics of LCH.

Comparative expression profile of CD10 and cyclin D1 in cutaneous histiocytofibroma and dermatofibrosarcoma.

Dermatofibrosarcoma protuberans (DFSP) and histiocytofibroma (HF) are two rare fibrohistiocytic tumors, with some overlapping pathologic features. Immunohistochemistry is very useful in these cases. CD34 is a commonly used marker. However, the increasing cases of CD34 negative DFSP make it pressing to test other immunohistochemical markers that could help in the differential diagnosis. DFSP is known to harbor COL1A1-PDGFB rearrangement. Tumors in the differential diagnosis of DFSP usually lack this molecular signature. Recent studies suggested the interaction of PDGFB and PDGF receptor b with various signaling pathways, including the Akt-mTOR pathway. Cyclin D1, one of the oncoproteins activated in this pathway, may represent a promising useful biomarker in the differential diagnosis. On the other hand, CD10 expression in specialized mesenchymal skin cells, and especially in fibrohistiocytic skin tumors has been reported, which raises the interest of using this biomarker in HF and DFSP. In this study, we aimed to compare the expression of CD10 and cyclin D1 in 15 cases of DFSP and 15 cases of HF and discuss their potential contribution in the differential diagnosis.

EpCAM (MOC-31) - immunohistochemical expression in papillary thyroid carcinoma and non invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

INTRODUCTION: Ep-CAM, is a cell adhesion glycoprotein located on the basolateral cell membrane surface and in the cytoplasm of most normal epithelial cells. It has also been described to be expressed in several malignancies such as lung, digestive, prostate and renal carcinomas suggesting it has a potential role in carcinogenesis.  In thyroid carcinoma, Ep-CAM expression has rarely been studied especially in papillary thyroid carcinoma. OBJECTIVE: We sought to describe and compare the immunohistochemical expression of MOC31 in papillary thyroid carcinoma and in non invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). METHODS: We have retrospectively collected 33 cases of PTC diagnosed in the pathology department of the Security forces hospital during a period of 13 years (2008-2021). We have microscopically reviewed all cases and reclassified 9 of 33 cases as NIFTP.  An immunohistochemical  automated study have been performed with MOC-31 antibody.  The immunostaining was considered positive when it was membranous and/or cytoplasmic. The intensity of staining was scored as weak (score 1), moderate (score 2), and strong (score 3). We have used an immunoscore for assessing level of expression of MOC31 as follows: 0 for <5% of positive cells, 1 for 5-30%, 2 for 31-50%, 3 for 51-70%.The total score resulted by summing the percentage score with the intensity score; the final score was varying from 0 to 7, considered low between 1-4 and high 5-7. RESULTS: The mean age of patients was 45,2 years-old for PTC cases and 48,1 years-old for NIFTP cases. A net female predominance was found in both groups (male to female ratio of respectively 0,4 and 0,3). MOC31 expression was found in 19 cases of PTC with a percentage of positive cells varying from 5 to 90%. Percentage of positive cells was variable from 5 to 90%. The immunoscore for positive cells was: 0 in 5/24cases, 1 in 4/24cases, 3 in 9/24cases and 4 in 6/24cases. The intensity of staining was assessed score2 (moderate) in 8 cases and score 3 (high) in 7cases (Figure1-2). Final MOC31 staining score was low in 37,5% (9/24) and high in 62.5% (15/24). Patients with advanced pt2-pt3 stages mostly showed high score of MOC31 staining (61,5%).One case was associated with lymph node involvement and was of a high score. 6 cases showed vascular invasion and was of high MOC31 score. MOC31 was expressed in all NIFTP cases with variable proportion of positive cells (5%-80%). The immunoscore for positive cells was: 0 in 1/9cases, 1 in 2/9cases, 2 in 3/9cases, 3 in 1/9cases and 4 in 2/9cases. The intensity of staining was assessed score 1 (weak) in one case, score 2 (moderate) in 6 cases and score 3 (high) in one case (Figure3-4). The final combined score was low in 66,7 (6/9) and high in 33,3% (3/9). CONCLUSION: Our study revealed different immunohistochemical profile of MOC31 in benign and malignant tumors. It has somewhat a diffuse and marked staining in the first group.  The changes of MOC31 location as well as its score of staining in PTC and NIFTP could hence be helpful in the differential diagnosis. Our findings also support the potential prognostic value of this molecule that deserves further investigations.

SARS-CoV-2 vaccine induced Sweet syndrome : a case report.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis is a rare cutaneous disorder characterized by specific clinical, biological and microscopic findings. Although the exact cause of SS is still unknown, it may be triggered by infections, malignancies and drugs but also occurring after vaccinations such as bacille calmette guerin vaccination and influenza vaccine. While the recently discovered SARS COV2 vaccines are almost safe, many cutaneous and extracutaneous minor adverse effects are reported. We herein describe the fourth case of Sweet Syndrome induced by SARS-COV2 vaccine.

A remarkable concept of learning in times of educational confinement Social media and pathologist.

Social media are inevitably becoming part of our lives. The increasing popularity of these platforms revolutionized communication among healthcare workers and has irrevocably changed the terms of classic learning models. Pathologists all over the world are very active on social media making it a new pedagogical paradigm in pathology education. A virtual community of pathologists is constantly present especially on Twitter and Facebook for sharing and discussing interesting cases, reporting original scientific researcher's results, or simply energizing our field. Tunisian pathologists are not taking advantage of these platforms, some do not master the use of social media, others are reluctant about their use in the health field. However, it is of crucial importance for us Tunisian pathologists, especially in these times of social distancing due to SARS-COV2 pandemic, to join this virtual community and implement new ways of learning. This article aimed primary to assess the popularity of these platforms as a pedagogic tool among Tunisian pathologist. Secondly, we introduced the basic use and rules of social media, benefits and potential risks, and to provided tips for effective social media use in pathology.

Prognostic value of CD44s expression in urothelial bladder tumors.

Urothelial bladder carcinoma (UBC) includes a large group of malignancies with a variable clinical behavior. Despite remarkable developments in recognition of bladder carcinogenesis and prognostic factors, the recurrence rate is still high. Thus, identification of novel biomarkers involved in tumor cell invasion and metastatic dissemination is a constant challenge. AIM: To assess the prognostic impact of CD44 standard (CD44s) expression in UBT. METHODS: We assessed the immunohistochemical expression of CD44 in 38 samples of endoscopically resected UBT. Only membranous staining was considered positive. We analyzed topographic distribution of CD44s staining. Correlation of CD44s expression, clinicopathological features and disease progression was analyzed by Chi2 and Fisher tests. Kaplan-Meier analysis was used to investigate CD44s prognostic value. RESULTS: The mean age of patients was 61,24 years with male to female ratio of 18/1. CD44s expression was positive in 33 cases (87%). There was no significant correlation between CD44 expression and the parameters:  age, gender, tumor size, focality, tumor site, stage, recurrence and tumor progression. CD44s loss of expression is, nevertheless, correlated with a high tumor grade. Topographic distribution of CD44s staining was associated with focality, grade and stage. Basal/parabasal staining expanded to the tumor layers in homogeneous "laminate" pattern used to be of better prognosis, compared to the heterogeneous "islets" or "dispersed" pattern. CONCLUSIONS: Our results highlighted the prognostic value of CD44 expression in UBT. Focusing especially on staining pattern offers a better understanding of bladder carcinogenesis mechanisms.

Mixed tumor of the kidney.

Mixed epithelial and stromal tumour (MEST) of the kidney, is a recently recognized and rare entity .We herein reported the case of a 56 years old post-menopausal woman who presented with right abdominal pain. Her physical examination was unremarkable. Ultrasonography revealed the presence of a right cystic renal mass in the interpolar region extending into the pelvis. The tumor was considered Bosniak 4 category and a right nephro-ureterectomy was performed. The histological examination of the tumor revealed a mixed tumor with both epithelial and stromal pattern.

Autoimmune gastritis: assessment of OLGA and OLGIM staging systems.

BACKGROUND: Autoimmune gastritis present a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to reveal the high progressive risk forms (stages III and IV). AIM: To evaluate the OLGA and OLGIM staging systems in chronic autoimmune gastritis. METHODS: A descriptive single institution study of 30 cases of autoimmune gastritis. was performed over a 4-year period. The revaluation of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed to identify respectively the stages of OLGA and OLGIM systems. RESULTS: Our autoimmune gastritis were at high-risk stages in 26,5% of cases  according to two classifications. 95% of low-risk gastritis acoording to OLGA staging presented moderete to severe corpus atrophy. A significant association was present between high-risk gastritis according to OLGA staging and neuroendocrine hyperplasia. Both OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 2%. CONCLUSIONS: The OLGA and OLGIM staging systems in autoimmune gastritis, allow probably selection of high risk forms of chronic gastritis requiring convenable care.