Mismatch repair protein deficiency in triple-negative breast carcinomas.

BACKGROUND: Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant global health burden. Chemotherapy was the mainstay treatment for TNBC patients until immunotherapy was introduced. Studies indicate a noteworthy prevalence (0.2% to 18.6%) of mismatch repair protein (MMRP) deficiency in TNBC, with recent research highlighting the potential of immunotherapy for MMRP-deficient metastatic breast cancer. This study aims to identify MMRP deficiency in TNBC patients using immunohistochemistry. METHODS: A retrospective cohort study design was used and included TNBC patients treated between 2015 and 2021 at King Hussein Cancer Center. Immunohistochemistry was conducted to assess MMRP expression. RESULTS: Among 152 patients, 14 (9.2%) exhibited deficient MMR (dMMR). Loss of PMS2 expression was observed in 13 patients, 5 of whom showed loss of MLH1 expression. Loss of MSH6 and MSH2 expression was observed in one patient. The median follow-up duration was 44 (3-102) months. Despite the higher survival rate (80.8%, 5 years) of dMMR patients than of proficient MMR patients (62.3%), overall survival did not significantly differ between the two groups. CONCLUSION: Approximately 9% of TNBC patients exhibit dMMR. dMMR could be used to predict outcomes and identify patients with TNBC who may benefit from immunotherapy.

Effectiveness of Dermal Regeneration Templates in Managing Acute Full-thickness and Deep Dermal Burn Injuries: A Comparison with Split-thickness Skin Grafts.

Background: The therapeutic challenge of managing acute full-thickness burns is significantly ameliorated with the introduction of dermal regeneration templates (DRTs). However, an updated synthesis of evidence-based data on the efficacy and safety of different DRTs is required. Methods: This systematic review and meta-analysis conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines aims to evaluate the role of various DRTs in comparison with split-thickness skin grafting in managing acute burn injuries after excision and debridement. A total of 28 randomized clinical trials were assessed, encompassing a wide array of DRTs. Results: The study outcomes pointed to the diverse effectiveness of DRTs, with Integra demonstrating peripheral nerve reinnervation potential and TransCyte promoting rapid re-epithelialization. Some DRTs showed scar formation and skin quality comparable to those of autologous skin grafts. In terms of wound infection, certain treatments, including TransCyte, exhibited a significantly low infection rate. The evaluation of scar quality suggested that various interventions produced acceptable or improved outcomes without hypertrophic scarring. Recovery rates after the interventions displayed a range, with certain treatments showing rapid recovery and satisfactory results. Conclusions: The current systematic review points to the potential benefits of DRTs in managing burn wounds. Further research is necessary to shed light on the long-term impacts of these interventions on wound healing, scar quality, and patient recovery.

Esophagogastroduodenal Findings in Patients with Intraductal Papillary Mucinous Neoplasms.

The association between intraductal papillary mucinous neoplasms (IPMNs) and extra-pancreatic malignancies is controversial. This cross-sectional study compared esophagogastroduodenal findings in 340 IPMN patients to those of age- and gender-matched controls without known IPMNs who underwent esophagogastroduodenoscopies (EGDs) for similar clinical reasons. The presence of gastric and esophageal cancer, Barrett's esophagus, neuroendocrine tumors (NETs), gastrointestinal stromal tumors (GISTs), gastric adenomas, and ampullary tumors was assessed. The results showed that 4/340 (1.2%) of the IPMN patients had gastric cancer and 1/340 (0.3%) had esophageal cancer. The matched control group had a similar incidence of gastric cancer (5/340) (1.5%), with no esophageal cancer cases (p > 0.999). The overall incidence of other esophagogastroduodenal conditions did not significantly differ between the IPMN patients and the controls. However, the incidence of gastric cancer in the IPMN patients was higher than expected based on national cancer registry data (standardized incidence ratio of 31.39; p < 0.001; CI 8.38-78.76). In conclusion, IPMN patients have a significantly higher incidence of gastric cancer compared to the general population. However, the incidence of esophagogastroduodenal findings, including gastric and esophageal cancer, is similar between IPMN patients and those who undergo an EGD for similar clinical indications. Further research is needed to determine optimal surveillance strategies for IPMN patients regarding their risk of developing gastric cancer.

SARS-CoV-2 vaccine alleviates disease burden and severity in liver transplant recipients even with low antibody titers.

BACKGROUND AND AIMS: We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. PATIENTS AND METHODS: One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). RESULTS: In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. CONCLUSION: Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.

Programmed death-ligand 1 expression in diffuse large B-cell lymphoma is associated with poor prognosis.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression in some tumors has prognostic implications. This work aims at investigating PD-L1 expression in diffuse large B-cell lymphoma (DLBCL) and to study its association with clinicopathological variables. METHODS: The study consisted of 75 DLBCL patients who were cared for at the King Hussein Cancer Center during the period 2015-2018. The expression of PD-L1 in tumor tissue was assessed by immunohistochemistry using the anti-human PD-L1 (Clone 22C3) monoclonal antibody. The correlation between gender, age, clinical stage, pre-treatment-LDH level, tumor location, response to therapy, overall and event-free survival with PD-L1 expression was studied. RESULTS: Six patients were excluded from further analysis as they were in relapse at the time of tissue sampling. The tumor proportion score (TPS) was ≥1% in 16/69 (23.2%) of DLBCL cases while the combined positive score (CPS) at a cut-off of ≥20 was observed in 23/69 (33.3%) cases. No significant difference in PD-L1 expression was found between germinal center B-cell-like (GCB) and non-GCB subtypes. Similarly, no differences in PD-L1 expression (at CPS ≥20 and TPS ≥1) were found between different genders, age groups, clinical stages, tumor location, and patient response to therapy. However, base-line lactate dehydrogenase was significantly elevated in patients with PD-L1 CPS ≥20. The overall survival was not significantly different between PD-L1-positive and -negative groups. On the other hand, the median event-free survival was higher in either of the PD-L1 TPS or CPS negative groups at 107months each versus 54 months in the PD-L1 positive group of either category. CONCLUSIONS: PD-L1 expression can predict event-free survival in DLBCL cases and therefore poor prognosis.

Impact of margin ablation after EMR of large nonpedunculated colonic polyps in routine clinical practice.

BACKGROUND AND AIMS: Owing to its simplicity, effectiveness, and safety, EMR is the preferred treatment for the majority of large (≥20 mm) nonpedunculated colonic polyps (LNPCPs); however, residual and recurrent adenomas (RRAs) encountered during surveillance constitute a major limitation. Thermal ablation of the post-EMR mucosal defect margin has been shown to be highly efficacious in reducing RRA in a randomized trial setting, but data on effectiveness in clinical practice are scarce. We aimed to determine the effectiveness of this technique for reducing RRAs in routine clinical practice. METHODS: We analyzed data collected in 3 hospitals in Israel: Prospective data were available in 2 hospitals where margin thermal ablation with snare-tip soft coagulation (STSC) is routinely performed after EMR of LNPCP (TA-EMR). Only retrospective data were available from the third center, which exclusively did not perform STSC (standard EMR] [S-EMR]), during the study period. Surveillance was performed 4 to 6 months after resection. RRA was assessed endoscopically with high-definition white light and optical chromoendoscopy. The primary endpoint was RRA at first surveillance colonoscopy. RESULTS: Data from 764 patients with 824 LNPCPs were analyzed. The patient and lesion characteristics were similar between the groups. Four hundred sixty-four LNPCPs were treated by TA-EMR and 360 LNPCPs by S-EMR. RRA at first surveillance colonoscopy was detected in 14 (3.6%) of lesions in the TA-EMR group compared with 96 (31.6%) in the S-EMR group (P < .001; RR = .14; 95% CI, .07-.29). Adverse events were comparable between the 2 groups. CONCLUSION: TA-EMR leads to a significant reduction in post-EMR recurrence in routine clinical practice.

Dietary trends and obesity in Saudi Arabia.

Introduction: Dietary habits in Saudi Arabia have been shifting toward the Western diet, which is high in fat, salt, and sugar, leading to a high obesity rate. Different dietary strategies such as the Ketogenic Diet (KD), Intermittent Fasting (IF), Gluten Free Diet (GFD), and Calorie Restriction Diet (CRD) have shown an influential role in weight loss. This study aimed to compare trending diets and correlate different types of diet with obesity and lifestyle among adults in Saudi Arabia. Methods: A cross-sectional study was performed on Saudis and non-Saudis over 18 years old. We used convenience sampling, an online questionnaire distributed via social media channels, including WhatsApp, LinkedIn, and Twitter. SPSS 28 software was applied for data analysis. The chi-square test was used to determine associations between different variables. Statistical significance was considered at a value of p less than 0.05. Results: Most participants were females residing in the Eastern and Central regions of Saudi Arabia. Although most do not follow any dietary plan, they exhibited acceptable exercise and lifestyle. The minority of the study population followed different types of diet plans, such as KD, IF, and GFD. The purpose of most of the participants who have used these strategies was for weight loss but failed to sustain the dietary plan for more than 1 month. Conclusion: Obesity remains a challenging issue in Saudi Arabia. Adherence to dietary regimes could help in controlling obesity. Increasing the awareness of the benefits of each dietary plan for health, choosing the appropriate one, and sustaining a balanced nutrition pattern.

PAX5 and TDT-Negative B-Acute Lymphoblastic Leukemia with Unusual Genetic Mutations: A Case Report.

B-acute lymphoblastic leukemia (B-ALL) is commonly encountered in clinical practice. Patients present with increased percentage of lymphoblasts in bone marrow and/or peripheral blood. Immunophenotypic study by flow cytometry or immunohistochemistry is essential to establish the diagnosis. Paired box-5 (PAX5) is a B cell lineage protein and terminal deoxynucleotidyl transferase (TDT) is an immature marker, both of which are routinely tested in the pathologic workup of acute leukemia. In this report, we describe a case of B-ALL in a 37-year-old woman in which both PAX5 and TDT were negative. Next-generation sequencing test detected mutations in DNA methyltransferase 3 α and Fms related receptor tyrosine kinase 3 genes, which are frequently mutated in acute myeloid leukemia rather than B-ALL. The constellation of these rare findings in a single case signifies the importance of examining a wide panel of markers when the diagnosis of ALL is suspected.

Programmed Death Ligand-1 is Frequently Expressed in Primary Acute Myeloid Leukemia and B-Acute Lymphoblastic Leukemia.

BACKGROUND: The introduction of checkpoint inhibitors in solid cancer therapy showed successful results. The role of Programmed Death-1/Programmed Death-Ligand 1 (PD1/PD-L1) in hematologic malignancies is currently being investigated and clinical trials are ongoing. Preliminary findings showed conflicting results. In this study, we examined the degree of PD-L1 and PD-L2 expression in primary acute leukemia patients. METHODS: Flow cytometry expression of PD-L1 and PD-L2 was evaluated in de novo acute leukemia in the collaborating institutions between 2018 - 2020. RESULTS: One hundred forty patients were identified. PD-L1 was positive in 34/70 (49%) of AML, 25/50 (50%) of B-ALL, and none (0/20) of T-ALL patients. In contrast, PD-L2 was solely expressed in eight (19%) AML patients. The expression of PD-L1 showed statistically significant correlation with the type of acute leukemia (AML and B-ALL > T-ALL, p < 0.001) and with age group (adults > children, p = 0.048), but not with blast count, immunophenotype or cytogenetic mutations. The positivity for PD-L1 was associated with worse overall survival in AML, but not in B-ALL. CONCLUSIONS: The expression of PD-L1 is common among newly diagnosed AML and B-ALL patients and is not restricted to relapsed cases as previously described. PD-L2 is less commonly expressed and is accompanied by PD-L1 expression. Positive PD-L1 patients may benefit from treatment with immune checkpoint inhibitors, especially in AML. Further studies are recommended.

Combined utility of CD177, P53, CD105 and c-kit immunohistochemical stains improves the detection of myelodysplastic syndrome.

The diagnosis of myelodysplastic syndrome (MDS) relies primarily on identifying peripheral blood cytopenia and morphologic dysplasia as well as detecting cytogenetic aberrations in a subset of patients. Accumulating data points to the importance of examining certain immunophenotypic changes characteristic of MDS, most of which are tested by flow cytometry. The role of immunohistochemistry in the diagnostic workup of MDS is less known. In this study, we used immunohistochemistry to survey the expression patterns of CD177, P53, CD105 and c- kit in a cohort of MDS bone marrow specimens (n = 57) and compared the results with a control group of patients who had cytopenia for other benign conditions (n = 49). MDS cases showed significant higher rates of: CD177-loss (13/57, 23% vs 1/49, 2%; P = .0016), P53 overexpression (8/57, 14% vs none; P = .005) and the presence of clusters of CD105-positive cells (6/57, 11% vs none; P = .021). Increased c-kit-positive cells was more common in MDS patients, but not statistically significant (17/57, 30% vs 8/49, 16%; P = .102). On multivariate analysis, only loss of CD177 expression was significantly higher in MDS group (P = .014). These findings suggest that a panel of immunohistochemical stains could serve as an adjunct tool in investigating unexplained cytopenias and warrant further comparative studies with flow cytometry.

Papillary thyroid carcinoma in a 5-year old child, mimicking lymphoma in presentation.

Thyroid cancer is very rare in children and papillary thyroid carcinoma (PTC) represents the most common type. Patients are frequently in the second decade of life and complain of painless enlargement of the gland. Pediatric PTC has unique clinicopathologic characteristics that make it different from the adult counterpart. The biologic behavior tends to be aggressive and patients frequently present with advanced disease. Herein, we report a case with an unusual presentation. A 5-year-old child manifested with fever, night sweats, cervical lymphadenopathy, and weight loss for 2 months. He also complained of mild cough and shortness of breath. Clinical suspicion of tuberculosis or lymphoma was raised, but laboratory workup was unremarkable. Cervical lymph node excision was done, and the histopathologic examination showed metastatic PTC. The patient underwent surgical and radioactive therapy and remained in complete remission for 5 years. Unfortunately, the disease ultimately relapsed with disseminated metastasis and the patient passed away.

Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP): a 13-year retrospective review at Jordan University Hospital.

OBJECTIVE: Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) is the term to describe what was previously known as encapsulated follicular variant of papillary thyroid carcinoma. This new paradigm shift was agreed upon by experts in the field. The objective of this study is to evaluate cases previously diagnosed as follicular adenomas, follicular variant of papillary thyroid carcinoma and hyperplastic nodules to be reclassified as NIFTP according to the new criteria. Furthermore, the clinical follow-up of these NIFTP cases is evaluated. METHODS: This retrospective study reviewed potential NIFTP cases over the last 13 years, at Jordan University Hospital. RESULTS: A total of 811 thyroid surgery reports were identified and revised to identify the potential NIFTP cases. The review yielded 173 cases identified as potential NIFTP cases. Further pathological slide review resulted in a revised diagnosis of 32 cases of NIFTP according to the new criteria. The NIFTP cases comprised 4% of the total number of thyroidectomy cases and 16.1% of the total pool of previously diagnosed papillary thyroid carcinoma cases at our institution. While 111 cases retained their original diagnosis. Follow-up showed that all patients are alive and well with no evidence of disease. CONCLUSION: Patients with NIFTP are not uncommon and the diagnosis is made only after a thorough evaluation of excision. Therefore, initial conservative management of solitary thyroid nodules suspicious for NIFTP in the form of lobectomy is recommended to avoid unnecessary total thyroidectomies. Our follow-up of NIFTP cases is similar to all previous reports.

Differential expression, diagnostic and prognostic significance of stathmin-1 and CD147 in various uterine smooth muscle tumors / Expresión diferencial, diagnóstico y significado de pronóstico de stathmin-1 y CD147 en diferentes tumores del músculo liso uterino

SUMMARY: Uterine smooth muscle tumors (USMT) are common, behavior-distinct gynecological tumors; including: leiomyoma (ULM), leiomyosarcoma (ULMS), and smooth muscle tumors of undetermined malignant potential (STUMP). Pre-operative distinction is difficult, thus diagnosis relies on histopathology. Immunohistochemistry (IHC) had been used to help in distinction. We studied two markers (stathmin-1 and CD147) to demonstrate whether they have diagnostic/ prognostic assist. Sixty seven USMT are studied. Age, follow up, and recurrence/metastasis data were collected. Representative slides were stained and Histologic score (HS) calculated as stain intensity (SI) X percentage of positive tumor cells (PP). Results were grouped as low expression (LE) and high expression (HE); then correlated to tumor types, and risk of recurrence/ metastasis. Statistical analysis (P < 0.05); Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were calculated. Stathmin-1 HS (p= 0.000) and HE (p=0.002) were different among groups. Same as for CD147 HS and HE (both p=0.000), with a gradient increase from LM to STUMP to ULMS. Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were as following: For stathmin-1 HS: 92 %; 20 %; 42 %; and 80 % (CI= 44-96 %). For Stathmin-1 HE: 80 %; 66 %; 60 %; and 84 % (CI=66-94 %). For CD147 HS: 85 %; 22 %; 41 %; and 69 %. For CD147 HE: 58 %; 49 %; 42 %; and 65 % (CI= 45-80 %), respectively. Recurrence / metastasis were documented in 6 cases (4 ULMS; 2 STUMP) with follow up ranging from 6 months to 102 months. 5 tumors had stathmin-1 HE (p=0.099); 2 had CD147 HE (p=0.393) in the primary tumors. STMN1 and CD147 are helpful diagnostic tests for USMT sub-typing, especially for ULMS. Gradient increase of expression from LM, to STUMP, to ULMS may indicate a role in malignant transformation in USMT, and in increased risk of recurrences/metastasis.

RESUMEN: Los tumores del músculo liso uterino (USMT, por sus siglas en inglés) son tumores ginecológicos comunes y de comportamiento distinto; incluyendo: leiomioma (ULM), leiomiosarcoma (ULMS) y tumores de músculo liso de potencial maligno indeterminado (STUMP). La distinción preoperatoria es difícil, por lo que el diagnóstico se basa en la histopatología. La inmunohistoquímica (IHQ) se había utilizado para ayudar en la distinción. Estudiamos dos marcadores (stathmin-1 y CD147) para demostrar si había efecto diagnóstico / pronóstico. Se estudiaron 67 USMT. Se recopilaron los datos de edad, seguimiento y recurrencia / metástasis. Las muestras representativas se tiñeron y la puntuación histológica (HS) se calculó como la intensidad de la tinción (IS) x porcentaje de células tumorales positivas (PP). Los resultados se agruparon como expresión baja (EB) y expresión alta (EA); luego se correlacionaeon con los tipos de tumores y el riesgo de recurrencia / metástasis. Análisis estadístico (P <0,05); se calcularon la sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS. Stathmin-1 HS (p = 0,000) y HE (p = 0,002) fueron diferentes entre los grupos. Igual que para CD147 HS y HE (ambos p = 0,000), con un aumento de gradiente de LM a STUMP a ULMS. La sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS fueron los siguientes: Para stathmin-1 HS: 92 %; 20 %; 42 %; y 80 % (IC = 44-96 %). Para Stathmin-1 HE: 80 %; 66 %; 60 %; y 84 % (IC = 66-94 %). Para CD147 HS: 85 %; 22 %; 41 %; y el 69 %. Para CD147 HE: 58 %; 49 %; 42 %; y 65 % (IC = 45-80 %), respectivamente. La recurrencia / metástasis se documentaron en 6 casos (4 ULMS; 2 STUMP) con un seguimiento que osciló entre 6 meses y 102 meses. Cinco tumores tenían stathmin-1 HE (p = 0,099); dos tenían CD147 HE (p = 0,393) en los tumores primarios. STMN1 y CD147 son pruebas de diagnóstico útiles para la subclasificación de USMT, especialmente para ULMS. El aumento en el gradiente de la expresión de LM, a STUMP, a ULMS puede indicar un papel en la transformación maligna en USMT y en un mayor riesgo de recurrencias / metástasis.