Histological Examination Research Articles

Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of diabetes mellitus

This study aimed to identify the suitable induction protocol to produce highly qualified insulin producing cells (IPCs) from human adipose tissue derived stem cells (ADSCs) and evaluate the efficacy of the most functionally IPCs in management of diabetes mellitus (DM) in rats. The ADSCs were isolated and characterized according to the standard guidelines. ADSCs were further induced to be IPCs in vitro using three different protocols. The success of trans-differentiation was assessed in vitro through analysis of pancreatic endocrine genes expression, and insulin release in response to glucose stimulation. Then, the functionalization of the generated IPCs was evaluated in vivo. The in vitro findings revealed that the laminin-coated plates in combination with insulin-transferrin-selenium, B27, N2, and nicotinamide could efficiently up-regulate the expression of pancreatic endocrine genes. The in vivo study indicated effectual homing of the PKH-26-labelled IPCs in the pancreas of treated animals. Moreover, IPCs infusion in diabetic rats induced significant improvement in the metabolic parameters and prompted considerable up-regulation in the expression of the pancreatic related genes. The regenerative effect of infused IPCs was determined through histological examination of pancreatic tissue. Conclusively, the utilization of laminin–coated plates in concomitant with extrinsic factors promoting proliferation and differentiation of ADSCs could efficiently generate functional IPCs.

The Level of Serum Selenium in Patients with Cervical Intraepithelial Neoplasia in Medical City/ Baghdad Teaching Hospital

Introduction: Selenium is an essential trace element involved in different physiological functions of the human body. An inverse relationship between serum selenium levels and cervical intraepithelial neoplasia has been reported. cervical intraepithelial neoplasia is regarded as a potentially premalignant transformation of squamous cells of the cervix. Objectives: To evaluate the relationship between the serum level of selenium and cervical intraepithelial neoplasia. Methods: A case-control study was conducted at Baghdad Teaching Hospital and Iraqi National Cancer Research Center in the University of Baghdad during the period from July 2021 to July 2022. A convenient sample of 100 women was enrolled in the current study and included case group which consisted of 50 women who were diagnosed with cervical intraepithelial neoplasia and control group which consisted of 50 women who did not have cervical intraepithelial neoplasia as confirmed through histological examination after punch biopsy by colposcopy. Results: The serum level of the selenium was significantly lower in the case groups compared to the control groups (P-value=0.001). In addition, the proportion of the participant with abnormal levels of selenium was significantly higher in the case group compared to the control group (P-value=0.001). In the case group, there was a significant difference between the cervical intraepithelial neoplasia grade regarding the serum level of selenium, the level of selenium significantly decreased with the progression of the disease (P-value=0.001). Conclusions: Selenium deficiency may significantly increase the incidence of cervical intraepithelial neoplasia. In addition, it significantly impacts the transformation to a higher degree as there was a significant difference between cervical intraepithelial neoplasia I, II, and III regarding the level of serum selenium.

Bergapten attenuates sepsis-induced acute lung injury in mice by regulating Th17/Treg balance

Background The abnormality of the immune system caused by infection is a contributor to the organ dysfunctions associated with sepsis. The balance between Th17/Treg cells is essential for maintaining immune homeostasis. Bergapten is a natural furocoumarin and has been reported to alleviate the Th17/Treg imbalance. Here, we explored the effects of bergapten on the inflammation and immune state in mouse models of sepsis. Methods The model was established using the cecal ligation and puncture method. Mice were administered 30 mg/kg bergapten. Histological examination, RT-qPCR, enzyme-linked immunosorbent assay, immunoblotting, immunofluorescence, immunohistochemistry, and flow cytometry were used to evaluate the effects of bergapten in vivo. Results Bergapten ameliorated lung damage, reduced lung wet/dry weight ratio, inhibited myeloperoxidase activity, and reduced inflammatory cell infiltration. Bergapten also restrained sepsis-induced inflammation via inhibition of inflammatory cytokines and NF-κB signaling. These effects were accompanied by the restored Th17/Treg balance induced by bergapten. Bergapten decreased the number of Th17 cells and elevated the number of Tregs, and this effect was mediated by the signal transducer and activator of transcription 5 (STAT5)/Forkhead box P3 (Foxp3) and STAT3/retinoid-related orphan receptor-γt (RORγt) pathways. Conclusions Bergapten exerted anti-inflammatory effects in acute lung injury by improving the Th17/Treg balance, which suggested a potential of bergapten as an immunomodulatory drug treating sepsis-associated diseases.

Follow-up analysis of lesion characteristics of enchondromas and atypical cartilaginous tumours of the knee and shoulder region on MRI.

Enchondromas (ECs) and atypical cartilaginous tumours (ACTs), respectively, represent benign and intermediate cartilaginous bone tumours. Differentiation between these tumour entities bears difficulties, as histology and MRI cannot always provide exact diagnoses. Observation of the natural course of ECs/ACTs via follow-up MRIs might support tumour distinction without needing biopsy harbouring sampling error. Reports of patients that had undergone MRI exams of the knee (n = 44.762) or shoulder (n = 21.550) at a single radiology institute between 01.01.2007 and 01.03.2020 were searched for ECs/ACTs with at least one follow-up MRI. Scans of 176 patients (with 182 cartilage lesions) fulfilling these criteria were subsequently re-examined together with corresponding MRI reports to evaluate morphological tumour development over time, focusing on potential alterations of lesion size, tumour-related oedema, and scalloping. Median follow-up time was 27 ± 53 months for knee tumours and 26 ± 32 months for shoulder lesions. Presence of tumour growth was significantly higher in ACTs than in ECs both at the knee (p = 0.04) and shoulder (p = 0.03). While ACTs were associated with median tumour growth rates of 0.039 mm/month (knee) and 0.083 mm/month (shoulder), ECs of the knee and shoulder showed lower median growth rates equivalent to 0.0 mm/month (p < 0.01, p < 0.01). ECs and ACTs both presented stable regarding tumour-related oedema and scalloping during follow-up. ACTs and ECs show different tumour growth rates. Growth rates are slow for both, ECs and ACTs, supporting the current concept of watchful waiting. ECs may decrease in size. Follow-up MRIs may support the radiological differentiation of cartilage lesions. Question Both singular MRI and histological examination have limitations regarding differentiation of enchondromas (EC) and atypical cartilaginous tumours (ACTs). Findings Median ACT growth rates were 0.039 mm/month (knee) and 0.083 mm/month (shoulder), while median growth rates of EC in the knee and shoulder were 0.0 mm/month. Clinical relevance Active surveillance is a safe strategy when dealing with ECs and ACTs of the long bones; follow-up MRIs may support tumour distinction of cartilage lesions, as ECs and ACTs show different growth behaviour.

Protective effect of Tecoma stans (L.) Juss.ex Kunth in CFA-induced arthritic rats

Ethnopharmacological relevanceTecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. Aim of the studyThe objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat. Materials and methodThe ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors. ResultsThe ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities −10.4, −7.4, −7 and −6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study. ConclusionsThe observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.

Neuroprotective Efficacy of β-caryophyllene on Cerebellar Changes Caused by Bisphenol A in Rats via Alleviating Oxidative Stress

Exposure to bisphenol A (BP), an environmental pollutant, is potentially harmful to both human health and the environment. The purpose of the current research was to evaluate the effectiveness of β-caryophyllene (CF) (200 mg/kg) on rat cerebellar tissues exposed to BP (250 mg/kg). Thirty-five randomly selected male rats were split into five groups as: control (CON), olive oil (OL), BP, CF, and CF+BP. On day 15 of the experiment, all rats' cerebellar tissues were immediately extracted, followed by stereological and histological examination. Our results revealed that MDA level was significantly elevated in the BP group compared to the CON group (p&lt;0.05). While no significant difference was detected in the mean cerebellar volume among the experimental groups, the BP group’s the Purkinje cell number was significantly reduced when compared to the CON group (p&lt;0.05). In the CF+BP group, we found a significantly lower level of MDA and higher number of Purkinje cells compared to the BP group (p&lt;0.05). Histopathological examination revealed that the BP group had the marked neuronal deterioration; however, in the CF+BP group, this structural alteration was not as severe than the BP group. Our findings showed that exposure to BP caused oxidative damage to cerebellar tissues, and administration of CF attenuated BP-induced toxicity via improvement of oxidative stress.

Relapses of congenital mesoblastic nephroma: description of three clinical cases and literature review

Congenital mesoblastic nephroma (CMN) is a rare renal tumor of young children with intermediate biological behavior, accounting for 3.5-4% of all renal tumors in children. СMN is characterized by a favorable prognosis in case of radical surgical treatment. Relapses of CMN are considered to be quite a rare occurrence (4% of all cases), however, both local and metastatic relapses are possible. There are no fully standardized treatment approaches for patients with relapsed CMN. In our study, we performed a retrospective analysis of patients (n = 3) with a verified relapse of CMN who had received treatment at the D. Rogachev NMRCPHOI between 2012 to 2022 (132 months). At relapse, all the patients underwent at least one part of treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The diagnosis of CMN was established at the Pathology Department of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation, based on a histological examination. The patients with the cellular histological subtype of CMN underwent fluorescent in situ hybridization testing for ETV6 gene rearrangements. The demographic characteristics, clinical data, the extent of initial treatment and relapse therapy were assessed. Here, we describe three clinical cases of relapse in patients with CMN. The median age at initial diagnosis was 0.8 months (range 0.7–1.4). Our analysis of the extent of primary surgical treatment, including nephrectomy, in all cases revealed the following factors associated with a higher risk of relapse: preoperative tumor rupture – 1, intraoperative tumor rupture – 1, inability to confirm tumor-free margins – 1. The distribution of histological subtypes was as following: classical CMN (n = 1), cellular CMN (n = 1), and mixed CMN (n = 1). One patient had local stage II and 2 patients had local stage III. The median time from diagnosis to disease relapse was 0.8 months (range 2.3–4.3). One patient with mixed CMN died 10.6 months after diagnosis from complications of intensive therapy carried out for extremely aggressive relapse. Two patients are alive after repeated surgical treatment (R1 resection) and adjuvant therapy with actinomycin D and vincristine (AV regimen) for 27 weeks in one case, and neoadjuvant therapy (AV regimen for 4 weeks), delayed surgery (R0 resection), and adjuvant therapy (AV regimen for 4 weeks) in the other case. These patients were followed up for 92.2 and 21.3 months, respectively. By acknowledging the possibility of recurrent CMN, it seems important to provide multidisciplinary clinical care to young children with renal tumors involving a detailed planning of surgical procedures, radical surgeries in accordance with practice guidelines and standards in surgical oncology, and careful follow-up, especially during the first year after surgery. The patients' parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.

Rare Presentation of Extraskeletal Osteosarcoma Mimicking Phyllodes Tumor

Abstract Introduction/Objective A 57-year-old female presented with a palpable mass in the left breast, measuring up to 9 cm by ultrasound. core needle biopsy identified an atypical spindle cell lesion. The differential diagnosis included a metaplastic carcinoma, borderline phyllodes tumor, malignant phyllodes tumor with potential sarcomatous transformation. Methods/Case Report Histological examination of the tumor was performed, and immunohistochemical stains were conducted to characterize the lesion. Further consultation with a specialized pathologist at the University of Michigan was sought to confirm the diagnosis. Molecular analysis was performed to assess for specific genetic alterations and expression patterns. The histological examination revealed a proliferation of atypical spindle cells forming a fascicular and storiform pattern, with numerous large, pleomorphic, multinucleated tumor cells and a high mitotic rate. Immunohistochemical stains showed strong positivity for CD10 and vimentin, with focal weak expression for desmin, and negativity for a broad panel of cytokeratins and other markers. Consultation with Dr. Abbott at the University of Michigan supported the diagnosis of extraskeletal osteosarcoma. Molecular analysis revealed PD-L1 expression and absence of NTRK gene fusions. FISH analysis showed suggestive alterations including loss of BRAF gene, loss of MYC, and suggestive gains or polysomy of PTEN gene. Results (if a Case Study enter NA) NA Conclusion The case represents a rare presentation of extraskeletal osteosarcoma in the breast, with distinctive histological and immunohistochemical features. The comprehensive workup including histology, immunohistochemistry, and molecular analysis aids in accurate diagnosis and potential therapeutic implications. Further research may elucidate the underlying mechanisms and treatment options for this uncommon malignancy.

A case of EBV-Negative Primary Intestinal Diffuse Large B Cell Lymphoma Involving Multiple Anatomic Sites and Lymph Nodes

Abstract Introduction/Objective Extranodal lymphomas in the gastrointestinal tract are rare, with colonic lymphomas representing less than 0.5% of colorectal neoplasms. The most common type is Non-Hodgkin lymphoma. Treatment typically involves chemotherapy and surgical resection, with prognosis depends on various factors including age, genetic alteration, and bone marrow involvement. Methods/Case Report An 82-year-old female patient presented with abdominal pain and constipation. Radiological imaging revealed a mass in the ascending colon extending to the ileum. Histological examination following biopsy revealed to be a diffuse large B-cell lymphoma (DLBCL) of germinal center origin. The resected specimen showed two separate centrally ulcerated fungating masses in the ileum (4 x 4 x 1 cm) and ascending colon (8.5 x 5 x 4 cm). Microscopic examination showed a diffuse infiltrate of large, discohesive, atypical lymphoid cells with vesicular chromatin and prominent nucleoli. Abundant mitoses and apoptotic bodies are evident. The lesional cells were diffusely infiltrating into the lamina propria, submucosa, muscularis propria, and serosa associated with geographic necrosis. The appendix was also transmurally involved by the neoplastic cells. Multiple pericolonic lymph nodes were also involved by the lesional cells (6/15). Immunnohistochemical stains showed the neoplastic cells are positive for CD20, CD10, BCL6, while negative for MUM1, BCL2, C-MYC, and EBER. Ki67 index was 70%. CMV was negative. FISH result for MYC gene rearrangement with reflex to BCL2 and BCL6 was negative, which excludes double/triple-hit high grade B-cell lymphomas. The patient received chemotherapy with R-CHOP after the surgery and stayed recurrence-free for 15 months. Results (if a Case Study enter NA) NA Conclusion We reported a case of EBV-negative primary intestinal diffuse large B-cell lymphoma with germinal center cell origin involving multiple anatomic sites and pericolonic lymph nodes in an elderly immunocompetent woman.

Investigation of the Effects of Ozon and Propolis on the Healing of Bone Defects: An Experimental Study

Background/aim: This study explores the effects of ozone and propolis on the healing of critically sized bone defects at both the histologic and molecular levels, and the locations and concentrations of osteopontin and osteonectin during healing; both proteins play roles during bone healing. Materials and methods: This study used 56 adult male Sprague-Dawley rats of an average weight of 350 g, divided into four groups of 14: a control group, a topical ozone group (O), a topical ozone + systemic propolis (O + PO) group, and a systemic propolis group (PO). Seven rats from each group were sacrificed at the end of week 4 and the other seven at the end of week 6. Tissues were subjected to histologic and immunohistochemical examinations in a fixative solution. The results were analyzed using the statistical software package SPSS 23 (Statistical Package for the Social Sciences—IBM). Results were considered significant at the 95% confidence level (P&lt;0.05). Results: Graft sections were immunostained for osteonectin. Staining was low in the control group but moderate in the other three groups; the differences were significant. The three experimental groups did not differ significantly. Graft sections were also immunostained for osteonectin. At 4 weeks, staining was low in the control group but moderate in the other 3 groups. At 6 weeks, stronger staining was apparent in the 3 experimental groups. At both 4 and 6 weeks, the differences between the control and experimental groups were significantly different, but the differences among the experimental groups were not. Conclusion: The authors' results are compatible with the literature. Ozone and propolis, given separately or together, improved bone healing, increased bone formation, and reduced bone destruction. However, further research is required.

Pseudomyogenic Hemangioendothelioma: A Case Report of a Rare Tumor with Unusual Presentation

Abstract Introduction/Objective Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare neoplasm recently categorized by the World Health Organization (WHO) as an intermediate-grade vascular soft tissue tumor affecting young adults. While most documented cases exhibit local aggressiveness, we present a case with unusual presentation characterized by multiple pelvic and femoral lytic bone lesions associated with documented liver metastases. Methods/Case Report A mid-forties female presented with progressive left hip pain persisting for 2 weeks. Radiological assessments showed multiple lytic lesions in the left superior pubic ramus, right iliac wing, and left greater trochanter with associated pathologic fractures and soft tissue involvement. Additionally, multiple indeterminate hepatic and splenic hypodensities were noted. Histologic examination of the bone and liver biopsies revealed a neoplasm composed of spindled and epithelioid cells with hyperchromatic nuclei and eosinophilic cytoplasm. The neoplastic cells are arranged haphazardly and in short fascicles within a fibromyxoid stroma or sinusoidal spaces (in the liver) associated with scattered acute and chronic inflammation. Frequent mitoses are noted; however, no necrosis was identified. Tumor cells were positive for CD31, ERG, FOSB with equivocal staining for pankeratin and CK8/18. The top differential consideration was epithelioid hemangioendothelioma (EHE); however, sarcoma fusion next-generation sequencing panel exhibited features of a vascular neoplasm with WWTR1-FOSB, favoring PHE. Results (if a Case Study enter NA) NA Conclusion Pseudomyogenic hemangioendothelioma is a rare tumor that is prone for local recurrence and usually affect young adults (mean age: 30 years). Metastases are uncommon. To the best of our knowledge, we report a case of PHE with unusual presentation of early metastases to liver and possibly the spleen and highlights the complexity of PHE diagnosis.

Molecular Testing Prevents Overdiagnosis of Epithelioid Hemangioma

Abstract Introduction/Objective Epithelioid hemangiomas (EH) are mostly solitary benign vascular tumors commonly involving the dermal and subcutaneous areas of the head and neck. However, reports of multifocality are increasing, specially in same anatomic region. Some reported cases of EH show morphologic features that may mimic malignant vascular tumors such as hemangioendotheliomas or angiosarcomas. However, there are no reported overlaps in the molecular characteristics of these tumors. We describe a multifocal EH with atypical features, suspicious for angiosarcoma, which needed molecular testing to resolve the diagnosis. Methods/Case Report The patient is a previously healthy 42-year-old male with a 5-month history of multiple growing painless penile nodules. Biopsy of one of the nodules was done. Histologic examination showed multifocal dermal- based ill-circumscribed nodules with interspersed inflammatory infiltrates and focal areas of necrosis. Tumor periphery shows vasoformative growth with intraluminal and extravasated red blood cells. Neoplastic cells were large and ovoid with abundant eosinophilic cytoplasm, large vesicular pleomorphic nuclei and prominent nucleoli. Immunohistochemical stains showed strong expression of ERG, FLI-1, and CD31 and negativity for AE1/AE3, CD34, HHV8 and EMA. The morphologic and immunohistochemical features of the specimen showed significant overlap of two primary differential diagnoses - epithelioid angiosarcoma and epithelioid hemangioma. Ultimately, molecular testing revealed ZFP36-FOSB fusion, confirming the diagnosis of EH. Results (if a Case Study enter NA) NA Conclusion Differentiating benign and malignant epithelioid vascular neoplasms can sometimes be challenging. There can be overlap in terms of architectural variety, presence of necrosis, vasoformation, inflammatory cell components and cytologic features, especially in EH with atypical features and epithelioid angiosarcoma (EA). Both of these tumors show positive immunoreactivity for CD31, CD34, FLI1 and ERG, and negativity for most keratins. Currently, the most reliable way to distinguish each tumor is molecular testing, with EH having FOS/FOSB rearrangements and EA with MYC or FLT4 amplification. Benign and malignant epithelioid vascular tumors can be indistinguishable morphologically and immunohistochemically. Molecular tests can help differentiate these neoplasms to better tailor patient management.

Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen.

Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models.

An Anaplastic Lymphoma Kinase (ALK) Immunohistochemical Pitfall: ALK-positive Histiocytosis versus Angiomatoid Fibrous Histiocytoma

Abstract Introduction/Objective The 5th Edition WHO classification expanded the histiocytic/dendritic cell neoplasms to include ALK-positive histiocytosis, which can present as multisystem or single-site disease, affecting various age groups. These tumors lack high-grade cytologic features but express ALK by immunohistochemistry, typically indicating ALK locus rearrangements. In this case study, a cutaneous mass initially suspected as ALK-positive histiocytosis was found to be angiomatoid fibrous histiocytoma (AFH) with ALK expression, highlighting the potential diagnostic pitfall due to overlapping histomorphology and ALK expression. Methods/Case Report A previously healthy twelve-year-old boy sought evaluation for a growing and ulcerating mass on his left arm, which developed gradually over a year post-injury. Laboratory tests showed elevated inflammatory markers and mild anemia. A biopsy of the ulcer revealed Staphylococcus aureus infection. Initial histological examination revealed mixed inflammatory infiltrates with focal necrosis, prominent histiocytes, and giant cells. Despite favoring an infectious cause, immunostains were performed. AE1/AE3, ERG, CD34, CD30, S100, SOX10, SMA, and MyoD1 were negative, while INI1 was retained. However, ALK was strongly positive in some histiocytoid cells, suggesting ALK-positive histiocytosis. Surgical resection was subsequently performed to manage the abscess and characterize the lesion. Histologic examination revealed a solid nodule containing spindled and epithelioid cells with a bland histiocytoid appearance, arranged in a compact syncytial growth pattern within the dermis and subcutis. Surrounding the tumor, there was a distinct cuffing of fibrosis with organized lymphoplasmacytic cells. Break apart fluorescence in situ hybridization studies showed rearrangement of EWSR1 but not ALK. The diagnosis of angiomatoid fibrous histiocytoma was rendered. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of understanding immunohistochemical features, especially those that are unusual and unexpected in rare diseases. With the growing use of minimally invasive sampling techniques, this case study underscores the significance of integrating molecular diagnostics with clinical, histological, and immunophenotypic evaluations to achieve an accurate diagnosis in surgical pathology.

Histologic parameters driving completion thyroidectomy for papillary thyroid carcinoma in a high-volume institution: A retrospective observational study

BackgroundWhen the histological examination indicates papillary thyroid carcinoma (PTC), there is no unanimity on the need to proceed with completion thyroidectomy (CT). This study aims to assess the histologic parameters that influenced the decision to perform CT. Materials and methodsThis study included PTC patients who underwent thyroid lobectomy between 2019 and 2022. Group A included patients who underwent thyroid lobectomy without further treatments, whereas Group B included those who underwent CT based on histological findings. Differences in terms of histologic parameters were analyzed. ResultsGroup A included 291 patients (68.3 ​%), whereas Group B 135 patients (31.7 ​%). Multivariate analysis identified associations between CT and tumor size (p ​< ​0.001), aggressive variant (p ​= ​0.009), and vascular invasion (p ​< ​0.001). ROC curve analysis established a tumor size cut-off of 21 ​mm for CT. At ROC curve analysis, the cut-off number of aggressive factors required for CT was 2. ConclusionA thorough comprehensive assessment encompassing all pathological characteristics might be necessary in case of PTC with aggressive histologic features after thyroid lobectomy.

Metabolic and histopathological impact of local resource food consumption on blood markers in rats previously subjected to moderate acute malnutrition

Malnutrition is caused by dietary and nutritional imbalances that can have an impact on blood parameters and vital organs. The use of local agricultural resources for adapted diets appears to be an effective solution to post-weaning infant malnutrition. The aim of this study was to evaluate the effectiveness of four newborn diets made from local agricultural resources in improving biochemical, hematological, and histological parameters in rats that had previously experienced mild acute malnutrition. A total of 42 juvenile male rats, with an average age of 80 ±5 days and an average weight of 103.46 ± 5.10 g, were divided into six groups. Each group consisted of seven rats, with two control groups (LTC and LSA) and four experimental groups (LAR1A, LAR1B, LAR2A, and LAR2B). The experiment had three distinct phases: an initial adaptation period lasting 5 days, followed by a phase of inducing malnutrition lasting 19 days, and finally a phase of nutritional rehabilitation lasting 14 days. At the conclusion of the malnutrition induction and nutritional rehabilitation phases, blood samples were collected and used to evaluate biochemical and haematological markers. Kidneys and liver were removed for histological analysis.The findings revealed that the period of inducing malnutrition had a detrimental impact on several parameters, such as urea, triglyceride, total protein, C-reactive protein, albumin, ALAT, ASAT, WBC, hemoglobin, hematocrit, and MCV. Nevertheless, the ingestion of LAR diet derived from indigenous ingredients successfully returned all of these blood markers to the required levels for rats. Furthermore, histological examinations demonstrated that there were no kidney or liver abnormalities at the end of the trial.The LAR diets have rehabilitative effects on the biochemical and haematological parameters of rats. This suggests that these diets can be used therapeutically to treat moderate acute malnutrition and meet the nutritional needs of children aged 6 to 36 months.

An unusual case of a de novo high-grade B cell neoplasm with MYC and BCL2 rearrangements, strong TdT expression, and BRAF V600E mutation

Abstract Introduction/Objective Aggressive de novo B cell neoplasms can rarely exhibit overlapping features of B- lymphoblastic leukemia/lymphoma (B-ALL) and high-grade B cell lymphoma (HGBL) making their definitive classification challenging. The distinction between mature and immature B cell neoplasms is critical as treatment approaches differ. We report a unique case of an aggressive B cell neoplasm that not only posed diagnostic difficulties but was also found to harbor a BRAF V600E mutation, an unusual finding in such cases. Methods/Case Report A 33-year-old man without any significant past medical history presented for evaluation of a large tonsil mass and diffuse lymphadenopathy. The tonsil was excised, and histologic examination showed a diffuse atypical infiltrate composed of medium to large monomorphic lymphoid cells with high-grade cytology. By immunohistochemistry, the atypical cells were positive for CD19, CD79a, CD22, PAX5, CD10 (strong), CD45 (strong), BCL2, MYC, and TdT (strong). Ki67 showed a high proliferation index (80%). The atypical cells were negative for CD20, CD34, CD1a, CD30, Cyclin D1, T cell markers, myeloid markers, HHV8, and EBER. Flow cytometry detected a CD10 positive B cell population that was negative for CD20, CD34, and surface light chain expression. Fluorescence in-situ hybridization (FISH) detected BCL2 and MYC rearrangements. Staging marrow showed diffuse involvement by a neoplastic infiltrate with similar features to those observed in the tonsil. Chromosome analysis showed a complex karyotype. The patient was treated with two cycles of da-EPOCH-R. A neck lymph node biopsy two months later showed persistent disease. Next-generation sequencing (NGS) on this sample demonstrated a BRAF V600E mutation at 31% allele frequency. A mutation-specific BRAF-VE1 immunostain was diffusely positive. Results (if a Case Study enter NA) NA Conclusion This was a diagnostically challenging case of a de novo B-cell lineage neoplasm with high-grade features, MYC and BCL2 rearrangements, and strong diffuse TdT expression. There is limited literature on mutational profiles and prognostic data for such cases, and whether they are best classified (and treated) as HGBL or B-ALL remains challenging and controversial. In our case, we also discovered an unexpected finding of a BRAF V600E mutation, which has not been reported in similar cases in the existing literature and could serve as a potential therapeutic target. Additional reporting and genetic profiling of such cases may help further elucidate their biology and guide treatment protocols.

Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins diagnosed at autopsy in association with novel FOXF1 variant

Abstract Introduction/Objective Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV) is a rare disorder characterized by abnormal development of the pulmonary vasculature resulting in intractable pulmonary hypertension in neonates. Affected newborns present with progressive hypoxemia that is nearly always fatal. ACD/MPV is typically seen in the setting of other congenital anomalies, including gastrointestinal, genitourinary, and cardiac systems. Although the pathogenesis of ACD/MPV is poorly understood, inactivating mutations in the FOXF1 gene have been implicated. We present a case of ACD/MPV with associated gastrointestinal/cardiac anomalies and a novel heterozygous mutation of FOXF1. Methods/Case Report A complete autopsy was perfomed. Rapid whole exome sequencing of whole blood was done via reference laboratory. Results (if a Case Study enter NA) A 36-week gestational age male was born via cesarean delivery following a pregnancy course complicated by polyhydramnios. The neonate developed respiratory failure requiring intubation and Extracorporeal Membranous Oxygenation (ECMO). Further clinical evaluation revealed a patent foremen ovale and ductus arteriosus with right to left shunting. After 18 days on ECMO, he was transferred to comfort care where he later died. The body was that of a small for gestational age, phenotypic male neonate without gross dysmorphia noted on external examination. Internal examination revealed duodenal atresia, a patent ductus arteriosus and foramen ovale, and heavy, edematous lungs. Histologic examination of the lungs demonstrated prominent congested veins abutting small arteries with medial hypertrophy within shared adventitial sheaths. The interlobar septa contained dilated lymphatic spaces. Airspaces showed a dense neutrophilic exudate. Rapid whole exome sequencing revealed heterozygous mutations in FOXF1 (c.182T&amp;gt;C, p.Ile61Thr), NOTCH1 (c.7495A&amp;gt;C, p.Ser2499Arg) and a hemizygous mutation in SSR4 (c.20G&amp;gt;T, p.Gly7Val). The FOXF1 mutation was predicted to be damaging and has not yet been reported in the literature; however, its clinical significance was interpreted as uncertain. The significance of the NOTCH1 and SSR4 mutations were considered unknown. Given these findings, a diagnosis of ACD/MPV was given as the cause of death. Conclusion This case illustrates the classic clinical, gross and histologic findings described in ACD/MPV. Additionally, a novel heterozygous mutation of FOXF1 was identified and predicted to be damaging, supporting the role of FOXF1 mutations in the pathogenesis of ACD/MPV.

Ganglioneuroma in Head and Neck: A Case Report of a Laryngeal Ganglioneuroma and a Systematic Review of the Literature.

Introduction: Ganglioneuroma (GN) is a rare, benign tumor of the autonomic nervous system. It is seldom located in the head and neck (HN) region. GN typically presents as a slow-growing, painless mass, often leading to delayed diagnosis. Case report: We report a unique case of laryngeal-originating GN in a 43-year-old female who presented with worsening dysphonia and dyspnea. Imaging revealed a large mass originating from the larynx. Histological examination confirmed the diagnosis. The tumor was surgically excised with preservation of key structures in the neck. At the follow-up, the patient experienced a significant improvement in symptoms. Material and methods: A systematic literature review following PRISMA guidelines was conducted in January 2024 to investigate the common sites of GN in the HN region and the complications associated with its treatment. Results: In a total of 58 articles, we studied 65 patients, mostly under 30 years old. Surgical excision remains the primary treatment, and post-operative complications were mostly neurological. Discussion: GNs are generally slow-growing and asymptomatic, but they can reveal themselves when compressing nearby structures, especially in the HN region. In symptomatic cases or when the tumor exhibits significant growth or hormonal activity, surgical resection is required. The lateral cervical approach is the most common one. The risk of postoperative complications and recurrence underscores the need for careful surgical planning and long-term follow-up. Conclusion: This unique laryngeal GN case highlights the importance of considering GN in the differential diagnosis of HN masses. Further large-scale studies are warranted to establish evidence-based protocols for their management, especially in the HN region.

Clinical Rarity Unveiled: Adenocarcinoma with Enteroblastic Differentiation at the Gastroesophageal Junction in a Young Patient - A Diagnostic Challenge Shaping Therapeutic Paradigms

Abstract Introduction/Objective This report details a case of a young patient diagnosed with an adenocarcinoma with enteroblastic differentiation at the gastroesophageal junction (GEJ), characterized by Alpha-Fetoprotein (AFP) production. This manifestation previously rarely documented in young patients (25-44 years old), underscores the critical role of precise pathology diagnosis in guiding effective patient management. Methods/Case Report The patient’s clinical presentation included chest pain, abdominal pain, and weight loss, prompting imaging studies revealing liver masses, lesions in the lung and adrenal gland, and retroperitoneal adenopathy with unremarkable testicular findings. Rapidly progressing dysphagia led to a liver biopsy and esophagogastroduodenoscopy (EGD), where a fungating mass extending from the distal esophagus into the stomach was biopsied. A subsequent serologic test unveiled an elevated serum AFP level (approximally 31, 000 ng/ml). Results (if a Case Study enter NA) Histological examination revealed similarities between the liver and distal esophageal tumors, characterized by moderately differentiated carcinoma with solid and glandular growth patterns. The tumor cells, resembling fetal gut epithelium, exhibited positive immunostaining for SALL4, AFP, CK8-18, CK19, and CDX2. A diagnosis of adenocarcinoma with enteroblastic differentiation at the GEJ was determined, correlating with clinical and radiological assessments. Despite initiating one cycle of gastrointestinal related chemotherapy, the patient succumbed to tumor lysis syndrome within a month of diagnosis. Conclusion This case highlights the critical need for a comprehensive differential diagnosis when encountering young patients with AFP-producing malignancies. Although metastatic non-seminomatous germ cell cancer is a primary consideration, upper gastrointestinal adenocarcinoma with unique characteristics, as demonstrated in this case, requires distinct therapeutic approaches, emphasizing the importance of accurate and timely diagnosis.