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The article discusses keratin-positive giant cell tumors of bone and soft tissue in children under 10 with HMGA2::NCOR2 fusion, focusing on three cases. The tumors are classified based on molecular alterations, with HMGA2::NCOR2 fusions distinguishing them from other giant cell-rich tumors. The youngest patient, a neonate with metastatic disease, showed a remarkable response to imatinib therapy. The study expands the understanding of these tumors and their response to targeted therapy, highlighting the importance of molecular characterization in diagnosis and treatment. [Extracted from the article]

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a leading infectious disease with varied manifestations. We report a rare presentation of gastric TB in a 50-year-old immunocompetent woman from the Middle East with no prior medical history. The patient presented with persistent epigastric pain, weight loss, nausea, and vomiting over a 2-month duration. Imaging studies and an infectious disease panel were inconclusive. However, upper endoscopy revealed a subepithelial lesion at the pylorus, with biopsies demonstrating caseating granuloma and multinucleated giant cells. A QuantiFERON test was subsequently positive for TB. The patient was successfully treated with standard TB quadruple therapy, resulting in significant improvement in symptoms during follow-up. This case underscores the importance of considering extrapulmonary TB in immunocompetent patients with atypical gastrointestinal symptoms and highlights the efficacy of prompt antitubercular therapy. [ABSTRACT FROM AUTHOR]

Osteoclasts are bone-resorbing multinucleated giant cells formed by the fusion of monocyte/macrophage lineages. Various small GTPases are involved in the multinucleation and differentiation of osteoclasts. However, the roles of small GTPases regulatory molecules in osteoclast differentiation remain unclear. In the present study, we examined the role of Dennd2c, a putative guanine nucleotide exchange factor for Rab GTPases, in osteoclast differentiation. Knockdown of Dennd2c promoted osteoclast differentiation, resorption, and expression of osteoclast markers. Morphologically, Dennd2c knockdown induced the formation of larger osteoclasts with several protrusions. In contrast, overexpression of Dennd2c inhibited the multinucleation and differentiation of osteoclasts, bone resorption, and the expression of osteoclast markers. Dennd2c-overexpressing macrophages exhibited spindle-shaped mononuclear cells and long thin protrusions. Treatment of Dennd2c-overexpressing cells with the Cdc42 inhibitor ML-141 or the Rac1 inhibitor 6-thio-GTP prevented protrusion formation. Moreover, treatment of Dennd2c-overexpressing cells with the actin polymerization inhibitor latrunculin B restored multinucleated and TRAP-positive osteoclast formation. These results indicate that Dennd2c negatively regulates osteoclast differentiation and multinucleation by modulating protrusion formation in macrophages. [ABSTRACT FROM AUTHOR]

Background/Objectives: Myocarditis is an inflammatory disease of the myocardium and remains to this day a challenging diagnosis. A promising novel imaging method uses the expression of somatostatin receptors (SSTRs) on inflammatory cells to visualize myocardial inflammation. However, little is known about the histopathological correlate of SSTR imaging in different forms of myocarditis. Methods: In the present retrospective histopathological study, we systematically analysed the expression of SSTR subtype 2 (SSTR2) on inflammatory cells of 33 patients with biopsy- or explant-proven myocarditis (lymphocytic myocarditis (n = 5), giant-cell myocarditis (n = 11), and cardiac sarcoidosis (n = 17)), and in eight controls (multi-organ donors) without signs of myocardial inflammation and/or scars. Results: In all patients, immunohistochemical staining for SSTR2 was positive in areas with CD68-positive macrophages and multinucleated giant cells. Staining for SSTR2 was most prominent in the presence of multinucleated giant cells. The colocalization of both SSTR2 and CD68 on the same cell could be confirmed using immunofluorescence microscopy. Western blotting confirmed the upregulated expression of SSTR2 in cases of granulomatous inflammation (sarcoidosis) of the skeletal and heart muscle, in comparison with controls. Conclusions: In conclusion, our findings demonstrate the expression of SSTR2 on the protein level on CD68-positive macrophages and multinucleated giant cells in various forms of myocarditis, which provides a clear rationale for the diagnostic use of SSTR imaging in this patient group. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a 6-month-old male with a rare inborn error of immunity that initially presented as acute respiratory failure. The patient's condition worsened despite treatment for bronchiolitis, leading to further investigations that revealed Pneumocystis jiroveci pneumonia (PJP) secondary to CD40L deficiency. CD40L deficiency is associated with various clinical manifestations and poor prognosis, but early management with IVIG and antibiotic prophylaxis can reduce life-threatening infections, with hematopoietic stem cell transplant (HSCT) being the only cure. The patient was discharged home after treatment and remains on prophylactic medications while awaiting HSCT. [Extracted from the article]

Aims Methods and Results Conclusion Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra‐alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear‐resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease.We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs.These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism. [ABSTRACT FROM AUTHOR]

The article "Unveiling the Mechanism: Injectable Poly-L-Lactic Acid's Evolving Role—Insights From Recent Studies" in the Journal of Cosmetic Dermatology delves into the use of Sculptra poly-L-lactic acid in aesthetic dermatology to address volume loss, skin laxity, and wrinkles. It examines how PLLA stimulates collagen production, triggers adipogenesis, and promotes new extracellular matrix formation, potentially increasing volume in treated areas. The research suggests a complex relationship between PLLA, fibroblasts, macrophages, and adipocytes in achieving desired aesthetic outcomes, with unanswered questions remaining about PLLA's cell recognition mechanism. Further studies are needed to comprehend PLLA's effects on adipogenesis, immunological responses, angiogenesis, and interactions with other cells. The study was funded by Galderma, and the data are publicly accessible on PubMed. [Extracted from the article]

ABSTRACT Objective Materials and Methods Results Conclusion To analyze the characteristics of a series of oral reactions to injectable soft tissue fillers.Cases diagnosed as oral reactions to injectable soft tissue fillers were selected from eight Pathology laboratories. Information was retrieved from the laboratory charts and from the review of the hematoxylin and eosin‐stained histological slides.The 151 patients showed a mean age of 54.9 years, and 136 (90.1%) were females. Mean time of onset was 20.4 months, and the lips were the most frequent location (72.8%). Most cases presented as asymptomatic isolated nodules, with a mean size of 17.4 mm. Silicone (38.5%), polymethylmetacrylate (33%), and hyaluronic acid (11.9%) were the three most common fillers. Granulomas, foamy macrophages, and multinucleated giant cells were observed in 44%, 51.5%, and 65.3% of the cases, respectively. Time of onset was shorter for males (p = 0.033), and symptoms were common in the upper lip, buccal mucosa, and lower vestibule (p = 0.010). Foamy macrophages were more common in association with silicone and collagen (p < 0.001), whereas multinucleated giant cells were more common in association with polymethylmetacrylate, hydroxiapatite, and polylactic acid (p = 0.012).Clinicians should consider reactions to injectable soft tissue fillers when evaluating asymptomatic submucosal nodules affecting the lips of adult/older females. [ABSTRACT FROM AUTHOR]

This article discusses two cases of severe hypercalcemia in lung transplant recipients, which were diagnosed as Pneumocystis jirovecii pneumonia (PJP). Both patients were successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) and showed improvement in symptoms and calcium levels. The article highlights the importance of considering PJP as a possible cause of hypercalcemia in immunocompromised patients and suggests further research on risk factors and prophylaxis strategies. [Extracted from the article]

Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility. [ABSTRACT FROM AUTHOR]

The article discusses a case of erythema nodosum (EN) induced by a tumor necrosis factor‐alpha (TNF‐α) inhibitor in a 60‐year‐old female patient with peripheral spondyloarthritis. The patient developed painful nodules on her legs after treatment with adalimumab and later etanercept. The article provides a comprehensive literature review of similar cases and highlights the importance of considering EN as a potential side effect of anti‐TNF therapy. The authors emphasize the need for a thorough diagnostic workup to rule out other causes of EN and suggest collaborative management with a dermatologist while maintaining anti‐TNF therapy if it effectively controls the underlying autoimmune condition. [Extracted from the article]

HIV establishes long-term latent infection in memory CD4+ T cells and also establishes sustained long-term productive infection in macrophages, especially in the central nervous system (CNS). To better understand how HIV sustains infection in macrophages, we performed RNAseq analysis after infection of human monocytederived macrophages (MDMs) with the brain-derived HIV-1 strain YU2 and compared this with acute infection of CD4+ T cells. HIV infection in MDM and CD4+ T cells altered many gene transcripts, but with few overlaps between these different cell types. We found interferon pathways upregulated in both MDM and CD4+ T cells, but with different gene signatures. The interferon-stimulated gene RSAD2/Viperin was among the most upregulated genes following HIV infection in MDMs, but not in CD4+ T cells. RSAD2/Viperin was induced early after infection with various HIV strains, was sustained over time, and remained elevated in established MDM infection even if new rounds of infection were blocked by antiretroviral treatment. Immunofluorescence microscopy revealed that RSAD2/Viperin was induced in HIV-infected cells, as well as in some uninfected neighboring cells. Knockdown of RSAD2/Viperin following the establishment of infection in MDMs reduced the production of HIV transcripts and viral p24 antigen. This correlated with the reduction in the number of multinucleated giant cells, and changes in the HIV DNA and chromatin structure, including an increased DNA copy number and loss of nucleosomes and histone modifications at the long terminal repeat (LTR). RNAseq transcriptomic analysis of RSAD2/Viperin knockdown during HIV infection of MDMs revealed the activation of interferon alpha/beta and gamma pathways and the inactivation of Rho GTPase pathways. Taken together, these results suggest that RSAD2/Viperin supports the sustained infection in macrophages, potentially through mechanisms involving the alteration of the LTR chromatin structure and the interferon response. [ABSTRACT FROM AUTHOR]

A 4-year 9-month-old Amami spiny rat reared in a zoo died following a history of anorexia, weight loss, and respiratory distress. At necropsy, neoplastic tissues were found along the pleura and adhered to the thoracic wall, heart, and lungs. Histologically, the tumor was composed of diffuse, patternless sheets of large round to polygonal neoplastic cells with abundant eosinophilic cytoplasm, and multinucleated giant cells were often present. Metastatic lesions were observed in the abdominal lymph nodes. Neoplastic cells were immunopositive for vimentin, Iba-1, and CD204, and negative for E-cadherin and S100. Based on these findings, the tumor was diagnosed as histiocytic sarcoma. Compression of the lungs by the tumor may have caused respiratory failure and led to death. [ABSTRACT FROM AUTHOR]

Abstract Cell–cell fusion is a vital biological process where the membranes of two or more cells merge to form a syncytium. This phenomenon is critical in various physiological and pathological contexts, including embryonic development, tissue repair, immune responses, and the progression of several diseases. Osteoclasts, which are cells from the monocyte/macrophage lineage responsible for bone resorption, have enhanced functionality due to cell fusion. Additionally, other multinucleated giant cells (MGCs) also arise from the fusion of monocytes and macrophages, typically during chronic inflammation and reactions to foreign materials such as prostheses or medical devices. Foreign body giant cells (FBGCs) and Langhans giant cells (LGCs) emerge only under pathological conditions and are involved in phagocytosis, antigen presentation, and the secretion of inflammatory mediators. This review provides a comprehensive overview of the mechanisms underlying the formation of multinucleated cells, with a particular emphasis on macrophages and osteoclasts. Elucidating the intracellular structures, signaling cascades, and fusion-mediating proteins involved in cell–cell fusion enhances our understanding of this fundamental biological process and helps identify potential therapeutic targets for disorders mediated by cell fusion.

Abstract Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.

Background. Local antibacterial therapy in the treatment of osteomyelitis significantly increases the effectiveness of surgical debridement.The aim of the work. To assess in an in vivo experiment the dynamics of perifocal tissue reactions to the application of an original polyvinylpyrrolidone-based antimicrobial gel in a one-stage treatment of implant-associated infection in the hip joint in rabbits.Methods. Implant-associated infection was modeled by inserting Staphylococcus aureus-infected wires into the medullary canal of the femur of rabbits (n = 12). On the day 14, we removed the wire and performed radical surgical treatment of the suppurative focus and hip replacement. The animals were divided into two groups: experimental group – with application of the original antimicrobial gel at the stage of hip replacement (n = 6); comparison group – without gel application (n = 6). For morphological studies, animals were sacrificed on the days 10, 45 and 90 after hip replacement, changes in soft tissues and the bone marrow canal were assessed, and cell populations were counted with statistical data processing.Results. The application of the original antimicrobial gel causes statistically significant decrease in the number of neutrophils in the soft tissues surrounding the implant in the comparison group at all stages. Moreover, in the experimental group, at early stages the number of lymphocytes, plasmacytes and macrophages was statistically significantly higher; on the day 45, a statistically significantly larger number of lymphocytes was registered, and on the day 90 – a statistically significantly larger number of multinucleated and epithelioid cells.Conclusion. The experiment histologically confirmed the effectiveness of application of the original antimicrobial gel to stop infectious inflammation in soft tissues and the bone marrow canal during surgical debridement of an osteomyelitic lesion followed by hip replacement. A pronounced giant cell reaction aimed at removing the polyvinylpyrrolidone-based gel requires further research in terms of its outcomes.

Bone is a dynamic organ which continuously undergoes remodeling throughout one's lifetime. Cellular production of reactive oxygen species (ROS) is essential for regulating bone homeostasis. Osteoclasts, multinucleated giant cells differentiated from macrophage lineage, are responsible for osteolytic bone conditions which are closely linked to ROS signaling pathways. In this study, an anti‐ROS enzyme, peroxiredoxin 1 (Prdx1) was found to be expressed both in bone marrow macrophages and osteoclasts. Recombinant Prdx1 protein was found to dose‐dependently inhibit ROS production and osteoclast differentiation. Mechanistically, Prdx1 protein also attenuated NFATc1 activation as well as the expression of C‐Fos, V‐ATPase‐d2, Cathepsin K, and Integrin αV. Collectively, Prdx1 is a negative regulator on osteoclast formation via inhibiting RANKL‐mediated ROS activity, thus suggesting its potential application for treating osteoclast related disorders. [ABSTRACT FROM AUTHOR]

The presence of fungi in tracheal wash (TW) of horses was recently linked to mild-moderate equine asthma, indicating a possible causal role; however, increased numbers of fungi may also stem from asthma-related alteration of tracheal mucus clearance or from environmental exposure. Our objective was to elucidate the association between the presence of fungi in TW and asthma status while controlling for relevant confounders. We conducted a retrospective case-control study involving 73 horses, including 34 controls and 39 asthmatic cases. Each asthmatic horse was matched with a control from the same barn to account for the influence of environmental exposure. All horses underwent respiratory clinical scoring, endoscopy, TW, and bronchoalveolar lavage (BAL). The association between asthma status and presence of TW fungi was tested with multivariable logistic regression modelling, accounting for selected management factors, tracheal mucus accumulation, and selected TW and BAL cytological characteristics, including multinucleated giant cells (MGCs) in the TW. Given the variability in MGC definitions in the literature, particularly concerning their morphology and number of nuclei, we constructed two distinct models for each outcome (asthma status or presence of fungi in TW): one considering MGCs as cells with ≥ 3 nuclei, and another using a criterion of ≥ 10 nuclei. Horses with a tracheal mucus score ≥ 2 exhibited 3.6 to 4.3 higher odds of being asthmatic, depending on the MGC definition. None of the other variables examined were associated with either asthma status or TW fungi detection. Notably, the presence of fungal elements in the TW was not associated with equine asthma. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by systemic fibro-inflammatory infiltrates and an unfavorable prognosis. The disease has gained increasing interest due to a rise in cases, and consensus guidelines for diagnosis and management have been developed. ECD is generally diagnosed in middle-aged adults, with a higher incidence in males. Diagnostic challenges arise due to the variety of clinical manifestations and the need for differential diagnosis with other conditions such as idiopathic retroperitoneal fibrosis and chronic recurrent multifocal osteomyelitis. Thorough assessment and biopsy of fibrous tissue are recommended for accurate diagnosis and targeted genetic therapies. [Extracted from the article]

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions. During evolution, they contributed to the innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at mid-gestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac, AGM, and fetal liver-derived tissue-resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for the discovery of dendritic cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity. [ABSTRACT FROM AUTHOR]

Aims: Low‐grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin‐specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft‐tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6‐rearranged tumours resembling NF with atypical features have been reported. Methods and Results: One index case of LGMS of the deltoid in a 56‐year‐old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break‐apart probe identified two additional cases. These cases were investigated with RNA‐sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low‐quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast‐like multinucleated giant cells, and peripheral lymphoid aggregates. Conclusion: Our findings support the notion that among soft‐tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Aspergillosis is an important fungal disease occurring in avian fauna, especially in birds kept in captivity. In Psittaciformes, severe disease occurs in the lungs and air sacs, with the development of white-to-yellow caseous nodules and plaques in the organs, in addition to greenish-grey fungal growth in the air sacs. Herein, we report the presence of disseminated infection with Aspergillus fumigatus in a 3-year-old male scarlet macaw parrot (Ara macao) that was presented to the Exotic Animal Clinic at the Faculty of Veterinary Medicine, Iași University of Life Sciences (Iași, Romania) for its postmortem examination. The confirmation of the fungal infection was achieved using histopathological, microbiological, and molecular methods. Since birds suffering from Aspergillus spp. do not always show respiratory issues, or their clinical signs are non-specific, this may create diagnostic difficulty for clinicians unfamiliar with the parrots' pathology. Therefore, for a definitive diagnosis, the demonstration of fungal presence by cytology or histopathology and its identification using culturing and molecular techniques is required. A 3-year-old male scarlet macaw parrot (Ara macao) was presented to the Exotic Animal Clinic at the Faculty of Veterinary Medicine, Iași University of Life Sciences (Iași, Romania) for its postmortem examination. According to the owner, the parrot had been raised only in captivity and after 5 days of inappetence, lethargy, and mild respiratory clinical signs, the parrot died. The post mortem examination revealed various-sized granulomas and caseous plaques in the lungs, air sacs, spleen, intestinal serosa, and liver. Microscopically, the granulomas were characterized by a necrotic center and the infiltration of numerous multinucleated giant cells and epithelioid-like cells and by the presence of hyphae typical of Aspergillus spp. Moreover, in the liver tissue, a diffuse inflammation, with numerous fungal hyphae, was noted. The fungal culture and the PCR assay allowed for the isolation and identification of Aspergillus fumigatus from the lung and liver samples. The macroscopical lesions and the histopathological findings, with the fungal isolation and molecular confirmation of Aspergillus fumigatus by nested PCR, provided the basis for the diagnosis of disseminated aspergillosis. To the authors' best knowledge, this is the first report of disseminated infection caused by Aspergillus fumigatus in a scarlet macaw parrot (Ara macao). [ABSTRACT FROM AUTHOR]

The objective of our study was to evaluate early and late macroscopic and histological changes associated with the use of polycaprolactone dermal filler (PCL) in the orofacial region. Forty-eight female Wistar rats were divided into the PCL group and the control group. The material was applied to the ventral tongue and submandibular region, and the animals were euthanized at three time points—24 h, and 30 and 90 days. In the PCL group, yellowish nodules were observed on the tongue at all experimental time points. At the 24 h mark, the histological analysis revealed the presence of the PCL and a predominance of lymphocytes, plasma cells, and neutrophils. At 30 and 90 days, macrophages and multinucleated giant cells predominated around the PCL spheres. Collagen density in the dermis was higher in the PCL group when compared to the control at 30 and 90 days. In the submandibular glands, an inflammatory process similar to that observed at other sites was noted, with no alterations in acinar or ductal morphology. The results of this study highlight the effectiveness of PCL as a collagen biostimulator. Nevertheless, the development of nodular lesions on the tongue signals the potential risk of complications in mobile anatomical structures. [ABSTRACT FROM AUTHOR]

Ovarian aging results in reduced fertility, disrupted endocrine signaling, and an increased burden of chronic diseases. The factors contributing to the natural decline of ovarian follicles throughout reproductive life are not fully understood. Nevertheless, local inflammation may play an important role in driving ovarian aging. Inflammation progressively rises in aged ovaries during the reproductive window, potentially affecting fertility. In addition to inflammatory markers, recent studies show an accumulation of specific immune cell populations in aging ovaries, particularly lymphocytes. Other hallmarks of the aging ovary include the formation and accumulation of multinucleated giant cells, increased collagen deposition, and increased markers of cellular senescence. Collectively, these changes significantly impact the quantity and quality of ovarian follicles and oocytes. This review explores recent literature on the alterations associated with inflammation, fibrosis, cell senescence, and the accumulation of immune cells in the aging ovary. [ABSTRACT FROM AUTHOR]

Polyploid giant cancer cells (PGCCs) are characterized by the presence of either a single enlarged nucleus or multiple nuclei and are closely associated with tumor progression and treatment resistance. These cells contribute significantly to cellular heterogeneity and can arise from various stressors, including radiation, chemotherapy, hypoxia, and environmental factors. The formation of PGCCs can occur through mechanisms such as endoreplication, cell fusion, cytokinesis failure, mitotic slippage, or cell cannibalism. Notably, PGCCs exhibit traits similar to cancer stem cells (CSCs) and generate highly invasive progeny through asymmetric division. The presence of PGCCs and their progeny is pivotal in conferring resistance to chemotherapy and radiation, as well as facilitating tumor recurrence and metastasis. This review provides a comprehensive analysis of the origins, potential formation mechanisms, stressors, unique characteristics, and regulatory pathways of PGCCs, alongside therapeutic strategies targeting these cells. The objective is to enhance the understanding of PGCC initiation and progression, offering novel insights into tumor biology. [ABSTRACT FROM AUTHOR]

This article provides an overview of dermatological disorders that can lead to varioliform scars, which resemble smallpox scars. The disorders are divided into two categories: those that cause generalized skin lesions and those that cause localized skin lesions. The article discusses various disorders in each category, including chickenpox, smallpox, papulonecrotic tuberculid, secondary syphilis, acne necrotica, and lupus miliaris disseminatus faciei. The goal of the article is to classify these disorders, explain their causes, and offer a clinical approach for patients with varioliform scars. It is a valuable resource for library patrons researching skin disorders and their potential to cause varioliform scars. [Extracted from the article]

In breast cancer, Targeted Axillary Dissection (TAD) allows for the selective excision of the sentinel lymph node (SLN) during primary tumor surgery. TAD consists of the resection of labelled SLNs prior to neoadjuvant chemotherapy (NACT). Numerous clinical and preclinical studies have explored the use of carbon-based colloids for SLN tattooing prior to NACT. However, carbon vectors show varying degrees of inflammatory reactions and, in about one fifth of cases, carbon particles migrate via the lymphatic pathway to other nodes, causing the SLN to mismatch the tattooed node. To overcome these limitations, in this study, we explored the use of melanin as a staining endogenous pigment. We synthesized and characterized melanin-loaded polymeric nanoparticles (Mel-NPs) and used them to tattoo lymph nodes in pig animal models given the similarity in the size of the human and pig nodes. Mel-NPs tattooed lymph nodes showed high identification rates, reaching 83.3% positive identification 16 weeks after tattooing. We did not observe any reduction in the identification as time increased, implying that the colloid is stable in the lymph node tissue. In addition, we performed histological and ultrastructural studies to characterize the biological behavior of the tag. We observed foreign-body-like granulomatous inflammatory responses associated with Mel-NPs, characterized by the formation of multinucleated giant cells. In addition, electron microscopy studies showed that uptake is mainly performed by macrophages, and that macrophages undergo cellular damage associated with particle uptake. [ABSTRACT FROM AUTHOR]

This article presents two case studies of zebra finches that exhibited unusual symptoms. The first bird had infertility and swelling around the eyes, with abnormalities found in the oviduct and periocular skin. The second bird had oviductal prolapse, periocular dermatitis, and osteomyelitis. The cause of the symptoms in both cases was not definitively determined, but mycobacterium was found in the second bird. These findings emphasize the need for further research on the causes and impacts of these symptoms in zebra finches. [Extracted from the article]

The article in the journal "Histopathology" discusses a case of NTRK fusion cervical sarcoma with rhabdoid cells in a 42-year-old woman with a history of metastatic papillary thyroid carcinoma. The article details the histopathological findings, differential diagnosis, immunohistochemical studies, and molecular testing conducted to confirm the NTRK fusion sarcoma diagnosis. The study highlights the importance of comprehensive molecular testing in cases with rare morphological features and emphasizes the evolving nature of the diagnosis and classification of NTRK-rearranged gynaecological tumors. [Extracted from the article]

The article discusses a rare condition known as Facial Afro-Caribbean Childhood Eruption (FACE) that primarily affects dark-skinned prepubescent children. The case study presented in the article describes successful treatment of FACE with topical erythromycin and tretinoin (TRT), suggesting a new potential therapy for this condition. The article emphasizes the importance of differentiating FACE from other dermatological conditions and highlights the need for further research to confirm the efficacy of TRT as a treatment for FACE. [Extracted from the article]

The article discusses a case of sarcoidal foreign body reaction to permanent makeup involving M2 macrophages in a 50-year-old Japanese woman. The patient experienced itching, pain, swelling, and raised yellowish lesions on her eyebrows after having permanent makeup applied nine years prior. Treatment with monthly steroid injections led to improvement in symptoms and aesthetic outcomes. The study highlights the role of M2 macrophages in the reaction and provides insights into the mechanisms underlying such reactions. [Extracted from the article]

This article discusses a case report of a patient with eosinophilic granulomatosis with polyangiitis (EGPA), a rare systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The patient presented with a choroidal granuloma near the optic disk, which was highlighted through multimodal imaging. The article describes the patient's medical history, examination findings, and treatment. The authors emphasize the importance of optical coherence tomography (OCT) in diagnosing and imaging retinal pseudo-tumors. This case report provides valuable insights into the ophthalmologic manifestations of EGPA and the utility of multimodal imaging in diagnosing and monitoring the condition. [Extracted from the article]

Central Giant Cell Granuloma (CGCG) is a reactive, benign bony lesion primarily affecting the jaw bones of unknown etiology. Its widespread clinical manifestations can make diagnosis challenging. It is usually seen in mandible but can also involve the maxilla and hence should be considered as a differential diagnosis. Both surgical and non-surgical method can be considered but conservative surgical excision is the widely used treatment approach for management of CGCG.

Dermatophytic pseudomycetoma (DPM), which is a deeper dermal and/ or subcutaneous infection of dermatophytes, has been rarely reported in Domestic Korean Short Hair Cats. A 3-year-old, spayed female, domestic Korean Short Hair Cat presented with a history of crusts, nodules, and pruritus for 1 year. At the initial presentation, multifocal ulcerative nodules covered with yellowish grains were noted on her ventral thorax, abdomen, flank, and left hindlimb. Cytology of ulcerative nodules revealed degenerative neutrophils, macrophages, multinucleated giant cells, and hyphae. Histological examination of nodules revealed pyogranulomatous dermatitis with fungal plaques, and Microsporum canis and Staphylococcus aureus were identified in the culture. Therefore, the cat was diagnosed with DPM with secondary pyoderma. Oral itraconazole (10 mg/kg, once a day) was administered, but no significant improvement was observed. Therefore, intralesional (IL) injection of amphotericin B (0.6 mg/nodule) and oral administration of terbinafine (30 mg/kg, twice a day) were administered to the cat. With these medications, ulceration and the number and size of nodules decreased significantly, although large dome-shaped nodules remained. Skin lesions were treated with oral terbinafine and itraconazole administration for 5 months. However, after 6 months, recurrence of multifocal ulcerative nodules was observed, and the cat died 10 months after initial presentation. In this case, IL amphotericin B and oral terbinafine administration were partially effective in DPM treatment, suggesting that this may be an option for DPM treatment. Further studies to determine dose and frequency of IL amphotericin B in the management of DPM are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Pathological destruction of the axis vertebra leads to a highly unstable condition in an upper cervical spine. As surgical resection and anatomical reconstruction of the second cervical vertebrae represents a life threatening procedure, less radical approaches are preferred and only few cases of C2 prosthesis are described in literature. Case Description: The focus of this case report is a 21-year-old man with a pathological fracture of C2 managed primarily surgically with the C1-C3 dorsal fusion. Due to the progression of giant cell tumor and destruction of the axis vertebra, C2 prosthesis through anterior approach and dorsal occipito-cervical fusion C0-C4 were performed. Postoperative infection was managed surgically with a 2-staged dorsal debridement, ostheosynthesis material change and autologous bone graft. After a 4 week-intravenous therapy with the ceftriaxone in combination with the amoxicillin/clavulanate, followed by 12 week per oral therapy with amoxicillin/clavulanate in combination with ciprofloxacin, the complete recovery of the infection was achieved. Radiotherapy was initiated 2 months after the last revision surgery and the patient showed a good clinical outcome with stable construct at a 1 year follow-up. A review of literature of all reported C2 prosthesis cases was performed Conclusion: C2 prosthesis allows a more radical resection in pathological processes involving the axis vertebra. Combined with the posterior fusion, immediate stability is achieved. Anterior surgical approach is through a highly unsterile oral environment which presents a high-risk of postoperative infection. [ABSTRACT FROM AUTHOR]

Purpose: Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. Methods: We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. Results: Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17–0.77, p = 0.008) and DFS (HR = 0.59, 0.36–0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17–0.46, p < 0.001) and DFS (HR 0.44, 0.31–0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. Conclusion: NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice. [ABSTRACT FROM AUTHOR]

The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79‐year‐old man presented with a red–purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2‐40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow‐up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important. [ABSTRACT FROM AUTHOR]

Background: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. Methods: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. Results: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11–85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow‐up duration. Clinically, patients often exhibited symmetric ill‐defined patches/plaques involving intertriginous regions with tan‐yellow hyperpigmentation and follicular‐based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow‐up. T‐cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small–medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). Conclusions: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia. [ABSTRACT FROM AUTHOR]

The classic morphology of clear cell renal cell carcinoma consists of nests of cells with clear cytoplasm. Nevertheless, other histologic patterns may be seen including cells with eosinophilic cytoplasm, bizarre multinucleated giant tumor cells and pseudopapillary structures. In this article, we present the first case of clear cell renal cell carcinoma with a prominent micropapillary pattern. [ABSTRACT FROM AUTHOR]

The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered. [ABSTRACT FROM AUTHOR]

Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear. The current study investigated the following: (1) the characteristics of MGC formation after ICH, (2) whether it was impacted by complement C3 deficiency in mice and (3) whether it also influenced hematoma degradation (hemosiderin formation). Young and aged male mice, young female mice and C3-deficient and -sufficient mice received a 30 μL injection of autologous whole blood into the right basal ganglia. Brain histology and immunohistochemistry were used to examine MGC formation on days 3 and 7. Hemosiderin deposition was examined by autofluorescence on day 28. Following ICH, MGCs were predominantly located in the peri-hematoma region exhibiting multiple nuclei and containing red blood cells or their metabolites. Aging was associated with a decrease in MGC formation after ICH, while sex showed no discernible effect. C3 deficiency reduced MGC formation and reduced hemosiderin formation. Peri-hematomal MGCs may play an important role in hematoma resolution. Understanding how aging and complement C3 impact MGCs may provide important insights into how to regulate hematoma resolution. [ABSTRACT FROM AUTHOR]

Background: A central giant cell granuloma (CGCG) is a benign, proliferative, intraosseous, and non-odontogenic lesion occurring primarily in children and young adults. On the histological level, it is characterized by numerous multinucleated giant cells scattered randomly throughout a sea of spindle-shaped mesenchymal stromal cells which are dispersed throughout the fibrovascular connective tissue stroma containing areas of haemorrhage. When it comes to radiographic features, CGCG can have an array of variations, ranging from well-defined expansile lesions to ill-defined and destructive lesions, with or without expansion. Case presentation: This case report reviews an 11-year-old Caucasian patient with a chief complaint of slow-growing swelling involving the right posterior mandibular region. The cone beam computed tomography (CBCT) revealed an ill-defined mixed lesion mimicking both fibro-osseous lesion and hemangioma. However, microscopic examination revealed multinucleated giant cells in a fibrous stroma suggestive of central giant cell granuloma. Conclusion: Our intent in reporting this case is to highlight the importance of thorough clinical, radiographical and histopathological examination for accurate diagnosis and therapeutic interventions as well as to emphasize the importance of taking different possibilities into consideration when examining bony swellings in the head and neck region. [ABSTRACT FROM AUTHOR]

Giant cell tumor of soft tissue (GCTST) is a locally aggressive mesenchymal neoplasm of intermediate malignancy that predominantly occurs in the superficial soft tissue of the extremities. It is histologically similar to a giant cell tumor of bone (GCTB) and shows a mixture of round to oval mononuclear cells and osteoclast-like multinucleated giant cells. Currently, immunohistochemistry plays a very limited role in the diagnosis of GCTST. Primary or secondary malignant GCTST has recently been described and tumors exhibiting high-grade histological features demonstrate higher rates of distant metastasis. GCTST lacks the H3-3A gene mutations that are identified in the vast majority of GCTBs, suggesting a different pathogenesis. Surgery is the standard treatment for localized GCTST. Incomplete surgical resection is usually followed by local recurrence. Radiation therapy may be considered when the close proximity of critical structures prevents microscopically negative surgical margins. The systemic treatment options for advanced or metastatic disease are very limited. This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm. [ABSTRACT FROM AUTHOR]