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In vitro models serve as valuable tools for understanding the complex cellular and molecular interactions involved in granuloma formation, providing a controlled environment to explore the underlying mechanisms of their development and function. Various models have been developed to replicate granulomatous diseases, even though they may lack the sophistication needed to fully capture the variability present in clinical spectra and environmental influences. Traditional cultures of PBMCs have been widely used to generate granuloma models, enabling the study of aggregation responses to various stimuli. However, growing cells on a two-dimensional (2D) plastic surface as a monolayer can lead to altered cellular responses and the modulation of signaling pathways, which may not accurately represent in vivo conditions. In response to these limitations, the past decade has seen significant advancements in the development of three-dimensional (3D) in vitro models, which more effectively mimic in vivo conditions and provide better insights into cell–cell and cell–microenvironment interactions. Meanwhile, the use of in vivo animal models in biomedical research must adhere to the principle of the three Rs (replacement, reduction, and refinement) while ensuring that the models faithfully replicate human-specific processes. This review summarizes and compares the main models developed to investigate granulomas, focusing on their contribution to advancing our understanding of granuloma biology. We also discuss the strengths and limitations of each model, offering insights into their biological relevance and practical applications. [ABSTRACT FROM AUTHOR]

Cherubism is a rare genetic disorder caused by SH3BP2 mutations. This sterile autoinflammatory disease is characterized by jaw osteolysis, in which bone tissue is replaced by multinucleated giant cells containing fibrous tissue. The cherubism mouse model (Sh3bp2 KI) is characterized by systemic bone loss as well as inflammatory phenotypes induced and maintained by TNFα. IL-1β, produced by the NRLP3 inflammasome through recruitment of Caspase-1, is involved in the development of sterile autoinflammatory disease. We previously reported a cherubism patient with elevated serum IL-1β, and cherubism mice also have elevated serum IL-1β levels. Thus, we wanted to disentangle the role of IL-1β in cherubism. To that end, we deleted Caspase-1 in Sh3bp2 KI mice to tamp down IL-1β production. However, deleting Caspase-1 did not rescue the systemic bone and inflammatory phenotypes. [ABSTRACT FROM AUTHOR]

Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B. pseudomallei strains, variants of hcp1 have recently been identified. This study aimed to examine the prevalence of hcp1 variants in clinical isolates of B. pseudomallei, assess the antigenicity of the Hcp1 variants, and the ability of strains expressing these variants to stimulate multinucleated giant cell (MNGC) formation in comparison to strains expressing wild-type Hcp1 (Hcp1wt). Sequence analysis of 1,283 primary clinical isolates of B. pseudomallei demonstrated the presence of 8 hcp1 alleles encoding three types of Hcp1 proteins, including Hcp1wt (98.05%), Hcp1variant A (1.87%) and Hcp1variant B (0.08%). Compared to strains expressing Hcp1wt, those expressing the dominant variant, Hcp1variant A, stimulated lower levels of Hcp1variant A-specific antibody responses in melioidosis patients. Interestingly, when Hcp1variant A was expressed in B. pseudomallei K96243, this strain retained the ability to stimulate MNGC formation in A549 cells. In contrast, however, similar experiments with the Hcp1variant B demonstrated a decreased ability of B. pseudomallei to stimulate MNGC formation. Collectively, these results show that B. pseudomallei strains expressing variants of Hcp1 elicit variable antibody responses in melioidosis patients and differ in their ability to promote MNGC formation in cell culture. Author summary: Hcp1 is a component of the virulence-associated Type VI Secretion System 1 (T6SS1) that plays a significant role in the MNGC formation of B. pseudomallei in hosts. In addition to its importance in bacterial pathogenesis, Hcp1 is recognized by the host immune system, resulting in strong antigen-specific humoral and cellular responses in melioidosis patients and protective immunity in animal models. Our analysis of hcp1 sequences from 1,283 clinical B. pseudomallei isolates revealed genetic diversity and identified 8 hcp1 alleles and 3 types of Hcp1. We demonstrated that Hcp1variant A, associated with several amino acid changes, could still function in cell-to-cell spread similar to Hcp1wt, but it exhibited decreased specific antibody levels in plasma of melioidosis patients compared to the levels stimulated by Hcp1wt. Understanding the impact of possible antigenic variation with respect to immune responses and bacterial pathogenesis will be necessary to determine if expression of different Hcp1 proteins may have implications for the development of effective treatments and vaccines. [ABSTRACT FROM AUTHOR]

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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: Dermal fillers such as hyaluronic acid (HA) have been widely used in recent years as a less surgically invasive cosmetic treatment. Although delayed foreign body granuloma may occur as a rare adverse reaction after the procedure, detailed histological reports are still limited. When occurring on the buccal mucosa of the oral cavity, the histopathology may resemble some lesions of minor salivary gland origin due to the material properties of HA. Here we report a delayed foreign body granuloma associated with HA showing eosinophilic infiltration of the buccal mucosa, with characteristic histological and immunohistological features. Case Presentation: A 61‐year‐old woman presented with swelling and a burning sensation in the right buccal mucosa. On initial examination, a 25 × 20‐mm mass was palpated on the anterior margin of the right masseter muscle. Examination of a biopsy specimen revealed multiple pseudoduct‐like structures containing mucoid substance within the mucosal lamina propria. The mucoid substance was positively stained with Alcian blue (AB) and surrounded by CD68‐positive epithelioid cells and multinucleated giant cells. Many histiocytes had infiltrated into the surrounding area, and numerous eosinophilic infiltrates were also evident. After a review of the patient's history, a diagnosis of delayed foreign body granuloma associated with HA injection was made. Conclusion: We have reported a case of delayed foreign body granuloma with eosinophilic and histiocytic infiltration following injection of HA. It was suggested that the marked eosinophilic infiltration around macrophages was due to not only an allergic reaction, but also in part to increased macrophage aggregation. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive soft tissue sarcoma with a poor prognosis. The patients are usually found to have metastasis when the primary tumor is diagnosed. Eccrine syringofibroadenoma (ESFA) is a rare cutaneous adnexal lesion of eccrine duct origin. There are five subtypes, one of which is reactive ESFA, known to occur in reaction to an inflammatory or neoplastic process. In this article, we report a case of the co-existence of both UPS and ESFA in a 70-year-old male patient, presenting with a painless, erythematous, irregular surface nodule with a peripherally extended brownish hyperkeratotic plaque on the right palm. The histologic findings revealed an ill-defined dermal tumor of atypical epithelioid and spindle-shaped cells with large pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm. Some of those cells were multinucleated giant cells in the stroma with vascular proliferation and mixed inflammatory cell infiltrate. The tumor cells, which were only positive for vimentin, supported the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Meanwhile, the overlying epidermis demonstrated hyperkeratosis, papillated epidermal hyperplasia, and proliferation of anastomosing slender cords and strands of cuboid cells within loose fibrovascular stroma. These findings are the characteristics of eccrine syringofibroadenoma (ESFA). We describe here a patient in whom reactive ESFA occurred on and surrounded the UPS tumor. [ABSTRACT FROM AUTHOR]

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]

Purpose: To study the morphological and histological characteristics of the fibrous capsule formed around a novel biodegradable glaucoma drainage device (GDD) implant made of oxidized regenerated cellulose (ORC) after 1 and 3 months of its implantation. Methods: It was a prospective, interventional, preclinical experimental study using New Zealand white rabbits. All animals underwent GDD implantation with a novel biodegradable device. The device's body was made of ORC and attached to a silicone tube, connecting the body to the anterior chamber. Histopathology (hematoxylin and eosin/Masson's trichrome staining) and immunohistochemistry (Alpha-Smooth Muscle Actin expression) characteristics of the bleb formed around the novel device were noted at 1 and 3 months. Results: One month post implantation, the biodegradable material produced a significant foreign body type of reaction evidenced by the exuberant infiltration by macrophages, lymphocytes, and multinucleated giant cells. The granulomatous response subsided by 3 months with disorganized collagen deposition on Masson's trichrome staining. The silicone tube was an internal control, and histopathology demonstrated well-organized collagen deposition around it at 3 months. Immunohistochemistry for α-smooth muscle actin also demonstrated more myofibroblast transformation at the site of the tube than the biodegradable implant. Conclusions: Our results indicate that the tissue response around a biodegradable GDD was different from the response to conventional devices. A diffuse, loose vascularized mesh was observed to develop, which may be more compatible with sustained IOP control over a longer period, in contrast to the usual thick and dense capsule formed around the non-biodegradable devices. [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]

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]

Primary breast osteosarcomas are rare. We report an unusual case of a 58-year-old female presenting with a right breast lump for 1 month. Mammography showed an ill-defined, heterogeneous, and coarse calcification measuring 4 cm over the upper inner quadrant of the right breast. She received an upfront partial mastectomy after core needle biopsy showed osteoid-like tissue with the presence of atypical cells and some multinucleated giant cells. The final pathology revealed Grade 3 extraosseous osteosarcoma, osteoblastic type. Four cycles of adjuvant doxorubicin and cisplatin followed by radiotherapy were given due to the close surgical margin. She has since been free of recurrence for 3 years. [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]

The article in the Oman Journal of Ophthalmology discusses the case of an 11-month-old infant girl with unusual iris lesions in her left eye. The child was diagnosed with juvenile xanthogranuloma (JXG) and treated with steroid eye drops, resulting in a significant improvement and complete resolution of the lesions. JXG is a rare non-Langerhans cell histiocytosis that typically presents with yellow skin papules and can involve the eyes, requiring careful monitoring and treatment to prevent vision impairment. The article emphasizes the importance of timely identification and appropriate management of ocular JXG to ensure optimal outcomes for affected children. [Extracted from the article]

The article discusses a case report of a 48-year-old businessman with an atypical presentation of adult-onset hydroa vacciniforme, a rare photo-dermatosis. The patient experienced recurrent itchy skin eruptions in sun-exposed areas, leading to hypertrophic scars. Diagnosis was confirmed through histopathological examination and direct immunofluorescence (DIF) positivity. Treatment involved sun protection, hydroxychloroquine, and beta-carotene supplementation. The case underscores the importance of considering hydroa vacciniforme in adults with vesiculobullous eruptions on sun-exposed skin for early diagnosis and management. [Extracted from the article]

A 53-year-old woman with a 16-year history of epilepsy underwent microsurgical tumor resection for a mass in her left temporal lobe. The tumor was identified as a Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters. This rare entity predominantly affects pediatric patients but can also occur in older individuals, with distinct radiological and histopathological characteristics. Patients with this tumor generally have a favorable prognosis following surgical resection, although larger studies are needed to further understand these rare tumors. [Extracted from the article]

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.

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]

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]

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]

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 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]

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]

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.

The article "Response to Correspondence: Polylactic Acid: Is It Everything the Same?" published in the Journal of Cosmetic Dermatology discusses a study that aimed to analyze the microscopic composition of two PLLA formulations, Sculptra and Elleva. The authors found previously undocumented differences between the two formulations through histopathological analysis, highlighting the presence of crystals in Sculptra and acidic mucins in Elleva. The study emphasizes the importance of these findings in understanding tissue reactions and complications related to nodule formation. The authors acknowledge the valuable insights provided by the correspondence and suggest further research to validate opinions and relevance. [Extracted from the article]

The article discusses a case of acute drooling and anorexia in a Black Angus steer, which was euthanized and examined postmortem. The steer exhibited prominent soft tissue swelling under the chin and an enlarged, firm, and ulcerated tongue. The diagnosis was lingual actinobacillosis (wooden tongue), caused by Actinobacillus lignieresii, with treatment involving sodium iodide and antibiotics. The article provides detailed histopathological and microbiological findings, differential diagnoses, and treatment options for this condition. [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]

A 75-year-old man presented with subcutaneous indurations in his left upper arm and scrotum after receiving injections of leuprorelin acetate (LA) for prostate cancer. The indurations were diagnosed as sclerosing lipogranuloma in the scrotum and foreign body granuloma in the left upper arm. The patient's condition improved with treatment, and further studies are needed to understand the phenomenon of granuloma formation at LA injection sites. The article highlights the importance of patient consent and declares no conflicts of interest. [Extracted from the article]

The article discusses a case study of a 34-year-old female with persistent papules and pustules on her lower abdomen. The physical examination revealed red papules with central pustules surrounded by an erythematous halo. The histopathology indicated a diagnosis of localised perforating follicular granuloma annulare, a rare subtype of granuloma annulare. The article highlights the unique pathological features of the case and discusses differential diagnoses and treatment options. [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]

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]

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]

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]

The article titled "Understanding the Term 'Necrobiosis'" explains the term "necrobiosis" in dermatopathology and its various interpretations. It discusses the confusion caused by different authors describing the term differently. The article suggests using simpler terminology like "altered collagen" or "altered dermal connective tissue" when describing histological sections or generating skin biopsy reports. Necrobiosis refers to histopathological changes in the dermal connective tissue, including the presence of flame figures and structural alterations in collagen fibers. It can be seen in conditions like granuloma annulare, lupus miliaris disseminatus faciei, and sarcoidosis, but using more specific descriptions may be more helpful. [Extracted from the article]

This article presents a case report of a 46-year-old woman who had surgery for atypical carcinoid while also having active pulmonary tuberculosis. Atypical lung carcinoids are uncommon tumors with medium malignancy. Pulmonary tuberculosis is a leading cause of death from infectious diseases. The patient recovered after surgery and is now being monitored by a pulmonologist oncologist. The article provides information on the characteristics of atypical carcinoid tumors and the prevalence of pulmonary tuberculosis. It emphasizes the challenge of accurately identifying the cause of chronic cough and highlights the importance of considering rare pathologies even when more common conditions are present. [Extracted from the article]

Key Clinical Message: Giant cell tumor of bone (GCT) is a rare neoplasm which often presents as a lytic lesion in the epiphyseal region of long bones and which are usually accompanied by pain, swelling, and restricted movement. Giant cell tumor of bone (GCT) is a rare neoplasm that affects individuals in their third and fourth decades of life. Clinically, it often presents as a lytic lesion in the epiphyseal region of bones, notably the distal femur and proximal tibia. Radiologically, GCT appears as a distinct lytic lesion in the epiphyseal region. Histopathologically, GCTs are composed of mononuclear cells, macrophages, and multinuclear giant cells, indicative of osteoclastogenic stromal tumors. A 37‐year‐old man presented with left wrist pain, swelling, and restricted movement persisting for a year, worsening over the last 7 months. Radiographic assessments revealed a distal radius bone mass involving the radiocarpal joint. Biopsy confirmed a GCT with extension into peripheral muscle. PET/CT scan showed localized pathology without metastasis. Histopathologically, GCT exhibited multinucleated giant cells, spindle cells, and aneurysmal bone cyst‐like regions with coagulation necrosis. Surgical resection involved en‐bloc removal and reconstruction with a non‐vascularized radius bone graft. Postoperatively, the patient showed no complications at the one‐year follow‐up, suggesting successful intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: Buffalo are country animals, with great adaptability, and thrive in diverse environments. The State of Pará has the largest herd of buffalo in Brazil, which can be found mainly on Marajó Island in the northern region of the state. As a result, buffalo farming has become widespread in Brazil, and it offers several products to the consumer market. However, in the State of Pará, skin diseases stand out among the diseases that affect this species. This study reports the first case of dermatitis caused by Pelodera spp. in buffalo (Bubalus bubalis) on Marajó Island, Pará. This is the first report of parasitic granulomatous dermatitis caused by Pelodera spp. in a buffalo. The affected buffalo was about seven years old, was a female of the Murrah breed and belonged to a property located on Marajó Island in the State of Pará. During the clinical examination, the animal was in a standing position and presented several multifocal nodular and placoid masses throughout the body, mostly on the forelimbs, hindlimbs, abdomen, mammary glands, perineum, vulva and tail. These masses were also observed on the nasal mucosa, head, neck, back and chest. On macroscopic examination, the skin had several multifocal-to-coalescent sessile nodular and placoid lesions. Histopathology of the skin showed a marked reduction in the number of hair follicles. In the superficial dermis, there was significant multifocal-to-coalescent inflammatory infiltration, consisting of macrophages, epithelioid macrophages, lymphocytes, plasma cells and multinucleated giant cells. In the remaining hair follicles, there were numerous cross and longitudinal sections of small rhabditoid nematodes characterized by a thin cuticle, platymyarian musculature, an intestinal tract, a rhabditiform esophagus and lateral alae (morphologically compatible with Pelodera spp.). The diagnosis of parasitic dermatitis was confirmed by histopathological skin lesions associated with the presence of intralesional rhabditiform larvae morphologically compatible with Pelodera spp. [ABSTRACT FROM AUTHOR]

Background: Pilomatrixoma is a benign adnexal tumor with differentiation towards the matrix of the hair follicle and occurs mostly in the head, neck, and upper extremities of the child. Pilomatrixoma of the breast is considered a very rare tumor. Case presentation: Herein, we present a 47-year-old woman who was referred to the surgery ward for a palpable right breast mass. Imaging studies revealed a wellcircumscribed lesion categorized as BIRADs3. Because clinically the lesion was large and had a stony hard consistency, the patient underwent surgery and intraoperative consultation was negative, revealing a well-defined lesion composed of basaloid cells, multinucleated giant cells admixed with bone trabeculae, and nests of ghost cells. Immunohistochemical (IHC) studies were done and the cells were positive for AE1/AE3, Beta-catenin, and BCL2 and negative for Mart1 and CD117. Based on H&E and IHC studies, pilomatrixoma of the breast tissue was confirmed. Conclusion: Breast pilomatrixoma is a very rare benign neoplasm that could clinically mimic malignant neoplasm and should be considered in the differential diagnosis of breast masses. [ABSTRACT FROM AUTHOR]

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm comprising perivascular epithelioid cells that express myomelanocytic immunophenotype, while stain negative for epithelial markers. We describe a case of prostatic PEComa in a 55-year-old man, who had one month history of frequent urination, hesitancy, and sensation of incomplete voiding. Radiological imaging disclosed prostatomegaly. Despite the medical treatment offered, episodes of urinary retention persisted. Subsequently, he underwent endoscopic transurethral resection of the prostate, histology showed tumor arranged in nests surrounded by thin delicate vessels. The tumor cells were epithelioid with abundant clear-to-eosinophilic cytoplasm, round nuclei, and inconspicuous nucleoli. Bizarre multinucleated giant cells, conspicuous mitosis and focal necrosis were evident. On immunohistochemistry, the tumor cells were diffusely positive for Human Melanoma Black (HMB45) and smooth muscle actin, negative for anti-cytokeratin monoclonal antibodies (AE1/AE3), Homeobox protein (NKX3.1), GATA Binding Protein 3 (GATA3), synaptophysin, Transcription Factor Binding to Immunoglobulin Heavy Constant Mu (IGHM) Enhancer 3 (TFE3), desmin, and SRY (sex determining region Y) -Box Transcription Factor 10 (SOX10). This uncommon case illustrates our diagnostic ordeal with a brief discussion on its nosology and a comprehensive literature review. [ABSTRACT FROM AUTHOR]