Search Results (31)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily causes mild to moderate respiratory illness in humans, but infection can also lead to long-term complications, including chronic fatigue, respiratory and cardiac issues, or even death. In November 2021, the emergence of the highly transmissible Omicron variant marked a significant shift in the pandemic, with its subvariants rapidly spreading and continuing to evolve worldwide. The continuing introduction of Omicron subvariants underscores the need for the development of up-to-date vaccines, as well as for appropriate animal models in which they can be evaluated. Among these subvariants, XBB.1.5 stands out for its ability to evade the immune response from previous infection or vaccination. The objective of this study was to determine the disease course in African green monkeys (AGMs) following intranasal exposure to the XBB.1.5 subvariant. In four intranasally exposed AGMs, histopathological findings in the lungs consistent with SARS-CoV-2 infection included lymphohistiocytic and neutrophilic bronchiolitis with variable numbers of syncytial cells, to terminal bronchiole-centric, bronchointerstitial pneumonia with alveolar type II (AT2) pneumocyte hyperplasia, with evidence of acute alveolar injury, including alveolar septal necrosis and hyaline membrane formation. The two males showed more severe pneumonia compared to the two females. SARS-CoV-2 RNA was detected in the lungs or tracheobronchial lymph nodes in the males but not in the females, which correlated with higher cumulative lung pathology scores in the males. In the females, SARS-CoV-2 RNA was limited to the colon and nasal turbinates. Our results indicate that AGMs exhibit a disease course similar to most humans when exposed intranasally, making them a suitable model for studying mild to moderate SARS-CoV-2 infection. Therefore, further work is warranted to determine if this model could have utility for the evaluation of vaccine and therapeutic candidates against contemporary SARS-CoV-2 variants. Full article

Background: Castleman’s disease (CD), also known as angiofollicular lymph node hyperplasia, describes a rare group of diseases manifesting with enlarged lymph nodes and various inflammatory symptoms. The association between Castleman’s disease, paraneoplastic pemphigus and bronchiolitis obliterans has been described in the literature and is depicted thoroughly in this case. Case Presentation: We present a case of severe bronchiolitis obliterans developing in a 17-year-old female with paraneoplastic pemphigus and unicentric Castleman’s disease. Conclusion: Surgical resection of unicentric Castleman’s disease remains the treatment of choice due to its efficacy in preventing the recurrence of associated morbidity caused by bronchiolitis obliterans and paraneoplastic pemphigus. Full article

Background and Clinical Significance: Cervical lymphadenopathy is a common condition in children, most often caused by reactive hyperplasia due to viral infections, followed by bacterial infections and, less commonly, malignancies. Supraclavicular lymphadenopathy in children warrants thorough evaluation due to its higher association with malignancy compared to anterior cervical lymphadenopathy. Kikuchi–Fujimoto disease (KFD) is a rare, benign, and self-limiting condition characterized by cervical lymphadenopathy, predominantly affecting young adults—especially Asian women—and is rarely observed in children. We present a case of a 14-year-old girl with cervical and supraclavicular lymphadenopathy diagnosed with KFD. Case Presentation: A previously healthy 14-year-old girl was admitted with a 20-day history of cervical and supraclavicular lymphadenopathy, fever, and 5 kg weight loss. Laboratory investigations revealed leukopenia and lymphopenia, with a weakly positive ANA titer (1:160) and no other significant abnormalities. Extensive infectious workup was negative. Cervical ultrasound showed multiple enlarged, hypoechoic, rounded lymph nodes. CT imaging revealed paraaortic lymphadenopathy without additional findings. Due to the persistence of lymphadenopathy and inconclusive workup, a lymph node biopsy was performed to rule out malignancy. Histopathology was consistent with Kikuchi–Fujimoto disease. Conclusions: This case highlights a rare pediatric presentation of KFD, particularly notable for supraclavicular lymphadenopathy. It underscores the importance of considering a broad differential diagnosis in persistent lymphadenopathy, including rare conditions such as Kikuchi–Fujimoto disease. Full article

Background/Objectives: The major question that confronts a pathologist when evaluating a lymph node biopsy is whether the process is benign or malignant, and the differential diagnosis between follicular lymphoma and reactive lymphoid tissue can be challenging. Methods: This study designed a convolutional neural network based on ResNet architecture to classify a large series of 221 cases, including 177 follicular lymphoma and 44 reactive lymphoid tissue/lymphoid hyperplasia, which were stained with hematoxylin and eosin (H&E). Explainable artificial intelligence (XAI) methods were used for interpretability. Results: The series included 1,004,509 follicular lymphoma and 490,506 reactive lymphoid tissue image-patches at 224 × 244 × 3, and was partitioned into training (70%), validation (10%), and testing (20%) sets. The performance of the training (training and validation sets) had an accuracy of 99.81%. In the testing set, the performance metrics achieved an accuracy of 99.80% at the image-patch level for follicular lymphoma. The other performance parameters were precision (99.8%), recall (99.8%), false positive rate (0.35%), specificity (99.7%), and F1 score (99.9%). Interpretability was analyzed using three methods: grad-CAM, image LIME, and occlusion sensitivity. Additionally, hybrid partitioning was performed to avoid information leakage using a patient-level independent validation set that confirmed high classification performance. Conclusions: Narrow artificial intelligence (AI) can perform differential diagnosis between follicular lymphoma and reactive lymphoma tissue, but it is task-specific and operates within limited constraints. The trained ResNet convolutional neural network (CNN) may be used as transfer learning for larger series of cases and lymphoma diagnoses in the future. Full article

Here, the authors report the first case of a primary mast cell tumor originating from the inguinal lymph node in a nine-year-old intact female Maltese dog that had undergone a left ureteral stent, ureterotomy and splenectomy, and left-side mastectomy, including inguinal lymph node removal and ovariohysterectomy, in South Korea in May 2024. The splenic mass, mammary gland mass, and inguinal lymph node underwent histopathological examination, resulting in the diagnosis of nodular hyperplasia, grade 1 mammary complex carcinoma, and a mast cell tumor (MCT), respectively. To clarify the origin of the MCT from the inguinal lymph node, a computed tomography (CT) scan was performed. In addition, through a blood smear test, mast cell leukemia was ruled out. After CT scanning by veterinary radiologists and a biopsy of all possible masses, it was finally concluded that the MCT primarily originated from lymph nodes, which is extremely rare in dogs. The patient is recovering well as of February 2025, just 7 months after the first diagnosis, following surgery and 16 weeks of chemotherapy with a combination of prednisolone and vinblastine, considering the C-kit PCR results of the left inguinal lymph node after the surgical removal of the MCT. This report is significant for two reasons, firstly because of the rarity of MCTs originating from lymph nodes other than the skin and gastrointestinal organs, and secondly because the authors propose a hypothesis for the rarity of primary lymph node mast cell tumors and the correlation between mammary gland tumors and mast cell tumor growth based on a comparative literature review in humans, focusing on molecular mechanisms. Full article

Objective: Inflammatory arthritis (IA) has been linked to a number of adverse pregnancy outcomes (APOs), but the mechanisms linking IA-related immune dysregulation to compromised reproductive success remain poorly understood. This project will examine how IA affects pregnancy outcomes and alters the associated immune microenvironment using SKG (ZAP70^W163C) mice, a mouse model that suffers from arthritis resembling human IA. Methods: IA was induced in SKG mice on a C57BL/6J background via mannan exposure. Wild-type C57BL/6 mice served as controls. Pregnancy rates, conception time, embryo resorption rates, and immune parameters (cytokine levels and splenic/lymph node/placental immune cell subsets) were analyzed. Joint pathology was evaluated via histology (HE is staining) and anti-CCP antibody levels. Flow cytometry was used to analyze immune populations within the spleen along with the associated lymphatic nodes. Results: Synovial hyperplasia, elevated anti-CCP, and systemic inflammation were all observed in IA mice. Compared to controls, IA mice demonstrated a reduced mating success rate, prolonged conception time, decreased pregnancy rates, and increased embryo resorption. IA mice showed elevated Th1/Th17 cytokines-IFN-γ, TNF-α, and IL-17, and an expansion of pro-inflammatory immune cells, including NK cells, CD11b+ myeloid cells, neutrophils, M1 macrophages, and Tc1, in the spleen/lymph nodes. Placental immune dysregulation featured increased NKT, NK, and CD4+ cell infiltration. Conversely, anti-inflammatory subsets, such as M2 macrophages and dendritic cells, were reduced. Conclusions: IA increased APOs and skewed the immune microenvironment toward a pro-inflammatory state dominated by Th1/Th17/Tc1 responses and cytotoxic cell activation. These findings highlight immune dysregulation as a key driver of IA-associated pregnancy complications, providing mechanistic insights for therapeutic intervention. Full article

Multiplex immunostaining (mIHC) allows the simultaneous detection of multiple antigenic targets within the same tissue section, providing a deeper understanding of spatial variation in cellular distribution. The aim of the present study is to apply this technique to examine the spatial variation of lymphocyte populations in swine lymph nodes during PCV2-SD and PRRSV lymphadenopathy compared with reactive lymphoid hyperplasia. A triple immunohistochemical stain with CD3, CD20 and IBA1 antibodies for the concurrent detection of T lymphocytes, B lymphocytes and macrophages, respectively, was performed. Multiplex immunohistochemistry (mIHC) revealed that, compared to reactive hyperplasia, the most significant changes in lymph node cell populations occurred in the follicles for both PCV2 and PRRSV infections. Additionally, in PCV2 cases, notable alterations were also observed in the interfollicular areas. In PCV2-affected lymph nodes, follicles not only significantly decreased in number but also showed a marked significant reduction in CD20⁺ and CD3⁺ cells. The interfollicular region in these cases also exhibited a significant reduction in CD3⁺ cells. In contrast, PRRSV-associated lymphadenopathy showed significantly increased CD20⁺ cells in the follicles, with a similar trend noted in the interfollicular region. mIHC provides more informative results on a single tissue section, thus preserving the topographical information of the tissue and allowing a comprehensive study of cellular composition, cellular functionality and cell–cell interactions, proving to be a valuable tool for studying and understanding disease dynamics. Full article

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article

Lyme disease (LD), caused by infection with the tick-borne bacteria, Borrelia burgdorferi, is associated with a wide array of symptoms in human patients. Variations in clinical manifestations are thought to be influenced by genetic differences among B. burgdorferi strains. In this study, we evaluated the infectivity, tissue bacterial load, pathology, and immunogenicity of five strains of B. burgdorferi sensu stricto (297 Ah130, Bb16-54, B31-A3, Bb16-126, JD1) in female C3H/HeN mice at three infectious doses (10⁴, 10⁵, 10⁶ spirochetes). We found that strains Bb16-126 and JD1 were the most infectious, resulting in 100% infection across all the tested doses. Strain Bb16-126 caused the highest bacterial burden in the heart tissue and significant carditis, whereas JD1 exhibited the lowest spirochete load in the heart and minimal carditis. In comparison, strain B31-A3 demonstrated the highest abundance in the tibiotarsal joint. Infection with all the strains induced severe lymph node hyperplasia, with JD1 producing the greatest increase in cellularity. Using a diagnostic C6 peptide ELISA, all the strains induced significant anti-C6 IgM and IgG antibody titers at 14 days post-infection; however, strain B31-A3 elicited the highest anti-C6 IgM titers. Our findings demonstrate the importance of strain diversity in shaping B. burgdorferi pathogenesis in a mouse model and provide insights for developing strain-specific diagnostic, therapeutic, and vaccine strategies. Full article

Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate diagnosis and classification of endometrial hyperplasia are crucial. Since the treatment for atypical endometrial hyperplasia is the same as that for early-stage endometrial cancer (i.e., total hysterectomy and bilateral salpingo-oophorectomy), researchers have questioned whether sentinel lymph node mapping could also have a prognostic role in atypical endometrial hyperplasia. Methods: A literature search was conducted in PubMed and Scopus from 2014 to 2025. Of the 65 papers found, 31 relevant articles were selected based on inclusion criteria, focusing on sentinel lymph node staging in patients with atypical endometrial hyperplasia. This review aims to assess whether sentinel lymph node mapping can be routinely used for prognostic and therapeutic purposes in clinical practice. Results: Sentinel lymph node biopsy represents a promising diagnostic technique for patients with atypical endometrial hyperplasia, reducing the need for invasive procedures and postoperative risks. However, its application requires advanced surgical skills and access to specific technologies, raising ethical and financial concerns, while future studies could improve patient selection and the reliability of the procedure through technological innovations. Conclusions: Sentinel lymph node biopsy is a safe and effective method for staging early-stage endometrial cancer and atypical hyperplasia, with low metastasis rates, but future research should focus on identifying patients who would benefit most from this procedure, considering its costs and required expertise. Full article

Background and Objectives: Robotic-assisted laparoscopy (RS) has been widely adopted for the management of endometrial cancer (EC) due to favorable perioperative outcomes, especially in the context of obesity, which is an established risk factor for EC. This study retrospectively evaluated the perioperative outcomes of RS versus conventional laparoscopy (LS) in treating EC and atypical endometrial hyperplasia (AH). Methods: Between November 2021 and October 2023, 138 patients with AH or EC underwent surgery at the Clinic of Obstetric and Gynecological—Azienda Sanitaria Universitaria Friuli Centrale, Udine. All patients had total hysterectomy with bilateral salpingo-oophorectomy, with or without lymphadenectomy or sentinel lymph node biopsy. The study included 62 patients treated with LS and 62 with RS. Results: The median BMI was higher in the RS group (35.5 vs. 24 kg/m², p = 0.001). There was no significant difference in operative time between the laparoscopic group and the robotic console time (median 130 vs. 130 min, p = 0.131). No significant differences were found in terms of blood loss, conversion to laparotomy, intraoperative complications, hospital stay, or early postoperative complications between the two groups. Conclusions: Our data confirm the feasibility of robotic surgery in obese patients, allowing surgical results comparable to those of laparoscopy in normal-weight patients. Full article

Background: The association of intravenous prostacyclin therapy, essential for improving prognosis and survival in pulmonary arterial hypertension (PAH), with gastric epithelial neoplasms is uncertain. This study aimed to analyze the clinicopathologic features of gastric neoplasms in patients with PAH undergoing continuous intravenous prostacyclin therapy. Methods: We screened the registry of patients with pulmonary hypertension who visited the NHO Okayama Medical Center. Of the patients with PAH managed between January 2003 and December 2022, those who underwent esophagogastroduodenoscopy (EGD) were assessed for gastric neoplasms. Their clinical, endoscopic, and histopathological data were reviewed. Results: Among the 186 patients with PAH, 56 underwent EGD, revealing 4 patients (aged 37–50 years) with gastric epithelial neoplastic lesions. All four patients received continuous intravenous prostacyclin therapy for a median of 151 months. Of the 98 patients who received prostacyclin, 28 patients underwent EGD; the incidence of gastric epithelial neoplasms was 4.1% (4/98) and the endoscopic detection rate was 14.3% (4/28). All patients had multiple tumors against a background of hypertrophic gastropathy (histologically being foveolar epithelial hyperplasia), with shared features of distal location, elevated morphology, and absent submucosal invasion. However, lymph node metastasis was observed in one lesion. By immunohistochemistry, the tumors exhibited gastric-predominant mucus phenotype and were managed by surgical or endoscopic resection without recurrence. Conclusions: The consistent clinicopathologic features of these cases suggest an association between continuous intravenous prostacyclin therapy and the development of hypertrophic gastropathy with potential progression to gastric epithelial neoplasia. Further prospective clinical trials are warranted to ensure safer prostacyclin use. Full article

Deoxynivalenol (DON) is a mycotoxin commonly found worldwide and is implicated in various health effects. We recently demonstrated that subacute oral exposure to DON significantly exacerbates symptoms of type 2 helper T-cell-mediated allergic diseases in a model. We aim to investigate the role of oral DON exposure in type 17 helper T-cell-mediated immunoreactive diseases using a mouse psoriasis model. Psoriasis was induced by the dermal administration of 5% imiquimod in female BALB/c mice. A standard rodent diet was supplemented with DON to achieve a final concentration of 0.3 ppm (1.5 μg/kg bw/day), which was administered daily for 14 days. Skin thickness, scratching behavior, and transepidermal water loss (TEWL) were continuously measured during imiquimod administration. Mice exposed to DON exhibited significant increases in skin thickness, TEWL, and scratching behavior. Histological evaluations revealed aggravated hyperplasia, neutrophil infiltration, and inflammatory cell accumulation in the dermis. Furthermore, DON exposure significantly increased the number of CD4+ helper T cells and CD11c+ MHC class II+ dendritic cells in the auricular lymph nodes, along with elevated TNF-α and IL-17 levels in stimulated T cells. The gene expression of IL-17 in skin tissue was also significantly up-regulated in DON-treated mice. Collectively, these findings suggest that oral exposure to DON aggravates symptoms in a mouse psoriasis model. Full article

The purpose of the present study is to contribute to the establishment of a standard method for evaluating the adverse effects of nanomaterials by intratracheal administration. Low and high doses of multi-walled carbon nanotubes (MWCNTs) were administered to rats in a single administration or the same final dose as the single administration but divided over four administrations. Bronchoalveolar lavage examination on day 14 showed an inflammatory reaction and cytotoxicity in the lung, generally greater at the higher dose, and tending to be greater in the rats with four administrations at both the low and high doses. Histopathologic findings showed increased alveolar macrophages and MWCNT deposition (fibers phagocytosed by alveolar macrophages and fibers that were not phagocytosed) in the alveolar space, granulomatous changes, and MWCNT deposition in bronchus-associated lymphoid tissue (BALT) and lung-related lymph nodes on days 14, 28, and 91. In addition, alveolar type II epithelial hyperplasia was observed on day 91, and fibrosis of the alveolar wall was observed on days 28 and 91. Fewer alveolar macrophages with phagocytosed MWCNTs were present at day 91 compared to day 28. MWCNT deposition tended to be higher in the BALT after a single administration, whereas deposition was higher in the lung-related lymph nodes after four administrations. MWCNTs were considered to be transported from the lungs or BALT to the lymph nodes over time. There were no significant differences in MWCNT deposition in the lung after the single administration compared with four administrations at either the low or high doses, and the histopathological findings were similar after single and four administrations, at both the low and high doses. Based on the above findings, a toxicity evaluation of the nanomaterials can be sufficiently performed by intratracheal administration, even with a single intratracheal administration. Full article

Background and Aim: Ex vivo fluorescence confocal microscopy (FCM) systems are innovative optical imaging tools that create virtual high-resolution histological images without any standard tissue processing, either freezing or fixing in formalin and embedding in paraffin. These systems have opened an era that would revolutionize pathological examination by providing rapid, real-time assessments across various pathology subspecialties, potentially replacing conventional methods that are tissue- and time-consuming. This study aimed to present the first utilization of FCM in pediatric surgical oncology, focusing on assessing the benefits, particularly in facilitating rapid and accurate diagnosis. Methods: This preliminary study comprised five consecutive patients undergoing surgical biopsy for disease characterization and surgical strategy selection. After biopsy, tissue samples were prepared and analyzed using FCM without sectioning. A pathologist who evaluated macroscopic and microscopic images, once obtained remotely, could promptly indicate any interventions that require timeliness. Samples were then evaluated with conventional methods. Results: All five lesions were deemed suitable for evaluation. Preliminary diagnoses utilizing FCM included atypical Spitz nevus (1), Wilm’s tumor (1), lymph node reactive hyperplasia (1), malignant germ cell tumor of the testis (1), and Hodgkin’s lymphoma (1). Final histopathological analyses revealed atypical Spitz nevus (1), Wilm’s tumor (1), hyperplastic lymphadenopathy with a prevalent marginal pattern (1), mixed nonseminomatous malignant germinal neoplasm consisting of embryonal carcinoma (90%) and yolk sac tumor (10%), and Hodgkin’s lymphoma nodular sclerosis variant (1). In the case of diagnosis of atypical Spitz nevus, the widening of the resection margins was performed in the same surgery. In the case of testicular neoplasm, radical orchiectomy was performed. A high level of agreement between FCM evaluation and definitive histological examination was observed for all parameters evaluated. Conclusions: FCM represents a significant advancement in pathological imaging technology, offering potential benefits in enhancing traditional tissue processing methods. This preliminary report marks the first application of FCM in pediatric surgical oncology. Our findings underscore the promising role of FCM as an adjunctive tool in pediatric oncology, facilitating prompt diagnosis and treatment initiation. Full article