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Systemic amyloidosis involves the deposition of misfolded proteins in organs/tissues, leading to progressive organ dysfunction and failure. Congo red is the gold-standard chemical stain for visualizing amyloid deposits in tissue, showing birefringence under polarization microscopy. However, Congo red staining is tedious and costly to perform, and prone to false diagnoses due to variations in amyloid amount, staining quality and manual examination of tissue under a polarization microscope. We report virtual birefringence imaging and virtual Congo red staining of label-free human tissue to show that a single neural network can transform autofluorescence images of label-free tissue into brightfield and polarized microscopy images, matching their histochemically stained versions. Blind testing with quantitative metrics and pathologist evaluations on cardiac tissue showed that our virtually stained polarization and brightfield images highlight amyloid patterns in a consistent manner, mitigating challenges due to variations in chemical staining quality and manual imaging processes in the clinical workflow. Detecting amyloid deposits in tissue with Congo red can be limited by several factors, which can potentially lead to false diagnoses. Here, the authors use virtual birefringence imaging and virtual Congo red staining using autofluorescence of label-free human tissue, highlighting amyloid deposits in a consistent manner. [ABSTRACT FROM AUTHOR]

* Context.--The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility. Objective.--To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format and method of observation compared with the current standard glass slide microscopy, this study is critical to potential clinical adoption of digital pathology. Design.--The study enrolled a total of 2045 cases enriched for more difficult diagnostic categories and represented as 5849 slides were curated and provided for diagnosis by a team of 19 reading pathologists separately as WSI or as glass slides viewed by light microscope. Cases were reviewed by each pathologist in both modalities in randomized order with a minimum 31-day washout between modality reads for each case. Each diagnosis was compared with the original clinical reference diagnosis by an independent central adjudication review. Results.--The overall major discrepancy rates were 3.64% for WSI review and 3.20% for manual slide review diagnosis methods, a difference of 0.44% (95% CI, -0.15 to 1.03). The time to review a case averaged 5.20 minutes for WSI and 4.95 minutes for glass slides. There was no specific subset of diagnostic category that showed higher rates of modality-specific discrepancy, though some categories showed greater discrepancy than others in both modalities. Conclusions.--WSIs are noninferior to traditional glass slides for primary diagnosis in anatomic pathology., Histopathology interpretation remains an essential, foundational method for disease diagnosis in medical practice. (1) Standard histopathology assessment is initiated through interpretation of hematoxylin and eosin--stained glass microscope slides prepared from [...]

Introduction: Large cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC) tumor are two distinct types of pulmonary neuroendocrine tumors (NETs) that are considered genetically unrelated. AC is categorized as a well-differentiated NET, while LCNEC is considered a poorly differentiated NET with a significantly poorer prognosis. Case Presentation: In this case report, we present an 83-year-old male who presented with 2-day history of hemoptysis and subsequently diagnosed with a right upper lobe carcinoid tumor on pre-excision biopsy. After evaluation of the entire excised specimen, the tumor was subsequently reclassified as LCNEC. This case is rare as the tumor displayed pathologic features of AC (areas with low mitotic activity and punctate necrosis) alternating with areas of LCNEC (high mitotic activity with sheets of necrosis). Subsequent molecular studies were more characteristic of AC, with no mutations detected in Rb1 or p53. The patient underwent surgical resection (right upper lobectomy with bronchoplasty and mediastinal lymph node dissection) to remove the tumor. Conclusion: This report outlines the clinical presentation and the underlying pathology of this rare case, which underscores the complex molecular landscape of neuroendocrine neoplasms and the need for nuanced molecular analyses in refining diagnostic approaches. [ABSTRACT FROM AUTHOR]

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Background The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs). Methods We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed. Results We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage ( p = 0.0008), in the presence of capillary neutrophilic inflammation ( p = 0.0014), and in samples with endotheliitis ( p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs. Conclusions Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain. [ABSTRACT FROM AUTHOR]

Little is known about the efficacy of COVID-19 vaccines during acute lymphoblastic leukemia therapy (ALL); data for COVID-19 vaccine immune responses in pediatric leukemia remain sparse. We conducted a single center study of patients aged 5-25 years undergoing ALL chemotherapy who received COVID-19 vaccination. Twenty-one patients were enrolled; efficacy was evaluable in 20. Twenty were vaccinated while receiving chemotherapy. Twenty received the BNT162b2 mRNA vaccine. Spike reactive antibodies (S-IgG) and/or T-cells (SRT) were detected in 16 of 20 (80%) vaccinated patients; 13 (65%) and 9 (45%) were positive for S-IgG and SRT, respectively. Six (30%) showed both spike reactive B and T-cell responses. Eleven of the 13 with S-IgG positivity were negative for anti-Nucleocapsid IgG, an antibody profile consistent with a vaccine induced immune response. All 13S-IgG+ patients showed neutralizing antibodies. SRT included CD4+ (7) and CD8+ (6) T-cells; both CD4+ and CD8+ SRT were seen in 4. SRT were multifunctional (producing multiple cytokines) in most patients (8 of 9); 4 showed SRT with triple cytokine and B-cell co-stimulatory responses, indicating a multimodal adaptive immune response. Immune responses were seen among patients vaccinated in the settings of lymphopenia (6 of 12) intensive chemotherapy (3 of 4), and Peg allergy (6 of 8). Sequencing revealed public CD4+ and CD8+ TCR sequences reactive to epitopes across the spike protein. In conclusion, COVID-19 vaccination induced B and/or T-cell responses in a majority of children and young adults undergoing ALL chemotherapy., (© 2024 UICC.)

This study analyzed the histologic effects of and host response to subdermally injected liquid silicone to augment soft-tissue cushioning of the bony prominences of the foot. A total of 148 postmortem and surgical specimens of pedal skin with attached soft tissue were obtained from 49 patients between July 1, 1974, and November 30, 2002. The longest period that silicone was in vivo was 38 years. The specimens were then processed into paraffin blocks and examined for specific findings. The variables considered included distribution of silicone within the tissue, host response, migration to regional lymph nodes, and viability of the host tissue after treatment. The host response to silicone therapy consisted primarily of delicate-to-robust fibrous deposition and histiocytic phagocytosis, with eventual formation of well-formed elliptic fibrous pads. The response in the foot appears different from that in the breast and other areas of the body previously studied. No examples of granulomas, chronic lymphoplasmacytic inflammation, or granulation tissue formation were seen, with only rare foreign-body giant cells present. Silicone injections in fat pads for the treatment of atrophy and loss of viable tissue show a histologically stable and biologically tolerated host response that is effective, with no evidence of any systemic changes.