Archives of pathology & laboratory medicine最新文献

Context.—: Since the early 2000s, noninvasive tests (NITs) such as serum biomarkers (eg, fibrosis index based on the 4 factors [FIB-4], aspartate aminotransferase-to-platelet ratio index) and imaging techniques such as transient elastography (FibroScan) have been used to assess hepatic fibrosis. Although they have been validated in pretransplant cohorts, their posttransplant accuracy remains uncertain.

Objective.—: To assess concordance between liver biopsy (LBx) and 2 widely used NITs-FibroScan and FIB-4-and identify drivers of discordance in the posttransplant setting.

Design.—: Adult liver transplant recipients who underwent LBx (2015-2024), with FibroScan data available within 6 months and laboratory values available within 1 month, were included. Stage of trichrome fibrosis, percentage steatosis, liver stiffness measurement, and FIB-4 scores were analyzed. Concordant and discordant cases were compared.

Results.—: Among 108 patients (median age, 63 years; range, 27-76 years), common diagnoses included recurrent (n = 49; 45.4%) and de novo (n = 29; 26.8%) steatotic liver disease (SLD), recurrent chronic hepatitis C (n = 9; 8.3%), and allograft rejection (n = 8; 7.4%). Median fibrosis was stage 1 by LBx, whereas median liver stiffness measurement and FIB-4 corresponded to stage 2. Overall, correlation with LBx was low (r = 0.227, P = .02 for FibroScan; r = 0.077, P = .43 for FIB-4). FibroScan overestimated fibrosis in 23.8% (21 of 88) of early-stage and underestimated 30% (6 of 20) of advanced fibrosis. FIB-4 misclassified 29.5% (26 of 88) without advanced fibrosis as F3 through F4 and missed 45% (9 of 20) with advanced fibrosis.

Conclusions.—: NITs show limited concordance with LBx in posttransplant fibrosis assessment. Discrepancies may stem from confounders such as severe steatosis, body mass index 30 kg/m2 or higher, inflammation, rejection, infiltrative processes (eg, amyloidosis), and nodular regenerative hyperplasia (NRH).

Context.—: Stratified mucin-producing intraepithelial lesions (SMILEs) and invasive stratified mucin-producing carcinoma (ISMC) are well studied in the uterine cervix. These lesions have recently been described in the anorectal canal; however, understanding about their clinicopathologic features and clinical implications is limited.

Objective.: -To investigate the clinicopathologic features and behavior of SMILE/ISMC in the anorectal canal.

Design.—: We identified 4 cases containing SMILE/ISMC in the anorectal canal between 2013 and 2024. Clinical data and histopathologic slides were reviewed.

Results.—: The SMILE/ISMC component was associated with conventional adenocarcinoma (n = 1), squamous cell carcinoma (n = 2), or adenosquamous carcinoma (n = 1). We observed SMILE in 2 of 4 cases, ISMC in 1 of 4 cases, and both components in 1 of 4 cases. Histopathologic features included intracytoplasmic mucin, pseudostratification (all cases), various degrees of peripheral palisading, apoptosis, intratumoral neutrophils (all cases), and mitoses (3 of 4 cases). A p16 immunohistochemical stain showed diffuse positivity (3 strong and 1 weak) in all SMILE/ISMC, and in situ hybridization for human papillomavirus 16/18 RNA was positive in 2 cases. Three of 3 cases were mismatch repair proficient, p53 wild type, and HER2 negative. All 4 patients were alive on follow up (median, 16.5 months). One patient was found to have a separate focus of human papillomavirus-driven invasive adenocarcinoma 4 months post-excision of SMILE/adenocarcinoma. None showed residual/recurrent disease at the site.

Conclusions.—: SMILE is often associated with invasive carcinoma and may be a harbinger of neoplasia similar to its cervical counterpart. Close examination is necessary for accurate diagnosis, and further study is warranted to determine the potential benefits of closer follow-up.

Context.—: In the past decade, central nervous system (CNS) tumor diagnosis has shifted toward molecular classification. Tools like DNA/RNA sequencing and methylation array analysis are now supportive tools, as reflected in the World Health Organization Classification of Tumours of the Central Nervous System, 5th edition. However, implementing these sophisticated and costly methods remains challenging for health care services in most developing countries.

Objective.—: To report the implementation and utility of methylation array-based classification in CNS tumor cases at a Brazilian pathology reference laboratory, and to explore practical challenges and opportunities for achieving diagnostic precision in resource-constrained environments.

Design.—: This study analyzed 319 CNS tumor cases that underwent methylation analysis. Cases were stratified into 6 categories: (1) Methylation Confirms or Narrows Initial Diagnosis; (2) Diagnosis Modified by Methylation; (3) Diagnosis Confirmed With Molecular Subclassification; (4) Specification of Initially Descriptive Diagnosis; (5) Emerging Entities; and (6) Unclassified/Inconclusive. We analyzed diagnostic impact, costs, and turnaround time.

Results.—: DNA methylation profiling was successfully completed in most cases, with preanalytical failures mainly due to insufficient DNA quantity or quality. Turnaround time varied with regional logistics. Classifier outputs yielded confident matches for most cases. However, 47 cases (14.7% of cohort) produced "no match" results due to low confidence scores (≤0.30) or divergent classifier outputs. Additional testing was performed when available.

Conclusions.—: DNA methylation profiling improves diagnostic accuracy and reclassifies a meaningful proportion of brain tumor cases. Broad implementation requires evidence of cost-effectiveness, streamlined workflows, and capacity building, particularly in low- and middle-income settings.

Context.—: Lymph node (LN) assessment plays a critical role in cancer staging and prognosis but remains a time-consuming and labor-intensive task in pathology. While artificial intelligence (AI) tools have shown promise in improving diagnostic accuracy, their real-world clinical utility in LN metastasis detection across multiple cancer types remains underexplored.

Objective.—: To evaluate the diagnostic performance and efficiency of an AI module in detecting LN metastases from gastric, colorectal, and breast cancers, and to assess its impact on pathologists' workflow.

Design.—: A retrospective study was conducted by using 314 whole slide images from 95 patients who underwent resection for gastric, colorectal, or breast cancer. Three board-certified pathologists reviewed the slides with and without AI assistance. Diagnostic accuracy, review time, and number of mouse clicks required to detect metastases were recorded and compared.

Results.—: AI assistance increased sensitivity-which ranged from 91.8% to 93.9%-to 95.9% for all pathologists, while specificity remained high (97.0%-98.9%). Time to detect LN metastases decreased by up to 78% for some cancer types. The AI-guided click-based review required an average of 1.4 to 5.2 clicks depending on tissue type, with colorectal metastases detected most efficiently. Challenging subtypes, such as breast carcinoma with apocrine differentiation, required more extensive interaction. Micrometastases across all 3 cancer types were successfully identified by the AI.

Conclusions.—: The AI module improved pathologists' sensitivity in detecting LN metastases and significantly reduced review time, particularly for positive nodes. These findings support the integration of AI tools to enhance diagnostic efficiency and accuracy in routine pathology practice.

Context.—: In patients with melanoma, the predictive and prognostic relevance of programmed death ligand 1 (PD-L1) protein expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and of alterations in the gene encoding PD-L1, CD274, are not yet established.

Objective.—: To address these gaps in knowledge.

Design.—: We retrospectively evaluated 64 patients with melanoma treated with immune checkpoint blockade therapy (ICBT) who underwent whole genome sequencing. PD-L1 immunohistochemistry using clone 28-8 was available for 33 of 64 patients. Tumor cell PD-L1 expression was categorized as negative (<1% of cells staining), low (1%-10%), or high (>10%), and TIL PD-L1 expression as low (≤30% of TILs expressing PD-L1) or high (>30%). Event-free survival (EFS) and overall survival were assessed in relation to genetic and histopathologic factors.

Results.—: CD274 alterations were identified in 19% (12 of 64) of tumors and were associated with higher tumor mutational burden. Of 33 tumors assessed by immunohistochemistry, 21 showed PD-L1 positivity in tumor cells, which correlated with higher N category, reduced microsatellite stability, and elevated BRAF (B-Raf proto-oncogene, serine/threonine kinase) alteration rate. High PD-L1 expression on TILs was linked to more advanced disease and increased lymphovascular invasion. Among patients with similar clinical stage, patients receiving PD-L1-targeted ICBT had better EFS and overall survival than patients receiving non-ICBT or excision. Notably, patients with gene amplifications of undetermined significance identified on whole genome sequencing had reduced EFS.

Conclusions.—: Our findings suggest that CD274 alterations, PD-L1 expression on tumor cells and TILs, BRAF mutations, genomic amplifications, and tumor mutational burden may provide meaningful prognostic information in patients with melanoma. Prospective validation in larger cohorts is warranted to confirm the utility of these markers in guiding therapeutic decisions.

Context.—: Promoting diversity, equity, and inclusion (DEI) is crucial for an academic institution's environment and growth. Studies assessing the DEI climate in pathology and laboratory medicine departments are limited and need more data to promote more inclusive workplaces.

Objective.—: To assess the DEI climate and to identify specific, actionable items for improvement in academic pathology and laboratory medicine.

Design.—: A DEI climate assessment survey was prepared with questions related to background demographic information, discriminatory acts, and perceptions of the DEI climate in the workplace and was distributed to 473 people, including faculty, staff, and trainees in the Departments of Anatomic Pathology and Laboratory Medicine at our institution. Data were collected from December 2020 to January 2021.

Results.—: One hundred sixty-four participants responded (35% participation). Up to 48% (76 of 159) reported experiencing some form of discrimination at least once. Gender, age, and race were the most reported bases of discrimination. Females perceived more discrimination (77%; 48 of 62) than male participants (59%; 41 of 69). The top basis of discrimination was race for non-White (14%; 12 of 84) and gender for White (26%; 20 of 78) participants. Trainees were the most common targets and faculty members were the most common source of discrimination. Stress related to reporting was the most common cause that prevented participants from reporting discrimination. Participants reported insufficient DEI mentorship support, discomfort around discussing microaggressions with faculty members, and disbelief in DEI-related contributions being valued for promotion.

Conclusions.—: Performing an anonymous DEI climate survey is an effective way to understand department-specific issues and identify action items for pathology and laboratory medicine departments.

Context.—: Undifferentiated round cell sarcomas (URCSs) are tumors of bone and soft tissue that are heterogeneous in terms of driver events and diverse in their clinical course.

Objective.—: To compare the pediatric BCL6 corepressor (BCOR) and capicua transcriptional repressor (CIC) sarcomas clinically while assessing the utility of advanced diagnostic algorithms.

Design.—: Forty-two histologically diagnosed undifferentiated round cell sarcomas were molecularly characterized using polymerase chain reaction assay, RNA sequencing, and/or NanoString digital bar code technology.

Results.—: The diagnosis of BCOR sarcoma was confirmed in 23 cases, including 17 cases of BCOR::cyclin B3 (CCNB3), 2 cases of BCOR internal tandem duplication, and single cases of BCOR::mastermind like transcriptional coactivator 3 (MAML3) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE)::NUT family member 2B (NUTM2B); in 2 cases, the verification was based on gene expression profiles. The primary lesion was localized intraosseously (15 cases; 65%) or originated from soft tissues (8 cases; 35%). Three-year overall survival was 96.0% ± 0.04%. The diagnosis of CIC sarcoma was confirmed in 14 cases, including 5 cases of CIC::double homeobox 4 (DUX4), 4 cases of CIC exon 21 fused to an intergenic region, 2 cases of CIC::double homeobox 4 like 9 (pseudogene) (DUX4L9) and 1 case of CIC::NUTM2B; in 2 cases, verification was based on gene expression profiles. The primary lesion was localized in soft tissues (12 cases; 86%) or intraosseously (2 cases; 14%). Three-year overall survival was 34.4% ± 16.0%.

Conclusions.—: Despite the relatively favorable outcomes in BCOR sarcomas, the relapse rate is considerable, whereas pediatric patients with CIC sarcoma typically develop metastatic disease and have poor outcomes. The data provide a prospective foundation for genetically based therapeutic strategies and risk stratification.