Archives of pathology & laboratory medicine最新文献

Context.—: Recent neoadjuvant clinical trials in lung cancer have demonstrated the survival benefits in carefully selected patients. Standardization of the assessment of pathologic response to neoadjuvant therapy in surgically resected specimens is required.

Objective.—: To review the current pathology practices in the gross processing and microscopic assessment of surgically resected non-small cell lung carcinoma specimens after neoadjuvant therapy.

Data sources.—: PubMed publications and experience of the author.

Conclusions.—: Gross processing of the surgically resected lung carcinoma after neoadjuvant therapy needs further refinement and standardization in clinical trials and in a real-world clinical practice. Microscopic assessment of the response includes quantification of viable tumor, necrosis, and stroma. The best approach would be to use a single standardized and most reproducible scoring system. Published studies on gross processing of lung carcinoma specimens in the neoadjuvant setting and microscopic assessment of pathologic response provide a good foundation for the future standardization of pathology practice.

Context.—: Biomedical research relies on available biomaterials and associated data, and the quality of this starting material can have a significant impact on the quality of the experimental results. In the 2000s, best-practice documents and guidelines for biorepositories were published, followed in the 2010s by standards documents used to support accreditation. The College of American Pathologists Biorepository Accreditation Program and the International Standards Organization's standard 20387 were launched in 2012 and 2018, respectively.

Objective.—: To identify quantitative and qualitative differences between the two aforementioned biorepository accreditation standards for use by the larger biomedical research community; the results will empower biorepositories to select an accreditation program that best fits their goals.

Design.—: Individual requirements of both accreditation standards were identified and a bidirectional crosswalk was performed to identify gaps. Requirements were assigned to one of several standardized categories to enable comparison of the relative emphasis of different categories between the standards.

Results.—: Quantitatively, the College of American Pathologists program is comprehensive and stands alone, with 523 requirements, whereas the International Standards Organization program contains 167 requirements and is comprehensive through its incorporation and reference to numerous related standards documents. Qualitatively, both programs rely heavily on the implementation of an overarching quality management system and both programs can accommodate different types of biobanks (eg, human and animal).

Conclusions.—: The standards differ in number of requirements, distribution of requirements across categories, and amount of reliance on separate standard documents. This information may aid in selection of an appropriate accreditation standard.

Context.—: Diagnostic strategies for endometrial cancer have been evolving, with cytologic analysis being considered a key method in integrated oncologic diagnostics because of its less invasive nature and adaptability to various assessments. Liquid-based cytology (LBC) has emerged as a promising method for intact DNA preservation; it exhibits improved efficiency in advanced sequencing applications such as next-generation sequencing. However, despite the use of LBC in panel assays, its application in whole-exome sequencing (WES) for comprehensive genomic profiling remains underexplored.

Objective.—: To investigate whether molecular classification is possible based on WES using DNA derived from LBC specimens.

Design.—: We combined WES with targeted gene panel analysis to compare genomic findings of LBC and traditional tissue samples obtained from 7 cases of endometrial cancer. We investigated pathogenic mutations, tumor mutational burden, and microsatellite instability, and achieved molecular classification with high accuracy.

Results.—: We found a substantial concordance between LBC and traditional tissue samples in terms of pathogenic mutation detection, with a 95% match in the LBC samples and 94% in the tissue samples. Notably, our results highlight the importance of combining WES with panel-based analysis in identifying the ultramutated status of a case that had been missed during panel analysis.

Conclusions.—: Our findings emphasize the potential of LBC samples in the precise and noninvasive genomic analysis of cases of endometrial cancer and offer a new avenue for developing diagnostic and therapeutic strategies in precision oncology.

Context.—: Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited.

Objective.—: To evaluate tissue morphologic and viral features in transbronchial biopsies of long COVID patients (immunocompetent and immunocompromised).

Design.—: This retrospective observational study included 18 patients (9 immunocompetent and 9 immunocompromised) who were consecutively referred to outpatient clinic for post-COVID pneumonia, undergoing transbronchial biopsy. Several histologic changes were analyzed by computer-assisted morphometric analysis. As organizing pneumonia (OP) was consistently detected, fibrosis and inflammation were also evaluated in transbronchial biopsies from 28 control patients with histologic confirmation of OP. Tissue SARS-CoV-2 and the subgenomic transcripts were investigated. Morphologic findings were correlated with clinical and radiologic data.

Results.—: Long COVID patients showed lower inflammation than controls (P < .001) despite a similar fibrotic extension. When considering separately the 2 long COVID groups, the same inflammatory infiltrate extension was found, whereas a higher fibrotic remodeling characterized the immunocompetent subgroup (P = .05). Molecular investigation showed that SARS-CoV-2 was present in tissue samples obtained from 3 long COVID patients.

Conclusions.—: Long COVID patients showed a peculiar OP pattern, with more vascular and fibrotic changes. SARS-CoV-2 RNA, even in replicative status, can be detected in lung biopsies of both immunocompetent and immunocompromised patients. This pilot study is a forerunner of more in-depth lung tissue investigations to gain a better understanding of long COVID pathobiology.

Context.—: Sarcomas are rare and highly heterogeneous mesenchymal tumors with deceptive morphologic features that pose a challenge for precise diagnostics. Chromosomal rearrangements generating pathognomonic gene fusions are useful diagnostic markers, traditionally tested using single-plex standard of care assays with limited diagnostic yield. NanoString nCounter technology has emerged as a robust solution with multiplexing capabilities.

Objective.—: To optimize NanoString effective coverage of specific entities and conduct a validation study to support its clinical implementation.

Design.—: We reconfigured a NanoString's codeset by including a set of probes for detecting gene fusion variants of solitary fibrous tumors, low-grade fibromyxoid sarcomas/sclerosing epithelioid fibrosarcomas, and undifferentiated small round cell sarcomas, totaling 188 probes. A technical validation study was conducted with 96 retrospective samples. Additionally, 76 prospective samples were evaluated to assess the assay's clinical performance.

Results.—: Both technical and clinical validation studies showed that NanoString's codeset reached >88% sensitivity and 100% specificity, compared with standard of care methods, and superior diagnostic yield as a first-line test. Our design enabled the detection of almost all fusion variants of NGFI-A binding protein 2 (NAB2) with signal transducer and activator of transcription 6 (STAT6) in solitary fibrous tumors, as well as cAMP responsive element binding protein 3 like 1/2 (CREB3L1/2) rearrangements in all low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma cases. Identification of specific gene fusions of undifferentiated small round cell sarcoma was also improved, but additional strategies are necessary to attain full coverage.

Conclusions.—: The NanoString platform demonstrated good sensitivity, specificity, and superior diagnostic yield. It is a cost-effective assay with rapid turnaround time, low sample consumption, streamlined analysis, and easy customization. Therefore, it is a promising alternative first-line diagnostic tool for routine sarcoma testing.

Context.—: Myelodysplastic syndromes (MDSs) are rare in children and have unique clinical manifestations and implications.

Objective.—: To review the clinical features, pathogenesis, and classification of pediatric MDS.

Data sources.—: Published literature and personal experience.

Conclusions.—: Pediatric MDS vastly differs from adult MDS. Evaluation for the presence of an underlying germline predisposition syndrome is critical for optimal classification and management. Because of the rarity of cases, resources to aid with the recognition, diagnosis, and management of pediatric MDS are limited, and multi-institutional collaborative studies are needed for the future.

Context.—: Assessment of placental villous maturation is among the most common tasks in perinatal pathology. However, the significance of abnormalities in morphology is unclear and interobserver variability is significant.

Objective.—: To develop a machine learning model of placental maturation across the second and third trimesters and quantify the impact of different pathologist-diagnosed abnormalities of villous morphology.

Design.—: Digitize placental villous slides from more than 2500 placentas at 12.0 to 42.6 weeks. Build whole slide learning models to estimate obstetrician-determined gestational age for cases with appropriate maturation and normal morphology. Define the model output as "placental age" and compare it to the chronologic gestational age.

Results.—: Our model showed an r2 of 0.864 and mean absolute error of 1.62 weeks for placentas with appropriate maturation in the test set. Pathologist diagnosis of accelerated maturation was associated with a 2.56-week increase in placental age (±2.91 weeks, P < .001), while delayed maturation was associated with a 0.92-week decrease in placental age (±1.82 weeks, P < .001). Intrauterine fetal demise causes diverse changes to placental age, driven by the nature of the demise. We tested the impact of training a model, using all live births. The resulting r2 was 0.874 and mean absolute error was 1.73 weeks. Furthermore, by including cases with abnormal maturation in the training data, the effect size of accelerated maturation was blunted to only 0.56 ± 2.35 weeks (P < .001).

Conclusions.—: We show that various abnormalities of villous maturation and morphology correlate with abnormalities in placental age. This "no pathologist" model could be useful in situations where pathologists are unavailable or the need for consistency outweighs the utility of expertise.

Context.—: The COVID-19 pandemic irreversibly altered the pathology education landscape. It exacerbated workforce shortages, restricted in-person activities, and highlighted critical means in curricula evaluation to limit the expansion of medical knowledge gaps in postpandemic society. Training enacted swift changes toward online learning (e-learning) practices to minimize potential deficiencies in pathology education. Today, a breadth of widely available online pathology curricular tools, including e-learning and digital pathology, are increasingly being used by medical students, trainees, and pathologists worldwide.

Objective.—: To critically address the continued role of e-learning and digital pathology in postpandemic pathology education and scholarship, as a current paucity of literature exists and lingering workflow effects of this pandemic affecting many anatomic and clinical pathology departments globally persist.

Data sources.—: A qualitative review of relevant literature is synthesized to create a timely, narrative discussion to bridge this literature gap. Peer-reviewed sources and other original or primary documents will be assessed.

Conclusions.—: Because of the subjective nature of curricular development and defining what constitutes scholarship, no widely established consensus is present, though it has been touched on in previous literature. It may be years until we better understand how e-learning and digital pathology shape curricular practices, scholarship production, and patient-care delivery, though recent studies support sustained blended curricula beyond the COVID-19 pandemic. The education landscape continues to become increasingly digitalized, and infrastructures may soon be able to support complete digital pathology practice as the education norm. Future and theoretical insight for pathology and laboratory departments globally are provided.

Context.—: The diagnosis of pulmonary alveolar proteinosis (PAP) relies on a limited set of stains, namely hematoxylin-eosin and periodic acid-Schiff-diastase (PAS-D), demonstrating abundant alveolar material representing mostly surfactant. As cells harboring surfactant also express Napsin-A (pneumocytes and macrophages), we hypothesized that it would also be expressed within alveoli in PAP.

Objective.—: To evaluate the sensitivity and specificity of Napsin-A in the diagnosis of PAP.

Design.—: A 12-year retrospective case control study was designed to identify cases of PAP and potential histologic mimics (intra-alveolar fibrin, pulmonary edema, diffuse alveolar damage, and alveolar mucinosis). PAS-D staining and Napsin-A immunohistochemistry were performed. Distribution and intensity were evaluated by using a semiquantitative 3-point scale. Positivity was defined as 2+ intensity score, regardless of distribution.

Results.—: Eleven cases of PAP and 46 control cases were identified. Napsin-A showed positivity in all PAP cases and 3 of 12 cases of edema. Among positive cases, all those with a 2+ distribution were PAP cases, with heterogeneous (1+) staining in all cases of edema. PAS-D showed positivity in all cases of PAP and most controls, except cases of edema. Sensitivity and specificity of Napsin-A for PAP were 100% and 94%, respectively, and of PAS-D for PAP, 100% and 21%, respectively. Double positivity for Napsin-A and PAS-D was 100% specific and sensitive for PAP.

Conclusions.—: This study is the first to demonstrate that Napsin-A is highly specific for the diagnosis of PAP, more so than PAS-D. It also shows that the combined positivity of Napsin-A and PAS-D is 100% specific and sensitive for PAP.

Context.—: Tumor contaminants were incidentally noted in frozen section margins of oropharyngeal squamous cell carcinoma.

Objective.—: To estimate the frequency of tumor contaminants in frozen section slides of patients who underwent surgery for pharyngeal cancer, and to characterize the surgical and pathologic context of these incidents.

Design.—: A retrospective search was conducted to identify pharyngeal resections from 2016 to 2022. Surgical pathology, operative reports, and frozen section slides were reviewed. Preanalytical phase tumor contaminants were defined as tumor contaminants that occurred in frozen section slides with or without occurrence in permanent slides.

Results.—: Eighty-one pharyngeal resections with intraoperative tumor bed margins for squamous cell carcinoma were identified. These included 308 tumor bed margins represented in 641 slides. Preanalytical contaminants occurred among 9 patients (11.1% of all and 21.4% of robotic surgeries) and in 3.8% of the 308 intraoperative tumor bed margins. A statistically significant association was found between contaminants and larger tumor size (Student t test, P = .04) and surgical approach (robotic versus open oropharyngectomy: Fisher exact test, P < .001). All patients with contaminants had intraoperative tumor disruption. Two frozen section deferrals (0.6%) and 2 discrepancies with final diagnosis (0.6%) attributed to contaminants were identified; however, clinical or surgical management was not affected in any patient.

Conclusions.—: Preanalytical contaminants may cause confusion in intraoperative margin assessment. They are more likely to occur in margins of nonkeratinizing squamous cell carcinoma resected by transoral robotic surgery if there is intraoperative tumor disruption. Rarely, preanalytical contaminants lead to frozen section deferral or discrepancy with final diagnosis.