Archives of pathology & laboratory medicine最新文献

Context.—: Precise determination of biomarker status is necessary for clinical trial enrollment and endpoint analyses, as well as for optimal treatment determination in real-world practice. However, variabilities may be introduced into this process due to the processing of clinical specimens by different laboratories and assessment by distinct pathologists. Machine learning tools have the potential to minimize inconsistencies, although their use is not presently widespread.

Objective.—: To assess the applicability of machine learning to the quality control process for biomarker scoring in oncology, we developed and validated an automated machine learning model to be applied as a quality control tool for monitoring the assessment of human epidermal growth factor-2 (HER2).

Design.—: The model was trained using whole slide images from multiple sources to quantify HER2 expression and measure immunohistochemistry stain intensity, tumor area, and the presence of artifacts or ductal carcinoma in situ across breast cancer phenotypes. The quality control tool was deployed in a real-world cohort of HER2-stained breast cancer sample images collected from routine diagnostic practice to evaluate trends in HER2 testing quality indicators and between pathology laboratories.

Results.—: Automated image analysis for HER2 scoring is consistent and reliable using this algorithm. Deployment of the HER2 quality control tool across 3 clinical laboratories revealed interlaboratory variability in HER2 scoring and inconsistencies in data reporting.

Conclusions.—: These results support the future incorporation of quality control algorithms for real-time monitoring of clinical laboratories contributing to clinical trials in oncology and in the real-world setting of HER2 immunohistochemistry testing in local clinical laboratories and hospitals.

Context.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.

Objective.—: To investigate, beyond BRCA, the association between the morphology of HGSOC and the presence of homologous recombination deficiency (HRD).

Design.—: We reviewed 522 of 806 cases of HGSOC from the PAOLA-1 clinical trial, including 163 cases with tumor BRCA mutation, 345 cases without tumor BRCA mutation, and 14 cases with inconclusive BRCA tests. Regarding HRD status (myChoice HRD Plus assay), 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD-), and 55 (10%) inconclusive. Morphologic analysis included tumor architecture (with more than 25% of solid, pseudoendometrioid, and transitional patterns defining a SET architecture), tumor-infiltrating intraepithelial lymphocytes (ieTILs), and tumor stromal lymphocytes (sTILs).

Results.—: SET architecture (51% versus 40%, P = .02), high number of ieTILs (16% versus 8%, P = .007), and more than 10% of sTILs (27% versus 18%, P = .02) were associated with tumor BRCA mutation, mostly for tumors with a BRCA1 mutation. These criteria were also associated with HRD status: 54% versus 33% (P < .001) for SET architecture, 14% versus 6% (P = .008) for high number of ieTILs, and 27% versus 15% (P = .003) for more than 10% of sTILs. SET architecture was also significantly associated with HRD+ tumors without tumor BRCA mutation (P < .001) when compared with HRD- tumors. The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97-0.99) but low sensitivity (0.07; 95% CI, 0.04-0.10).

Conclusions.—: The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.

Context.—: Atypical apocrine adenosis (AAA) is a rare breast lesion defined as presence of cytologic atypia in apocrine adenosis. World Health Organization Classification of Tumours, 5th edition, defines cytologic atypia as at least 3-fold variation in nuclear size and prominent nucleoli. Currently, owing to the rarity of the lesion, the clinical behavior of AAA is not well understood.

Objective.—: To further investigate the risk of upgrade to malignant histology on follow-up excision after a diagnosis of isolated atypical apocrine adenosis (iAAA) on core needle biopsy (CNB).

Design.—: We identified 22 female patients with diagnosis of iAAA on CNBs across 3 institutions between 2000 and 2024, with an average age of 58 years. The most common indication for CNB was presence of a mass. We reviewed pathology reports and available histology slides of CNBs and subsequent surgical excisions.

Results.—: Of 22 patients, 17 underwent surgical excision and 5 were followed up with mammogram for an average of 38 months. The diagnosis for 2 of 17 patients (12%) who underwent excision was upgraded to malignancy (ductal carcinoma in situ), 3 had atypical ductal hyperplasia (1 with AAA), and 2 additional patients had residual iAAA. iAAA was the target lesion in 7 of 21 cases (33%). Among these 7 cases, 5 patients presented with a mass; 2 of 5 (40%) were upgraded to DCIS and 1 of 5 had residual iAAA. The 5 patients who were followed up did not have any adverse outcomes.

Conclusions.—: We recommend surgical excision of iAAA when found on CNB, especially when the target lesion is a mass. However, larger studies are necessary to further understand this entity.

Context.—: Lymphangioleiomyomatosis is a rare multisystem disorder belonging to the family of neoplasms exhibiting perivascular epithelioid differentiation. It primarily affects women of childbearing age. The disease is characterized by a proliferation of smooth muscle-like cells (lymphangioleiomyomatosis cells) within all lung compartments, leading to cystic parenchymal destruction and, in some cases, respiratory failure. These cells carry mutations in one or both tuberous sclerosis (TSC) genes and coexpress smooth muscle and melanocytic markers. Female hormones, particularly estrogens, influence the course of the disease. Symptoms of lymphangioleiomyomatosis vary significantly among patients, ranging from exertional dyspnea and coughing to chest pain and recurrent pneumothorax.

Objective.—: To present the latest advancements in the understanding of disease pathogenesis and diagnosis, illustrate the pathologic and radiologic findings, provide a reference for pathologists and other health care professionals, briefly discuss recent evidence-based therapeutic approaches, and emphasize the importance of adopting a multidisciplinary approach to diagnosis and optimization of patient care.

Data sources.—: A comprehensive review of pertinent medical literature published in the last 30 years, focusing on publications written in the English language, was performed.

Conclusions.—: Despite the recent significant advancements in the understanding and management of lymphangioleiomyomatosis, there are still significant gaps in our knowledge of its pathophysiology and the role of the immune system in the genesis and progression of the disease. The current changes in diagnostic algorithms favor the adoption of minimally invasive procedures as the standard of care. As a result, the clinical laboratory will play a larger role in the diagnosis of lymphangioleiomyomatosis, and surgical pathologists will likely be less involved in the diagnosis of pulmonary lymphangioleiomyomatosis than they currently are.

Context.—: Quality communication between clinicians and pathologists is required for optimal cancer care. The College of American Pathologists provides anatomic site-specific cancer protocols that facilitate synoptic reporting for efficient communication, contributing to accuracy and completeness of cancer staging.

Objective.—: To evaluate synoptic cancer pathology reporting across the Department of Veterans Affairs (VA), the largest integrated health system in the United States, for 4 common cancers: melanoma and colon, bladder, and kidney cancer.

Design.—: For each cancer type, we investigated at least 200 biopsy and 200 resection reports from 2019 to 2021. In each report, we determined whether a synoptic format was used. The reports were selected using random sampling across all VA health care facilities. We also identified a set of core elements that were underdocumented.

Results.—: Among 1618 pathology reports, 778 (48%; 95% CI, 46%-50%) were synoptic reports. Synoptic reporting was much more common among resections (621 of 811; 77%; 95% CI, 74%-79%) than among biopsies (157 of 807; 19%; 95% CI, 17%-22%). It was most common in colorectal resections (200 of 206; 97%; 95% CI, 94%-99%) and least common in colon biopsy reports (1 of 200; 0.5%; 95% CI, 0%-3%). Core elements that were underdocumented included procedure and regional lymph nodes for resections of bladder and kidney cancer and of melanoma.

Conclusions.—: Synoptic reporting was used about three-quarters of the time for resections and about 1 in 5 times for biopsies. Future work should develop implementation strategies to improve synoptic reporting, especially for biopsy specimens and core elements that were relatively underdocumented.

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.

Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but 31 patients (4%) had unusual blasts that were either completely or partially negative for CD34. Of the latter, recurrent genetic abnormalities were identified in 13 (42%) including 10 with nucleophosmin 1 (NPM1) mutation, 1 with lysine methyltransferase 2A (KMT2A) rearrangement, and 2 with t(3;5)(q25.3;q35.1)/NPM1::myeloid leukemia factor 1 (MLF1). These cases were classified as MDS prior to the 2022 classifications, but 9 of 13 (69%) and 7 of 13 (54%) cases would be reclassified as AML according to the 5th edition of the World Health Organization classification and the International Consensus Classification, respectively. Eight cases (26%) had multihit tumor protein p53 (TP53) mutation, and 6 of them were ultimately diagnosed as or quickly evolved to pure erythroid leukemia. Of the remaining 10 cases, 4 uncharacteristically had no detectable molecular genetic abnormalities.

Conclusions.—: Our data show that if a presumptive MDS shows a nonprimitive blast phenotype, caution is needed to rule out AML with recurrent genetic abnormality with an oligoblastic presentation, high-risk myeloid neoplasms with double-hit TP53 mutation with abnormal erythroid proliferation, and MDS with molecular-genetic and clinical features more akin to AML.

Context.—: Small biopsies are used for histologic, immunophenotypic, cytogenetic, molecular genetic, and other ancillary studies. Occasionally, this diagnostic tissue is exhausted before molecular testing can be performed.

Objective.—: To investigate a simple banking protocol for currently discarded tissues trimmed off prior to the initial hematoxylin-eosin section, as an alternative source of DNA for molecular studies.

Design.—: Mock biopsies of lung adenocarcinomas, benign testes, and B-cell lymphomas were constructed from biobank blocks; these simulated biopsies were assessed via epidermal growth factor receptor (EGFR) p.L858R droplet digital polymerase chain reaction (PCR), Biomed B-cell clonality testing by PCR, or a custom next-generation sequencing panel for lymphomas. For each cancer mock biopsy, DNA amounts and molecular test results from the "trimmings" samples were compared to data from corresponding molecular samples acquired via a "standard" clinical protocol.

Results.—: The data show that although trimmings samples usually contained less DNA than standard samples, both sample classes generally had sufficient DNA for testing and produced essentially identical molecular results. A single sample showed low-level carryover contamination on droplet digital PCR testing.

Conclusions.—: Tissue trimmings banked by using the studied protocol demonstrated value as a potential alternative sample for molecular testing.

Context.—: Opportunities to improve transfusion safety occur at lower hemoglobin (Hgb) thresholds and single-unit transfusions. Efforts to improve compliance with transfusion guidelines and single-unit transfusion practices reduce transfusions and lead to improved outcomes.

Objective.—: To evaluate demographic and practice characteristics associated with lower Hgb thresholds and single red blood cell (RBC) unit transfusion practices.

Design.—: This study used the College of American Pathologists (CAP) Q-Probes format with the recent 2020 and 2017 surveys of participating institutions.

Results.—: High rates of transfusion review and compliance were observed with institutions reporting RBC transfusions meeting institutional guidelines. CAP inspection participants and those with a formal policy to encourage single-unit transfusions showed a trend toward greater compliance. Comparison of 2020 and 2017 survey results showed favorable downward trends in the Hgb threshold for transfusion compliance review and pretransfusion and posttransfusion Hgb values. Institutions reporting initiatives to decrease transfusions, teaching hospitals, and those with updated guidelines in alignment with recent literature reported lower pretransfusion Hgb levels in both studies. The 2020 study showed greater single-unit transfusion use among hospitals with patient blood management programs, larger institutions, and those training pathology residents. Single-unit transfusion rates varied by hospital service, with highest rates reported within hematology/oncology (99 of 138 [71.7%]), intensive care (147 of 215 [68.4%]), and medicine (419 of 666 [62.9%]) services.

Conclusions.—: Transfusion practice improvement programs to decrease RBC transfusions include the use of single-unit transfusions and lower institutional pretransfusion Hgb thresholds. Opportunities to lower transfusion thresholds and increase single-unit transfusions exist in surgical and obstetrics services.

Context.—: Test-ordering practices vary widely between and within health care organizations, and methods used to benchmark test utilization data are unstandardized.

Objective.—: To develop and apply standardized methodology to compare inpatient test utilization data submitted by laboratories enrolled in a College of American Pathologists Q-Probes study.

Design.—: Participating laboratories provided inpatient test volumes for 50 designated analytes and total inpatient days for 2019 or a recent 12-month period. Test utilization patterns were characterized by studying test volumes standardized per 1000 inpatient days. Test volume variability used the standardized median absolute deviation; standardized test volumes were evaluated by calculating comparative ranges for each analyte. Standardized test volumes falling outside their respective comparative ranges are referred to as outliers in this study. Volume data were tested for association with stewardship practices and institutional demographics.

Results.—: Methodology using standardized test volume data identified test groups that are commonly used in the inpatient setting and efficiently identified volume outliers. High test volume outliers included creatine kinase myocardial band, free prostate-specific antigen, myoglobin, serotonin release assay, and hepatitis B serologies; no low-volume outliers were observed. Among 33 participants, 13 (39%) had no test volume outliers, while 5 (15%) showed multiple tests (13-34) with comparatively high volumes. No statistically significant relationships were found between stewardship practices and test-ordering patterns.

Conclusions.—: Our approach can be used to measure inpatient test volume data across organizations and for identifying test volumes falling outside of the standardized comparative ranges that may require interventions to change test utilization practices.

Context.—: Histologic assessment of tumor regression grade (TRG) on esophagogastrectomy specimens after neoadjuvant therapy is an excellent predictor of local recurrence rate and long-term survival in esophageal adenocarcinomas. Although several grading systems exist globally, the modified Ryan system suggested by the College of American Pathologists (CAP) is widely used in North America. Most systems rely on quantitative percentage estimation of the residual tumor with or without additional qualitative descriptors, which is relatively subjective with poor interobserver agreement.

Objective.—: To test a morphometric-based approach using the microscopic objective lens to estimate the size of the largest focus of the residual tumor.

Design.—: A total of 69 esophageal specimens post neoadjuvant therapy were evaluated. Tumor size was morphometrically determined by the microscopic field, using an Olympus microscope with ×10/×22 eyepieces. Residual viable tumor was categorized into 4 groups, using ×2, ×4, and ×10 objectives: ≤ ×10, > ×10 and ≤ ×4, > ×4 and < ×2, and ≥ ×2.

Results.—: Morphometric measurements significantly correlated with the CAP treatment effect scores. There was no significant difference in overall survival between ≥ ×2 and ×2 to ×4 groups; however, a 3-tier system (TRG1: ≤ ×10, TRG2: > ×10 and ≤ ×4, and TRG3: > ×4) showed significant survival differences (P = .01). Significant differences in the percentage of lymphovascular and perineural invasion, advanced TNM stage, and lymph node metastasis were identified among the 3 groups.

Conclusions.—: The proposed 3-tier morphometric approach based on microscopic field size is a simple and easy-to-use method, which helps stratify patients into 3 groups with distinct histopathologic features and overall survival.