Archives of pathology & laboratory medicine最新文献

Context.—: Digital pathology requires pathologists to assess tissue digitally rather than on an analog microscope, which has been the mainstay tool for tissue assessment for more than a century. The impact of different digital interaction configurations on pathologists' performance is not well understood. This work focuses on the impact of the display window size for diagnostic assessment.

Objective.—: To determine the effect of digital image viewer window size on pathologists' diagnostic performance when searching for tumors in lymph nodes while under a time limit.

Design.—: Six pathologists assessed 8 breast lymph node whole slide images using 4 digital image viewer window sizes (8, 14, 24, and 32 inches) for tumors in lymph nodes while under a time limit. Eye-gaze data were collected. Pathologists were subsequently asked to rate their preference of window sizes.

Results.—: The fraction of window not covered with foveated vision was significantly associated with window size ranging from 43% for 32 inches to 5% for 8 inches (P < .001). There was no statistically significant relationship between the number of false negatives or assessment time and window size (P = .21 and P = .28, respectively). The distance traversed per panning instance ranged from 301 pixels for 32-inch to 193 pixels for 8-inch windows (P = .002). All pathologists preferred the largest window size as it provided more context for diagnostic assessment.

Conclusions.—: Window size does not significantly affect pathologists' diagnostic performance when searching for tumors in lymph nodes. However, pathologists adapted their slide navigation approach to accommodate the amount of context the window size permitted.

Context.—: Aided by tissue microarray (TMA) technology, several RNA-correlated immunohistochemistry-based algorithms have been developed for cell-of-origin (COO) prediction in diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS). However, there is currently no empirical evidence to guide the optimal application of these algorithms to whole tissue sections (WTSs).

Objective.—: To assess the impact of various scoring methods on the accuracy and reproducibility of the popular Hans algorithm.

Design.—: We compared 3 different WTS-based scoring methods, designated as global, selective, and hotspot scoring, to a matched TMA evaluation and gold standard RNA analysis (Lymph2Cx; germinal center B cell n = 64; activated B cell/unclassified n = 68) using a representative series of 132 excisional biopsies of de novo DLBCL-NOS. Positivity scores (10% increments) were submitted by 3 expert lymphoma pathologists, with 30% or more defining positivity.

Results.—: Sixty-eight of the 132 cases of DLBCL-NOS (52%) exhibited variation in Hans immunohistochemistry marker phenotype as a consequence of scoring method and/or interscorer discordance. Although this led to changes in Hans COO assignment in 27 of 132 cases (20%), none of the WTS-based scoring methods were statistically inferior to one another in terms of raw accuracy. Hotspot scoring yielded the lowest proportion of borderline scores (20%-40% range) for BCL6 transcription repressor (BCL6) and IRF4 transcription factor (MUM1) but negatively impacted the balance between sensitivity and specificity for these markers. Selective scoring was associated with significantly worse interscorer concordance compared to TMA evaluation, which it was designed to replicate.

Conclusions.—: Overall, our data favor the use of global scoring for its noninferior accuracy, solid interscorer concordance, nonnegative influence on individual Hans markers, and current widespread use.

Context.—: The adoption of digital pathology may enable pathologists to perform primary diagnosis in both local and remote whole slide image viewing settings, improving logistics and convenience.

Objective.—: To test the performance of a new whole slide imaging system (Aperio GT 450 DX), both local intranet-based and remote internet-based viewing were compared with manual glass slide light microscopy.

Design.—: A total of 1161 curated cases, enriched with difficult clinical diagnoses, were enrolled in this accuracy study and digitally scanned on 3 Aperio GT 450 DX instruments at 3 clinical sites. Ten reading pathologists across the 3 study sites viewed images either locally (directly connected to the image server) or remotely (viewed over an internet connection). Each diagnosis was scored (concordant, minor discrepancy, or major discrepancy) by a separate team of 3 adjudication pathologists. The diagnostic accuracy of the Aperio GT 450 DX was tested by comparing the whole slide image review diagnosis with the conventional light microscope manual slide review diagnosis.

Results.—: The difference in the major discrepancy rate between whole slide image review diagnosis and manual slide review diagnosis was 2.40% (95% CI, 1.40%-3.39%), meeting the predefined acceptance criterion of the 95% CI upper bound of 4% or less. Secondary end points were also met, including an upper bound of 7% or less and both local-only and remote-only upper-bound discrepancy rates of 4% or less. Major discrepancies were slightly lower for the remotely viewed cases (2.17%) compared with local direct server connection (2.61%), and time per read was not different.

Conclusions.—: The diagnoses made using the Aperio GT 450 DX, using both local and remote access image data, were noninferior to the diagnoses made using conventional light microscopy.

Context.—: The co-occurrence of plasma cell neoplasm (PCN) and lymphoplasmacytic lymphoma (LPL) is rare, and their clonal relationship remains unclear.

Objective.—: To evaluate the clinicopathologic characteristics of concomitant LPL/PCN.

Design.—: Retrospectively analyzed clinical and laboratory data of 14 cases.

Results.—: Three patients initially presented with immunoglobulin (Ig) M paraprotein, 1 with IgG paraprotein, and 10 had simultaneous diagnoses of PCN and LPL. In 13 cases, flow cytometry detected both LPL and PCN in marrow biopsies. Furthermore, immunohistochemistry highlighted the 2 neoplastic populations, demonstrating an increased proportion of plasma cells and their expression of cyclin D1, CD56, and/or a non-IgM isotype restriction. All cases exhibited discordant heavy-chain isotypes between LPL and PCN. Thirteen of the 14 cases (92.9%) had concordant light-chain restrictions between the 2 neoplasms, and the remaining case (7.1%) showed discordant light-chain restrictions. Of the 12 patients with follow-up, 5 were treated with myeloma regimens, 2 with LPL regimens, 3 with combined therapy, and 2 with observation alone. Follow-up ranged from 2 to 146 months (median, 12.5 months). One patient died of PCN progression, one died of comorbidity, and 10 patients were alive with or without disease. Survival analysis showed no significant difference from the control.

Conclusions.—: The discordant heavy-chain isotype restrictions between PCN and LPL suggest biclonal B-cell neoplasms, which is supported by PCN's phenotypic distinction, such as the expression of cyclin D1 and/or CD56. However, our series exhibited a tendency toward concordant light-chain restrictions between the 2 neoplasms, raising the possibility that PCN may evolve from LPL through class switching.

Context.—: The College of American Pathologists Hematology and Clinical Microscopy Committee implemented a hemoglobinopathy proficiency testing and education program to monitor and assess the performance of participating laboratories.

Objective.—: To evaluate the performance of clinical laboratories for hemoglobinopathy proficiency testing from 2005 to 2023.

Design.—: The hemoglobinopathy challenges are composed of clinical case summaries and electrophoretic and chromatographic gel and tracing images. The participants are asked to determine (1) what hemoglobin chain is affected and (2) the hemoglobinopathy diagnosis.

Results.—: A total of 365 to 676 laboratories were enrolled in the proficiency testing program each year. Overall, the error rates for determination of the affected globin chain and a hemoglobinopathy diagnosis ranged from 0.6% to 56.5% and 0.5% to 86.5%, respectively. Twenty-three of 66 surveyed hemoglobinopathies (34.8%) had an error rate exceeding the consensus threshold of 20%. The globin gene detection error rate of the compound hemoglobinopathies was significantly higher when compared with just the α (P = .01) and β (P = .003) gene disorders. However, the error rate for the overall compound α/β-globin interpretation, although high at 23%, was not statistically significant when compared with just the α- or β-globin chain disorders. In repeat testing of the variants, there was no consistent improvement in performance.

Conclusions.—: The program participants demonstrated variable performance with one-third of the surveys exceeding the 20% error rate. The error rate for compound hemoglobinopathies was even higher. Our data illustrate a critical need for continuing educational efforts with an algorithmic approach to hemoglobin disorders.

Context.—: Complex surgical specimens are associated with complex Current Procedural Terminology (CPT) coding.

Objective.—: To assess and optimize the accuracy of CPT coding of complex genitourinary specimens at our institution.

Design.—: Baseline CPT codes for nephrectomy and cystectomy surgical pathology specimens were examined during a 3-month period. Pathology reports were reviewed for accurate CPT coding, and commensurate tests of change were implemented. Post-test-of-change data were re-collected, analyzed, and compared to the baseline data.

Results.—: Baseline data consisted of 71 genitourinary specimens (April to June 2021) and demonstrated undercoding in 46% (n = 33 of 71) of specimens, mostly in specimens with 2 or more billable organs. From findings in baseline data, we implemented test-of-change efforts consisting of awareness, education, and increased documentation and communication between all involved parties. Marked improvement was noted in the coding accuracy of specimens with 2 billable organs (pretest: n = 4 of 21, 19%; posttest: n = 14 of 21, 67%) and 3 or more billable organs (pretest: n = 0 of 16, 0%; posttest: n = 7 of 12, 58%) (P value = .002). Problematic areas included nephrectomy specimens resected with adrenal glands (pretest: n = 2 of 12, 17%; posttest: n = 12 of 14, 86%) and ureters for urothelial carcinoma (pretest: n = 0 of 10, 0%; posttest: n = 3 of 6, 50%), as well as regional lymph nodes commingled with resection specimens (pretest: n = 0 of 11, 0%; posttest: n = 7 of 9, 78%).

Conclusions.—: A comprehensive approach involving all stakeholders is necessary for CPT coding of complex surgical specimens. Documentation and familiarity with coding rules, specifically bundling and unbundling, as well as clinical indications for resection, are important factors in optimizing CPT coding.

Context.—: Frozen section (FS) evaluation of pediatric bone and soft tissue (BST) lesions is infrequently encountered and may pose considerable diagnostic challenges. Limited data exist about the accuracy and related diagnostic difficulties.

Objective.—: To identify and analyze discrepancies between the FS diagnosis and final diagnosis in order to increase the awareness of common diagnostic pitfalls in FS evaluation of pediatric BST lesions.

Design.—: We retrospectively reviewed 595 consecutive FSs of pediatric BST lesions from 373 patients and analyzed the accuracy and causes for interpretation errors.

Results.—: Discrepant diagnoses were found in 23 of 595 FSs (3.9%). Discrepancy rates were slightly higher in benign soft tissue lesions and FSs requested for diagnosis/adequacy, although no statistically significant difference was observed. Pathologist misinterpretation contributed to discrepancy in 17 of 23 FSs (73.9%), which were classified into 6 patterns of error. For margin, 3 patterns were found: normal hematopoietic elements versus malignant cells in Ewing sarcoma bone marrow margin (n = 3), prominent sinonasal vasculature and stroma versus sinonasal tract angiofibroma (n = 3), and atrophic skeletal muscles versus malignant cells in rhabdomyosarcoma and Ewing sarcoma (n = 2). For diagnosis, another 3 patterns were identified: misclassification of benign bone tumors (n = 5), misclassification of benign spindle neoplasms (n = 2), and vascular malformation versus normal tissue (n = 2).

Conclusions.—: FS is a valuable tool for guiding surgical management of pediatric BST lesions, which can be challenging entities and represent significant diagnostic pitfalls. Awareness of these FS pitfalls may help in further increasing diagnostic accuracy.

Context.—: All member boards of the American Board of Medical Specialties have continuing certification (ie, maintenance of certification) programs. The efficacy of these programs has been questioned and, therefore, warrants study.

Objective.—: To determine if the American Board of Pathology CertLink program, as structured, is associated with an improvement in the performance of participants on the assessment of content that was previously missed (ie, inaccurately answered).

Design.—: We reviewed the performance of American Board of Pathology CertLink participants from January 2022 through December 2023 on the readministration of the content from 110 036 multiple-choice items that were previously missed by the participants in a program with enhanced learning strategies and incentives.

Results.—: The correct response rate upon the assessment of readministered content that was previously missed increased from 0% to 62.2% (68 394 of 110 036), which exceeds that which would be achieved by guessing (P < .001).

Conclusions.—: The American Board of Pathology CertLink program, which incentivizes learning and was constructed from adult learning principles and modern educational precepts to improve knowledge retention, interrupt forgetting, and introduce practice-relevant content, is associated with an improvement in the performance of diplomates on continuing certification knowledge assessments.

Context.—: Morphologic evaluation of peripheral blood smears provides valuable information to diagnose and manage a variety of hematologic disorders.

Objective.—: To measure the competency of the technical staff in the morphologic evaluation of peripheral blood smears and provide performance trends.

Design.—: Participating technologists accessed 10 whole slide-imaged peripheral blood smears through a web-based imaging tool in 2 separate studies. Participants performed a 100-cell differential and morphologic evaluation for each slide image. Grading criteria, determined by 3 hematopathologists, were weighted according to their clinical significance (score range, 0-100 for each case). Each institution and participant answered a questionnaire to assess the impact of current practices and educational programs on competency scores.

Results.—: A total of 776 technologists from 92 institutions participated in study 1 and 1495 technologists from 179 institutions participated in study 2. Median performance scores for institutions were 78.9 and 87.6 for studies 1 and 2, respectively, encompassing a range of hematologic disorders. Based on results of the questionnaire for study 1, higher performance scores were seen when institutions required a specific number of continuing education credits per year through an agency (P = .005). In study 2, institutions with remediation procedures following a failed competency demonstrated higher performance scores (P = .03).

Conclusions.—: Medical technologist competency of peripheral blood smears improves with level of experience and is positively impacted through attending educational programs. Whole slide images offer a convenient means of assessing technical competence and provide data to allow institutions to appropriately focus their procedures and educational efforts.

Context.—: Fine-needle aspiration is an effective tool for sampling thyroid nodules; its results are classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), whose categories define malignancy risks.

Objective.—: To compare the histologic outcomes and disease-free survival (DFS) with the preceding BSRTC categories, we hypothesized that the initial cytologic categories may reflect long-term outcomes in follicular thyroid carcinoma (FTC), similar to those observed in papillary thyroid carcinoma.

Design.—: This retrospective study enrolled 134 patients with FTC who underwent preoperative cytology between April 2011 and December 2020. Results were classified into 6 categories according to the BSRTC: nondiagnostic, benign, atypia of uncertain significance (AUS), follicular neoplasm (FN), suspicious for malignancy, or malignant.

Results.—: Overall, 8 of 134 patients (6.0%) were categorized as having a nondiagnostic FTC, 35 of 134 (26.1%) as benign, 51 of 134 (38.1%) as AUS, and 40 of 134 (29.9%) as FN. No lesions were classified as suspicious for malignancy or malignant. The nondiagnostic, AUS, and FN categories were associated with a progressively higher risk of vascular invasion, disease recurrence, and high-risk FTC, based on the 2022 World Health Organization classification (P for trend = .01, .01, and .01, respectively). Disease-free survival was lower in the FN group (log-rank P = .01).

Conclusions.—: The initial BSRTC results may reflect not only the risk of malignancy but also the presence of vascular invasion and poor prognosis when the thyroid nodule is diagnosed as FTC. These results may provide prognostic information for therapeutic decision-making and clinical management of FTC.