Archives of pathology & laboratory medicine最新文献

Context.—: Social media has become widely adopted by pathologists and other physicians for professional purposes. While engagement has likely increased over time, there remain few concrete data regarding attitudes toward its use.

Objective.—: To assess pathologists' use of and attitudes toward social media over time.

Design.—: We created a survey regarding personal and professional use of social media and circulated it via multiple channels in December 2017 and again in February 2022. Results of the 2 surveys were compared for statistically significant differences.

Results.—: The 2017 survey was completed by 97 participants, and the 2022 survey by 305 participants. Respondents were predominantly female and academics, included pathologists in all age categories and all time-in-practice length. In both surveys, Twitter (now X) was the most popular platform for professional use and Facebook was the most popular for personal use. Professional barriers to social media use remained consistent between the 2 surveys, including the amount of time required. Education was seen as the main benefit of social media use in both surveys, while other benefits such as networking and increasing professional visibility were endorsed significantly less often in the second survey. While the second survey received more than 3 times as many responses as the first, several aspects of social media use (mainly demographics) remained similar during the timeframe, while other aspects (such as usage and perceived values) decreased.

Conclusions.—: Pathologists continue to find social media valuable. Barriers remain, though overall pathologists of all ages and practice settings appear receptive to using social media to further educational and other opportunities.

Context.—: Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data.

Objective.—: To define the clinicopathologic spectrum of neoplastic and nonneoplastic diseases observed in resected mass lesions in the chest of pediatric patients, and to identify somatic alterations observed in primary neoplasms.

Design.—: Clinicopathologic features of thoracic mass lesions (n = 385) resected from 373 patients aged ≤21 years in a 25-year period (1993-2018) were included. Primary neoplasms having sufficient material were tested by a laboratory-developed comprehensive genomic profiling assay that assesses tumor mutational burden, microsatellite instability, somatic sequence variants, gene amplifications, fusions, and specific transcript variants.

Results.—: The most commonly resected space-occupying lesions were nonneoplastic mass lesions and cysts or malformations, resected in 117 (31.4%) and 58 of 373 patients (15.5%) respectively. Metastatic neoplasms were observed in 169 of 373 patients (45.3%; mean age 14.4 years, range 1-21 years); the most common was osteosarcoma (68 of 169; 40.2% of metastases). Primary lung neoplasms occurred in 24 of 373 patients (6.4%; mean age 14.5 years, range 6 months-21 years), and 16 patients had primary extrapulmonary thoracic tumors. Carcinoid tumor was the most common primary lung neoplasm (7 typical, 3 atypical). Molecular testing showed a prevalence of somatic pathogenic or likely pathogenic mutations and copy-number alterations. No fusions or splice variants were identified. Tumors were microsatellite-stable with low tumor mutational burden.

Conclusions.—: Resected pediatric thoracic mass lesions are more likely to be metastatic lesions, congenital cysts or malformations, or nonneoplastic lesions compared to primary thoracic neoplasms, which are encountered at a low frequency and tend to have relatively simple genetic profiles.

Context.—: Accurate interpretation of drug test results is key to appropriate patient care in numerous settings including pain management. Despite recommendations that providers should consult laboratory professionals for guidance when necessary, literature demonstrating laboratorian expertise in drug test interpretation is lacking.

Objective.—: To evaluate participating laboratories' performance on the case-based, interpretive ("dry") challenge included with each Drug Monitoring for Pain Management proficiency testing program from 2012-2023.

Design.—: All challenges (n = 23) required participants to identify if drug test results were consistent or inconsistent with prescribed medications in the case history. Relevant medications, presumptive and confirmatory drug test results, and participant responses were extracted from program summary reports and examined for performance and common themes.

Results.—: Overall, 91.8% (6821 of 7431) of participant responses correctly identified whether drug testing was consistent with medications. There were 8 challenges with participant scores below 91.8% (range, 59.8% [49 of 82 responses] to 88.9% [193 of 217 responses]). Common knowledge gaps identified in these challenges included false-positive presumptive (screening) results, minor metabolism of opiates, and recognizing that presence of a nonprescribed drug is inconsistent with prescribed medications. Although some participants repeatedly responded incorrectly, there were no associations between laboratory type, personnel responding, or analytical performance with incorrect responses to interpretative challenges.

Conclusions.—: Program participants performed well overall, but several concerning educational gaps were identified. Laboratorians have a role in providing interpretative guidance for drug testing and should emphasize ongoing education to ensure competence in the setting of constantly changing prescribed and nonprescribed drug use.

Context.—: The Sustainable Predictive Oncology Therapeutics and Diagnostics quality assurance pilot study (SPOT/Dx pilot) on molecular oncology next-generation sequencing (NGS) reportedly demonstrated performance limitations of NGS laboratory-developed tests, including discrepancies with a US Food and Drug Administration-approved companion diagnostic. The SPOT/Dx pilot methods differ from those used in proficiency testing (PT) programs.

Objective.—: To reanalyze SPOT/Dx pilot data using PT program methods and compare to PT program data.Also see p. 136.

Design.—: The College of American Pathologists (CAP) Molecular Oncology Committee reanalyzed SPOT/Dx pilot data applying PT program methods, adjusting for confounding conditions, and compared them to CAP NGS PT program performance (2019-2022).

Results.—: Overall detection rates of KRAS and NRAS single-nucleotide variants (SNVs) and multinucleotide variants (MNVs) by SPOT/Dx pilot laboratories were 96.8% (716 of 740) and 81.1% (129 of 159), respectively. In CAP PT programs, the overall detection rates for the same SNVs and MNVs were 97.2% (2671 of 2748) and 91.8% (1853 of 2019), respectively. In 2022, the overall detection rate for 5 KRAS and NRAS MNVs in CAP PT programs was 97.3% (1161 of 1193).

Conclusions.—: CAP PT program data demonstrate that laboratories consistently have high detection rates for KRAS and NRAS variants. The SPOT/Dx pilot has multiple design and analytic differences with established PT programs. Reanalyzed pilot data that adjust for confounding conditions demonstrate that laboratories proficiently detect SNVs and less successfully detect rare to never-observed MNVs. The SPOT/Dx pilot results are not generalizable to all molecular oncology testing and should not be used to market products or change policy affecting all molecular oncology testing.

Context.—: Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy.

Objective.—: To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases on diagnosis and 3 months post treatment and its relation with histologic Oxford classification.

Design.—: In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using Oxford Classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used.

Results.—: Significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008).

Conclusions.—: Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies.

Context.—: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors.

Objective.—: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better.

Design.—: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases.

Results.—: The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression.

Conclusions.—: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

Context.—: Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological criteria used for biopsy specimens in real-world practice remains undetermined.

Objective.—: To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies.

Design.—: We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis.

Results.—: The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization.

Conclusions.—: The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied.

Context.—: Folate receptor-α (FRα, encoded by the FOLR1 gene) is overexpressed in several solid tumor types, including epithelial ovarian cancer (EOC), making it an attractive biomarker and target for FRα-based therapy in ovarian cancer.

Objective.—: To describe the development, analytic verification, and clinical performance of the VENTANA FOLR1 Assay (Ventana Medical Systems Inc) in EOC.

Design.—: We used industry standard studies to establish the analytic verification of the VENTANA FOLR1 Assay. Furthermore, the VENTANA FOLR1 Assay was used in the ImmunoGen Inc-sponsored SORAYA study to select patients for treatment with mirvetuximab soravtansine (MIRV) in platinum-resistant EOC.

Results.—: The VENTANA FOLR1 Assay is highly reproducible, demonstrated by a greater than 98% overall percent agreement (OPA) for repeatability and intermediate precision studies, greater than 93% OPA for interreader and greater than 96% for intrareader studies, and greater than 90% OPA across all observations in the interlaboratory reproducibility study. The performance of the VENTANA FOLR1 Assay in the SORAYA study was evaluated by the overall staining acceptability rate, which was calculated using the number of patient specimens that were tested with the VENTANA FOLR1 Assay that had an evaluable result. In the SORAYA trial, data in patients who received MIRV demonstrated clinically meaningful efficacy, and the overall staining acceptability rate of the assay was 98.4%, demonstrating that the VENTANA FOLR1 Assay is safe and effective for selecting patients who may benefit from MIRV. Together, these data showed that the assay is highly reliable, consistently producing evaluable results in the clinical setting.

Conclusions.—: The VENTANA FOLR1 Assay is a robust and reproducible assay for detecting FRα expression and identifying a patient population that derived clinically meaningful benefit from MIRV in the SORAYA study.

Context.—: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine.

Objectives.—: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4.

Design.—: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT.

Results.—: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5.

Conclusions.—: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.