Journal of Clinical Pathology最新文献

Aim: The digital transformation of the pathology laboratory is being continuously sustained by the introduction of innovative technologies promoting whole slide image (WSI)-based primary diagnosis. Here, we proposed a real-life benchmark of a pathology-dedicated medical monitor for the primary diagnosis of renal biopsies, evaluating the concordance between the 'traditional' microscope and commercial monitors using WSI from different scanners.

Methods: The College of American Pathologists WSI validation guidelines were used on 60 consecutive renal biopsies from three scanners (Aperio, 3DHISTECH and Hamamatsu) using pathology-dedicated medical grade (MG), professional grade (PG) and consumer-off-the-shelf (COTS) monitors, comparing results with the microscope diagnosis after a 2-week washout period.

Results: MG monitor was faster (1090 vs 1159 vs 1181 min, delta of 6-8%, p<0.01), with slightly better performances on the detection of concurrent diseases compared with COTS (κ=1 vs 0.96, 95% CI=0.87 to 1), but equal concordance to the commercial monitors on main diagnosis (κ=1). Minor discrepancies were noted on specific scores/classifications, with MG and PG monitors closer to the reference report (r=0.98, 95% CI=0.83 to 1 vs 0.98, 95% CI=0.83 to 1 vs 0.91, 95% CI=0.76 to 1, κ=0.93, 95% CI=077 to 1 vs 0.93, 95% CI=0.77 to 1 vs 0.86, 95% CI=0.64 to 1, κ=1 vs 0.50, 95% CI=0 to 1 vs 0.50, 95% CI=0 to 1, for IgA, antineutrophilic cytoplasmic antibody and lupus nephritis, respectively). Streamlined Pipeline for Amyloid detection through congo red fluorescence Digital Analysis detected amyloidosis on both monitors (4 of 30, 13% cases), allowing detection of minimal interstitial deposits with slight overestimation of the Amyloid Score (average 6 vs 7).

Conclusions: The digital transformation needs careful assessment of the hardware component to support a smart and safe diagnostic process. Choosing the display for WSI is critical in the process and requires adequate planning.

Aim: Primary malignant melanomas in the bladder or urethra are exceedingly rare. Diagnosing these tumours presents substantial challenges due to their close resemblance in gross appearance and histology to urothelial carcinomas.

Methods: A retrospective review of our department archives from 2000 to 2023 identified four cases of primary malignant melanoma in the urinary tract. Demographic and clinical data were extracted from electronic medical records.

Results: This retrospective case series investigates the clinical presentations, histopathological characteristics, immunohistochemical profiles and molecular features of four unique cases of primary malignant melanoma in the bladder or urethra.

Conclusion: Our analysis aims to deepen the understanding of the diagnostic and management strategies for this extremely rare disease.

Aims: This study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cell lung carcinomas (SWI/SNF-dNSCLC) and to address cases with intermediate features.

Methods: The pathology department archive was searched for all primary mediastinal, pleural and lung-based malignancies that showed aberrant expression of two SWI/SNF proteins the Brahma (BRM) aka SMARCA2 and/or (Brahma-related gene 1 (BRG1) aka SMARCA4. Patient demographics, treatment and clinical outcomes were collected from records and telephonic interviews. Differences in histopathological features and immunohistochemical stains were analysed. Cases with characteristics intermediate between both tumour entities were sequenced to advance our understanding of their biology and to assign them a more accurate classification.

Results: We identified 50 tumours with SMARCA4 and/or SMARCA2 deficiencies, including 23 (46%) SMARCA4-dUT, 18 (36%) SMARCA4-dNSCLC and 2 (4%) SMARCA2-dNSCLC. Dyscohesive or undifferentiated cellular morphology versus frank gland formation along with keratin, claudin-4 and expression of >1 stem cell marker helped classify the SWI/SNF deficient tumours as SMARCA4-dUT or SWI/SNF-dNSCLC (p<0.05). Seven (14%) cases with BRG1 deficiency displayed 'intermediate' features of both SMARCA4-dNSCLC and SMARCA4-dUT and had the shortest overall survival. The smoking-related gene signature was observed on sequencing in all four cases examined.

Conclusion: Tumours with intermediate features between SMARCA4-dUT and SWI/SNF-dNSCLC exist and portend an equally poor prognoses. Immunostains, including keratin, claudin-4, TTF1, HepPar1, stem cell markers, along with BRG1 and BRM testing, are essential adjuncts to morphology, while molecular studies can offer supplementary evidence in challenging cases.

There is an ongoing explosion of new information regarding the underlying molecular alterations driving a variety of salivary gland neoplasms. The volume of this emerging data makes it difficult to keep up with and may cause pathologists to believe that salivary gland neoplasms cannot be diagnosed without genetic analysis. This review focuses on the practical diagnostic applications of molecular tools in surgical pathology specimens.

Aims: To investigate the clinicopathological features and molecular characteristics of sporadic hypertrophic and nodular port-wine stains (PWS).

Methods: We analysed the clinicopathological and molecular characteristics of 27 sporadic hypertrophic and nodular PWS retrieved from our pathology database from 2013 to 2023 and reviewed the relevant literature.

Results: There were 13 men and 14 women who ranged in age from 10 to 66 years. The main sites were the head and neck (23/27, 85%), which showed irregular thickening and darkening of purplish-red patches on the skin surface and the development of nodularity. Histologically, immature venule-like channels with irregular dilation are arranged in clusters or honeycombs, which are widely distributed primarily in the papillary layer and deep dermis and partly extend into the subcutaneous fat layer and other deep tissues. Dilated vessels with irregular shapes often exhibit fibrous thickening and an increased number of large vessels without vascular endothelial cell proliferation. All vessels showed similar characteristics, with positive staining for CD34, ERG and GNAQ in the endothelial cells, and negative staining for elastic fibres. Nine patients had somatic GNAQ mutations (9/11, 82%), including exon four mutations (6 cases, p.R183Q), exon five mutations (2 cases, p.Q209R) and exon two mutations (one case, p.G48V). Two patients had somatic BCL6 corepressor-like 1 (BCORL1) gene mutations (2/11, 18%), including exon 3 mutations (p.T1111M) and exon 7 mutations (p.G1391R).

Conclusions: Sporadic hypertrophic and nodular PWS are mostly related to somatic GNAQ mutations. This is the first study to identify the Rare GNAQ G48V and somatic BCORL1 mutations.

Aims: During detailed analysis of H&E-stained histological slides of 710 unbiased conventional renal cell carcinomas (cRCCs), 141 tumours displayed partial regressive changes showing strong similarity to that of wound healing. We aimed to analyse the molecular processes occurring in regressive tumours.

Methods: Immunohistochemistry was applied to analyse the signalling molecules in 12 selected tumours, and statistical analysis was used to estimate the correlation between regression and the outcome of the disease.

Results: The regressive areas displayed inflammatory granulation tissue expressing transforming growth factor beta-1 (TGFB1), interleukin-1 beta and interleukin-6 (IL1B and IL6), proliferation of alpha smooth muscle actin (αSMA) positive naïve activated fibroblasts and a diffuse fibronectin 1 (FN1) network. In the central areas of regressive tissues, parallel-running myofibroblasts showed FN1, collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1) positive immunoreaction. Partial tumour regression is associated with a better postoperative course of the disease.

Conclusions: Partial regression is a frequent event in cRCCs. Recognising complex molecular processes involved in tumour regression might help to find a way towards 'healing' cRCC.

EWSR1 is the most commonly rearranged gene in mesenchymal neoplasia, and its myriad chimeric oncoproteins drive widely disparate neoplasms. Here, we survey selected EWSR1 rearrangements, including well-described EWSR1 fusions with CREB family members, ATF1 and CREB1, as well as fusions in emerging entities such as mesenchymal neoplasms with EWSR1::PATZ1 and EWSR1::NFATC2 fusions. We also discuss recent data demonstrating the imperfect specificity of EWSR1::WT1 and, possibly, EWSR1::FLI1 fusions.