Journal of Clinical Pathology最新文献

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.

Background and aims: Diagnosing end-stage primary cicatricial alopecia (PCA) on routine histology is challenging since the major diagnostic feature (inflammatory infiltrate) may be minimal or absent. This study aimed to assess various staining patterns and diagnostic utility of elastic tissue staining by Verhoeff-Van Gieson (VVG) method and trichoscopy in PCA.

Study design: Cross-sectional study.

Methods: Fifty-three patients clinically diagnosed with PCA underwent biopsy and trichoscopy in this cross-sectional study. Clinically active edge, if present, was biopsied. Twenty serial tissue sections were stained using H&E and VVG stain. Clinicopathological diagnoses were lichen planopilaris (LPP), discoid lupus erythematosus (DLE), folliculitis decalvans and unclassified PCA (UPCA) in 30 (56.6%), 11 (20.75%), 1 (1.9%) and 11 (20.75%) patients, respectively. Utility of VVG stain was ascertained considering clincopathological correlation (CPC) as the reference standard. Association of characteristic trichoscopic and VVG staining patterns was ascertained.

Results: Diagnostic definition was achieved on VVG staining in 19/30 sections of LPP (wedge-shaped pattern) with 63.33% sensitivity; 7/11 cases of DLE (absent upper and mid dermal elastic fibres) with 63.64% sensitivity and 7/11 cases of UPCA (wedge-shaped pattern-3/7; recoil pattern-4/7). Routine histology suggested diagnosis only in 13/53 sections (24.52%). However, diagnosis on VVG staining corresponded with diagnosis on CPC in 33/53 cases (62.3%). Comparison of H&E versus VVG stain both overall and in the LPP and UPCA cohorts proved utility of VVG staining using Fisher's exact test (p<0.05). Statistical significance was also noted when trichoscopy was correlated with patterns on VVG staining (p<0.05).

Conclusion: Increased diagnostic yield is noted with trichoscopy and VVG stain in PCA especially when routine histopathology is non-diagnostic.

Aims: Angioimmunoblastic T cell lymphoma (AITL) is a T cell lymphoma with aberrant immune activity. It is characterised by inflammatory and immune reactions. However, the impact of regulatory T (Treg) cells on AITL remains unclear.

Methods: We retrospectively collected 46 AITL cases and performed immunohistochemical analysis of forkhead box P3 (FOXP3) expression. The number of immunostained FOXP3 cells was determined using a digital pathology system with whole-slide imaging. The average number of FOXP3+ cells per high-power field (HPF) was determined by randomly counting 20 HPFs. AITL cases were categorised into high-expression and low-expression groups based on the median count of FOXP3+ cells in all analysed samples. The relationship between FOXP3 expression and clinicopathological features was assessed.

Results: Among the studied patients, 14 (30.4%) were females and 32 (69.6%) were males, and the median age at diagnosis was 64.1 years. The median expression of FOXP3 was 84.9 positive cells/HPF. FOXP3 expression negatively correlated with Epstein-Barr virus-encoded small RNA positivity in tumour (p=0.041). The patients with low FOXP3 expression presented with aggressive clinical behaviour, including advance-staged diseases (p=0.043), splenomegaly (p=0.008), B symptoms (p=0.019) and extranodal involvement (p=0.019). The neutrophil-to-lymphocyte ratio was higher in the patients with low FOXP3 expression, compared with those with high FOXP3 expression. Low FOXP3 expression had an adverse effect on progression-free survival (PFS, p=0.033), and increased the risk of recurrence 2.320-fold (HR 2.320 (95% CI 1.109 to 4.856); p=0.025).

Conclusions: Patients with AITL with low FOXP3 expression tend to have aggressive clinical presentation and shortened PFS. These findings may help with risk stratification and determination of new treatment strategy.

Diagnostic errors affect patient management, and as blood gas analysis is mainly performed without the laboratory, users must be aware of the potential pitfalls. The aim was to provide a summary of common issues users should be aware of.A narrative review was performed using online databases such as PubMed, Google Scholar and reference lists of identified papers. Language was limited to English.Errors can be pre-analytical, analytical or post-analytical. Samples should be analysed within 15 min and kept at room temperature and taken at least 15-30 min after changes to inspired oxygen and ventilator settings, for accurate oxygen measurement. Plastic syringes are more oxygen permeable if chilled. Currently, analysers run arterial, venous, capillary and intraosseous samples, but variations in reference intervals may not be appreciated or reported. Analytical issues can arise from interference secondary to drugs, such as spurious hyperchloraemia with salicylate and hyperlactataemia with ethylene glycol, or pathology, such as spurious hypoxaemia with leucocytosis and alkalosis in hypoalbuminaemia. Interpretation is complicated by result adjustment, for example, temperature (alpha-stat adjustment may overestimate partial pressure of carbon dioxide (pCO₂) in hypothermia, for example), and inappropriate reference intervals, for example, in pregnancy bicarbonate, and pCO₂ ranges should be lowered.Lack of appreciation for patient-specific and circumstance-specific reference intervals, including extremes of age and altitude, and transformation of measurements to standard conditions can lead to inappropriate assumptions. It is vitally important for users to optimise specimen collection, appreciate the analytical methods and understand when reference intervals are applicable to their specimen type, clinical question or patient.

Aims: Thymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that share similar morphology and immunophenotype with conventional markers. Therefore, additional antibodies are needed to differentiate between these tumours.

Methods: For this purpose, a panel of immunohistochemical stains including PAX2, PAX5, PAX8 (all monoclonal) and CD70 was used on whole tumour sections of 30 thymic carcinomas and 30 atypical thymomas to determine the expression pattern of these antibodies. In addition, all tumours were stained with markers that are well known to be expressed in both tumours, including pancytokeratin and cytokeratin 5/6. The percentage of positive tumour cells as well as the intensity of staining were evaluated and scored.

Results: PAX5 stained close to 70% of thymic carcinomas while all atypical thymomas were negative for this marker. CD70 was expressed in 18 thymic carcinomas (60%) and in 1 case of atypical thymoma (3%). On the other hand, monoclonal PAX8 was negative in all cases while PAX2 was positive in a single thymic carcinoma. Of the established stains, pancytokeratin and cytokeratin 5/6 were equally positive in both tumours.

Conclusions: Among the markers explored, only PAX5 and CD70 appear to be differentially expressed and are predominantly restricted to thymic carcinomas. Therefore, in small biopsy specimens and in resections in which the morphological features remain equivocal, application of these particular stains may facilitate separation of thymic carcinoma and atypical thymoma.