Journal of Clinical Pathology最新文献

Aims: Papillary carcinoma diagnosed in core needle biopsy (CNB) refers to carcinoma with papillary features but no definitive invasion, including papillary ductal carcinoma in situ (DCIS), papilloma with DCIS, encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC). This study assesses the upgrade rate of papillary carcinoma in CNB and supports the use of 'papillary carcinoma' as an umbrella term.

Methods: A retrospective review identified 41 CNB cases of non-invasive papillary carcinoma with subsequent excision (2011-2018). H&E and immunohistochemistry slides from CNBs were reviewed, and excisional diagnoses were retrieved.

Results: All 41 CNB cases were either DCIS or upgraded to invasive carcinoma upon excision, with an overall upgrade rate to invasive carcinoma of 39% (16/41). Subtypes showed varying upgrade rates: 16.7% (1/6) for papillary DCIS, 25% (1/4) for papilloma with DCIS, 83.3% (5/6) for SPC, 100% (1/1) for EPC and 33.3% (8/24) for unclassifiable papillary carcinoma. No lymph node metastases, recurrences or breast cancer-related mortality were observed during the follow-up period.

Conclusions: Given the high upgrade rate, subclassification of papillary carcinoma in CNB lacks clinical significance. The term 'papillary carcinoma' should be used in CNB, and lymph node removal warrants further investigation.

Aims: A synthetic lifting agent, ORISE, used for endoscopic mucosal resections, has been recalled from the market since November 2022 due to clinical complications. Despite this, the impact of ORISE-associated complications is expected to persist in the foreseeable future. We present a large single institutional series of therapeutic resections from patients for whom ORISE was used for initial endoscopic procedures, highlighting the pitfalls and complications associated with its use.

Methods: All specimens showing lifting agent granulomata (LAGs) associated with the use of ORISE were identified. The H&E slides were reviewed to define the morphological characteristics and extent of LAG in the intestinal wall and other organs. The clinical impression and gross findings were compared with the final pathological diagnosis.

Results: 34 cases (28 resections and 6 repeat endoscopic mucosal resection specimens) showed LAG. On microscopy, 20.5% showed no residual disease, 64.7% also showed residual precursor lesion and 14.7% also showed malignancy. In 64.2% of cases, a mass lesion was seen grossly but no malignancy was identified microscopically. ORISE was present in vascular spaces (n=9), lymph nodes (n=2), other organs such as appendix (n=1) and omentum/peritoneum (n=1). The major discordance between clinical impression (mass/neoplasm) and final pathology (no residual malignancy) was seen in 4/34 (11.8%) cases. LAGs were seen up to 10 months after the use of ORISE in the prior endoscopic procedure.

Conclusion: ORISE deposits may mimic residual/disseminated neoplasm and prompt inadvertent changes in surgical decisions. Awareness of this pitfall is essential to prevent unwarranted surgical resections in patients undergoing follow-up for endoscopically resected lesions.

p53 immunohistochemistry (IHC) is widely used as a rapid surrogate for detecting TP53 mutations, with TP53 mutations being a key biomarker for poor outcomes in lymphomas. We developed two algorithms using digital quantification tools to assess p53 expression from whole slide images of 77 lymphoma samples. An experienced pathologist visually evaluated the p53 slides, classifying cases as likely wild-type or mutated TP53 genotype. We correlated the results of the algorithms and visual inspection with the actual TP53 genotype. For cases with p53 overexpression (likely missense mutations), the algorithms achieved 86.7% sensitivity and 98.2% specificity (visual inspection: 80% and 95.2%). For cases with reduced p53 expression (likely 'other' mutations), the algorithms showed 92.7% sensitivity and 100% specificity (visual inspection: 40% and 95.8%). This study demonstrates that combining digital pathology with digital quantification tools-based algorithms can reliably predict TP53 genotype from p53 IHC patterns, with comparable or slightly superior performance to an experienced pathologist.

We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into 'essential' and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma classification, providing guidance on how to apply the WHO classification in resource-limited settings.

Aims: To investigate immunohistochemical expression of the E26 transformation-specific factors (ETS)-related gene (ERG) in a large number of soft tissue neoplasms using a tissue microarray technique.

Methods: 489 cases of soft tissue neoplasms, including benign and malignant entities, were collected from the files of the respective institutions and constructed into tissue microarrays. Tissue microarrays were stained for ERG immunohistochemistry using two antibodies, EP111 and EPR3864.

Results: A total of 25 cases (5.1%) were identified that were positive for ERG using the monoclonal antibody EP111 and 15 cases (3%) using the monoclonal antibody EPR3864, including rhabdomyosarcoma, peripheral nerve sheath tumours, synovial sarcoma, myxofibrosarcoma, epithelioid sarcoma, dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, nodular fasciitis and dedifferentiated liposarcoma. The most consistently stained tumours included synovial sarcoma, rhabdomyosarcoma and benign and malignant peripheral nerve sheath tumours. Various other fibroblastic proliferations, including dermatofibrosarcoma protuberans, myxofibrosarcoma, low-grade fibromyxoid sarcoma and nodular fasciitis, also showed positive staining in a small fraction of cases. One case of dedifferentiated liposarcoma showed nuclear positivity for ERG, and one case of epithelioid sarcoma was also positive.

Conclusions: This study supports the value of ERG as a highly sensitive and specific marker for the diagnosis of vascular neoplasms but also demonstrates rare cases of aberrant staining and underscores the need to assess soft tissue tumours using a panel of stains and interpret the results of immunohistochemistry in the appropriate histological and clinical context.

Aims: Next generation sequencing (NGS) on tumour tissue is integral to the delivery of personalised medicine and targeted therapy. NGS on liquid biopsy, a much less invasive technology, is an emerging clinical tool that has rapidly expanded clinical utility. Gene mutations in cell-free total nucleic acids (cfTNA) circulating in the blood are representative of whole tumour biology and can reveal different mutations from different tumour sites, thus addressing tumour heterogeneity challenges.

Methods: The novel Ion Torrent Genexus NGS system with automated sample preparation, onboard library preparation, templating, sequencing, data analysis and Oncomine Reporter software was used. cfTNA extracted from plasma was verified with the targeted pan-cancer (~50 genes) Oncomine Precision Assay (OPA). Assessment criteria included analytical sensitivity, specificity, limits of detection (LOD), accuracy, repeatability, reproducibility and the establishment of performance metrics.

Results: An ISO 15189 accredited, minimally invasive cfTNA NGS diagnostic service has been implemented. High sensitivity (>83%) and specificity between plasma and tissue were observed. A sequencing LOD of 1.2% was achieved when the depth of coverage was >22 000×. A reduction (>68%) in turnaround time (TAT) of liquid biopsy results was achieved: 5 days TAT for in-house analysis from sample receipt to a final report issued to oncologists as compared with >15 days from reference laboratories.

Conclusion: Tumour-derived somatic variants can now be reliably assessed from plasma to provide minimally invasive tumour profiling. Successful implementation of this accredited service resulted in: Appropriate molecular profiling of patients where tumour tissue is unavailable or inaccessible. Rapid TAT of plasma NGS results.

Aims: To reveal clinicopathological characteristics of alcoholic foamy degeneration (AFD)-an uncommon form of alcoholic liver injury.

Methods: Clinicopathological features of AFD (n=9) were examined in comparison to those of severe alcoholic hepatitis (SAH; n=12).

Results: Patients with AFD presented with either biochemical liver dysfunction (n=1) or clinical jaundice (n=8). One case had undergone liver transplantation for alcohol-related cirrhosis and hepatocellular carcinoma 2 years and 3 months before presentation. AFD cases were histologically classified into three groups. The non-jaundiced case had mixed macro- and microvesicular bland steatosis. Seven jaundiced cases showed more complex microscopic features with lobular inflammation, acidophilic bodies, cholestasis and lobular distortion. Hepatocytes were pleomorphic, some extensively enlarged with clear cytoplasm, somewhat resembling ballooning degeneration; however, it was mainly due to accumulated lipid droplets ('pseudoballooning'). The remaining case also had predominant changes of AFD, but a few foci showed classical ballooning hepatocytes and Mallory-Denk bodies, in keeping with mixed AFD and steatohepatitis. When compared with patients with SAH, those with AFD had lower white blood cell and neutrophil counts and higher cholesterol levels (all p<0.001). On imaging, ascites and varices were less common in AFD than in SAH (11% vs 75%, p=0.014; 0% vs 67%, p=0.008, respectively). All seven patients with AFD who successfully abstained from alcohol experienced rapid improvement in liver function.

Conclusions: Microscopic findings of AFD are more complex than currently thought, and some cases may be mistaken for steatohepatitis. AFD may also develop in conjunction with steatohepatitis or following liver transplantation.

Aims: This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and calcium levels.

Methods: A historical cohort study was conducted on adult patients with solitary PTA removed in the Gold Coast Health Precinct, Australia, between 2017 and 2022.

Results: PTA weight is correlated with the change in day 1 PTH level (r=0.26, p=0.036), the change in day 1 corrected calcium level (r=0.20, p=0.033), and the change in follow-up corrected calcium level (r=0.47, p<0.001). The largest dimension (size) of PTA is also correlated with the change in day 1 PTH (r=0.30, p=0.011) and the change in follow-up corrected calcium level (r=0.40, p<0.001). Adjusted for age and gender, a statistically significant negative correlation was found between day 1 PTH level and adenoma size, resulting in a 0.5% change in size for every percentage change in PTH level (equating to a 5.0% increase in variance explained, p=0.038). Similarly, a negative correlation was identified in day 1 corrected calcium levels and weight, with a 4.7% change in weight for every percentage of change in day 1 corrected calcium level (an increase of 5.6% variance explained, p=0.010). In addition, a negative correlation was identified, where every 3.1% change in size (an increase of 17.4% variance explained, p<0.001) and 7.6% change in weight (an increase of 22.7% variance explained, p<0.001) was seen with every percentage change in follow-up corrected calcium levels. Clear-cell PTA had the most significant percentage fall in day 1 corrected calcium levels compared with other PTA subtypes (p=0.007).

Conclusions: Preoperative calcium and PTH levels correlate with PTA weight and size. The degree of change in postoperative corrected calcium levels behaved differently in the clear-cell subtype.

Aims: For phyllodes tumours (PT), local and distant recurrence rates increase with higher grades and are difficult to predict. The Singapore nomogram has been used to predict recurrence events for PT. We aimed to test this nomogram for accuracy in a US cohort and to compare with a histological score.

Methods: Patients with PT were selected from a prospective institutional database. Histological parameters and margin status were used to estimate the nomogram score and the histological score, as previously defined. Multivariable analyses were used to estimate the association of recurrence-free survival (RFS) with individual factors, nomogram score and histological score. Harrel's C-index was estimated.

Results: Of 81 PT cases, 25.9% were benign, 40.7% borderline and 33.3% malignant. Recurrences occurred in 33.3% (n=27). The adjusted RFS analysis including the four factors used in the Singapore nomogram performed well (C-index of 0.78). However, despite a higher nomogram score being associated with increased risk of recurrence (HR 1.03, 1.01-1.05, p=0.007), the individual numeric scale defined in the nomogram only moderately fit our data (C-index of 0.66). Patients with higher histological scores also had an increased risk of recurrence (HR 1.25, 1.07-1.47, p=0.005; C-index of 0.70).

Conclusion: Histological score more accurately predicted PT recurrence in our cohort, which includes a higher proportion of higher-grade PT. Refining the nomogram to include factors specific to malignant PT and factors with more variance, as well as refining the assigned weights, may result in improved performance. This study identifies an opportunity for international collaboration to refine the predictive model.