Histopathology最新文献

Aims: We present a series of patients with chronic, ulcerative oesophagitis refractory to proton-pump inhibitor therapy and rich in IgG4-positive plasma cells that do not strictly meet criteria for IgG4-related disease; aiming to characterize the clinical and histological pattern of this disorder.

Methods and results: We retrieved cases of chronic ulcerative oesophagitis rich in IgG4-positive plasma cells, diagnosed from 2019 to 2025. Histological and immunohistochemical slides were re-evaluated and findings correlated with clinical data, including patients' symptoms, endoscopic findings and follow-up information. A total of 12 patients with a mean age of 63.1 years were included. Dysphagia was the most common symptom (9/12 patients), followed by heartburn (8/12 patients). Serum levels of IgG4 were elevated in four patients, in three accompanied by increased IgG levels. Other organ involvement by IgG4-RD was not observed. Endoscopy showed ulceration in 100% and stricture in 50% of cases, respectively; the lower third of the oesophagus was most commonly affected. Histology illustrated dense plasma cell-rich infiltration with a mean number of IgG4-positive plasma cells of 70/HPF (range 25-100) and a mean IgG4/IgG ratio of 73% (range 50%-90%). Corticosteroids led to improvement of symptoms in 8/9 and histological remission in 4/5 patients, respectively.

Conclusion: Chronic ulcerative oesophagitis rich in IgG4-positive plasma cells may exert a severe clinical impact on affected individuals but appears to respond well to corticosteroid therapy. This case series demonstrates clinicopathological findings of the disorder and highlights the importance of IgG4 immunohistochemistry in therapy-refractory cases of chronic oesophageal ulceration with dense plasma cell-rich inflammation.

Aims: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma characterised by myxoid matrix, multilobular architecture, eosinophilic ovoid to short spindle cells arranged in cords, clusters or reticular patterns and NR4A3 gene rearrangement. However, some EMCs show morphological variations or non-EWSR1::NR4A3 fusion. We described herein five cases of variant EMCs.

Methods and results: The five patients included two females and three males, aged 24-59 years (median: 49 years). The tumours were located in the dorsal region, buttock, thigh, paravertebral region and elbow, respectively. Grossly, the tumour sizes ranged from 4.0 to 16.0 cm (median: 6.5 cm) in greatest dimension. Morphological examination revealed tumours with varied growth patterns, including solid variants with eosinophilic proteinaceous fluid (n = 2), classic EMC morphology with rhabdoid cells (n = 1), a biphasic variant, composed of fibroblastic/myofibroblastic-like cells and oval to short spindle-shaped cells (n = 1), and a spindle-cell morphology with a myxoid stroma and prominent haemorrhagic cystic spaces (n = 1). Immunohistochemically, all cases showed variable expression of CD117. Next-generation sequencing (NGS) identified an EWSR1::NR4A3 fusion, a novel FUS::NR4A2 fusion, a novel ACTB::NR4A3 fusion, and two FUS::NR4A3 fusions. Follow-up for all five patients showed no signs of local recurrence or distant metastasis.

Conclusion: These five cases of EMC highlight the continuous morphological spectrum of this tumour, demonstrating significantly greater histological diversity than classically described. The identification of novel fusion partners further expands its genetic landscape.

Aims: Plaque-like CD34-positive dermal fibroma (PDF), previously termed medallion-like dermal dendrocyte hamartoma, is a rare CD34-positive superficial spindle cell fibroblastic tumour that may closely mimic dermatofibrosarcoma protuberans. Recent studies have identified recurrent kinase gene fusions in a subset of congenital and paediatric CD34-positive plaque-like superficial spindle cell tumours with overlapping clinicopathologic features, highlighting an emerging molecular framework for this group. However, the molecular spectrum of lesions meeting classic histopathologic criteria for PDF remains an area of active investigation.

Methods and results: Four cases of PDF were identified retrospectively, and histopathologic and immunohistochemical findings were reviewed. RNA-based next-generation sequencing was performed to evaluate for potential oncogenic gene fusions. All cases demonstrated a superficial, dermal-based proliferation of bland spindle cells with a preserved Grenz zone and diffuse CD34 expression, without S100 expression. Two of four cases harboured in-frame NTRK3 fusions, including a novel SPTBN1::NTRK3 fusion and a PPFIBP1::NTRK3 fusion, both retaining the NTRK3 tyrosine kinase domain. Available clinical follow-up demonstrated indolent behaviour in all patients.

Conclusions: NTRK3 gene fusions occur in a subset of plaque-like CD34-positive dermal fibromas, providing additional molecular insight into this rare superficial spindle cell lesion. Together with emerging literature, these findings support a role for recurrent kinase gene rearrangements in a subset of CD34-positive plaque-like superficial spindle cell tumours, while underscoring the continued importance of clinicopathologic correlation in defining this evolving spectrum.

Introduction: As the nature of spread through air spaces (STAS) in non-small cell lung cancers (NSCLC) remains a matter of debate, this paper presented the first application of 3D X-ray virtual histology to shed light on the origin of these elements.

Methods: Five adenocarcinomas and two squamous cell carcinomas were selected from a cohort of NSCLC cases to serve as representative examples of neoplasms in which the presence of STAS had already been assessed through conventional histology. Although available only for research purposes, synchrotron radiation X-ray phase-contrast micro-tomography (μCT) allows virtual sectioning of whole paraffin blocks with spatial and contrast resolution similar to that of histology, thus enabling examination of STAS patterns (e.g., single and clustered tumour cells, micropapillary, solid nests).

Results: The 3D results demonstrated that free-floating STAS (i.e., micropapillary and solid patterns) were observed to be only the edges of tumour cell clusters connected to the primary tumour. In contrast, STAS located near alveolar walls or vascular structures suggested tumour cell migration along these surfaces away from the primary tumour.

Conclusion: These findings indicate that most STAS types are clusters of cells connected to the main tumour mass. 3D X-ray virtual histological investigation helps to understand the morphological composition and spatial evolution of the tumour, as well as the presence of a tumour larger than that visible in the histological slide. From a radiological and surgical perspective, these findings may influence the assessment of the extent of parenchymal involvement and help guide the surgical approach.

Aims: Accurate diagnosis of histiocytosis remains challenging due to overlapping morphologic and immunophenotypic features among subtypes, including Langerhans cell histiocytosis (LCH), Erdheim-Chester disease/xanthogranuloma (ECD/XG) and Rosai-Dorfman disease (RDD). RDD is a rare disorder characterized by large S100-positive histiocytes with emperipolesis; however, emperipolesis may be difficult to recognize due to abundant admixed inflammatory cells or stromal fibrosis. Moreover, unlike LCH and ECD, RDD does not harbour BRAF V600E mutation, limiting the utility of high-sensitivity molecular analysis and mutant-specific immunohistochemistry for BRAF, which are available in many institutions. We observed the expression of CD71 in histiocytes in RDD. Therefore, we investigated the diagnostic utility of CD71 immunohistochemistry for RDD.

Methods and results: We retrospectively reviewed electronic medical records to identify the cases of histiocytosis and reactive histiocytic proliferations. Clinical data and molecular results were also reviewed. The cohort comprised 58 cases, including RDD (n = 22), LCH (n = 6), non-LCH/ECD/XG (n = 14), histiocytic sarcoma (n = 4) and benign reactive cases (n = 12). CD71 demonstrated membranous and cytoplasmic staining in all RDD cases (22/22, 100%). In contrast, lesional cells in LCH were uniformly negative for CD71. Most non-RDD cases lacked CD71 expression, although dim cytoplasmic staining was observed in a subset of cases. Two sarcoidosis cases and one histiocytic sarcoma showed CD71 expression comparable to RDD.

Conclusions: CD71 immunohistochemistry is a sensitive marker for identifying histiocytes in RDD and serves as a useful adjunct in distinguishing RDD from other histiocytic proliferations.

Aims: To investigate the associated histopathology and immunohistochemical (IHC) profile of pseudoangiomatous stromal hyperplasia (PASH) of the breast in a large, contemporary cohort.

Methods and results: We reviewed 193 benign breast biopsies with PASH from 185 patients without history of breast atypia or carcinoma. A tissue microarray was created and subjected to a panel of IHC. Ischemic fat necrosis was the most common finding in biopsies with PASH (181/193; 93.8%), while fibrocystic changes (170/193; 88.1%) were frequently present. PASH showed consistent, diffuse, strong staining for CD34 (193/193; 100%) and variable positivity for BCL-2 (66/193; 34.2%), SMA (47/193; 24.4%), desmin (11/193; 5.7%) and TRPS-1 (2/193; 1%), while all were negative for ERG and β-catenin. PR and ER positivity was identified in 33.7% (65/193) and 29% (56/193) of cases, respectively. Hormone receptor positive PASH was significantly associated with a higher rate of non-proliferative fibrocystic changes as compared to hormone receptor negative PASH (163/193; 84.5% vs 104/193; 53.9%, respectively) (P = 0.047). Subsequent breast atypia or carcinoma was uncommon (10/185; 5.4%), with median follow-up of 6.2 years (range 5.3-7.3 years).

Conclusions: ER/PR expression in PASH is less frequent than previously reported by some studies. However, the frequency of fat necrosis and associated fibrocystic changes in PASH support a chronic, hormone-related process. Consistent CD34 positivity and absence of markers seen in histologic mimics aid in the diagnosis of PASH in challenging cases. PASH does not appear to impart increased cancer risk.

Background: Ossifying spindled and epithelioid tumour (OSET) is a recently defined soft tissue neoplasm with characteristic features, including a peripheral shell of bone or pseudocapsule, keratin expression, and indolent behaviour. Here, we present five unique cases of OSET with novel clinical and morphologic features.

Materials and methods: Cases of OSET were collected. Clinicopathologic and molecular features were documented.

Results: Cases of OSET were collected from lesions arising in the extremities of five patients, ranging in age from 8 to 58 years. Histologically, all tumours were well circumscribed and keratin-positive. Three showed a mixed spindle and epithelioid cell morphology, whereas two were composed predominantly of epithelioid cells. Two cases harboured mitotic rates of ≥5 mitotic figures per 10 high-power fields and contained necrosis. While peripheral pseudoencapsulation was consistent, two cases contained minimal peripheral ossification (approximately 5%), and two were entirely non-ossifying. One OSET case showed multifocal disease with synchronous tumours involving the elbow and wrist of the upper extremity; another represented a local recurrence 7 years after resection of the primary tumour; the remaining three patients are disease-free. Next-generation sequencing of tumour RNA revealed an SRSF7::NFATC3 fusion in the three cases evaluated.

Conclusion: Our cohort expands the clinical and morphologic spectrum of this entity to include tumours with increased mitotic activity and necrosis, as well as highlights the first two examples of non-ossifying OSET. Moreover, while confirming the overall indolent behaviour of OSET, we described cases that demonstrate primary multifocal disease and local recurrence.

The 6th Edition of the WHO Classification of Digestive System Tumours represents a significant update to the 5th edition. It integrates pathological, new molecular, and clinical insights to refine the taxonomy of digestive system neoplasms. The revised classification continues to emphasise standardisation in terminology, coding, and diagnostic criteria to facilitate global consistency in diagnosis, treatment, epidemiological reporting and research. Structural reorganisation of book chapters describes epithelial tumours by anatomical site, while separating neuroendocrine, mesenchymal and haematolymphoid tumours into dedicated chapters that are aligned with other WHO tumour volumes. Genetic tumour syndromes are classified by mechanisms, pathways and genes, whereas metastatic disease is comprehensively covered under other tumours and metastases. Key structural and diagnostic refinements include consolidation of gastric dysplasia entities; separation of duodenal/ampullary from jejuno-ileal tumours; clearer categorisation of colorectal serrated polyps and novel carcinoma grading; introduction of small- and large-duct intrahepatic cholangiocarcinoma as separate entities, and redefinition of undifferentiated carcinoma to include 'carcinoma with mesenchymal differentiation'. Several new entities are introduced, including oesophageal epidermoid metaplasia, colorectal intramucosal adenocarcinoma, low-grade tubuloglandular adenocarcinoma and lymphoglandular complex-like adenocarcinoma, intraductal tubulopapillary and intraductal oncocytic papillary neoplasms of the bile ducts and sonic hedgehog hepatocellular adenoma. The concept of amphicrine-like carcinoma (ALC) is distinguished from MiNEN and broadens the understanding of tumours with dual neuroendocrine-non-neuroendocrine differentiation. Grading systems are simplified to two-tier classifications (low/high grade) across precursor lesions, with enhanced criteria for neuroendocrine tumour grading. Anal canal neoplasia terminology is harmonised with human papillomavirus (HPV) related Lower Anogenital Squamous Terminology (LAST) and mass-forming biliary and gallbladder cancer precursors share similar terminology. Finally, carcinoma of unknown primary (CUP) is included in a separate section for the first time, classified by molecular and immunophenotypic profiles to guide therapy. Overall, the 6th edition strengthens tumour diagnostic precision and molecular alignment across the digestive system.

Aim: To understand whether the worldwide implementation of PD-L1 testing in triple-negative breast cancer (TNBC) can be achieved in routine clinical practice.

Methods and results: The multicentre retrospective observational VANESSA study consecutively and uniformly enrolled patients treated with systemic therapy for early or metastatic (e/m)TNBC diagnosed between 2014 and 2017. PD-L1 status was retrospectively assessed locally and centrally using the VENTANA PD-L1 (SP142) Assay (PD-L1 expression on tumour-infiltrating immune cells covering ≥1% of the tumour area). The primary objective was to determine the prevalence of PD-L1 positivity assessed locally on primary and/or metastatic tumour tissue. Concordance between local and central testing was a secondary endpoint. PD-L1-positive prevalence was 38% in eTNBC (728/1902) and 20% in mTNBC (30/152) and was higher in submitted tissue size >5 versus <5 mm diameter (eTNBC: 43% versus 16%; mTNBC: 24% versus 13%). Among 1967 samples tested both centrally and locally, concordance was 75% (Cohen's κ coefficient 0.52, 95% CI 0.48-0.55) and was similar regardless of cohort (eTNBC versus mTNBC), sample collection method (biopsy versus resection) or sample origin (primary versus metastatic). PD-L1-positive prevalence was higher by central versus local assessment (eTNBC: 55% versus 39%; mTNBC: 26% versus 20%).

Conclusion: In this real-world study, PD-L1-positive prevalence was lower than in prospective trials assessing PD-L1 status centrally, lower in mTNBC than eTNBC, lower in smaller than larger tissue samples and lower by local than central assessment. These findings underline the importance of central PD-L1 testing on sufficiently large samples to ensure optimal selection for therapies targeting PD-(L)1 in mTNBC.