Histopathology最新文献

Aims: Mesonephric-like adenocarcinoma (MLA) of the endometrium or ovary is a rare but distinct endometrial carcinoma which has a combination of characteristic morphological, immunohistochemical (IHC) and molecular features. SOX17 has been recently identified as a highly sensitive and specific marker for endometrial and ovarian carcinomas. In this study, we aimed to investigate SOX17 expression in MLA together with other IHCs to differentiate MLAs from other endometrial carcinomas.

Methods: Seventeen previously diagnosed endometrial/ovarian MLAs were collected, and multiple IHCs were performed. Additionally, we performed SOX17, PAX8 and ER on tissue microarrays (TMAs) composed of 652 endometrial carcinomas from 2012 to 2015 when MLA diagnostic criteria were not established.

Results: All 17 MLAs showed diffuse strong positive PAX8, negative ER and variable TTF1/GATA3 staining. Notably, all MLAs showed negative (n = 10) or focal weak/moderate (n = 7) staining for SOX17, which is more diffuse and stronger than PAX8 in other endometrial carcinoma subtypes. This finding prompted us to screen TMAs with 652 endometrial carcinomas diagnosed before MLA by an approach of combined SOX17 and PAX8 IHCs, and 14 cases with positive PAX8 but negative/focal weak SOX17 were identified. We further studied the 14 cases by examining morphology and performing additional IHCs (TTF1, GATA3, ER and CD10) and would classify seven (50%) of them as MLAs based on morphological features and positive CD10, TTF1 and/or GATA3 staining.

Conclusion: Our results suggest that a combination of SOX17 and PAX8 IHCs would aid in diagnosing MLA if the results show strong positive PAX8, but negative SOX17.

Aims: Melanomas are recognised for their remarkable morphological plasticity. Some tumours may lose conventional features and/or acquire non-melanocytic characteristics, referred to as undifferentiated, dedifferentiated and transdifferentiated melanoma. Despite this phenotypical variability, melanomas typically maintain their cancer driver aberrations, affecting genes such as BRAF, NRAS and NF1. Currently, little is known about whether the DNA methylation profile follows the loss or change of differentiation or is retained despite extensive morphological transformation.

Methods and results: In this study we analysed 11 melanoma cases, comprising six males and five females, with a median age of 67 years, including five undifferentiated, four trans-differentiated and two de-differentiated melanomas. Undifferentiated and trans-differentiated tumours either arose in a patient with known melanoma and/or presented in the groin/axilla with molecular alterations consistent with melanoma. Cases with heterologous differentiation resembled chondrosarcoma, osteosarcoma, angiosarcoma and rhabdomyosarcoma both morphologically and immunohistochemically, while undifferentiated tumours resembled undifferentiated pleomorphic sarcoma. Methylome profiling was performed, and unsupervised clustering analysis revealed nine cases (five undifferentiated, three trans-differentiated and one de-differentiated) to cluster closely together with conventional melanomas from a reference set. Two cases clustered separately with a distinct group of conventional melanomas exhibiting H3K27me3 loss.

Conclusions: Despite loss of differentiation and phenotypical plasticity, methylation patterns seem to be retained in undifferentiated, de-differentiated and trans-differentiated melanomas and represent useful diagnostic tools to enhance diagnostic precision in these diagnostically challenging cases.

Aim: Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies.

Methods: We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP.

Results: A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm² and fibroblast foci/mm² was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent.

Conclusions: In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

What will be the next disruptive technology that will change pathology's routine practice again? In this editorial we make a case for the need of more complex biomarkers in oncology diagnostics, to match the inherent complexity of cancer biology. This complexity will be achieved by the validation of technology able to generate more meaningful biological datapoints (epitomized in tissue pathology by technologies such as multiplex immunofluorescence) and, more important, by the systematic analysis of multimodal technology outputs with artificial intelligence tools, which is the essence of integrated diagnostics. While describing these processes, the authors highlight the pivotal role that histopathology will play, once again, in yet another transformation in diagnostics.

Malignant papillary lesions, and in particular, encapsulated papillary carcinoma (EPC) of the breast, continue to present diagnostic challenges for the practising pathologist. In addition to the relative rarity of these lesions, the lack of evidence-based diagnostic criteria, differences in the biological characteristics, and the clinical behaviour of in situ and invasive forms, variable use of immunohistochemical markers, and overlap with other tumour types including high-grade circumscribed forms of invasive breast carcinomas has resulted in diagnostic discordance with potentially significant clinical and management implications. Pathologists should be familiar with the range of morphology observed in malignant papillary tumours, EPC, and EPC-like tumours and the existence of tumours with overlapping features. In this review we summarize the common diagnostic pitfalls in malignant papillary tumours and provide an approach to the diagnostic evaluation and categorisation of these enigmatic entities.

Lymph node metastases (LNM) play a central role in the tumour-node-metastasis (TNM) classification for colorectal cancer (CRC), with extranodal extension (ENE) as an adverse feature. ENE has never been directly compared to tumour deposits (TD). The aim of this study was to perform an up-to-date systematic review, including a network meta-analysis to compare their prognostic value. A comprehensive search was conducted on PubMed, Embase, Web of Science and Cochrane databases to identify all prognostic studies on ENE and TD. A total of 20 studies were included, with 7719 cases. The primary outcome was 5-year disease-free survival (DFS); secondary outcomes were overall survival (OS) and disease-specific survival (DSS). Frequentist paired and network meta-analyses were performed using the netmeta package in R. For univariable DFS analysis, LNM + TD+ cases had a significantly worse outcome compared with LNM + ENE+ cases [hazard ratio (HR) = 1.27, 95% confidence interval (CI) = 1.06-1.53], which was no longer significant for multivariable DFS analysis (HR = 1.13, 95% CI = 0.87-1.46). All OS and multivariable DSS analyses showed a significantly worse outcome for LNM + TD+ cases compared with LNM + ENE cases. For all outcomes, both LNM + TD+ and LNM + ENE+ had a significantly increased hazard compared with LNM+ cases. This study shows that there is a trend towards worse outcome for LNM + TD+ than LNM + ENE+, not statistically significant in multivariable DFS analysis. Both groups perform significantly worse than cases with LNM only. To improve the accuracy of CRC staging, we recommend to put more emphasis on both ENE and TD in the TNM classification, with the most prominent role for TD.

Aim: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs).

Methods and results: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02).

Conclusion: SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis.