PATHOLOGICA最新文献

Invasive lobular carcinoma of the breast is the most common special type breast cancer. It has been defined using morphological features, has a characteristic immunophenotype associated with the loss of E-cadherin mediated intercellular adhesion, and the background of this immunohistochemistry and morphology is generally a biallelic genetic alteration of the CDH-1 gene coding E-cadherin. However, the morphology may often deviate from the classical, and immunohistochemistry may also deviate from the typical, and then the diagnosis of invasive lobular carcinoma becomes less straight forward. Eventually, the definitions of this histological type, although similar, are not identical and this may also give ground to occasional different interpretations. This review summarizes different approaches to invasive lobular carcinomas and the deviations from what is considered normal.

P53-abnormal endometrial carcinomas are high-grade and aggressive tumors which should be treated with chemo-/radiotherapy. In low-grade endometrioid carcinoma (LGEC), abnormal expression of p53 is an exceptional finding and is typically accompanied by patchy p16 positivity and diffuse hormone receptor expression.

Herein, we report a case of LGEC exhibiting both p53 and p16 overexpression, highlighting the diagnostic pitfalls related to such phenotype.

A 60-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy due to a deeply myoinvasive endometrial mass. The tumor showed glandular architecture, low-grade nuclei and glandular differentiation. Focal lymphovascular space invasion and no lymph node metastases were observed. Immunohistochemically, the tumor showed p53 overexpression, p16 block-type positivity, diffuse hormone receptors positivity and retained mismatch repair proteins expression. No POLE mutations were identified. A diagnosis of p53-abnormal LGEC was eventually made.

A glandular neoplasm with p53 and/or p16-overexpression on endometrial biopsy specimens may raise the concern of other entities such as serous carcinoma, HPV-related endocervical adenocarcinoma, and gastric-type adenocarcinoma. An immunohistochemical panel including hormone receptors, p53, p16 and mismatch repair proteins appears necessary for an accurate diagnosis of uterine adenocarcinomas.

Objective: Prostate cancer (PCa) is the most common cause of cancer-related deaths in men worldwide. BRCA1/2 genes are reported altered in approximately 1% and 8% of PCa cases, respectively. To date, formalin-fixed paraffin-embedded (FFPE) tissues have a consolidate use in the clinical practice, but with a significant drawback related to DNA/RNA degradation during the pre-analytical process. The purpose of this study is to evaluate the feasibility of detecting BRCA1/2 alterations in DNA extracted from FFPE tissues collected from PCa patients after various years of storage in seven Italian hospitals.

Methods: A total of 241 DNA samples were extracted from FFPE tissue with different storage times (1-12 y) and sequenced with NGS technology. BRCA1/2 evaluability was assessed performing data analysis with a chi-square test to study the impact of the storage time on the DNA degradation.

Results: The data collected showed a strict relation not only between the storage time and the BRCA1/2 evaluability, but even between the storage time and DNA degradation (DIN). Taken together, all the parameters considered decrease with an increase in the storage time.

Conclusions: Excessive FFPE tissues storage time (more than 3 years) can harshly affect DNA analysis and evaluability, hindering the achievement of a result useful in the clinical practice. Hence, it should be considered to perform the analysis as soon as possible to increase the evaluability of the test.

According to the recently published paper by the Lancet Commission on prostate cancer (PCa) ¹, the projections of new cases of PCa will rise from 1.4 million in 2020 to 2.9 million by 2040. Such a rise cannot be prevented by public health interventions and lifestyle changes. Late diagnosis of PCa is "widespread worldwide but especially in low-income and middle-income countries" ¹. The best way to cope with the harm due to the increase in case numbers is to develop systems for earlier diagnosis. Early diagnosis systems will have to integrate the growing power of artificial intelligence (AI), including digital pathology (DP) diagnostics, to aid the interpretation of prostate tissue specimens ¹. This contribution aims to point out how DP and AI can help pathologists for the prostate cancer "tsunami" about to come.

Objective: ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations represent fundamental predictive biomarkers for advanced non-small cell lung cancer (NSCLC) patients to ensure the best treatment choice. In this scenario, RNA-based NGS approach has emerged as an extremely useful tool for detecting these alterations. In this study, we report our NGS molecular records on ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations detected by using a narrow RNA-based NGS panel, namely SiRe fusion.

Methods: We retrospectively reviewed data on 201 advanced stage NSCLC patients who were referred to our laboratory for RNA-based molecular evaluation of ALK, ROS1, RET, NTRK gene rearrangements as well as MET exon 14 skipping.

Results: Overall, 23 (11.4%) positive cases were retrieved. Regarding molecular assessment, 11 (5.5%), 2 (1.0%), 9 (4.5%), and 1 (0.5%) out of 201 harbored an ALK, ROS1, RET gene rearrangement, or MET exon 14 skipping, respectively.

Conclusions: In this study, we provide real-world experience on RNA-based NGS analysis in patients with advanced stage NSCLC.

An asymptomatic 79-year old woman presented with a 40 mm pancreatic cystic lesion, located in the pancreatic body-tail and consistent with branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) without "high risk stigmata". During a 4-year follow-up period, imaging showed no mural nodules or main pancreatic duct dilation, and serum CEA and CA19.9 were within normal range. Later, computed tomography showed a rapid increase in cyst size up to 59 mm, which led to a clinical suspicion of malignant transformation. The patient underwent distal pancreatectomy, and final histology revealed the presence of three distinct pancreatic neoplasms: serous cystadenoma (SCA), BD-IPMN, and well-differentiated G1 neuroendocrine tumour (PanNET-G1). The co-occurrence of pancreatic neuroendocrine and exocrine tumours is exceedingly rare. To the best of our knowledge, this is the first reported case of the concomitant presence of three different pancreatic tumors in the same pancreatic specimen arose adjacent one to each other within the same macroscopic lesion.

Objective: The uPath PD-L1 (SP263) is an AI-based platform designed to aid pathologists in identifying and quantifying PD-L1 positive tumor cells in non-small cell lung cancer (NSCLC) samples stained with the SP263 assay.

Methods: In this preliminary study, we explored the diagnostic performance of the uPath PD-L1 algorithm in defining PD-L1 tumor proportion score (TPS) and predict clinical outcomes in a series of patients with advanced stage NSCLC treated with single agent PD-1/PD-L1 checkpoint blockade previously assessed with the SP263 assay in clinical practice.

Results: 44 patients treated from August 2015 to January 2019 were included, with baseline PD-L1 TPS of ≥ 50%, 1-49% and < 1% in 38.6%, 25.0% and 36.4%, respectively. The median uPath PD-L1 score was 6 with a significant correlation with the baseline PD-L1 TPS (r: 0.83, p < 0.01). However, only 27 cases (61.4%) were scored within the same clinically relevant range of expression (≥ vs < 50%). In the study population the baseline PD-L1 TPS was not significantly associated with clinical outcomes, while the uPath PD-L1 score showed a good diagnostic ability for the risk of death at the ROC curve analysis [AUC: 0.81 (95%CI: 0.66-0.91), optimal cut-off of ≥ 3.2], resulting in 19 patients (43.2%) being u-Path low and 25 patients (56.8%) being uPath high. The objective response rate in uPath high and low was 51.6% and 25.0% (p = 0.1), respectively, although the uPath was significantly associated with overall survival (OS, HR 2.45, 95%CI: 1.19-5.05) and progression free survival (PFS, HR 3.04, 95%CI: 1.51-6.14). At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS.

Conclusions: This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC.

Pathology is pivotal in diagnosing skin tumors, and the precision of diagnosis is crucial to devise customized treatment plans and enhance patient care in dermatology. The latest edition of the World Health Organization's classification of skin tumors serves as a comprehensive compendium, summarizing and categorizing all recent advancements in both anatomical-pathological and molecular aspects of cutaneous neoplasms. Several relevant advances have been introduced and new entities have been described. While the fundamental structure of the classification remains unchanged, notable additions include three new sections aimed at providing a more exhaustive description of skin lesions: nail unit tumors, skin metastases, and genetic tumor syndromes associated with skin malignancies. Recent strides in molecular pathology have led to significant breakthroughs in decoding the underlying mechanisms of various skin tumors, ranging from adnexal neoplasms to hematolymphoid neoplasms, soft tissue tumors, and melanocytic lesions. Of particular importance is the evolution in our understanding of melanocytic neoplasms, with the introduction of the term "melanocytoma" reserved for lesions exhibiting "intermediate" biological behavior and characterized by specific molecular mutations. The pathologic diagnosis process integrates morphological, immunohistochemical, and molecular features, playing a crucial role in clinical decision-making. The WHO classification serves as a valuable tool in promoting multidisciplinarity in the management of cutaneous neoplasms with the aim of translating novel pathological discoveries into more effective treatments. This review aims to distill the major updates introduced by the new classification, providing a synthesis of the latest scientific insights.

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome part of the epidermal nevus syndromes group, characterized by the presence of sebaceous nevi and other extracutaneous lesions genetically related to RAS family gene mutations. Sialadenoma papilliferum (SP) is a rare benign intraoral neoplasm which is usually BRAF or HRAS mutated. We report a case of a young female girl diagnosed with a LNSS who developed a SP which had a KRAS mutation. This is the first case of SP with a KRAS mutation in the context of a LNSS.