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(A) Oesophageal biopsy section showing low grade squamous dysplasia with only mild cytological atypia within the lower half of the epithelial thickness (magnification x40). (B) Oesophageal biopsy section showing high grade squamous dysplasia with severe cytological atypia in more than half of the epithelium (magnification x40). (C) Dysplastic squamous epitelium and invasive squamous cell carcinoma (magnification x10). (D) Invasive squamous cell carcinoma with keratin pearl formation (arrow) (magnification x20).
Source publication
Oesophageal and gastro-oesophageal junction (GOJ) neoplasms, and their predisposing conditions, may be encountered by the practicing pathologist both as biopsy samples and as surgical specimens in daily practice. Changes in incidence of oesophageal squamous cell carcinomas (such as a decrease in western countries) and in oesophageal and GOJ adenoca...
Contexts in source publication
Context 1
... lesion -oesoPhageal squamous DysPlasia (Fig. 1) Oesophageal squamous dysplasia (OSD) (also known as oesophageal squamous intra-epithelial neoplasia) is an unequivocal neoplastic alteration of the oesophageal squamous epithelium, without invasion. Squamous dysplasia can occur anywhere in the oesophagus and it is likely to follow the distribution of squamous cell carcinoma 1 . The ...
Context 2
... . Macroscopic and Microscopic description. Macroscopically, OSCC often presents as an ulcerative mass, especially when advanced. The most useful macroscopic classification is provided by Japan Esophageal Society 29 . Histology shows a typical, invasive squamous carcinoma with both vertical and horizontal growth beyond the basement membrane ( Fig. 1). Histological grading is based on the degree of cytological atypia, mitotic activity and presence of keratinization. A three-tiered system is commonly applied: -Grade 1 (well differentiated): shows enlarged cells with abundant eosinophilic cytoplasm and keratin pearl production. Cytological atypia is minimal and the mitotic rate low. ...
Similar publications
Barrett’s oesophagus (BO) is one of the most important complications of gastro-oesophageal reflux disease as it may progress to oesophageal adenocarcinoma. There is currently a rising incidence of BO. The pathogenesis of BO is not well-understood although genetic and environmental factors play significant roles. BO can be dysplastic or non-dysplast...
Citations
... EGJA, on the other hand, follows a neoplastic sequence in which gastroesophageal reflux leads to metaplastic modification of the squamous epithelium at the distal esophagus. Barrett's esophagus is the substitution of squamous epithelium with columnar mucosa, and the presence of intestinal metaplasia is associated with an increased risk of dysplasia (low grade and high grade) and invasive adenocarcinoma [14]. ...
... Following the approval by the FDA 5 and ESMO 6 of anti-HER2 and anti-PD-1 agents in combination with chemotherapy in the first-line setting for locally advanced unresectable and metastatic gastric/gastroesophageal cancer patients, the assessment of HER2 and PD-L1 in biopsy samples should be mandatory before the initiation of first-line systemic therapy [7][8][9] . The assessment of mismatch repair proteins (MMR) by immunohistochemistry (IHC) and Epstein-Barr Virus status by in situ hybridization is also recommended, according to tissue availability 10 . ...
PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint inhibitors. At present, PD-L1 is routinely assessed on biopsy samples of advanced gastroesophageal cancer patients before initiating first-line treatment. However, PD-L1 is still a suboptimal biomarker, due to changing cut-off values and scoring systems, interobserver and interlaboratory variability. This practical illustrated review discusses the range of staining patterns of PD-L1 and the potential pitfalls and challenges that can be encountered when evaluating PD-L1, focusing on gastric and gastroesophageal adenocarcinoma (G/GEA) and esophageal squamous cell carcinoma (ESCC).
... Intestinal-type gastric cancer and Barrett's adenocarcinoma develop through a multistep carcinogenetic cascade triggered primarily by longstanding inflammatory insults. The progressive phenotypic dedifferentiation which entails the progression from normal mucosa to intestinal metaplasia (Barrett's esophagus or atrophic gastritis with intestinalized glands) to dysplasia and invasive carcinoma underlies a progressive accumulation of genetic alterations [10,11]. Our group has already investigated the dysregulation of molecular biomarkers in gastroesophageal dysplastic lesions, including HER2 [12], PD-L1 [13], mismatch repair (MMR) status [13], and EBER [14]. ...
Gastric adenocarcinoma has recently been classified into several subtypes on the basis of molecular profiling, which has been successfully reproduced by immunohistochemistry (IHC) and in situ hybridization (ISH). A series of 73 gastroesophageal dysplastic lesions (37 gastric dysplasia and 36 Barrett dysplasia; 44 low-grade dysplasia and 29 high-grade dysplasia) was investigated for mismatch repair proteins, E-cadherin, p53, and EBER status, to reproduce The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) molecular clustering. Overall, the dysplastic lesions were classified as follows: according to TCGA classification, EBV, 0/73 (0%), MSI, 6/73 (8.2%), GS, 4/73 (5.5%), CIN, 63/73 (86.3%); according to ACRG molecular subtyping, MSI, 6/73 (8.2%), MSS/EMT, 4/73 (5.5%), MSS/TP53 ⁻ , 33/73 (45.2%), MSS/TP53 ⁺ , 30/73 (41.1%). A positive association was found between MSS/TP53 ⁻ and Barrett dysplasia ( p = 0.0004), between MSS/TP53 ⁺ and LG dysplasia ( p = 0.001) and between MSS/TP53 ⁺ and gastric dysplasia ( p = 0.0018). Gastroesophageal dysplastic lesions proved to be heterogenous in terms of TCGA/ACRG classes, but with a different distribution from that of cancers, with no EBV-positive cases, an increasing presence of mismatch repair deficiency from low grade to high grade lesions, and a prevalence of p53 aberrations in Barrett dysplasia. The present study further demonstrated that gastroesophageal dysplastic lesions may be characterized by alterations in predictive/prognostic biomarkers, and this should be considered in routine diagnostic.
... EE may lead to serious complications such as gastrointestinal bleeding or esophageal stenosis. On the other hand, BE is among the strongest known risk factors for esophageal adenocarcinoma, incidence of which has risen 6-fold over the last 40 years [8,9]. Esophageal cancer is the sixth most common cause of cancer-related deaths, with a 5-year survival rate of <20.0% ...
Background:
Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett's esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients.
Methods:
The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR).
Results:
The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs.
Conclusions:
Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.
... All cases with available tissue samples were re-evaluated by two gastrointestinal pathologists to assess the quality of samples for immunohistochemical analyses, to con-firm the primary tumor site and pathological characteristics [29,30]. The tissues were collected and processed similarly according to standard protocols, with formalin fixation time <48 h. ...
The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (n = 280) and GECs (n = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (p = 0.0035), positive EBV status (p = 0.002), high stage (III, IV) at diagnosis (p = 0.003), peritoneal involvement (p < 0.001) and lower incidence of liver metastases (p = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.
