Immature squamous metaplasia of esophageal glands associated with squamous cell carcinoma.

Background: Esophageal immature squamous metaplasia is hardly reported in the literature. This entity can, however, be misinterpreted as high grade dysplasia or invasive squamous cell carcinoma and hence represent a potential pitfall. Case presentation: Histopathological examination of a superficial esophageal lesion removed by endoscopic submucosal dissection revealed a squamous cell carcinoma associated with immature squamous cell metaplasia arising from esophageal glands. Immunohistochemical stainings allowed to distinguish malignant from metaplastic cells. Conclusions: Immunohistochemistry for Ber-EP4 is helpful in making the distinction between esophageal squamous cell carcinoma and immature squamous metaplasia. This can avoid overstaging and overtreatment, especially in early esophageal cancer.

Polypoid colon mucosa in a leukemia patient.

A woman, followed for chronic myeloid leukaemia, presented for a routine examination. Her medical history was marked by recurrent Helicobacter pylori gastritis and polymyalgica rheumatica. She was under dasatinib and hormone replacement therapy. At clinical examination, she complained about digestive disorders with altered bowel habits. Biology, including leucocyte count, remained normal. A colonoscopy was performed. Endoscopic examination revealed a colonic mucosa covered by multiple tiny nodular lesions (<5mm) from the hepatic angle to the sigmoid and with an abnormal pattern of vascularisation (Fig. 1). Staged biopsies were taken. Microscopic examination revealed discrete achi-tectural distortions. The stroma contained a mixed inflammatory infiltrate composed of neutrophils, eosinophils and lymphocytes. Immunohistochemistry for CD3, CD5, CD20 and CD79 did not bring arguments for a lymphoma. There were no malignant or dysplastic cells. (Fig. 2). What is your diagnosis?

Isolated oesophageal Crohn's disease mimicking oesophageal carcinoma treated by Merendino procedure.

Oesophageal involvement is a very rare presentation of Crohn's disease. It can occur as an isolated mass causing dysphagia and can be mistaken for malignancy. Here, we report a case of a 75-year-old woman presenting with dysphagia and weight loss. Gastroscopy showed an ulcerating mass, and her barium swallow showed a bird beak appearance at the level of the gastro-oesophageal junction (GEJ). Repetitive biopsies were inconclusive. Fluorodeoxyglucose-positron emission tomography showed high glucose uptake (standardised uptake value: 10.2) at the level of the GEJ. Endoscopic ultrasound classified the lesion as uT3N1. Step-by-step surgical exploration revealed an oesophageal mass. A frozen section examination showed an absence of malignancy and the presence of inflammatory tissue. A partial oesophagogastrostomy was performed, and reconstruction was achieved by a Merendino procedure. Definitive histopathological examination revealed isolated oesophageal Crohn's disease.

Accuracy and other quality indicators of solid pancreatic mass endoscopic ultrasound-guided fine needle aspiration and biopsy in two academic endoscopy centers.

BACKGROUND AND AIMS: Endoscopic ultrasound fine-needle aspiration/biopsy (EUS-FNA/FNB) is highly accurate, but discrepancies between cytological and surgical diagnoses are still observed. We aimed to determine its accuracy and monitor quality indicators in our facilities. PATIENTS AND METHODS: We performed a retrospective review of all cases of pancreatic solid lesions evaluated by EUS-FNA/FNB, between July 2015 and June 2018, in two centers. Cytological and surgical findings were categorized into five groups: benign, malignant, suspect of malignancy, undetermined and insufficient for diagnosis. Final diagnosis was based on surgical diagnosis and, in patients who did not undergo surgery, on clinical outcome after 6 months follow-up. RESULTS: Altogether, 142 patients were included. FNA was the preferred tissue acquisition method (88%), with a predilection for the FNA 22G needle (57%). Cytology was insufficient for diagnosis in 2 cases, therefore a full diagnostic sample was available in 98.6% of the patients (>90%, ESGE target). Fifty-five (38.7%) patients underwent surgery. In term of cancer diagnosis, comparison with final surgical pathology (n=55) revealed 89% true positives, 5.5% true negatives, 3.6% false positives and 1.8% false negatives. When combining surgical diagnosis and clinical outcomes together, EUS-guided sampling sensitivity was 97.4% (92.5-99.5), specificity was 92.3% (74.9-99.1), positive predictive value was 98.2% (93.6- 99.5), negative predictive value was 88.9% (72.3-96.1) and accuracy was 96.4% (91.9-98.8). Post-procedural acute pancreatitis was reported in 2 patients (1.4%). CONCLUSIONS: These results reveal a performance for diagnostic tissue sampling well above the ESGE proposed target standard. Also, the uncommon high specificity illustrates the determining role of the pathologist's final interpretation and diagnosis.

Guidelines for an optimal management of a malignant colorectal polyp. What is essential in a pathology report ?

Colorectal cancer (CRC) has become the most common malignancy in our country. Routine screening colonoscopy is on the rise. With the recent advances in endoscopic treatment, many T1 colorectal carcinomas are now found and their percentage amenable to endoscopic resection has increased. Endoscopists and pathologists dealing with the steadily increasing number of excised colorectal polyps have to collaborate closely to optimize patient care. Therapeutic management of patients after endoscopic resection is based on precise histological criteria that determine the risk of metastasis and the need for complementary surgery. This paper summarizes the procedures for the macroscopic management of endoscopic excisions and presents the identified risk factors which should be included in a standardized pathology report.

Benign, premalignant and malignant pancreatic cystic lesions: the pathology landscape.

Pancreatic cystic lesions are being increasingly detected in last years. Pancreatic cysts can be classified grossly into pseudocysts and true cysts. In the true cysts group, it is important to distinguish mucinous from non-mucinous cysts because the former are considered being premalignant lesions. In this article the major types of pancreatic cysts are reviewed, with emphasis on the histopathological aspects. Molecular markers in the cyst fluid are being increasingly studied in recent years ; the clinical utility of such biomarkers should be addressed in future studies.

Pancreatic adenocarcinoma: general histological overview.

In Belgium, approximately 1100 new cases of pancreatic ductal adenocarcinoma are diagnosed each year. Although in the last twenty years several advances have been registered in the field of pancreatic pathology, few therapies are efficacious, and it remains one of the deadliest of all cancers. Histological variants with a somewhat different prognosis have been recognised, and precursor lesions identified. This article reviews the histological aspects of ductal adenocarcinoma, its variants and the precursor lesions. Study and knowledge of these precursor lesions offers the best hope for treating pancreatic cancer before an incurable invasive tumour develops.

Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.

BACKGROUND: Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC). METHODS: Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at the time of surgery. Staining in the epithelial compartment was quantitatively evaluated using image analysis, and results were related to clinical variables. Antibody specificity was tested using small-interfering RNA transfection in hTERT-immortalised myofibroblasts. RESULTS: Varying degrees of cytoplasmic FHL2 expression by neoplastic epithelial cells were detectable in all cases. Higher FHL2 expression in the epithelial compartment was an independent adverse prognostic factor. Multivariate Cox analysis shows that expression in the tumour invasion front (P<0.001) as well as in the centre of the tumour (P<0.001) was associated with metachronous metastases independently of the clinicopathological variables; expression in the tumour invasion front was also associated with overall survival independently of the clinicopathological variables (P<0.01). CONCLUSION: Higher FHL2 expression is involved in CRC progression and correlates with the development of metachronous metastases and overall survival, suggesting that FHL2 is an independent adverse prognostic indicator for CRC.

Hepatic expression of CCL2 in alcoholic liver disease is associated with disease severity and neutrophil infiltrates.

Serum levels and liver expression of CCL2 are increased in patients with alcoholic hepatitis (AH). In an experimental model of alcoholic liver disease (ALD), CCL2 was implicated in proinflammatory cytokines activation and hepatic lipid metabolism, but its role in human disease is currently unknown. In a large cohort of ALD patients, we analysed plasma levels and liver expression of CCL2 and their association with liver disease severity and histological lesions. We also studied the relationship between -2518 A > G CCL2 and CCR2 190 A/G polymorphisms and severity of ALD. We show that CCL2 plasma levels are increased in ALD patients compared with healthy subjects. AH patients had significantly higher plasma levels and hepatic expression of CCL2 than patients without AH. Plasma levels and hepatic expression of CCL2 were associated with disease severity. CCL2 liver expression was correlated with neutrophil infiltrate and interleukin (IL)-8 expression, but not with steatosis. Moreover, there were more G-allele carriers of -2518 A > G CCL2 polymorphism in severe AH patients than in other ALD patients. Our results demonstrate that CCL2 is increased in ALD, particularly in severe forms, and suggest a role for CCL2 in the pathogenesis of ALD via neutrophil recruitment.

Molecular changes in pancreatic cancer: implications for molecular targeting therapy.

Pancreatic ductal adenocarcinoma has a high mortality rate, which is generally related to the initial diagnosis coming at late stage disease combined with a lack of effective treatment options. Gemcitabine has been the most commonly used drug over the past decade and is still the cornerstone of therapy in adjuvant and metastatic settings. Intrinsic or acquired resistance of tumours to gemcitabine is, however, a major clinical problem. New therapeutic strategies are urgently needed whereas we also need to identify new prognostic and predictive biomarkers. This article focuses on gemcitabine resistance, on the role of chemokines and chemokine receptors in pancreatic carcinoma initiation and progression, and on stellate cells as partners in crime with neoplastic epithelial cells.

Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolising enzyme that induces immune tolerance by modulating T-cell responses. Carcinomas may create an immunosuppressive state via IDO1 expression. Here we examined a possible contribution of IDO1 on this phenomenon and investigated whether IDO1 has prognostic value in colorectal cancer (CRC). METHODS: IDO1 expression was investigated by quantitative PCR and western blotting in three colon cancer cell lines, in basal state and after interferon (IFN)-γ stimulation. Semi-quantitative immunohistochemistry was used to evaluate IDO1 expression in 265 pT1-4N0-2Mx-staged CRCs. Results were related to clinical variables and correlated with amounts of CD3(+) and CD8(+) T lymphocytes, which were quantitatively evaluated using image analysis. RESULTS: In vitro expression of IDO1 depended on IFN-γ stimulation. Higher IDO1 expression at the tumour invasion front was an independent adverse prognostic factor in pT1-4N1Mx-staged CRC. It was associated with overall survival (P=0.001) and with metachronous metastases (P=0.018). IDO1 expression was not associated with the presence of CD3(+) or CD8(+) T lymphocytes. CONCLUSION: Higher IDO1 expression at the tumour invasion front is involved in CRC progression and correlates with impaired clinical outcome, suggesting that IDO1 is an independent prognostic indicator for CRC.