Spatial heterogeneity for APRIL production by eosinophils in the small intestine.

Eosinophils may reside in the lower intestine to play several homeostatic functions. Regulation of IgA+ plasma-cell (PC) homeostasis is one of these functions. Here, we assessed regulation of expression for a proliferation-inducing ligand (APRIL), a key factor from the TNF superfamily for PC homeostasis, in eosinophils from the lower intestine. We observed a strong heterogeneity, since duodenum eosinophils did not produce APRIL at all, whereas a large majority of eosinophils from the ileum and right colon produced it. This was evidenced both in the human and mouse adult systems. At these places, the human data showed that eosinophils were the only cellular sources of APRIL. The number of IgA+ PCs did not vary along the lower intestine, but ileum and right colon IgA+ PC steady-state numbers significantly diminished in APRIL-deficient mice. Use of blood cells from healthy donors demonstrated that APRIL expression in eosinophils is inducible by bacterial products. Use of germ-free and antibiotics-treated mice confirmed the dependency on bacteria for APRIL production by eosinophils from the lower intestine. Taken together, our study shows that APRIL expression by eosinophils is spatially regulated in the lower intestine with a consequence on the APRIL dependency for IgA+ PC homeostasis.

FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm.

Myoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term "myoepithelioma-like" tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

Supraspinatus Intramuscular Calcified Hematoma or Necrosis Associated with Tendon Tear.

Introduction. Rotator cuff intramuscular calcification is a rare condition usually caused by heterotopic ossification and myositis ossificans. Case Presentation. We describe a patient with voluminous calcified mass entrapped in supraspinatus muscle associated with corresponding tendon tear. Histological examination corresponded to a calcified hematoma or necrosis. Patient was surgically managed with open excision of the calcified hematoma and rotator cuff arthroscopic repair. At 6 months, supraspinatus muscle was healed, and functional outcome was good. Discussion and Conclusion. We hypothesized that supraspinatus intramuscular calcified hematoma was responsible for mechanical stress on the tendon. This association has never been described.

Standardized terminology and nomenclature for pancreatobiliary cytology: The Papanicolaou Society of Cytopathology Guidelines.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) biopsy, techniques of EUS-FNA, terminology and nomenclature of pancreatobiliary disease, ancillary testing and post-biopsy treatment and management. All documents are based on the expertise of the authors, a review of the literature, discussion of the draft document at several national and international meetings over an 18 month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology web site [www.papsociety.org]. This document selectively presents the results of these discussions and focuses on a proposed standardized terminology scheme for pancreatobiliary specimens that correlate cytological diagnosis with biological behavior and increasingly conservative patient management of surveillance only. The proposed terminology scheme recommends a six-tiered system: Non-diagnostic, negative, atypical, neoplastic [benign or other], suspicious and positive. Unique to this scheme is the "neoplastic" category separated into "benign" (serous cystadenoma) or "other" (premalignant mucinous cysts, neuroendocrine tumors and solid-pseudopapillary neoplasms (SPNs)). The positive or malignant category is reserved for high-grade, aggressive malignancies including ductal adenocarcinoma, acinar cell carcinoma, poorly differentiated neuroendocrine carcinomas, pancreatoblastoma, lymphoma and metastases. Interpretation categories do not have to be used. Some pathology laboratory information systems require an interpretation category, which places the cytological diagnosis into a general category. This proposed scheme provides terminology that standardizes the category of the various diseases of the pancreas, some of which are difficult to diagnose specifically by cytology. In addition, this terminology scheme attempts to provide maximum flexibility for patient management, which has become increasingly conservative for some neoplasms.

Standardized terminology and nomenclature for pancreatobiliary cytology: the Papanicolaou Society of Cytopathology guidelines.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy, techniques of EUS-FNA, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and postbiopsy treatment and management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18-month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology web site (www.papsociety.org). This document selectively presents the results of these discussions and focuses on a proposed standardized terminology scheme for pancreatobiliary specimens that correlate cytological diagnosis with biological behavior and increasingly conservative patient management of surveillance only. The proposed terminology scheme recommends a six-tiered system: Nondiagnostic, Negative, Atypical, Neoplastic (benign or other), Suspicious and Positive. Unique to this scheme is the "Neoplastic" category separated into "benign" (serous cystadenoma), or "Other" (premalignant mucinous cysts, neuroendocrine tumors, and solid-pseudopapillary neoplasms). The positive or malignant category is reserved for high-grade, aggressive malignancies including ductal adenocarcinoma, acinar cell carcinoma, poorly differentiated neuroendocrine carcinomas, pancreatoblastoma, lymphoma, and metastases. Interpretation categories do not have to be used. Some pathology laboratory information systems require an interpretation category, which places the cytological diagnosis into a general category. This proposed scheme provides terminology that standardizes the category of the various diseases of the pancreas, some of which are difficult to diagnose specifically by cytology. In addition, this terminology scheme attempts to provide maximum flexibility for patient management, which has become increasingly conservative for some neoplasms.

Grading epithelial atypia in endoscopic ultrasound-guided fine-needle aspiration of intraductal papillary mucinous neoplasms: an international interobserver concordance study.

BACKGROUND: Preoperative cytological analysis of cyst fluid from intraductal papillary mucinous neoplasms (IPMN) contributes to risk stratification for malignancy. To the authors' knowledge, agreement among pathologists in grading epithelial atypia in IPMN cyst fluids has not been studied to date. METHODS: Blinded to the histological grade, 4 observers independently graded 60 cell groups from endoscopic ultrasound-guided fine-needle aspiration samples of 24 IPMNs of various grades as either 0 (nonlesional), 1 (low-grade dysplasia), 2 (intermediate-grade dysplasia [IGD]), 3 (high-grade dysplasia), or 4 (invasive adenocarcinoma). The percentage of agreement and the kappa (k) coefficient were calculated for these 5 tiers and a reduced 2-tier grouping (low-grade [LG] [0-1 and 0-2] vs high-grade [HG] [2-4 and 3-4]). Agreement between the 2 most experienced reviewers established a consensus diagnosis that was compared with the histological grade. RESULTS: Among the 4 reviewers there was poor agreement using a 5-tiered system and fair agreement with the 2-tiered system. LG and HG grouping of IGD did not appear to greatly affect agreement, with 54% agreement for grouping 0 to 2 and 3 to 4 (k = 0.45) and 52% agreement for grouping 0 to 1 and 2 to 4 (k = 0.44). The 2 most experienced reviewers had 87% agreement for the 0 to 2 and 3 to 4 grouping (k = 0.74) and 88% for the 0 to 1 and 2 to 4 grouping (k = 0.71). HG atypia on cytology with IGD grouped as LG yielded a sensitivity of 82%, with a specificity of 70% for detecting a cyst with HG morphology. CONCLUSIONS: Grading cellular atypia in cyst fluids requires experience, which results in very good interobserver agreement and good correlation with histology using a 2-tiered LG and HG grading system and IGD classified as LG.

Common bile duct adenocarcinoma in a patient with situs inversus totalis: report of a rare case.

BACKGROUND: Situs inversus totalis represents an unusual anomaly characterized by a mirror-image transposition of the abdominal and thoracic viscera. It often occurs concomitantly with other disorders that make difficult diagnosis and management of abdominal pathology. The relationship between situs inversus totalis and cancer remains unclear. CASE PRESENTATION: We describe a 33-year old Guinean man with situs inversus totalis who presented with obstructive jaundice. Imaging and endoscopic modalities demonstrated a mass of distal common bile duct which biopsy identified an adenocarcinoma. The patient was successfully treated by cephalic pancreaticoduodenectomy followed by adjuvant chemoradiation and he is doing well without recurrence 8 months after surgery. CONCLUSION: The occurrence of bile duct adenocarcinoma in patient with situs inversus totalis accounts as a rare coincidence. In this setting, when the tumor is resectable, surgical management should be considered without contraindication and must be preceded by a careful preoperative staging.

Association between lymphoepithelial cysts of the pancreas and HIV infection.

BACKGROUND & AIMS: To report the association of lymphoepithelial cysts (LEC) of the pancreas with Human Immunodeficiency Virus (HIV) infection. An association between LEC and HIV infection is already established in the parotid gland (PG). METHODS: Report of the first two cases of LEC of the pancreas associated with HIV infection and comparison of the clinical and histopathological aspects of LECs of the pancreas and of the PG. RESULTS: LECs of the pancreas were discovered by CT imaging in 2 patients with a history of HIV infection. Notably, LEC completely resolved in one patient after initiation of antiretroviral therapy. CONCLUSION: This is the first report of an association of LEC of the pancreas and HIV infection. In the presence of LEC of the pancreas, we propose a systematic screening for HIV infection and associated lesions in the PG. Antiretroviral therapy should be initiated in untreated patients. Surgery should be reserved for symptomatic patients in whom medical therapy has failed.

Cytological analysis of small branch-duct intraductal papillary mucinous neoplasms provides a more accurate risk assessment of malignancy than symptoms.

OBJECTIVES: The Sendai guidelines for management of patients with clinically suspected intraductal papillary mucinous neoplasms (IPMN) recommend resection of cysts > 30 mm, a dilated main pancreatic duct (MPD) > 6 mm, a mural nodule (MN), symptoms or positive cytology. Although sensitive, asymptomatic cysts, nonspecific symptoms, and a high threshold for positive cytology limit the specificity of the guidelines. We have assessed the value of cytology relative to symptom for predicting malignancy in IPMNs without high-risk imaging features. MATERIALS AND METHODS: We retrospectively reviewed the clinical, radiological, and cytological data of 31 small branch-duct IPMNs without a MN. The cytological presence of high-grade atypical epithelial cells (HGA) was considered true positive, with a corresponding histology of high-grade dysplasia or invasive carcinoma. The performance of cytology versus symptoms was evaluated by calculating the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: The sensitivity (0.80), specificity (0.85), and accuracy (0.84) of HGA were higher than the corresponding performance characteristics of symptoms (0.60, 0.45, and 0.48, respectively). The NPV of no HGA on cytology was > 95%. CONCLUSIONS: Cytology is a better predictor of malignancy than symptoms, for the conservative management of small branch-duct IPMNs. Cytology contributes to a highly accurate triple negative test for malignancy in small IPMN: No dilated MPD, MN or HGA.

Cytology adds value to imaging studies for risk assessment of malignancy in pancreatic mucinous cysts.

OBJECTIVE: Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. BACKGROUND: The Sendai Guidelines list symptoms, cyst size >30 mm, dilated main pancreatic duct (MPD) >6 mm, mural nodule (MN) and "positive" cytology as high risk stigmata for malignancy warranting surgical triage. METHODS: We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) [≥high-grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated. RESULTS: Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size >30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (≤30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39%-44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features. CONCLUSIONS: Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN.

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis.

BACKGROUND: Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear. METHODS: We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model. RESULTS: 43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001). CONCLUSIONS: In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.

Acinar cell carcinoma: a possible diagnosis in patients without intrapancreatic tumour.

BACKGROUND: Acinar cell carcinomas of the pancreas are rare neoplasms. Usually diagnosed at an advanced stage, in general they are large solid pancreatic tumours with an average size of more than 10 cm. AIMS AND RESULTS: We report 3 cases of acinar cell carcinomas involving the peripancreatic lymph nodes, the liver hilum and the colon respectively, without clinical or pathological evidence of pancreatic tumours. These highly cellular neoplasms showed a predominantly acinar cell differentiation intermingled with a ductal component, with intracellular or extracellular mucin production by at least 25% of tumour cells. In addition, one case showed endocrine differentiation. Diffuse immunoreactivity for acinar enzymes trypsin and chymotrypsin was present in all cases. CONCLUSION: The occurrence of acinar cell carcinomas outside the pancreas underlines the notion that acinar cell carcinomas may originate in extrapancreatic sites and probably develop from heterotopic or metaplastic pancreatic foci present along the biliary tract.

Gastric hyperplastic polyps: a heterogeneous clinicopathologic group including a distinct subset best categorized as mucosal prolapse polyp.

BACKGROUND: Gastric hyperplastic polyps are the second most common subtype of gastric polyps. There has been an ongoing debate about their precise diagnostic criteria and etiological associations. MATERIALS AND METHODS: A total of 208 gastric polyps that were originally diagnosed as hyperplastic polyps in our department during an 8-year period were reviewed using recently emphasized diagnostic criteria, and their clinicopathologic associations were explored. RESULTS: Only 41 cases were confirmed as hyperplastic polyps, whereas 103 cases (49%) were reclassified as polypoid foveolar hyperplasia, and 64 cases (31%) were diagnosed as gastric mucosal prolapse polyps. Gastric mucosal prolapse polyps were distinguished by basal glandular elements, hypertrophic muscle fibers ascending perpendicularly from the muscularis mucosae, and by thick-walled blood vessels. This hitherto undescribed polyp is more commonly sessile than hyperplastic polyps (P=0.0452) and is found more often in the antropyloric region (P: 0.0053). Only 20.6% of hyperplastic polyps were associated with Helicobacter pylori infection. CONCLUSIONS: Our findings highlight that gastric polypoid lesions that have morphologic similarities may be related to various mechanisms, including inflammatory and prolapse processes. The predominantly antral location of gastric mucosal prolapse polyps, a zone of pronounced peristalsis, suggests that mucosal prolapse plays a role in the development of these common polyps. Evaluation of the prevalence and clinical associations of these distinctive polyps awaits further studies.

Role of proteomics to differentiate between benign and potentially malignant pancreatic cysts.

Pancreatic cystic neoplasms represent 10-15% of primary cystic masses of the pancreas. While pancreatic cysts are detected with an increasing frequency due to the use of advanced imaging modalities in clinical practice, the diagnosis of pancreatic cystic neoplasms remains unsatisfactory because available diagnostic techniques proved not sensitive enough so far. This study was designed to characterize the proteomic pattern of pancreatic cyst fluids obtained from various cystic lesions. Cyst fluids were collected by direct puncture during open surgery to avoid any possible contamination from other tissues. CEA, CA-19-9, and amylase concentrations were measured using specific immunoassays. After immunodepletion and fractionation by SDS-PAGE, proteins were digested and analyzed by LC-MS/MS. Specific histological lesions were found to be associated with distinct protein patterns. Interestingly, some of these proteins have been proposed as biomarkers of pancreatic cancer. Immunoblots allowed for verifying the differential expression in specific cyst fluids of two selected proteins, olfactomedin-4 and mucin-18. Finally, immunohistochemistry was performed to correlate these data with the expression pattern of olfactomedin-4 and mucin-18 in pancreatic cyst tissues. Results from this study indicate that proteomic analysis of cyst fluid could provide reliable candidates for developing new biomarkers for the preoperative management of malignant and premalignant pancreatic cysts.

Islet autotransplantation after extended pancreatectomy for focal benign disease of the pancreas.

BACKGROUND: Extended pancreatectomy is associated with the risk of surgical diabetes. Islet autotransplantation is successful in the prevention of diabetes after pancreas resection for chronic pancreatitis (CP), with insulin independence rates of 50% at 1 year. The aim of the present study is to demonstrate the safety and efficiency of islet autotransplantation after extended left pancreatectomy for benign disease. METHODS: Between 1992 and 2009, 25 patients underwent extended pancreatectomy and islet autotransplantation for benign disease. Of these, 15 patients were operated for focal lesions located at the neck of the pancreas (14 benign tumors and 1 traumatic pancreatic section), the remainder being CP cases. After unequivocal diagnosis of benignity, the rest of the pancreas was processed and infused into the portal vein. Metabolic results were analyzed and isolation results were compared with those obtained from patients with CP or donors with brain death (DBD). RESULTS: There was no mortality and a low morbidity (Streptococcus mitis bacteremia in 1 patient), no portal thrombosis or pancreatic fistula occurred. Median follow-up was 90 months. Actuarial patient survival was 100% at 10 years. Actuarial insulin independence was 94% at 10 years. All patients had positive basal and stimulated C-peptide levels and normal HbA1c. Mean islet yields were 5455 IEQ/gram vs. 1457 in CP (P=0.001) and 3738 in DBD (P=0.003). CONCLUSIONS: Islet autotransplantation after extensive pancreatic resection for benign disease is a safe and successful procedure. Islet yields after isolation, which are equivalent to the live donor situation, are significantly better than those from DBD donors.

[Endoscopic resection of digestive tumors: indications, quality criteria and results]. / Résection endoscopique des tumeurs digestives: indications, critères de qualité et résultats.

Endoscopic resection of digestive tumors: indications, quality criteria and results In the past decade, two developments have changed the approach to superficial digestive tumors: 1) new endoscopic techniques allow "en bloc" resection of superficial tumors with almost no limit in tumor diameter and 2) the risk of lymph node metastases is better stratified (e.g., in the colon, the risk of lymph node metastasis is negligible for superficial malignant invasion of the submucosa). Endoscopic submucosal dissection (ESD) allows "en bloc" resection of large laterally-spreading tumors, in contrast with prior resection techniques (endoscopic mucosal resection - EMR) that required piecemeal resection for large tumors. As a result, relapse rate is lower with ESD compared to EMR. Pathological examination is also more reliable with "en bloc" specimens; it must precisely assess resection margins and the depth of malignant invasion.

[Drug-induced injury in the gastrointestinal tract: a clinico-pathological review]. / Atteintes médicamenteuses du tractus gastro-intestinal: une revue clinico-pathologique.

Many drugs are known to have adverse effects on the gastrointestinal tract. The consequences can range from asymptomatic histological lesions in the gastrointestinal mucosa to fatal complications such as haemorrhage or perforation. On the biopsies (or on surgical specimens), there is a limited number of injury pattern that should suggest drug-induced pathology. They are mostly non specific (ex: ulcer). However, some drugs may induce pathognomonic histological lesions. For this reason, the diagnosis of a drug-induced gastrointestinal pathology depends on a clinicopathological correlation and implies a good communication between the pathologist and the clinician. In this review, we focus on the most common and well-described drug-related clinico-pathological conditions of the gastrointestinal tract using an organ and lesion based approach.

High-grade atypical epithelial cells in pancreatic mucinous cysts are a more accurate predictor of malignancy than "positive" cytology.

BACKGROUND: The Sendai guidelines for risk assessment of malignancy in patients with mucinous cysts lists "positive" cytology as a high-risk feature. In the current study, the authors hypothesized that a cytological threshold of high-grade atypical epithelial cells (AEC) is a more accurate predictor of malignancy. METHODS: The clinical, radiological, and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas were reviewed. Cytology slides were blindly reviewed and cells were classified as benign, AEC, or malignant. On histology, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (high-grade dysplasia/carcinoma in situ and invasive carcinoma). RESULTS: There were 92 patients with an intraductal papillary mucinous neoplasm (IPMN) and 20 with a mucinous cystic neoplasm; 39 were malignant and 73 were benign (42 with low-grade dysplasia and 31 with moderate dysplasia). Only 28% (11 of 39) of the malignant cysts were cytologically malignant with a sensitivity of 29%, a specificity of 100%, and an accuracy of 75%. AEC detected 17 additional cancers (44% of all malignant cysts; 16% more than detected on the basis of "positive" cytology). By using AEC as a surgical triage threshold, the sensitivity was 72%, the specificity was 85%, and the accuracy was 80%, with similar values for small (≤ 3 cm) branch duct IPMN. Nine of 73 (12%) benign cysts were identified with AEC, 4 of which had moderate dysplasia. AEC had a positive predictive value of 87% for the detection of a mucinous cyst with moderate dysplasia or worse. CONCLUSIONS: AEC are a more accurate predictor of malignancy than "positive" cytology in aspirates of pancreatic mucinous cysts, including small branch duct IPMN. AEC warrant a "suspicious" interpretation for appropriate surgical triage.

Do eosinophil numbers differentiate eosinophilic esophagitis from gastroesophageal reflux disease?

CONTEXT: Although the healthy esophageal mucosa contains no eosinophils, eosinophilic infiltration is observed in 2 major clinicopathologic settings: gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EE). The prevalence of EE is increasing in many countries, and this increase seems only partly to be due to a better awareness of the pathology, following the relatively recent description of EE. Gastroesophageal reflux disease and EE represent 2 entities that do not respond to the same treatment modalities and, thus, need to be distinguished. However, diagnostic criteria of EE have been defined arbitrarily, and the more recent articles tend to prove that the overlap with GERD is probably greater than initially believed, leading the authors to advise strict exclusion of GERD before considering the diagnosis of EE. OBJECTIVES: To provide pathologists with the currently proposed histologic criteria of GERD and EE, to stress the need to combine these criteria with clinical data and endoscopic findings, and to outline the remaining controversies. DATA SOURCES: This review is based on selected articles identified by a PubMed (US National Library of Medicine, Bethesda, Maryland) search of the literature in English for GERD and EE, a recent review by the American Gastroenterological Association (Bethesda), the Proceedings of the First International Gastrointestinal Eosinophil Research Symposium, and the authors' experience. CONCLUSION: Proper identification of the etiology of eosinophilic infiltration of the esophagus allows accurate medical or surgical treatment and follow-up. Eosinophilic esophagitis and GERD diagnoses require integration of the histologic findings with the clinical and endoscopic data.

Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis.

Biliary intraepithelial neoplasia (BilIN), a preneoplastic condition that may precede invasive intrahepatic cholangiocarcinoma (ICC), has been compared to pancreatic intraepithelial neoplasia (PanIN), a precursor lesion of pancreatic carcinoma. Biliary tract carcinoma development and progression is associated with several gene alterations, but BilIN lesions have yet to be studied in detail by molecular techniques. We describe a case of extensive intrahepatic biliary dysplasia, with lesions ranging from BilIN-1 to BilIN-3 lesions, and multifocal microscopic ICC in hepatitis C virus (HCV)- and alcohol-related cirrhosis. The small ICC foci had remained undetected prior to transplantation. Fluorescence in situ hybridization (FISH) analysis was performed on three foci of BilIN-3 lesions and on three microinvasive ICC foci with a combination of three FISH probes directed against genes frequently altered in pancreatic and biliary tract carcinomas. FISH analysis revealed a CDKNA2 heterozygous deletion in one BilIN-3 focus, and in one non-contiguous ICC focus, although the deletion was just above the chosen threshold. No deletions were detected in the genomic regions encoding TP53 and SMAD4. This report documents for the first time the development of multifocal ICC in the setting of extensive biliary dysplasia in a patient with three risk factors, HCV infection, alcohol abuse, and cirrhosis, and suggests heterogeneous carcinogenesis in ICC and possible involvement of the CDKNA2 gene.