AXL Promotes Metformin-Induced Apoptosis Through Mediation of Autophagy by Activating ROS-AMPK-ULK1 Signaling in Human Esophageal Adenocarcinoma.

AXL receptor tyrosine kinase promotes an invasive phenotype and chemotherapy resistance in esophageal adenocarcinoma (EAC). AXL has been implicated in the regulation of autophagy, but the underlying molecular mechanism remains poorly understood. Herein, we investigate the mechanistic role of AXL in autophagy as well as metformin-induced effects on the growth and survival of EAC. We demonstrate that AXL mediates autophagic flux through activation of AMPK-ULK1 signaling in a reactive oxygen species (ROS)-dependent mechanism by glucose starvation. AXL positively regulates basal cellular ROS levels without significantly affecting mitochondrial ROS production in EAC cells. Pharmacological inhibition of cellular ROS using Trolox abrogates glucose starvation-induced AMPK signaling and autophagy. We demonstrate that AXL expression is required for metformin-induced apoptosis in EAC cells in vitro. The apoptosis induction by metformin is markedly attenuated by inhibition of autophagy through genetic silencing of Beclin1 or ATG7 autophagy mediators, thereby confirming the requirement of intact autophagy for enhancing metformin-induced apoptosis in EAC cells. Our data indicate that metformin-induced autophagy displays a pro-apoptotic function in EAC cells. We show that the metformin-induced suppression of tumor growth in vivo is highly dependent on AXL expression in a tumor xenograft mouse model of EAC. We demonstrate that AXL promotes metformin-induced apoptosis through activation of autophagy in EAC. AXL may be a valuable biomarker to identify tumors that are sensitive to metformin. Therefore, AXL expression could inform the selection of patients for future clinical trials to evaluate the therapeutic efficacy of metformin in EAC.

Civatte Bodies in Pediatric Esophageal Biopsies: Does Lichen Esophagitis Pattern Occur in Children?

PURPOSE AND CONTEXT: Civatte bodies (CB) are associated with cutaneous and mucosal lichen planus in adults. They are a distinct feature of Lichen Esophagitis Pattern, which is not well described in children. We characterized clinicopathologic associations of archival esophageal CB at our Children's Hospital to determine whether lichen planus or Lichen Esophagitis Pattern occurs in children. METHOD: Pathology records were queried for pediatric esophageal biopsy diagnoses containing "CB," "apoptosis, "necrosis," or "dyskeratosis." Cases with concurrent eosinophilic/acute esophagitis were excluded. H&E slides and clinical reports were reviewed. KEY RESULTS: Biopsies with CB or similar were identified from 19 patients and had been termed "dyskeratotic cells" in 8 reports. Patients had variable age and presenting symptoms, male predominance (74%), and frequent clinical history of polypharmacy (47%), Crohn disease (42%), and/or celiac disease (21%). Civatte bodies were prominent in the distal esophagus (95%), as few isolated cells (63%), and with variable chronic inflammation (absent, pauci-inflammatory, and lichen planus-like in approximately one-third of cases each). CONCLUSIONS: We show that esophageal CB from pediatric patients are under-recognized and may have different features and implications compared to Lichen Esophagitis Pattern in adults. Recognition and documentation of pediatric esophageal CB is needed to understand their clinical significance.

Gastrointestinal Tract Injury by Yttrium-90 Appears Largely Restricted to Resin Microspheres But Can Occur Years After Embolization.

Radioembolization therapy utilizes yttrium-90 (Y90) impregnated resin (SIR-Spheres) or glass (TheraSpheres) microspheres to selectively target hepatic lesions via transarterial radioembolization. Occasional cases of gastrointestinal tract injury, secondary to nontargeted delivery of microspheres, have been reported, but large descriptive pathology series are lacking. We identified 20 cases of histologically confirmed mucosal injury associated with Y90 from 17 patients and assessed the corresponding clinical and pathologic sequelae. The mucosal biopsies were obtained from 1 to 88 months following Y90 therapy (median: 5 mo). Most cases were gastric (17, 85%), while the remaining were duodenal. Endoscopic ulceration was seen in the majority of cases (16, 80%), and mucosal erythema in the remaining 4. Histologically, a majority (19, 95%) of cases showed rounded, dark blue to purple microspheres measuring 4 to 30 µm, consistent with resin microspheres. A single case with glass microspheres demonstrated 26 µm translucent beads. Histologic evidence of ulceration was appreciated in 14 (70%) cases, and the microspheres were clearly intravascular in 6 (30%). A foreign body giant cell reaction to the microspheres was uncommon (3 cases, 15%). We additionally performed a retrospective review of all gastrointestinal tissue obtained postprocedure from 784 sequential patients treated with Y90 microspheres. Three patients (0.4%) demonstrated the presence of resin microspheres upon histologic examination. No cases involving glass-based Y90 were identified ( P =0.0078), despite the majority of patients having received glass radioembolization (630, 80%). This increased risk of secondary sphere dissemination is likely related to the increased number of particles required per activity for resin versus glass microspheres. We conclude that Y90 microspheres may be encountered in the gastrointestinal tract years after initial liver-targeted therapy and, when present, are often associated with mucosal ulceration. This finding is less likely to be encountered in patients who received Y90 radioembolization utilizing glass microspheres.

Secondary malignancy after urologic reconstruction procedures: a multi-institutional case series.

Urinary diversion and reconstructive urologic procedures are most often performed by incorporating various intestinal segments into the urinary tract. Although the risk of malignancy, among other complications, is well recognized and occurs most frequently after ureterosigmoidostomies and cystoplasties, data on the histopathologic and immunohistochemical characteristics of these tumors are scant. This study aims to evaluate the clinicopathological features of secondary tumors arising after urologic reconstruction procedures. Eleven cases were identified among five collaborating academic institutions. The average age was 51.7 years, and the M:F ratio was 8:3. Surgical procedures included 7 ileal conduits, 2 gastrocystoplasties, 1 augmentation cystoplasty not otherwise specified (NOS), and 1 Indiana pouch. Median time from reconstruction to malignancy was 36 years. Malignancy included adenocarcinoma in 10 patients (intestinal type in 6, gastric in 2, signet-ring cell in 1, undetermined type after neoadjuvant treatment in 1) and squamous cell carcinoma in 1. By immunohistochemistry, the adenocarcinomas were CK7 (45%), CK20 (89%), CK903 (78%), CDX2 (89%), SATB2 (67%), and beta-catenin (100%) positive. GATA-3 was negative in all cases. Pathologic stage was T1 (30%), T2 (40%), T3 (20%), and T4 (10%). Regional lymph node and distant metastasis were present in 60% and 20%, respectively. Treatment included multimodality therapy in most patients. On follow-up (mean, 27.4 months), 2 patients were dead (1 of disease), 3 were alive with disease, 4 were alive without disease, and 2 were lost to follow-up. Secondary malignancy arising within urologic reconstruction is rare, most frequently has adenocarcinoma morphology, presents late, and behaves aggressively.

Key histopathologic features in idiopathic noncirrhotic portal hypertension: an interobserver agreement study and proposal for diagnostic criteria.

Histologic features of idiopathic noncirrhotic portal hypertension (INCPH), loosely termed as obliterative portal venopathy (OPV), are heterogenous, often subtle, and overlap with other entities. To this date, no consensus histopathologic diagnostic criteria have been established for INCPH. For these reasons, rendering a reproducible consensus histologic diagnosis of OPV on a liver biopsy may often be challenging even for experienced hepatopathologists. We report herein a two-phase interobserver agreement study on the diagnosis of OPV and assessed the relative value of histologic features in 104 liver biopsies in distinguishing between INCPH and non-INCPH with the goal to obtain a consensus on specific practical diagnostic criteria. Six hepatopathologists blinded to clinical information and original pathologic diagnosis reviewed internet-based case study sets with high-resolution whole-slide images. The initial interobserver agreement on OPV was expectedly low, but significantly improved (moderate agreement in most categories) upon adopting a consensus view recognizing portal vein sclerosis as the only strong independent histologic predictor for INCPH, and that contrary to the conventional view, aberrant portal/periportal vessels does not significantly contribute to the positive assignment of OPV status. We propose a three-tiered classification with diagnostic criteria to facilitate the histologic assignment of OPV status for the evaluation of INCPH. Furthermore, we have validated the performance of the proposed criteria either based on histology alone or coupled with clinicopathologic correlation. This classification may aid in practical histologic assessment of liver biopsies with or without portal hypertension and help to improve diagnostic consistency and accuracy.

Co-overexpression of AXL and c-ABL predicts a poor prognosis in esophageal adenocarcinoma and promotes cancer cell survival.

Background: Esophageal adenocarcinoma (EAC) is highly aggressive and characterized by poor prognosis. AXL expression has been linked to Barrett's tumorigenesis and resistance to chemotherapy, which is associated with c-ABL intracellular localization. However, the molecular and functional relationship between AXL and c-ABL and the clinical significance of the co-expression of these proteins in EAC remain unclear. Methods: We used immunohistochemical analysis (IHC) on tissue microarrays containing human EAC samples (n=53) and normal esophageal tissues (n=11) in combination with corresponding deidentified clinicopathological information to evaluate the expression and the prognostic significance of AXL and c-ABL in EAC. The data were statistically analyzed using Kruskal-Wallis, the chi-square, the Fisher's exact, and Pearson tests. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate cancer patient survival. We used a serum deprivation EAC cell model to investigate the pro-survival function of AXL and c-ABL using cell viability, apoptosis, and lactate dehydrogenase activity assays. We performed in vitro assays, including Western blotting, quantitative real-time PCR, and translational chromatin immunoprecipitation (TrIP-Chip) to study the molecular relationship between AXL and c-ABL in EAC cells. Results: IHC analysis revealed that AXL and c-ABL were overexpressed in 55% and 66% of EAC samples, respectively, as compared to normal tissues. Co-overexpression of the two proteins was observed in 49% of EAC samples. The chi-square test indicated a significant association between AXL and c-ABL expression in the EAC samples (χ2 = 6.873, p = 0.032), and the expression of these proteins was significantly associated with EAC patient age (p < 0.001), tumor stage (p < 0.01), and lymph node status (p < 0.001). AXL and c-ABL protein expression data analysis exhibited an identical clinicopathological association profile. Additionally, we found a significant association between expression of AXL (χ2 = 16.7, p = 0.002) or c-ABL (χ2 = 13.4, p = 0.001) and survival of EAC patients. The Cox proportional hazards model and log rank test predicted a significant increase in mortality of patients with high expression of AXL [hazard ratio (HR): 2.86, 95% confidence interval (CI): 1.53 - 5.34, p = 0.003] or c-ABL [HR: 3.29, 95% CI: 1.35 - 8.03, p = 0.001] as compared to those patients with low expression of AXL or c-ABL proteins. Molecular investigations indicated that AXL positively regulates c-ABL protein expression through increased cap-dependent protein translation involving phosphorylation of EIF4E in EAC cells. Next, we investigated the functional relationship between AXL and c-ABL in EAC cells. We demonstrated that the pro-survival activity of AXL requires c-ABL expression in response to serum deprivation. Conclusion: This study highlights the importance of the co-overexpression of AXL and c-ABL proteins as a valuable prognostic biomarker and targeting these proteins could be an effective therapeutic approach in EAC or other solid tumors expressing high levels of AXL and c-ABL proteins.

PD-L1 Expression Patterns in Microsatellite Instability-High Intestinal Adenocarcinoma Subtypes.

OBJECTIVES: To investigate patterns of programmed death protein-1 (PD-L1) expression in microsatellite instability (MSI)-high intestinal carcinomas and correlate them with pathologic and molecular features. METHODS: One hundred and fifteen MSI-high and 41 microsatellite stable carcinomas were included. Tumor sections were immunohistochemically labeled for PD-L1. The results were correlated with histologic subtypes, MSI, and BRAF status. RESULTS: As expected, MSI status was associated with PD-L1 expression. Among 115 MSI-high tumors, PD-L1 expression was observed on tumor cells in 28 tumors and on tumor-associated inflammatory cells in 77 tumors. Medullary carcinoma demonstrated more frequent PD-L1 expression on tumor cells than mucinous and typical adenocarcinoma. PD-L1 expression was more frequent in medullary and typical adenocarcinoma than in mucinous adenocarcinoma based on combined positive scores. Tumors with more nucleotide shifts by PCR-based MSI testing were more likely to express PD-L1. CONCLUSIONS: Expression of PD-L1 is different among different histologic subtypes of MSI-high intestinal carcinomas.

Phase I study combining the aurora kinase a inhibitor alisertib with mFOLFOX in gastrointestinal cancer.

Overexpression and cellular mis-localization of aurora kinase A (AURKA) in gastrointestinal cancers results in chromosomal instability, activation of multiple oncogenic pathways, and inhibition of pro-apoptotic signaling. Inhibition of AURKA causes mitotic delays, severe chromosome congression, and activation of p53/p73 leading to cell death. Our preclinical data showed cooperative activity with the AURKA inhibitor alisertib and platinum agents in cell lines and xenografts, and suggested an optimal treatment window. Therefore, this study was designed to determine the maximum-tolerated dose (MTD) of alisertib in combination with modified FOLFOX (mFOLFOX), as this is a standard platinum-based therapy for gastrointestinal cancers. Standard 3 + 3 dose escalation was used, where the starting dose of alisertib was 10 mg twice daily (Days 1-3), with leucovorin (400 mg/m2) and oxaliplatin (85 mg/m2) on Day 2 followed by continuous 46-h 5-FU (2400 mg/m2) infusion on Days 2-4 in 14-day cycles. Fourteen patients with advanced gastrointestinal cancers were enrolled and two doses explored; two patients were not evaluable for dose-limiting toxicity (DLT) and replaced. Two patients experienced DLTs at 20 mg of alisertib (Grade 3 fatigue (n = 2); Grade 3 nausea, vomiting, dehydration with hospitalization (n = 1)). MTD was 10 mg alisertib with 85 mg/m2 oxaliplatin and 2400 mg/m2 5-FU. Most frequent toxicities were nausea (57%), diarrhea, fatigue, neuropathy, and vomiting (43%), and anorexia and anemia (36%); most were Grade 1-2. One patient with colorectal cancer had a partial response of 12 evaluable patients, and four patients had stable disease. Alisertib in combination with mFOLFOX did not demonstrate unexpected side effects, but the regimen was only tolerable at the lowest dose investigated.

Correction to: Phase I study combining the aurora kinase a inhibitor alisertib with mFOLFOX in gastrointestinal cancer.

The authors would like to note that the investigator affiliations have been corrected to reflect the actual affiliations of each author. The authors would also like to note an amendment to the first name of the second author. Nilo Azad was changed to reflect the full name of the author, which is Nilofer S. Azad as shown above. The original article has been corrected.

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone.

PD-1 inhibitor gastroenterocolitis: case series and appraisal of 'immunomodulatory gastroenterocolitis'.

AIMS: PD-1 inhibitors facilitate immune response against certain tumour types, including melanoma. These drugs have led to prolonged survival but can also result in autoimmune-type side effects, including gastrointestinal inflammation. The histopathological effects of this medication class have not been well studied. METHODS AND RESULTS: We identified 37 gastrointestinal tract biopsies from 20 patients taking a PD-1 or PD-L1 inhibitor and evaluated clinicopathological findings. Diarrhoea was the most common symptom, and endoscopic findings ranged from mild erythema to erosion/ulceration. Common histological findings included lamina propria expansion, villous blunting (if applicable), intra-epithelial neutrophils and increased crypt/gland apoptosis, although intra-epithelial lymphocytes were rarely prominent. A few cases showed crypt rupture with resultant histiocytic/granulomatous response. Most patients responded to drug cessation and/or steroids, but follow-up endoscopies were not performed. CONCLUSIONS: PD-1/PD-L1 inhibitors can cause gastritis, enteritis and colitis, similar to other immunomodulatory antibodies (such as CTLA-4 inhibitors and PI3Kδ inhibitors), but the histological findings vary somewhat among drug classes. Clinical history, lack of prominent intra-epithelial lymphocytes and crypt rupture may help to distinguish PD-1 inhibitor gastroenterocolitis from mimics, which include other medication effect, inflammatory bowel disease, graft-versus-host disease, cytomegalovirus infection and autoimmune enteropathy.

A phase I trial investigating pulsatile erlotinib in combination with gemcitabine and oxaliplatin in advanced biliary tract cancers.

Advanced biliary tract cancers (ABTC) are among the deadliest malignancies with limited treatment options after progression on standard-of-care chemotherapy, which includes gemcitabine (GEM) and oxaliplatin (OX). The epidermal growth factor receptor inhibitor erlotinib has been explored in ABTC with modest efficacy. Erlotinib given continuously may antagonize the action of chemotherapy against cycling tumor cells, but pulsatile dosing of erlotinib with chemotherapy may improve efficacy. The purpose of this study was to assess the safety of pulsatile erlotinib with GEMOX. This was a single-institution phase Ib study that enrolled adult patients with unresectable or metastatic biliary tract, pancreas, duodenal, or ampullary carcinomas that have not received any prior treatment for their disease. Dose escalation followed a standard 3 + 3 design, and dose-limiting toxicities (DLTs) were any treatment-related, first course non-hematologic grade ≥ 3 toxicity, except nausea/vomiting, or grade 4 hematologic toxicity. A dose expansion cohort in ABTC was treated at the MTD. Twenty-eight patients were enrolled and 4 dose levels were explored. The MTD was erlotinib 150 mg + GEM 800 mg/m2 + OX 85 mg/m2. DLTs were diarrhea and anemia. Most frequent toxicities were nausea (78 %), fatigue (71 %), neuropathy (68 %), and diarrhea (61 %), predominantly grade 1-2. In the ABTC patients, the objective response and disease control rates were 29 % and 94 %, respectively, and median overall survival was 18 months. Erlotinib plus GEMOX was well tolerated. Encouraging anti-tumor activity was seen as evidenced by a high disease control rate and longer median OS than standard chemotherapy in the patients with ABTC.

Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms include well-differentiated pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine carcinomas (NECs) with well-differentiated PanNETs accounting for most cases. Other pancreatic primaries and metastatic carcinomas from other sites can mimic pancreatic neuroendocrine neoplasms. Immunohistochemical studies can be used to aid in the differential diagnosis. However, no specific markers are available to differentiate PanNETs from NETs of other sites. Although NECs are uniformly deadly, PanNETs have variable prognosis. Morphology alone cannot predict the tumor behavior. Although some pathologic features are associated with an aggressive course, Ki67 is the only prognostic molecular marker routinely used in clinical practice.

A Comparative Clinicopathologic Study of Collagenous Gastritis in Children and Adults: The Same Disorder With Associated Immune-mediated Diseases.

Collagenous gastritis is a rare condition characterized by surface epithelial damage, subepithelial collagen deposition, and a lamina propria inflammatory infiltrate. Previous studies have proposed 2 clinicopathologic subtypes: (1) children (18 y of age or younger) presenting with severe anemia, nodular gastric mucosa, and isolated gastric disease; and (2) adults with chronic watery diarrhea that is associated with diffuse collagenous involvement of the gastrointestinal tract. However, notable exceptions exist. In fact, broad variability in clinical presentation, etiology, treatment and disease course has been reported. To better define the clinicopathologic features of collagenous gastritis, we have collected 10 pediatric and 21 adult cases and describe their clinical, endoscopic, pathologic, and follow-up findings. Both children and adults presented with similar clinical symptoms such as anemia (50%, 35%, respectively), epigastric/abdominal pain (50%, 45%), and diarrhea (40%, 55%). Concomitant immune disorders were identified in 2 (20%) children and 3 (14%) adults. Further, 7 of 17 (41%) adults were taking medications associated with other immune-related gastrointestinal diseases including olmesartan and antidepressants. Histologically, there were no differences between children and adults with collagenous gastritis in the location of gastric involvement, mean collagenous layer thickness, and prominence of eosinophils (P>0.05). Extragastric collagenous involvement was also seen with comparable frequencies in each cohort (44%, 59%). Follow-up information was available for 22 of 31 (71%) patients and ranged from 2 to 122 months (mean, 33.6 mo). Despite medical management in most cases, persistence of symptoms or collagenous gastritis on subsequent biopsies was seen in 100% of children and 82% of adults. Of note, treatment for 1 adult patient involved cessation of olmesartan resulting in resolution of both symptoms and subepithelial collagen deposition on subsequent biopsies. Contrary to prior reports, no clinicopathologic differences were identified among pediatric and adult patients with collagenous gastritis. Whereas collagenous gastritis remains an enigmatic condition, our findings suggest that immune abnormalities and medications, such as olmesartan, may be possible triggers. However, current treatment options have had limited success and, thus, highlight the need for improved therapeutic regimens.

Primary hepatic tumors with myxoid change: morphologically unique hepatic adenomas and hepatocellular carcinomas.

Mucin production in primary liver neoplasms is typically interpreted as evidence for biliary differentiation. However, we have observed benign and malignant liver tumors that have abundant extracellular myxoid/mucinous material, yet have only evidence of hepatocellular differentiation. To further characterize these unusual findings, 9 cases were identified and further studied. Four cases were hepatic adenomas, whereas 5 were hepatocellular carcinomas. Extracellular myxoid/mucinous material was diffuse in 7 cases and patchy in 2 cases. The extracellular myxoid/mucinous material was typically weakly mucicarmine positive (N=6) and Alcian blue positive (N=8). All tumors were well differentiated, and none had evidence for biliary differentiation by morphology or immunohistochemistry. The hepatic adenomas arose in nondiabetic and nonobese patients. Both the hepatic adenomas and the hepatocellular carcinomas were strongly and diffusely HepPar1 positive, CK19 negative, and showed loss of LFABP protein expression. These findings indicate that extracellular myxoid/mucinous material in isolation should not be interpreted as cholangiocarcinoma. Furthermore, the unique morphology, the clinical characteristics, and the immunophenotype results suggest that myxoid hepatic adenomas and hepatocellular carcinoma may be unique tumor variants.

Granular cell tumor of the ulnar nerve: MR neurography characterization.

The authors report an unusual case of ulnar neuropathy caused by granular cell tumor. The report describes the anatomic 3 Tesla MR Neurography and functional diffusion tensor findings of the case, which was subsequently confirmed on surgical excision and histopathology.

Upper GI tract lesions in familial adenomatous polyposis (FAP): enrichment of pyloric gland adenomas and other gastric and duodenal neoplasms.

Patients with familial adenomatous polyposis (FAP), an autosomal dominant cancer predisposition syndrome caused by mutations in the APC gene, develop neoplasms in both the upper and lower gastrointestinal (GI) tract. To clarify the upper GI tract lesions in FAP patients in a tertiary care setting, we reviewed specimens from 321 endoscopies in 66 patients with FAP. Tubular adenomas in the small bowel were the most common neoplasms (present in 89% of patients), although only 1 patient developed invasive carcinoma of the small bowel. Several types of gastric neoplasms were identified--65% of patients had at least 1 fundic gland polyp, and 23% of patients had at least 1 gastric foveolar-type gastric adenoma. Pyloric gland adenomas were also enriched, occurring in 6% of patients--this is a novel finding in FAP patients. Despite the high frequency of gastric neoplasms, only 1 patient developed carcinoma in the stomach. The very low frequency of carcinoma in these patients suggests that current screening procedures prevent the vast majority of upper GI tract carcinomas in patients with FAP, at least in the tertiary care setting.

Lichenoid esophagitis: clinicopathologic overlap with established esophageal lichen planus.

Lichen planus (LP) affects mucocutaneous surfaces and is characterized by intraepithelial and lamina propria lymphocytosis and squamous cell apoptosis (Civatte bodies). Lichen planus esophagitis (LPE) is underrecognized; concurrent cutaneous disease is present in some patients, but LPE alone is more common. We diagnose patients with characteristic pathologic findings of LPE and known correlation with skin disease or immunofluorescence (IF) results as LPE but use descriptive terminology ("lichenoid esophagitis pattern" [LEP]) when confirmation is unavailable. We reviewed clinicopathologic features of patients diagnosed at our institution with LPE or LEP. There were 88 specimens with LPE or LEP from 65 patients. Most patients were female. Seventeen patients had LPE confirmed by IF. Five patients had both esophageal (1 with IF) and skin LP. Strictures were a prominent presenting feature in LPE patients, with disease distribution more frequent in the upper and lower esophagus. Dysphagia was a common reason for endoscopy in LEP patients. Rheumatologic diseases are more common in patients with LPE compared with LEP. Viral hepatitides and human immunodeficiency virus (HIV) infections are associated with LEP. We defined polypharmacy as patients taking >3 medications; this finding was present in both LPE and LEP cohorts; however, this is a prominent feature in those with established LPE. Progression to dysplasia was noted in both cohorts. About 5% of LPE patients have tandem skin manifestations. LPE is more likely than LEP to arise in women, result in stricture formation, and be associated with rheumatologic disorders and polypharmacy, whereas LEP is associated with viral hepatitis and HIV. Both can progress to neoplasia. As the risk of stricture formation is high in patients with LPE, it is worth performing pertinent IF studies to confirm LPE, although knowledge of the clinical association of LEP with viral hepatitis, HIV, and use of multiple medications is of value in daily practice.