Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.

In Fig. 4e of this Article, the labels for 'Control' and 'HFD' were reversed ('Control' should have been labelled blue rather than purple, and 'HFD' should have been labelled purple rather than blue). Similarly, in Fig. 4f of this Article, the labels for 'V' and 'GW' were reversed ('V' should have been labelled blue rather than purple, and 'GW' should have been labelled purple instead of blue). The original figure has been corrected online.

Esophageal adenocarcinoma heterogeneity in clinicopathology and prognosis: A single center longitudinal study of 146 cases over a 20-year period.

Recent genomic studies suggest that esophageal adenocarcinoma (EAC) is not homogeneous and can be divided into true (tEAC) and probable (pEAC) groups. We compared clinicopathologic and prognostic features between the two groups of EAC. Based on endoscopic, radiologic, surgical, and pathologic reports, tumors with epicenters beyond 2 cm of the gastroesophageal junction (GEJ) were assigned to the tEAC group (N = 63), while epicenters within 2 cm of, but not crossing the GEJ, were allocated to the pEAC group (N = 83). All 146 consecutive patients were male (age: median 70 years, range: 51-88) and White-predominant (98.6 %). There was no significant difference in gastroesophageal reflux disease, obesity, comorbidity, and the prevalence of Barrett's esophagus, and cases diagnosed during endoscopic surveillance. However, compared to the pEAC group, the tEAC group had significantly more cases with hiatal hernia (P = 0.003); their tumors were significantly smaller in size (P = 0.007), more frequently with tubular/papillary adenocarcinoma (P = 0.001), had fewer cases with poorly cohesive carcinoma (P = 0.018), and demonstrated better prognosis in stage I disease (P = 0.012); 5-year overall survival (34.9 months) was significantly longer (versus 16.8 months in pEACs) (P = 0.043). Compared to the patients without resection, the patients treated with endoscopic or surgical resection showed significantly better outcomes, irrespective of stages. We concluded that EACs were heterogeneous with two distinct tEAC and pEAC groups in clinicopathology and prognosis; resection remained the better option for improved outcomes. CONDENSED ABSTRACT: Esophageal adenocarcinoma can be divided into true or probable groups with distinct clinicopathology and better prognosis in the former than in the latter. we showed that resection remained the better option for improved outcomes.

High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.

Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-δ) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-δ recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-δ-dependent manner. Notably, HFD- and agonist-activated PPAR-δ signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-δ signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-δ activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.

Cutaneous mucinosis in a patient taking ustekinumab for palmoplantar psoriasis.

Discrete papular lichen myxedematosus (DPLM), asubset of localized lichen myxedematosus, is a rarecutaneous mucinosis of unknown etiology. We reporta case of a 57-year-old woman with palmoplantarpsoriasis who developed DPLM 8 weeks after addingustekinumab to a long-term course of methotrexate.The patient had previously failed 2 prior tumor necrosisfactor (TNF) inhibitors, adalimumab and etanercept.This case demonstrates an association between TNFinhibitor and ustekinumab use in a psoriasis patientand localized lichen myxedematosus for the secondtime in the literature. The presented case is of interestbecause of the rare diagnosis of DPLM, especially inassociation with the start of the anti-IL 12/23 agentustekinumab. The appearance of DPLM in this settingsuggests a possible etiology for the disease.

Tissue IgG4-positive plasma cells in inflammatory bowel disease: a study of 88 treatment-naive biopsies of inflammatory bowel disease.

The distinction of Crohn's disease from ulcerative colitis is based on clinical, endoscopic, radiological, and histological findings, a paradigm that remains unchanged despite the advent of new understanding of the immunological and genetic basis of inflammatory bowel disease. There is a strong correlation between inflammatory bowel disease, predominantly ulcerative colitis, and autoimmune pancreatitis. We hypothesized that colonic biopsies from patients with inflammatory bowel disease would demonstrate increased numbers of IgG4-positive plasma cells and that this elevation might be restricted to ulcerative colitis. We examined a cohort of 78 cases of inflammatory bowel disease: 50 ulcerative colitis and 38 Crohn's disease. We identified treatment-naive biopsies. Additionally, four cases of inflammatory bowel disease associated with autoimmune pancreatitis and 15 cases of lymphocytic/collagenous colitis were also identified. Immunohistochemical stains for IgG4 were performed. Biopsies from patients with ulcerative colitis showed significantly higher numbers of IgG4-bearing plasma cells than those with Crohn's disease (mean IgG4 counts per high-power field (hpf) 9.8 vs 2.8, P=0.001). Samples from 19 (38%) ulcerative colitis patients had IgG4 counts >10/hpf, compared with only two (5%) patients with Crohn's disease; the sensitivity and specificity of a cutoff at 10 IgG4-positive plasma cells per hpf was 38 and 95%, respectively. Among individuals <18 years, there were no statistically differences in the IgG4 counts between the two subforms of inflammatory bowel disease. Among adult patients, a cutoff of 5 IgG4+ plasma cells distinguished ulcerative colitis from Crohn's disease with a sensitivity of 53% and specificity of 83%. In comparison to inflammatory bowel disease, patients with lymphocytic/collagenous colitis showed significantly lower numbers of IgG4-positive plasma cells (P=0.0001). Ulcerative colitis with pancolitis showed higher numbers of IgG4-bearing plasma cells (mean IgG4 12.8 vs 5.8 per hpf; P=0.09). An immunohistochemical stain for IgG4 may aid in making the distinction between ulcerative colitis and Crohn's disease (with exclusion of the pediatric cases), albeit with a relatively low sensitivity. This study also provides additional support to the hypothesis that a subset of ulcerative colitis cases is associated with a Th2 response.

Prognostic factors in clinicopathology of oesophagogastric adenocarcinoma: a single-centre longitudinal study of 347 cases over a 20-year period.

Oesophagogastric adenocarcinoma (EGA) includes oesophageal (EA), gastro-oesophageal junctional (GEJA), and gastric (GA) adenocarcinomas. The prognostic values of clinicopathological factors in these tumours remain obscure, especially for GEJA that has been inconsistently classified and staged. We studied the prognosis of EGA patients among the three geographic groups in 347 consecutive patients with a median age of 70 years (range 47-94). All patients were male, and 97.1% were white. Based on tumour epicentre location, EGAs were sub-grouped into EA (over 2 cm above the GEJ; n=3, 18.1%), GEJA (within 2 cm above and 3 cm below the GEJ; n=231, 66.6%), and GA (over 3 cm below the GEJ; n=53, 15.3%). We found that the median overall survival (OS) was the longest in EA (62.9 months), compared to GEJA (33.4), and GA (38.1) (p<0.001). Significant risk factors for OS included tumour location (p=0.018), size (p<0.001), differentiation (p<0.001), adenocarcinoma subtype (p<0.001), and TNM stage (p<0.001). Independent risk factors for OS comprised low-grade papillary adenocarcinoma [odds ratio (OR) 0.449, 95% confidence interval (CI) 0.214-0.944, p<0.05), mixed adenocarcinoma (OR 1.531, 95% CI 1.056-2.218, p<0.05), adenosquamous carcinoma (OR 2.206, 95% CI 1.087-4.475, p<0.05), N stage (OR 1.505, 95% CI 1.043-2.171, p<0.05), and M stage (OR 10.036, 95% CI 2.519-39.993, p=0.001)]. EGA was further divided into low-risk (common well-moderately differentiated tubular and low-grade papillary adenocarcinomas) and high-risk (uncommon adenocarcinoma subtypes, adenosquamous carcinoma) subgroups. In this grouping, the median OS was significantly longer in the low-risk (83 months) than in the high-risk (10 months) subgroups (p<0.001). In conclusion, the prognosis of EGA patients was significantly better in EA than in GEJA or GA and could be stratified into low and high-risk subgroups with significantly different outcomes.

Peutz-Jeghers syndrome: a critical look at colonic Peutz-Jeghers polyps.

Peutz-Jeghers syndrome is an autosomal dominant condition characterized by gastrointestinal hamartomatous polyps. The pathologic identification of a Peutz-Jeghers polyp is integral to the diagnosis of this syndrome that often remains undiagnosed until after these polyps are identified. Histologically, Peutz-Jeghers polyps are characterized by a distinctive arborization of smooth muscle within the lamina propria. Colonic Peutz-Jeghers polyps, however, may mimic mucosal prolapse polyps or virtually any colonic polyp that undergoes prolapse. In this paper, we explore the morphological features of colonic Peutz-Jeghers polyps and the diagnostic challenges associated with these polyps. Colonic polyps from patients with Peutz-Jeghers syndrome were identified (n=34). The control cohort, included mucosal prolapse polyps (n=5), hyperplastic polyps (n=10) and tubular adenomas with prolapse (n=9), ganglioneuromatous polyps (n=2) and juvenile polyps (n=14). Intramucosal smooth muscle fibers were identified in all classes of polyps. Twenty-three of the 34 colonic Peutz-Jeghers polyps were characterized by lobulated clusters of colonic crypts. On immunohistochemistry, desmin-positive smooth muscle fibers were seen surrounding these lobules. This lobular organization of the crypts was not identified in mucosal prolapse polyps and hyperplastic polyps or tubular adenomas with prolapse; only one of the 14 juvenile polyps showed this pattern of reactivity on a desmin stain. Our data suggests that the histologic hallmark of colonic Peutz-Jeghers polyps is the lobular organization of the crypts, and that an arborizing pattern of smooth muscle proliferation is neither sensitive nor a specific marker of colonic Peutz-Jeghers polyps. The presence of desmin-positive smooth muscle fibers surrounding the lobules is a helpful diagnostic feature of colonic Peutz-Jeghers polyps, and facilitates the distinction of these polyps from non-Peutz-Jeghers polyps with prolapse-like changes.

Autoimmune pancreatitis: a guide for the histopathologist.

Autoimmune pancreatitis (AIP) is a distinct form of pancreatitis with a characteristic histological appearance. Clinically and radiologically, many of these patients show enlargement of pancreas and pancreatic duct/bile duct strictures, thus mimicking pancreatic carcinoma. There are 2 forms of the disease: (1) type 1 AIP characterized by storiform type fibrosis, obliterative phlebitis, and elevated numbers of immunoglobulin G4 (IgG4) positive plasma cells, typically >50 per high-power field, and, (2) type 2 AIP characterized by granulocytic epithelial lesions and only occasional IgG4-bearing plasma cells, typically <10 per high-power field. The type 1 variant of AIP is the pancreatic manifestation of IgG4-related disease, thus both pancreatic and extrapancreatic recurrences are common. The type 2 variant is unrelated to IgG4-related disease, and disease recurrence is uncommon. Both forms of the disease show a swift response to immunosuppressive therapy. This review highlights the clinical and pathological differences between the 2 forms of AIP. We also review guidelines that assist in distinguishing AIP from its closest mimic, pancreatic adenocarcinoma.

Coherent confocal light scattering spectroscopic microscopy evaluates cancer progression and aggressiveness in live cells and tissue.

The observation of biological structures in live cells beyond the diffraction limit with super-resolution fluorescence microscopy is limited by the ability of fluorescence probes to permeate live cells and the effect of these probes, which are often toxic, on cellular behavior. Here we present a coherent confocal light scattering and absorption spectroscopic microscopy that for the first time enables the use of large numerical aperture optics to characterize structures in live cells down to 10 nm spatial scales, well beyond the diffraction limit. Not only does this new capability allow high resolution microscopy with light scattering contrast, but it can also be used with almost any light scattering spectroscopic application which employs lenses. We demonstrate that the coherent light scattering contrast based technique allows continuous temporal tracking of the transition from non-cancerous to an early cancerous state in live cells, without exogenous markers. We also use the technique to sense differences in the aggressiveness of cancer in live cells and for label free identification of different grades of cancer in resected tumor tissues.

Fine needle aspiration diagnosis of carotid body tumor in a case of multiple paragangliomas presenting with facial palsy: a case report.

BACKGROUND: Carotid body tumors (CBTs) constitute the most common extraadrenal paragangliomas. Many lesions diagnosed as CBTs by fine needle aspiration (FNA) cytology are clinically unsuspected. The main differential diagnosis is a thyroid neoplasm. The location of the mass in the lateral neck with prolonged history, hemorrhagic FNA and cytologic features resembling the endocrine neoplasm help in arriving at a suggestive diagnosis of paraganglioma. CASE: A 32-year-old male presented with left-sided facial palsy and swelling in the left side of the neck of 8 months' duration. The FNA sample was hemorrhagic and showed loosely arranged groups and acini formed by round to oval cells. A diagnosis of CBT was suggested. It was supplemented by additional noninvasive methods, such as ultrasonography of the neck region with color Doppler, computed tomography and magnetic resonance imaging of the brain, which also revealed a neoplasm suggestive of carotid body tumor in the right side of the neck and neoplastic lesion in the left cerebellopontine angle, suggestive of paraganglioma. CONCLUSION: FNA, with the other noninvasive radiologic investigations, plays an important role in the diagnosis of CBT. We present this case of multiple paragangliomas for its unusual presentation and FNA diagnosis.

Mucinous cystic neoplasms of the pancreas: high-resolution cross-sectional imaging features with clinico-pathologic correlation.

PURPOSE: To describe the high-resolution cross-sectional (MDCT/MRI) features of mucinous cystic neoplasms (MCN) of the pancreas with clinico-pathologic correlation; to identify imaging predictors of high-grade dysplasia/carcinoma; and to estimate MCN growth rate. MATERIALS AND METHODS: Thirty-two women (mean age: 46; range, 25-79 years) with resected MCN who underwent preoperative MDCT (n = 20) or MRI (n = 12) examinations over a 14-year period were included. Two radiologists examined retrospectively in consensus the following MDCT/MRI features: MCN location, size/volume, presence of capsule and thickness of the capsule, and presence of mural nodules, enhancing septations, calcifications, chronic pancreatitis, and main pancreatic duct dilation. Imaging features were correlated with clinical symptoms, biochemistry results, and histopathologic features. A univariate model was analyzed for the prediction of high-grade dysplasia/carcinoma. Preoperative MCN growth rate was assessed using a subset of patients with more than one imaging study available (n = 6). RESULTS: Twenty-five (78%) patients presented with symptoms and 8 (25%) patients had abnormal serum biochemical values. Mean MCN maximum dimensions were 48 × 45 × 45 mm with a mean volume of 169 mL. MCN were located in the tail (n = 18), body (n = 10), neck (n = 2), and (head = 2); 30 (93.5%) MCN were encapsulated, 3 (9%) had calcifications, 4 (12%) showed enhancing nodules, 9 (28%) had enhancing septations, and 5 (15%) had main pancreatic duct dilation. Associated chronic pancreatitis was observed in 4 (12%) patients. The only predictors for high-grade dysplasia/carcinoma were MCN size and volume. Using a cut-off size greater than 8.5 cm, the specificity and sensitivity for high-grade dysplasia/carcinoma were 97 and 60%, respectively (p = 0.003; OR 81, 95% CI 3.9-1655.8). Mean MCN growth rate was estimated at 4.2 mm/year with a doubling time of 8.23 years. CONCLUSION: MCN size (> 8.5 cm) and volume are the only features on MDCT/MR imaging that correlate with high-grade dysplasia/carcinoma. The average growth rate for MCNs is slow at approximately 4 mm per year.

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy.

Pancreatic cancers are usually detected at an advanced stage and have poor prognosis. About one fifth of these arise from pancreatic cystic lesions. Yet not all lesions are precancerous, and imaging tools lack adequate accuracy for distinguishing precancerous from benign cysts. Therefore, decisions on surgical resection usually rely on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Unfortunately, cyst fluid often contains few cells, and fluid chemical analysis lacks accuracy, resulting in dire consequences, including unnecessary pancreatic surgery for benign cysts and the development of cancer. Here, we report an optical spectroscopic technique, based on a spatial gating fibre-optic probe, that predicts the malignant potential of pancreatic cystic lesions during routine diagnostic EUS-FNA procedures. In a double-blind prospective study in 25 patients, with 14 cysts measured in vivo and 13 postoperatively, the technique achieved an overall accuracy of 95%, with a 95%confidence interval of 78-99%, in cysts with definitive diagnosis.

Difficult Diagnostic Problems in Pancreatobiliary Neoplasia.

CONTEXT: Many common diagnostic dilemmas are encountered in pancreatobiliary pathology, frequently resulting in uncertainty on behalf of the pathologist and referral for a second opinion. OBJECTIVES: To review 4 common diagnostic dilemmas encountered in the practice of pancreatobiliary pathology: (1) pancreatic ductal adenocarcinoma versus chronic pancreatitis; (2) pancreatic ductal carcinoma versus adenocarcinomas arising in the ampulla and intrapancreatic common bile duct; (3) the distinction of uncommon intraductal neoplasms--intraductal oncocytic papillary neoplasm, intraductal tubulopapillary neoplasm, and intraductal acinar cell carcinoma; and (4) intrahepatic cholangiocarcinoma versus metastatic carcinoma. DATA SOURCES: A review of pertinent literature, along with the authors' personal experience, based on institutional and consultation materials. CONCLUSIONS: Important diagnostic features for a few challenging problems in pancreatobiliary pathology are reviewed. Careful study of the microscopic features along with awareness of differential diagnoses and diagnostic pitfalls generally allows distinction of these entities. We also highlight established and novel ancillary studies that help to arrive at an accurate diagnosis.

A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma.

PURPOSE: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS AND MATERIALS: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. RESULTS: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). CONCLUSIONS: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS(G12D) status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

Rethinking Ormond's disease: "idiopathic" retroperitoneal fibrosis in the era of IgG4-related disease.

Idiopathic retroperitoneal fibrosis (RPF) is a periaortic sclerotic disease that encases adjacent retroperitoneal structures, particularly the ureters. A subset of idiopathic RPF cases can be associated with IgG4-related disease, but the frequency of this association is not clear. We selected 23 cases of idiopathic RPF and identified IgG4-related RPF cases based on the presence of IgG4+ plasma cells in the tissue, using an IgG4/IgG ratio cutoff of >40%. We then compared the IgG4-related RPF patients and the non-IgG4-related RPF patients in terms of both the presence of histopathologic features typical of IgG4-related disease and the simultaneous occurrence (or history) of other organ manifestations typical of IgG4-related disease. The IgG4-related RPF and non-IgG4-related RPF groups were also analyzed in terms of clinical, laboratory, and radiologic features and treatment review. We identified 13 cases of IgG4-related RPF (57% of the total cohort). The distinguishing features of IgG4-related RPF were histopathologic and extra-organ manifestations of IgG4-related disease. The IgG4-related RPF patients were statistically more likely than non-IgG4-related RPF patients to have retroperitoneal biopsies showing lymphoplasmacytic infiltrate (p = 0.006), storiform fibrosis (p = 0.006), or tissue eosinophilia (p = 0.0002). Demographics of the 2 groups, including a middle-aged, male predominance (mean age, 58 yr; 73% male), were similar. IgG4-related disease accounts for a substantial percentage of patients with "idiopathic" RPF. Histopathologic features such as storiform fibrosis, obliterative phlebitis, and tissue eosinophilia are critical to identifying this disease association. Extraretroperitoneal manifestations of IgG4-related disease are also often present among patients with IgG4-related RPF. Elevated IgG4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic.

IgG4-related disease and hypertrophic pachymeningitis.

Hypertrophic pachymeningitis (HP) is an inflammatory condition in which the dura mater of the cranium or spine becomes thickened, leading to symptoms that result from mass effect, nerve compression, or vascular compromise. The differential diagnosis of HP includes immune-mediated conditions such as rheumatoid arthritis and vasculitis, malignancies, and infections. Many times, no diagnosis is reached; in such cases, the disease has been described as idiopathic HP. IgG4-related disease (IgG4-RD) is a recently described inflammatory condition known to cause tumefactive lesions at myriad anatomical locations. Both IgG4-RD and idiopathic HP share similar demographics, histopathology, and natural history. We hypothesized that IgG4-RD is a common cause of idiopathic HP.To investigate this hypothesis, we identified all pathology specimens diagnosed as noninfectious HP during 25 years at our institution. Fourteen cases had stained slides and paraffin blocks to permit review of the original hematoxylin and eosin stained slides as well as immunostaining of cell blocks. Recently published consensus guidelines describing characteristic histopathology and the necessary quantity of IgG4+ plasma cell infiltrate were used to diagnose IgG4-RD.Four cases (66.6%) that had been regarded previously as representing idiopathic HP were diagnosed as IgG4-RD; of all the reviewed cases, IgG4-RD represented 29% of cases. Of the remaining cases, 3 cases were associated with granulomatosis with polyangiitis (GPA), 2 with lymphoma, and 1 each with rheumatoid arthritis, giant cell arteritis, and sarcoidosis. Two of the cases could not be diagnosed more precisely and were classified as undifferentiated HP. Clinical history, serologic tests, cerebrospinal fluid studies, and radiology alone could not identify the cause of HP. Rather, biopsy with histopathology and immunostaining was necessary to reach an accurate diagnosis. Significant IgG4+ plasma cell infiltrates were observed in rheumatoid arthritis, granulomatosis with polyangiitis, and lymphoma, underscoring the importance of histopathology in making the diagnosis of IgG4-RD.This case series demonstrates that IgG4-RD may be the most common etiology of noninfectious HP and highlights the necessity of biopsy for accurate diagnosis.

Does autoimmune pancreatitis increase the risk of pancreatic carcinoma?: a retrospective analysis of pancreatic resections.

OBJECTIVES: To estimate the risk of malignancy in autoimmune pancreatitis (AIP). METHODS: We examined resected pancreata to compare the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP and 30 cases of chronic pancreatitis not otherwise specified (CP-NOS). We also reviewed a cohort of 84 AIP cases. RESULTS: The mean age of the AIP cohort (57 years) was significantly higher than that of the cohort of CP-NOS (47 years) (P = 0.01). Twenty-three cases (82%) of AIP showed PanIN, and 7 cases (25%) showed grade 2 PanIN. Grade 3 PanIN was identified in one case of AIP. There was no statistically significant difference in the number of cases with high-grade PanIN lesions between the cases of type 1 as opposed to type 2 AIP. In comparison to CP-NOS, a comparable percentage of patients with AIP had PanIN (82% of AIP cases vs 63% of CP-NOS cases) (P = NS) and PanIN 2 (25% AIP vs 20% CP-NOS) (P = NS). Of the 84 AIP cases at our institution (mean follow-up, 49 months), 2 cases of pancreatic carcinoma were identified 6 and 10 years after the diagnoses of AIP. CONCLUSIONS: These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.