Identification of a Subset of Stage I Colorectal Cancer Patients With High Recurrence Risk.

BACKGROUND: A challenge in early-stage colorectal cancer (CRC) is identifying biomarkers that predict an increased risk for recurrence. A potential clinically adaptable biomarker is focal adhesion kinase (FAK), a tyrosine kinase that promotes invasion and metastasis. METHODS: An initial, single-institution, 298-patient cohort with all stages of CRC and long-term follow-up was assessed for FAK with tissue microarrays using immunohistochemistry. FAK expression was scored and dichotomized into high and low. Subsequently, a validation cohort of 517 early-stage CRCs from a separate institution was evaluated. All statistical tests were 2-sided. RESULTS: FAK overexpression did not correlate with any known histologic feature and was an early event in CRC, increasing from normal colon to stage I, and stage I to II, but not different at higher stages. High FAK was associated with decreased 10-year recurrence-free survival (RFS) among stage I patients (70.2% for high FAK vs 94.1% for low, P = .02), but not among higher stages in the initial cohort. The same finding was seen in the validation cohort (73.1% for high FAK vs 93.1% for low, P = .004). Multivariable survival analysis for stage I patients showed only two statistically significant factors predicting RFS: FAK (hazard ratio = 5.27, 95% confidence interval = 1.81 to 15.33, P = .002) and perineural invasion (hazard ratio = 7.38, 95% confidence interval = 1.01 to 53.96, P = .049). FAK was the only statistically significant factor in multivariable analysis across RFS, overall, and disease-specific survivals. CONCLUSIONS: High FAK expression identified a subset of stage I CRC patients with high incidence of recurrence and reduced survival, suggesting that FAK has important prognostic value. These patients would immediately benefit from more rigorous surveillance protocols for recurrent disease.

Impact of a deep learning assistant on the histopathologic classification of liver cancer.

Artificial intelligence (AI) algorithms continue to rival human performance on a variety of clinical tasks, while their actual impact on human diagnosticians, when incorporated into clinical workflows, remains relatively unexplored. In this study, we developed a deep learning-based assistant to help pathologists differentiate between two subtypes of primary liver cancer, hepatocellular carcinoma and cholangiocarcinoma, on hematoxylin and eosin-stained whole-slide images (WSI), and evaluated its effect on the diagnostic performance of 11 pathologists with varying levels of expertise. Our model achieved accuracies of 0.885 on a validation set of 26 WSI, and 0.842 on an independent test set of 80 WSI. Although use of the assistant did not change the mean accuracy of the 11 pathologists (p = 0.184, OR = 1.281), it significantly improved the accuracy (p = 0.045, OR = 1.499) of a subset of nine pathologists who fell within well-defined experience levels (GI subspecialists, non-GI subspecialists, and trainees). In the assisted state, model accuracy significantly impacted the diagnostic decisions of all 11 pathologists. As expected, when the model's prediction was correct, assistance significantly improved accuracy (p = 0.000, OR = 4.289), whereas when the model's prediction was incorrect, assistance significantly decreased accuracy (p = 0.000, OR = 0.253), with both effects holding across all pathologist experience levels and case difficulty levels. Our results highlight the challenges of translating AI models into the clinical setting, and emphasize the importance of taking into account potential unintended negative consequences of model assistance when designing and testing medical AI-assistance tools.

Primary pancreatic leiomyosarcoma with metastasis to the liver diagnosed by endoscopic ultrasound-guided fine needle aspiration and fine needle biopsy: A Case Report and Review of Literature.

Primary pancreatic leiomyosarcomas are rare tumors of the pancreas that are usually diagnosed after resection or by biopsy. One case in the literature has utilized endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology. We report a second case of a primary pancreatic leiomyosarcoma that yielded diagnostic material on EUS-FNA cytology. A 72-year-old female presented with 3-4 months of abdominal pain. A CT scan showed a large heterogeneous, lobulated pancreatic head and uncinate mass and multiple hypoattenuating liver lesions. An EUS-FNA was performed on one of the liver lesions with a 25-gauge needle, yielding an adequate sample with lesional cells. The initial read was a spindle cell neoplasm. A subsequent endoscopic ultrasound-guided fine needle biopsy with a 22-gauge needle was performed on the pancreatic head mass to rule out two primaries and to provide tissue for a mitotic index in the case of gastrointestinal tumor. Both the cell block of the EUS-FNA and the core biopsy were equally cellular and showed interlacing spindle cells that stained positive for SMA and negative for DOG-1, CD 117, and CD34. In addition, the core biopsy of the pancreas stained positive for Desmin. A diagnosis of a primary pancreatic leiomyosarcoma was made and the patient was started on systemic chemotherapy. Primary pancreatic leiomyosarcomas are rare pancreatic tumors that may yield diagnostic material by EUS-FNA with a 25-gauge needle. Diagn. Cytopathol. 2016;44:1070-1073. © 2016 Wiley Periodicals, Inc.

Black Endobronchial Ultrasound.

The infrequent bronchoscopic finding of black airway pigmentation due to a variety of causes has been labeled as "Black Bronchoscopy." Black bronchioalveolar lavage has been sometimes described in tobacco, marijuana, and crack cocaine smokers. To add to this interesting panorama of bronchoscopic findings, we describe cases of black endobronchial ultrasound-guided transbronchial needle aspirates due to metastatic melanoma and anthracotic lymph nodes.

Targeting myeloid cells in the tumor microenvironment enhances vaccine efficacy in murine epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages, and is associated with a high relapse rate. Patients in remission are ideal candidates for immunotherapy aimed at cure or prolonging disease-free periods. However, immunosuppressive pathways in the tumor microenvironment are obstacles to durable anti-tumor immunity. In a metastatic syngeneic mouse model of EOC, immunosuppressive macrophages and myeloid-derived suppressor cells (MDSCs) accumulate in the local tumor environment. In addition, resident peritoneal macrophages from non-tumor-bearing mice were highly immunosuppressive, abrogating stimulated T cell proliferation in a cell contact-dependent manner. Immunization with microparticles containing TLR9 and NOD-2 ligands (MIS416) significantly prolonged survival in tumor-bearing mice. The strategy of MIS416 immunization followed by anti-CD11b administration further delayed tumor progression, thereby establishing the proof of principle that myeloid depletion can enhance vaccine efficacy. In patients with advanced EOC, ascites analysis showed substantial heterogeneity in the relative proportions of myeloid subsets and their immunosuppressive properties. Together, these findings point to immunosuppressive myeloid cells in the EOC microenvironment as targets to enhance vaccination. Further studies of myeloid cell accumulation and functional phenotypes in the EOC microenvironment may identify patients who are likely to benefit from vaccination combined with approaches that deplete tumor-associated myeloid cells.

Cytologic mimics of non-Hodgkin lymphoma in the head and neck.

Non-lymphoid small round blue cell tumors of the head and neck are particularly difficult to diagnose when metastatic to a lymph node. The cytopathologist or surgical pathologist evaluating these lesions has to be aware of the various non-hematopoetic neoplasms that present in the head and neck area that can mimic non-Hodgkin lymphoma. Presented here are the various lesions commonly seen which needs to be entertained depending on where in the head and neck the lesion is located. More recently, a plethora of HPV related head and neck tumors has been described and these lesions add to the mix in this challenging milieu of cases.

Pancreatic hepatoid carcinoma: a rare form of pancreatic neoplasm.

Primary pancreatic hepatoid carcinoma (PHC) is extremely rare, resembling hepatocellular carcinoma (HCC) in terms of morphology and immunohistochemical features. Hepatoid carcinoma can present in other organs, most noticeably in the stomach. PHC is present in two forms either a pure form like HCC or admixed with other histologic tumor components characteristic of the underlying primary site (endocrine tumors, ductal, or acinar adenocarcinomas). Here, we report a 69-year-old male patient with distal pancreatic mass incidentally found during a CT scan workup for a pulmonary nodule suspicious for metastatic prostate adenocarcinoma. We described the clinical, cytological, and histological finding and conducted a literature review.

Leiomyosarcoma of the pulmonary artery diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration.

Leiomyosarcoma of the pulmonary vasculature is an extremely rare condition that has not been previously diagnosed by endobronchial ultrasound (EBUS) bronchoscopy. We present the case of a 43-year-old white male with a history of leiomyosarcoma who was diagnosed with pulmonary embolism 2 years ago. As the filling defects on follow-up chest computed tomography continued to worsen despite anticoagulation, EBUS-guided transbronchial needle aspiration (EBUS-TBNA) of the right pulmonary artery lesion was safely and successfully performed. Cytopathological examination revealed the "thrombus" to be metastatic leiomyosarcoma. In experienced hands, and carefully selected cases, EBUS-TBNA seems to be a safe and effective in diagnosing thoracic endovascular lesions.

High focal adhesion kinase expression in breast carcinoma is associated with lymphovascular invasion and triple-negative phenotype.

BACKGROUND: Focal adhesion Kinase (FAK) is a nonreceptor protein tyrosine kinase that is overexpressed in tumors and plays a significant role in tumor survival and metastasis. The purpose of the study is to perform correlation of FAK expression with patient prognostic factors using tissue microarrays (TMA) samples. METHODS: We analyzed FAK expression by immunohistochemical staining in 196 breast primary tumor samples from stage II-IV patients and in 117 metastatic tissues matched to the primary tumors using TMA that were stained with FAK monoclonal antibody. RESULTS: High FAK expression in primary tumors was associated with a younger age of patients (p = 0.033), lymphovascular invasion (p = 0.001) and with the triple-negative phenotype (p = 0.033). FAK expression in 117 metastatic tissues positively correlated with FAK expression in matched primary tumors by Spearman correlation analysis. In addition, a strong positive correlation was observed between high FAK expression and shorter overall survival and progression free survival in patients with metastatic tumors. CONCLUSIONS: The data demonstrate a high potential for FAK as a therapeutic target, especially in triple-negative breast cancer patients with high FAK expression.

The prognostic significance of focal adhesion kinase expression in stage I non-small-cell lung cancer.

INTRODUCTION: Focal adhesion kinase (FAK) plays a significant role in cancer cell survival signaling and is overexpressed in various malignancies, including lung cancer. Previous studies suggest that FAK overexpression is an independent factor predicting poor prognosis in non-small-cell lung cancer (NSCLC). The aim of this study is to confirm these findings specifically in stage I NSCLC. METHODS: A retrospective tissue microarray (TMA) analysis of FAK protein expression by immunohistochemistry was performed in 157 surgically resected stage I NSCLC specimen and in the corresponding matched normal lung tissue. The FAK 4.47 monoclonal antibody was used for FAK immunostaining. The scoring system of triplicate tumor cores included intensity of staining plus extent of staining for a composite score that ranged from 0 to 6. The association between FAK score and survival was evaluated. RESULTS: There were 103 stage IA and 54 stage IB patients, with mean follow-up of 5.5 years. Normal lung alveoli and interstitial tissue had mean FAK score of 0 (median score 0, range 0 to 2). Tumor samples had mean FAK score 3.1 (median score 3.5, range 0-6), with 57% of the samples having FAK score ≥ 3. Continuous FAK score was not associated with demographic data, tumor histology, or grade, nor survival in this cohort of stage I NSCLC patients. CONCLUSIONS: FAK is expressed in more than 50% of stage I NSCLC lung cancer but not in normal lung alveoli and interstitial tissue. FAK expression is not associated with survival outcome in this North American cohort.

Validation of 31 of the most commonly used immunohistochemical antibodies in cytology prepared using the Cellient(®) automated cell block system.

The Cellient(®) cell block system has become available as an alternative, partially automated method to create cell blocks in cytology. We sought to show a validation method for immunohistochemical (IHC) staining on the Cellient cell block system (CCB) in comparison with the formalin fixed paraffin embedded traditional cell block (TCB). Immunohistochemical staining was performed using 31 antibodies on 38 patient samples for a total of 326 slides. Split samples were processed using both methods by following the Cellient(®) manufacturer's recommendations for the Cellient cell block (CCB) and the Histogel method for preparing the traditional cell block (TCB). Interpretation was performed by three pathologists and two cytotechnologists. Immunohistochemical stains were scored as: 0/1+ (negative) and 2/3+ (positive). Inter-rater agreement for each antibody was evaluated for CCB and TCB, as well as the intra-rater agreement between TCB and CCB between observers. Interobserver staining concordance for the TCB was obtained with statistical significance (P < 0.05) in 24 of 31 antibodies. Interobserver staining concordance for the CCB was obtained with statistical significance in 27 of 31 antibodies. Intra-observer staining concordance between TCB and CCB was obtained with statistical significance in 24 of 31 antibodies tested. In conclusions, immunohistochemical stains on cytologic specimens processed by the Cellient system are reliable and concordant with stains performed on the same split samples processed via a formalin fixed-paraffin embedded (FFPE) block. The Cellient system is a welcome adjunct to cytology work-flow by producing cell block material of sufficient quality to allow the use of routine IHC.

Acute cholecystitis: do sonographic findings and WBC count predict gangrenous changes?

OBJECTIVE: The purpose of our study was to determine, first, if gallbladder wall striations in patients with sonographic findings suspicious for acute cholecystitis are associated with gangrenous changes and certain histologic features; and, second, if WBC count or other sonographic findings are associated with gangrenous cholecystitis. MATERIALS AND METHODS: Sixty-eight patients who underwent cholecystectomies within 48 hours of sonography comprised the study group. Sonograms and reports were reviewed for wall thickness, striations, Murphy sign, pericholecystic fluid, wall irregularity, intraluminal membranes, and luminal short-axis diameter. Medical records were reviewed for WBC count and pathology reports for the diagnosis. Histologic specimens were reviewed for pathologic changes. Statistical analyses tested for associations between nongangrenous and gangrenous cholecystitis and sonographic findings and for associations between wall striations and histologic features. RESULTS: Ten patients had gangrenous cholecystitis and 57, nongangrenous cholecystitis. One had cholesterolosis. Thirty patients had wall striations: 60% had gangrenous and 42% nongangrenous cholecystitis. There was no association with the pathology diagnosis (p = 0.32). There was no association between any histologic feature and wall striations (p ≥ 0.19). A Murphy sign was reported in 70% of patients with gangrenous cholecystitis and in 82% with nongangrenous cholecystitis; there was no association with the pathology diagnosis (p = 0.39). Wall thickness and WBC count were greater in patients with gangrenous cholecystitis than in those with nongangrenous cholecystitis (p ≤ 0.04). CONCLUSION: Gallbladder wall thickening and increased WBC counts were associated with gangrenous cholecystitis; however, there was considerable overlap between the two groups. Wall striations and a negative Murphy sign were not associated with gangrenous cholecystitis.

Training in EUS-Guided Fine Needle Aspiration: Safety and Diagnostic Yield of Attending Supervised, Trainee-Directed FNA from the Onset of Training.

Background. The optimal time to initiate hands-on training in endoscopic ultrasound fine needle aspiration (EUS-FNA) is unclear. We studied the feasibility of initiating EUS-FNA training concurrent with EUS training. Methods. Three supervised trainees were instructed on EUS-FNA technique and allowed hands-on exposure from the onset of training. The trainee and attending each performed passes in no particular order. During trainee FNA, the attending provided verbal instruction as needed but no hands-on assistance. A blinded cytopathologist assessed the adequacy (cellularity) and diagnostic yield of individual passes. Primary outcomes compared cellularity and diagnostic yield of attending versus fellow FNA passes. Results. We analyzed 305 FNA sites, including pancreas (51.2%), mediastinal/upper abdominal lymph node (LN) (28.5%) and others (20.3%). The average proportion of fellow passes with AC was similar to attending FNA-pancreas: 70.3 versus 68.8%; LN: 79.0 versus 81.7%; others 65.5 versus 68.7%; P > 0.05); these did not change significantly during the training period. Among cases with confirmed malignancy (n = 179), the sensitivity of EUS-FNA was 78.8% (68.4% fellow-only versus 69.6% attending only). There were no EUS-FNA complications. Conclusions. When initiated at the onset of EUS training, attending-supervised, trainee-directed FNA is safe and has comparable performance characteristics to attending FNA.

Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial.

BACKGROUND: Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. METHODS: Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. FINDINGS: Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline, DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group. At 3 months, 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs (p=0.054). The most common grade 3-4 toxicities were infection (five of 60 patients in the zoledronic acid group and six of 59 in the control group) and thrombosis (five of 60 in the zoledronic acid and two of 59 in the control group). There was one documented case of osteonecrosis in the zoledronic acid group. INTERPRETATION: Zoledronic acid administered with chemotherapy resulted in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery. Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs. FUNDING: Novartis Pharmaceuticals and Pfizer Inc.

A role for the epithelial microenvironment at tumor boundaries: evidence from Drosophila and human squamous cell carcinomas.

Recent work has shown an increasing appreciation for the importance of the tumor environment, most commonly the overlying stroma. Less emphasis has been placed on the importance of local communication between transformed cells and their neighbors within the epithelium at tumor boundaries. We previously reported a Drosophila model that highlighted the importance of local interactions within the epithelial microenvironment: Src-transformed cells (Csk-deficient) were influenced by their immediate normal neighbors. The result was a consistent change in 'border cells' at the edge of transformed patches including delocalized p120-catenin and E-cadherin as well as invasive migration through the basal lamina. Here we show that the invasive properties of the boundary cells depend on up-regulation of Drosophila matrix metalloproteinase-1 as assessed by promoter activity, protein levels, in situ enzymatic activity, and tests of genetic modifier activity. Further, we provide evidence that these events at tumor borders may be evolutionarily conserved. We detected changes in 'boundary cells' within histological sections of human squamous cell carcinomas that were similar to those observed in Drosophila: both E-cadherin and p120-catenin exhibited normal junctional localization at the centers of the tumors but were reduced or delocalized at the boundary. Further, matrix metalloproteinase-2 was up regulated within these same boundary cells. These results support the view that local cell-cell interactions within the epithelial microenvironment impact tumor invasion and progression.

Exclusion of malignancy in thyroid nodules with indeterminate fine-needle aspiration cytology after negative 18F-fluorodeoxyglucose positron emission tomography: interim analysis.

BACKGROUND: In all, 20% of fine-needle aspiration (FNA) biopsies of thyroid nodules have an indeterminate diagnosis; of these, 80% are found to be benign after thyroidectomy. Some previous reports indicate that positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) imaging may predict malignancy status. We now report results on the first 51 patients in the largest prospective study of FDG-PET in patients with an indeterminate thyroid nodule FNA. METHODS: Eligible patients had a dominant thyroid nodule that was palpable or >or=1 cm in greatest dimension as seen by ultrasonography, and indeterminate histology of the FNA biopsy specimen. Participants underwent preoperative neck FDG-PET alone or FDG-PET with computed tomography (FDG-PET/CT). Images were evaluated qualitatively and semiquantitatively using the maximum standardized uptake value (SUV(max)). Final diagnosis was determined by histopathologic analysis after thyroidectomy. Descriptive statistical analysis was performed. RESULTS: A total of 51 patients underwent preoperative FDG-PET or FDG-PET/CT. Studies without focally increased uptake localized to the lesion were considered negative. For all lesions (10 malignant, 41 benign), the sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) were 80%, 61%, 33%, and 93%, respectively. Postoperatively, two malignant and six benign lesions were found to be <1 cm by pathology examination; one lesion was not measured. When these lesions were excluded, the sensitivity, specificity, PPV, and NPV were 100%, 59%, 36%, and 100%, respectively. CONCLUSIONS: Based on these preliminary data, FDG-PET may have a role in excluding malignancy in thyroid nodules with an indeterminate FNA biopsy. This finding justifies ongoing accrual to our target population of 125 participants.

Role of ProExC: a novel immunoperoxidase marker in the evaluation of dysplastic squamous and glandular lesions in cervical specimens.

Minichromosome maintenance and topoisomerase II alpha proteins play an important role in the regulation of eukaryotic DNA replication, and are overexpressed in a number of dysplastic and malignant tissues. ProExC antibody is a novel biomarker cocktail containing antibodies against topoisomerase II alpha and minichromosome maintenance 2 proteins. Our purpose was to evaluate the sensitivity, specificity, and predictive value of ProExC in dysplastic squamous and glandular lesions of the cervix. Nine low-grade squamous intraepithelial lesion, 35 high-grade squamous intraepithelial lesion, 23 squamous metaplasia, and 14 adenocarcinoma in situ specimens were retrieved from our hospital files. ProExC immunostaining was performed. ProExC had sensitivity, specificity, and positive and negative predictive value of 89%, 100%, 100%, and 82%, respectively, for distinguishing high-grade squamous intraepithelial lesion from squamous metaplasia, and 93%, 100%, 100%, and 98%, respectively, for distinguishing adenocarcinoma in situ from reactive benign endocervix. ProExC is a valuable marker for distinguishing dysplastic squamous and endocervical lesions of the cervix from squamous metaplasia in histologic sections. ProExC may eventually be used in conjunction with morphologic and human papillomavirus evaluation for better classification of indeterminate cervical lesions in Papanicolaou smears.

Intraocular pigmented proliferations in the context of cytologic evaluation.

This article is written to give an overview of the various intraocular pigmented proliferations as it pertains to cytologic evaluation and interpretation. It reviews the various epithelial and melanocytic lesions, their location and the various clinical approaches the ophthalmologist uses to aspirate the lesion. It also reviews the current thinking in the differentiation between Class I and Class II melanomas and how molecular profiling may be necessary in its differentiation which could help stratify those patients whose tumors are refractory to treatment and may benefit from adjuvant chemotherapy and eye-sparing surgery.

Pancreatitis is frequent among patients with side-branch intraductal papillary mucinous neoplasia diagnosed by EUS.

BACKGROUND: Because of greater recognition and improved imaging capabilities, intraductal papillary mucinous neoplasms (IPMNs) are being diagnosed with increasing frequency. IPMNs of the main pancreatic duct cause symptoms and lead to pancreatitis. Side-branch (SB) IPMNs are thought to cause symptoms less frequently, and their association with pancreatitis is not well defined. OBJECTIVE: Our purpose was to ascertain whether an association exists between SB-IPMN and pancreatitis. DESIGN: Single-center, retrospective study. SETTING: Academic medical center. PATIENTS: A total of 305 patients underwent EUS examinations between October 2002 and October 2006 for pancreatic cystic lesions. MAIN OUTCOME MEASUREMENT: The main outcome measure was the frequency of acute or chronic pancreatitis that was not procedurally related. RESULTS: Thirty-two patients had SB-IPMNs, and 11 (34%) had pancreatitis. Three patients reported a single episode, and 8 patients reported having recurrent episodes of pancreatitis. Overall, 17 (53%) patients had symptoms possibly attributable to SB-IPMN. Female sex (73% vs 38%) and multiple pancreatic lesions (54% vs 24%) were more commonly seen in those with pancreatitis, but were not statistically significant factors. Larger cyst size or cyst fluid marker levels did not appear associated with pancreatitis occurrence. EUS-FNA demonstrated communication with the pancreatic duct in 94% and thick, mucinous fluid in 84%. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Pancreatitis was frequently associated with the presence of SB-IPMNs in our referral practice. SB-IPMNs should be considered in the differential diagnosis of patients with recurrent pancreatitis with cystic lesions seen on imaging studies. EUS-FNA was the most useful modality in helping to differentiate SB-IPMNs from other lesions.