Pancreatic Malakoplakia: A Rare Pathology Associated With Acute Pancreatitis.

Malakoplakia is a rare granulomatous tumor-like inflammatory condition, most frequently involving the genitourinary system and occurring in immunosuppressed patients. The gastrointestinal tract is the second most common site, where it is usually seen involving the colon. We report a case of malakoplakia presenting as a pancreatic mass. Imaging showed soft tissue along the pancreatic tail/greater curvature concerning for infiltrating tumor, but endoscopic ultrasound with biopsy showed malakoplakia. Our case discusses malakoplakia at an uncommon site, which was appropriately treated with antibiotics.

Esophageal retention cyst: Esophagogastric junction outflow obstruction (EGJOO) as a potential etiology and management with endoscopic mucosal resection (EMR).

INTRODUCTION AND IMPORTANCE: Esophageal retention cysts are acquired cysts with no known etiology. They are characterized by dilation of the submucosal glands. Symptomatic cysts are traditionally managed by surgical resection. CASE PRESENTATION: We present a case of progressive dysphagia and chest pain secondary to esophageal retention cysts in the mid and distal esophagus with associated esophagogastric junction outflow obstruction (EGJOO) and jackhammer esophagus on high resolution manometry (HRM). The patient underwent staged endoscopic mucosal resection (EMR) with subsequent improvement in her symptoms. However, EGJOO persisted after resection, suggesting it was the primary pathology and not a consequence of the obstruction from the cysts. CLINICAL DISCUSSION: Esophageal retention cysts are rarely reported in the literature with most descriptions coming from incidental post-mortems. The presented case suggests EGJOO as a potential etiology of retention cysts. The proposed mechanism is that a significant rise in esophageal intraluminal pressure creates a state of stasis in the esophagus, ideal for the development of these cysts. Symptomatic or malignant retention cysts should be resected. We demonstrate the feasibility of EMR as an alternative to surgical resection. CONCLUSION: Esophageal retention cyst is a rare entity, which may arise as a result of EGJOO. The natural history and malignant potential of these cysts are unknown, and no formal guidelines have been established for follow-up for patients with asymptomatic retention cysts. Endoscopic mucosal resection can be used to successfully manage these cysts.

Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome.

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

Metastatic malignant melanoma mimicking a salivary gland basaloid neoplasm after treatment with nivolumab.

Malignant melanoma is a well-known diagnostic pitfall, given its propensity to metastasize to different sites and mimic various entities. In this report, we present a fine-needle aspiration biopsy (FNA) of a metastatic melanoma with basaloid features that is occurring in the preauricular/parotid area. The patient is a 17-year-old male with a history of excision of melanoma of the left temple, and was undergoing adjuvant treatment with nivolumab. The prior excision was positive for S100, HMB-45, melan-A, and tyrosinase. On follow-up, he presented with non-FDG avid left preauricular area lesions. FNA was performed, and on-site evaluation demonstrated a cellular basaloid neoplasm with focal fibrillary stroma. Immunohistochemical stains revealed that the tumor cells were positive for SOX-10, S100, MITF, and HMGA2, and were negative for HMB-45, melan-A, tyrosinase, p63, cam 5.2 and PLAG1. The positive S100, SOX-10, and MITF results and negative cam 5.2 result supported the diagnosis of melanoma. Nivolumab was then stopped, Dabrafenib/Trametinib were started, and the patient underwent excision of the nodules. Nine-months later, he developed a rib metastasis that was positive for S100, SOX-10, melan-A, and tyrosinase. This report emphasizes that melanoma involving the parotid gland region has the potential to be misdiagnosed by FNA as a salivary gland neoplasm because of overlapping cytologic features and immunophenotypes. This pitfall is avoided by careful morphologic analysis and judicious use of ancillary studies.

Impact of molecular testing on detecting mimics of oncocytic neoplasms in thyroid fine-needle aspirates diagnosed as follicular neoplasm of Hürthle cell (oncocytic) type.

BACKGROUND: Some thyroid nodules cytologically presenting as follicular neoplasm, Hürthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously functioning thyroid nodules (AFTNs) with TSHR, GNAS, and EZH1 mutations or oncocytic metaplasia. A to be defined subset of FNHCT harbors genome haploidisation-type DNA copy number alterations (GH-CNA). Molecular profiling of FNHCT may distinguish oncocytic neoplasms from its mimics. METHODS: Consecutive fine-needle aspirates of 180 thyroid nodules over 37 months diagnosed as FNHCT and tested by ThyroSeq v3 were identified. Histologic follow-up was available for 79 of 180 nodules (44%). RESULTS: No molecular alterations were found in 76 of 180 nodules (42%), of which 15 were resected (oncocytic metaplasia, n = 7; follicular oncocytic adenoma, n = 8). Of nodules followed without surgery, 17 of 101 (17%) showed TSHR, EZH1, and GNAS mutations of AFTNs. Papillary thyroid carcinoma was identified by BRAF V600E (n = 2) and hyalinizing trabecular adenoma by PAX8-GLIS3 (n = 1). GH-CNA alone was detected in 42 of 180 FNHCT nodules (23%), of which 29 were resected and histologically diagnosed as follicular oncocytic neoplasms. All remaining resected nodules were histologically proven oncocytic neoplasms: 1) RAS-like alterations without GH-CNA (n = 25) and 2) TERT and/or TP53 mutations co-occurring with GH-CNA (n = 6), including anaplastic thyroid carcinoma arising from follicular oncocytic carcinoma with TP53, TERT mutations with GH-CNA (n = 2). CONCLUSIONS: A proportion of FNHCT nodules are AFTNs and oncocytic metaplasias, which can be suspected based on characteristic mutations or lack of alterations on molecular testing. Among resected FNHCTs, GH-CNAs characterize approximately half of histologically confirmed follicular oncocytic neoplasms.

Molecular alterations in Hürthle cell nodules and preoperative cancer risk.

Hürthle cell carcinoma (HCC) is a distinct type of thyroid cancer genetically characterized by DNA copy number alterations (CNA), typically of genome haploidization type (GH-type). However, whether CNA also occurs in benign Hürthle cell adenomas (HCA) or Hürthle cell hyperplastic nodules (HCHN), and have diagnostic impact in fine-needle aspiration (FNA) samples, remains unknown. To address these questions, we (1) analyzed 26 HCC, 24 HCA, and 8 HCHN tissues for CNA and other mutations using ThyroSeq v3 (TSv3) next-generation sequencing panel, and (2) determined cancer rate in 111 FNA samples with CNA and known surgical outcome. We identified CNA, more often of the GH-type, in 81% of HCC and in 38% HCA, but not in HCHN. Among four HCC with distant metastasis, all had CNA and three TERT mutations. Overall, positive TSv3 results were obtained in 24 (92%) HCC, including all with ATA high risk of recurrence or metastasis. Among 111 FNA cases with CNA, 38 (34%) were malignant and 73 (66%) benign. A significant correlation between cancer rate and nodule size was observed, particularly among cases with GH-type CNA, where every additional centimeter of nodule size increased the malignancy odds by 1.9 (95% CI 1.3-2.7; P = 0.001). In summary, the results of this study demonstrate that CNA characteristic of HCC also occur in HCA, although with lower frequency, and probability of cancer in nodules with CNA increases with nodule size. Detection of CNA, in conjunction with other mutations and nodule size, is helpful in predicting malignancy in thyroid nodules.

Evaluation of NR4A3 immunohistochemistry (IHC) and fluorescence in situ hybridization and comparison with DOG1 IHC for FNA diagnosis of acinic cell carcinoma.

BACKGROUND: Acinic cell carcinoma (AcCC) is diagnostically challenging on fine-needle aspiration because it can mimic several other neoplasms or even normal acinar tissue. Immunopositivity for DOG1, especially circumferential membranous staining, can support the diagnosis of AcCC but is not entirely specific, and it is prone to technical and interpretive challenges on small specimens. NR4A3 (nuclear receptor subfamily 4 group A member 3) translocation and nuclear NR4A3 overexpression were recently described in the majority of AcCCs. Here, the authors evaluate the performance of NR4A3 immunohistochemistry (IHC) and NR4A3 break-apart fluorescence in situ hybridization (FISH) on cell block preparations and compare them with DOG1 IHC in distinguishing AcCC from other entities in the differential diagnosis. METHODS: The authors identified 34 cytology cell blocks with lesional cells, including 11 specimens of AcCC (2 of which derived from 1 patient and showed high-grade transformation) as well as 2 secretory carcinomas, 7 salivary duct carcinomas, 4 mucoepidermoid carcinomas, 3 oncocytomas, 3 renal cell carcinomas, and 6 specimens containing nonneoplastic salivary gland tissue. NR4A3 IHC, DOG1 IHC, and NR4A3 FISH were attempted for all cases. RESULTS: NR4A3 IHC had 81.8% sensitivity and 100% specificity for AcCC, whereas NR4A3 FISH had 36.4% sensitivity and 100% specificity, although 4 cases (3 mucoepidermoid carcinomas and 1 salivary gland tissue sample) could not be analyzed because of low cellularity. Notably, no normal acinar tissue specimens showed NR4A3 positivity by IHC or FISH. In addition, DOG1 IHC had 72.7% sensitivity and 92% specificity. CONCLUSIONS: NR4A3 IHC is highly specific for the diagnosis of AcCC and is more sensitive than DOG1 IHC and NR4A3 FISH. In addition, NR4A3 IHC performance is not improved by the inclusion of DOG1 IHC. Finally, NR4A3 positivity resolves the perennial problem of distinguishing AcCC from normal acinar tissue.

Thyroid cytology smear slides: An untapped resource for ThyroSeq testing.

BACKGROUND: Molecular testing of thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology is commonly used to guide patient management and is typically performed on freshly collected FNA samples. In this study, the authors evaluated the performance of the ThyroSeq test in cytology smear slides. METHODS: Air-dried Diff-Quik (DQ)-stained and alcohol-fixed Papanicolaou (Pap)-stained smears were used to determine required cellularity and sensitivity of mutation detection and to compare ThyroSeq v3 Genomic Classifier (GC) results obtained in cytology smears and fresh FNA samples from the same nodules. RESULTS: ThyroSeq testing of 31 cytology smears revealed that 25 smears (81%) were adequate for ThyroSeq analysis, including 14 Pap-stained smears (100%) and 11 DQ-stained smears (65%), whereas 6 DQ-stained smears (35%) failed RNA sequencing. The overall accuracy for detecting molecular alterations was 98%, with 100% concordance for mutations and gene expression alterations, 96% concordance for fusions, and 94% concordance for copy number alterations. Cytology smears were adequate for ThyroSeq analysis when at least 200 to 300 cells were present in 1 to 3 slides. ThyroSeq detected all studied mutations down to 5% allele frequency and BRAF mutations down to 1% allele frequency. Testing of smears yielded a positive ThyroSeq GC result in all nodules originally classified as positive. CONCLUSIONS: Thyroid FNA cytology smear slides with adequate cellularity can be successfully used for ThyroSeq GC testing in approximately 80% of cases, with an even higher success rate in Pap-stained smears. Compared with FNA samples collected into preservative solution, 94% to 100% of different genetic alterations could be accurately detected in smears, validating cytology smears as an alternative for ThyroSeq testing in patients with indeterminate thyroid cytology.

KRAS amplification in metastatic colon cancer is associated with a history of inflammatory bowel disease and may confer resistance to anti-EGFR therapy.

Mutations in RAS occur in 30-50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF, and PIK3CA. Molecular testing was performed on 1286 consecutive mCRC from 1271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS, and HRAS for 15, 5, and 2 cases, respectively (6-21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology, and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggest the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.

Molecular-derived estimation of risk of malignancy for indeterminate thyroid cytology diagnoses.

INTRODUCTION: One of the key features of the Bethesda System for Reporting Thyroid Cytopathology is the risk of malignancy (ROM), which guides management for each diagnostic category. However, calculation of the ROM can be challenging for indeterminate diagnoses because only a portion of cases will be resected for cytologic-histologic correlation (CHC) analyses. In the present study, we used the probability of cancer information from ThyroSeq, version 3, reports to calculate the molecular-derived (MD) ROM for indeterminate categories. MATERIALS AND METHODS: Cytology cases with indeterminate BSRTC diagnoses and adequate molecular test results were retrieved from our cytopathology laboratory for a 12-month period. The probability of cancer information from the ThyroSeq, version 3, molecular reports were tabulated, and the mean ROM was calculated for each diagnostic category. The MDROM included noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) as a "malignant" outcome because it is considered a surgical disease. RESULTS: A total of 361 cases had adequate material for molecular testing. The diagnostic distribution was as follows: atypia of undetermined significance/follicular lesion of undetermined significance, 271 cases (75.1%), follicular neoplasm/suspicious for a follicular neoplasm, 59 cases (16.3%), and Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type, 31 cases (8.6%). The corresponding estimated MDROMs were 14.9%, 32.6%, and 34.4%. A comparison with the CHC data was performed, and the 95% confidence intervals of the MDROMs overlapped well with the 2 endpoint CHC values. CONCLUSIONS: Calculation of the MDROMs provides a new method to approximate the ROMs of indeterminate diagnoses and has the advantage of potentially evaluating all cases, not just those resected. Furthermore, for those using the same platform, interinstitutional comparisons will be possible.

Comparison of the collection approaches of 2 large thyroid fine-needle aspiration practices reveals differing advantages for cytology and molecular testing adequacy rates.

INTRODUCTION: At our institution, almost all thyroid fine-needle aspiration (FNA) procedures are performed by either Endocrinology or Radiology personnel. In this study, we compared the cytology and molecular adequacy rates of these 2 thyroid FNA practices, which differ on several aspects of specimen procurement. MATERIALS AND METHODS: All thyroid FNA specimens from Endocrinology and Radiology practices between September 2008 and December 2016 were included. Over this time frame, the molecular testing modality transitioned from polymerase chain reaction (PCR)-based (7-gene panel era) to next generation sequencing (NGS)-based (ThyroSeq era). In measuring cytology adequacy, the Bethesda System unsatisfactory rate was determined. Molecular adequacy was categorized as Optimal, Limited Thyroid Epithelial Cells, Limited Nucleic Acids, or Failed. These parameters were compared for the 2 practices. RESULTS: The study cohorts comprised 5810 specimens from Endocrinology and 4597 from Radiology. More Endocrinology specimens were satisfactory for cytology diagnosis than those from Radiology (94.7% versus 90.0%, P < 0.001). For molecular adequacy, fewer Endocrinology specimens were optimal than specimens from Radiology for both the 7-gene panel era (76.2% versus 82.9%, P < 0.001) and the ThyroSeq era (88.1% versus 91.9%, P = 0.049). CONCLUSIONS: The 2 thyroid FNA practices varied inversely in their adequacy rates for cytology and molecular testing. Had one practice been superior for both cytology and molecular adequacy, a recommendation for the method of choice would have been straightforward. However, our results show that optimization of FNA practice for the current practice of thyroid cytology requires further investigation due to the complex nature of specimen procurement.

Artificial intelligence in cytopathology: a review of the literature and overview of commercial landscape.

Artificial intelligence (AI) has made impressive strides recently in interpreting complex images, thanks to improvements in deep learning techniques and increasing computational power. Researchers have started applying these advanced techniques to pathology images, although most efforts have been focused on histopathology. Cytopathology, however, remains the original field of pathology for which AI models for clinical use were successfully commercialized, to assist with automating Papanicolaou test screening. Recent AI efforts have focused on whole slide images of both gynecologic and non-gynecologic cytopathology. This review summarizes the literature and commercial landscape of AI as applied to cytopathology.

Histopathological Predictors of Recurrence in Stage III Colon Cancer: Reappraisal of Tumor Deposits and Tumor Budding Using AJCC8 Criteria.

Patients with stage III colonic adenocarcinoma have a spectrum of risk for recurrent disease, and histopathological variables that predict recurrence can help stratify patients into prognostic groups. To identify histopathological predictors of recurrence, we investigated the effect of implementation of the eighth edition of the American Joint Committee on Cancer (AJCC8) staging system definition of tumor deposits and International Tumor Budding Consensus Conference (ITBCC) criteria for tumor budding compared with other known prognostic variables in 256 resected colonic adenocarcinomas, including 150 stage III and 106 stage II tumors. In stage III colon cancer, tumor deposits and high tumor budding were the only independent histological variables that predicted disease recurrence. In a multivariable analysis in stage III colon cancer, tumor deposits and high tumor budding were associated with a 2.2- and 1.5-fold increased risk of developing disease recurrence, respectively (95% CI = 1.1-4,2, P = .02, and 95% CI = 1.1-2.1, P = .01, respectively). The negative prognostic effect of tumor deposits was most pronounced in patients with stage IIIB disease in which tumor deposits were associated with a 3.2-fold increased risk of disease recurrence (95% CI = 1.4-7.1; P = .005). Within the N1 cohort, patients with tumor deposits without concurrent positive lymph nodes (N1c) had a significantly decreased disease-free survival compared with patients with N0 tumors ( P < .001) and patients with N1a/b tumors ( P = .02). As independent risk factors for recurrence, tumor deposits and high tumor budding are important histopathological variables and should be included as a part of a routine comprehensive pathological risk assessment in stage III colon cancer.

Benign call rate and molecular test result distribution of ThyroSeq v3.

BACKGROUND: The benign call rate (BCR) is the percentage of cytomorphologically indeterminate cases with subsequent benign or negative molecular results. For rule-out tests, the BCR is an important parameter because these molecular "negative" cases may be managed similarly to those with a benign cytology diagnosis. Although earlier versions of ThyroSeq molecular tests were less effective in excluding malignancy, the extensively expanded v3 version with a high negative predictive value is considered to represent a rule-out test. In the current study, the authors evaluated the BCR and the overall molecular result distribution of ThyroSeq v3. METHODS: All indeterminate thyroid fine-needle aspiration cases (except those deemed suspicious for malignancy) with available ThyroSeq v3 results from November 2017 to June 2018 were retrieved from the cytopathology files. Because the ThyroSeq v3 genomic classifier was designed for thyroid follicular-derived lesions, cases in which parathyroid and medullary carcinoma molecular markers were detected and those that were inadequate or limited for molecular testing were excluded from the study. For the remaining cases, the indeterminate diagnoses were correlated with molecular and histologic results. RESULTS: Among the 224 indeterminate cases (except those deemed suspicious for malignancy), the overall ThyroSeq v3 molecular test BCR was 74.1% (166 of 224 cases). The category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) had higher BCRs compared with the other indeterminate diagnostic categories. RAS mutations were the most common positive results. CONCLUSIONS: The high BCR demonstrates that ThyroSeq v3 is potentially effective in sparing the large majority of indeterminate cases with "negative" results from surgery while offering risk assessment for the positive cases and guiding clinical management.

Site-specific Differences in Colonic Adenocarcinoma: KRAS Mutations and High Tumor Budding Are More Frequent in Cecal Adenocarcinoma.

Recent literature indicates that adenocarcinomas of the cecum differ with respect to molecular alterations compared with noncecal proximal colon adenocarcinomas and that cecal tumor site may be a prognostically relevant variable. We compared molecular alterations, histopathologic features, and disease-specific survival in a series of 328 colonic adenocarcinomas identified over a 2-year period and stratified by tumor location (cecum, right colon, and left colon). Overall, cecal adenocarcinomas demonstrated the highest frequency of molecular abnormalities with 74% harboring either a KRAS exon 2 or 3 mutation, a BRAF mutation, or DNA mismatch repair protein deficiency. KRAS mutations were more frequently seen in the cecum compared with all other tumor sites (P=0.03). KRAS mutations were identified in 46% of cecal adenocarcinomas compared with only 25% of adenocarcinomas of the right colon (P=0.004). Cecal adenocarcinomas more frequently displayed adverse histopathologic features, in particular high tumor budding (31%), compared with tumors of the right colon (18%; P=0.04) and tumors of the left colon (17%; P=0.02). Overall stage was the most important independent predictor of disease-specific survival in the multivariable analysis; however, cecal tumor site and high tumor budding were also predictive of poor survival, particularly in patients with stage III or IV tumors. In conclusion, cecal adenocarcinomas are characterized by a high frequency of KRAS mutations compared with noncecal right colon tumors, frequently display high tumor budding, and may be a prognostically relevant variable, particularly in patients with stage III or IV disease.

Jejunoileal Neuroendocrine Tumors Complicated by Intestinal Ischemic Necrosis Are Associated With Worse Overall Survival.

CONTEXT: -Jejunoileal neuroendocrine tumors (JINETs) are slow-growing, malignant tumors that are often associated with protracted survival, despite their frequent presentation at an advanced stage. A subset of JINETs is complicated by intestinal ischemic necrosis (IIN), which leads to their initial clinical presentation. OBJECTIVE: -To assess the effect of IIN on overall survival in patients with JINETs. DESIGN: -Ten JINETs with IIN during a 14-year period and a control group of 52 JINETs without IIN were identified retrospectively. The hematoxylin-eosin slides and gross descriptions were reviewed, and pathologic features were assessed. Overall survival was compared between the 2 groups using the Kaplan Meier method and Cox proportional hazards model. RESULTS: -At 1 year postresection, only 40% (4 of 10) of the patients with IIN were alive, whereas 94% (49 of 52) of those without IIN were alive (P < .001). Patients with IIN were significantly older than those without IIN (median, 83 years versus 65.5 years, P = .001). By univariate Cox proportional hazards regression, IIN was associated with a 4.30-fold increased risk of death (95% confidence interval 1.75-10.56; P = .001). When controlling for age, advanced stage (stage III or IV), tumor grade, and synchronous carcinoma in a multivariate analysis, IIN showed a trend toward prognostic significance (2.31-fold increased risk of death; 95% confidence interval, 0.85-6.27; P = .10). CONCLUSIONS: -The pathologic identification of tumor-associated IIN portends a worse overall survival among patients with JINETs.

A Model Based on Pathologic Features of Superficial Esophageal Adenocarcinoma Complements Clinical Node Staging in Determining Risk of Metastasis to Lymph Nodes.

BACKGROUND & AIMS: It is important to identify superficial (T1) gastroesophageal adenocarcinomas (EAC) that are most or least likely to metastasize to lymph nodes, to select appropriate therapy. We aimed to develop a risk stratification model for metastasis of superficial EAC to lymph nodes using pathologic features of the primary tumor. METHODS: We collected pathology data from 210 patients with T1 EAC who underwent esophagectomy from 1996 through 2012 on factors associated with metastasis to lymph nodes (tumor size, grade, angiolymphatic invasion, and submucosal invasion). Using these variables, we developed a multivariable logistic model to generate 4 categories for estimated risk of metastasis (<5% risk, 5%-10% risk, 15%-20% risk, or >20% risk). The model was validated in a separate cohort of 39 patients who underwent endoscopic resection of superficial EAC and subsequent esophagectomy, with node stage analysis. RESULTS: We developed a model based on 4 pathologic factors that determined risk of metastasis to range from 2.9% to 60% for patients in the first cohort. In the endoscopic resection validation cohort, higher risk scores were associated with increased detection of lymph node metastases at esophagectomy (P = .021). Among patients in the first cohort who did not have lymph node metastases detected before surgery (cN0), those with high risk scores (>20% risk) had 11-fold greater odds for having lymph node metastases at esophagectomy compared with patients with low risk scores (95% confidence interval, 2.3-52 fold). Increasing risk scores were associated with reduced patient survival time (P < .001) and shorter time to tumor recurrence (P < .001). Patients without lymph node metastases (pT1N0) but high risk scores had reduced times of survival (P < .001) and time to tumor recurrence (P = .001) after esophagectomy than patients with pT1N0 tumors and lower risk scores. CONCLUSIONS: Pathologic features of primary superficial EACs can be used, along with the conventional node staging system, to identify patients at low risk for metastasis, who can undergo endoscopic resection, or at high risk, who may benefit from induction or adjuvant therapy.

Simulating Kinect Infrared and Depth Images.

With the emergence of the Microsoft Kinect sensor, many developer communities and research groups have found countless uses and have already published a wide variety of papers that utilize the raw depth images for their specific goals. New methods and applications that use the device generally require an appropriately large ensemble of data sets with accompanying ground truth for testing purposes, as well as accurate models that account for the various systematic and stochastic contributors to Kinect errors. Current error models, however, overlook the intermediate infrared (IR) images that directly contribute to noisy depth estimates. We, therefore, propose a high fidelity Kinect IR and depth image predictor and simulator that models the physics of the transmitter/receiver system, unique IR dot pattern, disparity/depth processing technology, and random intensity speckle and IR noise in the detectors. The model accounts for important characteristics of Kinect's stereo triangulation system, including depth shadowing, IR dot splitting, spreading, and occlusions, correlation-based disparity estimation between windows of measured and reference IR images, and subpixel refinement. Results show that the simulator accurately produces axial depth error from imaged flat surfaces with various tilt angles, as well as the bias and standard lateral error of an object's horizontal and vertical edge.

Statistical analysis-based error models for the Microsoft Kinect(TM) depth sensor.

The stochastic error characteristics of the Kinect sensing device are presented for each axis direction. Depth (z) directional error is measured using a flat surface, and horizontal (x) and vertical (y) errors are measured using a novel 3D checkerboard. Results show that the stochastic nature of the Kinect measurement error is affected mostly by the depth at which the object being sensed is located, though radial factors must be considered, as well. Measurement and statistics-based models are presented for the stochastic error in each axis direction, which are based on the location and depth value of empirical data measured for each pixel across the entire field of view. The resulting models are compared against existing Kinect error models, and through these comparisons, the proposed model is shown to be a more sophisticated and precise characterization of the Kinect error distributions.

BRAF-mutated microsatellite stable colorectal carcinoma: an aggressive adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical expression.

Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS) colorectal carcinoma has not been reported. We analyzed 205 colorectal carcinomas including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF-mutated MSS colorectal carcinomas were more frequently stage IV at presentation compared to patients with BRAF-mutated MSI-H colorectal carcinomas and BRAF wild-type MSS colorectal carcinomas (32% versus 8% versus 15%, P < .001). BRAF-mutated MSS colorectal carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF-mutated MSS colorectal carcinoma compared to both BRAF-mutated MSI-H colorectal carcinoma and BRAF wild-type MSS colorectal carcinoma (39% versus 6% versus 6%, P = .0001). BRAF-mutated MSI-H colorectal carcinomas were less often CK20 positive compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF-mutated MSS colorectal carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF-mutated MSS colorectal carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.