Spectrum Of Adenocarcinoma Research Articles

Thoracic Frozen Section Pitfalls: Lung Adenocarcinoma Versus Selected Mimics.

Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging. To describe selected pitfalls in thoracic frozen sections with a focus on the differential diagnosis between adenocarcinoma and its mimics, and to provide tips to prevent misinterpretation. Peer-reviewed literature and the author's experience. A common challenge in thoracic frozen sections is the differential diagnosis between lung adenocarcinoma and its mimics. Diagnostic difficulties arise because mimics of adenocarcinoma often entrap reactive lung epithelium that can appear atypical on frozen section slides. Entities that can be misinterpreted as adenocarcinoma include ciliated muconodular papillary tumor/bronchiolar adenoma, hamartoma, inflammatory myofibroblastic tumor, and pulmonary Langerhans cell histiocytosis. Knowledge of the key clinical, radiologic, and histologic features of these entities can help prevent overdiagnosis of adenocarcinoma. Pathologic findings that facilitate the distinction between adenocarcinoma and its mimics at frozen section include the appearance and contour of the lesion at low magnification, growth patterns, cilia, stromal features, shape of the epithelial cells (cuboidal versus columnar), nuclear features of malignancy (crowding, hyperchromasia, irregular contours), and abruptness of the junction between the lesion and adjacent uninvolved lung. Knowledge of the clinical context, imaging findings, and the surgical consequence of the intraoperative diagnosis can also prevent diagnostic errors. Finally, since adenocarcinomas of the lung are often relatively bland and lack the stromal desmoplasia seen in adenocarcinomas of other organs, familiarity with the morphologic spectrum of lung adenocarcinomas at frozen section analysis is important.

Evaluation of fine-needle core biopsy specimens for pancreatic ductal adenocarcinoma: Diagnostic utility and helpful histological features.

With the advent of new biopsy devices, fine-needle core biopsy specimens can be obtained from pancreas masses. This study aimed to report the histological spectrum of intrapancreatic adenocarcinoma on fine-needle core biopsy and the accuracy of sampling. We identified 423 SharkCore™ fine-needle core biopsies taken from patients with a high clinical concern for pancreatic adenocarcinoma. For each, we recorded patient age and sex, percentage of diagnostic tissue in each sample and tumour site, size and histological findings. The cases came from 392 patients (193 men, 199 women; mean age 69 years). Median diagnostic tissue amount in the samples was 30%. Common histological findings included desmoplasia (36%), single atypical cells (44%), haphazard glandular growth pattern (68%), nuclear pleomorphism > 4:1 (39%), incomplete gland lumens (18%) and detached atypical epithelial strips (37%). Additional levels were ordered on 143 cases. Final clinical diagnoses associated with the 423 cases were adenocarcinoma (n = 343), pancreatitis (n = 22), intraductal neoplasm or other benign/low-grade process (n = 16) and unknown (n = 42, patients lost to follow-up). Of the adenocarcinoma cases, the diagnosis was established by the evaluated fine-needle core biopsy sample alone in 178, by fine-needle aspiration biopsy alone in 30, by both concurrently in 89 and by subsequent biopsy or resection in 37 cases. Among 68 cases called suspicious on fine-needle core biopsy, 78% ultimately represented adenocarcinoma. Fine-needle core biopsy allows for histological diagnosis of pancreatic adenocarcinoma, using known histological parameters. Common findings include single atypical cells, desmoplasia, haphazard gland growth and nuclear pleomorphism. Cases interpreted as suspicious often represent malignancy.

Ex-vivo 1.5T MR Imaging versus CT in Estimating the Size of the Pathologically Invasive Component of Lung Adenocarcinoma Spectrum Lesions.

The purpose of this study was to investigate whether ex-vivo MRI enables accurate estimation of the invasive component of lung adenocarcinoma. We retrospectively reviewed 32 patients with lung adenocarcinoma who underwent lung lobectomy. The specimens underwent MRI at 1.5T. The boundary between the lesion and the normal lung was evaluated on a 5-point scale in each three MRI sequences, and a one-way analysis of variance and post-hoc tests were performed. The invasive component size was measured histopathologically. The maximum diameter of each solid component measured on CT and MR T1-weighted (T1W) images and the maximum size obtained from histopathologic images were compared using the Wilcoxon signed-rank test. Inter-reader agreement was evaluated using intraclass correlation coefficients (ICC). T1W images were determined to be optimal for the delineation of the lesions (P < 0.001). The histopathologic invasive area corresponded to the area where the T1W ex-vivo MR image showed a high signal intensity that was almost equal to the intravascular blood signal. The maximum diameter of the solid component on CT was overestimated compared with the maximum invasive size on histopathology (mean, 153%; P < 0.05), while that on MRI was evaluated mostly accurately without overestimation (mean, 108%; P = 0.48). The interobserver reliability of the measurements using CT and MRI was good (ICC = 0.71 on CT, 0.74 on MRI). Ex-vivo MRI was more accurate than conventional CT in delineating the invasive component of lung adenocarcinoma.

Assessment of interobserver concordance in radiomic tools for lung nodule classification, with a focus on BRODERS and SILA

While CT lung cancer screening reduces lung cancer-specific mortality, there are remaining challenges. Radiomic tools promiss to address these challenges, however, they are subject to interobserver variability if semi-automated segmentation techniques are used. Herein we report interobserver variability for two validated radiomic tools, BRODERS (Benign versus aggRessive nODule Evaluation using Radiomic Stratification) and CANARY (Computer-Aided Nodule Assessment and Risk Yield). We retrospectively analyzed the CT images of 95 malignant lung nodules of the adenocarcinoma spectrum using BRODERS and CANARY. Cases were identified at Mayo Clinic (n = 45) and Vanderbilt University Medical Center and Nashville/Veteran Administration Tennessee Valley Health Care System (n = 50). Three observers with different training levels (medical student, internal medicine resident and thoracic radiology fellow) each performed lung nodule segmentation. All methods were carried out in accordance with relevant guidelines and regulations. Interclass correlation coefficients (ICC) of 0.77, 0.98 and 0.97 for the average nodule volume, BRODERS cancer probability and Score Indicative of Lesion Aggression (SILA) which summarizes the distribution of the CANARY exemplars indicated good to excellent reliability, respectively. The dice similarity coefficient was 0.79 and 0.81 for the data sets from the two institutions. BRODERS and CANARY are robust radiomics tools with excellent interobserver variability. These tools are simple and reliable regardless the observer/operator’s level of training.

A clinical spectrum of resectable lung adenocarcinoma with micropapillary component (MPC) concurrently presenting as mixed ground-glass opacity nodules.

In clinical practice, preoperative identification of mixed ground-glass opacity (mGGO) nodules with micropapillary component (MPC) to facilitate the implementation of individualized therapeutic strategies and avoid unnecessary surgery is increasingly importantOBJECTIVE: This study aimed to build a predictive model based on clinical and radiological variables for the early identification of MPC in lung adenocarcinoma presenting as mGGO nodules. The enrolled 741 lung adenocarcinoma patients were randomly divided into a training cohort and a validation cohort (3:1 ratio). The pathological specimens and preoperative images of malignant mGGO nodules from the study subjects were retrospectively reviewed. Furthermore, in the training cohort, selected clinical and radiological variables were utilized to construct a predictive model for MPC prediction. The MPC was found in 228 (43.3%) patients in the training cohort and 72 (41.1%) patients in the validation cohort. Based on the predictive nomogram, the air bronchogram was defined as the most dominant independent risk factor for MPC of mGGO nodules, followed by the maximum computed tomography (CT) value (> 200), adjacent to pleura, gender (male), and vacuolar sign. The nomogram demonstrated good discriminative ability with a C-index of 0.783 (95%[CI] 0.744-0.822) in the training cohort and a C-index of 0.799 (95%[CI] 0.732-0.866) in the validation cohort Additionally, by using the bootstrapping method, this predictive model calculated a corrected AUC of 0.774 (95% CI: 0.770-0.779) in the training cohort. This study proposed a predictive model for preoperative identification of MPC in known lung adenocarcinomas presenting as mGGO nodules to facilitate individualized therapy. This nomogram model needs to be further externally validated by subsequent multicenter studies.

Brief Report: Increasing Prevalence of Ground-Glass Nodules and Semisolid Lung Lesions on Outpatient Chest Computed Tomography Scans

IntroductionThe increased use of cross-sectional imaging frequently identifies a growing number of lung nodules that require follow-up imaging studies and physician consultations. We report here the frequency of finding a ground-glass nodule (GGN) or semisolid lung lesion (SSL) in the past decade within a large academic health system. MethodsA radiology system database review was performed on all outpatient adult chest computed tomography (CT) scans between 2013 and 2022. Radiology reports were searched for the terms “ground-glass nodule,” “subsolid,” and “semisolid” to identify reports with findings potentially concerning for an adenocarcinoma spectrum lesion. ResultsA total of 175,715 chest CT scans were performed between 2013 and 2022, with a steadily increasing number every year from 10,817 in 2013 to 21,916 performed in the year 2022. Identification of GGN or SSL on any outpatient CT increased from 5.9% in 2013 to 9.2% in 2022, representing a total of 2019 GGN or SSL reported on CT scans in 2022. The percentage of CT scans with a GGN or SSL finding increased during the study period in men and women and across all age groups above 50 years old. ConclusionsThe total number of CT scans performed and the percentage of chest CT scans with GGN or SSL has more than doubled between 2013 and 2022; currently, 9% of all chest CT scans report a GGN or SSL. Although not all GGN or SSL radiographic findings represent true adenocarcinoma spectrum lesions, they are a growing burden to patients and health systems, and better methods to risk stratify radiographic lesions are needed.

Molecular Imaging in Precision-Cut Non-Small Cell Lung Cancer Slices

BackgroundSmall animal models remain invaluable for the preclinical study of emerging molecular imaging agents. However, the data obtained in this setting are generated in genetically homogenous animals that do not mimic human pathophysiology. The purpose of this study was to prospectively validate precision-cut lung slices (PCLSs) obtained from patients with lung cancer as a translational tool for the development of targeted fluorophores. MethodsThe lung tissue was gently inflated with 2% Low-Melt Agarose (Fisher, 16520050) to avoid lung damage and minimize inflation pressure. The slices were then loaded into specialized cylindrical cartridges and inserted into a compressotome, and slices 150 to 350 μm thick were cut. Samples were incubated with fluorophore conjugates for ex vivo validation and immunohistochemical staining for receptor expression. ResultsA total of 184 unique 3-dimensional, architecturally preserved normal lung and non-small cell lung cancer samples were obtained between 2020 and 2022. The median nodule size was 1.1 ± 0.21 cm for benign lesions and 2.1 ± 0.19 cm for malignant nodules. A total of 101 of 135 (74.8%) malignant lesions were adenocarcinoma spectrum lung cancers. The median viability was 9.78 ± 1.86 days, and 1 μM of FAPL-S0456 (high-affinity fibroblast activation protein [FAP] targeting ligand linked to the near-infrared fluorophore S0456, On Target Laboratories)–targeted near-infrared fluorochrome localization demonstrated correlative labeling of FAP-positive tumor areas with a correlation coefficient of +0.94 (P < .01). There was no FAP fluorochrome uptake in normal lungs (r = −1; P < .001). ConclusionsPCLSs comprise a novel human tissue–based translational model that can be used to validate the efficacy of molecular imaging fluorochromes. PCLSs preserve the tumor microenvironment and parenchymal architecture that closely resemble the interactions of the immune and stromal components in humans.

Spectrum of Colorectal Adenocarcinomas: A 4 year experience in a tertiary care centre from Western Maharashtra

Colorectal cancer is the third most common cancer in both men and women. Environmental and genetic factors play a role in the development of colorectal carcinomaThe majority of colorectal cancers are sporadic, with hereditary cancer syndrome accounting for 10% of cases. Precursor lesions like adenoma that transform into adenocarcinoma cause the majority of colorectal cancers. : A total of 72 of colorectal malignancies were studied for histopathological features. The histologic features were studied for site, grade, tumor -infiltrating lymphocytes, Crohn -like lymphocytic reaction, mucinous histology, signet ring cell histology, and medullary growth pattern.: The mean age of the patients was 59.52 ± 11.80 years with M:F 1.76:1. Light microscopy showed TILs in 16 (22.2%) patients, followed by mucinous areas in 5 (6.9%), crohn like lymphocytic reaction in 4 (5.6%) and signet ring morphology in 2 (2.8%) patients.This study concludes that colorectal carcinomas are more common in 5th and 6th decade of life with slight male preponderance. The most common malignant lesion being moderately differentiated adenocarcinomas. This study highlights age and gender prevalence, as well as histopathological characteristics of colorectal carcinomas in this demographic region .

An integrated nomogram combined semantic-radiomic features to predict invasive pulmonary adenocarcinomas in subjects with persistent subsolid nodules.

Patients with persistent pulmonary subsolid nodules have a relatively high incidence of lung adenocarcinoma. Preoperative early diagnosis of invasive pulmonary adenocarcinoma spectrum lesions could help avoid extensive advanced cancer management and overdiagnosis in lung cancer screening programs. In total, 260 consecutive patients with persistent subsolid nodules ≤30 mm (n=260) confirmed by surgical pathology were retrospectively investigated from February 2016 to August 2020 at the Kaohsiung Veterans General Hospital. All patients underwent surgical resection within 3 months of the chest CT exam. The study subjects were divided into a training cohort (N=195) and a validation cohort (N=65) at a ratio of 3:1. The purpose of our study was to develop and validate a least absolute shrinkage and selection operator-derived nomogram integrating semantic-radiomic features in differentiating preinvasive and invasive pulmonary adenocarcinoma lesions, and compare its predictive value with clinical-semantic, semantic, and radiologist's performance. In the training cohort of 195 subsolid nodules, 106 invasive lesions and 89 preinvasive lesions were identified. We developed a least absolute shrinkage and selection operator-derived combined nomogram prediction model based on six predictors (nodular size, CTR, roundness, GLCM_Entropy_log10, HISTO_Entropy_log10, and CONVENTIONAL_Humean) to predict the invasive pulmonary adenocarcinoma lesions. Compared with other predictive models, the least absolute shrinkage and selection operator-derived model showed better diagnostic performance with an area under the curve of 0.957 (95% CI: 0.918 to 0.981) for detecting invasive pulmonary adenocarcinoma lesions with balanced sensitivity (92.45%) and specificity (88.64%). The results of Hosmer-Lemeshow test showed P values of 0.394 and 0.787 in the training and validation cohorts, respectively, indicating good calibration power. We developed a least absolute shrinkage and selection operator-derived model integrating semantic-radiomic features with good calibration. This nomogram may help physicians to identify invasive pulmonary adenocarcinoma lesions for guidance in personalized medicine and make more informed decisions on managing subsolid nodules.

Updates in Cholangiocarcinoma.

Cholangiocarcinoma is a spectrum of invasive adenocarcinomas that arise in the intrahepatic, perihilar, or distal biliary tree, and is classified by location. During JADPRO Live Virtual 2021, Kristen O’Hagan, MSN, RN, ANP-BC, AOCNP®, discussed this complex disease, current treatment strategies, and the role of targeted therapy and how it's changing the treatment landscape for cholangiocarcinoma.

Next-generation Sequencing Reveals Age-dependent Genetic Underpinnings in Lung adenocarcinoma.

Background: More than 40% of lung cancer patients are diagnosed at ages over 70. However, the genomic and clinical characteristics among them remain elusive. Here, we performed targeted capture sequence to characterize the mutational spectrum of Chinese lung adenocarcinoma (LUAD) patients across ages.Patients and Methods: 2025 LUAD patients were divided into three groups: young (≤50 years old) (n=416, 20.54%), intermediate (51~69 years old) (n=1271, 62.77%), and aged (≥70 years old) (n=338, 16.69%). 1,021-gene panel and 59-gene panel were used for sequencing with tissue samples. Genetic alterations and tumor mutation burden (TMB) in LUAD patients were investigated.Results: The frequency of mutations affecting 20 genes were significantly higher in aged group than in young group, and fourteen of them were not reported before, including involved in cell cycle/apoptosis signaling (FAT1, FAT2), DNA damage repair (FANCA and FANCM), chromatin histone modification (KDM6A), RTK/RAS/PI3K signaling (FLT4 and MTOR), NOTCH signaling (NOTCH1, NOTCH2 and NOTCH4) and other signaling pathway or cellular regulatory factor (KEAP1, ASXL1, EPHB1 and ABCB1). Six previously reported mutated genes (RBM10, KRAS, LRP1B, CDKN2A and KMT2C/D) were also significantly more frequent in aged group. Among clinical actionable mutation sites, KRAS mutation was presented more common in aged group; both MET exon 14 skipping and MET amplification were significantly positively correlated with old age; the fusions of ALK, ROS1, RET and ERBB2 exon 20 insertion were less frequent in aged group. Furthermore, a higher level of TMB was found in aged group compared with young group.Conclusion: In this study, we revealed the differences of somatic genetic mutations and TMB between young and aged LUAD patients, which may provide directions of targeted therapy and advantages of immunotherapy for the elderly in the future.

Olfactomedin 4 Is Not a Precise Marker for Human Intestinal Stem Cells, But Is Involved in Intestinal Carcinogenesis

Olfactomedin 4 Is Not a Precise Marker for Human Intestinal Stem Cells, But Is Involved in Intestinal Carcinogenesis

A case of haemoptysis and bilateral areas of lung consolidation sparing the right lower lobe.

Multiple primary lung cancers (MPLC) are often neglected. Obtaining pre-operative specimens through bronchoscopy could play a role. It is important to distinguish aerogenous metastasis from MPLC in the adenocarcinoma spectrum due to the different prognosis. https://bit.ly/3zbdVrw

3D Specimen Mapping Expedites Frozen Section Diagnosis of Nonpalpable Ground Glass Opacities

BackgroundPulmonary ground glass opacities (GGOs) are early-stage adenocarcinoma spectrum lesions that are not easily palpable. Challenges in localizing GGOs during intraoperative pathology can lead to imprecise diagnoses and additional time under anesthesia. To improve localization of GGOs during frozen section diagnosis, we evaluated a novel technique, 3-dimensional near-infrared specimen mapping (3D-NSM). MethodsFifty-five patients with a cT1 GGO were enrolled and received a fluorescent tracer preoperatively. After resection, specimens were inspected to identify lesions. Palpable and nonpalpable nodules underwent 3D-NSM and the area of highest fluorescence was marked with a suture. Time for 3D-NSM, time for frozen section diagnosis, and number of tissue sections examined were recorded. To compare 3D-NSM with standard-of-care techniques, a control cohort of 20 subjects with identical inclusion criteria were enrolled. Specimens did not undergo 3D-NSM and were sent directly to pathology. Results3D-NSM localized 54 of 55 lesions with 1 false negative. All 41 palpable lesions were identified by 3D-NSM. Thirteen (92.8%) of 14 nonpalpable lesions were located by 3D-NSM. Time to diagnosis for the 3D-NSM cohort was 23.5 minutes, compared with 26.0 minutes in the control cohort (P = .04). 3D-NSM did not affect time to diagnosis of palpable lesions (23.2 minutes vs 21.4 minutes; P = .10). 3D-NSM significantly reduced time to diagnosis for nonpalpable lesions (23.3 minutes vs 34.4 minutes; P < .0001). 3D-NSM also reduced the number of tissue sections analyzed in nonpalpable lesions (4.50 vs 11.00; P < .0001). Conclusions3D-NSM accurately localizes GGOs and expedites intraoperative diagnosis by reducing the number of tissue sections analyzed for nonpalpable GGOs.

Evaluation of OTL38-Generated Tumor-to-Background Ratio in Intraoperative Molecular Imaging-Guided Lung Cancer Resections.

Cancer surgery has multiple challenges including localizing small lesions, ensuring negative margins, and identifying synchronous cancers. One of the tools proposed to address these issues is intraoperative molecular imaging (IMI). An important consideration in IMI is the quantification of the tumor fluorescence during the procedure and using that data to add clinical value. Currently, the most commonly cited measure of quantification is the tumor-to-background ratio (TBR). Our goal was to evaluate the clinical value of TBR measured with OTL38 NIR tracer during a lung cancer resection. Intraoperative data was retrospectively reviewed from a prospectively collected 5-year database. Between 2015 and 2020, 279 patients were included in the study. For standardization, all patients underwent infusion of the same targeted molecular optical contrast agent (OTL38) for lung cancer resections; then, the mean fluorescence intensity of the tumors and background tissues were calculated. To evaluate the clinical efficacy of the TBR calculation, the results were correlated with patient, biologic, tumor, and technological factors. For pulmonary surgery, patient factors such as gender, age, smoking history, and time from infusion of OTL38 to surgery did not have any statistical significance in predicting the TBR during surgery. In addition, TBR measurements did not correlate with location of the tumor in the lung (p= 0.123). There was no statistical correlation of preoperative positron emission tomography measurements (standardized uptake value) with intraoperative TBR. However, there was statistically significant negative correlation of in situ TBR measurement and the distance of the lesion from the surface of the organ (p< 0.001). Adenocarcinoma spectrum lesions overall had statistically significant correlation with in situ fluorescence compared to other NSCLC malignancies (p< 0.01) but TBR measurements could not identify histopathologic subtype on univariate analysis (p= 0.089). There was a tendency for in situ fluorescence for moderately and well-differentiated adenocarcinoma spectrum lesions, but this was not statistically significant. When comparing the in situ TBR of benign to malignant nodules in the lung, there was no statistically significant association (p= 0.145). In subset analysis, adenocarcinoma spectrum lesions tend to fluoresce at brighter with OTL38 compared to other histologic subtypes. In our various iterations, the results of our retrospective analysis did not show that TBR measurements during OTL38-guided surgery provide clinically useful information about the nature of the nodule or cancer. The true value of IMI is in the ability for the surgeon to use the fluorescence to guide the surgeon to the tumor and margins, but that sophisticated quantification of the amount of fluorescence may not have clinical utility.

Clinical Features, Molecular Alterations and Prognosis of Colorectal Adenocarcinoma With Mucinous Component in Chinese Patients.

Mucinous adenocarcinoma (MAC) is conventionally diagnosed by WHO definition when the extracellular mucin is >50% of the tumor area, while tumors with <50% mucin are designated as having a mucinous component. The study is aimed at analyzing the clinicopathologic characteristics, mutation spectrum, and prognosis of colorectal adenocarcinoma with mucinous component (CAWMC). Mutation analyses for exon 2 to 4 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing. Expression of DNA mismatch repairs and P53 proteins were evaluated by immunohistochemistry. Density of tumor-infiltrating lymphocyte (TIL) status was scored. We also evaluated the percentage of glands producing mucin and the morphology of the different tumor cell types in mucin pools. We retrospectively analyzed the prognosis of 43 patients with stage II/III. The overall frequencies of KRAS and BRAF mutations were 36% and 8%, respectively. Patients with MAC exhibiting high levels of mucin were related to the increase of tumor diameter (P=0.038) but were not associated with any of the other clinicopathologic parameters. The proportion or variable morphology of mucinous component did not stratify progression-free survival in stage II/III cases. TIL was the most significant predictor of progression-free survival among stage II/III CAWMC. It is interesting to note that signet ring cell carcinoma does not portend a worse prognosis for patients with high TIL levels. Combining use the grade of TIL status with the WHO grade of the entire tumor can help identify patients with a high risk of recurrence more accurately.

SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the “SalvGlandDx” panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

A comparative study to evaluate CT-based semantic and radiomic features in preoperative diagnosis of invasive pulmonary adenocarcinomas manifesting\xa0as subsolid nodules

This study aims to predict the histological invasiveness of pulmonary adenocarcinoma spectrum manifesting with subsolid nodules ≦ 3 cm using the preoperative CT-based radiomic approach. A total of 186 patients with 203 SSNs confirmed with surgically pathologic proof were retrospectively reviewed from February 2016 to March 2020 for training cohort modeling. The validation cohort included 50 subjects with 57 SSNs confirmed with surgically pathologic proof from April 2020 to August 2020. CT-based radiomic features were extracted using an open-source software with 3D nodular volume segmentation manually. The association between CT-based conventional features/selected radiomic features and histological invasiveness of pulmonary adenocarcinoma status were analyzed. Diagnostic models were built using conventional CT features, selected radiomic CT features and experienced radiologists. In addition, we compared diagnostic performance between radiomic CT feature, conventional CT features and experienced radiologists. In the training cohort of 203 SSNs, there were 106 invasive lesions and 97 pre-invasive lesions. Logistic analysis identified that a selected radiomic feature named GLCM_Entropy_log10 was the predictor for histological invasiveness of pulmonary adenocarcinoma spectrum (OR: 38.081, 95% CI 2.735–530.309, p = 0.007). The sensitivity and specificity for predicting histological invasiveness of pulmonary adenocarcinoma spectrum using the cutoff value of CT-based radiomic parameter (GLCM_Entropy_log10) were 84.8% and 79.2% respectively (area under curve, 0.878). The diagnostic model of CT-based radiomic feature was compared to those of conventional CT feature (morphologic and quantitative) and three experienced radiologists. The diagnostic performance of radiomic feature was similar to those of the quantitative CT feature (nodular size and solid component, both lung and mediastinal window) in prediction invasive pulmonary adenocarcinoma (IPA). The AUC value of CT radiomic feature was higher than those of conventional CT morphologic feature and three experienced radiologists. The c-statistic of the training cohort model was 0.878 (95% CI 0.831–0.925) and 0.923 (0.854–0.991) in the validation cohort. Calibration was good in both cohorts. The diagnostic performance of CT-based radiomic feature is not inferior to solid component (lung and mediastinal window) and nodular size for predicting invasiveness. CT-based radiomic feature and nomogram could help to differentiate IPA lesions from preinvasive lesions in the both independent training and validation cohorts. The nomogram may help clinicians with decision making in the management of subsolid nodules.

LINC01133: an emerging tumor-associated long non-coding RNA in tumor and osteosarcoma.

Emerging evidence suggested that long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis. LINC01133 is a newly identified lncRNA first discovered as an oncogene in lung squamous cell carcinoma. Subsequent studies further demonstrated this lncRNA was deregulated in a wide spectrum of tumors, including colorectal, gastric, lung, and pancreatic ductal adenocarcinoma as well as osteosarcoma and hepatocellular carcinoma. Intriguingly, this lncRNA exerted oncogenic or tumor-suppressive action in a tissue-dependent manner. This review sought to summarize our current understanding concerning the deregulation of LINC01133 in human tumors in relation to its molecular mechanisms and cellular functions. The clinical utilization of LINC01133 as a potential prognostic biomarker and a treatment target is also discussed.

Clinicopathological Characteristics and Mutation Spectrum of Colorectal Adenocarcinoma With Mucinous Component in a Chinese Cohort: Comparison With Classical Adenocarcinoma.

Background: Colorectal adenocarcinoma with mucinous component (AWMC) is a special entity of colorectal cancer. The study is aimed at analyzing the clinicopathological characteristics, mutation spectrum, and prognosis of AWMC and comparing it with classical adenocarcinoma (AC) in a Chinese cohort.Methods: One hundred eight AMWC and 204 AC patients were included. Targeted next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded (FFPE) tissues. AWMC was further divided into two groups: AWMC with signet ring cell component and AWMC without signet ring cell component. Clinicopathological features, mismatch repair protein (MMR) status, genetic alterations, and survival outcomes were analyzed after tumor location was taken into consideration.Results: AWMC had larger tumor size (p = 0.014) and showed predilection for proximal colon (p < 0.001) compared with AC. Regardless of primary sites, AWMC was associated with less metastasis (p < 0.001) and earlier AJCC stage (p < 0.001). Mismatch repair protein deficiency (dMMR) was more commonly detected in AWMC than in AC for right-sided colon (p < 0.001), but the difference was not significant for left-sided colon (p = 0.081). The five most commonly mutated genes in AWMC were KRAS (45.4%), TP53 (39.8%), APC (22.2%), PIK3CA (22.2%), and SMAD4 (10.2%). AWMC showed a significantly lower mutation rate of TP53 than AC, both in right-sided colon and in left-sided colon (p < 0.001 and p = 0.033, respectively). In left-sided colon, AWMC with signet ring cell component had a significantly smaller size than tumors with signet ring cell component (p = 0.034). No dMMR cases were detected in AWMC with signet ring cell component (n = 7). Moreover, AWMC with signet ring cell component had a significantly lower KRAS mutation rate than AWMC without signet ring cell component, both in right-sided colon and in left-sided colon (p = 0.036 and p = 0.012, respectively). The disease-specific survival (DSS) for AWMC and AC were not statistically different (p = 0.0587). Multivariate analysis showed that AWMC was not an independent predictor of prognosis.Conclusion: Regardless of primary sites, AWMC demonstrates less metastasis, earlier stages, more frequent dMMR, and lower TP53 mutation rate than AC. Our results indicate that different molecular pathogenesis might underlie mucinous morphology in colorectal carcinoma. Mucinous component is not an independent factor of outcome.