Spectrum Of Adenocarcinoma Research Articles

Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial.

Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

Lipiodol lOcalization for Ground-glass opacity mInimal Surgery: Rationale and design of the LOGIS trial

ObjectivesThe diagnosis and treatment of ground-glass opacity (GGO) lesions have become important issues because subsolid nodules including GGO are known to frequently represent the histologic spectrum of lung adenocarcinoma. Because small GGO lesions cannot usually be palpated or visualized during surgery, several marking techniques have been reported for localization during thoracoscopic surgery, such as lipiodol and hook-wire localization. This study is designed to demonstrate the usefulness and safety of the lipiodol localization technique for individuals undergoing GGO VATS resection compared to the hook-wire localization technique. MethodsTwo hundred fifty participants will be prospectively enrolled in a 1:1 manner to the lipiodol or hook-wire group according to the inclusion criteria. All study participants will undergo preoperative lung localization using either the lipiodol or hook-wire method. Thoracoscopic surgery will be performed by experienced thoracoscopic surgeons within several hours after marking under general anesthesia. The primary endpoint is the procedure success rate, and the secondary endpoints are the procedure complication rate, procedure time, surgery time and the margin from the lesion in the resected specimen. ResultsPatient enrollment will be completed within 2years. We will analyze the procedure success rate and the presence of complications with regard to the CT results. In addition, the procedure and surgery times, and the safety margin will be also compared between the 2 techniques. ConclusionIf the aims of this study are achieved, then the use of lipiodol localization technique will be widespread in the localization of non-palpable pulmonary lesions that are indicated for surgical resection. (ClinicalTrials.gov: NCT02180568)

PTH-276 Adenocarcinoma of rectum – a composite of 3 different subtypes with varying outcomes?

<h3>Introduction</h3> Considerable confusion exists with regards to the terminology of mucin secreting adenocarcinomas of the rectum. The WHO classification system needs to be followed accurately for comparing the outcomes of mucinous and signet ring cell carcinomas. We hypothesised that clinico-pathological outcome measures like margins, tumour regression grade, recurrence rates and survival vary with histology. <h3>Method</h3> We conducted a retrospective analysis of a prospectively maintained database. All Stage I-III rectal adenocarcinoma patients were included. <h3>Results</h3> Between May 2010 and August 2013, 273 patients underwent curative resection. Both the mucin secreting variants were more common in young age and presented at a more advanced stage.14%of tumours had signet ring cell histology whereas 8% had mucinous histology. 54% and 48% of signet ring cell carcinoma (SRCC) and mucinous adenocarcinoma (MAC) patients were node positive in contrast to the classical variant (30%). CRM positivity was 24% with MAC and 19% with SRCC as compared to 4% with the classical variant. The DFS among the classical and mucinous variants was 38.5 and 37.4 months, respectively, whereas it was 28.6 months in the SRCC group. OS did not differ significantly. <h3>Conclusion</h3> There is a high incidence of aggressive mucin secreting variants in India. There exists a spectrum of adenocarcinomas of rectum with progressively worsening outcomes from classical to MAC to SRCC. These aggressive variants might warrant more aggressive resections. <h3>Disclosure of interest</h3> None Declared.

Radial endobronchial ultrasound images for ground-glass opacity pulmonary lesions.

Radial endobronchial ultrasound (R-EBUS) is a useful tool for precise localisation of peripheral pulmonary lesions, but there have been no detailed reports about the use of R-EBUS images for ground-glass opacity (GGO). The R-EBUS images of 116 patients with GGO, who were diagnosed as having adenocarcinoma by R-EBUS with a guide sheath (EBUS-GS), were compared with the respective chest computed tomography findings. In 103 patients, R-EBUS images were correlated with the histological surgical specimens. R-EBUS images of GGO were identified based on the internal structure of the lesion and classified into two groups. Blizzard showed an enlarged, diffuse hyperintense acoustic shadow. Mixed blizzard showed a combination of blizzard and some diffuse heterogeneity with several hyperechoic dots and vessels. All pure GGO lesions (nine out of nine) were blizzard on R-EBUS. For part-solid GGOs, the percentage of mixed blizzard was inversely related to the amount of the GGO component. Histological findings from surgery revealed that all blizzard lesions were on the spectrum of adenocarcinoma in situ to well differentiated adenocarcinoma while majority (33 out of 64) of mixed blizzard lesions were moderately to poorly differentiated adenocarcinoma. R-EBUS types are important to locate GGOs prior to transbronchial sampling with EBUS-GS.

Noninvasive Risk Stratification of Lung Adenocarcinoma using Quantitative Computed Tomography

Lung cancer remains the leading cause of cancer-related deaths in the United States and worldwide. Adenocarcinoma is the most common type of lung cancer and encompasses lesions with widely variable clinical outcomes. In the absence of noninvasive risk stratification, individualized patient management remains challenging. Consequently a subgroup of pulmonary nodules of the lung adenocarcinoma spectrum is likely treated more aggressively than necessary. Consecutive patients with surgically resected pulmonary nodules of the lung adenocarcinoma spectrum (lesion size ≤3 cm, 2006-2009) and available presurgical high-resolution computed tomography (HRCT) imaging were identified at Mayo Clinic Rochester. All cases were classified using an unbiased Computer-Aided Nodule Assessment and Risk Yield (CANARY) approach based on the quantification of presurgical HRCT characteristics. CANARY-based classification was independently correlated to postsurgical progression-free survival. CANARY analysis of 264 consecutive patients identified three distinct subgroups. Independent comparisons of 5-year disease-free survival (DFS) between these subgroups demonstrated statistically significant differences in 5-year DFS, 100%, 72.7%, and 51.4%, respectively (p = 0.0005). Noninvasive CANARY-based risk stratification identifies subgroups of patients with pulmonary nodules of the adenocarcinoma spectrum characterized by distinct clinical outcomes. This technique may ultimately improve the current expert opinion-based approach to the management of these lesions by facilitating individualized patient management.

Glandular neoplasms of the urachus: a report of 55 cases emphasizing mucinous cystic tumors with proposed classification.

Published experience remains limited for glandular neoplasms of the urachus, especially mucinous cystic tumors. We reviewed 55 glandular urachal neoplasms to evaluate their clinical features and histopathologic spectrum and to devise a classification system for the mucinous cystic forms. Within the 55 cases studied, we observed 2 groups with differing clinical, gross, and histopathologic features. The first group, invasive, noncystic adenocarcinomas (n=24), had clinicopathologic features in accord with the known spectrum of urachal adenocarcinoma (mean age 50 y, female:male ratio 1.7, with recurrence or death from disease in 9/16 cases over a 45 mo mean follow-up). The second group, mucinous cystic tumors (n=31), morphologically resembled mucinous cystic tumors of the ovary and appeared classifiable by the same approach (mean age 47 y, female:male ratio 1.4) and included mucinous cystadenoma (n=4), mucinous cystic tumor of low malignant potential (n=22, including 2 cases with intraepithelial carcinoma), and mucinous cystadenocarcinoma with microscopic (n=4) or frank invasion (n=1). Follow-up information was available for 13 patients with mucinous cystic tumors (mean 41 mo); we observed no local recurrence or distant metastasis. This experience suggests that there is a distinct group of glandular, cystic tumors of the urachus that is classifiable in a manner similar to ovarian neoplasms and that has a favorable prognosis after complete excision. As with cystic neoplasms of other organs, rigorous sampling is recommended to identify potentially small foci of carcinoma that could be missed by inadequate sampling. Accordingly, classification based on methods other than complete surgical excision may be hazardous.

Current Issues in Gynecologic Pathology

Current Issues in Gynecologic Pathology

Management strategy of pulmonary nodule in 2013

Lung nodules are commonly found on computed tomography (CT) and need a standardized approach in order to avoid misdiagnosing lung cancer and delaying surgical excision whilst simultaneously avoiding unnecessary invasive procedures if the lesions prove to be benign. Great advances have been made in the last decade in various areas affecting the management of lung nodules: the understanding of the molecular mechanisms behind carcinogenesis, a new classification of lung adenocarcinoma, new data on lung cancer screening, widespread use of multi-detector row CT and development of volumetric analysis software for nodules. Recent decision-making algorithms are based on the size, density and follow-up of the nodule. The distinction between solid nodules, sub-solid nodules and pure ground glass nodules is fundamental, and has a strong correlation with the histologic spectrum of adenocarcinoma. In the absence of criteria suggesting benign disease, the radiologist's report should offer one of the following two options: follow-up based on the recommendations if the nodule is equivocal, or multidisciplinary discussion to consider invasive management if the nodule is highly suspicious of malignancy. Recent data from this statement are reviewed and practical guidelines are offered based on international expert consensus opinion.

Noninvasive Characterization of the Histopathologic Features of Pulmonary Nodules of the Lung Adenocarcinoma Spectrum using Computer-Aided Nodule Assessment and Risk Yield (CANARY)—A Pilot Study

Pulmonary nodules of the adenocarcinoma spectrum are characterized by distinctive morphological and radiologic features and variable prognosis. Noninvasive high-resolution computed tomography-based risk stratification tools are needed to individualize their management. Radiologic measurements of histopathologic tissue invasion were developed in a training set of 54 pulmonary nodules of the adenocarcinoma spectrum and validated in 86 consecutively resected nodules. Nodules were isolated and characterized by computer-aided analysis, and data were analyzed by Spearman correlation, sensitivity, and specificity and the positive and negative predictive values. Computer-aided nodule assessment and risk yield (CANARY) can noninvasively characterize pulmonary nodules of the adenocarcinoma spectrum. Unsupervised clustering analysis of high-resolution computed tomography data identified nine unique exemplars representing the basic radiologic building blocks of these lesions. The exemplar distribution within each nodule correlated well with the proportion of histologic tissue invasion, Spearman R = 0.87, p < 0.0001 and 0.89 and p < 0.0001 for the training and the validation set, respectively. Clustering of the exemplars in three-dimensional space corresponding to tissue invasion and lepidic growth was used to develop a CANARY decision algorithm that successfully categorized these pulmonary nodules as "aggressive" (invasive adenocarcinoma) or "indolent" (adenocarcinoma in situ and minimally invasive adenocarcinoma). Sensitivity, specificity, positive predictive value, and negative predictive value of this approach for the detection of aggressive lesions were 95.4, 96.8, 95.4, and 96.8%, respectively, in the training set and 98.7, 63.6, 94.9, and 87.5%, respectively, in the validation set. CANARY represents a promising tool to noninvasively risk stratify pulmonary nodules of the adenocarcinoma spectrum.

Subsolid pulmonary nodules

Given the higher rate of malignancy of subsolid pulmonary nodules and the considerably lower growth rate of ground-glass nodules (GGNs), dedicated standardized guidelines for management of these nodules have been proposed, including long-term low-dose computed tomography (CT) follow-up (≥3 years). Physicians must be familiar with the strategic management of subsolid pulmonary nodules, and should be able to identify imaging features that suggest invasive adenocarcinoma requiring a more aggressive management. Low-dose CT screening studies for early detection of lung cancer have increased our knowledge of pulmonary nodules, and in particular our understanding of the strong although imperfect correlation of the subsolid pulmonary nodules, including pure GGNs and part-solid nodules, with the spectrum of preinvasive to invasive lung adenocarcinoma. Serial CT imaging has shown stepwise progression in a subset of these nodules, characterized by increase in size and density of pure GGNs and development of a solid component, the latter usually indicating invasive adenocarcinoma. There is close correlation between the CT features of subsolid nodules (SSNs) and the spectrum of lung adenocarcinoma. Standardized guidelines are suggested for management of SSNs.

Anterior gradient 2 profiling in Barrett columnar epithelia and adenocarcinoma

Barrett esophagus is the precancerous lesion leading to Barrett adenocarcinoma. The natural history of Barrett metaplasia and its neoplastic progression are still controversial. Anterior gradient 2 is up-regulated in both Barrett intestinal metaplasia and Barrett adenocarcinoma, but no information is available on anterior gradient 2 expression in the spectrum of the phenotypic changes occurring in the natural history of Barrett adenocarcinoma (Barrett esophagus cardiac-type metaplasia, Barrett esophagus intestinal metaplasia, low-grade intraepithelial neoplasia [formerly called low-grade dysplasia], and high-grade intraepithelial neoplasia [formerly called high-grade dysplasia]). Applying immunohistochemistry and reverse transcription and quantitative real-time polymerase chain reaction, this study addressed the role of anterior gradient 2 in Barrett carcinogenesis. Anterior gradient 2 expression was assessed semiquantitatively in 125 consecutive biopsy samples in the adenocarcinoma spectrum arising in Barrett esophagus (Barrett esophagus cardiac-type metaplasia, 25; Barrett esophagus intestinal metaplasia, 25; low-grade intraepithelial neoplasia, 25; high-grade intraepithelial neoplasia, 25; Barrett adenocarcinoma, 25). Additional biopsy samples of esophageal squamous mucosa (n=25) served as controls. Anterior gradient 2 messenger RNA expression was also tested (reverse transcription and quantitative real-time polymerase chain reaction) in a different series of 40 samples (esophageal squamous mucosa, 10; Barrett esophagus cardiac-type metaplasia, 10; Barrett esophagus intestinal metaplasia, 10; Barrett adenocarcinoma, 10). Anterior gradient 2 was never expressed in squamous esophageal epithelium but consistently overexpressed (to much the same degree) in the whole spectrum of Barrett disease (Barrett esophagus cardiac-type metaplasia, Barrett esophagus intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and Barrett adenocarcinoma). Anterior gradient 2 messenger RNA was expressed significantly more in Barrett esophagus cardiac-type metaplasia, Barrett esophagus intestinal metaplasia, and Barrett adenocarcinoma than in native squamous epithelium (P<.001), with no significant differences between the 3 groups. Anterior gradient 2 overexpression affects the whole spectrum of the metaplastic/neoplastic lesions involved in Barrett carcinogenesis. This study supports the biological similarity of the nonintestinal and intestinal types of Barrett metaplasia as precursors of Barrett adenocarcinoma.

SnapShot: Lung Cancer Models

from endogenous locus. Viral cre delivery via adenoviral or lentiviral inoculation (intranasal or intratracheal).Adenocarcinoma spectrum histology (i.e., in situ and invasive neoplasia) in lung; metastasis not reported.K-ras somatic mutations identified in ~20%-30% of lung adenocarcinomas. Mouse models of the oncogenic K-ras allele have been used in preclinical studies of cisplatin resistance and combination targeted therapies.K-ras

Noninvasive Characterization of Tissue Invasion by Pulmonary Nodules of the Lung Adenocarcinoma Spectrum Using CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) - A Pilot Study

PURPOSE: Due to increased use of high-resolution computed tomography (HRCT), sub-solid pulmonary nodules of the adenocarcinoma spectrum with unknown clinical significance are increasingly identified. New strategies for non-invasive risk stratification to guide individualized treatment decisions regarding radiological observation versus surgical intervention, and the extent of the required resection are urgently needed. In these tumors, absent or minimal histopathologic tissue invasion has been associated with excellent patient outcomes.

Carcinomes bronchiolo-alvéolaires : du concept aux stratégies thérapeutiques innovantes

Bronchioloalveolar carcinoma (BAC) is a primary pulmonary adenocarcinoma (ADC) developped from the terminal respiratory unit. Its restrictive definition adopted by the 1999 WHO pathological classification needs a complete tumor resection to exclude any signs of histological invasion. Although IIIB-IV tumors were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 had focussed on the need to include in the same spectrum of disease pure BAC and ADC with BAC feature (ADC-WBF). BAC and ADC-WBF affect more frequently women, non-smokers and Asian people than other non-small cell carcinoma. Their predominant lepidic and aerogenous tumor progression results in a frequent pneumonic, multifocal or diffuse presentation and explains why death is more frequently related to bilateral pulmonary involvement than extrathoracic metastasis. Natural history is slower and prognosis better than for other ADC. Within this entity, there are different cytological subtypes: mucinous, non-mucinous and mixed and according to them different clinical and biological phenotypes, with different sensitivity to therapeutic agents. At present, the diagnosis, the staging and the therapeutic strategy does not differ from that of non-small lung carcinoma cells. In localized forms, surgical resection remains the best therapeutic option for localized tumors. In diffuse forms, high frequency of epidermal growth factor receptor (EGFR) expression on tumor cells and its gene amplification and/or mutation as well as a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors offer new strategy of therapeutical management in patients with non-resectable tumor. However, the place of chemotherapy has recently been revisited in this entity known until now as chemoresistant tumors. The results are being evaluated. It is necessary to continue therapeutic trials to determine criteria for choosing a first-line TKI or conventional chemotherapy in that entity. Cytological subtype will probably have an important role to play in this choice.

Subsolid Pulmonary Nodules and the Spectrum of Peripheral Adenocarcinomas of the Lung: Recommended Interim Guidelines for Assessment and Management

Subsolid Pulmonary Nodules and the Spectrum of Peripheral Adenocarcinomas of the Lung: Recommended Interim Guidelines for Assessment and Management

Differential Pathologic Variables and Outcomes across the Spectrum of Adenocarcinoma of the Esophagogastric Junction

Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors. We adapted a large prospective database (n=520: 180 type I, 182 type II, 158 type III) to compare AEG tumors under the new TNM system Pathological variables associated with prognosis were compared (pT, pN, stage, differentiation, R status, lymphovascular invasion, perineural involvement, number of positive nodes, percent of positive nodes, and tumor length), as well as overall survival. Compared with AEG type I tumors, type II and type III tumors had significantly (p<0.05) more advanced pN stages, greater number and percentage of positive nodes, poorer differentiation, more radial margin involvement, and more perineural invasion. In AEG type I, 14/180 patients (8%) had >6 involved nodes (pN3), compared with 16 and 30% of patients classified type II and III, respectively. Median survival was significantly (p=0.03) improved for type I patients (38months) compared with those with tumors classified as type II (28months) and type III (24months). In multivariate analysis node positivity and pN staging but not AEG site had an impact on survival. In this series AEG type I is associated with more favorable pathologic features and improved outcomes compared with AEG type II and III. This may reflect earlier diagnosis, but an alternative possibility, that type I may be a unique paradigm with more favorable biology, requires further study.

Subsolid pulmonary nodules and the spectrum of peripheral adenocarcinomas of the lung: recommended interim guidelines for assessment and management

Subsolid pulmonary nodules and the spectrum of peripheral adenocarcinomas of the lung: recommended interim guidelines for assessment and management

Cytology, Pathology, Frozen Section and Occult Primaries in Head and Neck Cancers

Abstract Whilst squamous cell carcinomas take center stage in the head and neck area, almost any mass disease that can occur in the rest of the body can theoretically occur here too. This includes the spectrum of adenocarcinomas, lymphomas, melanomas and sarcomas, not forgetting the diversity of salivary gland and thyroid tumors. Diagnoses by FNAC, open biopsy or frozen section have their own inherent, site specific, individualistic problems, and some of the basic principles will be highlighted. Frozen sections for resection margins and staging will be dealt with. Finally the challenge of the occult primary with metastasis in the head and neck, and understanding the need for immunohistochemistry are also touched upon.

Subsolid Pulmonary Nodules and the Spectrum of Peripheral Adenocarcinomas of the Lung: Recommended Interim Guidelines for Assessment and Management

Pulmonary nodule characterization is currently being redefined as new clinical, radiologic, and pathologic data are reported, necessitating a reevaluation of the clinical management, especially of subsolid nodules. These are now known to frequently, although not invariably, fall into the spectrum of peripheral adenocarcinomas of the lung. Strong correlation between the Noguchi histologic classification and computed tomographic (CT) appearances of these lesions, in particular, has been reported. Serial CT findings have further documented that stepwise progression of lesions with ground-glass opacity, manifested as an increase in size or the appearance and/or subsequent increase of solid components, does occur in a select subset of patients. As a consequence, recognition of the potential association between subsolid nodules and peripheral adenocarcinomas requires a review of current guidelines for the management of these lesions, further necessitated by a differential diagnosis that includes benign lesions such as focal inflammation, focal fibrosis, and organizing pneumonia. Specific issues that need to be addressed are the need for consensus regarding an appropriate CT classification, methods for precise measurement of subsolid nodules, including the extent of both ground-glass and solid components, as well as accurate assessment of the growth rates as means for predicting malignancy and prognosis. It is anticipated that interim guidelines may serve to standardize our current management of these lesions, pending further clarification of their natural history.

Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model: translational implications for diagnosis and therapy

Esophageal adenocarcinoma arises in the backdrop of Barrett metaplasia-dysplasia sequence, with the vast majority of patients presenting with late-stage malignancy. Mesothelin, a glycophosphatidylinositol-anchored protein, is aberrantly overexpressed on the surface of many solid cancers. Mesothelin expression was assessed in esophageal tissue microarrays encompassing the entire histological spectrum of Barrett-associated dysplasia and adenocarcinoma. Mesothelin expression was observed in 24/84 (29%) of invasive adenocarcinomas and in 5/34 (15%) lymph node metastases. In contrast, normal squamous and cardiac mucosa, as well as noninvasive Barrett lesions, failed to label with mesothelin. Mesothelin was expressed in the esophageal adenocarcinoma cell line JH-EsoAd1 but not in primary human esophageal epithelial cells. Anti-mesothelin antibody–conjugated CdSe/CDS/ZnS quantum rods were synthesized, and confocal bioimaging confirmed robust binding to JH-EsoAd1 cells. Anti-mesothelin antibody–conjugated nanoparticles can be useful for the diagnosis and therapy of mesothelin-overexpressing esophageal adenocarcinomas.