Neuroendocrine neoplasms of the appendix, colon and rectum.

Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most recent WHO classification as neuroendocrine tumors (NET), neuroendocrine carcinomas (NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNENs). NECs and MiNENs are aggressive neoplasms requiring multimodal treatment strategies. By contrast, NETs are, in most cases, indolent lesions occurring as incidental findings in the appendix or as polyps in the rectum. While most appendiceal and rectal NETs are considered relatively non-aggressive neoplasms, a few cases, may show a more aggressive clinical course. Unfortunately, clinical/pathological characteristics to select patients at high risk of recurrence/metastases are poorly consolidated. Diagnosis is generally easy and supported by the combination of morphology and immunohistochemistry. Differential diagnostic problems are for NECs/MiNENs with poorly differentiated adenocarcinomas, when immunohistochemical neuroendocrine markers are not obviously positive, whereas for NETs they are represented by the rare appendiceal tubular and clear cell variants (which may be confused with non-neuroendocrine cancers) and rectal L-cell tumors which may be chromogranin negative and prostatic marker positive.

Augmented-reality robot-assisted radical prostatectomy using hyper-accuracy three-dimensional reconstruction (HA3D™) technology: a radiological and pathological study.

OBJECTIVES: To assess the use of hyper-accuracy three-dimensional (HA3D™; MEDICS, Moncalieri, Turin, Italy) reconstruction based on multiparametric magnetic resonance imaging (mpMRI) and superimposed imaging during augmented-reality robot-assisted radical prostatectomy (AR-RARP). PATIENTS AND METHODS: Patients with prostate cancer (clinical stages cT1-3, cN0, cM0) undergoing RARP at our Centre, from June 2017 to April 2018, were enrolled. In all cases, cancer was diagnosed with targeted biopsy at the level of index lesion based on high-resolution (1-mm slices) mpMRI. HA3D reconstruction was created by dedicated software to obtain the 3D virtual model of the prostate and surrounding structures. A specific system was used to overlay virtual data on the endoscopic video displayed by the remote da Vinci® surgical console (Intuitive Surgical Inc., Sunnyvale, CA, USA), and the virtual images were superimposed by the surgeon by the means of the TilePro™ multi-input display technology (Intuitive Surgical Inc.). The AR technology was used in four standardised key steps during RARP. The procedures were modulated differently in cases of prostate cancer without extracapsular extension (ECE) at mpMRI (Group A) or in cases of prostate cancer with ECE (Group B) at mpMRI. In Group A, the virtual image of the prostate was overlaid on the endoscopic view and the intraprostatic lesion was marked on the prostate surface by a metallic clip at the level of the suspicious lesion as identified by the 3D virtual AR image. In Group B, the same step was performed; moreover, a metallic clip was placed at the level of the suspicious ECE on the neurovascular bundles (NVBs) according to the virtual images. Finally, selective biopsies were taken from the NVBs at this level, and then, the entire NVBs were removed for final pathological examination, according to standard clinical indications. For Group A, the pathologist performed a targeted needle biopsy at the level of the metallic clip on the surface of prostate before the sample reduction. For Group B, the presence of tumour was evaluated during the reduction phase, at the level of metallic clip on the prostate surface and at the level of NVBs, sent separately. Finally, an image 3D scanner (Kinect, Microsoft) was used to perform a dimensional comparison between the mpMRI-based 3D virtual reconstruction and the whole-mount specimen. RESULTS: In all, 30 patients were enrolled in the present study, 11 (36.6%) included in Group A and 19 (63.4%) in Group B. In all cases (30/30), final pathology confirmed the location of the index lesion, as cancer was found at the level of the metallic clip. The suspected ECE was confirmed on final pathology in 15/19 cases (79%). The AR-guided selective biopsies at the level of the NVBs confirmed the ECE location, with 11/15 (73.3%) biopsies at the level of NVBs positive for cancer. The mismatch between the 3D virtual reconstruction and the prostate 3D scanning based on the whole-mount specimen was <3 mm in >85% of the gland. CONCLUSION: Our results suggest that a HA3D virtual reconstruction of the prostate based on mpMRI data and real-time superimposed imaging allow performance of an effective AR-RARP. Potentially, this approach translates into better outcomes, as the surgeon can tailor the procedure for each patient.

The Sulfolobus solfataricus RecQ-like DNA helicase Hel112 inhibits the NurA/HerA complex exonuclease activity.

ATPase/Helicases and nucleases play important roles in DNA end-resection, a critical step during homologous recombination repair in all organisms. In hyperthermophilic archaea the exo-endonuclease NurA and the ATPase HerA cooperate with the highly conserved Mre11-Rad50 complex in 3' single-stranded DNA (ssDNA) end processing to coordinate repair of double-stranded DNA breaks. Little is known, however, about the assembly mechanism and activation of the HerA-NurA complex. In this study we demonstrate that the NurA exonuclease activity is inhibited by the Sulfolobus solfataricus RecQ-like Hel112 helicase. Inhibition occurs both in the presence and in the absence of HerA, but is much stronger when NurA is in complex with HerA. In contrast, the endonuclease activity of NurA is not affected by the presence of Hel112. Taken together these results suggest that the functional interaction between NurA/HerA and Hel112 is important for DNA end-resection in archaeal homologous recombination.

Three-dimensional automatic artificial intelligence driven augmented-reality selective biopsy during nerve-sparing robot-assisted radical prostatectomy: A feasibility and accuracy study.

Objective: To evaluate the accuracy of our new three-dimensional (3D) automatic augmented reality (AAR) system guided by artificial intelligence in the identification of tumour's location at the level of the preserved neurovascular bundle (NVB) at the end of the extirpative phase of nerve-sparing robot-assisted radical prostatectomy. Methods: In this prospective study, we enrolled patients with prostate cancer (clinical stages cT1c-3, cN0, and cM0) with a positive index lesion at target biopsy, suspicious for capsular contact or extracapsular extension at preoperative multiparametric magnetic resonance imaging. Patients underwent robot-assisted radical prostatectomy at San Luigi Gonzaga Hospital (Orbassano, Turin, Italy), from December 2020 to December 2021. At the end of extirpative phase, thanks to our new AAR artificial intelligence driven system, the virtual prostate 3D model allowed to identify the tumour's location at the level of the preserved NVB and to perform a selective excisional biopsy, sparing the remaining portion of the bundle. Perioperative and postoperative data were evaluated, especially focusing on the positive surgical margin (PSM) rates, potency, continence recovery, and biochemical recurrence. Results: Thirty-four patients were enrolled. In 15 (44.1%) cases, the target lesion was in contact with the prostatic capsule at multiparametric magnetic resonance imaging (Wheeler grade L2) while in 19 (55.9%) cases extracapsular extension was detected (Wheeler grade L3). 3D AAR guided biopsies were negative in all pathological tumour stage 2 (pT2) patients while they revealed the presence of cancer in 14 cases in the pT3 cohort (14/16; 87.5%). PSM rates were 0% and 7.1% in the pathological stages pT2 and pT3 (<3 mm, Gleason score 3), respectively. Conclusion: With the proposed 3D AAR system, it is possible to correctly identify the lesion's location on the NVB in 87.5% of pT3 patients and perform a 3D-guided tailored nerve-sparing even in locally advanced diseases, without compromising the oncological safety in terms of PSM rates.

Exploitation of Plant Growth Promoting Bacteria for Sustainable Agriculture: Hierarchical Approach to Link Laboratory and Field Experiments.

To feed a world population, which will reach 9.7 billion in 2050, agricultural production will have to increase by 35-56%. Therefore, more food is urgently needed. Yield improvements for any given crop would require adequate fertilizer, water, and plant protection from pests and disease, but their further abuse will be economically disadvantageous and will have a negative impact on the environment. Using even more agricultural inputs is simply not possible, and the availability of arable land will be increasingly reduced due to climate changes. To improve agricultural production without further consumption of natural resources, farmers have a powerful ally: the beneficial microorganisms inhabiting the rhizosphere. However, to fully exploit the benefits of these microorganisms and therefore to widely market microbial-based products, there are still gaps that need to be filled, and here we will describe some critical issues that should be better addressed.

MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting.

BACKGROUND: The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer. METHODS: A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN-negative and 15 pN-positive at histology. RESULTS: Unsupervised cluster analysis segregated surgical pN-negative and pN-positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN-positive versus pN-negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin-releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR-154-3p, miR-299-5p, miR-376a-3p, and miR-302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance. CONCLUSIONS: MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting.

Gross Specimen Handling Procedures Do Not Impact the Occurrence of Spread Through Air Spaces (STAS) in Lung Cancer.

Spread Through Air Spaces (STAS) is a form of invasion characterized by neoplastic cell dissemination in the lung parenchyma surrounding the outer edge of the tumor. Its possible artifactual origin is widely debated in the literature. The aim of this study is to investigate the potential impact of gross sampling procedures in causing STAS. A prospective series of 51 surgical lung specimens was collected (35 adenocarcinomas, 68.6%; 13 squamous cell carcinomas, 25.5%; 2 large-cell neuroendocrine carcinomas, 3.9%; 1 atypical carcinoid, 2%). The fresh tissue was sectioned with a new and clean blade for each cut, to obtain a tissue slice comprising the upper lung parenchyma, the tumor, and the lower parenchyma. This slice was cut in half and separately processed. The same procedure was repeated in the residual (specular) specimen after formalin fixation. STAS was identified in 33/51 (64.7%) cases, the predominant pattern being cluster formation (29 cases, 87.9%), the remaining 4 cases having single-cell invasion. Comparing STAS detection in upper and lower lung parenchyma areas (ie, before and after the blade crossed the tumor), no significant preferential STAS distribution was observed, indeed being almost overlapping (60.6% and 63.6% for fresh and 61.3% and 65.6% for fixed tissues, respectively). There was no difference between STAS occurrence in freshly cut and fixed corresponding samples. These findings indicate that STAS is not a pathologist-related artifactual event because of knife transportation of tumor cells during gross specimen handling and support the notion that it is a phenomenon preexisting to surgical tissue processing.

Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung.

Spread through air spaces (STAS) have been recently recognized as a prognostic factor for adenocarcinoma and squamous cell carcinoma of the lung. Pulmonary neuroendocrine neoplasms (NENs) include tumors with different morphology and a heterogeneous clinical behavior. Among atypical carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine carcinomas, to assess the presence and potential prognostic role of STAS. STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses. STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and small-cell carcinomas in the control group. In the carcinoid group, presence of STAS was significantly correlated with unfavorable parameters, such as high tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy.

Three-dimensional Elastic Augmented-reality Robot-assisted Radical Prostatectomy Using Hyperaccuracy Three-dimensional Reconstruction Technology: A Step Further in the Identification of Capsular Involvement.

BACKGROUND: In prostate cancer (PCa) surgical procedures, in order to maximize potency recovery, a nerve-sparing (NS) procedure is preferred. However, cancer abutting or focally extending beyond the prostate capsule increases the risk of a positive surgical margin. OBJECTIVE: To evaluate the accuracy of our new three-dimensional (3D) elastic augmented-reality (AR) system in identifying capsular involvement (CI) location of PCa during the NS phase of robot-assisted radical prostatectomy (RARP). Secondarily, the accuracy of this technology was compared with two-dimensional (2D)-based cognitive procedures. DESIGN, SETTING, AND PARTICIPANTS: A prospective study, enrolling 40 patients with PCa undergoing RARP at our center, from May to October 2018. SURGICAL PROCEDURE: Patients underwent 3D AR RARP or, in case of unavailability of this technology, 2D cognitive RARP. In all patients, total anatomical reconstruction was used. MEASUREMENTS: Clinical data were collected. In order to compare the two groups, nonparametric Mann-Whitney and chi-square tests were performed. A metallic clip was placed at the level of suspicious CI on the basis of images given by the 3D AR or magnetic resonance imaging (MRI) report. The pathological analysis evaluated the presence of tumor at the level of the clip. RESULTS AND LIMITATIONS: Twenty patients were enrolled in each group. Focusing on the 3D AR group at macroscopic evaluation, the metallic clip was placed at the tumor and capsular bulging in all cases. At microscopic assessment, cancer presence was confirmed in the suspicious area in 95.4% of the cases. Moreover, CI was correctly identified in 100.0% of the cases, thanks to the 3D image overlap. These results were compared with the 2D MRI cognitive group, showing, at microscopic analysis, statistically significant superiority of the 3D AR group in CI detection during the NS phase (100% vs 47.0%; p<0.05). The main limitation of this technique is that the segmentation and overlapping of the images are performed manually. CONCLUSIONS: Our findings suggest that, with the introduction of the elastic 3D virtual models, prostate deformation is correctly simulated during surgery and lesion location is correctly identified, even in dynamic reality with a subsequent potential reduction of positive surgical margin rate and, in the meantime, maximization of functional outcomes. PATIENT SUMMARY: On the basis of our findings, the three-dimensional elastic augmented-reality technology seems to help the surgeon in lesion location identification even in a dynamic phase of the intervention, optimizing the oncological outcomes.

Ki-67 Evaluation for Clinical Decision in Metastatic Lung Carcinoids: A Proof of Concept.

Accrual of metastatic pulmonary carcinoid patients for therapy is usually relied on clinical and histologic characterization, with no role for the proliferation activity as defined by Ki-67 labelling index (LI). A total of 14 carcinoid patients with tumour primaries (TP) and 19 corresponding tumour metastases (TM) were blindly reviewed by 2 different pathologists for necrosis, mitotic count, and Ki-67 LI. Ki-67 LI outperformed histologic subtyping, mitotic count, and necrosis with good to almost excellent (0.40-0.75) inter-observer agreement. About 10% cut-off Ki-67 LI predicted survival better than histology for TP and TM for both observers. The TM patients survived differently according to diverse treatments (somatostatin analogues [SSAs], analogues plus additional treatments except for platinum; platinum-based chemotherapy) in close correlation with <10%, 10% to 20%, and >20% cut-off thresholds of Ki-67 LI, respectively. There was also a trend for an increase in Ki-67 LI in TM as compared with TP. This is the first proof of concept in which a clinical potential is preliminarily suggested for Ki-67 LI to better stratify pulmonary metastatic carcinoid patients for treatment according to a criterion of histology-independent biological aggressiveness.

Fast Regulation of Hormone Metabolism Contributes to Salt Tolerance in Rice (Oryzasativa spp. Japonica, L.) by Inducing Specific Morpho-Physiological Responses.

Clear evidence has highlighted a role for hormones in the plant stress response, including salt stress. Interplay and cross-talk among different hormonal pathways are of vital importance in abiotic stress tolerance. A genome-wide transcriptional analysis was performed on leaves and roots of three-day salt treated and untreated plants of two Italian rice varieties, Baldo and Vialone Nano, which differ in salt sensitivity. Genes correlated with hormonal pathways were identified and analyzed. The contents of abscisic acid, indoleacetic acid, cytokinins, and gibberellins were measured in roots, stems, and leaves of seedlings exposed for one and three days to salt stress. From the transcriptomic analysis, a huge number of genes emerged as being involved in hormone regulation in response to salt stress. The expression profile of genes involved in biosynthesis, signaling, response, catabolism, and conjugation of phytohormones was analyzed and integrated with the measurements of hormones in roots, stems, and leaves of seedlings. Significant changes in the hormone levels, along with differences in morphological responses, emerged between the two varieties. These results support the faster regulation of hormones metabolism in the tolerant variety that allows a prompt growth reprogramming and the setting up of an acclimation program, leading to specific morpho-physiological responses and growth recovery.

Eighth Edition of the UICC Classification of Malignant Tumours: an overview of the changes in the pathological TNM classification criteria-What has changed and why?

The TNM classification of malignant tumours is a mainstay tool in clinical practice and research for prognostic assessment of patients, treatment allocation and trial enrolment, as well as for epidemiological studies and data collection by cancer registries worldwide. Pathological TNM (pTNM) represents the pathological classification of a tumor, assigned after surgical resection or adequate sampling by biopsy, and periodical updates to the relative classification criteria are necessary to preserve its clinical relevance by integrating newly reported data. A structured approach has been put in place to fulfil this need and, based upon this process, the Eighth Edition of Union for International Cancer Control (UICC) TNM Classification of Malignant Tumours has been published, introducing many significant changes, including novel classification criteria for specific tumour types. In this review, we aim to describe the major changes introduced in the pTNM classification criteria and to summarize the evidence supporting these changes.

Distinctive pathological and clinical features of lung carcinoids with high proliferation index.

Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities. The 2015 WHO classification restricts the Ki-67 role to biopsy or cytology samples, rather than for prognostic prediction. We aimed to investigate whether values and patterns of Ki-67 alone would allow for a clinically meaningful stratification of lung carcinoids, regardless of histological typing. Ki-67 proliferation index and pattern (homogeneous versus heterogeneous expression) were assessed in a cohort of 171 TCs and 68 ACs. Cases were subdivided into three Ki-67 ranges (<4/4-9/≥10%). Correlations with clinicopathological data, univariate and multivariate survival analyses were performed. The majority of cases (61.5%) belonged to the <4% Ki-67 range; 25.1 and 13.4% had a proliferation index of 4-9% and ≥10%, respectively. The <4% Ki-67 subgroup was significantly enriched for TCs (83%, p < 0.0001); ACs were more frequent in the subgroup showing Ki-67 ≥ 10% (75%, p < 0.0001). A heterogeneous Ki-67 pattern was preferentially seen in carcinoids with a Ki-67 ≥10% (38%, p < 0.02). Mean Ki-67 values ≥4 and ≥10% identified categories of poor prognosis both in terms of disease-free and overall survival (p = 0.003 and <0.0001). At multivariate analysis, the two thresholds did not retain statistical significance; however, a Ki-67 ≥ 10% identified a subgroup of dismal prognosis even within ACs (p = 0.03) at univariate analysis. Here, we describe a subgroup of lung carcinoids showing brisk proliferation activity within the necrosis and/or mitotic count-based categories. These patients were associated with specific clinicopathological characteristics, to some extent regardless of histological subtyping.

Classification of pulmonary neuroendocrine tumors: new insights.

Neuroendocrine tumors of the lung (Lu-NETs) embrace a heterogeneous family of neoplasms classified into four histological variants, namely typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). Defining criteria on resection specimens include mitotic count in 2 mm2 and the presence or absence of necrosis, alongside a constellation of cytological and histological traits including cell size and shape, nuclear features and overall architecture. Clinically, TC are low-grade malignant tumors, AC intermediate-grade malignant tumors and SCLC/LCNEC high-grade malignant full-blown carcinomas with no significant differences in survival between them. Homologous tumors arise in the thymus that occasionally have some difficulties in differentiating from the lung counterparts when presented with large unresectable or metastatic lesions. Immunohistochemistry (IHC) helps refine NE diagnosis at various anatomical sites, particularly on small-sized tissue material, in which only TC and small cell carcinoma categories can be recognized easily on hematoxylin & eosin stain, while AC and LCNEC can only be suggested on such material. The Ki-67 labeling index effectively separates carcinoids from small cell carcinoma and may prove useful for the clinical management of a metastatic disease to help the therapeutic decision-making process. Although carcinoids and high-grade neuroendocrine carcinomas in the lung and elsewhere make up separate tumor categories on molecular grounds, emerging data supports the concept of secondary high-grade NETs arising in the preexisting carcinoids, whose clinical and biological relevance will have to be placed into the proper context for the optimal management of these patients. In this review, we will discuss the selected, recent literature with a focus on current issues regarding Lu-NET nosology, i.e., classification, derivation and tumor evolution.

Cytological features of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" and their correlation with tumor histology.

Among thyroid papillary carcinomas (PTCs), the follicular variant is the most common and includes encapsulated forms (EFVPTCs). Noninvasive EFVPTCs have very low risk of recurrence or other adverse events and have been recently proposed to be designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features or NIFTP, thus eliminating the term carcinoma. This proposal is expected to significantly impact the risk of malignancy associated with the currently used diagnostic categories of thyroid cytology. In this study, we analyzed the fine needle aspiration biopsy (FNAB) cytology features of 96 histologically proven NIFTPs and determined how the main nuclear features of NIFTP correlate between cytological and histological samples. Blind review of FNAB cytology from NIFTP nodules yielded the diagnosis of "follicular neoplasm" (Bethesda category IV) in 56% of cases, "suspicious for malignancy" (category V) in 27%, "atypia of undetermined significance/follicular lesion of undetermined significance" (category III) in 15%, and "malignant" (category VI) in 2%. We found good correlation (κ=0.62) of nuclear features between histological and cytological specimens. NIFTP nuclear features (size, irregularities of contours, and chromatin clearing) were significantly different from those of benign nodules but not from those of invasive EFVPTC. Our data indicate that most of the NIFTP nodules yield an indeterminate cytological diagnosis in FNAB cytology and nuclear features found in cytology samples are reproducibly identified in corresponding histology samples. Because of the overlapping nuclear features with invasive EFVPTC, NIFTP cannot be reliably diagnosed preoperatively but should be listed in differential diagnosis of all indeterminate categories of thyroid cytology.

Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the Lung.

INTRODUCTION: Mucin-rich lung adenocarcinomas (ADCs), namely mucinous and colloid ADCs, are classified as ADC variants according to the World Health Organization 2015 classification. A correlation between morphological patterns and mutational status of these rare entities is not well established. METHODS: We investigated the mutational profile of mucin-rich lung ADCs in correlation with histopathological and morphological features with the goal of identifying biological tumor characteristics of potential prognostic and therapeutic interest. A series of 54 surgically resected primary mucinous lung ADC samples were retrospectively analyzed for clinicopathological characteristics and by targeted next-generation sequencing. RESULTS: Fifty cases were invasive mucinous ADCs (32 pure and 18 mixed) and four were colloid-predominant ADCs. Invasive mucinous ADC cases with a pure mucinous pattern were associated with a lower risk of vascular invasion (p = 0.01), absence of signet ring cells (p = 0.03), negative nodal status (p = 0.006), and early clinical stage (p = 0.02). The most prevalent mutations involved the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and tumor protein p53 gene (TP53). Most mutations clustered in the mitogen-activated protein/protein kinase B pathway and in the p53/DNA repair pathway. A few uncommon epidermal growth factor receptor gene (EGFR) mutations were found. A correlation between a higher number of mutations and favorable clinical outcome was seen (p < 0.001). CONCLUSIONS: Our data showed that mucinous ADCs have peculiar pathological and molecular features that might suggest the need for a differentially tailored therapeutic approach compared with that to conventional lung ADC.