Non-mucinous Adenocarcinoma Research Articles

Exploratory evidence maps for the WHO Classification of Tumours 5th edition for lung and thymus tumors.

The WHO Classification of Tumours (WCT) guides cancer diagnosis, treatment, and research. However, research evidence in pathology continuously changes, and new evidence emerges. Correct assessment of evidence in the WCT 5th edition (WCT-5) and identification of high level of evidence (LOE) studies based on study design are needed to improve future editions. We aimed at producing exploratory evidence maps for WCT-5 Thoracic Tumours, specifically lung and thymus tumors. We extracted citations from WCT-5, and imported and coded them in EPPI-Reviewer. The maps were plotted using EPPI-Mapper. Maps displayed tumor types (columns), descriptors (rows), and LOE (bubbles using a four-color code). We included 1434 studies addressing 51 lung, and 677 studies addressing 25 thymus tumor types from WCT-5 thoracic tumours volume. Overall, 87.7% (n = 1257) and 80.8% (n = 547) references were low, and 4.1% (n = 59) and 2.2% (n = 15) high LOE for lung and thymus tumors, respectively. Invasive non-mucinous adenocarcinoma of the lung (n = 215; 15.0%) and squamous cell carcinoma of the thymus (n = 93; 13.7%) presented the highest number of references. High LOE was observed for colloid adenocarcinoma of the lung (n = 11; 18.2%) and type AB thymoma (n = 4; 1.4%). Tumor descriptors with the highest number of citations were prognosis and prediction (n = 273; 19.0%) for lung, and epidemiology (n = 186; 28.0%) for thymus tumors. LOE was generally low for lung and thymus tumors. This study represents an initial step in the WCT Evidence Gap Map (WCT-EVI-MAP) project for mapping references in WCT-5 for all tumor types to inform future WCT editions.

Data set for the reporting of lung cancer: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early-stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened. Essential core elements and suggested non-core elements were identified for inclusion in the resected lung cancer pathology data set based on predetermined levels of evidence as well as consensus expert opinion. A lung cancer histopathology reporting guide was developed that includes relevant clinical, macroscopic, microscopic and ancillary testing. Critical review and discussion of current evidence was incorporated into the new data set including changes from the 2021 World Health Organisation (WHO) Classification of Thoracic Tumours, fifth edition, new requirements for grading invasive non-mucinous adenocarcinomas, assessment of response to neoadjuvant therapy and requirements for molecular testing in early-stage resected lung carcinomas. This ICCR data set represents incorporation of all relevant parameters for histology reporting of lung cancer resection specimens. Routine use of this data set is recommended for all pathology reporting of resected lung cancer and it is freely available worldwide on the ICCR website (https://www.iccr-cancer.org/datasets/published-datasets/). Widespread implementation will help to ensure consistent and comprehensive pathology reporting and data collection essential for lung cancer patient care, clinical trials and other research.

SOX17 expression in tumor-penetrating vessels in relation to CD8+ T-cell infiltration in cancer stroma niches.

Sex-determining region Y-related high-mobility group box 17 protein (SOX17), a proangiogenic transcription factor, is specifically expressed in tumor endothelial cells (TECs) of implanted Lewis lung carcinoma. However, the expression profile of SOX17 is largely unknown in human lung cancer. We aimed to elucidate SOX17 expression in cancer cells and the tumor microenvironment of lung adenocarcinoma. In the present study, we examined SOX17 expression in whole-tissue specimens of 83 lung adenocarcinomas by immunohistochemistry. SOX17 immunoreactivity was minimal in lung adenocarcinoma cells, except in five non-mucinous adenocarcinomas in situ. SOX17 was also expressed in cultured A549 lung adenocarcinoma cells, which is widely used as a model of malignant alveolar type II epithelial cells. Notably, SOX17 immunoreactivity was found in endothelial cells of tumor-penetrating vessels in 19 of 83 lung adenocarcinoma tissue specimens, with statistical significance to stromal infiltration of CD8+ T cells (p < 0.01) but was not associated with the number of tertiary lymph nodes. Although not statistically significant, SOX17 immunoreactivity was related to favorable patient outcomes. Our findings indicate that SOX17 might play a pleiotropic role in lung adenocarcinoma in cancer cells and stromal niches. SOX17-mediated CD8+ T-cell-rich tumor microenvironment might attract interest in improving the effect of cancer immunotherapy.

Prognostic Impact of Non–Predominant Lepidic Components in Pathologic Stage I Invasive Nonmucinous Adenocarcinoma

IntroductionThis study investigated the prognostic impact of non–predominant lepidic components in invasive nonmucinous adenocarcinoma. MethodsPatients who underwent lobectomy and were diagnosed with pathologic stage I nonmucinous, non–lepidic-predominant invasive adenocarcinoma were included. Tumors were staged according to the eighth edition of TNM classification and categorized on the basis of the presence of lepidic components in the final pathology. Overall survival (OS) and recurrence-free survival (RFS) were analyzed before and after applying inverse probability of treatment weighting. Competing risk analyses for recurrence were also compared in the two groups. ResultsOf the 1270 patients, 858 (67.6%) had lepidic components (+). The pathologic stage and histologic grade were higher in the lepidic (−) group (p < 0.001, respectively). The 5-year OS and RFS were significantly worse in the lepidic (−) group than in the lepidic (+) group (OS: 88.2% versus 94.9%, p < 0.001; RFS: 79.4% versus 91.9%, p < 0.001). These trends were consistent after weighted analysis (OS: 92.4% versus 96.4%, p = 0.029; RFS: 85.6% versus 92.3%, p = 0.007). The 5-year cumulative incidence of any recurrence was 14.0% in the lepidic (−) group and 4.1% in the lepidic (+) group (p < 0.001). Multivariable Fine-Gray regression analysis found that the lepidic (+) group exhibited a lower risk of recurrence than did the lepidic (−) group (hazard ratio = 0.52, 95% confidence interval: 0.29–0.93, p = 0.031). ConclusionsIn pathologic stage I invasive nonmucinous adenocarcinoma, the presence of histologically diagnosed non–predominant lepidic components might be associated with a better prognosis after curative surgery.

Driver gene alterations in NSCLC patients in southern China and their correlation with clinicopathologic characteristics.

In this study, we aimed to explore the relationship between clinicopathological features and driver gene changes in Chinese NSCLC patients. Amplification refractory mutation system PCR was used to detect the aberrations of 10 driver oncogenes in 851 Chinese NSCLC patients, and their correlation with clinicopathological characteristics was also analyzed. Moreover, three models of logistic regression were used to analyze the association between histopathology and EGFR or KRAS mutations. The top two most frequently aberrant target oncogenes were EGFR (48.06%) and KRAS (9.51%). These were followed by ALK (5.41%), HER2 (2.35%), MET (2.23%), RET (2.11%), ROS1 (1.88%), BRAF (0.47%), NRAS (0.24%), and PIK3CA (0.12%). Additionally, 11 (1.29%) patients had synchronous gene alterations in two genes. The main EGFR mutations were exon 21 L858R and exon 19-Del, which accounted for 45.97% and 42.79% of all EGFR mutations, respectively. Logistic regression analysis showed that the frequency of EGFR mutations was positively correlated with women, non-smokers, lung adenocarcinoma, and invasive non-mucinous adenocarcinoma (IA), and negatively correlated with solid nodule, micro-invasive adenocarcinoma, and solid-predominant adenocarcinoma. KRAS mutations were positively associated with men and longer tumor long diameters and negatively correlated with lung adenocarcinoma (P < 0.05 for all). Our findings suggest that the EGFR mutation frequency was higher in women, non-smokers, lung adenocarcinoma, and the IA subtype in lung adenocarcinoma patients, while the KRAS mutation rate was higher in men and patients with longer tumor long diameter and lower in lung adenocarcinoma patients.

Surgical prognosis of lung invasive mucinous and non-mucinous adenocarcinoma: propensity score matched analysis.

Invasive mucinous adenocarcinoma exhibits distinct prognostic outcomes compared to non-mucinous adenocarcinoma (ADC). This study investigated and compared the clinical outcomes and prognostic factors of invasive mucinous and non-mucinous ADC patients. This retrospective study included patients who underwent curative surgery for ADC between 2011 and 2021. Patient characteristics were balanced using propensity score matching. Cumulative incidence was analysed to evaluate cancer recurrence incidence, and the Kaplan-Meier method was used to calculate overall survival (OS) for each group. A total of 6101 patients were included. After matching, the non-mucinous group and mucinous groups comprised 798 and 408 patients, respectively. The patients in the mucinous group had a lower recurrence incidence than those in the non-mucinous group (P = 0.014). The recurrence incidence in the mucinous group was between those of grades 1 (P = 0.011) and 2 (P = 0.012) and the OS rates were comparable to those of grades 2 (P = 0.6) and 3 (P = 0.2). Multivariable analysis revealed that the maximal standardized uptake value [hazard ratio (HR): 1.13, P = 0.11] and progressed pathological stages (pStage II, HR: 3.9, P = 0.028; pStage III, HR: 8.33, P = 0.038) served as adverse prognostic factors for the mucinous group. Patients with mucinous ADC demonstrated lower recurrence incidence and similar OS rates compared to those with non-mucinous ADC. The recurrence incidence of mucinous ADC was between those of International Association for the Study of Lung Cancer grades 1 and 2, with the OS rates comparable to those of grades 2 and 3. None.

LVI-PathNet: Segmentation-classification pipeline for detection of lymphovascular invasion in whole slide images of lung adenocarcinoma

Lymphovascular invasion (LVI) in lung cancer is a significant prognostic factor that influences treatment and outcomes, yet its reliable detection is challenging due to interobserver variability. This study aims to develop a deep learning model for LVI detection using whole slide images (WSIs) and evaluate its effectiveness within a pathologist's information system. Experienced pathologists annotated blood vessels and invading tumor cells in 162 WSIs of non-mucinous lung adenocarcinoma sourced from two external and one internal datasets. Two models were trained to segment vessels and identify images with LVI features. DeepLabV3+ model achieved an Intersection-over-Union of 0.8840 and an area under the receiver operating characteristic curve (AUC-ROC) of 0.9869 in vessel segmentation. For LVI classification, the ensemble model achieved a F1-score of 0.9683 and an AUC-ROC of 0.9987. The model demonstrated robustness and was unaffected by variations in staining and image quality. The pilot study showed that pathologists' evaluation time for LVI detecting decreased by an average of 16.95%, and by 21.5% in “hard cases”. The model facilitated consistent diagnostic assessments, suggesting potential for broader applications in detecting pathological changes in blood vessels and other lung pathologies.

Uniportal Thoracoscopic Complex Combined Seg-Sub-subsegmentectomy of RS9+10bii: Dual-Display Method and Combined Approaches (Trans-fissure and Trans-ligament).

Uniportal thoracoscopic lateral basal segmentectomy is the most technically challenging anatomic segmentectomy,1-3 especially when it involves combined subsegmentectomy or sub-subsegmentectomy. Therefore, there are very few reports detailing its technical aspect. In this multimedia article, we describe a very complex uniportal thoracoscopic combined seg-sub-subsegmentectomy of RS9+10bii through the oblique fissure approach and the inferior pulmonary ligament approach, following a single-direction strategy4,5 to advance the procedure, utilizing the stem-branch method3,6 for segmental/subsegmental/sub-subsegmental structure tracking, and employing dual-display method, which comprises the intravenous ICG injection method and the inflation/deflation method, to identify intersegmental and inter-seg-sub-subsegmental planes. The operation lasted 169min, with approximately 20mL of blood loss. The patient experienced an active hemothorax and two spontaneous pneumothoraxes on postoperative days 1, 4, and 19, respectively, all of which resolved promptly after treatment. Histopathological examination of the specimen documented invasive non-mucinous adenocarcinoma with negative surgical margins and lymph nodes. The staging was determined as pT1bN0M0, stage IA2. During the 14-month follow-up period, there were no signs of tumor recurrence or metastasis observed. The FVC, FEV1, and FEV1%pred decreased by 11.9%, 12.5%, and 12.8%, respectively, at postoperative month 6. Complex basal segmentectomies, which necessitate combined subsegmental or sub-subsegmental resections, such as RS9+10bii, are feasible using the dual-display and combined approaches method. This method simplifies the steps of the very complex combined subsegmentectomy, averting the need for extensive lung resection. In addition, when performing these combined segmentectomies, precise anatomical dissection is crucial to prevent complications such as minor bronchopleural fistulas.

Clinicopathological features and prognosis analysis of proximal colonic mucinous adenocarcinoma

Mucinous adenocarcinoma (MAC) is a distinct subtype of colorectal cancer. Previous studies have confirmed the poor prognosis of rectal or left-sided colon MAC, while the prognosis and response to chemotherapy in proximal colon MAC remains controversial. The aim of this study was to investigate the clinicopathological characteristics, prognosis, response to chemotherapy, and risk prediction factors of proximal colon MAC. Patients with proximal colon MAC and non-mucinous adenocarcinoma (NMAC) were retrospectively analyzed in this study. The analyzed variables included gender, age, smoking, drinking, chemotherapy, metastasis, pathological stage, and tumor size. Overall survival (OS) was the primary outcome. Kaplan–Meier analysis was used to assess the impact of mucinous subtype and chemotherapy on OS. We conducted univariate and multivariate Cox regression analyses to determine prognosis factors for proximal colon MAC and NMAC. A total of 284 cases of proximal colon MAC and 1384 cases of NMAC were included in the study. Compared to NMAC, proximal colon MAC was diagnosed at a younger age. The proportion of synchronous and metachronous metastasis was also higher, as well as the pathological stage and tumor size. Proximal colon MAC had a worse prognosis than NMAC, especially in stage 3. Moreover, the prognosis of proximal colon NMAC improved after chemotherapy, while MAC showed no improvement in prognosis after chemotherapy. Advanced age, N1 and N2 stage were independent prognostic factors for adverse outcomes in MAC. For proximal colon adenocarcinoma, the independent predictors of adverse outcomes included mucinous subtype, order age, N1 and N2 stages, and pathological stage 4. Proximal colon MAC had a worse prognosis compared to NMAC. Chemotherapy did not improve the prognosis of proximal colon mucinous adenocarcinoma.

Factors associated with pathological complete remission after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world clinical setting.

This study aims to identify factors associated with achieving a pathological complete remission (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). We conducted a cohort analysis of 171 LARC patients who underwent curative resection post-nCRT at the First Affiliated Hospital of Guangxi Medical University between January 2015 and December 2021. The data encompassed clinical and pathological information. Univariate and binary logistic regression multivariate analyses were employed to examine the factors influencing pCR achievement after nCRT. Kappa value tests were utilized to compare clinical staging after nCRT with postoperative pathological staging. Postoperative histopathology revealed that of the 171 patients, 40 (23.4%) achieved TRG 0 grade (pCR group), while 131 (76.6%) did not achieve pCR, comprising 36 TRG1, 42 TRG2, and 53 TRG3 cases. Univariate analysis indicated that younger age (p=0.008), reduced tumor occupation of intestinal circumference (p =0.008), specific pathological types (p=0.011), and lower pre-nCRT CEA levels (p=0.003) correlated with pCR attainment. Multivariate analysis identified these factors as independent predictors of pCR: younger age (OR=0.946, p=0.004), smaller tumor occupation of intestinal circumference (OR=2.809, p=0.046), non-mucinous adenocarcinoma pathological type (OR=10.405, p=0.029), and lower pre-nCRT serum CEA levels (OR=2.463, p=0.031). Clinical re-staging post-nCRT compared to postoperative pathological staging showed inconsistent MRI T staging (Kappa=0.012, p=0.718, consistency rate: 35.1%) and marginally consistent MRI N staging (Kappa=0.205, p=0.001, consistency rate: 59.6%). LARC patients with younger age, presenting with smaller tumor circumferences in the intestinal lumen, lower pre-nCRT serum CEA levels, and non-mucinous adenocarcinoma are more likely to achieve pCR after nCRT. The study highlights the need for improved accuracy in clinical re-staging assessments after nCRT in LARC.

Nomogram model for the diagnosis of solitary nodular pulmonary mucinous adenocarcinoma

The objective of this study was to develop a nomogram model based on the natural progression of tumor and other radiological features to discriminate between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. A retrospective analysis was conducted on 15,655 cases of lung adenocarcinoma diagnosed at our institution between January 2010 and June 2023. Primary nodular invasive mucinous adenocarcinomas and non-mucinous adenocarcinomas with at least two preoperative CT scans were included. These patients were randomly assigned to training and validation sets. Univariate and multivariate analyses were employed to compare tumor growth rates and clinical radiological characteristics between the two groups in the training set. A nomogram model was constructed based on the results of multivariate analysis. The diagnostic value of the model was evaluated in both the training and validation sets using calibration curves and receiver operating characteristic curves (ROC). The study included 174 patients, with 58 cases of mucinous adenocarcinoma and 116 cases of non-mucinous adenocarcinoma. The nomogram model incorporated the maximum tumor diameter, the consolidation/tumor ratio (CTR), and the specific growth rate (SGR) to generate individual scores for each patient, which were then accumulated to obtain a total score indicative of the likelihood of developing mucinous or non-mucinous adenocarcinoma. The model demonstrated excellent discriminative ability with an area under the receiver operating characteristic curve of 0.784 for the training set and 0.833 for the testing set. The nomogram model developed in this study, integrating SGR with other radiological and clinical parameters, provides a valuable and accurate tool for differentiating between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. This prognostic model offers a robust and objective basis for personalized management of patients with pulmonary adenocarcinomas.

Pathological Diagnostic Testing and Biomarkers for Perioperative System Therapy

Optimal personalized treatment planning for resectable lung cancer requires quality-assured, standardized and prompt processing of tissue samples in pathological laboratories, as well as the determination of relevant predictive and prognostic biomarkers. Pathological diagnostic testing includes histological tumor typing, staging and tumor grading, resection status and, if necessary, regression grading after neoadjuvant systemic therapy. Histopathological typing is performed according to the current WHO classification and includes adenocarcinomas, squamous cell carcinomas, other non-small cell lung carcinomas (NSCLCs), carcinoids, small cell and large cell neuroendocrine carcinomas. Standardized tumor grading currently plays an important role in invasive non-mucinous adenocarcinoma in particular and enables prognostic risk assessment. The R classification and regression grading are also prognostically relevant. In the early stages of NSCLC, molecular biomarkers such as EGFR, ALK and PD-L1, are relevant for decisions on individual treatment. Testing is performed on FFPE tissue samples and must be carried out in a quality-assured manner and in accordance with international standards.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma

BackgroundLung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC.MethodsThis retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC.ResultsThe results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group.ConclusionThe newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

MpMRI features of mucinous prostate cancer: two case reports

BackgroundMucinous adenocarcinoma of the prostate (MACP) is one of the rarest variants of prostatic neoplasm, with more aggressive behavior than non-mucinous prostatic cancer. Previous studies suggested that these tumors exhibit different imaging magnetic resonance imaging (MRI) features compared with those of non-mucinous adenocarcinoma of the prostate upon which the conventional PIRADS v2.1 is based. To the best of our knowledge, this case series is the first to describe the multiparametric magnetic resonance imaging features of the MACP.ResultsWe presented two cases of biopsy proven mucinous adenocarcinoma of the prostate studied with multiparametric MRI. In both cases, diagnosis was late because of the different MRI features of MACP than those of the more common adenocarcinoma of the prostate. In both mpMRI, MACP appears to be hyperintense on T2WI, there was not a significant decrease in diffusivity in ADC maps and it exhibits early enhancement in DCE-MRI; the septa resulted in hypointense on T2WI compared to the PZConclusionsAccording to our experience, the conventional PIRADS v2.1 score is not suitable for mucinous prostate adenocarcinoma. MACP appears to be hyperintense on T2WI, has a lower ADC value, and exhibits early enhancement in DCE-MRI; the septa are usually hypointense on T2WI compared to the PZ. It is imperative for radiologists and urologists to be cognizant of this rare variant of prostate cancer to promptly identify and diagnose it, thereby preventing any diagnostic delays.

The utility of the lineage specific immunohistochemical stains SATB2, CDX2, and villin, and the mucin glycoproteins MUC2, MUC5AC, and MUC6 to distinguish pulmonary invasive mucinous adenocarcinoma from metastatic colorectal carcinoma

ContextThe lungs are a common site of tumor metastasis. While morphology and immunophenotype can help differentiate primary from metastatic tumors, distinguishing pulmonary invasive mucinous adenocarcinoma (PIMA) from metastatic colorectal adenocarcinoma (CRC) may occasionally be challenging due to overlapping morphological and immunohistochemical features. Lineage-specific markers such as CDX2, TTF-1, and napsin A are helpful with pulmonary non-mucinous adenocarcinoma (PNMA), however they are non-specific and insensitive when applied to PIMA. SATB2 is a newer marker that distinguishes CRC from upper gastrointestinal and pancreaticobiliary tumors; its utility in distinguishing CRC from PIMA has not been fully elucidated. ObjectiveTo evaluate the performance of lineage-specific and mucin glycoprotein immunostains in distinguishing PIMA and CRC. DesignWe stained tissue microarrays comprising 34 PNMA, 31 PIMA, and 32 CRC with CK7, CK20, SATB2, CDX2, villin, TTF-1, napsin A, and gel-forming mucins MUC2, MUC5AC, and MUC6. ResultsPIMA showed significant (>50% of cells) expression of SATB2 (6%), CDX2 (6%), villin (74%), TTF-1 (13%), and napsin A (23%). However, significant CK7 expression was seen in nearly all PIMA (30/31) and none of the metastatic CRC. ConclusionOur results suggest that CK7 remains one of the most useful markers for distinguishing primary PIMA from metastatic CRC. Expression of the mucin glycoproteins MUC5AC and MUC6 and lack of expression of MUC2 favored a diagnosis of PIMA, but expression of these markers was too heterogeneous to be of clinical utility. To our knowledge this is the only study comparing the immunohistochemical profile of PIMA and metastatic CRC in lung metastasectomy specimens.

Different clinicopathological features between young and older patients with pulmonary adenocarcinoma and ground-glass opacity

After the recommendation of computed tomography as a routine procedure for lung cancer screening, an increasing number of young adults have been diagnosed with pulmonary ground-glass opacity (GGO). Up to 63% of pulmonary nodules with a GGO component can be malignant. Since young cancer patients have limited exposure to environmental mutagens, they have special characteristics and needs. This study sought to compare the clinicopathological characteristics of young and old patients with GGO-associated lung adenocarcinoma (GGO-LUAD). Clinicopathological data from 203 patients who underwent video-assisted thoracoscopic surgery between January 2018 and April 2020 for pulmonary GGO component nodules were reviewed. Lung nonmucinous adenocarcinoma patients younger than 40 years old and older than 40 years old were enrolled: 103 patients ≤ 40 years old and 100 patients > 40 years old. The relevant clinicopathological features, including sex, smoking status, tumor size, pathological characteristics, radiographic features and prognosis of pulmonary nodules, were evaluated. Univariate analyses were applied for comparisons between groups. The differences in baseline characteristics (sex, smoking status, tumor location) between the different age groups were not significant. Young patients were more likely to have tumors < 1 cm in size, while older patients predominantly had tumors > 2 cm in size. The mean percentage of invasive adenocarcinoma was greater in the elderly group. Young and older patients seemed to have similar subtypes of adenocarcinoma (p > 0.05) but had different degrees of differentiation (p < 0.001). The 3-year overall survival (OS) and recurrence-free survival (RFS) of the young group were 100% and 99.03%, respectively, while the 3-years OS and RFS of the older group were 99% and 98%, respectively. Our work revealed that young patients with malignant pulmonary nodules and GGOs have distinct pathological subtypes. Patients with GGOs of different ages have different clinicopathological characteristics. The 3-year prognosis of young patients with malignant pulmonary nodules with GGOs is satisfactory.

Morphological and Clinical Analysis of Colorectal Cancer: Findings from a Cross-Sectional Study

Background: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, with increasing incidence in developing countries like Pakistan. This study aims to evaluate the distribution patterns of colorectal cancer morphologies among patients treated at Liaquat University of Medical &amp; Health Sciences (LUMHS) Jamshoro. Methodology: This descriptive, cross-sectional study was conducted over two years (January 2022 to December 2023) at the Department of Gastroenterology, Asian Institute of Medical Sciences, in collaboration with the Department of Pathology, LUMHS Jamshoro. A total of 150 patients diagnosed with CRC and who underwent surgical resection were included in the study. Data were collected on socio-demographic characteristics, clinical presentations, histopathological types, tumor grading, and staging. Statistical analysis was performed using SPSS version 25, with Fisher’s exact test applied to assess associations between variables. Results: The mean age of the patients was 58.7 years (± 11.2), with the majority being male (60%). Most tumors were classified as non-mucinous adenocarcinomas (56%), followed by mucinous adenocarcinomas (28%) and signet-ring cell carcinomas (16%). A strong positive correlation was found between tumor size and Dukes' staging (ρ = 0.42, p &lt; 0.001), as well as between Dukes' staging and tumor grading (ρ=0.46, p&lt;0.001). Rectal bleeding was significantly associated with advanced Dukes’ stages (ρ=0.44, p &lt;0.001). Conclusion: This study highlights the aggressive nature of colorectal cancer in the studied population, with significant associations between age, tumor size, staging, and grading. The findings underscore the need for early detection strategies and tailored treatment approaches to address CRC in this region. Keywords: Colorectal Cancer, Dukes’ Staging, Histopathology, Tumor Grading.

GATA4 is diagnostically useful for distinguishing primary ovarian mucinous carcinomas from metastatic colorectal adenocarcinomas to the ovary.

Determining the primary origin of an ovarian mucin-producing carcinoma can be challenging at times because some metastases of primary colorectal origin may exhibit gross, microscopic, and/or immunohistochemical features that overlap with those of primary ovarian mucinous carcinomas (OMCs). We hypothesized that GATA binding protein 4 (GATA4) might be a novel, useful marker for differentiating primary OMCs from metastatic colorectal adenocarcinomas to the ovary. For comparison with the usefulness of other markers (special AT-rich sequence-binding protein 2 (SATB2) and caudal type homeobox 2 (CDX2)), we elucidated the expression profiles of GATA4 in OMCs, colorectal non-mucinous adenocarcinomas (CNMACs), and colorectal mucinous adenocarcinomas (CMACs) using immunohistochemistry. We confirmed GATA4 expression (H-score ≥50 points) in 93%, SATB2 in 0%, and CDX2 in 64% of 14 OMCs. GATA4 was expressed in 13%, SATB2 in 90%, and CDX2 in 93% of 30 CNMACs. GATA4 was expressed in 20%, SATB2 in 73%, and CDX2 in 100% of 30 CMACs. The expression of GATA4 in a mucus-producing ovarian tumor strongly supports it being a primary OMC rather than a metastatic colorectal carcinoma: GATA4 expression indicates OMC and SATB2 expression indicates colorectal adenocarcinoma. However, three cases of colorectal adenocarcinoma were GATA4-positive and SATB2-negative, so the GATA4/SATB2 marker combination is not absolute for determining the primary site. Further research for more markers is necessary to find the ideal combination.

Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma.

This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.

Correlation between common driver gene variations and clinicopathological typing in lung adenocarcinoma

Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. Results: There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (P<0.05). Conclusions: Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.