Node Metastasis Research Articles

Accurate preoperative prediction of nodal metastasis in papillary thyroid microcarcinoma: Towards optimal management of patients.

To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.

Abstract B099: A common WNT4 polymorphism drives gynecologic cancer phenotypes and health disparities

Abstract Introduction: Beyond BRCA1/2 mutations, there is a limited understanding of gynecologic cancer etiology and risk. An underexplored risk factor is Wnt ligand WNT4, central to ovarian and uterine organogenesis. A single nucleotide polymorphism (SNP) at a key WNT4 regulatory site (rs3820282) is associated with 10-25% increased risk for gynecologic pathologies, including ovarian cancer (OvCa), but the mechanism is unknown. Importantly, rs3820282 variant allele frequency (VAF) is ~0% in African populations, ~15% in Caucasians, 20-40% in Latinx populations, and 45-55% in Asian populations, paralleling increased incidence of aggressive OvCa subtypes in Asian populations. We hypothesize the rs3820282 variant drives OvCa health disparities by aberrant activation of WNT4, mediating distinct cancer etiology, therapy resistance, and poor patient outcomes. Methods: To address our hypothesis, we employed global untargeted metabolomics, SNP genotyping, WNT4 overexpression, WNT4 siRNA-mediated knockdown, cell viability assays, and Reverse Phase Protein Array (RPPA). We assessed both OvCa cell lines, murine syngeneic tumor models (ID8 Tp53-/- and ID8 Tp53-/-, Brca2-/-), formalin-fixed pre- and post-chemotherapy primary human tumors (18 pairs), and snap frozen primary gynecologic tumors (n=103). Statistical tests performed in Prism GraphPad and include multi-comparison ANOVA, paired t-test, and unpaired t-test. Results: WNT4-overexpression in the ID8 model drove cisplatin resistance in vitro, and resistance and metastatic outgrowth in vivo (n=5 mice/model; post-treatment metastatic nodule mass: control = 5±8mg; WNT4 = 42±18mg; p=0.0078). In paired OvCa tumors pre-/post-treatment with chemotherapy (n=18 pairs), we found WNT4 in the top 10 most-strongly induced genes post-chemotherapy (>4-fold, p =0.0005). In OvCa cell lines, WNT4 siRNA only suppressed growth in WNT4 variant lines (60% reduced growth in n=4 variants, vs n=4 wild-type p=0.010). WNT4 siRNA dysregulated mitochondrial function only in WNT4 variant lines, linking the rs3820282 variant to WNT4-driven metabolic remodeling. RPPA analysis of gynecologic tumors (52% het.+variant); note this is one of the largest proteomic studies enriched for patient diversity (47% from non-White). We identified differential metabolic signaling; AMPK activation was increased in variant tumors (AMPKα1-pT172 + AMPKα2-pS345; p=0.031) along with AMPK signaling targets. Conversely, glucose metabolism proteins were increased in wild-type tumors, and inversely correlated with AMPK activation (Spearman ρ=-0.34, p=0.0005), suggesting that WNT4 genotype underpins AMPK activation and metabolic remodeling. Conclusions: The rs3820282 variant permits aberrant activation of WNT4, driving AMPK-mediated metabolic remodeling and therapy resistance. As the rs3820282 VAF differs widely across populations, WNT4 polymorphism may drive disparities in gynecologic cancer risk and outcomes. Understanding WNT4 signaling and regulation via the rs3820282 variant can lead to precision treatments exploiting cellular dependencies on WNT4 signaling. Citation Format: Benjamin G. Bitler, Madeleine T. Shackleford, Lindsey Trevino, Linda S. Cook, Matthew J. Sikora. A common WNT4 polymorphism drives gynecologic cancer phenotypes and health disparities [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B099.

Abstract B069: Bone marrow-derived adipocytes promote ovarian cancer progression and metastasis

Abstract B069: Bone marrow-derived adipocytes promote ovarian cancer progression and metastasis

Auto-segmentation of neck nodal metastases using self-distilled masked image transformer on longitudinal MR images.

Auto-segmentation promises greater speed and lower inter-reader variability than manual segmentations in radiation oncology clinical practice. This study aims to implement and evaluate the accuracy of the auto-segmentation algorithm, "Masked Image modeling using the vision Transformers (SMIT)," for neck nodal metastases on longitudinal T2-weighted (T2w) MR images in oropharyngeal squamous cell carcinoma (OPSCC) patients. This prospective clinical trial study included 123 human papillomaviruses (HPV-positive [+]) related OSPCC patients who received concurrent chemoradiotherapy. T2w MR images were acquired on 3 T at pre-treatment (Tx), week 0, and intra-Tx weeks (1-3). Manual delineations of metastatic neck nodes from 123 OPSCC patients were used for the SMIT auto-segmentation, and total tumor volumes were calculated. Standard statistical analyses compared contour volumes from SMIT vs manual segmentation (Wilcoxon signed-rank test [WSRT]), and Spearman's rank correlation coefficients (ρ) were computed. Segmentation accuracy was evaluated on the test data set using the dice similarity coefficient (DSC) metric value. P-values <0.05 were considered significant. No significant difference in manual and SMIT delineated tumor volume at pre-Tx (8.68 ± 7.15 vs 8.38 ± 7.01 cm3, P = 0.26 [WSRT]), and the Bland-Altman method established the limits of agreement as -1.71 to 2.31 cm3, with a mean difference of 0.30 cm3. SMIT model and manually delineated tumor volume estimates were highly correlated (ρ = 0.84-0.96, P < 0.001). The mean DSC metric values were 0.86, 0.85, 0.77, and 0.79 at the pre-Tx and intra-Tx weeks (1-3), respectively. The SMIT algorithm provides sufficient segmentation accuracy for oncological applications in HPV+ OPSCC. First evaluation of auto-segmentation with SMIT using longitudinal T2w MRI in HPV+ OPSCC.

Magnetic resonance imaging accuracy in assessing depth of invasion in tongue squamous cell carcinomas and predicting cervical nodal metastasis.

The aim of this study was to evaluate magnetic resonance imaging (MRI) accuracy in assessing the depth of invasion (DOI) compared to pathological DOI in oral tongue squamous cell carcinoma (SCC) and to determine whether MRI-measured DOI can predict lymph node metastasis in the cervical region. This retrospective study comprised 36 patients diagnosed with oral tongue SCC who underwent head and neck MRI 1-30 days before surgery and were surgically treated at King Fahad Medical City between January 2017 and November 2022. Relevant information was collected from the patients' records, and the data were analyzed to determine the radiological-histopathological correlations for the DOI and ascertain the cutoff point for nodal metastasis. A value for Pearson's correlation coefficient between MRI-measured and pathological DOI was 0.86, indicating that these measures were highly associated and consistent with each other. The MRI-measured DOI coronal view (CV) was slightly overestimated than the pathological DOI by 1.72 mm. The cutoff values for the MRI-measured DOI CV and pathological DOI that indicated nodal metastasis were 7.08 mm and 9.04 mm, respectively. Preoperative MRI is a valuable tool to accurately stage oral tongue SCC by measuring the depth of tumor invasion.

Surgical Resection Improves Overall Survival in cT4b Major Salivary Gland Cancer.

To compare surgical and nonsurgical definitive treatment in cT4b major salivary gland cancer (MSGC). Retrospective cohort study. The 2004 to 2019 National Cancer Database. The NCDB was queried for patients with cT4b MSGC (N = 976). Patients undergoing definitive treatment with (1) surgical resection + adjuvant therapy, (2) radiotherapy (RT) alone, or (3) chemoradiotherapy (CRT) were included in Kaplan-Meier and Cox survival analyses. Of 219 patients undergoing definitive treatment, 148 (67.6%) underwent surgical resection + adjuvant therapy and 71 (32.4%) underwent RT or CRT. There were no documented mortalities within 90 days of surgical resection. Tumor diameter and nodal metastasis were associated with decreased odds of undergoing definitive treatment (P < 0.025). Patients with positive surgical margins (PSM) had higher 5-year overall survival (OS) than those undergoing definitive RT or CRT (48.5% vs30.1%, P = 0.018) and similar 5-year OS as those with negative margins (48.5% vs54.0%, P = 0.205). Surgical resection + adjuvant therapy (adjusted hazard ratio: 0.55, 95% confidence interval [CI]: 0.37-0.84) was associated with higher OS than definitive RT or CRT (P < 0.025). A separate cohort of 961 patients with cT4a tumors undergoing surgical resection + adjuvant therapy was created; cT4a and cT4b (hazard ratio: 1.02, 95% CI: 0.80-1.29, P = 0.896) tumors had similar OS. A minority of patients with cT4b MSGC undergo definitive treatment. Surgical resection + adjuvant therapy was safe and associated with higher OS than definitive RT or CRT, despite high rate of PSM. In the absence of clinical trial data, appropriately selected patients with cT4b MSGC may benefit from surgical resection.

Papillary thyroid microcarcinoma with and without nodal metastasis: A comparative analysis.

To assess the demographics and clinical factors of papillary thyroid microcarcinoma (PTMC) patients in Saudi Arabia and compared and analyzed the differences between the patients with and without lymph node metastasis (LNM). Papillary thyroid microcarcinoma (PTMC) is a common thyroid cancer and is not usually detectable clinically but found incidentally after pathologic evaluation of thyroid tissue following surgery for benign thyroid disorders. However, these tumors have a significant risk of LNM. All PTMC patients who underwent surgery at King Abdulaziz University Hospital, King Fahad Medical City, and King Abdulaziz Medical City from 2012 to 2022 were included. The incidence rate of LNM was 9.17%. The patients' average age was 44.05. Most of the patients were female. Prevalence of LNM among PTMC patients is 9.17% (n=31). The PTMC patients showed the following significant risk factors for LNM: higher Bethesda class, type of pathology, extrathyroidal extension, extracapsular extension, lymphovascular invasion, and residual tumors in patients who had received radioactive iodine. Presence of thyroiditis, multifocality, goitrous thyroid, neural invasion, and tumor size were unrelated to the LNM in the PTMC patients. Higher Bethesda class, pathology type, extrathyroidal extension, extracapsular extension, lymphovascular invasion, and RAI-treated residual tumors were strongly linked to LNM.

Weishaar's classification system for nodal metastasis in sentinel lymph nodes: Clinical outcome in 94 dogs with mast cell tumor.

The therapeutic role and prognostic relevance of lymphadenectomy in mast cell tumor (MCT) has historically been evaluated on regional rather than sentinel lymph nodes. To update information about the association of histological nodal (HN) classes with clinical outcome in dogs with MCT after tumor excision and extirpation of normal-sized sentinel nodes (SLN) guided by radiopharmaceutical. Ninety-four dogs with histologically-confirmed treatment-naïve MCT (71 cutaneous, 22 subcutaneous and 1 conjunctival MCT) were included if without: distant metastases, lymphadenomegaly, concurrent mixed cutaneous, and subcutaneous MCT. This was a monoistitutional cohort study. Tumors characteristics were retrieved and SLNs were classified according to Weishaar's system. Incidence of MCT-related events (local, nodal, distant relapse), de novo MCT or other tumors and death (MCT-related and non-MCT-related), were recorded. Incidence curves were compared among the HN classes. Twenty-seven dogs had HN0, 19 HN1, 37 HN2, and 11 HN3 SLN. Thirteen (2 HN0, 4 HN2, and 7 HN3) received adjuvant chemotherapies. Kiupel high grade, increasing number of SLN and lymphocentrums were associated with higher HN classes. Five dogs died for MCT-related causes: 1 low-grade (HN0) and 1 subcutaneous (HN3) had a local relapse, 2 high-grade had distant relapse (HN3-HN0) and 1 dog developed disease progression from a de novo subcutaneous MCT. No nodal relapse was registered. Fourteen dogs developed de novo MCTs. Low grade/low-risk MCT with nonpalpable and normal sized SLN have a favorable outcome independently from the HN. Result should be considered strictly related to the successful SLN detection guided pre- and intraoperative by radiopharmaceutical markers.

Multiparametric evaluation of mediastinal lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers.

This study aimed to determine the predictive factors of lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers, so as to help making surgical strategy. From January 2016 to December 2017, patients with clinical T0-T1c stage non-small-cell lung cancers were retrospectively reviewed. We elucidated the lymph node metastatic incidence and distribution according to the primary tumour radiographic findings and maximal standard uptake values, and extracted the associated clinicopathological factors. Univariable and multivariable logistic regressions were used to identify independent predictive parameters for lymph node metastases. The performance of predictive model was evaluated using receiver operating characteristic analysis. A total of 517 patients were included. Seventy-two patients had lymph node metastases. Among patients with pure ground-glass nodule and solid component size ≤10 mm, none had any lymph node metastasis. Multivariable logistic regression analysis demonstrated that age, carcinoembryonic antigen level, solid component size, consolidation-tumour ratio and tumour maximal standard uptake values were independent predictors of lymph nodal metastases. Receiver operating characteristic analyses indicated that the area under the curve of predictive model in evaluating lymph node metastases was 0.838 (95% CI 0.791-0.886). Younger age, elevated carcinoembryonic antigen level, larger solid component size, higher consolidation-tumour ratio and tumour maximal standard uptake values were associated with lymph node involvement. Employing such a predictive model in the future may affect the surgical option of lymph node excision for patients in cT1 stage non-small-cell lung cancer.

Optimal lymph node yield in oesophagectomy for oesophageal cancer: a nationwide population-based study.

The desirable lymph node count was determined to maximize the survival time expectancy according to the lymph node count among patients who have undergone oesophagectomy for oesophageal cancer. The data of national Finnish population-based cohort including all patients who have undergone oesophagectomy due to oesophageal cancer during 2002-2016 were used. Restricted mean survival time (RMST) estimates were determined by lymph node count, and the desirable count was determined using locally estimated scatterplot smoothing regression. A total of 883 patients with the median follow-up time of 3.73 (interquartile range 1.43-7.50) years were included. The lymph node count of 27 (95% confidence interval 25-28) was associated with the highest RMST estimates. Sensitivity analyses indicated that in pN0 patients, the highest RMST estimates was observed at 26 (95% confidence interval 24-28) lymph nodes and in pN+ patients, the RMST estimates peaked at 28 (95% confidence interval 25-33) lymph nodes. According to the findings of this study, at least 24 examined lymph nodes is the recommended target for the lymph node count after oesophagectomy for oesophageal cancer. The beneficial effect of this count on survival may be achieved regardless of nodal metastases.

High-risk histopathologic features in local advanced conjunctival melanoma.

To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

Myxoid Liposarcoma of the Parotid Gland.

Liposarcoma is extremely rare in the parotid gland. In this article, we report the case of an 87-year-old man who presented to our department with swelling in the left parotid region. Magnetic resonance imaging (MRI) revealed a tumor in the superficial lobe of the parotid gland. Total parotidectomy and ipsilateral lymph node dissection were performed. Histologic examination confirmed the diagnosis of myxoid liposarcoma of the parotid gland. On imaging, there was no evidence of nodal or distant metastasis. Radiation therapy was planned, but the patient refused to receive treatment. After a follow-up of 3 years, MRI showed no sign of tumor recurrence and the patient remained symptom-free. The case is original by the tumor's location. Only 8 cases of primary parotid liposarcoma have been reported in the literature. The purpose of this article was to discuss, through our case, clinical and anatomopathological features of parotid gland liposarcomas as well as its treatment options and prognosis.

Role of Perifacial Lymph Node in Nodal Metastasis in Oral Squamous Cell Carcinoma: A Prospective Study.

Nodal involvement in oral squamous cell carcinoma is common due to its lymphatic spread. First echelon group of lymph nodes are to be removed in such scenarios. Perifacial lymph nodes are one of the suspected groups to be affected in metastasis and also missed in dissection due to position. So separate evaluation of this group is important surgically.

Comparison of Early Inguinal Lymph Node Dissection and Neoadjuvant Chemotherapy in Penile Cancer Patient with Bulky Nodal Metastasis: A Cohort Study.

Penile cancer is a rare malignancy, where extranodal extension in inguinal or pelvic lymph nodes is associated with decreased 5-year cancer-survival rate in this study, we try to assess survival and quality of life in a penile cancer patient with bulky lymph node. We retrospectively reviewed data from penile cancer patients with bulky lymph nodes who underwent treatment between July 2016 and July 2021 at tertiary referral hospital care. The inclusion criteria (age >18 yr, histologically proven penile cancer, and completion of last treatment 6 months prior to this study) yielded a cohort of 20 eligible penile cancer patients with bulky lymph nodes (> 4 cm/bilateral mobile/unilateral fixed). Only patients who had completed therapy at least 6 months prior to the study were included. After obtaining consent, they were asked to complete the EORTC QLQ-C30 questionnaire to evaluate the patient's quality of life. Out of 20 patients, 5 patients underwent direct ILND and 15 patients underwent chemotherapy. Median follow-up after primary diagnosis was 114+32 months in patients with early ILND and 52+11 months in patients who underwent delayed lymph node dissection. Out of 5 patients who underwent early ILND, all of them survived during follow-up, and achieved cancer-free status without residual tumor and with excellent functional outcomes (Karnofsky 90). There was no significant difference in social function (p-value = 0.551), physical function (p-value = 0.272), role function (p-value = 0.546), emotional function (p-value = 0.551), cognitive function (p-value = 0.453), and global health status (p-value = 0.893) between patient which treated with early ILND and Neoadjuvant Chemotherapy. However, patients who underwent early ILND showed a relatively better clinical outcome. Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more favourable than neoadjuvant TIP chemotherapy.

Can Ethanol Ablation Achieve Durable Control of Neck Nodal Recurrences in Adults With Stage I Papillary Thyroid Cancer?

Results of ethanol ablation (EA) for controlling neck nodal metastases (NNM) in adult patients with papillary thyroid carcinoma (APTC) beyond 6 months have rarely been reported. We now describe outcome results in controlling 71 NNM in 40 node-positive stage I APTC patients followed for 66 to 269 months. All 40 patients were managed with bilateral thyroidectomy and radioiodine therapy and followed with neck ultrasound (US) for >48 months after EA. Cumulative radioiodine doses ranged from 30 to 550 mCi; pre-EA 27 patients (67%) had 36 additional neck surgeries. Cytologic diagnosis of PTC in 71 NNM selected for EA was confirmed by US-guided biopsy. EA technique and follow-up protocol were as previously described. The 40 patients had 1 to 4 NNM; 67/71 NNM (94%) received 2 to 4 ethanol injections (total median volume 0.8 cc). All ablated 71 NNM shrank (mean volume reduction of 93%); nodal hypervascularity was eliminated. Thirty-eight NNM (54%) with initial volumes of 12-1404 mm3 (median 164) disappeared on neck sonography. Thirty-three hypovascular foci from ablated NNM (pre-EA volume range 31-636 mm3; median 147) were still identifiable with volume reductions of 45% to 97% observed (median 81%). There were no complications and no postprocedure hoarseness. Final results were considered to be ideal or near ideal in 55% and satisfactory in 45%. There was no evidence of tumor regrowth after EA. Our results demonstrate that for patients with American Joint Committee on Cancer stage I APTC, who do not wish further surgery or radioiodine, and are uncomfortable with active surveillance, EA can achieve durable control of recurrent NNM.

Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication.

The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. 3 Laryngoscope, 134:3230-3237, 2024.

SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree

IntroductionPrimary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. Methods and resultsWe retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6–78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). ConclusionIt is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Factors Associated With Long-term Survival in Children With Bronchial and Lung Carcinoid Tumors

Background and aimsBronchial carcinoids are rare in children and the treatment is based on tumor behavior in adults. The purpose of this study was to determine factors and management strategies associated with long-term survival in the pediatric population using a national cohort. MethodsPatients aged ≤20 years with bronchial carcinoid tumors were identified in the 2004–2020 National Cancer Database using ICD-O-3 codes. Tumor characteristics and management were compared among typical (TC) and atypical (AC) histological subtypes using Chi-square and Fisher's exact tests. Kaplan–Meier and univariate Cox proportional hazards analyses were used to assess survival. ResultsOf 273 patients, 251 (92%) had TCs, and 22(8%) had ACs. The median (IQR) age was 18 (16,19) years. Most patients underwent lobectomy or bilobectomy (67%), followed by sublobar resection (17%), no resection or bronchoscopic excision or ablation (8%), and pneumonectomy (7.7%). Margins were negative in 96%. Lymph node (LN) assessment was performed in 216 patients (84%) with a median (IQR) of 7(3,13) LNs, and 50 (23%) had ≥1 positive LN. There was no difference in age, resection, margin status, LN assessment, or positivity between TC and AC (all p > 00.05). Detection of nodal metastasis did not increase beyond the resection of 1–3 LNs (p = 0.72). Ten-year survival was worse for AC than TC (79% (41, 100) vs 98% (95, 100), HR = 6.9 (95% CI: 1.2–38.3, p = 0.03). Ten-year survival among those with and without LN assessment was 97% (94, 100) vs 91% (81, 100), HR = 4.0, 95% CI: 0.8–19.9, p = 0.09). There were no deaths in those with negative LN while 10-year survival was 89% (72, 100) in those with ≥1 positive LN. ConclusionAmong children with bronchial carcinoids, survival is excellent with TC or negative LN. Atypical histology and positive LN have poor survival and should prompt close monitoring. These risk factors may be missed in the absence of surgical resection and lymph node sampling. Level of EvidenceIII. Type of StudyRetrospective Study.

Breast Cancer Molecular Subtyping in Practice: A Real-World Study of the APIS Breast Cancer Subtyping Assay in a Consecutive Series of Breast Core Biopsies.

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the seven parameters including three biomarkers routinely assessed in all the newly diagnosed breast cancers (BC), oestrogen receptor (ER), progesterone receptor (PR) and HER-2 and an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2 and KIF23. Taken together, the data are used to produce a molecular subtype for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridisation (ISH) in breast cancer patients. The data were presented at the weekly breast multidisciplinary team (MDT) meeting. A total of 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsies of nodal metastases yielding 100 cases were assessed. IHC and APIS results were available for 100 and 99 cases. ER was concordant in 97% cases, PR was concordant in 89% and HER-2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% of cases when compared with MK167 alone but discordant in 24% when compared with the four-gene proliferation signature. In conclusion, our study indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER-2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnosed breast cancer (BC) specimens.

Risk of lymph node metastasis in T1 esophageal adenocarcinoma: a meta-analysis.

Patients with early (T1) esophageal adenocarcinoma (EAC) are increasingly having definitive local therapy endoscopically. Endoscopic resection is not able to pathologically stage or treat lymph node metastasis (LNM). Accurate identification of patients having nodal metastasis is critical to select endoscopic therapy over surgery. This study aimed to define the risk of LNM in T1 EAC. A meta-analysis of studies of patients who underwent surgery and lymphadenectomy with assessment of LNM was performed according to PRISMA. Main outcome was probability of LNM in T1a and T1b disease. Secondary outcomes were risk factors for LNM and rate of LNM in submucosal T1b (SM1, SM2, and SM3) disease. Registered with PROSPERO (CRD42022341794). Twenty cohort studies involving 2264 patients with T1 EAC met inclusion criteria: T1a (857 patients) with 36 (4.2%) node positive and T1b (1407 patients) with 327 (23.2%) node positive. Subgroup analysis of T1b lesions was available in 10 studies (405 patients). Node positivity for SM1, SM2, and SM3 was 16.3%, 16.2%, and 29.4%, respectively. T1 substage (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.45-13.38, P < 0.01), tumor differentiation (OR 2.82, 95% CI 2.06-3.87, P < 0.01), and lymphovascular invasion (OR 13.65, 95% CI 6.06-30.73, P < 0.01) were associated with LNM. T1a disease demonstrated a 4.2% nodal metastasis rate and T1b disease a rate of 23.2%. Endoscopic therapy should be reserved for T1a disease and perhaps select T1b disease, which has a moderately high rate of nodal metastasis. There were inadequate data to stratify T1b SM disease into 'low-risk' and 'high-risk' based on tumor differentiation and lymphovascular invasion.