scholarly journals Genomic and Transcriptomic Characterization of Papillary Microcarcinomas With Lateral Neck Lymph Node Metastases

2019 ◽  
Vol 104 (10) ◽  
pp. 4889-4899 ◽  
Author(s):  
Dilmi Perera ◽  
Ronald Ghossein ◽  
Niedzica Camacho ◽  
Yasin Senbabaoglu ◽  
Venkatraman Seshan ◽  
...  

Abstract Context Most papillary microcarcinomas (PMCs) are indolent and subclinical. However, as many as 10% can present with clinically significant nodal metastases. Objective and Design Characterization of the genomic and transcriptomic landscape of PMCs presenting with or without clinically important lymph node metastases. Subjects and Samples Formalin-fixed paraffin-embedded PMC samples from 40 patients with lateral neck nodal metastases (pN1b) and 71 patients with PMC with documented absence of nodal disease (pN0). Outcome Measures To interrogate DNA alterations in 410 genes commonly mutated in cancer and test for differential gene expression using a custom NanoString panel of 248 genes selected primarily based on their association with tumor size and nodal disease in the papillary thyroid cancer TCGA project. Results The genomic landscapes of PMC with or without pN1b were similar. Mutations in TERT promoter (3%) and TP53 (1%) were exclusive to N1b cases. Transcriptomic analysis revealed differential expression of 43 genes in PMCs with pN1b compared with pN0. A random forest machine learning–based molecular classifier developed to predict regional lymph node metastasis demonstrated a negative predictive value of 0.98 and a positive predictive value of 0.72 at a prevalence of 10% pN1b disease. Conclusions The genomic landscape of tumors with pN1b and pN0 disease was similar, whereas 43 genes selected primarily by mining the TCGA RNAseq data were differentially expressed. This bioinformatics-driven approach to the development of a custom transcriptomic assay provides a basis for a molecular classifier for pN1b risk stratification in PMC.

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 144-144
Author(s):  
Jasper Groen ◽  
Suzanne Gisbertz ◽  
Mark I Van Berge Henegouwen ◽  
Annelijn E Slaman ◽  
Sybren Meijer ◽  
...  

Abstract Background Celiac trunk metastases are an independent factor for inferior survival in patients with esophageal cancer. Detecting these metastases before esophagostomy would aid clinical decision making. The aim of our study was to evaluate the accuracy of integrated PET and CT (PET-CT) using 18F-FDG in detecting these metastases in patients with esophageal cancer after neoadjuvant chemoradiotherapy (nCRTx) followed by esophagectomy. Methods All patients with a carcinoma of the mid-to-distal esophagus or the gastroesophageal junction (GEJ) who underwent esophageal resection with curative intent following nCRTx between January 2011 and January 2017 were included. The PET-CT scans after nCRTx were reviewed by nuclear radiologists and lymph nodes within a margin of 2 cm around the celiac trunk were expressed in SUVmax. Lymph nodes with SUVmax > 2.0 were deemed positive. The truncal nodes were extracted during esophagectomy and reviewed by different pathologists using standard pathology protocol. To assess the accuracy of the PET-CT in detecting lymph node metastases near the celiac trunk the sensitivity, specificity and positive and negative predictive value were calculated. Results A total of 448 patients were included. There were 24 patients (5.4%) with positive truncal nodes on the PET-CT versus 424 patients (90.6%) with negative truncal nodes on the PET-CT. Out of these 24 patients 20 (83.3%) had truncal node metastases confirmed in the resection specimen (positive predictive value of 83.3%). In the other 424 patients 40 (9.4%) had truncal node metastases confirmed in the resection specimen (negative predictive value of 90.6%). This results in a sensitivity of 33.3% and a specificity of 99.0%. Conclusion The sensitivity and specificity of the PET-CT in detecting lymph node metastases near the celiac trunk in patients with esophageal cancer who underwent nCRTx were respectively 33.3% and 99.0% This shows that the PET-CT is accurate in detecting truncal lymph node metastases in this patient group. Disclosure All authors have declared no conflicts of interest.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Caitlin Harrington ◽  
Rebecca Carr ◽  
Smita Sihag ◽  
Prasad Adusumilli ◽  
Manjit Bains ◽  
...  

Abstract   Although the pattern of nodal metastasis and the prognosis of number and location of positive nodes have been well described with esophageal cancer undergoing upfront surgery, little is known about nodal metastasis after neoadjuvant treatment. The aim of this study is to assess the pattern of nodal metastases in esophageal adenocarcinoma treated with neoadjuvant chemoradiation and surgery and evaluate its effect on prognosis. Methods All patients with esophageal adenocarcinoma who had undergone neoadjuvant chemoradiation and an R0 esophagectomy between 2010 and 2018 at our institution were included (n = 577). Pathology reports were reviewed for sites of lymph node metastases. Patients were excluded if nodal stations were not listed separately (n = 40). Age, sex, race, tumor location, TRG, pT stage, number of positive lymph nodes, number of positive nodal stations, and specific nodal stations were analyzed for risk of recurrence using univariable Cox regression, and significant covariates were included in multivariable Cox regression model. Results Of 537 patients, 193(36%) had pathologic nodal metastases. 153 patients(28%) had single-station disease: 135(88%) at the paraesophageal station, 16(10%) at the left gastric, 1 at the subcarinal and 1 at the paratracheal station(0.65% each). 32 patients(6.0%) had two-station and 8(1.5%) had three-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal(90%) and/or left gastric artery stations(60%). On multivariable analysis, the number of positive nodal stations (HR 1.59, CI 1.35–1.84, p < 0.001), subcarinal (HR 2.78, CI 1.54–5.03, p < 0.001), and paraesophageal stations (HR 2.0, CI 1.58–2.54, p < 0.001) were associated with increased risk of recurrence. Conclusion Patients who have undergone neoadjuvant and R0 esophagectomy for adenocarcinoma often have lymph node metastases at time of surgery, most commonly at the paraesophageal station. The number of nodal stations, along with subcarinal and paraesophageal metastases, were associated with increased risk of recurrence.


2020 ◽  
Vol 19 ◽  
pp. 153303382096208
Author(s):  
Xin Wu ◽  
Binglu Li ◽  
Chaoji Zheng ◽  
Wei Liu ◽  
Tao Hong ◽  
...  

Purpose: Medullary thyroid carcinoma is a rare endocrine malignancy; 75% of patients with this disease have sporadic medullary thyroid carcinoma. While surgery is the only curative treatment, the benefit of prophylactic lateral neck dissection is unclear. This study aimed to analyze the clinicopathological risk factors associated with lateral lymph node metastases and determine the indication for prophylactic lateral neck dissection in patients with sporadic medullary thyroid carcinoma. Methods: The medical records of patients with medullary thyroid carcinoma who were treated at our hospital between January 2002 and January 2020 were retrospectively reviewed; a database of their demographic characteristics, test results, and pathological information was constructed. The relationship between lateral lymph node metastases and clinicopathologic sporadic medullary thyroid carcinoma features were analyzed using univariate and multivariate analyses. Results: Overall, 125 patients with sporadic medullary thyroid carcinoma were included; 47.2% and 39.2% had confirmed central and lateral lymph node metastases, respectively. Univariate and multivariate analyses identified 2 independent factors associated with lateral lymph node metastases: positive central lymph node metastases (odds ratio = 9.764, 95% confidence interval: 2.610–36.523; p = 0.001) and positive lateral lymph nodes on ultrasonography (odds ratio = 101.747, 95% confidence interval: 14.666–705.869; p < 0.001). Conclusion: Medullary thyroid carcinoma is a rare endocrine malignancy. Lymph node metastases are common in patients with sporadic medullary thyroid carcinoma. Prophylactic lateral neck dissection is recommended for patients who exhibit positive central lymph node metastases and/or positive lateral lymph nodes on ultrasonography.


2010 ◽  
Vol 95 (6) ◽  
pp. 2655-2663 ◽  
Author(s):  
Andreas Machens ◽  
Henning Dralle

Abstract Context: Preoperative neck ultrasonography may yield false-negative findings in more than one-third of medullary thyroid cancer (MTC) patients. If not cleared promptly, cervical lymph node metastases may emerge subsequently. Reoperations entail an excess risk of surgical morbidity and may be avoidable. Objective: This comprehensive investigation aimed to evaluate in a head-to-head comparison the clinical utility of pretherapeutic biomarker serum levels (basal calcitonin; stimulated calcitonin; carcinoembryonic antigen) for indicating extent of disease and providing biochemical stratification of pretherapeutic MTC risk. Design: This was a retrospective analysis. Setting: The setting was a tertiary referral center. Patients: Included were 300 consecutive patients with previously untreated MTC. Interventions: The intervention was compartment-oriented surgery. Main Outcome Measure: Stratified biomarker levels were correlated with histopathologic extent of disease. Results: Higher biomarker levels reflected larger primary tumors and more lymph node metastases. Stratified basal calcitonin serum levels correlated better (r = 0.59) with the number of lymph node metastases than carcinoembryonic antigen (r = 0.47) or pentagastrin-stimulated calcitonin (r = 0.40) levels. Lymph node metastases were present in the ipsilateral central and lateral neck, contralateral central neck, contralateral lateral neck, and upper mediastinum, respectively, beyond basal calcitonin thresholds of 20, 50, 200, and 500 pg/ml. Bilateral compartment-oriented neck surgery achieved biochemical cure in at least half the patients with pretherapeutic basal calcitonin levels of 1,000 pg/ml or less but not in patients with levels greater than 10,000 pg/ml. Conclusions: Most newly diagnosed MTC patients, i.e. those with pretherapeutic basal calcitonin levels greater than 200 pg/ml, may need bilateral compartment-oriented neck surgery to reduce the number of reoperations.


2005 ◽  
Vol 23 (12) ◽  
pp. 2813-2821 ◽  
Author(s):  
Andrea G. Rockall ◽  
Syed A. Sohaib ◽  
Mukesh G. Harisinghani ◽  
Syed A. Babar ◽  
Naveena Singh ◽  
...  

Purpose Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node–specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. Methods Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. Results Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The κ statistic was 0.93. Conclusion Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.


2008 ◽  
Vol 123 (2) ◽  
pp. 401-408 ◽  
Author(s):  
Hong Lok Lung ◽  
Paulisally Hau Yi Lo ◽  
Dan Xie ◽  
Suneel S. Apte ◽  
Arthur Kwok Leung Cheung ◽  
...  

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Victor McPherson ◽  
Bernard H. Bochner ◽  
Shawn Dason ◽  
Priscilla Baez ◽  
Eugene Pietzak ◽  
...  

2004 ◽  
Vol 14 (1) ◽  
pp. 104-109 ◽  
Author(s):  
J. Balega ◽  
H. Michael ◽  
J. Hurteau ◽  
D. H. Moore ◽  
J. Santiesteban ◽  
...  

A functional and widely accepted definition of microinvasive cervical adenocarcinoma remains elusive. The purpose of this study was to determine at which depth of invasion the likelihood of lymph node metastasis or disease recurrence was so small that conservative surgery could be considered appropriate. Charts of patients with adenocarcinoma of the cervix (ACC) who underwent radical hysterectomy and pelvic lymphadenectomy (n = 98) at Indiana University Medical Center from 1987 to 1998 were retrospectively reviewed. Patients with stage IA1–IB1 lesions were included in the study. Patients treated with preoperative radiotherapy were excluded. Pathologic parameters evaluated included histologic type, depth of stromal invasion (DOI), and the presence of lymphatic vascular space invasion, or lymph node metastases. The patient median age was 39 years (20–65). The median time of follow-up was 30 months (4–124). Lymph node metastases were found in ten patients and 11 developed recurrences. The precise DOI could be measured in 84 patients. Of the 48 patients with cancers with a DOI ≤ 5 mm, none had involved parametria or nodes; whereas eight of the 36 with a DOI > 5 mm had nodal metastases (P = 0.00069). None of these 48 patients with a tumor DOI ≤ 5 mm developed a recurrence whereas six of the 36 patients with a tumor DOI > 5 mm developed recurrent disease (P = 0.0048). The risk of nodal metastases and recurrence is so low in patients with ACC and DOI ≤ 5 mm that for patients with such depth documented on conization with negative margins pelvic lymphadenectomy may be omitted.


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