Histopathologic Tumor Grade Research Articles

Assessment of Apparent Diffusion Coefficients and SUVs as Predicators of Histological Differentiation in Anal Squamous Cell Carcinoma.

The study aims to assess minimal apparent diffusion coefficient (ADCmin) and SUVmax as predictors of histological differentiation in patients with anal squamous cell carcinoma (ASCC) and to determine cutoff values for each histopathological tumor grade. A retrospective study of 41 ASCC patients (14 males, 27 females; mean age, 65 ± 13 years) staged with FDG PET/CT and MRI (mean scan time interval, 21 ± 11 days). SUVmax and ADCmin values were measured and compared with histopathological tumor grading obtained from biopsy. The mean size and tumor volume were 3 ± 2 cm and 16.5 ± 27.3 cm3, respectively. The mean ADCmin values for well-, moderately, and poorly differentiated ASCC were 935 ± 179, 896 ± 123, and 637 ± 114, respectively. The mean SUVmax for well-, moderately, and poorly differentiated ASCC were 6.9 ± 1.8, 11.5 ± 4.1, and 13.4 ± 2.6, respectively. The difference in mean ADCmin values between poorly and moderately/well-differentiated tumors was statistically significant, whereas this was not significant between moderately and well-differentiated tumors. Differences in SUVmax values were statistically significant between poorly/moderately and well-differentiated tumors, whereas there was no statistical significance between poorly and moderately differentiated tumors. By combining the 2 modalities using cutoff values of 675 × 10-6 mm2·s-1 for ADCmin and 8.5 for SUVmax, it was possible to differentiate the tumor categories with a sensitivity, specificity, positive predictive value, and negative predictive value, respectively, of 84.6%, 96.4%, 91.7%, and 93.1% for well-differentiated ASCC, 76.5%, 87.5%, 81.3%, and 84% for moderately, and 90.9%, 89.3%, 76.9%, and 96.2% for poorly differentiated ASCC, respectively. ADCmin and SUVmax values correlated with the degree of differentiation in ASCC and can be used as predictors of tumor grading and aggressiveness. Combined ADCmin and SUVmax cutoff values can therefore be used for early patient risk stratification and treatment decision making.

The fate of paratesticular masses: 13 years' experience in a tertiary referral centre.

Paratesticular neoplasms exhibit different behaviours, depending on the embryological tissue of origin. Treatment modalities can depend on the differential diagnosis. The aim of this study is to present the clinical, morphological and histopathological features of patients with paratesticular masses and their follow-ups and is intended to increase awareness of the issues. We included 31 excisions of paratesticular masses, after radiological diagnosis as paratesticular mass in our hospital between 2007-2020. Information on treatment modalities, tumour recurrence, metastasis, and survival rates were obtained from hospital archives. All patients were evaluated by taking patients' history, physical examination, scrotal ultrasound, chest radiography, and serum tumour markers. Treatment modality was selected according to intraoperative findings. Haematoxylin-eosin sections were examined, and immunohistochemical analyses were performed for smooth muscle actin, desmin, Ki67, CD34, S100, and myogenin. Ten high-power fields were counted to document Ki67 and p53 nuclear positivity rates. A total of 31 operations were performed with recurrence in three patients. Histomorphological and immunohistochemical examination revealed eleven malignant masses; eight rhabdomyosarcomas, a leiomyosarcoma, a liposarcoma and a large B cell lymphoma. Other excised masses were benign and infective lesions. Paratesticular masses are heterogeneous tumours that follow different clinical courses. Clinicians must be aware of this histological diversity in order to plan a treatment pathway. This study is one of the largest published series, with a long follow-up period. It shows that the most critical features in determining prognosis are histopathological subtype and tumour grade.

Study of β-Catenin as Immunohistochemistry Marker in Women with Breast Cancer

Background & Objective: Breast cancer (BC) is the most prevalent disease among women around the world, considered the world's leading cause of death (15% of the total cancer deaths) in women in 2018. β-catenin is a multifunctional protein located in the cytoplasm and/or nucleus of the cell. Several studies suggested that β-catenin expression plays a critical role in cancer invasion and metastasis. This research sought to examine β-catenin expression in breast cancer and its associations with clinico-pathological features (such as histopathological types, grade, and invasion depth of tumor as well as lymph node involvement) and breast cancer patient survival. Methods: The study was performed in the period from 1 January to July 2019 on 40 female breast cancer patients. The control group involved 40 healthy females with no history of cancer. Tissue blocks from histologically confirmed patient and control subjects were fixed in formalin and embedded in paraffin . β-catenin was evaluated by immunohistochemistry (IHC). Results: The immunohistochemical study of the subcellular localization of β-catenin demonstrated that 75% of the patients showed 1-3 score for β- catenin compared to only 27.5% of controls who had such score, with a highly significant difference. Conclusions: The use of β-catenin IHC markers can be effective throughout the treatment of progressive BC.

Lung Cancer Attributed Mortality Among 316,336 Early Stage Breast Cancer Cases Treated by Radiotherapy and/or Chemotherapy, 2000-2015: Evidence From the SEER Database.

ObjectiveTo estimate the risk of death from lung cancer in patients treated for breast cancer (BC) in relation to the general population.MethodsBC data, covering 2000 to 2015, were extracted from the Surveillance, Epidemiology and End Results-18 (SEER-18) cancer registry database. A comparison of lung cancer attributed mortality between BC patients and the general population was performed using standardized mortality ratios (SMRs) and SMRs conditional on survival length (cSMRs). Prognostic factors of lung cancer mortality were identified using flexible parametric modelling. Our model adjusts the effect of downstream (histopathological BC tumor grade and hormone receptor status) and upstream (age at diagnosis, ethnicity, and marital status) factors.ResultsThe median follow-up was 6.4 years (interquartile range, 3.0–10.3 years). BC cases who received only radiotherapy (cSMR = 0.93; 95%CI: 0.77–1.13), only chemotherapy (cSMR = 0.91; 0.62–1.33), and radio-and chemotherapy (cSMR = 1.04; 0.77–1.39) had no evidence of increased lung cancer mortality relative to the general population. The adjusted model identified that lung cancer mortality was higher for women who were older at diagnosis compared to those <50 years (ranging from HR50-59 = 3.41 [95%CI: 2.72–4.28] to HR70-79 = 10.53 [95%CI: 8.44–13.13]) and for cases with negative estrogen and progesterone receptors (HR =1.38; 95% CI: 1.21–1.57). Compared to married cases, widowed, divorced, single or others had a 76%, 45%, and 25% higher hazard of lung cancer mortality, respectively. Lung cancer mortality was lower for American Indian/Alaska Native and Asian/Pacific Islander ethnicities (HR = 0.51; 95% CI: 0.40–0.64) compared to BC cases with white ethnic background.ConclusionsThere is no evidence for a higher lung cancer mortality in BC patients when compared to the general population.

Correlation between contrast enhancement, standardized uptake value (SUV), and diffusion restriction (ADC) with tumor grading in patients with therapy-naive neuroendocrine neoplasms using hybrid 68Ga-DOTATOC PET/MRI

ObjectivesTo investigate a correlation between 68Ga-DOTATOC PET/MR imaging parameters such as arterial and venous contrast enhancement, diffusion restriction, and maximum standardized uptake value (SUVmax) with histopathological tumor grading in patients with neuroendocrine neoplasms (NEN). Material and methodsA total of 26 patients with newly diagnosed, therapy-naive neuroendocrine neoplasms (NEN) were enrolled in this prospective study and underwent 68Ga-DOTATOC PET/MRI. Images were evaluated regarding NEN lesion number and location, predominant tumor signal intensity on precontrast T1w and T2w images and on postcontrast arterial and portal venous phase T1w images, apparent diffusion coefficient (ADC) and SUVmax. Histopathological tumor grading was assessed and related to PET/MRI features using Pearson’s correlation coefficient and Fisher’s exact t-test. A binary logistic regression analysis was performed to evaluate a potential relation with an aggressive tumor biology and odds ratios (OR) were calculated. ResultsThere was a moderate negative correlation between arterial contrast enhancement and tumor grading (r=-0.35, p = 0.005), while portal venous enhancement showed a weak positive correlation with the Ki-67 index (r = 0.28, p = 0.008) and a non-significant positive correlation with tumor grading (r = 0.19, p = 0.063). Features that were significantly associated with an aggressive tumor biology were the presence of liver metastases (OR 2.6, p = 0.042), T1w hyperintensity in comparison to muscle (OR 12.7, p = 0.0001), arterial phase hyperenhancement (OR 1.4, p = 0.001), diffusion restriction (OR 2.8, p = 0.02) and SUVmax above the hepatic level (OR 7.0, p = 0.001). ConclusionThe study reveals that PET/MRI features might be useful for prediction of NEN grading and thus provide a preliminary assessment of tumor aggressiveness.

Histogram-based analysis of cerebral blood flow using arterial spin labeling MRI in de novo brain gliomas: relationship to histopathologic grade and molecular markers.

We developed multiple histogram-based CBF indices and evaluated their association with histopathologic grade in de novo brain tumor patients. Furthermore, the associations between these advanced CBF indices and molecular markers, including IDH1 mutation, ATRX loss, and 1p/19q co-deletion were also investigated. Thirteen de novo brain tumor patients (age 21-68years, 9M/4F) who were enrolled in our prospective study were scanned on 3T MRI using a pCASL perfusion sequence following IRB-approved written informed consent. All patients have since undergone surgical intervention with tissue sampling for histopathologic tumor grading and molecular marker assessment. Tumor region of interest (ROI) were manually delineated on FLAIR images including the full extent of the tumor and peritumoral edema. Fourteen rCBF indices were derived from the histogram of the voxels with the ROI. Multi-linear regression was then used to compare rCBF indices with histopathologic tumor grade and molecular markers. Averaged rCBF in top 10 and top 20 voxels (p < 0.004), but not the entire tumor ROI, was positively associated with WHO tumor grade. After accounting for tumor grade, the presence of 1p/19q co-deletion was associated with higher rCBF in top voxels, as well as with standard deviation of rCBF in the tumor ROI (p < 0.001). ATRX retention was related to higher rCBF, and this effect appears to be present in both higher-perfusion (p < 0.004) and low-perfusion (p < 0.05) voxels. IDH mutation was not significantly associated with any of the CBF indices investigated. ASL MRI may provide useful supplemental noninvasive imaging assessment of brain tumor grade and molecular marker status.

Mucoepidermoid Carcinoma: A Demographic and Histopathological Profile

Background: To find the frequency and clinico-pathological presentation of mucoepidermoid carcinoma (MEC).Materials and Methods:In this study, we included all the malignant salivary gland tumors. Among these the frequency of mucoepidermoid carcinoma was considered. Age, gender, histopathological grading and anatomical site of tumor were included in data analysis.Results:Out of 60 malignant salivary gland tumors reported to the histopathology department, 30 tumors were diagnosed as mucoepidermoid carcinomas. The patient’s age having mucoepidermoid carcinoma ranged from 6 to 88 years, mean age of 44.9±19.2SD. The male patients were 23 in number while female were 7. Out of 30 cases, 73.3% patients had tumor in parotid gland, while13.3% patients in submandibular gland . Other tumors were in palate, retromolar area, and in posterior 1/3rdof tongue (13.3%). According to histopathological grading 26.6% cases of MEC were of high grade, 26.6 % were intermediate grade and 36.6% were low grade.Conclusions:According to this study, the frequency of MEC was 50% among all salivary gland tumors. MEC was mostly found in parotid gland and histopathologically low grade type was the most common.

Prospective Correlation of Prognostic Immunohistochemical Markers With SUV and ADC Derived From Dedicated Hybrid Breast 18F-FDG PET/MRI in Women With Newly Diagnosed Breast Cancer.

The aim of this study was to correlate prognostically relevant immunohistochemical parameters of breast cancer with simultaneously acquired SUVs and apparent diffusion coefficient (ADC) values derived from hybrid breast PET/MRI. Fifty-six women with newly diagnosed, therapy-naive, histologically proven breast cancer (mean age, 54.1 ± 12.0 years) underwent dedicated prone 18F-FDG breast PET/MRI. Diffusion-weighted imaging (b-values: 0, 500, 1000 s/mm2) was performed simultaneously with the PET acquisition. A region of interest encompassing the entire primary tumor on each patient's PET/MRI scan was used to determine the glucose metabolism represented by maximum and mean SUV as well as into corresponding ADC maps to assess tumor cellularity represented by mean and minimum ADC values. Histopathological tumor grading and prognostically relevant immunohistochemical markers, that is, Ki67, progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2), were assessed. Pearson correlation coefficients were calculated to compare SUV and ADC values as well as the immunohistochemically markers and molecular subtype. For the comparison with the tumor grading, a Wilcoxon test was used. A significant inverse correlation between SUV and ADC values derived from breast PET/MRI (r = -0.49 for SUVmean vs ADCmean; r = -0.43 for SUVmax vs ADCmin; both P's < 0.001) was found. Tumor grading and Ki67 both showed a positive correlation with SUVmean from breast PET/MRI (r = 0.37 and r = 0.32, P < 0.01). For immunohistochemical markers, HER2 showed an inverse correlation with ADC values from breast PET/MRI (r = -0.35, P < 0.01). Molecular subtypes significantly correlate with SUVmax and SUVmean (r = 0.52 and r = 0.42, both P's < 0.05). In addition, estrogen receptor expression showed an inverse correlation with SUVmax and SUVmean from breast PET/MRI (r = -0.45 and r = -0.42, P < 0.001). The present data show a correlation between increased glucose metabolism, cellularity, tumor grading, estrogen and HER2 expression, as well as molecular subtype of breast cancer primaries. Hence, simultaneous 18F-FDG PET and diffusion-weighted imaging from hybrid breast PET/MRI may serve as a predictive tool for identifying high-risk breast cancer patients in initial staging and guide-targeted therapy.

Cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: a retrospective study on pattern of involvement and clinical analysis.

Background The study was performed with an aim to map the pattern of metastasis of squamous cell carcinomas of buccal mucosa to various cervical lymph node levels and analyze its correlation with primary tumor size and histo-pathological grading. Material and Methods 254 patients with squamous cell carcinoma of the buccal mucosa treated with surgery first approach were analyzed retrospectively. The tumor size was noted from pre-operative CT Scans and were divided into early and advanced tumors. The resected specimen was studied to note the histo-pathological grading of the squamous cell carcinoma and the metastatic deposits at various lymph node levels. Results Out of 254 patients (149 females, 105 males), 145 patients showed histo-pathologically proven metastatic deposits in one or more lymph nodes out of which there were 56 patients showing occult metastasis. 78/145 patients showed metastatic involvement of level IB and/or IA lymph nodes, 31 showed involvement of level II and/or I lymph nodes, 27 showed involvement of level III with or without involvement of level I and II and 9 showed metastasis to level IV and V lymph nodes with or without level I, II or III lymph nodes. Cervical lymph node metastasis had statistically significant association with tumor size with advanced tumors showing worse pattern of metastatic spread beyond level I and II lymph nodes. As the degree of differentiation of squamous cell carcinoma reduced, they were more prone for cervical metastasis with moderately and poorly differentiated squamous cell carcinoma showing higher involvement of level III, IV and V lymph nodes. Conclusions The majority of buccal mucosa cases showed metastasis to level I, II and III lymph nodes out of which level IB and/or IA was most frequently involved. Metastasis to level IV and V lymph nodes was rare and was seen especially in patients with advanced primary tumor and poor histo-pathologic differentiation. Key words:Oral squamous cell carcinoma (OSCC), cervical lymph node metastasis, histologic differentiation, locally advanced disease.

Study of p53 gene over expression as a prognostic marker in squamous cell carcinoma of the oral cavity

The present study entitled ”Study of p53 gene expression as a prognostic marker in squamous cell carcinoma of oral cavity” was conducted in the department of pathology SRMSIMS Bareilly, 66 cases diagnosed on histopathology as squamous cell carcinoma of oral cavity from Jan 2016 to Jan 2017 were included in the study. Various parameters analysed for each case included age, gender, site, history of tobacco chewing, smoking &, alcohol consumption, histopathological grade of tumor and p53 expression. The patients age ranged from 24 to 85 years with mean age; 52.09 years and median age; 53 years. Maximum no of patients were male 54(81.8%) and 12 (18.2%) were female. Male: female ratio was 9:2. The most common site of presentation was lateral border of tongue (34.8). In the present study 89.4% were tobacco chewers, 72.7% were alcoholics and 57.6% were smokers.34 cases (51.5%) were diagnosed as well differentiated, 26 cases(39.4%) as moderately differentiated and 6 cases (9.1)% as poorly differentiated squamous cell carcinoma. The p53 expression was observed in 41(62.1%) of cases. The expression of p53 increased with the grade of tumor. The positivity being 17(50%) in cases of well differentiated, 19(73%) in moderately differentiated and 5(83%) in poorly differentiated squamous cell carcinoma. In present study p53 expression is found to be significantly related with tobacco chewing (p value= 0.034), smoking (p value= 0.0046) and tumor grade (p value=0.030). However no association was found with alcohol consumption (p value=0.917) the increasing prevalence of p53 expression with increasing grade of tumor suggests that it can be used as a prognostic indicator in oral cavity cancers. Keywords: Squamous cell carcinoma, p53 expression, Prognostic indicator, Oral cancer.

Clinicpathological study of ovarian tumors: A 5 year study

A wide spectrum of neoplasms are encountered in the ovary because of the totipotential and multipotential capacity of ovarian germ cells and mesenchymal cells. Ovarian neoplasms are the cause of highest mortality in female genital tract neoplasms. Aim: this study was undertaken to assess the age distribution, presentation and the morphological variants of ovarian neoplasms. Materials and Methods: a retrospective and prospective study was undertaken in the department of pathology from January 2013 to December 2017. Results: out of 105 cases analysed, 98.10% were primary ovarian neoplasms while 1.90% were metastatic tumors. Majority, 85.71% were benign while 8.57% were malignant. Commonest tumors were the surface epithelial tumors (72.38%) followed by 18.09% germ cell tumors and 7.61% sex cord stromal tumors. Benign tumors were common in 4th decade while malignant were common in the 5th decade. The most common presenting complaint was pain in abdomen. Conclusion: Evaluating the exact morphological type is essential in today’s era of targeted therapy for cancer. Further studies on larger population groups are essential to evaluate the outcome with respect to histopathological typing, grading and staging of ovarian tumors. Keywords: Ovarian tumor, Histopathology.

Occult Nodal Metastasis in Oral Cavity Cancers

Introduction: In squamous cell carcinoma (SCC) of the oral cavity, there is always a risk of occult metastasis to neck nodes in the clinically and radiologically negative neck (N0). Therefore, elective neck dissection (END) has ever been under discussion since the beginning of their routine use for the management of neck for oral carcinomas. The purpose of the current study is to identify the percentage of occult nodal metastasis to neck levels I-V in the cases of oral carcinoma who were treated for the N0 with END.Methods: Patients who were treated between June 2005 and May 2010 with END from neck levels I to V for the management of N0 with oral SCC had been identified from the database of Aga Khan University Hospital. Those who met the inclusion and exclusion criteria were included in the study. Data were analyzed using SPSS 16 software. Using descriptive statistics, the mean was computed for the quantitative variable (age). Frequencies and percentages were calculated for gender, site, tumor grade, and lymph node involvement for each neck level.Results: A total of 50 patients were included in the study. There were 38 males and 12 females. The mean age was 47 (range 25-72). The most common site of the tumor was buccal mucosa in 50% of the cases followed by tongue 20%, then floor of mouth 14%, dentoalveolar ridge 8%, retromolar area 4%, lip 2%, and hard palate 2%. Histopathological grading of tumors showed well-differentiated 28%, moderately differentiated 33%, and poorly differentiated 6%. Twenty-seven out of 50 patients were found positive for nodal metastasis on final postoperative histopathology. Neck node metastasis at level I was found in 22 patients, at level II in 16 patients, at level III in seven patients, and at level IV in two patients. The level V was found free of metastasis in all of the cases.Conclusion: The rate of occult metastatic disease to the neck nodes was similar to that found in the literature. Both early and advanced local disease is associated with a risk of occult metastasis. END for neck levels I-V is, therefore, recommended for the management of the N0 in all cases of oral SCCs. Spread to levels IV and V is rare and these levels should not be a part of routine END.

Survival among women diagnosed with screen-detected or interval breast cancer classified as true, minimal signs, or missed through an informed radiological review

Objectives“True” breast cancers, defined as not being visible on prior screening mammograms, are expected to be more aggressive than “missed” cancers, which are visible in retrospect. However, the evidence to support this hypothesis is limited. We compared the risk of death from any cause for women with true, minimal signs, and missed invasive screen-detected (SDC) and interval breast cancers (IC).MethodsThis nation-wide study included 1022 SDC and 788 IC diagnosed through BreastScreen Norway during 2005–2016. Cancers were classified as true, minimal signs, or missed by five breast radiologists in a consensus-based informed review of prior screening and diagnostic images. We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of death from any cause associated with true, minimal signs, and missed breast cancers, adjusting for age at diagnosis, histopathologic tumour diameter and grade, and subtype. Separate models were created for SDC and IC.ResultsAmong SDC, 463 (44%) were classified as true and 242 (23%) as missed; among IC, 325 (39%) were classified as true and 235 (32%) missed. Missed SDC were associated with a similar risk of death as true SDC (HR = 1.20, 95% CI (0.49, 2.46)). Similar results were observed for missed versus true IC (HR = 1.31, 95% CI (0.77, 2.23)).ConclusionsWe did not observe a statistical difference in the risk of death for women diagnosed with true or missed SDC or IC; however, the number of cases reviewed and follow-up time limited the precision of our estimates.Key Points• An informed radiological review classified screen-detected and interval cancers as true, minimal signs, or missed based on prior screening and diagnostic mammograms.• It has been hypothesised that true cancers, not visible on the prior screening examination, may be more aggressive than missed cancers.• We did not observe a statistical difference in the risk of death from any cause for women with missed versus true screen-detected or interval breast cancers.

Time to Local Recurrence as a Predictor of Survival in Patients With Soft Tissue Sarcoma of the Extremity and Abdominothoracic Wall.

ObjectiveThe purpose of this retrospective study was to identify the prognostic significance of time to local recurrence (TLR) with regard to overall survival (OS) and survival after local recurrence (SAR) in patients with soft tissue sarcoma (STS) of the extremity and abdominothoracic wall.MethodsWe identified 477 patients who underwent R0 resection for localized STS of the extremity and abdominothoracic wall, from January 1995 to December 2016, of whom 190 patients developed local recurrence as their first recurrent event. Based on TLR, patients were divided into two groups: early local recurrence (ELR, <12 months) and late local recurrence (LLR, ≥12 months). The Kaplan–Meier method and Cox regression analysis were used to estimate the OS and SAR, and to identify factors associated with patient outcomes.ResultsThe median follow-up time for the entire cohort was 118.4 months, and was 118.5 months for the 190 patients who developed local recurrence. Deep tumor location (HR 1.73, 95% CI 1.27–2.37, P = 0.001) and tumor grade ≥2 (G2 vs. G1: HR 1.75, 95% CI 1.21–2.53, G3 vs. G1: HR 2.57, 95% CI 1.66–3.98, P < 0.001) were associated with a higher rate of local recurrence. There were 99 patients in the ELR group and 91 in the LLR group, with a median TLR of 10.8 months for the entire cohort. Patients from the ELR group had a shorter OS and a lower 5-year OS rate than the LLR group. Univariate and multivariate analyses demonstrated TLR as an independent prognostic factor for SAR and OS, in addition to tumor grade. Also, surgical treatment and absence of metastasis after local recurrence were associated with longer SAR.ConclusionsIn patients with STS of the extremity and abdominothoracic wall, ELR after R0 resection indicated a worse prognosis than those with LLR, and TLR can be considered an independent prognostic factor for OS and SAR. Furthermore, local recurrence was significantly influenced by the depth and the histopathological grading of the primary tumor, and reoperation after local recurrence could improve survival, which means salvage surgery may still be the preferred treatment when there are surgical indications after recurrence.

Increased Expression of DNA Methyltransferase 1 and 3B Correlates with Tumor Grade in Laryngeal Squamous Cell Carcinoma

Background: DNA methyltransferase (DNMT) enzymes, encoded by DNMT1, DNMT3A andDNMT3B genes, play a major role in the development of cancers through aberrant promotermethylation. Due to little information about the biological and clinical significance of expressionchanges of these genes in Laryngeal Squamous Cell carcinoma (LSCC), the current study wasdesigned to evaluate the contribution of DNMTs expression as potential diagnostic biomarkersin progression of LSCC. Methods: DNMT1, DNMT3A and DNMT3B expressions in tumoral and normal tissues fromthirty-three LSCC patients were evaluated by relative comparative real-time PCR, prior toany therapeutic intervention. Relationship between genes expression and clinicopathologicalfeatures were also analyzed. Results: The mRNA expression levels of all three DNMTs (DNMT1, DNMT3A and DNMT3B)were significantly elevated in LSCC tumor specimens compared to that of non-tumor tissues(P&lt;0.0001, P=0.011 and P&lt;0.0001, respectively). The expression of DNMT1 and DNMT3Bwas strongly associated with histopathological tumor grade. Moreover, the mRNA expressionlevels of DNMT3A were significantly correlated with laryngopharyngeal reflux. No significantrelationships existed with other clinicopathological parameters. Conclusion: Data showed that the expression levels of DNMT1, DNMT3A and DNMT3Bmarkedly increased in LSCC tissues. DNMT1 and DNMT3B were mainly overexpressed in highgrade LSCC tumors, therefore, they may have a role in LSCC progression. It seems that thesegenes may serve as diagnostic biomarkers in development of LSCC.

Superior prognosis stratification for stage III colon cancer using log odds of positive lymph nodes (LODDS) compared to TNM stage classification: the Japanese study group for postoperative follow-up of colorectal cancer.

Objectives: The aim of this study is to examine whether prognosis stratification in staging of Stage III colon cancer using T factor and log odds of positive lymph nodes (LODDS) categories is superior to that of the TNM staging system.Materials and Methods: The subjects were 5,919 patients with Stage III colon cancer who underwent curative resection at 24 Japanese institutions. Univariate analysis of LODDS categories and clinicopathologic factors was conducted using a Cox proportional hazards regression model for cancer-specific survival (CSS). Independent prognostic factors for CSS were extracted in multivariate analysis using factors with significance in univariate analysis. Effect sizes of risk factors for CSS were compared using the LogWorth statistic. Combinations of T factor and LODDS categories were used to create L-stage subgroups A, B and C. Stratification of prognosis with L-stage and TNM was compared using the Akaike information criterion (AIC).Results: In multivariate analysis, LODDS was identified as an independent prognostic factor, together with age, maximum tumor diameter, histopathological grade, L, V, pT, and pN. The LogWorth of LODDS was 17.149, which was the second highest after pT (31.562), and that of pN was 7.434. The 5-year CSS was 96.5%, 88.5%, and 66.6% in TNM stages IIIA, IIIB, and IIIC, respectively, and 96.0%, 87.6%, and 59.3% in L-stage A, B, and C, respectively (p < 0.0001). AICs for TNM and L-stage were 14,795.5 and 14,707.8, respectively.Conclusions: Prognosis stratification of the stage classification for Stage III colon cancer was superior with L-stage compared to TNM stage classification.

Occult Lymph Node Metastasis in Early-Stage Glottic Cancer in the National Cancer Database.

Early-stage glottic cancer (cT1-T2 cN0) may be treated by primary surgery or radiation. Elective treatment of the neck in clinically N0 disease is usually not performed due to low rates of regional lymph node metastasis. This study examines the role of elective neck dissection (END) and rate of occult nodal metastasis in cT1-T2 cN0 glottic cancer treated with primary surgery. Retrospective cohort study. The National Cancer Database was used to identify patients treated for early-stage glottic cancer. Demographic variables, disease characteristics, and overall survival were compared between the subgroups of patients who did and did not receive END. Factors predictive of occult lymph node metastasis were also identified using a multivariate logistic regression model. Thirty-eight percent of the 991 patients in this cohort underwent END. Younger age, treatment at an academic facility, advanced T-stage, and higher tumor grade were associated with receiving END. Sixteen percent of the 372 patients undergoing END had occult nodal metastasis. Higher tumor histopathologic grade was associated with occult metastasis (P = .004). While undergoing END did not affect significantly survival, those with occult metastasis had poorer survival (P < .001). END should be considered in cT1-T2 N0 glottic cancers with poorly differentiated or undifferentiated tumor histopathology. While END itself may not improve overall survival, identification of occult nodal metastasis is an important finding for prognostication. Level 3 Laryngoscope, 131:E1139-E1146, 2021.

Is there a connection between immunohistochemical markers and grading of lung cancer with apparent diffusion coefficient (ADC) and standardised uptake values (SUV) of hybrid 18F-FDG-PET/MRI?

To correlate tumour grading and prognostic immunohistochemical markers of lung cancer with simultaneously acquired standardised uptake values (SUV) and apparent diffusion coefficient (ADC) derived from hybrid PET/MRI. In this retrospective study, 55 consecutive patients (mean age 62.5±9.2years) with therapy-naïve, histologically proven lung cancer were included. All patients underwent whole-body PET/MRI using 18F-flourdeoxyglucose (18F-FDG) as a radiotracer. Diffusion-weighted imaging of the chest (DWI, b-values: 0, 500, 1000s/mm2 ) was performed simultaneously with PET acquisition. Histopathological tumour grading was available in 43/55 patients. In 15/55 patients, immunohistochemical markers, that is, phospho-AKT Ser473 (pAKTS473), phosphorylated extracellular signal-regulated kinase (pERK), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (erbB2) were available. The average SUVmax, SUVmean, ADCmin and ADCmean in lung cancer primaries were 12.6±5.9, 7.7±4.6, 569.9±96.1s/mm2 and 825.8±93.2s/mm2 , respectively. We found a significant inverse correlation between the ADCmin and SUVmax (r=-0.58, P<0.001) as well as between the ADCmin and SUVmean (r=-0.44, P<0.001). Tumour grading showed a significant positive correlation with SUVmax and SUVmean (R=0.34 and R=0.31, both P<0.05) and a significant inverse correlation with ADCmin and ADCmean (r=-0.30 and r=-0.40, both P<0.05). In addition, erbB2 showed a significant inverse correlation with SUVmax and SUVmean (r=-0.50 and r=-0.49, both P<0.05). The other immunohistochemical markers did not show any significant correlation. 18F-FDG-PET/MRI showed weak to moderate correlations between SUV, ADC, tumour grading and erbB2-expression of lung cancer. Hence, 18F-FDG-PET/MRI may, to some extent, offer complementary information to the histopathology of lung cancer, for the evaluation of tumour aggressiveness and treatment response.

Outcomes assessment in intrahepatic cholangiocarcinoma using qualitative and quantitative imaging features

BackgroundTo assess the performance of imaging features, including radiomics texture features, in predicting histopathologic tumor grade, AJCC stage, and outcomes [time to recurrence (TTR) and overall survival (OS)] in patients with intrahepatic cholangiocarcinoma (ICC).MethodsSeventy-three patients (26 M/47F, mean age 63y) with pre-operative imaging (CT, n = 37; MRI, n = 21; CT and MRI, n = 15] within 6 months of resection were included in this retrospective study. Qualitative imaging traits were assessed by 2 observers. A 3rd observer measured tumor apparent diffusion coefficient (ADC), enhancement ratios (ERs), and Haralick texture features. Blood biomarkers and imaging features were compared with histopathology (tumor grade and AJCC stage) and outcomes (TTR and OS) using log-rank, generalized Wilcoxon, Cox proportional hazards regression, and Fisher exact tests.ResultsMedian TTR and OS were 53.9 and 79.7 months. ICC recurred in 64.4% (47/73) of patients and 46.6% (34/73) of patients died. There was fair accuracy for some qualitative imaging features in the prediction of worse tumor grade (maximal AUC of 0.68 for biliary obstruction on MRI, p = 0.032, observer 1) and higher AJCC stage (maximal AUC of 0.73 for biliary obstruction on CT, p = 0.002, observer 2; and AUC of 0.73 for vascular involvement on MRI, p = 0.01, observer 2). Cox proportional hazards regression analysis showed that CA 19–9 [hazard ratio (HR) 2.44/95% confidence interval (CI) 1.31–4.57/p = 0.005)] and tumor size on imaging (HR 1.13/95% CI 1.04–1.22/p = 0.003) were significant predictors of TTR, while CA 19–9 (HR 4.08/95% CI 1.75–9.56, p = 0.001) and presence of metastatic lymph nodes at histopathology (HR 2.86/95% CI 1.35–6.07/p = 0.006) were significant predictors of OS. On multivariable analysis, satellite lesions on CT (HR 2.79/95%CI 1.01–7.15/p = 0.032, observer 2), vascular involvement on MRI (HR 0.10/95% CI 0.01–0.85/p = 0.032, observer 1), and texture feature MRI variance (HR 0.55/95% CI 0.31–0.97, p = 0.040) predicted TTR once adjusted for the independent predictors CA 19–9 and tumor size on imaging. Several qualitative and quantitative features demonstrated associations with TTR, OS, and AJCC stage at univariable analysis (range: HR 0.35–19; p < 0.001–0.045), however none were predictive of OS at multivariable analysis when adjusted for CA 19–9 and metastatic lymph nodes (p > 0.088).ConclusionsThere was reasonable accuracy in predicting tumor grade and higher AJCC stage in ICC utilizing certain qualitative and quantitative imaging traits. Serum CA 19–9, tumor size, presence of metastatic lymph nodes, and qualitative imaging traits of satellite lesions and vascular involvement are predictors of patient outcomes, along with a promising predictive ability of certain quantitative texture features.

Diffusion-weighted MRI: impact of the size of the ROI in detecting metastases in subcentimeter lymph nodes in head and neck squamous cell carcinoma.

Our aim is to determine the impact of the size of ROI in detecting subcentimeter metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). Secondary aim is to determine the impact of the histopathologic grade of the primary cancer on the ADC value of the metastatic nodes. The prospective study included 51 patients with histopathologically proven HNSCC at the primary site. Primary site includes oral cavity, oropharynx, larynx, and hypopharynx. ADC values of the lymph nodes were measured on ADC maps by placing two ROIs in the lymph nodes (0.2 cm2 in the center of the node and the whole node). Lymph nodes were dissected by levels, marked by the surgeon, and sent to the pathologist. By applying a smaller ROI, ADC values have greater sensitivity, specificity, NPV, PPV, and AUC in detecting metastasis compared to the ADC value of the entire node (88.0%, 80.73%, 90.7%, 75.9%, 0.912% versus 80.0%, 77.98%, 85% ,71.4%, and 0.819%, respectively) p < 0.001. Statistically significant negative correlation was established between the tumor grade and the ADC of lymph node at ROI 0.2 cm2and ROI of the whole lymph node (rho = - 0.425; p = 0.002, and rho = - 0.298; p = 0.038, respectively). ROI size affects the ADC value of the nodes. The higher histopathological grade of the primary tumor is inversely correlated with the ADC value of the lymph nodes.