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Classic adenoid cystic carcinomas (C-AdCCs) of the breast are rare, relatively indolent forms of triple negative cancers, characterized by recurrent MYB or MYBL1 genetic alterations. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a rare variant of AdCC yet to be fully characterized. Here, we sought to determine the clinical behavior and repertoire of genetic alterations of SB-AdCCs. Clinicopathologic data were collected on a cohort of 104 breast AdCCs (75 C-AdCCs and 29 SB-AdCCs). MYB expression was assessed by immunohistochemistry and MYB-NFIB and MYBL1 gene rearrangements were investigated by fluorescent in-situ hybridization. AdCCs lacking MYB/MYBL1 rearrangements were subjected to RNA-sequencing. Targeted sequencing data were available for 9 cases. The invasive disease-free survival (IDFS) and overall survival (OS) were assessed in C-AdCC and SB-AdCC. SB-AdCCs have higher histologic grade, and more frequent nodal and distant metastases than C-AdCCs. MYB/MYBL1 rearrangements were significantly less frequent in SB-AdCC than C-AdCC (3/14, 21% vs 17/20, 85% P

Introduction A histologic grading system for invasive lung adenocarcinoma (ADC) has been proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee in June 2020. This study evaluated the prognostic value of the IASLC histologic grading system (the IASLC system) in a large Japanese cohort. Methods We performed comprehensive histologic subtyping using the semiquantitative estimation of five major patterns and complex glandular patterns in patients with a completely resected lung ADC and determined the histologic grade using the IASLC system. Concordance index and receiver-operating characteristic curves were used to evaluate the clinical utility of the IASLC system for recurrence and death; the comparison was performed with the architectural-pattern system (the Arch system) and the grading system on the basis of the two most predominant patterns (the Sica’s system). Results Of 1002 patients with invasive ADC, 235 had recurrent disease and 166 died of lung cancer. The concordance index and area under the curve of the IASLC system were 0.777 and 0.807 for recurrence and 0.767 and 0.776 for death, respectively. These were similar to those of the Arch system (0.763 and 0.796 for recurrence, 0.743 and 0.755 for death) and the Sica’s system (0.786 and 0.814 for recurrence, 0.762 and 0.773 for death). Conclusions We reported that the IASLC system for invasive lung ADC has prognostic significance by evaluating a large Japanese cohort. We believe that the IASLC grading system will provide physicians with better information for postsurgery treatment.

Background Recently, histologic grade was removed from salivary tumor nomenclature by the WHO to include disease of higher grade. One such entity, cribriform adenocarcinoma (CAC), is an aggressive group of polymorphous adenocarcinoma (PAC), with frequent nodal metastasis and locoregional recurrence. We aim to examine the biologic behavior of this disease as compared with the PAC general cohort inclusive of all subtypes. Methods A systematic review of the literature on polymorphous adenocarcinoma and cribriform adenocarcinoma was completed. A descriptive analysis was performed for the following predictor variables: nodal and distant metastasis, in addition to recurrence. The outcome variables, disease free recurrence, and disease specific survival, where plotted using Kaplan-Meier curves. Results PAC and CAC both show median age of diagnosis in the sixth decade of life and a female predominance. CAC occurs most frequently in the tongue and PAC in the palate. The 2 groups show a similar biologic behavior in regards to incidence of distant metastasis (4.1 vs 5.5%), recurrence (12.5 vs 17.8%), and death from disease (3 vs 2.7%). However, there was an increased incidence of nodal metastasis in CAC (53%) as compared with that in PAC of all subtypes (14%). Conclusions CAC exhibits more aggressive biologic behavior as compared with the PAC cohort. Although CAC is not an officially recognized entity, these tumors likely comprise a significant portion of the cases of PAC with poor outcomes and are deserving of attention and consideration for escalation in oncologic treatment.

Introduction Brain metastases (BM) are frequent among lung cancer patients, affecting prognosis and quality of life. The International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS) lung adenocarcinoma (LADC) classification (IASLC/ATS/ERS) has prognostic impact in early-stage disease; however, its role in the advanced setting is not precise. This study aims to determine the correlation between the predominant histological subtype and the risk of developing brain metastases (BM) in locally advanced and metastatic (stages IIIB-IV) LADC. Methods A total of 710 patients with LADC were treated at our institution from January 2010 to December 2017. After excluding patients with brain metastases at diagnoses (n = 151), they were categorized according to the IASLC/ATS/ERS LADC classification to estimate the risk of developing brain metastases. A competing risk analysis was employed, considering death a competing risk event. Results From 559 patients, the mean age was 59 ± 13.2 years, women (52.4 %), and clinical-stage IV (79.2 %). LADC subtypes distribution was lepidic (11.6 %), acinar (37.9 %), papillary (10.2 %), micropapillary (6.8 %), and solid (33.5 %). A total of 27.0 % of patients developed BM, 32.9 % died without brain affection, and 40.0 % did not progress. The predominantly solid subtype showed the greatest probability of all subtypes for developing BM [HR 4.0; 95 % CI (1.80−8.91), p = 0.0006], followed by micropapillary [HR1.11; 95 % CI (0.36−3.39), p = 0.85). The solid subtype, moderately differentiated tumors, age, and ECOG PS (>2) were associated with increased hazards in the multivariate analysis. CONCLUSION According to the IASLC/ATS/ERS classification, the predominantly solid pattern was significantly associated with an increased risk of developing BM in patients with locally advanced and metastatic LADC. Its prognostic value might help explore novel clinical approaches, modify monitoring for earlier detection, prevent complications, and reduce morbidity.

Histologic grade is a biomarker that is widely used to guide treatment of invasive breast cancer (IBC) and ductal carcinoma in situ of the breast (DCIS). Yet, currently, substantial grading variation between laboratories and pathologists exists in daily pathology practice. This study was conducted to evaluate whether an e-learning may be a feasible tool to decrease grading variation of (pre)malignant breast lesions. An e-learning module, representing the key-concepts of grading (pre)malignant breast lesions through gold standard digital images, was designed. Pathologists and residents could take part in either or both the separate modules on DCIS and IBC. Variation in grading of a digital set of lesions before and after the e-learning was compared in a fully-crossed study-design. Multiple outcome measures were assessed: inter-rater reliability (IRR) by Light’s kappa, the number of images graded unanimously, the number of images with both extreme scores (i.e., grade I and grade III), and the average number of discrepancies from expert-consensus. Participants were included as they completed both the pre- and post-e-learning set (DCIS-module: n = 36, IBC-module: n = 21). For DCIS, all outcome measures improved after e-learning, with the IRR improving from fair (kappa: 0.532) to good (kappa: 0.657). For IBC, all outcome measures for the subcategories tubular differentiation and mitosis improved, with >90% of participants agreeing on almost 90% of the images after the e-learning. In contrast, the IRR for the subcategory of nuclear pleomorphism remained fair (kappa: 0.523 vs. kappa: 0.571). This study shows that an e-learning module, in which pathologists and residents are trained in histologic grading of DCIS and IBC, is a feasible and promising tool to decrease grading variation of (pre)malignant breast lesions. This is highly relevant given the important role of histologic grading in clinical decision making of (pre)malignant breast lesions.

Background Despite the overall diagnostic utility of core needle biopsy (CNB) comparable to incisional biopsy, increased diagnostic errors have been suggested of CNB for myxoid soft tissue tumors. This study compared the diagnostic performance of CNB between myxoid and non-myxoid soft tissue tumors. Methods 369 patients who underwent ultrasound-guided CNB prior to resection for soft tissue tumors were classified into two groups according to resection pathology; myxoid group (n = 75) and non-myxoid group (n = 294). One-hundred and ninety-three patients were male and the median age of the patients was 40 years. Two-hundred and sixty-three tumors were malignant. Results CNB correctly diagnosed malignancy in 84% (58 of 69) for the myxoid group and 95% (184 of 194) for the non-myxoid group. For diagnosing histologic grade of soft tissue sarcoma, CNB correctly identified high grade in 78% (18 of 23) for the myxoid group and 74% (94 of 128) for the non-myxoid group. Correct diagnosis rate of histological type was significantly lower in the myxoid group (63% [47 of 75] in the myxoid group and 83% [242 of 294] in the non-myxoid group, p = 0.013). Conclusion Our study suggests that CNB is useful for myxoid soft tissue tumors of the extremity, with regard to diagnosing malignancy and histologic grade. However, CNB was less useful for identifying histologic subtype in myxoid tumors than in non-myxoid tumors.

Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiotherapy because of a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence that suggests that DCIS can be stratified according to risk of recurrence or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Recent technological advancements have enabled an era of precision medicine, where DCIS can be molecularly analyzed by tools, such as next-generation DNA and RNA sequencing, to identify molecular biomarkers for risk stratification. These findings have led to the development of tools such as the Oncotype DX Breast DCIS Score, a gene expression–based assay with the potential to prevent overtreatment in low-risk disease.

To investigate the factors that could cause a misdiagnosis in virtual touch tissue imaging and quantification (VTIQ) when differentiating benign and malignant breast lesions, and to analyze the imaging characteristics of those lesions with incorrect findings.The conventional ultrasound (CUS) features and the VTIQ parameters of 153 benign lesions and 99 malignant lesions were retrospectively analyzed and compared with histopathological and/or core-needle biopsy (CNB)-proven results. Independent variables that led to inaccurate VTIQ results were selected by binary logistic regression analysis.The maximum shear wave speed (SWS-max), the mean SWS (SWS-mean), the minimum SWS (SWS-min), the lesion-to-fat SWS ratio (SWS-L/F), and the lesion-to-gland SWS ratio (SWS-L/G) in malignant lesions were significantly higher than those in benign lesions (all P 0.001). The false-positive rate (FPR) of benign lesions and the false-negative rate (FNR) of malignant lesions were 9.8% and 19.2%, respectively, using an SWS-max cut-off value of 4.46 m/s. Diameter, depth, and posterior acoustic features were independent variables related to false-positive VTIQ findings (P: 0.049, 0.010 and 0.032, respectively). The invasive status and the histologic grade of infiltrating carcinoma were significantly associated with false-negative VTIQ findings (P: 0.026 and 0.015).Diameter, depth, posterior acoustic features, invasive status, and histologic grade have a significant influence on the accuracy of VTIQ results, and these characteristics of breast lesions should be taken into account when interpreting the results of VTIQ examinations.

Pathologic variables play an important role in prognostication in urologic malignancies. Histologic subtype, histologic grade, and anatomic extent of disease (pathologic tumor and nodal staging) influence treatment decisions in both the adjuvant and metastatic settings. This article discusses treatment paradigms for the most common urologic malignancies, followed by the evidence base to support the relationship between pathologic assessment and decision making by the medical oncologist.

Introduction The aim of this study is to identify factors associated to recurrence and survival in primary retroperitoneal liposarcomas. Methods Prospective database of 35 patients with primary retroperitoneal liposarcoma treated 2004–2015 were retrospectively analyzed. Exclusion criteria were recurrent and metastatic tumors. Overall survival (OS) and disease-free survival were reviewed. Patient data were compared between patients with or without recurrence within 12 months after surgery. Risk factors were determined using logistic regression analysis. Results Five-year OS was 61.1%. One and three-year disease-free survival were 68.6% and 17.1% respectively. OS in the early recurrence group was 36.4 months compared with 43.2 months in the group without early recurrence (P=.011). Early recurrence was associated with a reduction in OS (HR=4.05; CI95%: 1.27–12.96; P=.018). Multifocality and microscopic positive margins R1 were associated with early recurrence. Histologic subtype, margin of resection, histologic grade and multifocality were factors associated with recurrence. Contiguously involved organ resection had a beneficial effect on early recurrence and was associated with an increase in disease-free survival and OS. Adjuvant treatments had no protective effect on recurrence. Conclusions This study underlines the crucial role aggressive surgical approach in retroperitoneal Liposarcoma treatment, especially in those patients with histological characteristics that adversely the prognosis.

Background In this study, we developed and validated a nomogram to predict lymph node metastasis before surgery in patients with intrahepatic cholangiocarcinoma (ICC). Methods Using the data from January 2006 to January 2015, we enrolled a total of 218 eligible patients with clinicopathologically confirmed ICC as a primary cohort to develop the nomogram. After various variables before surgery were analyzed by multivariable logistic regression, we combined the preoperative carbohydrate antigen 19-9, primary site of tumor, lymphonodus size on computed tomography imaging, tumor growth pattern, and (if applicable) histologic grade to make two different predictive nomograms. Then, the results were validated in 62 consecutive ICC patients from February 2015 to December 2016. We also compared the performance of the different nomograms via calibration, discrimination, and clinical use. Results The nomogram displayed fine discrimination (the concordance index, 0.761) and fine calibration in the primary cohort. When applied to the validation cohort, the nomogram also showed fine discrimination (concordance index, 0.794) and fine calibration. After adding the histologic grade to the nomogram, the integrated discrimination for predictive performance improved significantly. Finally, the clinical usefulness of predictive nomogram was proven via the decision curve analysis. Conclusions The proposed nomograms can be selectively used to achieve more accurate lymph node metastasis predictions before surgery in patients with ICC, and this information can help with clinical management.

This consensus statement is a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM). It revises and updates the recommendations for the use of biomarkers in the diagnosis and treatment of breast cancer. The group of experts recommends that, in all cases of breast cancer, the histologic grade and the alpha-estrogen receptor (ER), progesterone receptor, Ki-67 and HER2 status should be determined, in order to assist prognosis and establish therapeutic options, including hormone therapy, chemotherapy and anti-HER2 therapy. One of the four available genetic prognostic platforms (MammaPrint ® , Oncotype DX ® , Prosigna ® or EndoPredict ® ) may be used in node-negative ER-positive patients to establish a prognostic category and decide, together with the patient, whether adjuvant treatment be limited to hormonal therapy. Newer technologies, including next generation sequencing, liquid biopsy, tumour infiltrating lymphocytes or PD-1 determination, are still investigational.

Objective This study aimed to investigate the incidence of ovarian malignant involvement in young and premenopausal endometrioid endometrial cancer and study the possible risk factors. Methods Premenopausal patients 45 years of age or younger with endometrioid endometrial cancer treated at the OB/GYN Hospital of Fudan University between 2009 and 2013 were identified. The incidence of ovarian malignant involvement in young and premenopausal endometrioid endometrial cancer patients were calculated and the possible risk factors were investigated. Results A total of 144 younger (age ≤ 45, premenopausal) patients with endometrioid endometrial cancer were identified and coexisting malignant ovarian neoplasms were detected in 6 patients. Univariate analysis revealed that deeper myometrial invasion, positive lymphonode metastasis, positive LVSI, and high histologic grade (G2-G3) were associated with ovarian involvement in younger endometrial cancer patients. However, multivariate analysis revealed that only deep myometrial invasion was an independent risk factors for ovarian involvement (OR = 12.81, P = 0.046). Conclusion In conclusions, the incidence of coexisting ovarian malignant neoplasms in young and premenopausal patients with endometrioid endometrial cancer is low, and these findings may facilitate preoperative counseling of patients and decision making at the time of surgery.

Bone-forming tumors are defined by neoplastic cells that differentiate along the lines of osteoblasts that deposit neoplastic bone. The morphology and biological spectrum of bone-forming tumors is broad, and their accurate diagnosis requires the careful correlation of their clinical, morphologic, and radiologic characteristics. Immunohistochemical and molecular analyses have an important role in select instances. At present, the identification of neoplastic bone largely depends on histologic analysis, which can be subjective. The major types of osteosarcoma are defined according to their morphology, origin within or on the surface of the bone, and their histologic grade.

The aim of this study was to access the prognostic value of 4 histopathologic grading systems of oral squamous cell carcinoma (OSCC): The World Health Organization (WHO), Anneroth, Bryne (1989), and Bryne (1992).Eighty-five cases of OSCC diagnosed between 1996 and 2010 at the Clinics Hospital of Porto Alegre (Porto Alegre, Brazil) were included. Slides stained with hematoxylin and eosin were obtained, and a histologic grade was assigned on the basis of the consensus of 3 expert oral pathologists, who were blinded to the clinicopathologic factors. Each system was correlated with proliferative labeling index, accessed through Ki67 immunostaining, clinicopathologic factors, patient outcome (alive or deceased), and survival time.The increase in Bryne (1992) histologic grades was accompanied by an increase in proliferative labeling index. Moreover, this system was the only one associated with patient outcome (P = .01) and survival. Bryne (1992) grading system grade III tumors were associated with poor disease-specific survival according to univariate and multivariate cox regression analyses and the log-rank test (P .05). The other systems evaluated presented no association with patients' outcome or survival.The Bryne (1992) grading system is more effective in predicting survival in OSCC compared with the systems proposed by the WHO, Anneroth, or Bryne (1989).

Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis.

Strong to moderate vascular endothelial growth factor (VEGF) expression may be a negative prognostic factor in canine mast cell tumors (MCTs). This study set out to determine the prognostic value of combined analysis of VEGF-A immunoreactivity, clinical presentation, patient staging, and tumor histologic grade in canine MCTs. In this study, intense VEGF staining was significantly associated with decreased survival (P = .025). Immunohistochemical expression of VEGF is not routinely employed as a prognostic factor in canine MCT workup. However, results of this study support the inclusion of this marker in the MCT prognostic panel. Investigation of VEGF expression may assist in the development of anti-VEGF drugs.

Soft tissue sarcomas comprise tumors originating from mesenchymal or connective tissue. Histologic grade is integral to prognosis. Because sarcoma management is multimodal, histologic subtype should inform optimum treatment. Appropriate biopsy and communication between surgeon and pathologist can help ensure a correct diagnosis. Treatment often involves surgical excision with wide margins and adjuvant radiotherapy. There is no consensus on what constitutes an adequate margin for histologic subtypes. An appreciation of how histology corresponds with tumor biology and surgical anatomic constraints is needed for management of this disease. Even with the surgical goal of wide resection being obtained, many patients do not outlive their disease.

To investigate whether Liver Imaging Reporting and Data System (LI-RADS) imaging features at preoperative gadoxetic acid-enhanced MRI can predict microvascular invasion (MVI) and histologic grade of hepatocellular carcinoma (HCC) and to evaluate their associations with recurrence after curative resection of single HCC.From July 2015 to September 2018, 111 consecutive patients with pathologically confirmed HCC who underwent gadoxetic acid-enhanced MRI within 1 month before surgery were included in this retrospective study. Significant MRI findings and clinical parameters for predicting MVI, high-grade HCCs and postoperative recurrence were identified by logistic regression model and Cox proportional hazards model.Twenty-six of 111 (23.4 %) patients had MVI and 36 of 111 (32.4 %) patients had high-grade HCCs, whereas 44 of 95 (46.3 %) patients experienced recurrence. Tumor size5 cm (OR = 9.852; p 0.001) and absence of nodule-in-nodule architecture (OR = 8.302; p = 0.001) were independent predictors of MVI. Enhancing capsule (OR = 4.396; p = 0.004) and corona enhancement (OR = 3.765; p = 0.021) were independent predictors of high-grade HCCs. Blood products in mass (HR = 2.275; p = 0.009), corona enhancement (HR = 4.332; p 0.001), and serum AFP level400 ng/mL (HR = 2.071; p = 0.023) were independent predictors of recurrence.LI-RADS imaging features can be used as potential biomarkers for predicting aggressive pathologic features and recurrence of HCC. The identification of prognostic LI-RADS imaging features may facilitate the selection of surgical candidates and optimize the management of HCC patients.

The purpose of this study was to clarify the diagnostic value of contrast-enhanced ultrasonography (CEUS) with perflubutane in determining the histologic grade in hepatocellular carcinoma (HCC). A total of 147 surgically resected HCCs were dichotomized as well differentiated HCC (wd-HCC) and moderately- or poorly-differentiated HCC (mp-HCC). CEUS findings were evaluated during the arterial phase (vascularity, level and shape of enhancement), portal phase (presence or absence of washout) and post-vascular phase (echo intensity and shape). Receiver operating characteristic (ROC) curve analysis for the diagnosis of mp-HCC yielded area under the ROC curve (Az) values for arterial phase vascularity and portal phase washout of 0.910 and 0.807, respectively. The Az value for the combination of vascularity and washout for the diagnosis of mp-HCC was 0.956 (95% confidence interval, 0.910-0.979), corresponding to high diagnostic value. In conclusion, CEUS can provide high-quality imaging assessment for determining the histologic grade of HCCs.

In 2014, more than 74,000 new cases and 15,000 deaths from bladder cancer were estimated to occur. The most reliable prognostic factors for survival are pathologic stage and histologic grade. Accordingly, a good understanding of the pathologic features of these cancers is essential to guide optimal clinical treatment, which requires a multidisciplinary team of pathologists, urologists, radiation oncologists, and medical oncologists. This review highlights several clinical scenarios in which detailed pathologic evaluation and accurate reporting impact clinical management.

The aim of this study was to evaluate the clinical and pathologic findings of patients with oral squamous cell carcinoma (OSCC) and compare them with the tumor-associated tissue eosinophilia (TATE) and serum eosinophilia (SE) quantifications. Clinical and anatomopathologic data were obtained from the medical records between 2006 and 2016. Tumors were classified according to histologic grade into 2 groups: well-differentiated carcinomas (group 1) and moderately/poorly differentiated (group 2). For analysis of TATE, the histologic slides were stained with Congo red, and stromal eosinophils were counted in 5 consecutive high-power fields using Image J 1.45 s. The SE count was performed by XE-2100 D Sysmex automated system after venous puncture. Of the 113 patients, 83 were from group 1 and 30 were from group 2. Most of the patients were white, smokers, alcoholics, and manual workers. Stage II of the disease predominated in both groups, and 8 patients died. There was no statistical difference between the groups in relation to TATE or SE (P = .16 and P = .19, respectively). However, there was a positive correlation between the TATE and SE (r = + 0.417, P = .048). TATE is directly associated with SE in OSCC patients, having no association with tumor aggressiveness, survival, or other clinical parameters.

Objective To study which variables involved in the process of selective sentinel node biopsy (SSNB) influence the intraoperative detection of the sentinel lymph node. Material and methods This was a prospective cross-sectional study in 210 patients (mean age, 54 years) diagnosed with breast cancer who underwent SSNB. We recorded clinical, radiological, radioisotope administration, surgical, and histological data as well as follow-up data. We did a descriptive analysis of the data and an associative analysis using multivariable regression. Results Deep injection alone was the most common route of radioisotope administration (72.7%). Most lesions were palpable (57.1%), presented as nodules (67.1%), measured less than 2 cm in diameter (64.8%), were located in the upper outer quadrant (49.1%), were ductal carcinomas (85.7%), were accompanied by infiltration (66.2%), and had a histologic grade of differentiation of II (44.8%). Preoperative scintigraphy detected the sentinel node in 97.6% of cases and 95.7% were detected during the operation. One axillary relapse was observed. In the associative study, the variables “preoperative lymphoscintigraphy” and “histologic grade of differentiation of the tumor” were significantly associated with the detection of the sentinel lymph node during the operation. Conclusion The probability of not detecting the sentinel lymph node during the surgical intervention is higher in patients with high histologic grade tumors or in patients in whom preoperative lymphoscintigraphy failed to detect the sentinel node.

The aim of this study is to assess in bronchial carcinoid tumors, the prognostic factors in relation to the histology that would determine their most appropriate therapy. The histologic aggressiveness is a determining factor in tumor size and nodal involvement in these tumors. The knowledge of the histologic limits of typical and atypical carcinoid contributes to the recognition of a better valuation of the proportional significance that nodal involvement and histologic grade have in a tumor's prognosis.

Breast masses with a radiologic stellate pattern often transform into malignancies, but their tendency to be of low histologic grade yields a better survival rate compared with tumors with other patterns on mammography screening. This study was designed to investigate the correlation of histologic grade with stellate features extracted from the coronal plane of 3-D ultrasound images. A pre-processing method was proposed to facilitate the extraction of stellate features. Extracted features were statistically measured to derive a set of indices that quantitatively represent the stellate pattern. These indices then went through a selection procedure to build proper decision trees. The splitting rules of decision trees indicated that stellate tumors are associated with low grade. A set of indices from the low grade-associated rules has the potential to represent the stellate feature. Further investigation of the hypoechoic region of peripheral tissue is essential to establishment of a complete discriminating model for tumor grades.

Nearly all prostate biopsies are performed via the transrectal ultrasound (TRUS)-guided technique which suffers from its inability to accurately visualize and target suspicious lesions. Advances in prostate MR imaging now allow for the detection of suspicious regions of the prostate gland, opening the door for lesion-directed biopsy techniques. The ability to obtain a definitive histologic grade has become increasingly important due to the rise of active surveillance as a popular method to approach low-grade cancer. Biopsies obtained with MR guidance or MR imaging/transrectal ultrasound fusion can accurately identify and characterize cancers and thus appropriately stratify patients for specific therapies.

The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis.Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement.The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p0.001).In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis.

T1 (≤5 cm) soft tissue sarcoma (STS) may represent a distinct subgroup with different biological characteristics resulting in favorable outcomes, when compared with T2 (5 cm) STS. However, only few studies focusing on T1 STS have been reported.A retrospective review was conducted on 373 patients (163 with T1 STS [T1 group] and 210 with T2 STS [T2 group]) who underwent surgical removal of STS. Clinicopathologic characteristics and prognostic factors for local recurrence and disease-specific survival (DSS) of T1 STS was investigated and compared with those of T2 STS.T1 group was younger (p = 0.004), had fewer metastases at initial presentation (p0.001), more previous unplanned excisions (p0.001), more synovial sarcomas (p = 0.024), fewer liposarcomas (p0.001), lower histological grade (p = 0.013), and fewer deep-seated tumors (p0.001) than T2 group. For local recurrence, older age (p = 0.008), previous unplanned excision (p = 0.012), and malignant peripheral nerve sheath tumor subtype (p = 0.014) independently predicted poor prognosis in the T2 group whereas only anatomical site of lower extremity (p = 0.046) was a favorable prognostic factor in the T1 group. For DSS, higher histologic grade (p = 0.037) and larger tumor size (p = 0.020) predicted poor prognosis in T2 group whereas only older age (p = 0.005) was prognostic in the T1 group.Clinicopathological characteristics and prognostic factors of T1 STS differed from those of T2 STS. Established prognostic factors for STS were of limited value for T1 STS. These findings suggest the necessity of a different assessment strategy for T1 STS.

TNM cancer staging, conceived 70 years ago, was first applied to the esophagus in 1977. Prior staging was neither data-driven nor harmonized with stomach cancer. Machine-learning analysis of worldwide data addressed these shortcomings in the 7th edition. The 8th edition considers 6 problems in attempting to advance esophageal cancer staging.

The digestive organs contain a large number of neuroendocrine cells as part of the diffuse neuroendocrine system. Neuroendocrine tumors can occur in every digestive organ. It has long been recognized that this is a diverse group of tumors with very different clinical outcomes; however, well-recognized prognostic parameters had been elusive until recently. Over the years, there have been several different classification schemes, each with different strengths and weaknesses. In an effort to standardize the classification and grading criteria for gastroenteropancreatic neuroendocrine tumors, the current World Health Organization classification includes a histologic grade based on proliferative rate (mitotic rate and Ki67 index) and a TNM stage that varies from organ to organ. The prognostic value of both the grade and stage has been validated in multiple studies. However, several issues remain, including the lack of standardized methods to assess proliferative rate, potential discrepancies between the mitotic count and the Ki67 index; intratumoral heterogeneity in proliferative rate; and the need for refinement in proliferative cut-points to define the grades. More studies are needed to further improve the classification of neuroendocrine tumors, thus guiding optimal treatment for these tumors.

Rationale and Objectives A histologic grade in head and neck squamous cell carcinoma (HNSCC) is clinically important because of its association with prognosis. The purpose of this study was to investigate the efficacy of histographic analysis of apparent diffusion coefficient (ADC) maps on the basis of the entire tumor volume in differentiating histologic grades in HNSCC at standard (b = 1000 s/mm 2 ) and high (b = 2000 s/mm 2 ) b values. Materials and Methods Fifty-four patients with HNSCC, including well-differentiated (WD; n = 35), moderately differentiated (MD; n = 13) and poorly differentiated (PD; n = 6) carcinomas, were retrospectively evaluated. ADC maps were obtained at two different b values (1000 and 2000 s/mm 2 ) in each patient. Tumors were delineated on each slice of ADC maps, and data were collected to obtain a histogram for the entire tumor volume. Histographic parameters were calculated, including mean, standard deviation, kurtosis, skewness, and the ratio of the kurtosis measured at b values of 1000 and 2000 s/mm 2 . These parameters were correlated with histologic grades. Results There was no significant correlation between tumor grades and histographic parameters obtained from ADC maps at b = 1000 s/mm 2 . However, mean ADC at b = 2000 s/mm 2 was significantly higher in WD HNSCC (881 ± 131 × 10 −6 mm 2 /s) than in MD and PD HNSCC (770 ± 163 and 780 ± 158 × 10 −6 mm 2 /s, respectively) ( P P Conclusions Histographic analysis of ADC maps on the basis of the entire tumor volume can be useful in differentiating histologic grades of HNSCC using mean ADC at b = 2000 s/mm 2 and kurtosis ratio.

Purpose To study the radiological appearance and pathological features of breast phyllodes tumors (PTs), and to enhance the recognition of the tumor. Materials and methods Clinical and imaging findings were retrospectively reviewed in 24 women with PTs confirmed by surgical pathology. All of the 24 patients had preoperative MRI and sonography, and 10 had preoperative mammography. Results The histologic findings were benign, borderline and malignant PTs in 16.7% (4/24), 45.8% (11/24) and 37.5% (9/24) of cases, respectively. The tumor size ( p = 0.001), irregular shape on sonographic imaging ( p = 0.039), internal non-enhanced septations ( p = 0.009), silt-like changes in enhanced images ( p = 0.006) and signal changes from T2-weighted to enhanced images on MRI ( p = 0.001) correlated significantly with the histologic grade; the BI-RADS category of the MRI could reflect the PT's histologic grade with a correlation coefficient of 0.440 ( p = 0.031). If the category BI-RADS ≥4a was considered to be a suspicious malignant lesion, the diagnostic accuracy of mammography, US and MRI would be 70% (7/10), 62.5% (15/24) and 95.8% (23/24), respectively. Conclusion The tumor size and several US and MRI findings can be used to help preoperatively determine the histologic grade of breast PTs. When a patient presents with a progressively enlarging, painless breast mass, MRI should be recommended first.

Calcifications in mucoepidermoid carcinoma (MEC) of the salivary glands are considered to be exceptionally rare and are often associated with high-grade tumors. This study reviewed 30 cases of MECs to access the frequency of calcifications and the clinical profile of the patients and histopathologic aspects of the tumors. In total, 6 cases of calcifications (20%) were identified. Five patients were women and 1 was a man, patients' ages ranged from 22 to 69 years old, and calcifications were found in conventional and clear cell-type MECs. Areas of calcification showed positivity for periodic acid-Schiff and mucicarmine, supporting the hypothesis that they originate from the precipitation of mucous secretion. The presence of calcifications in MECs was independent of the histologic grade of the tumors and the histopathologic variants. Calcifications in salivary MECs may not be as rare as previously mentioned in the literature and may be not associated with high-grade tumors.

Different multi-gene expression signatures have been shown to outperform classic histopathologic variables and therefore represent an important step towards personalizing breast cancer treatment. In particular, gene profiles overcome many of the limitations observed with classic histopathologic variables. The Genomic Grade Index (GGI) is a gene expression signature developed to better define histologic grade assessment. GGI divides classic histologic grade into low and high risk, instead of grades 1, 2 and 3. The ability of GGI to predict response to chemotherapy and separate hormone receptor positive breast cancer subtypes has also been demonstrated. This article critically reviews the limitations inherent in classic histologic grade evaluation; it also reviews the process of gene signature development in general and then focuses on GGI, its biologic significance, comparison with different gene signatures, and its applicability to clinical practise.

Radical resection can offer a definitive cure of primary malignant sternal tumors, but the surgical management may be difficult because of the local aggressiveness of these tumors and a high recurrence rate. This article describes improvements in reconstruction techniques with musculocutaneous flaps that have made coverage of wide sternal defects reliable. A rigid reinforcement of the sternum can now be achieved with titanium bars and clips after a total sternectomy. Large sternal defects are safely reconstructed with a musculocutaneous flap. The completeness of the resection and the histologic grade of the tumors are the strongest survival predictors.

Background Blood transfusion has been shown to impact rejection after renal and cardiac transplantation, but it has not been studied after lung transplantation (LTx). In this study we assess: (1) patterns of transfusion, and (2) temporal interrelationships with histologic evidence of rejection. Methods From July 1998 to January 2006, 326 of 331 patients undergoing LTx had available for study both time-related post-operative blood transfusion data and their series of transbronchial biopsy evaluations of perivascular rejection grade (Grades A0 to A4). Longitudinal temporal decomposition for ordinal variables was used to characterize prevalence of rejection grade and simultaneously assess the influence of (a) red blood cell (RBC), (b) platelet and (c) plasma administration. Results Although peri-operative transfusion was common, transfusions continued at a low, steady rate throughout the life of LTx patients; patients received a total of 2,841 RBC units through follow-up. Immediately after LTx, the prevalence of Grade A0 rejection was 51%, and this increased to 84% by 6 months. RBC transfusion between biopsies was associated with lower histologic grade of rejection (70%, 73% and 77% with Grade A0 for 0, 1 and 12 units, respectively; p = 0.009), and this was particularly evident early after LTx. Histologic grade was not influenced by platelets or plasma. Conclusions Transfusion requirements are high and continue throughout life after LTx; causes and effective treatment of persistent anemia should be sought. RBC transfusion appears to have an immunosuppressive effect, particularly early after transplant.

BackgroundThe purpose of this study was to identify risk factors for disease recurrence and unfavorable prognosis after surgical resection for stage I non-small cell lung cancer in patients with tumor diameters of ≤20 mm.MethodsOne hundred sixty-three patients who had pathologic stage I non-small cell lung cancer with tumor diameters ≤20 mm and who had undergone a lobectomy with mediastinal lymph node dissection were retrospectively reviewed. The relationships between clinicopathologic factors and clinical outcomes, including recurrence and survival, were then examined. The clinicopathologic factors examined in this study were age, sex, smoking status, preoperative serum carcinoembryonic antigen level, pathologic tumor size, histologic subtype, histologic grade, and visceral pleural invasion.ResultsAmong the clinicopathologic factors that were examined, the histologic grade of the carcinoma status was significantly related to a high risk of recurrence when analyzed using univariate (p = 0.01) and multivariate analyses (p = 0.049). Regarding survival, patients with poorly differentiated carcinomas showed a significantly unfavorable overall survival (p < 0.001), disease-specific survival (p = 0.003), and disease-free survival (p = 0.002) compared with patients with well-/moderately differentiated carcinomas according to univariate analyses. A Cox proportional hazards model indicated that a poorly differentiated carcinoma status was the only independent factor for an unfavorable overall survival (p = 0.02), disease-specific survival (p = 0.046), and disease-free survival (p = 0.04).ConclusionsPoor differentiation of tumor was the only risk factor for recurrence and an unfavorable prognosis for stage I non-small cell lung cancer patients with tumor diameters of ≤20 mm.

The purpose of the study was to analyse the generalisability and geographic transportability of survival estimates produced by commonly used prognostic factors. We compared the influence of tumour size, histologic grade, axillary nodal status, oestrogen and progesterone receptor contents, age at diagnosis and two prognostication schemes (the Nottingham Prognostic Index and St. Gallen criteria) in two nationwide cohorts of patients diagnosed with breast cancer in 1991–2, the FinProg (n = 2923, Finland) and the SEER series (n = 43,249, the United States (US)). Eight-year estimates of breast cancer-specific (84% versus 80%), relative (86% versus 83%), and overall (70% versus 69%) survival were slightly more favourable in the SEER than in the FinProg series, respectively. Despite differences in demographic variables and the frequency of use of adjuvant therapies and mammography screening between the series, the prognostic factors examined produced close to overlapping survival curves with similar shapes. The results suggest that quantitative survival estimates based on frequently used prognostic factors and prognostication schemes are generalisable and transportable between large, unselected cohorts of breast cancer patients.

Resumen Introduccion La reduccion en la acumulacion intracelular de los farmacos, es uno de los mecanismos mas frecuentes de resistencia a los antineoplasicos. Las proteinas transportadoras de membrana juegan un papel esencial en este fenomeno. Material y Metodos Se recogieron 147 muestras tumorales procedentes de 143 pacientes. De estas, 35 eran broncoscopicas y 112 quirurgicas. Resultaron validas para el estudio 101 muestras correspondientes a 99 pacientes. Las muestras tumorales criocongeladas fueron sometidas a analisis inmunohistoquimico para la deteccion de las tres MDR-proteinas, Pgp, Mrp1 y Lrp Resultados No expresaban ninguna proteina, 16 casos. Expresaban una sola proteina, 32 casos: 3 Pgp, 11 Mrp1 y 18 Lrp=0. Expresaban dos proteinas, 34 casos: 24 Pgp y Lrp, 5 Mrp1 y Pgp, 5 Mrp1 y Lrp=0. Expresaban las tres proteinas, 17 casos.No hemos detectado relacion significativa entre la edad y la expresion de Pgp (p=0.74), Mrp1 (p=0.95), o Lrp (p=0.26). No detectamos diferencias significativas entre sexos, tanto al analizar por el numero (p=0.72), como por el tipo (p=0.39) de proteinas expresadas de forma simultanea.Tampoco detectamos diferencias significativas entre los diferentes estadios tumorales, tanto para el numero (p=0.55), como para el tipo (p=0.21) de MDR-proteinas expresada. Tampoco detectamos diferencias significativas entre los diferentes grados histologicos, tanto para el numero (p=0.59), como para el tipo (p=0.51) de MDR-proteinas expresadas simultaneamente esadas simultaneamente. La tendencia de Pgp y Lrp a expresase asociadas ha resultado muy significativa (p Conclusiones El cancer de pulmon expresa con frecuencia MDR-proteinas.De las tres MDR-proteinas estudiadas, Pgp Mrp1 y Lrp, es Lrp la mas frecuentemente expresada. Los adenocarcinomas expresan menos Mrp1 que el resto de los tipos histologicos.Los carcinomas escamosos expresan menos Lrp que los adenocarcinomas y carcinomas indiferenciados de celula grande.Una proporcion importante de pacientes expresan de forma simultanea mas de una MDR-proteina.Los carcinomas escamosos, son los que con mas frecuencia expresan Pgp, Mrp1 y Lrp de forma simultanea. Pgp se expresa fundamentalmente asociada a Lrp. La expresion de Pgp y el numero de proteinas expresadas simultaneamente, puede afectar de forma negativa la respuesta a la quimioterapia.

The relationship between endometrial carcinoma and coexistent adenomyosis uteri, endometriosis externa and myoma uteri has been reported in only a few studies. We studied the characteristics of the endometrial carcinomas accompanied by these benign diseases. The total number of endometrial carcinoma cases was 179, consisting of 29 (16%) endometrial carcinomas with adenomyosis uteri, 12 (7%) with endometriosis externa, 51 (28%) with myoma uteri, and 87 controls (49%) without these benign diseases. Seventy-nine, 75, and 65% of the endometrial carcinomas with adenomyosis uteri, endometriosis externa and myoma uteri, respectively, showed a low histologic grade (G1). In particular, the patients with adenomyosis uteri and endometriosis externa were relatively younger than the control patients (54.2, 54.1 years old versus 57.7 years old). Furthermore, these patients were all treated at stage 1 and had a good prognosis. In brief, there are some clinicopathologic differences between the endometrial carcinoma cases with benign hormone-dependent disease and the cases without these disease.

The appropriate diagnosis and treatment of patients with cancer are most correctly made through the cooperative efforts of a team of specialists, including an oncologist, surgeon, and pathologist. Preoperative determination of the tumor type and histologic grade, extent of the mass, and the patient's health status will result in the most comprehensive course of action. Diagnosis and staging of the tumor are paramount to preparing an optimal treatment plan. To ensure the best possible outcome, the preoperative, surgical, and postoperative plan should be customized to the individual cancer patient and their owner while following given guidelines. This article describes the basic principals for evaluation and operative management of the surgical oncology patient.

Although there are trends in the morphologic, metabolic, hemodynamic, and structural properties of untreated gliomas that are reflected in MR measurements, there is considerable heterogeneity both within and between lesions of the same histologic grade. The spatial extent of the abnormality in ADC and RA images is similar to the T2 lesion, but there is no obvious difference in intensity between grades. The rCBV is significantly increased in the enhancing volume of grade 4 lesions but is similar or reduced in intensity for most grade 3 lesions. There are clear differences between the enhancing volumes and the regions with increased Cho that may be highly significant for planning focal therapy. The location and intensity of the Lac/Lip peaks are consistent with those representing regions of necrosis for grade 4 lesions. The fact that small Lac/Lip peaks can also be seen in grade 2 and grade 3 lesions suggests that their presence may be indicative of regions that are likely to progress to a higher grade. If this were the case, it would be valuable for directing biopsies. The correlations between rCBV, Cho, and ADC suggest that cellularity, membrane turnover, and vascularity are linked in grade 4 lesions. It is not clear whether there is any relationship between these parameters regions in grade 2 or grade 3 gliomas. While further work is required to optimize the methodology associated with these MR parameters, it seems likely that combining the information from such measurements may be valuable for predicting outcome and tailoring therapy to individual patients.

Purpose : Endometrial carcinoma is the most common malignancy of the female genital tract. Recognized prognostic factors include FIGO stage, histologic grade, depth of myometrial invasion, and age. Although determination of these factors may seem clear and reproducible, the histologic grade has recently been the subject of debate. A retrospective analysis of long-term outcome and predictive factors in endometrial carcinoma was conducted, focusing on the prognostic value of tumor grade. Methods and Materials : The study included 253 patients with endometrial carcinoma Stages I to III, who were treated between 1984 and 1993. The histologic slides were reviewed and the prognostic value of stage, age, myometrial invasion (depth and pattern), tumor grade, and histologic subtype was analyzed. The end point was cancer-specific death; the median follow-up time was 11.7 years. Results : The actuarial 5- and 10-year cancer-specific survival rates (CSS) were 85% and 82%, respectively. Five-year vaginal and/or pelvic recurrence and distant relapse rates were 7% and 15%. In multivariate analysis, stage, pattern of myometrial invasion, tumor grade, and age were independent prognostic factors. At pathology review, a shift from Grade 2 to Grade 1 was seen in 112 of the original 144 Grade 2 (78%). There was no difference in CSS between Grade 1 and Grade 2 (94 vs. 90% for original grade and 92 vs. 95% for grade after review), whereas Grade 3 was found to be a significant adverse prognostic factor (p Conclusions : The independent prognostic factors for patients with endometrial cancer were stage, pattern of myometrial invasion, tumor grade, and age. Systematic grading led to a considerable shift from Grade 2 to Grade 1. However, there was no difference in prognostic significance between Grade 1 and 2, whereas Grade 3 was a major adverse prognostic factor. A two-tiered grading system, instead of the currently used three-tiered system seems preferable, because it has a better correlation with clinical outcome and is expected to have less interobserver variability.