Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6 years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

Local relapse patterns after preoperative radiotherapy of limb and trunk wall soft tissue sarcomas: Prognostic role of imaging and pathologic response factors.

Purpose: To retrospectively identify clinical, pathologic, or imaging factors predictive of local relapse (LR) after preoperative radiotherapy (RT) for soft tissue sarcomas (STS). Methods and Materials: This is a retrospective multicenter study of patients who underwent preoperative RT and surgery for limb or trunk wall STS between 2007 and 2018 in French Sarcoma Group centers and were enrolled in the "Conticabase". Patterns of LR were investigated taking into account the multimodal response after preoperative RT. Diagnostic and surgical samples were compared after systematic review by expert pathologists and patients were stratified by tumor grade. Log-rank tests and Cox models were used to identify prognostic factors for radiation response and LR. Results: 257 patients were included; 17 % had low-grade (LG), 72.5 % had high-grade (HG) sarcomas. In HG group, tumors were larger, mostly undifferentiated, and displayed more necrosis and perilesional edema after RT. Median follow-up was 32 months. Five-year cumulative incidence of LR was 20.3 % in the HG group versus 9.7 % in the LG group (p = 0.026). In multivariate analysis, trunk wall location (HR 6.79, p = 0.012) and proportion of viable tumor cellularity ≥ 20 % (HR 3.15, p = 0.018) were associated with LR. After adjusting for tumor location, combination of histotype and cellularity rate significantly correlated with LR. We described three prognostic subgroups for HG sarcomas, listed from the highest to lowest risk: undifferentiated sarcoma (US) with cellularity rates ≥ 20 %; non-US (NUS) with cellularity rates ≥ 20 % or US with cellularity rates < 20 %; and NUS with cellularity rates < 20 %, which shared similar prognostic risks with LG sarcomas. Conclusions: HG and LG tumors have different morphological and biological behaviors in response to RT. Combination of cellularity rate with histotype could be a major prognostic for LR. Patients with undifferentiated HG sarcomas with cellularity rates ≥ 20 % after preoperative RT had the highest risk of LR and disease-specific death.

Efficacy of avelumab maintenance therapy for advanced urothelial carcinoma with histologic subtype and divergent differentiation: a multicenter retrospective study conducted by the Uro-Oncology Group in Kyushu.

Background: The subtype of urothelial carcinoma (SUC) has been known to possess morphological diversity for histologic subtype or divergent differentiation. However, the efficacy of avelumab against SUC remains unclear. Therefore, the effect of the treatment as well as the survival results of avelumab monotherapy were evaluated as a first-line therapeutic maintenance in patients with advanced SUC. Methods: A retrospective analysis was conducted on consecutive patients from the Uro-Oncology Group in Kyushu study population with advanced lower and upper urinary tract cancer who underwent avelumab maintenance therapy without progression after first-line platinum-based chemotherapy. Patients with pure urothelial carcinoma (PUC) and SUC were comparatively analyzed based on objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS). Results: Out of 49 recorded patients, 38 and 11 had PUC and SUC, respectively. The most common subtype element was glandular differentiation (n=5), followed by squamous differentiation (n=3), micropapillary (n=1), and plasmacytoid subtypes (n=1). The SUC and PUC groups had comparable ORR (0% vs. 2.6%, P>0.99) and disease control rates (54.5% vs. 44.7%, P=0.73). These patient groups also showed no significant difference in PFS (median 3.9 vs. 3.1 months, P=0.33) or OS (median 16.7 vs. 22.1 months, P=0.47). Conclusions: The response of SUC and PUC to avelumab was comparable in patients with advanced lower and upper urinary tract cancer, indicating that avelumab maintenance therapy is also effective for SUC.

Five-Year Relative Survival Rates of Women Diagnosed with Uterine Cancer by County-Level Socioeconomic Status Overall and across Histology and Race/Ethnicity.

Understanding socioeconomic factors contributing to uterine cancer survival disparities is crucial, especially given the increasing incidence of uterine cancer, which disproportionately impacts racial/ethnic groups. We investigated the impact of county-level socioeconomic factors on five-year survival rates of uterine cancer overall and by histology across race/ethnicity. We included 333,013 women aged ≥ 30 years with microscopically confirmed uterine cancers (2000-2018) from the Surveillance, Epidemiology, and End Results 22 database followed through 2019. Age-standardized five-year relative survival rates were compared within race/ethnicity and histology, examining the differences across tertiles of county-level percent (%)

Contemporary review of papillary renal cell carcinoma-current state and future directions.

Historically, papillary renal cell carcinoma (PRCC) was divided into two types, type 1 and type 2, based solely on morphology. However, it is apparent that PRCC is far more complex and represents a histological, clinical, and molecular spectrum. There has been a significant evolution in our understanding of PRCC, highlighted by the recognition of new and molecularly defined entities that were previously included in PRCC type 2. This contemporary review addresses the evolving concepts regarding the PRCC, including why it is no longer needed to subtype PRCC, the current molecular landscape, prognostic parameters, and PRCC variants, including biphasic PRCC, papillary renal neoplasm with reverse polarity, and Warthin-like PRCC. Pathologists should also be aware of the potential mimickers of both low-grade and high-grade PRCCs as well as some new and emerging entities that may show papillary growth that should be excluded in the diagnostic workup. The evolving knowledge of PRCC biomarkers, morphologic patterns, and PRCC variants could also have important implications for clinical management. Lastly, the heterogeneity within the PRCC spectrum needs to be further studied, aiming to better stratify PRCC for appropriate clinical management and systemic therapy.

Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study.

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC.

Significance of histologic subtype size as a prognostic indicator in stage IA lung adenocarcinoma.

Background: Predicting prognosis is complex due to a unique characteristic in stage IA lung adenocarcinoma. The feature indicated heterogeneous histologic subtype and ground glass opacity (GGO). Many studies demonstrated different prognoses according to histologic subtype or non-GGO lesion. This study aimed to evaluate the clinical outcomes following each histologic subtype size in stage IA lung adenocarcinoma and identify the prognostic impact of each histologic subtype size. Methods: The medical records of 550 patients with pathological stage IA lung adenocarcinoma were reviewed. Histologic subtype size was estimated by multiplying the tumor's maximum diameter by the proportion of each histologic subtype. Univariate and multivariate analyses were conducted to identify the prognostic role of each histologic subtype size in stage IA lung adenocarcinoma. Results: The median age and tumor size were 63 [25-82] years and 1.8 [0.3-3] cm, respectively. Acinar (42.0%) and lepidic (44.4%) were the most common among the predominant subtype. Each subtype size was estimated and re-categorized following the current staging system. The disease-free interval (DFI) was significantly different following each histologic subtype size. Multivariate analysis for DFI revealed more acinar, micropapillary, and solid subtypes and fewer lepidic subtypes with worse prognoses. Conclusions: The prognosis for DFI is determined through a complex process by various variables in stage IA lung adenocarcinoma. Each subtype size has a more prognostic impact than the predominant subtype.

Tailoring pretext tasks to improve self-supervised learning in histopathologic subtype classification of lung adenocarcinomas.

Lung adenocarcinoma (LUAD) is a morphologically heterogeneous disease with five predominant histologic subtypes. Fully supervised convolutional neural networks can improve the accuracy and reduce the subjectivity of LUAD histologic subtyping using hematoxylin and eosin (H&E)-stained whole slide images (WSIs). However, developing supervised models with good prediction accuracy usually requires extensive manual data annotation, which is time-consuming and labor-intensive. This work proposes three self-supervised learning (SSL) pretext tasks to reduce labeling effort. These tasks not only leverage the multi-resolution nature of the H&E WSIs but also explicitly consider the relevance to the downstream task of classifying the LUAD histologic subtypes. Two tasks involve predicting the spatial relationship between tiles cropped from lower and higher magnification WSIs. We hypothesize that these tasks induce the model to learn to distinguish different tissue structures presented in the images, thus benefiting the downstream classification. The third task involves predicting the eosin stain from the hematoxylin stain, inducing the model to learn cytoplasmic features relevant to LUAD subtypes. The effectiveness of the three proposed SSL tasks and their ensemble was demonstrated by comparison with other state-of-the-art pretraining and SSL methods using three publicly available datasets. Our work can be extended to any other cancer type where tissue architectural information is important. The model could be used to expedite and complement the process of routine pathology diagnosis tasks. The code is available at https://github.com/rina-ding/ssl_luad_classification.

Clinical implication of the 2020 International Association for the Study of Lung Cancer histologic grading in surgically resected pathologic stage 1 lung adenocarcinomas: Prognostic value and association with computed tomography characteristics.

OBJECTIVES: To investigate the incremental prognostic value of the 2020 International Association for the Study of Lung Cancer (IASLC) histologic grading system over traditional prognosticators in surgically resected pathologic stage 1 lung adenocarcinomas and to identify the clinical and radiologic characteristics of lung adenocarcinomas reclassified by the 2020 histologic grading system. MATERIALS AND METHODS: We retrospectively enrolled 356 patients who underwent surgery for pathologic stage 1 adenocarcinoma between January 2016 and December 2017. The histologic grading was classified according to the predominant histologic subtype (conventional system) and the updated 2020 IASLC grading system. The clinical and computed tomography (CT) characteristics were compared according to the reclassification of the updated system. The performance of prognostic models for recurrence-free survival based on the combination of pathologic tumor size, histologic grade, and CT-based information was compared using the c-index. RESULTS: Postoperative recurrence occurred in 6.7% of patients during the follow-up period (mean, 1589.2 ± 406.7 days). Fifty-nine of 244 (24.2%) tumors with intermediate grades in the conventional system were reclassified as grade 3 with the updated grading system. They showed significantly larger solid proportions and higher percentages of pure solid nodules on CT compared to tumors without reclassification (n = 185) (P < 0.05). Prognostic prediction models based on pathology tumor size and histologic grades had significantly higher c-indices (0.754-0.803) compared to the model based on pathologic tumor size only (c-index:0.723, P < 0.05). CONCLUSION: The 2020 IASLC histologic grading system has significant incremental prognostic value over the pathologic stage in surgically resected pathologic stage 1 lung adenocarcinoma. Reclassified lung adenocarcinomas using the updated grading system have a larger solid proportion and a higher percentage of pure solid nodules on CT.

p53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma.

The present study aimed to determine the expression levels of p53 in patients with hepatocellular carcinoma (HCC) and to evaluate its association with several HCC-related prognostic factors and in particular, with tumor stage, grade and subtype. Therefore, a cross-sectional study, involving 41 patients with HCC, who underwent surgical resection between January, 2013 and December, 2020 was conducted. To assess the expression levels of p53 in all patients with HCC, immunohistochemical staining was performed. In addition, the association between p53 expression and the clinicopathological characteristics of patients with HCC, including prognostic factors, was evaluated by applying the appropriate statistical analysis methods. The results revealed that among the 41 patients enrolled, 35 patients (85.4%) were positive for p53 expression. A higher percentage of positive p53 expression was observed in male patients >60 years old, with single HCC nodules >5 cm in diameter and vascular invasion, compared with their counterparts. A positive p53 expression was associated with well- and poorly differentiated HCC, but not with tumor stage and subtype. No differences in p53 expression were observed across different tumor stages and subtypes. Additionally, patients with moderately and poorly differentiated HCC exhibited significantly higher p53 expression levels compared with those suffering from well-differentiated HCC. Overall, the results demonstrated that the rate of p53 immuno-positive cells was increased in patients with HCC. In addition, p53 expression was associated with well- and poorly differentiated HCC, thus suggesting its association with a poorer prognosis.

Metaplastic Breast Carcinoma Revisited; Subtypes Determine Outcomes: Comprehensive Pathologic, Clinical, and Molecular Review.

Metaplastic breast carcinoma (MpBC) is a heterogeneous group of tumors that clinically could be divided into low risk and high risk. It is important to recognize the different types of MpBC, as the high-risk subtypes have worse clinical outcomes than triple-negative breast cancer. It is important for the pathologist to be aware of the MpBC entities and use the proposed algorithms (morphology and immunohistochemistry) to assist in rendering the final diagnosis. Few pitfalls are discussed, including misinterpretation of immunohistochemistry and certain histomorphologies, particularly spindle lesions associated with complex sclerosing lesions.

Clinicopathologic Features and Genetic Alterations in Mixed-Type Ampullary Carcinoma.

Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations between mixed type and other subtypes, as well as the genetic differences between I-type and PB-type lesions in the mixed type, remain unclear. In this study, we compared the clinicopathologic features and prognosis of 110 ampullary carcinomas classified by hematoxylin and eosin and immunohistochemical staining as follows: 63 PB-type, 35 I-type, and 12 mixed-type carcinomas. A comparative analysis of genetic mutations by targeted sequencing of 24 genes was also performed in 3 I-type cases, 9 PB-type cases, and I and PB-type lesions of 6 mixed-type cases. The mixed subtype had a poorer prognosis than the other subtypes, and there was also a similar tendency in the adjuvant group (n = 22). A total of 49 genetic mutations were detected in all 18 lesions for which genetic alteration was analyzed. No genetic mutations specific to the mixed type were found, and it was not possible to determine genetically whether the mixed type had originally been I or PB type. However, 5 of 6 cases had mutations common to both I and PB-type lesions, and additional mutations were found only in either I or PB-type lesions. In support of this, the mixed type more frequently exhibited genetic heterogeneity intratumorally than the other subtypes. Mixed-type tumors are histologically, immunohistochemically, and genetically heterogeneous, and this heterogeneity is associated with poor prognosis and may affect treatment resistance.

Breast Cancer Pathology in the Era of Genomics.

The era of genomic medicine provides an opportunity for pathologists to offer greater detail about the molecular underpinnings of a patient's cancer and thereby more targeted therapeutic options. In this review article, the role of genomics in breast cancer pathology is discussed, as it pertains to risk management, classification of special tumor types, predictive and prognostic testing, identification of actionable therapeutic targets, and monitoring for disease progression or development of treatment resistance.

Validation Study of New IASLC Histology Grading System in Stage I Non-Mucinous Adenocarcinoma Comparing With Minimally Invasive Adenocarcinoma.

BACKGROUND: A new histologic grading system for pulmonary non-mucinous invasive adenocarcinoma was proposed by the International Association for the Study of Lung Cancer (IASLC). We evaluated its clinical impact on prognosis in stage I patients, including minimally invasive adenocarcinoma (MIA). PATIENTS AND METHODS: 919 patients underwent surgery for lung adenocarcinoma between 2012 and 2019. Stage I patients (n = 500) were retrospectively reviewed. They were divided into 4 categories: MIA and 3 new IASLC grades (grades 1-3). Cox proportional hazards analysis was performed to identify risk factors associated with recurrence and mortality. Furthermore, we compared the predictability of the IASLC grading system with different models that are based on the clinicopathologic characteristics (baseline model), TNM staging, and predominant histologic pattern. The area under the receiver operating characteristic curve (AUC) was calculated for comparison. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) were significantly stratified by the IASLC grading system in patients with stage I adenocarcinoma (P < .001 and P = .003, respectively). In multivariate analyses, IASLC grade 3 was a significant factor for RFS (hazard ratio [HR] 3.18, P < .001) and OS (HR 2.31, P = .013). The AUCs of the new IASLC model were 0.781 for recurrence and 0.770 for mortality, compared with those of the predominant pattern (0.769 for recurrence, 0.747 for death) and TNM staging (0.762 for recurrence, 0.747 for death). CONCLUSION: The IASLC grading system effectively predicted the prognosis of early-stage adenocarcinoma compared with previous models. The IASLC classification appears to improve the current system; therefore, precise pathologic examination for early-stage adenocarcinoma is warranted.

Bone metastases in newly diagnosed patients with thyroid cancer: A large population-based cohort study.

Background: Population-based estimates of the incidence and prognosis of bone metastases (BM) stratified by histologic subtype at diagnosis of thyroid cancer are limited. Methods: Using multivariable logistic and Cox regression analyses, we identified risk factors for BM and investigated the prognostic survival of BM patients between 2010 and 2015 via the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among 64,083 eligible patients, a total of 347 patients with BM at the time of diagnosis were identified, representing 0.5% of the entire cohort but 32.4% of the subset with metastases. BM incidence was highest (11.6%) in anaplastic thyroid cancer (ATC), which, nevertheless, was highest (61.5%) in follicular thyroid cancer (FTC) among the subset with metastases. The median overall survival among BM patients was 40.0 months, and 1-, 3-, and 5-year survival rates were 65.2%, 51.3%, and 38.7%, respectively. Compared with papillary thyroid cancer (PTC), FTC (aOR, 6.33; 95% CI, 4.72-8.48), medullary thyroid cancer (MTC) (aOR, 6.04, 95% CI, 4.09-8.92), and ATC (aOR, 6.21; 95% CI, 4.20-9.18) significantly increased the risk of developing BM. However, only ATC (aHR, 6.07; 95% CI, 3.83-9.60) was independently associated with worse survival in multivariable analysis. Additionally, patients with BM alone (56.5%) displayed the longest median survival (66.0 months), compared with those complicated with one extraskeletal metastatic site (lung, brain, or liver) (35.2%; 14.0 months) and two or three sites (8.3%; 6.0 months). The former 5-year overall survival rate was 52.6%, which, however, drastically declined to 23.0% in patients with one extraskeletal metastatic site and 9.1% with two or three sites. Conclusion: Closer bone surveillance should be required for patients with FTC, MTC, and ATC, and extraskeletal metastases at initial diagnosis frequently predict a poorer prognosis.

Trends in the Incidence and Survival Rates of Primary Ovarian Clear Cell Carcinoma Compared to Ovarian Serous Carcinoma in Korea.

Objective: To compare the incidence and survival rates of primary ovarian clear cell carcinoma (OCCC) and ovarian serous carcinoma (OSC) from a nationwide collected database. Methods: We extracted information of patients with primary OCCC and OSC from the Korea Central Cancer Registry recorded between 1999 and 2018, including age at diagnosis and the Surveillance, Epidemiology, and End Results summary stage. Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Baseline characteristics and overall survival (OS) were compared between the OCCC and OSC groups. Results: Overall, the incidence rate of primary OCCC increased markedly from 1999 (ASR, 0.16/100,000) to 2018 (0.76/100,000) (APC, 7.85%; P<0.0001). Patients with OCCC were significantly younger and had early-stage disease more frequently than those with OSC. Patients diagnosed with OCCC before the age of 50 showed better OS than those diagnosed after the age of 50 (P=0.0048). The 5-year OS of the OCCC group did not differ by study period [73.5% (1999-2008) vs. 75.4% (2009-2018), P=0.3187], whereas the 5-year OS of the OSC group improved from 54.4% to 58% (P=0.0003). Conclusions: Our nationwide registry-based study demonstrated that the incidence of OCCC in Korea increased significantly from 1999 to 2018. Early-stage OCCC had a relatively good prognosis, but advanced-stage OCCC had a worse OS than advanced-stage OSC. Therefore, the development of optimal treatment strategies for OCCC is warranted.

Does histologic subtype impact overall survival in observed T1a kidney cancers compared with competing risks? Implications for biopsy as a risk stratification tool.

OBJECTIVES: We sought to assess if adding a biopsy proven histologic subtype to a model that predicts overall survival that includes variables representing competing risks in observed, biopsy proven, T1a renal cell carcinomas, enhances the model's performance. METHODS: The National Cancer Database was assessed (years 2004-2015) for patients with observed T1a renal cell carcinoma who had undergone renal mass biopsy. Kaplan-Meier curves were utilized to estimate overall survival stratified by histologic subtype. We utilized C-index from a Cox proportional hazards model to evaluate the impact of adding histologic subtypes to a model to predict overall survival for each stage. RESULTS: Of 132 958 T1a renal masses identified, 1614 had biopsy proven histology and were managed non-operatively. Of those, 61% were clear cell, 33% papillary, and 6% chromophobe. Adjusted Kaplan-Meier curves demonstrated a difference in overall survival between histologic subtypes (P = 0.010) with greater median overall survival for patients with chromophobe (85.1 months, hazard rate 0.45, P = 0.005) compared to clear cell (64.8 months, reference group). Adding histology to a model with competing risks alone did not substantially improve model performance (C-index 0.65 vs 0.64 respectively). CONCLUSIONS: Incorporation of histologic subtype into a risk stratification model to determine prognostic overall survival did not improve modeling of overall survival compared with variables representing competing risks in patients with T1a renal cell carcinoma managed with observation. These results suggest that performing renal mass biopsy in order to obtain tumor histology may have limited utility. Future studies should further investigate the overall utility of renal mass biopsy for observed T1a kidney cancers.

Correlation of basal cell carcinoma subtype with histologically confirmed subclinical extension during Mohs micrographic surgery: A prospective multicenter study.

BACKGROUND: Traditionally "aggressive" histologic subtypes (HSs) of basal cell carcinoma (BCC) are more likely to quantitatively exhibit subclinical extension (SCE), requiring more stages during Mohs micrographic surgery (MMS) and, therefore, larger margins upon excision. However, the tendency for SCE has never been compared between HSs of BCC in a prospective manner. OBJECTIVE: To prospectively correlate the HS of BCC with the likelihood of SCE as defined by the number of MMS stages required to clear the tumor. METHODS: In a prospective, multicenter study involving 17 Mohs surgeons in 16 different practices across the United States, data regarding 1686 cases of BCC undergoing MMS were collected. Patient demographics, tumor characteristics, number of MMS stages required for tumor clearance, and specific BCC subtypes noted on both index biopsy and the final MMS stage were recorded. RESULTS: Analysis of the average number of MMS stages for each HS required to clear tumor revealed 2 distinct degrees of SCE (P < .0001): high (higher than average) risk of SCE (1.9 stages, 1.0 SD) and low (lower than average) risk of SCE (1.6 stages, 0.9 SD). Subtypes of BCC within the high category were morpheaform (2.1), infiltrative (1.9), metatypical (1.9), mixed (1.8), and superficial (1.8). The low category included BCC subtypes of basosquamous (1.6), micronodular (1.6), nodular (1.6), and unspecified (1.5). Three hundred twenty-four cases (22.0%) manifested HS drift or a change in subtype from index biopsy to the final MMS stage. Superficial BCC was the only subtype that showed an increase in prevalence from index biopsy to the final MMS stage (from 16.0% to 25.8%; P < .0002). LIMITATIONS: HSs from index biopsy may not be representative of all HSs present, resulting in sampling bias. CONCLUSION: SCE of superficial BCC was as likely as SCE of BCC subtypes that are considered "aggressive" and are deemed "appropriate" for MMS by the appropriate use criteria. Our study also found that when HS drift occurs, the most likely subtype to extend subclinically is superficial BCC.

Metaplastic Breast Carcinoma Revisited; Subtypes Determine Outcomes: Comprehensive Pathologic, Clinical, and Molecular Review.

Metaplastic breast carcinoma (MpBC) is a heterogeneous group of tumors that clinically could be divided into low risk and high risk. It is important to recognize the different types of MpBC, as the high-risk subtypes have worse clinical outcomes than triple-negative breast cancer. It is important for the pathologist to be aware of the MpBC entities and use the proposed algorithms (morphology and immunohistochemistry) to assist in rendering the final diagnosis. Few pitfalls are discussed, including misinterpretation of immunohistochemistry and certain histomorphologies, particularly spindle lesions associated with complex sclerosing lesions.

High-grade tumor classified by new system is a prognostic predictor in resected lung adenocarcinoma.

OBJECTIVES: A grading system for pulmonary adenocarcinoma has not been established; hence, the International Association for the Study of Lung Cancer (IASLC) pathology panel developed a new grading system for invasive adenocarcinoma. We aimed to evaluate the prognostic significance of the IASLC grading system for invasive pulmonary adenocarcinoma. METHODS: We conducted a retrospective analysis of 471 Japanese patients with resected lung adenocarcinoma. Tumors were classified in accordance with the IASLC grading system and 2015 World Health Organization classification. We analyzed recurrence-free probability (RFP) and overall survival (OS) using the log-rank test and compared the two grading systems using the Cox proportional hazards model. RESULTS: Grade 3 tumors of the IASLC system and high-grade tumors of the 2015 World Health Organization classification were present in 38% and 17% of patients, respectively. The 5-year RFP was lower in patients with IASLC Grade 3 tumors (45%) than in patients with IASLC Grade 1 and 2 tumors (91% and 83%, respectively). The 5-year RFP of patients with IASLC Grade 2 tumors (83%) was higher than of those with 2015 World Health Organization intermediate tumors (69%). On multivariate analysis for recurrence, IASLC Grade 3 was an independent prognostic factor of worse RFP. We showed similar results on analysis for the OS. CONCLUSIONS: The prognostic significance of IASLC Grade 3 tumors on recurrence-free probability was confirmed through both univariate and multivariate analyses. Thus, the IASLC Grade 3 tumor is an independent factor of poor prognosis in patients with resected lung adenocarcinoma.