Micropapillary Pattern Research Articles

A Clinicopathological Study of Small Lung Adenocarcinoma 1 cm or Less in Size: Emphasis on Histological Subtypes Associated With Lymph Node Metastasis and Recurrence.

The aim of this study was to assess the prognostic significance of the newly proposed 2015 World Health Organization (WHO) lung adenocarcinoma classification for patients undergoing resection for small (≤1 cm) lung adenocarcinoma. We also investigated whether lobectomy offers prognostic advantage over limited resection for this category of tumors. A retrospective study of resected pulmonary adenocarcinomas (n = 83) in sizes 1 cm or less was carried out in which comprehensive histologic subtyping was assessed according to the 2015 WHO classification on all consecutive patients who underwent lobectomy or limited resection between 2008 and 2015. Correlation between clinicopathologic parameters and the difference in recurrence between lobectomy and limited resection group was evaluated. Our data show that the proposed 2015 WHO classification identifies histological subsets of small lung adenocarcinomas with significant differences in prognosis. No recurrence was noted for patients with adenocarcinoma in situ and minimally invasive adenocarcinoma. Invasive adenocarcinomas displayed high heterogeneity and the presence of micropapillary component of 5% or greater in adenocarcinomas was significantly related to lymph node involvement and recurrence ( P < .001). Stage Ia patients who underwent limited resection had a higher risk of recurrence than did those treated by lobectomy (P < .05). Application of the 2015 WHO classification identifies patients with adenocarcinoma in situ and minimally invasive adenocarcinoma had excellent prognosis. Micropapillary pattern was associated with high risk of lymph node metastasis and recurrence.

Clinicopathologic features of mammary microglandular adenosis with carcinoma: a study of 5 cases

Objective: To study the clinicopathologic, immunohistochemical features, differential diagnoses and prognosis of mammary microglandular adenosis with carcinoma (MGACA) with micropapillary pattern. Methods: Five cases of MGACA were collected from 2010 to 2016 and reviewed for their clinical, histologic features and outcome.EnVision method were done for S-100 protein, cytokeratin (CK), p63, Calponin, smooth muscle myosin heavy chain (SMMHC), PR, ER and HER2. Results: Histologically, microglandular adenosis(MGA), atypical MGA (AMGA) and invasive carcinoma were seen in all five cases of MGACA. The invasive component was metaplastic carcinoma in one case and ductal in four cases. All epithelial cells were S-100 and CK positive in MGA, AMGA and invasive carcinoma. p63, Calponin and SMMHC negativity confirmed the lack of a myoepithelial cell layer in MGA, AMGA and MGACA. PR was weakly focally positive in one case, but ER and HER2 were negative in all cases (four cases were triple negative). Ki-67 index was 20% to 40%. Laminin and collagen Ⅳ staining showed the presence of basement membrane in MGA and AMGA, except MGACA. The follow-up time ranged from 3 months to 6 years, and all patients were alive without recurrence or distant metastasis. Conclusions: MGACA is a rare tumor with distinct morphological and IHC features. Compared to most triple-negative breast cancers, MGACA seems to have a relatively favorable outcome.

Evaluation of grading systems in stage I lung adenocarcinomas: a retrospective cohort study

AimsThere is no internationally accepted grading system for lung adenocarcinoma despite the new WHO classification. The architectural grade, the Kadota grade and the Sica score were evaluated and compared with...

Pathological prognostic factors of recurrence in early stage lung adenocarcinoma.

Histological heterogeneity is thought to be important for prognosis of lung adenocarcinoma. We investigated to determine pathological features with prognostic value for recurrence of early stage lung cancer. A total of 368 patients who underwent curative surgical resection for early stage lung adenocarcinoma between 2009 and 2012 were enrolled. Pathologic characteristics including the presence of visceral pleural invasion, micropapillary patterns, aerogenous spread, lymphovascular invasion, perineural invasion and necrosis were examined. The correlations between pathological factors and clinical outcomes were analysed to determine prognostic significance. Mean follow-up was 43.0 months (±14.56, ranging from 0.0 to 73.9 months). Three-year overall survival was 95.2% and disease-free survival was 89.8%. The recurrence rate was 9.0% (33 patients) and the mortality rate was 6.0% (22 patients). The presence of a micropapillary pattern (P < 0.002), lymphatic invasion (P < 0.000), aerogenous spread (P < 0.000), vascular invasion (P = 0.036) and necrosis (P < 0.000) were negative prognostic factors of recurrence in univariate analysis. In multivariate analysis, only aerogenous spread had prognostic value (P = 0.020). The recurrence hazard ratio for the presence of aerogenous spread was 3.2 (95% confidence interval 1.20-8.47). The presence of aerogenous spread was an independent pathological risk factor of recurrence in stage I lung adenocarcinoma. Micropapillary pattern had prognostic importance for recurrence in univariate analysis, but not in multivariate analysis.

Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma.

The aim of this study was to elucidate the clinicopathological characteristics of the micropapillary (MP) subtype and its correlation with survival in lung adenocarcinoma. We investigated the clinicopathological characteristics, including the incidence, sex, smoking history, tumor size, lymph node metastasis, lymphovascular invasion, distant metastasis, genetic alteration, and prognosis in lung adenocarcinoma with the MP pattern through a meta-analysis. From 48 eligible studies, 19,502 lung adenocarcinomas were included. The incidence rate of the MP pattern was 0.101 [95% confidence interval (CI) 0.075-0.136]. There was no significant difference between stage I and III tumors. Lung adenocarcinoma with the MP pattern showed higher rates of lymphatic invasion (0.526, 95% CI 0.403-0.645). MP pattern was found in 0.150 (95% CI 0.008-0.790) of lung adenocarcinoma with distant metastasis. In lung adenocarcinoma with the MP pattern, the estimated rates of ALK, EGFR, and KRAS mutations were 0.102 (95% CI 0.027-0.322), 0.620 (95% CI 0.444-0.769), and 0.118 (95% CI 0.027-0.393), respectively. The MP pattern of lung adenocarcinoma was significantly correlated with worse overall and disease-free survival rates (hazard ratio 1.704, 95% CI 1.216-2.387, and 2.082, 95% CI 1.541-2.813, respectively). Taken together, identification of the MP pattern in lung adenocarcinoma is useful for prediction of clinicopathological characteristics and prognosis of patients.

Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma.

BackgroundMucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. MethodsA total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). ResultsThe clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05). According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05). ConclusionsIn contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.

To evaluate the clinicopathologic characteristics and outcome of tumor cells spreading through air spaces in patients with adenocarcinoma of lung

Objective: To investigate the clinicopathologic features, molecular characteristics and prognosis of spread through air space (STAS) in patients with adenocarcinoma of the lung. Methods: Two hundred and eighty-eight lung adenocarcinoma patients with complete clinicopathologic and follow-up data were included. The patients were divided into STAS positive (178 cases) and negative (110 cases) groups.EGFR and KRAS gene mutations were detected by amplification refractory mutation system (ARMS), and ALK and ROS1 gene fusion were detected by fluorescence in situ hybridization method. The relationship between STAS and clinicopathologic, molecular features, and patient outcome was analyzed. Results: STAS was present in 61.8%(178/288) of lung adenocarcinomas. The positive rate of STAS in tumors >3 cm was significantly higher than that in tumors ≤3 cm (P=0.009), and was significantly higher in tumors with pleural invasion (P<0.01), venous invasion (P<0.01), lymphatic invasion (P<0.01), perineural invasion (P=0.029) and tumors with necrosis (P<0.01). STAS was also correlated with tumor recurrence (P<0.01) and advanced pathologic TNM stage (P=0.002). There was no significant correlation with patients' gender, age and smoking history. Histologically, STAS was present in 58.0%(91/157), 67.6%(50/74), 2/6, 64.3%(27/42) and 8/9 of acinar, papillary, lepidic, solid and micropapillary adenocarcinomas, respectively. In addition, the positive rates of STAS in tumor with micropapillary (>5%) and without micropapillary pattern were 80.9%(55/68) and 55.9%(123/220), respectively (P<0.01). STAS was significantly higher in EGFR negative group (P=0.034), ALK gene rearrangement group (P=0.003) and ROS1 gene rearrangement group (P=0.012), but there was no significant correlation with KRAS mutation. Univariate survival analysis showed that patients with STAS had a shorter progression-free survival (PFS, P<0.01) and overall survival (P=0.013). Multivariate analysis confirmed that STAS was an independent predictor of PFS in lung adenocarcinoma patients (HR: 2.749, 95%CI: 1.550-4.876, P=0.001). Conclusions: The presence of STAS in lung adenocarcinoma suggests high risk of recurrence and invasion and is thus an important prognostic factor. In addition, STAS is associated with EGFR mutation, ALK and ROS1 gene rearrangement.

TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary.

Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P<0.001) suggesting a potential function of the protein in that subtypes. Associations of TFF3 expression with FIGO stage and micropapillary pattern were significant in the overall cohort but confounded by their correlation with histological subtypes. The highly specific expression of TFF3 in MBOT may help to further clarify potential relationships of tumors with mucinous histology and warrants further studies.

Is MPP a good prognostic factor in stage III lung adenocarcinoma with EGFR exon 19 mutation?

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein encoded by a gene located in the short arm of chromosome 7. This study aimed to investigate the clinicopathologic characteristics of classic EGFR exon mutation in Chinese patients with TMN stage III lung adenocarcinoma who received radical surgery. A total of 1,801 lung adenocarcinomas were analyzed for mutations in EGFR; 35% exhibited mutation of classic EGFR exons. Clinical and pathologic characteristics of patients with EGFR exon 19 mutation were compared with those who harbored EGFR exon 21 mutation. Patients with EGFR exon 19 mutation had a higher overall survival (OS, p=0.023) than those harboring EGFR exon 21 mutation. Our results demonstrated that patients with a micropapillary pattern (MPP) pathologic type in EGFR exon 19 mutation had a higher OS (p=0.022), and patients with exon 19 mutation were more sensitive to EGFR–tyrosine kinase inhibitors (p=0.032). The results of the current study can be used in decision-making regarding the treatment of patients with classic EGFR exon mutations.

Colon cancer with micropapillary carcinoma component: a clinopathologic study of 9 cases.

Recently, colon cancer with micropapillary pattern (MPP) has been identified. MPP is defined as tight tufts surrounded by cleft-like space and lacking true fibrovascular cores and showing reverse polarity. In this article, we studied nine cases of colon cancer with MPP. MPP usually accounted for a minor component in total tumour volume, which ranged from 3 to 40% with a mean percentage of 19.2%. Associated histological subtype showed moderately differentiated tubular adenocarcinoma in all cases. The reverse polarity of villin (9/9, diffuse) in MPP component was superior to that of CA125 (5/9, focal) or CD10 (5/9, diffuse 2/9, focal 3/9). In clinicopathological indicators such as sex, tumour location, tumour depth, lymphovascular invasion, lymph node metastasis, or pathological stage and clinical behaviour, there was statistically no difference between the MPP group and the non-MPP group of the colon. In conclusion, colon cancer with MPP is characterised by frequent association with moderately differentiated tubular adenocarcinoma as a minor component. Villin immunohistochemistry is useful in the detection of reverse polarity of MPP of colon cancer.

P1.05-066 Impact of Micropapillary Pattern in Nodal Upstaging of Lung Adenocarcinoma 2cm or Less

Clinical and pathological determinations of lymph node staging are critical in the treatment of lung cancer. However, upstaging of nodal status frequently is necessitated by postoperative findings. It is now being recognized that lung adenocarcinoma (LAC) with tumor cells arranged in a micropapillary pattern (MPP) is more malignant than those without such pattern. Thus, this study was conducted to evaluate clinicopathologic features that impact nodal upstaging in patients with small-sized (≦2cm) LACs with MPP(LAC-MPP). We retrospectively reviewed the 182 radically resected lung adenocarcinomas at the Kitasato University Hospital, Japan, from January 2005 to December 2015. MPP was defined as a small papillary tumor cell tuft without an obvious fibrovascular core. Tumors with ≧1% of their tumor cells arranged in a MPP were diagnosed as LAC-MPP, while the remainders were diagnosed as conventional LAC. The histological subtypes and differentiation grade of LAC were determined according to the 4th WHO classification. The registry date of the patients with LAC and LAC-MPP were analyzed, and the clinicopathologic profiles and surgical outcomes of the patients were evaluated. One hundred and sixty (88%) of the total 182 were LAC whereas 22 (12%) were LAC-MPP. Among the two groups, there is no significant difference in age, sex, smoking habit, preoperative serum CEA level, or surgical procedures. Compared with the LAC, the LAC-MPP had worse statuses for lymphatic invasion (p=0.0096), pleural invasion (p=0.002), postoperative lymph node metastases (p<0.001) and postoperative recurrence (p=0.002). On the other hand in clinical stages, pleural lavage cytology, and postoperative stages, there is not significant deference statistically. Median follow up time was 48 months. The five-year overall survival rates were 92% in LAC group and 85% in LAC-MPP, statistically not significant deference (p=0.98). Also with regarding to the median relapse free survival rates, no significant difference was found between two groups (p=0.14). The follow-up term of patients was limited in this study. But, we concluded that LAC-MPP should be considered as an aggressive disease showing nodal upstage. Although lymph node metastasis and lymphatic infiltration should be usually reported in LAC-MPP patients, these are difficult to detect by preoperative imaging tools such as CT and PET canning. Therefore, MPP could be important factor to determine the indications for limited resection for LAC patients even if small-sized (≦2cm) LAC- MPP.

P1.05-039 Recurrence and Survival Outcome after Segmentectomy for Non-Small Cell Lung Cancer: A Long-Term Follow-Up Study at a Single Institute

This study aimed to investigate the factors associated with long-term outcomes of segmentectomy for non-small cell lung cancer (NSCLC) carried out at a single institute. 179 patients with stage I NSCLC who underwent a segmentectomy between 2005 and 2009 were investigated. Histological classification was reassessed according to the criteria of the 2015 WHO. 179 patients with stage I NSCLC (159 adenocarcinomas (ADCs), 14 squamous cell carcinomas (SQCs), 4 adenosquamous carcinomas, and 2 typical carinoids) who underwent segmentectomy between 2005 and 2009 were investigated. The mean follow-up was 73 months. The 5-year overall survival (5-OS) and 5-years disease-free survival (DFS) were 91.8% and 90.2%, respectively. Seven cases of distant recurrence and 8 local-regional recurrence occurred. Multivariate analysis revealed that lymphovascular invasion (LVI) was the independent predictor of 5-OS (P=0.005), and part-solid GGO (GGO ratio < 50%) and LVI were that for 5-DFS (P=0.043, P<0.001). Among invasive ADC patients, micropapillary pattern (MIP) ≧ 5% was identified as an independent predictor of recurrence (P=0.005) and survival (P=0.007). There were five local recurrences in patients with MIP more than 5 years after segmentectomy. LVI was an independent predictor of the recurrence and overall survival. In patients with invasive ADC, MIP≧5% was a multivariable predictor of recurrence and overall survival. In the patients who underwent a segmentectomy, 5 years without recurrence is not sufficient to conclude that patients with NSCLC is cured.

Poorly Differentiated Clusters in Colorectal Adenocarcinomas Share Biological Similarities with Micropapillary Patterns as well as Tumor Buds.

In colorectal carcinoma, poorly differentiated clusters (PDCs) are a poor prognostic indicator and show morphological continuity and behavioral similarities to micropapillary patterns (MPPs) as well as tumor buds (TBs). Epithelial-mesenchymal transition (EMT) and inhibition of cancer-stromal interactions may contribute to the development of PDCs. To clarify the biological nature of PDCs, we examined immunohistochemical stainings for β-catenin, Ki-67, E-cadherin, epithelial cell adhesion molecule (EpCAM), MUC1, and epithelial membrane antigen (EMA), which are associated with EMT and cancer-stromal interactions. The expression frequencies and patterns of PDCs, TBs, and differentiated neoplastic glands from the tumor center (TC) were compared. In the study group (117 cases), the nuclear β-catenin staining index was higher in PDCs (37.3%) and TBs (43.3%) than in neoplastic glands from TC (8.9%, P < 0.001). The mean Ki-67 labeling index in TC was 71.5%, whereas it was decreased in PDCs (31.2%) and TBs (10.2%, P < 0.001). E-cadherin and EpCAM displayed a tendency to be found along the cell membrane in TC samples (91.5% and 92.3%, respectively), whereas they showed loss of membranous staining in PDC (44.4% and 36.8%, respectively) and TB samples (60.7% and 68.4%, respectively). An inside-out pattern for MUC1 and EMA was frequently observed in PDC (48.7% and 45.3%, respectively) and TB samples (46.2% and 45.3%, respectively), but not in TC samples. Our data demonstrate that there is a pathogenetic overlap among PDCs, TBs, and MPPs and suggest that they might represent sequential growth patterns that branch from common biological processes such as dedifferentiation and alteration in cancer-stromal interactions.

OA24.06 Histologic Subtype of Early-Stage Lung Adenocarcinoma is a Predictor of Failure Patterns after Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. Histologic subtyping in surgically resected lung adenocarcinomas is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. Herein, we describe outcomes following SBRT for early-stage lung adenocarcinoma by histologic subtype. We identified 119 consecutive patients (124 lesions) with stage I-IIA lung adenocarcinoma who were treated with definitive SBRT at our institution between August 2008 and August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 WHO Classification. Thirty-seven tumors (30%) were of high risk subtype, defined as containing a component of solid and/or micropapillary pattern. Cumulative incidences of local, nodal, regional and distant failure were compared between high risk vs. non-high risk adenocarcinoma subtypes with Gray’s test, and multivariable-adjusted hazard ratios were estimated from propensity score-weighted Cox regression models. Median follow-up for the entire cohort was 17 months and 21 months for surviving patients. The 1-year cumulative incidence of local, nodal, regional and distant failure, respectively, in high risk and non-high risk lesions were 7.3%, 14.8%, 4.0%, 22.7% and 2.7%, 2.6%, 1.2%, 3.6%. Hazard ratios for local, nodal, regional and distant failure, respectively, of high risk lesions compared to non-high risk were 16.8 (95% CI 3.5-81.4), 3.8 (95% CI 0.95-15.0), 20.9 (95% CI 2.3-192.3), 6.9 (95% CI 2.2-21.1). No significant difference was seen with regard to overall survival. Outcomes following SBRT for early-stage adenocarcinoma of the lung are highly correlated with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, histologic subtype based on core biopsies is a novel prognostic factor and may have important implications for patient selection, adjuvant treatment, biopsy methods and clinical trial design.

MTE11.01 The Clinical Impact of the 2015 WHO Classification of Lung Tumors

MTE11.01 The Clinical Impact of the 2015 WHO Classification of Lung Tumors

Micropapillary pattern in a case of multilocular cystic renal neoplasm of low malignant potential

Micropapillary pattern in a case of multilocular cystic renal neoplasm of low malignant potential

OA12.06 A Retrospective Analysis of Patients with Small Lung Adenocarcinoma (≤2cm) by New World Health Organization Classification

We have recently demonstrated that the presence of the Spread Through Air Spaces (STAS) and the variety of histologic subtypes increase the risk of recurrence after resection for small lung adenocarcinoma (ADC). Currently, the new World Health Organization classification of lung cancers was revised and newly prescribed to describe the presence of each histologic subtypes and STAS. The purpose of this study is to examine the risk factor for recurrence other than TNM staging analyzing clinical information retrospectively. All available tumor slides from patients with clinical stage I, therapy-naive, surgically resected solitary lung ADC ≤2 cm in size (1998-2015) were reviewed. Each tumor was evaluated by comprehensive histologic subtyping, and the percentage of each histologic component was recorded in 5% increments. STAS was defined as the spread of tumor cells into air spaces in the lung parenchyma adjacent to the main tumor according to the WHO classification. Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method. 354 patients met inclusion criteria (52.3% men; median age: 67yrs; median tumor size: 1.3cm; 325 stage IA/ 29 stage IB; 91 partial resection/ 22 segmentectomy / 241 lobectomy or pneumonectomy). The prognosis didn’t differ significantly between sublobar resection group and lobectomy or pneumonectomy group (5-year RFP: 88.4% (N=113) vs. 91.9% (N=241), P=.162). Presence of STAS was identified in 74 cases (20.9%) (36 Micropapillary pattern / 55 Solid pattern / 15 Single cells). STAS was significantly associated with recurrence (5-year RFP: 94.3% vs. 76.2%, P < .0001). Histologic subtypes were 62 adenocarcinoma in situ (18%), 110 minimally invasive adenocarcinoma (31%) and 182 invasive adenocarcinoma (51%). The recurrence after sublobar resection was seen in 13 cases (1 partial resection (4.5%) / 12 segmentectomy (13%), 5 STAS (+)/ 8 STAS (-), 6 solid predominant / 5 acinar predominant / 2 lepedic predominant, 5 pulmonary recurrence / 4 lymph node recurrence / 2 local recurrence / 2 others). Patients with solid component had significantly worse prognosis (5-year RFP: 71.7% (N=83) vs. 96.3% (N=271), P<.0001). Among them, patients with sublobar resection had significantly more recurrence than with lobectomy or pneumonectomy (5-year RFP: 51.4% (N=19) vs. 77.7% (N=64), P=.0021). The patients of small ADC with STAS or solid component had worse prognosis. The patients after sublobar resection with solid component should be made follow-up closely. We propose that the presence of those features should be considered a factor to upgrade the pathologically defined T stage.

MA12.09 Comparative Histological Subtype Analysis of Lung Adenocarcinoma Tumor and Metastatic Lymph Nodes and the Prognostic Impact

The goal of this study is to investigate comprehensive comparative pathological analyses of both primary tumor and metastatic lymph node (LN) and correlate with lung cancer-specific death (LC-death) in patients with LN-positive lung adenocarcinoma. PN1/2 lung adenocarcinoma patients who underwent R0 resection without induction therapy (n=402, 2000-2012) were included in the study. In primary tumor, lymphatic/vascular/pleural invasion, necrosis, tumor spread through air spaces (STAS), as well as histologic subtypes according to 2015 WHO classification were evaluated. In metastatic LN, metastatic tumor size, extracapsular invasion, histologic subtypes were evaluated. Recurrence and LC-death were analyzed by Cox model. Micropapillary and solid predominant subtypes were more frequent in LN metastases than in primary tumors (Figure). In multivariable analyses, adjuvant chemotherapy, pleural invasion, extracapsular invasion of LN metastasis, micropapillary predominant subtype in LN metastasis were independent factors for recurrence; adjuvant chemotherapy, pleural invasion, tumor STAS, and extracapsular invasion were for LC-death (Table). In lung adenocarcinoma lymph node metastases, predominant micropapillary pattern and extracapsular invasion indicate high risk for recurrence and lung cancer-specific death.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Imaging Phenotyping Using Radiomics to Predict Micropapillary Pattern within Lung Adenocarcinoma

IntroductionLung adenocarcinomas (ADCs) with a micropapillary pattern have been reported to have a poor prognosis. However, few studies have reported on the imaging-based identification of a micropapillary component, and all of them have been subjective studies dealing with qualitative computed tomography variables. We aimed to explore imaging phenotyping using a radiomics approach for predicting a micropapillary pattern within lung ADC. MethodsWe enrolled 339 patients who underwent complete resection for lung ADC. Histologic subtypes and grades of the ADC were classified. The amount of micropapillary component was determined. Clinical features and conventional imaging variables such as tumor disappearance rate and maximum standardized uptake value on positron emission tomography were assessed. Quantitative computed tomography analysis was performed on the basis of histogram, size and shape, Gray level co-occurrence matrix–based features, and intensity variance and size zone variance–based features. ResultsHigher tumor stage (OR = 3.270, 95% confidence interval [CI]: 1.483–7.212), intermediate grade (OR = 2.977, 95% CI: 1.066–8.316), lower value of the minimum of the whole pixel value (OR = 0.725, 95% CI: 0.527–0.98800), and lower value of the variance of the positive pixel value (OR = 0.961, 95% CI: 0.927–0.997) were identified as being predictive of a micropapillary component within lung ADC. On the other hand, maximum standardized uptake value and tumor disappearance rate were not significantly different in groups with a micropapillary pattern constituting at least 5% or less than 5% of the entire tumor. ConclusionA radiomics approach can be used to interrogate an entire tumor in a noninvasive manner. Combining imaging parameters with clinical features can provide added diagnostic value to identify the presence of a micropapillary component and thus, can influence proper treatment planning.

The micropapillary/hobnail variant of papillary thyroid carcinoma: A review of series described in the literature compared to a series from one southern Italy pathology institution.

Papillary thyroid carcinoma (PTC) has a good prognosis with a 10-yr survival greater than 90%. Recently, a micro-papillary pattern with hobnail appearance (MPHC) in PTC has been indicated as associated with poor prognosis, but this suggestion is based only on a few cases from geographical areas different from ours. Two-hundred ninety-nine consecutive PTC cases were collected between the years of 1992 and 2014 at our institution. The corresponding histologic sections (at least 6 for each case) were stained with hematoxylin and eosin and reviewed independently by two pathologists to reach a consensus on the identification and quantification of the MPHC. As done in other cohorts, parallel serial sections were stained with antisera for thyroglobulin, epithelial membrane antigen, thyroid-transcription-factor-1 and Ki 67. BRAF gene mutation at codon 600 and RET/PTC1 gene rearrangements were searched. A comparative statistical analysis was done between the present series and previously published series. Of the 295 PTC, 124 (42.5%) were follicular, 104 (35%) classic, 34 (11.5%) sclerosing, 15 (5%) tall cells, 10 (3.4%) Warthin-like, and 8 (2.7%) MPHC. Four MHPC cases (50%) harbored the BRAF V600E variant, while one was positive for RET/PTC1 rearrangement. Our rate of MPHC-PTC (2.7%) is 2X to 8X greater than those reported previously for cohorts from North America + North Italy, Korea and Mexico. MPHC prognosis appears to be better compared to other cohorts, probably due to not only to the lower rate of the vascular invasion, but also to the smaller size of the MPHC-PTC nodule.