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• Positive blood and lymphatic vessel invasion collectively represented TVI. • TVI was a prognostic factor in Stage IA1-2 lung adenocarcinoma patients. • TVI did not affect the prognosis of Stage IA3 adenocarcinoma patients. • Stage IA1 adeno without TVI can possibly be classified as minimally invasive. The prognostic significance of blood and lymphatic vessel invasion in the 8th edition of the Tumor, Node, Metastasis (TNM) classification remains unclear. Therefore, this study aimed to evaluate the prognostic significance of blood and lymphatic vessel invasion in p-stage IA lung adenocarcinoma in the 8th edition of the TNM classification. We retrospectively examined patients with p-Stage 0-IA lung adenocarcinoma, reclassified according to the 8th edition of the TNM classification. Blood and lymphatic vessel invasion were evaluated using hematoxylin-eosin and Elastica van Gieson and hematoxylin-eosin and anti-podoplanin antibody staining, respectively. Combined blood and lymphatic vessel invasion constituted tumor vessel invasion (TVI). Overall, 306 patients were evaluated. The median follow-up period was 98.0 (range: 10–216) months. The 5-year recurrence-free survival differed significantly among patients with and without TVI in p-stage IA1 (TVI−: 100%, TVI+: 88.9%, P = 0.007) and IA2 (TVI−: 94.6%, TVI+: 80.8%, P = 0.012) but not in p-stage IA3 (TVI−: 66.7%, TVI+: 75.0%, P = 0.598). The 5-year lung cancer-specific survival also differed significantly among those with and without TVI in p-stage IA1 (TVI−: 100%, TVI+: 88.9%, P < 0.001) and IA2 (TVI−: 98.2%, TVI+: 88.7%, P = 0.043) but not in p-Stage IA3 (TVI−: 66.7%, TVI+: 75.0%, P = 0.858). No recurrence and lung cancer-specific deaths occurred in p-stage IA1 patients without TVI. On multivariate analysis, the presence of TVI was independently associated with recurrence and lung cancer-specific death in patients with p-stage IA1-2 lung adenocarcinoma. TVI did not affect the prognosis of those with p-stage IA3 adenocarcinoma. TVI is a prognostic factor in patients with p-stage IA1-2 lung adenocarcinoma. P-stage IA1 lung adenocarcinoma without TVI may therefore be classified as minimally invasive. [ABSTRACT FROM AUTHOR]

In the Eighth Edition of the Tumor Node Metastasis Classification System for Lung Cancer, the definitions of the clinical T and pathologic T descriptors have changed. Little has been reported on comparisons between the consolidation diameter in the lung window setting and the tumor diameter in the mediastinal window setting with respect to the correlations with pathologic invasive size (IS) and invasiveness. The present study was conducted to clarify which window setting was better for preoperatively estimating IS and invasiveness. We retrospectively reviewed 1,167 consecutive patients with lung adenocarcinomas measuring 3 cm or less in diameter. We measured three high-resolution computed tomography variables and examined correlations of IS with these variables, factors predictive of an IS of 5 mm or less, and other variables related to invasiveness. On receiver operating characteristic curve analysis, the tumor diameter in the mediastinal window setting more strongly predicted IS than did the consolidation diameter in the lung window setting (p < 0.001), and the consolidation diameter in the lung window setting more strongly predicted IS than did the maximum tumor diameter in the lung window setting (p < 0.001). Lymphatic, vascular, and pleural invasion were best predicted by the tumor diameter in the mediastinal window setting. We can estimate IS and other variables related to invasiveness most precisely by measuring the tumor diameter in the mediastinal window setting. The tumor diameter in the mediastinal window setting is an important variable that we should measure preoperatively. [ABSTRACT FROM AUTHOR]

Background Advanced unresectable pulmonary adenocarcinoma with the epidermal growth factor receptor ( EGFR ) exon 21 L858R point mutation (Ex21) is associated with a poor prognosis. However, for early-stage resectable adenocarcinoma, Ex21 tumors have a lower-grade malignancy than exon 19 deleted (Ex19) tumors. We therefore investigated the effect of EGFR mutations on the prognosis in patients with completely resected pN1-N2 adenocarcinoma. Methods Five-year disease-free survival (DFS) and overall survival (OS) were analyzed in 202 pN1-N2 pulmonary adenocarcinoma patients, 100 of whom had EGFR mutations, comprising Ex21 in 41 (20.3%), Ex19 in 55 (27.2%), and Ex18 in 4 (2%). Results Patients with and without EGFR mutations had similar DFS (26.2% vs 24.6%, respectively; p = 0.280) and OS (64.9% vs 54.2%, respectively; p = 0.564). Patients with Ex19 tumors had significantly better DFS (38.8% vs 11.8%, p = 0.001) and tended to have better OS (78.3% vs 48.3%, p = 0.123) than those with Ex21 tumors. For pN1, patients with Ex19 tumors had a longer disease-free interval (54.0 vs 22.3 months, p = 0.003) and median survival time (81.0 vs 50.6 months, p = 0.022) than those with Ex21 tumors. For pN2, patients with Ex19 tumors had longer disease-free interval than those with Ex21 tumors (43.6 vs 30.1 months, p = 0.109). Multivariate analysis showed Ex21 was a prognosticator of poor DFS (hazard ratio, 2.25; 95% confidence interval, 1.21 to 4.20). Conclusions For pN1-N2 pulmonary adenocarcinoma, Ex21 mutation was associated with poorer prognosis than Ex19 mutation. Thus, EGFR mutation status should be considered when predicting prognosis. [ABSTRACT FROM AUTHOR]

Background Detailed reports on mucinous adenocarcinoma (formerly “mucinous bronchioloalveolar carcinoma”) have not been published. We evaluated the correlation between thin-section computed tomography findings and the clinicopathologic characteristics and prognosis of mucinous adenocarcinoma. Methods From April 1997 to March 2008, 45 resected lung carcinomas were diagnosed as mucinous adenocarcinoma. Five cases of multiple lung cancers or ambiguous mucinous adenocarcinoma were excluded. Tumors were classified as “solitary-type” or “pneumonic-type” tumors according to the thin-section computed tomography findings. We evaluated the clinicopathologic characteristics and the epidermal growth factor receptor and KRAS gene mutation statuses and correlated the thin-section computed tomography findings with patient prognoses. Results Thirty patients had solitary-type and 10 had pneumonic-type tumors. The lesions in 23, 14, and 3 patients were classified as pathologic stage I, stage II, and stage III, respectively. Five patients had adenocarcinoma in situ, 9 had minimally invasive adenocarcinoma, and 26 had invasive mucinous adenocarcinoma. Thirteen patients showed recurrences, which were classified as intrapulmonary metastases in all patients. The 5-year overall and relapse-free survival rates were 83.3% and 88.8%, respectively, in patients with solitary-type tumors and 20.0% and 0%, respectively, in patients with pneumonic-type tumors ( p < 0.001). The median follow-up time for surviving patients was 81 months. KRAS mutations were detected in 30 patients, but epidermal growth factor receptor mutations were absent in all patients. Conclusions Our results indicated that thin-section computed tomography findings for mucinous adenocarcinoma were useful in predicting prognosis before surgical resection. Further studies are required to improve the treatment strategy for mucinous adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background Surgical treatment has become the mainstay of treatment for multiple primary lung cancers. In particular, the prevalence of synchronous primary lung adenocarcinomas (SPLA) has recently increased, but few studies have evaluated surgical outcomes of patients with SPLA. We reviewed the clinicopathologic features and surgical outcomes of SPLA to identify factors related to survival. Methods Data on 2,041 consecutive patients with primary non-small cell carcinoma who underwent surgical resection in our hospital from 1995 through 2009 were retrospectively analyzed. Results The SPLA was pathologically diagnosed in 93 patients, including 26 with bilateral tumors. The rates of overall survival and recurrence-free survival at 5 years were 87.0% and 81.8%, respectively. There was no surgical mortality at 30 days. On univariate analysis, lymph node metastasis ( p = 0.0000), nonlepidic predominant histologic subtype ( p = 0.0018), and a solid appearance of the largest tumor on computed tomography ( p = 0.0088) were significantly related to poor overall survival. On multivariate analysis, bilateral distribution of tumors ( p = 0.031), lymph node metastasis ( p = 0.004), and sublobar resection ( p = 0.042) were independent predictors of poor survival. Conclusions Surgery has good outcomes and should be aggressively performed for patients with SPLA. The evaluation of lymph node status has an important role in deciding whether surgery is indicated. Bilateral tumors are a predictor of poor outcomes, requiring that caution be exercised. Lobectomy has a high cure rate and should be performed whenever possible. However, sublobar resection should be considered for patients likely to have poor residual lung function postoperatively. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We examined the appropriate measurement for pathological tumor size by comparing radiological and pathological tumor size of resected lung adenocarcinoma in FSE. Materials and methods: We reviewed records of 59 resected specimens of lung adenocarcinoma for FSE from January to December 2008. Specimens were well-inflated with saline by using an injector before cutting into segments. After selecting the tumor segment of maximal diameter, we compared three ways of measuring pathological tumor size by using paired t-test: (I) macroscopic tumor size (MTS), measured with a metal straight ruler, (II) microscopic frozen section tumor size (FSTS), and (III) microscopic paraffin section tumor size (PSTS). We compared each discrepancy rate (DR) [DR=(CT tumor size−pathological tumor size)/CT tumor size×100] (%) between tumors that were air-containing type and solid-density type on CT scans, and also compared the tumors with lepidic component rates (LCR) ≥50% and LCR <50%, by using Mann–Whitney U-tests. Results: FSE could diagnose malignancy with 100% accuracy. The mean CT tumor size was 18.36mm, and the mean pathological tumor sizes (MTS, FSTS, and PSTS) were 17.81, 14.29, and 14.23mm, respectively. FSTS and PSTS were significantly smaller than CT tumor size (p <0.001). The DR calculated with PSTS was significantly larger in air-containing than in solid-density tumors, and also larger in LCR ≥50% than in LCR <50% tumors. Conclusion: FSE with the inflation method diagnosed malignancy with 100% accuracy. The lung specimen must be sufficiently inflated to prevent tissue shrinking, and we propose MTS as the definition for pathological tumor size in FSE. The greater discordance observed between CT tumor size and microscopic tumor size was assumed to be due to shrinkage of the lepidic component in the tumor. [Copyright &y& Elsevier]

Abstract: We report a rare case of lung adenocarcinoma in which micropapillary components were considered to cause stump recurrence. A woman in her fifties was diagnosed with lung cancer in the right middle lobe with invasion to the upper lobe, which was treated by a right middle lobectomy together with upper lobe partial resection. The cancer was pathologically diagnosed as adenocarcinoma and had a free surgical margin. There was no recurrence during the following 5 years and 8 months, and thus periodical surveillance, including computed tomography, was stopped. However, 2 years and 7 months after this, she was discovered to have an abnormal shadow on chest radiography, and a thorough examination revealed a 3-cm-sized tumor involving the previous surgical margin. Therefore, she underwent right upper lobectomy. We pathologically re-evaluated the first tumor and found that it was an adenocarcinoma with a micropapillary component in the periphery, 6mm away from the surgical margin. In addition, a few tiny clusters of tumor cells were found to be floating within the alveolar spaces near the margin. The first and second tumors showed almost the same histological mixture of components of adenocarcinoma and the same EGFR mutation. From these results, we concluded the second tumor was a stump recurrence originating from the first tumor resection. This case illustrates the importance of careful pathological investigation when an autosuture instrument is used for a partial resection in a case of lung adenocarcinoma with micropapillary components. In such cases, it is particularly important to clarify if micropapillary components are floating near a stump. [Copyright &y& Elsevier]

Abstract: Introduction: Squamous cell carcinomas (SqCCs) of the lung can be divided into two types according to the location of primary site; one is central type and another is peripheral type. Many reports on the central type revealed the clinicopathological characteristics relating carcinogenesis, therapeutics and prognosis. On the other hand, those on the peripheral type are very a few and prognostic indicators of peripheral type have not been enough elucidated. The aim of this study was to clarify clinicopathological prognostic factors of small peripheral SqCCs of the lung 30mm or less. Materials and methods: We evaluated various 15 clinicopathological parameters in 81 patients with peripheral type SqCCs, which are defined as tumors located in or more peripheral from the third branching bronchus, measuring 30mm or less in diameter. Results: Univariate analyses were performed using the log lank test and multivariate analyses using logistic regression model. As a result, two factors had a statistically significant influence on outcome of the patients in the univariate analysis; no relapse was observed in the patients with the ratio of alveolar space filling (ASF) area to tumor area of 70% or more and the maximum diameter of invasive area measuring 10mm or less in size (P =0.0214, P =0.0373, respectively). Meanwhile, multivariate analysis showed that the ASF ratio of 70% or more significantly affected the outcome of the patients (P =0.0337), however the maximum diameter of invasive area did not (P =0.2136). We could not show the unfavorable prognostic factor contributory to tumor relapse. Conclusions: We have shown that the ASF ratio is a significantly favorable prognostic factor for small peripheral type. Especially the focally invasive tumors with ASF ratio of 70% or more might be classified as “a microinvasive carcinoma” of the peripheral SqCCs of the lung and tumors with ASF ratio 100% as noninvasive carcinoma. [Copyright &y& Elsevier]

Background: Postoperative interstitial pneumonitis is a life-threatening complication after lung cancer surgery. We conducted this study to identify risk factors for postoperative interstitial pneumonitis in patients with no clinical evidence of interstitial lung disease. Methods: We retrospectively studied patients who underwent lung cancer resection. The characteristics of patients were analyzed by reviewing their clinical and surgical records and preoperative chest high-resolution computed tomographic scans. Postoperative interstitial pneumonitis was defined as acute severe hypoxemia accompanied by radiographic diffuse interstitial infiltrates of the lung with no apparent cause within a few weeks after surgery. Results: From 2002 through 2005, 651 patients were evaluated, operated on, and managed by the same team. Postoperative interstitial pneumonia developed in 7 patients (7 of 651, 1.1%). Five of these patients had local, but not diffuse, dorsal subpleural honeycombing occupying three or more segments in both lower lobes on high-resolution computed tomography (CT honeycombing). During the same period, 46 patients had CT honeycombing. The incidence of postoperative interstitial pneumonia was 10.9% (5 of 46) among patients with CT honeycombing and 0.3% (2 of 605) among those without CT honeycombing. Four of the 7 (57%) patients with postoperative interstitial pneumonia died of respiratory failure. Mortality among the patients who had postoperative interstitial pneumonia as well as CT honeycombing was 80% (4 of 5); in contrast, none of the patients without CT honeycombing died. Multivariate analyses showed that the presence of CT honeycombing and prolonged operation time were significant risk factors. Conclusions: Subpleural honeycombing on high-resolution computed tomography is a significant predictor of postoperative interstitial pneumonia in asymptomatic patients who undergo resection for lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: The fusion gene EML4–ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) was recently identified as a novel genetic alteration in non-small-cell lung cancer. The clinicopathological features of EML4–ALK-positive adenocarcinoma are reported to include its high incidence in young, non-smoking patients, tumors that show distinct solid or acinar growth patterns with or without signet-ring cell histology, and its mutually exclusive occurrence with mutations in EGFR and KRAS. However, the clinical findings have not been well described. Here, we report a case of EML4–ALK-positive lung adenocarcinoma that showed multiple metachronous lesions on the pleura and pulmonary field, suspected to be a recurrence of lung adenocarcinoma after a 20-year disease-free interval. The slow clinical course may be characteristic of EML4–ALK-positive lung adenocarcinoma. Therefore, long-term observation of patients with EML4–ALK-positive lung adenocarcinomas is required after surgery. [Copyright &y& Elsevier]

Summary: The purpose of this study was to identify histologic factors significantly associated with initial organ-specific metastasis by 1044 invasive ductal carcinomas (IDCs) of the breast with and without adjuvant therapy, separately, according to nodal status and pathologic TNM stage status. The following histologic factors were prospectively analyzed by multivariate analyses for distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy, and for distant organ metastasis, bone metastasis, liver metastasis, and lung metastasis in patients with IDC who received adjuvant therapy: (1) invasive tumor size, (2) histologic grade, (3) tumor necrosis, (4) fibrotic focus (FF), (5) lymphatic invasion, (6) blood vessel invasion, (7) adipose tissue invasion, (8) skin invasion, (9) muscle invasion, (10) age, (11) estrogen (ER)/progesterone (PR) status, and (12) nodal status. The results showed that FF diameter greater than 8 mm and FF fibrosis grade 1 were the factors that most accurately predicted distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy. In patients with IDC who received adjuvant therapy, FF diameter greater than 8 mm was the factor that most accurately predicted bone metastasis, and the presence of tumor necrosis and ER−/PR− were very important predictive factors for metastasis to the lung. Ten or more nodal metastases (N3) were the factor that most accurately predicted liver metastasis. Based on these findings, FF characteristics can be concluded to be the most important histologic factors for predicting metastasis to the bone, the presence of tumor necrosis and ER−/PR− for predicting metastasis to the lung, and N3 for predicting metastasis to the liver. [Copyright &y& Elsevier]

Background: The aim of this study was to analyze on a multivariate basis the prognostic significance of pre-resection and post-resection pleural lavage cytologies in surgically resected primary non-small cell lung cancer (NSCLC) patients, in relation to pathologic TNM factors in a large cohort of almost 1,200 patients. Methods: From August 1992 through March 2001, pleural lavage cytology (PLC) was performed in 1,214 NSCLC patients without pleural effusion or dissemination undergoing pulmonary resection. The cytologic evaluation was classified into three categories: negative, suggestive, and positive. To investigate the impact on patient survival, PLC results were analyzed with conventional clinicopathologic factors. Results: Definitive pre-resection PLC result was obtained in 1,194 patients and 38 had a positive result. The 5-year survival rates were 27% if pre-resection PLC was positive and 71% if negative. Of 1,198 patients 54 had a positive post-resection PLC result. The 5-year survival rates were 10% if post-resection PLC was positive and 73% if negative. On multivariate analysis, post-resection PLC was an independent prognostic factor as significant as established clinicopathologic factors. Conclusions: Pre-resection and post-resection PLC should be recognized as an essential prognostic factor and should be performed in NSCLC patients without pleural effusion and dissemination. Post-PLC, compared with pre-PLC, had a greater and independent impact on survival and needs to be incorporated in the pathologic staging of NSCLC in the future. [Copyright &y& Elsevier]

A 44-year-old man experiencing repeated episodes of epistaxis and respiratory aspiration was diagnosed with nasopharyngeal cancer. Although the tumor completely disappeared after chemoradiation, six pulmonary nodules developed in the right lower lobe within a year. Right lower lobectomy was performed. All nodules were metastases of the nasopharyngeal cancer. Surgery was performed despite a poor prognosis, and there has been no recurrence 12 years postoperatively. Aerogenous metastases were suggested owing to right lower lobe localization and the patient’s symptoms and prolonged survival. The possibility of aerogenous spread and the efficacy of local therapy should be further studied. [ABSTRACT FROM AUTHOR]

We previously reported that loss of heterozygosity (LOH) in tuberous sclerosis 1 (TSC1)-gene-associated region on chromosome 9q34, was frequently observed in adenocarcinoma (AC) of the lung and its putative precursor lesion, atypical adenomatous hyperplasia (AAH). Some novel tumor suppressor gene for AC of the lung may be present in this region, and the TSC1 gene located on chromosome 9q34 is one candidate. The aim of this study was to determine whether the TSC1 gene itself acts as a tumor suppressor gene in the pathogenesis of AC of the lung. DNA extracted from frozen tumor tissue was used to screen 47 ACs of the lung for the presence of mutations in 21 coding exons of the TSC1 gene. When using these bulk tissue specimens, three different types of mutations were detected in five ACs. These positive samples were then submitted to laser capture microdissection to selectively collect tumor cells, DNA extraction and finally analysis of LOH and mutations of the TSC1 gene. Mutations were detected in three ACs, and LOH was detected in another AC. No mutations or LOH was detected in the other AC. Loss of heterozygosity and mutations were not detected simultaneously in the same tumor. We concluded that the TSC1 gene itself does not act as a tumor suppressor gene in the pathogenesis of AC of the lung in accordance with classical Knudsen’s two-hit hypothesis. However, the frequent LOH in AC and AAH shown in our previous studies indicate the following possibility in the etiology of AC of the lung: the presence of a novel tumor suppressor gene close to the TSC1 gene, aberrant promoter methylation, or haploid insufficiency of the TSC1 gene. [Copyright &y& Elsevier]

Overexpression of receptor-type tyrosine kinases in various cancers is associated with an aggressive tumor phenotype and poor outcome, but their expression had never been evaluated in large cell neuroendocrine carcinoma (LCNEC) of the lung. In the present study, we investigated the expression of three receptor tyrosine kinases, epidermal growth factor receptor (EGFR), c-erbB-2, and c-kit protein, by comparing surgically resected 40 LCNECs with other neuroendocrine (NE) lung tumors: 9 typical carcinoids (TCs), 5 atypical carcinoids (ACs), and 13 small cell lung carcinomas (SCLCs). None of the NE lung tumors showed expression of EFGR or c-erbB-2, but c-kit was overexpressed in 55% of the LCNEC tumor cells and 46% of the SCLC tumor cells. None of the clinicopathologic factors in either the LCNEC or SCLC patients correlated with c-kit overexpression. The finding that c-kit expression in LCNEC is similar to its expression in SCLC suggests that inhibition of c-kit may be effective as a therapy targeting LCNEC as well as SCLC. [Copyright &y& Elsevier]

• Effect of EGFR mutations on the prognosis of stage 0–I (8th TNM) differed by stage. • EGFR mutation was not prognostic in stage 0–IA. • In stage IB, OS and DSS were significantly better in mutant than in wild-type EGFR. • EGFR mutation was a favorable prognostic factor for OS and DSS in stage IB. This study evaluated the effect of EGFR mutation on early-stage non-small cell lung cancer (NSCLC) based on the 8th TNM classification. The study retrospectively examined 1231 patients who underwent curative resection for pathological stage 0–I (8th TNM classification) NSCLC and EGFR mutation analysis from January 2006 to December 2018 at Kanagawa Cancer Center. The disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS) of EGFR-mutant lung cancer (Mt) and EGFR wild-type lung cancer (Wt) patients at each stage were compared between two patient groups using the log-rank test. Cox regression analyses were performed to identify prognostic factors. The number of stage 0, IA1, IA2, IA3, and IB Mt/Wt patients was 79/92, 202/189, 145/144, 45/75, and 74/186, respectively. There was no statistically significant difference in DFS between Mt and Wt patients at any pathological stage. The 5-year OS of Mt/Wt patients was 96.9 %/98.5 % for stage 0 (p = 0.671), 92.2 %/92.2 % for stage IA1 (p = 0.997), 93.9 %/82.6 % for stage IA2 (p = 0.039), 87.3 %/91.4 % for stage IA3 (p = 0.768), and 85.3 %/69.3 % for stage IB (p = 0.017). The 5-year DSS of Mt/Wt patients was 95.7 %/95.4 % for stage IA2 (p = 0.684) and 93.2 %/77.5 % for stage IB (p = 0.016). In Cox regression analyses, Mt was not identified as a prognostic factor for OS among stage IA2 NSCLC patients (HR, 0.62; 95 % CI, 0.20–1.93; p = 0.413). However, Mt was a favorable prognostic factor for OS (HR, 0.44; 95 % CI, 0.19–1.00; p = 0.049) and DSS (HR, 0.38; 95 % CI, 0.17–0.87; p = 0.022) among stage IB NSCLC patients. EGFR mutation had no effect on the prognosis of stage 0–IA NSCLC but significantly affected the OS and DSS of stage IB NSCLC. Effect of EGFR mutations on postoperative prognosis of patients with stage 0–I NSCLC differed with each stage. [ABSTRACT FROM AUTHOR]

Prostate biopsy is essential in diagnosing prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) and magnetic resonance imaging (MRI)-transrectal ultrasound fusion-guided biopsy are also useful for diagnosis. However, the burden of implementing and maintaining these techniques should be considered. Therefore, we investigated the significance of non-standardized pre-biopsy MRI abnormalities (conditions not in accordance with PI-RADS) and subsequent targeted biopsy. We collected clinicopathological data, including the presence or absence of MRI abnormalities, through biopsies from January 2017 to February 2022 at the Kanagawa Cancer Center and performed statistical analyses. We enrolled in 1086 cases: MRI abnormalities were observed in 861 cases (79.3%). In these 861 cases, the adenocarcinoma detection rate, number of positive cores, and length of the highest Grade Group (GG) lesions were significantly higher. In the multivariate analysis, MRI abnormalities were the most significant factor for detecting adenocarcinoma of ≥GG 2 (odds ratio: 4.52, 95% confidence interval: 3.08–6.63). Targeted biopsy showed a higher percentage of positive cores with ≥GG2 and longer highest GG lesion lengths than systematic biopsy. Furthermore, the highest GG was upgraded in 109 of 788 cases by targeted biopsy. However, several adenocarcinomas (125/788; 15.9%) could not be detected using only targeted biopsy. Non-standardized MRI abnormalities are powerful predictors of cancer and grading. Targeted biopsies based on MRI abnormalities provide several benefits. Owing to the relatively low implementation hurdle, these biopsies may serve as a bridge until the ideal approaches are popularized if the limitations are well understood. [ABSTRACT FROM AUTHOR]

A 41-year-old female smoker presented with a vaginal mass. Gynecological examination showed a mass filling the uterine corpus, cervix, and vagina. A total abdominal hysterectomy was performed. Macroscopic findings included a large fragile mass involving the uterine cavity, cervix, and vagina. Histology revealed atypical ducts admixed with solid components consisting of large atypical cells. The initial pathological diagnosis was grade 3 endometrioid adenocarcinoma. The patient was designated as stage II according to the 2008 International Federation of Gynecology and Obstetrics (FIGO) staging. Two years later, two nodules were found in the upper lobe of the left lung, and the patient underwent an upper lobectomy. The masses, which exhibited solid and organoid growth patterns of large atypical cells, had histological characteristics of large cell neuroendocrine carcinoma (LCNEC) of the lung. However, the tumor was immunohistochemically positive for neuroendocrine markers, such as synaptophysin in addition to estrogen receptor and progesterone receptor, and the tumor was negative for thyroid transcription factor-1. These immunohistochemical results were almost identical to those of the solid portions of the uterine carcinoma. The final diagnosis was LCNEC combined with endometrioid adenocarcinoma of the uterine corpus and lung metastasis of the LCNEC component of the endometrial carcinoma. LCNEC often arises in the lung, but it rarely arises in other organs. Some patients with metastatic components exhibited only a LCNEC pattern although the primary tumor was a mixed carcinoma consisting of LCNEC and other histology, like the present case. LCNEC is often poorly differentiated, especially in extrapulmonary primary organ LCNEC. Therefore, pathologists should consider metastatic carcinoma when they encounter lung LCNEC in a patient with a preceding extrapulmonary carcinoma composed of a poorly differentiated component or LCNEC component, and they should clarify tumor immunohistochemical characteristics to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Objectives We analyzed and validated the prognostic utility of the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) for clinical stage IA lung adenocarcinoma (ADC) classification of adenocarcinoma (ADC). Methods We retrospectively reviewed 347 patients with clinical stage IA nonmucinous ADC, who had undergone complete resection. The histological subtype was classified according to the predominant subtype, as proposed by the new IASLC/ATS/ERS ADC classification. Results The histopathological subtypes, defined according to the new IASLC/ATS/ERS ADC classification, were ADC in situ (AIS) in 56 patients (16.1%), minimally invasive ADC (MIA) in 15 (4.3%), lepidic-predominant ADC in 109 (31.4%), papillary-predominant ADC in 70 (20.2%), acinar-predominant ADC in 61 (17.6%), solid-predominant ADC in 30 (8.6%), and micropapillary-predominant ADC in 6 (1.7%). The 5-year disease-free survival (DFS) rate was 100% for both AIS and MIA. All cases of recurrence involved invasive ADC. The 5-year DFS for lepidic-predominant ADC was 99.0%; acinar-predominant ADC, 82.4%; papillary-predominant ADC, 80.8%; solid-predominant ADC, 73.6%; and micropapillary-predominant ADC, 33.3%. The predominant subtype of ADC was significantly correlated with DFS ( P < 0.0001). Multivariate analysis indicated that the pathological stage was an independent predictor of DFS ( P = 0.031). Other independent predictors of increased risk of recurrence were the presence of vascular or lymphatic invasion (HR = 4.96, P = 0.001), and a pathological stage more advanced than IB (HR = 2.87, P = 0.010). The coincidence between the clinical stage and pathological stage was 79.8%. The stage migration was found in 53.3% of solid-predominat ADC and in 83.3% of micropapillary-predominant ADC. Conclusion The new IASLC/ATS/ERS ADC classification has prognostic value in predicting the recurrence and survival of patients with clinical stage IA ADC. The frequency of stage migration was found in more than half of solid and micropapillary predominant ADCs. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (MTB) can disseminate to extrapulmonary organs, particularly in severely immunosuppressed patients. Confirmation of active MTB infection is often difficult in subjects with a contraindication for invasive procedures. A case of disseminated MTB infection after hematopoietic stem cell transplantation is reported herein. Circulating cell-free DNA from the patient showed positive amplification of an MTB complex-specific sequence using a digital PCR technique. The MTB infection was confirmed by positive acid-fast staining and an approved quantitative PCR assay using liver tissue obtained at autopsy. The detection of MTB in circulating cell-free DNA using this technique may represent a less invasive diagnostic tool for pulmonary and extrapulmonary MTB infections. [ABSTRACT FROM AUTHOR]

Abstract: Background: Maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been found to have prognostic value. We previously reported the correlation between SUVmax and pathological invasive area, and determined an SUVmax cut-off value of 2.15 for predicting the recurrence potential of an invasive area of diameter 5mm. Here, we evaluate the validity of FDG-PET for prediction of recurrence in pathological stage IA lung adenocarcinoma. Methods: From February 2006 to May 2008, 100 patients with pathological stage IA lung adenocarcinoma underwent complete resection at our hospital. Tumors were classified as air-type or solid-type based on thin-section computed tomography (TS-CT) findings and the influence of TS-CT classification, SUVmax, and clinicopathologic features were evaluated in terms of the incidence of recurrence. Results: Unlike air-type adenocarcinomas, recurrent disease was detected in 8 of 62 solid-type adenocarcinomas. SUVmax and diameter of invasive area were significantly correlated with recurrence and a shorter time to recurrence. All 8 recurrent cases had pathological invasive area >5mm. All except one case of recurrence were solid-type adenocarcinomas with SUVmax≥2.15. Three-year disease-free survival rates were 100% in air-type adenocarcinomas, 97.1% in solid-type adenocarcinomas with SUVmax<2.15, and 74.1% in solid-type adenocarcinoma with SUVmax≥2.15. Conclusion: Combined evaluation of TS-CT classification and SUVmax had significant value in predicting recurrence in stage IA lung adenocarcinoma, reflecting the aggressiveness of primary lung adenocarcinoma. Prediction of tumor aggressiveness could contribute to decision-making regarding the choice of surgical procedure and treatment after surgery. [Copyright &y& Elsevier]

Abstract: Objective: We divided pulmonary adenocarcinoma of ≤20mm into air-containing and solid-density types based on a percentage reduction of the maximum tumor diameter in the mediastinal window image compared to the area in the lung window image on thin-section (TS) CT of ≥50% (air-containing type) and <50% (solid-density type). No relapse occurred in patients with air-containing type. The prognosis of solid-density type may be poor even when the tumor size is 20mm or smaller. We investigated whether CT findings for these tumors could serve as prognostic factors. Methods: The subjects were 105 patients with solid-density type pulmonary adenocarcinoma that was identified on TSCT and found to have a diameter of 20mm or smaller after surgical resection during the period from April 1997 to November 2004. Notches, air bronchogram, pleural retraction, spiculation, venous involvement, and ground glass opacity were examined on TSCT, and their associations with pathological findings (i.e., pleural invasion, lymphatic permeation, vascular invasion, lymph node metastasis, and Noguchi''s classification) and relapse were investigated using chi-square test and Cox proportional hazards model. Results: The incidence of relapse was significantly higher in cases with notches. The incidence of notches increased with tumor growth and notches were frequent in Noguchi type D tumors, reflecting poorly differentiated adenocarcinoma. Lymphatic permeation and type D cases were independent factors associated with a poor prognosis using Cox proportional hazards model. Conclusions: TSCT findings may be useful for prediction of the prognosis of solid-density type pulmonary adenocarcinoma. [Copyright &y& Elsevier]

Abstract: Study objectives: Previously, we reported that small pulmonary adenocarcinomas (tumor diameter 20mm or less) could be classified according to attenuation on thin-section CT (TS-CT) images as either ‘air-containing type’ or ‘solid-density type’ (Lung Cancer 2002;36:49–57). Air-containing type was defined as having areas where TOM (tumor opacity on mediastinal window images) was half or less than half the size of those noted on lung window images. Solid-density type was defined as having areas where TOM was greater than half the size of those noted on lung window images. Our findings indicated that there was no microscopic evidence of metastasis with air-type nor any relapses nor deaths, after resection. By contrast, patients with solid-density types demonstrated a poor prognosis. At this time, the histopathological characteristics of areas of TOM have not been fully investigated. The purpose of this study is to define the correlations between TOM and histopathological findings of small lung adenocarcinomas. Method: We retrospectively reviewed the records and CT scans of 134 patients, who had undergone surgical resection of peripheral adenocarcninomas. All tumor diameters were 20mm or less in size. All 134 patients had undergone TS-CT prior to surgery. TS-CT Images were acquired by a model X-Vigor/Real or an Aquillion CT scanner (Toshiba Medical Systems). Thin-section images of tumors were obtained at 135kVp at 250mAs with 1–2mm section thicknesses. All images were photographed using mediastinal (level, 40HU; width, 400HU) and lung (level, −600HU; width, 1600HU) window settings. We researched the histopathological components corresponding to the areas of TOM. Results: Areas of TOM demonstrated five possible histopathological findings; (1) collapse (C), (2) collapse with bronchioloalveolarcell carcinoma (CwB), (3) adenocarcinoma cells (Cells), (4) fibroblasts (F), and (5) mucus (M). Areas of TOM in air-containing type adenocarcinomas (52 cases) demonstrated predominantly C and/or CwB (C/CwB type, 44 cases). Areas of TOM in solid-density type adenocarcinomas (82 cases), in comparison, demonstrated predominantly Cells and/or Cells/F (Cell/F type, 67 cases). We noted a statistically significant difference between the histopathological findings of the areas of TOM of air-containing type and solid-density type tumors. The 39 cases of Cell/F type adenocarcinomas revealed microscopic evidence of metastasis (pleural involvement, vascular invasion, lymphatic permeation, or lymphnode metastasis). Whereas, no C/CwB type adenocarcinomas cases revealed any microscopic metastasis. The prognosis of C/CwB type after resection is better than for Cell/F type. Conclusion: We found that air-containing type adenocarcinomas demonstrated C/CwB type, and that solid-density type adenocarcinomas demonstrated Cell/F type. The histopathological findings of small pulmonary adenocarcinomas could be classified into three groups: C/CwB type, Cell/F type and M type. The prognosis of C/CwB type is better than for Cell/F type. Our results indicate that there are clear correlations between the areas of TOM and the histopathological components of small pulmonary adenocarcinomas. Therefore TS-CT findings are a useful aid in determining the best surgical methods. [Copyright &y& Elsevier]

Abstract: Diagnostic criteria to identify small lung adenocarcinomas that relapse after resection have yet to be established. For this purpose, we developed a mathematical logistic model in the present study. We collected data for patients with lung adenocarcinoma of 2cm or less in size: the original cohort comprised 28 men and 25 women and the validation cohort comprised 11 men. By entering five clinicopathological factors (vascular invasion, lymphatic permeation, histological subtype, papillary carcinoma component, and smoking status) into the logistic model, we calculated a predictive function for relapse after surgery. The obtained predictive function accurately classified the patients into a recurrence or non-recurrence group: the overall accuracy of the predictive model for recurrence established from the male patients in the original cohort was 86%. Our predictive model is, however, currently limited to male patients only, because the original cohort included only one female patient with relapse. By applying the logistic model to the validation cohort, six patients were classified into a recurrence group and the other five into a non-recurrence group: four of the six patients in a recurrence group had relapsed, while all five patients in the non-recurrence group were well during their follow-up periods. Although the predictive ability of the logistic model did not reach a statistical significance (P =0.0606), nine of the 11 (82%) patients in the validation cohort were correctly classified. Consequently, using a logistic predictive model consisting of the five clinicopathological factors might enable us to predict the recurrence of resected small-sized lung adenocarcinomas in male patients. [Copyright &y& Elsevier]

Differentiating small cell neuroendocrine (NE) carcinoma (SCNC) of the prostate from adenocarcinoma with NE differentiation based on morphological features alone sometimes can be challenging. Given that treatment strategies vary depending on histological type, an accurate diagnosis is critical. This study aimed to identify the accurate diagnostic factors for SCNC of the prostate. Furthermore, the possibility of novel treatment strategies through genetic analysis was also investigated. Prostate biopsies conducted in our hospital between January 2017 and May 2020 were included. Consequently, seven cases of SCNC and four cases of adenocarcinoma with NE differentiation were identified. No significant differences in the serum neuron-specific enolase, pro-gastrin-releasing peptide, and prostate-specific antigen (PSA) levels were observed between both tumors. The Ki-67 labeling index was significantly higher, and PSA immunoreactivity tended to be lower in SCNC. Although the morphology was undetectable, genetic analysis confirmed several mutations, including those of PIK3CA and TP53. The fact that morphological findings are not apparent indicates that genetic investigation rather than only morphological findings would be important in the future. In conclusion, given the heterogeneity of serum NE markers in SCNC, diagnosis based on these markers alone is challenging. A high Ki-67 labeling index and low PSA immunoreactivity may be useful for diagnosis, but p53 immunoreactivity is insufficient in distinguishing. Although further studies are required to interpret the results of the genetic analysis involving ALK , PIK3CA , and TP53 mutations, the results of our genetic analysis suggest that PIK3CA mutations in SCNC of the prostate may provide a novel therapeutic strategy. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: If non-invasive lung carcinomas are distinguishable on computed tomography (CT), limited surgery can be indicated before operation as a radical procedure. The purpose of this study is to define high resolution CT (HRCT) findings that indicate pathologic T1N0M0 tumor without vessel invasion. Patients and methods: We reviewed HRCT findings and pathological specimens of 98 consecutive patients underwent lobectomy or pneumonectomy with systematic hilar and mediastinal lymph node dissection from January 1996 to October 1999 for 101 pulmonary peripheral adenocarcinomas smaller than 3 cm in diameter on HRCT. A total of 101 consecutive surgically resected peripheral adenocarcinomas of the lung measuring 3.0 cm or less in the maximum dimension on HRCT were examined both radiologically and histologically. All CT scans ware reviewed by three chest radiologists or pulmonologists. The following parameters were measured on HRCT: the greatest diameter of tumor on found on all CT cuts (Td), the greatest diameter of consolidation found on all CT cuts (Cdmax), and the greatest diameter of consolidation found on a particular CT cut (Cd). Consolidation to tumor size ratio at respective maximum dimensions was calculated as Cdmax/Td, and consolidation to tumor size ratio on the slice image with the maximum tumor dimension was calculated as Cd/Td. One pathologist reviewed all pathological specimens to determine the size of tumor, evidence of vessel invasion, etc. without any information of HRCT, and we compared CT findings with pathological findings. Results: There was a statistically significant difference between tumors with pathologic T1N0M0 adenocarcinoma without vessel invasion (least invasive disease: LID) and tumors with lymph node involvement or vessel invasion (invasive disease: ID) in each parameter. However, only when tumors with Cdmax/Td smaller than 0.5 were selected as LID tumors, could ID tumors be eliminated from the LID group. Five-year survival rate of this population is 95.7%. Conclusion: Consolidation to tumor size ratio at respective maximum dimensions was the best predictor of non-invasive peripheral adenocarcinoma. [Copyright &y& Elsevier]

A right malar mass developed in a 68-year-old man who had undergone right upper and middle bilobectomy for lung cancer 2 years previously. The mass was diagnosed to be a malar metastasis from lung cancer and was surgically resected because no other metastases were found. The patient is well without signs of recurrence 5 years after resection of the malar mass. This is the first report of a malar metastasis from lung cancer and of successful resection for malar metastasis. [Copyright &y& Elsevier]

Abstract: Background: The prognostic value of maximum standardized uptake value (maxSUV) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is known for localized pulmonary adenocarcinoma, which is most commonly non-mucinous adenocarcinoma. We examined the validity of thin-section computed tomography (TS-CT) and FDG-PET findings in mucinous adenocarcinoma. Materials and Methods: TS-CT and FDG-PET were performed on 25 patients with mucinous lung adenocarcinoma that was subsequently resected between January 2009 and March 2013. Based on the percentage reduction of maximum tumor diameter on the mediastinal window image compared with the diameter on the lung window image on TS-CT, tumors were classified as air-type (≥50%) or solid-type (<50%). All resected specimens were pathologically diagnosed according to the International Association for the Study of Lung Cancer (IASLC) classification, and the diameter of the pathological invasive area was assessed. Results: Most mucinous adenocarcinomas were located in the lower lobe. All except two were classified as solid-type tumor on TS-CT. Multiple regression analysis revealed the correlation of maxSUV with pathological tumor size and diameter of pathological invasive area; these two parameters showed no significant correlation with each other (r =0.354, p =0.083). maxSUV was significantly lower for tumors with invasive area ≤5mm than for tumors with invasive area >5mm (1.62 vs. 3.77, p =0.01), but no statistically significant difference was found in terms of other pathological invasive findings such as the presence of lymphatic or vascular invasion, pleural involvement, or predominant histological subtype. Conclusions: Most mucinous adenocarcinomas had appearances of solid-type tumor on TS-CT. maxSUV on FDG-PET indicates the pathological invasive area in mucinous adenocarcinoma as well as non-mucinous adenocarcinoma. [Copyright &y& Elsevier]

Abstract: Introduction: To study the characteristics of lung cancer, appearing as small solid nodules on initial computed tomography (CT) findings, and to determine an appropriate follow-up duration so as to differentiate between malignancy and benign tumor. Methods: We analyzed the records of 34 patients who had undergone surgical resection of lung cancer, which appeared as small solid nodules on initial CT findings. We studied the CT findings, volume doubling times (VDT), follow-up durations, pathological and clinical findings. Results: VDT is classified as follows: (1) slow growth group (SGG), with a VDT of more than 700 days and (2) rapid growth group (RGG), with a VDT of less than 700 days. The median VDT of the SGG was 1083 days, and the RGG was 256 days (p <0.01). The median duration for follow-up of the SGG was 1218 days, and 179 days for the RGG. A statistical difference was noted in the follow-up durations (p <0.01). There were no statistical differences in the preoperative thin-section CT (TSCT) findings, or in the pathological findings. The RGG included more patients with smoking histories. The CT findings of RGG tended to reveal changed in base lung field such as emphysema, and lung fibrosis. Conclusions: Generally, lung cancer appearing as small solid nodules on initial CT findings grew rapidly, but there were some cases which displayed slow growth patterns. These cases required follow up for over two years, before diagnosis was possible. We concluded the appropriate maximum followup duration is three years. [Copyright &y& Elsevier]

Abstract: Background: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is commonly used to distinguish benign from malignant lesion. Recently, maximum standardized uptake value (SUVmax) on FDG-PET has found to have prognostic value. We examined the relationship between SUVmax and proliferative activities as indicated by maximum diameter of tumor opacity on mediastinal-window images (TOM), Ki-67 index, and diameter of the pathological invasive area in lung adenocarcinomas ≤30mm. Methods: Thin-section computed tomography (TS-CT) and FDG-PET were performed on 140 patients with resectable lung adenocarcinomas ≤30mm between March 2006 and May 2008. Tumors were classified as air-type or solid-type based on TS-CT findings. In all resected specimens, diameter of the pathological invasive area and Ki-67 index were assessed. Results: SUVmax was significantly lower for air-type than for solid-type tumors (0.97 vs. 3.96, p <0.0001). In solid-type tumors, SUVmax correlated with diameter of TOM (r =0.450, p <0.0001), Ki-67 index (r =0.567, p <0.0001), and diameter of the pathological invasive area (r =0.672, p <0.0001). In multiple regression analysis, SUVmax correlated significantly with Ki-67 index and diameter of the pathological invasive area but not with diameter of TOM. The cut-off value of SUVmax for predicting invasive area >5mm was determined as 2.15 by ROC analysis, with sensitivity of 88.3% and specificity of 84.6%. Conclusions: SUVmax correlated significantly with Ki-67 index and diameter of the pathological invasive area. The present results suggest the potential role of FDG-PET in predicting adenocarcinomas with invasive characteristics. [ABSTRACT FROM AUTHOR]