Insight into the significance of Foxp3 + tumor-infiltrating lymphocytes in squamous cell lung cancer.

PURPOSE: Although developing a better understanding of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) might provide essential knowledge to predict response to immunotherapy and prognosis, our current knowledge about Foxp3 + TILs is inadequate. This study investigated the prognostic significance of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) in squamous cell lung cancer (SQ-LC) objectively. METHODS: Among patients with SQ-LC surgically resected in our institution between 2011 and 2017, those with pathological stage IA3-IIIA were immunohistochemically studied to evaluate Foxp3 + TILs in their tumor stroma. The impact of Foxp3 + TILs on relapse-free survival (RFS) was analyzed with Kaplan-Meier survival analysis and multivariate analysis using a Cox proportional hazards model/Fine-Gray model. RESULTS: This study analyzed 100 patients. Multivariate analysis showed that a large number of Foxp3 + TILs in the stroma does not associate with a poor prognosis, rather that a large number of Foxp3 + TILs (≥ 64 cells) tend to be associated with a more favorable prognosis than a small number of Foxp3 + TILs (< 64 cells) (large vs small number: HR, 0.56; 95% CI, 0.17-1.83; P = 0.34). Exploratory analysis also showed that in the two populations divided by a difference in Foxp3 expression levels, similar trends to the main analysis were observed. CONCLUSION: Our results showed that a large number of Foxp3 + TILs in the stroma may not associate with a poor prognosis in SQ-LC. To use the seemingly complicated information of Foxp3 + TILs as biomarkers, better understanding the diversity and heterogeneity of Foxp3 + TILs and analyzing their subpopulations that increase in the TME may be needed.

Micropapillary and solid components as high-grade patterns in IASLC grading system of lung adenocarcinoma: Clinical implications and management.

OBJECTIVES: The grading system proposed by the International Association for the Study of Lung Cancer is based on a combination of predominant histologic subtypes and the proportion of high-grade components with a cutoff of 20%. We aimed to examine the clinical implications of the grading system beyond the discrimination of patient prognosis, while assessing the biological differences among high-grade subtypes. METHODS: We retrospectively reviewed 648 consecutive patients with resected lung adenocarcinomas and examined their clinicopathologic, genotypic, and immunophenotypic features and treatment outcomes. Besides the differences among grades, the clinical impact of different high-grade components: micropapillary (MIP) and solid (SOL) patterns, was individually evaluated. RESULTS: Survival outcomes were well-stratified according to the grading system. Grade 3 tumors exhibited aggressive clinicopathologic features, while being an independent prognostic factor in multivariable analysis. A small proportion (<20 %) of high-grade components in grade 2 had a negative prognostic impact. The prognostic difference bordering on the 20 % cutoff of the MIP proportion was validated; however, the proportion of SOL component did not affect prognosis. A survival benefit from adjuvant chemotherapy was observed in grade 3 tumors regardless of histologic subtype, but not in grade 1-2 tumors. The molecular and immunophenotypic features were different among grades, but still heterogeneous in grade 3, with MIP harboring frequent EGFR mutation and SOL exhibiting high PD-L1 expression. The treatment outcome after recurrence was worse in grade 3, but tumors with MIP pattern had an equivalent prognosis to that of grade 1-2 tumors, reflecting the high frequency of molecular targeted therapy. CONCLUSIONS: In addition to stratifying patient prognosis, the current grading system could discriminate clinical course, therapeutic effects of adjuvant chemotherapy, and molecular and immunophenotypic features. Further stratification based on biological heterogeneity in grade 3 remains necessary to enhance the role of the grading system in guiding patient management.

Insight into the significance of CD8+ tumor-infiltrating lymphocytes in squamous cell lung cancer.

BACKGROUND: Although there are great expectations regarding the use of tumor-infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. METHODS: We objectively investigated the prognostic significance of tumor-infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ-LC). Among patients who underwent surgical resection of SQ-LC in 2011-2017, 100 patients with pathological stage IA3-III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse-free survival was analyzed using a Kaplan-Meier survival analysis and multivariate analyses using Fine-Gray and Cox proportional hazards models. RESULTS: The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29-1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21-1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91-7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. CONCLUSION: Our study provided partial but important information on the significance of CD8 + TILs in SQ-LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Prognostic implications of prostaglandin E-major urinary metabolite in resected non-small-cell lung cancer.

OBJECTIVES: Cyclooxygenase-2-derived prostaglandin E2 (PGE2) is highly involved in the promotion of cancer progression. The end product of this pathway, PGE-major urinary metabolite (PGE-MUM), is a stable metabolite of PGE2 that can be assessed non-invasively and repeatedly in urine samples. The aim of this study was to assess the dynamic changes in perioperative PGE-MUM levels and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS: Between December 2012 and March 2017, 211 patients who underwent complete resection for NSCLC were analysed prospectively. PGE-MUM levels in 2 spot urine samples taken 1 or 2 days preoperatively and 3-6 weeks postoperatively were measured using a radioimmunoassay kit. RESULTS: Elevated preoperative PGE-MUM levels were associated with tumour size, pleural invasion and advanced stage. Multivariable analysis revealed that age, pleural invasion, lymph node metastasis and postoperative PGE-MUM levels were independent prognostic factors. In matched pre- and postoperative urine samples obtained from patients who are eligible for adjuvant chemotherapy, an increase in PGE-MUM levels following resection was an independent prognostic factor (hazard ratio 3.017, P = 0.005). Adjuvant chemotherapy improved survival in patients with increased PGE-MUM levels after resection (5-year overall survival, 79.0 vs 50.4%, P = 0.027), whereas survival benefit was not observed in those with decreased PGE-MUM levels (5-year overall survival, 82.1 vs 82.3%, P = 0.442). CONCLUSIONS: Increased preoperative PGE-MUM levels can reflect tumour progression and postoperative PGE-MUM levels are a promising biomarker for survival after complete resection in patients with NSCLC. Perioperative changes in PGE-MUM levels may aid in determining the optimal eligibility for adjuvant chemotherapy.

Examination of the effectiveness of local therapy for oligo-recurrence of EGFR-mutated NSCLC.

BACKGROUND: The effectiveness of local therapy has been reported in patients with oligo-recurrence of non-small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR-mutated NSCLC. There is currently no consensus on treatment for oligo-recurrence of EGFR-mutated NSCLC. METHODS: From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo-recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR-mutated oligo-recurrence. RESULTS: We retrospectively examined and compared the effects of EGFR-TKIs with those of radical local therapy in patients with oligo-recurrent EGFR-mutated NSCLC. The five-year post-recurrence survival (PRS) rates of patients with EGFR-mutated oligo-recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo-recurrence (p = 0.551). CONCLUSION: Radical local therapy did not affect PRS in patients with oligo-recurrent EGFR-mutated NSCLC. Even in cases of oligo-recurrence, the administration of local therapy in patients with EGFR-mutated NSCLC might be carefully considered.

Factors associated with lymph node metastasis upstage after resection for patients with micropapillary lung adenocarcinoma.

BACKGROUND: Micropapillary adenocarcinoma has a poor prognostic histological pattern. Additionally, preoperative detection of lymph node metastases by preoperative examination is difficult in some patients with micropapillary adenocarcinoma, and postoperative upstage may occur. However, clinicopathological features of patients with micropapillary adenocarcinoma with nodal upstage have not been established, therefore this study aimed to identify the factors associated with potential lymph node metastases during preoperative examination to ensure effective surgical procedures. METHODS: Between January 2011 and December 2020, 1029 patients received complete resection for primary non-small-cell lung cancer by lobectomy or more extensive resection with systematic lymph node dissection at this institution. One hundred and thirty-one patients diagnosed with adenocarcinoma with micropapillary component were included in this study. The clinicopathological features of patients with nodal upstage whose postoperative N stage was more advanced than the preoperative N stage were examined. RESULTS: Forty patients had nodal upstage after resection. 18 F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) revealed that a maximum standardized uptake value (SUVmax) ≥5 for the primary lesion was significantly associated with postoperative nodal upstage. There were no significant differences in terms of sex, age, smoking history, surgical procedure, and diabetes. Among 38 patients with nodal upstage, 23 patients had no significant preoperative lymphadenopathy and showed no abnormal FDG uptake in the lymph nodes on 18 F-FDG-PET-CT, respectively. CONCLUSIONS: Lymph node metastases were suspected in patients preoperatively diagnosed with micropapillary adenocarcinoma with FDG SUVmax ≥5 for the primary tumor. Therefore, standard surgical resection and careful lymph node dissection should be performed for such patients.

Selection of preoperative stress electrocardiography test for appropriate patients with non-small cell lung cancer.

OBJECTIVE: Lobectomy is an established surgical procedure for treating non-small cell lung cancer; however, it significantly impacts postoperative cardiac function. The stress electrocardiography test is relatively easy to perform and is used to confirm the presence of coronary artery stenotic lesions. However, it has a low pre-test probability and may yield many false positives. We examined the factors that would enable the appropriate selection of patients for stress electrocardiography as a preoperative cardiovascular examination preceding lobectomy for non-small cell lung cancer. METHODS: From June 2016 to July 2018, 240 patients at our institution who underwent stress electrocardiography before lobectomy for primary lung cancer were included in this study. Clinical information was extracted from electronic medical records and evaluated retrospectively. Smoking history, diabetes, hypertension, dyslipidemia, and ischemic heart disease were considered risk factors for coronary artery stenosis. We determined the coronary risk factors that were applicable to each participant and calculated the total number of coronary risk factors as a risk score. RESULTS: Patients with coronary risk factor scores of ≥ 3 were significantly more likely to have abnormal stress electrocardiography results. In addition, these patients also underwent more comprehensive examinations to identify coronary diseases. There were no patients with complications that could be attributed to ischemic heart disease. CONCLUSION: Stress electrocardiography may be more useful before lobectomy in non-small cell lung cancer patients if the patients are appropriately selected, with the test utilized mainly in patients with coronary risk factor scores of ≥ 3.

Impact of the first surge of the coronavirus disease pandemic on general thoracic surgery practices in Kanagawa: a questionnaire survey by the Kanagawa General Thoracic Surgical Study Group.

OBJECTIVES: The first surge in severe acute respiratory syndrome coronavirus 2 infection had a significant impact on health care institutions. Understanding how the pandemic affected general thoracic surgery would provide valuable data for establishing a health care protocol for upcoming surges. METHODS: A questionnaire survey on coronavirus disease-related patient statistics and health care was conducted between February 2020 and June 2020 across 14 facilities affiliated with the Kanagawa General Thoracic Surgery Study Group. RESULTS: The average number of newly referred patients from February to June 2020 was 65% of that during the same period in 2019. Six facilities placed restrictions on medical care services, among which four restricted surgeries. At all institutions and those placed on surgical restriction, the total number of surgeries under general anesthesia was 92% and 78%, the total number of primary lung cancers was 94% and 86%, and the total number of surgeries for pneumothorax was 71% and 77% of that in the preceding year, respectively. Infection control and insufficient resources of the medical material were the most influential factors impacting the medical institutions' decision to restrict the services provided. CONCLUSIONS: Restrictions on surgery had a significant impact on the care provided by general thoracic surgery departments. To avoid patient inconvenience, establishing a collaborative system that refers patients to operational medical institutions in case of medical treatment restrictions may be useful.

Prognostic significance of galectin-3 expression in patients with resected NSCLC treated with platinum-based adjuvant chemotherapy.

BACKGROUND: Galectin-3 (GAL3), a protein encoded by the LGALS3 gene, plays diverse roles in cancer initiation, progression, and drug resistance. Accordingly, high GAL3 expression in tumor cells is associated with poor prognosis in non-small cell lung cancer (NSCLC). However, the prognostic impact of GAL3 expression on patients with resected NSCLC receiving platinum-based adjuvant chemotherapy (AC) remains unclear. This study aimed to determine the prognostic significance of GAL3 expression in NSCLC patients receiving platinum-based AC. METHODS: The study included 111 patients with completely resected stages II and IIIA NSCLC who were receiving platinum-based AC. GAL3 expression in cancer cells was evaluated immunohistochemically according to H-score ("histo score), with a score of ≥170 considered as high expression. The correlation of GAL3 expression with clinicopathological characteristics and survival was subsequently evaluated. RESULTS: In survival analysis, GAL3 expression was significantly associated with recurrence-free survival (RFS) and overall survival (OS). In multivariate analysis, GAL3 expression was an independent predictive factor of RFS rather than OS. CONCLUSIONS: GAL3 expression is a reliable biomarker to predict the prognosis of completely resected NSCLC patients receiving platinum-based AC.

Subxiphoid dual-port thymectomy for thymoma in a patient with post-aortic left brachiocephalic vein.

Post-aortic left brachiocephalic vein (PALBV) is one of the rare congenital vessel abnormalities associated with congenital heart disease. As only a few reports of surgical treatment for thymic tumor in patients with PALBV are available, this study reports the case of a patient with PALBV who underwent surgical treatment for thymoma. In a 60-year old woman, a nodule in the anterior mediastinum was detected on chest computed tomography (CT) during examination for arrhythmia. Thymoma was suspected, and surgical resection was considered. PALBV was detected on a contrast CT scan before surgery. Video-assisted thoracoscopic surgery was used to perform thymectomy using the subxiphoid dual-port approach. This method provided an appropriate view of the operative field and made it easy to confirm the presence of PALBV and identify the thymic veins branching off from the internal thoracic vein.

Comparison between quantitative computed tomography, scintigraphy, and anatomical methods for prediction of postoperative FEV1 and DLCO: effects of chronic obstructive pulmonary disease status and resected lobes.

BACKGROUND: Postoperative assessment of pulmonary function is important for estimating the risk of thoracic surgery and long-term disability following pulmonary resection, including predicted postoperative (ppo) forced expiratory volume (FEV) in one second (ppoFEV1) and percent predicted lung diffusion capacity for carbon monoxide (ppo%DLCO) estimation. The ppo values were compared using four different estimation methods between chronic obstructive pulmonary disease (COPD) and non-COPD patients and according to the resected lobe. METHODS: This prospective study included 59 eligible patients requiring single lobectomy and succeeded in performing pulmonary function tests at 3 and 12 months after lobectomy. The ppoFEV1 and ppo%DLCO were compared with poFEV1 and po%DLCO obtained at 3 and 12 months after lobectomy. The ppo values were estimated using the four usual methods: the 19-segment anatomical technique (S), perfusion scintigraphy (Q), quantitative CT (CT), and quantitative CT with low attenuation volume (CTLAV) subtraction. RESULTS: For non-COPD and COPD patients, the smallest mean difference between ppo and po values was observed by S for FEV1 and %DLCO. Based on the resected lobe, the smallest mean difference was observed by (I) Q for right upper lobectomy (RUL) excluding %DLCO at 12 months by S, (II) S for left upper lobectomy (LUL), (III) CT and CTLAV for right lower lobectomy (RLL), and (IV) CT and CTLAV for left lower lobectomy (LLL) at 12 months. The ppo values calculated by S for RUL (FEV1 at 3 and 12 months and %DLCO at 3 months) and by all four methods for LLL (FEV1 and %DLCO at 3 months) were smaller than the po values. CONCLUSIONS: The S method is adequate for calculating ppoFEV1 and ppo%DLCO when patients are classified as non-COPD and COPD. However, S sometimes overestimates the ppoFEV1 and ppo%DLCO when patients are classified according to the resected lobe. The CTLAV method may be the method of choice instead of S for calculating ppoFEV1 and ppo%DLCO in patients who undergo lung lobectomy despite the presence or absence of airflow limitation.

Resection of intra-pulmonary endometriosis by video-assisted thoracoscopic surgery under pre-operative CT-guided marking synchronized with menstrual cycle.

A 37-year-old woman experienced repeated catamenial hemoptysis. She had a history of intrauterine curettage. Computed tomography (CT) showed ground glass opacity (GGO) in the right upper lung lobe. We suspected pulmonary endometriosis and scheduled surgery coincides with her menstrual cycle. Then she underwent surgical resection after pre-operative CT-guided marking of the pulmonary endometrial lesion. A yellowish change of the pleura was observed near the marking and the lesion was resected using video-assisted thoracoscopic surgery. Histopathologically, endometrial glands and intimal interstitium were evident. She has no symptoms 2.5 years after surgery. In this case, scheduling the surgery at the time of her menstrual period and video-assisted thoracoscopic surgery (VATS) after CT-guided marking facilitated effective resection.

EGFR mutation genotyping and ALK status determination in liquid-based cytology samples of non-small cell lung cancer.

Personalised medicine for primary lung cancers (PLCs) requires molecular analysis of cancer tissue or cells. The primary objective of the present prospective study was to assess the concordance between epidermal growth factor receptor (EGFR) gene mutation detection and echinoderm microtubule-associated protein-like (EML) 4-anaplastic lymphoma kinase protein (ALK) expression using liquid-based cytology (LBC) samples and matched histology samples of PLC patients. A total of 117 patients who underwent surgical resection of non-small cell PLC were enrolled. Cytological specimens scratched from the resected PLC lesion were fixed in CytoRich Red. DNA extracted from LBC samples was examined for EGFR gene mutations. Anaplastic lymphoma kinase arrangement was analysed by immunostaining and fluorescence in situ hybridisation. Our patient cohort comprised 93 cases of adenocarcinoma, 16 squamous cell carcinoma, three adenosquamous carcinoma, two large cell neuroendocrine carcinoma, one pleomorphic carcinoma and two other cases. Sixty-six (58.4%) LBC samples harboured EGFR gene mutations. The overall concordance rate in EGFR gene mutation status, including minor mutations, between histologic and paired LBC specimens (N = 105) was 100%. The overall concordance rate of EGFR gene mutation status, including minor mutations and ALK status according to immunostains between histologic and paired LBC specimens, was 100% (105/105) and 100% (48/48), respectively. Genotyping and protein expression studies can be reliably performed using LBC samples prepared with CytoRich Red. Analysis of such samples may guide individual therapy in PLC patients.

Prognostic significance of IMMT expression in surgically-resected lung adenocarcinoma.

BACKGROUND: Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis. METHODS: IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival. RESULTS: High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation. CONCLUSION: Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.

Relevance of Intraoperative Pleural Lavage Cytology and Histologic Subtype in Lung Adenocarcinoma.

BACKGROUND: The association between pleural lavage cytology (PLC) and histologic subtype remains unknown. In this study, we evaluated the effect of a micropapillary pattern (MPP) in lung adenocarcinomas on results of PLC. METHODS: We retrospectively reviewed 600 consecutive patients with surgically resected pulmonary adenocarcinomas and investigated the relationship between PLC status and clinicopathologic factors, including a histologically identified MPP component. RESULTS: PLC was positive in 25 patients (4.2%). Positive PLC was significantly associated with MPP (p = 0.0001), lymph node metastasis (p = 0.01), and pleural invasion (p < 0.0001) according to multivariate analysis. Furthermore, the presence of MPP reinforced the effect of some established predictive factors, such as large tumor size, lymph node metastasis, pleural invasion, and lymphovascular invasion, on positive PLC. Two factors-MPP and positive PLC-were associated with a higher incidence of occult N2 lymph node metastases. The prognosis of adenocarcinomas in patients with MPP or positive PLC was significantly worse than that of patients without these features. Furthermore, the survival of MPP and positive PLC group (MPP+ PLC+) was significantly worse than that of MPP and negative PLC group (MPP+ PLC-, p = 0.03). CONCLUSIONS: The presence of MPP in lung adenocarcinoma can be an independent predictor of positive PLC. These two factors have complementary and synergistic roles as prognostic factors. Detailed preoperative or intraoperative examination of histologic subtype and PLC findings may provide important information for prediction of tumor progression and decisions regarding the surgical procedure.

Feasible and promising modified trans-subxiphoid thoracoscopic extended thymectomy for patients with myasthenia gravis.

BACKGROUND: We have used a promising, minimally invasive thoracoscopic technique of extended thymectomy for patients with myasthenia gravis (MG). The aim of this study was to report our promising technique, a modified single-port trans-subxiphoid approach (MTXA) and to compare perioperative outcomes and effects on MG between our approach and sternotomy. METHODS: We retrospectively reviewed records of all patients undergoing extended thymectomy for MG and/or thymoma between January 1, 2010 and December 31, 2016. The patients were divided into the MTXA group and Sternotomy group. RESULTS: Of the 50 consecutive patients undergoing extended thymectomy for MG, finally, 13 patients undergoing our MTXA extended thymectomy technique were compared with 20 patients undergoing extended thymectomy via sternotomy. Intraoperative blood loss, postoperative length of stay, and C-reactive protein value on postoperative day 1 were significantly more favorable in the MTXA group than the Sternotomy group (P<0.0001, P=0.0040 and P=0.0073, respectively). Furthermore, no significant differences in the frequency of patients with improvement of their Quantitative Myasthenia Gravis score and/or MG-Activities of Daily Living scale, decrease in the serum level of acetylcholine receptor antibody, and dose reduction of oral prednisone were seen between the two groups. CONCLUSIONS: Our approach to extended thymectomy might be more favorable than sternotomy in patients with MG.

Lung metastases of a uterine tumor resembling ovarian sex-cord tumor: Report of a rare case.

Uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a rare type of uterine neoplasm. We present an extremely rare case of lung metastases from a UTROSCT focusing on the cytologic features. A 69-year-old Japanese woman was admitted to our hospital for further examination and treatment for abnormal shadows in the right lung field. She had a history of total hysterectomy for UTROSCT. Moreover, she underwent wedge resection of the right middle lobe for lung metastasis of UTROSCT in 2011. Enhanced chest computed tomography scan revealed a solid nodule 8 mm in diameter in the right upper lobe and a well-demarcated 33-mm mass or nodule in the lower lobe. Under the diagnosis of metastatic tumors from UTROSCT, she underwent wedge resection of the right upper lobe and segmentectomy of the right S8. Cytologically, the stump smear from the resected tumors revealed round to short spindle-shaped neoplastic small cells arranged in sheets with poor cohesion and no cluster formation. The nuclei were irregular in shape, and the chromatin was finely granular, uniform, and increased. Mitotic figures were not observed. Necrosis was absent in the background. Histologically, the final diagnosis was UTROSCT group II. This is an unusual case of metastatic UTROSCT to the lung in which the cytologic features are described.

Molecular alterations in a new cell line (KU-Lu-MPPt3) established from a human lung adenocarcinoma with a micropapillary pattern.

PURPOSE: Lung adenocarcinomas with a micropapillary pattern (MPP) are characterized by more frequent and pronounced vascular invasion, higher incidence and more advanced lymph node involvement and poorer prognosis than papillary adenocarcinomas without an MPP. Here we established a new lung cancer cell line featuring micropapillary structure. METHODS: A 73-year-old never-smoker Japanese female, presenting with an abnormal chest shadow, was diagnosed with a clinical T2aN0M0 Stage IB lung adenocarcinoma and underwent left upper lobectomy with mediastinal lymph node dissection. Pathological study demonstrated a T2aN2M0 Stage IIIA micropapillary adenocarcinoma. Tumor cells were obtained from freshly resected lung material and used to establish the KU-Lu-MPPt3 cell line. RESULTS: The KU-Lu-MPPt3 cells featured adherent monolayers, adherent tufts, and suspended tufts without adhesion under the same culture conditions. The cells were positive for cytokeratin, epithelial cell-adhesion molecules, E-cadherin, mucin-1, thyroid transcription factor-1, vimentin, and anti-programmed death ligand 1. Xenograft tumors clearly demonstrated micropapillary structures. Sequencing and fragment analysis of the epidermal growth factor receptor in the primary tumor tissue and KU-Lu-MPPt3 cells revealed an in-frame deletion E746-A750 in exon 19. CONCLUSIONS: This cell line represents a new model system for molecular studies of lung adenocarcinoma which may be suitable for investigation of cancer spread and also for development of molecular-targeting and immunotherapies, both in vitro and in vivo.