Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners.

BACKGROUND: Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. METHODS: A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. RESULTS: Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. CONCLUSIONS: Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Increased expression levels of integrin α9ß1 and CD11b on circulating neutrophils and elevated serum IL-17A in elderly aspiration pneumonia.

BACKGROUND: Repeated aspiration pneumonia is a serious problem in the elderly. In aspiration pneumonia, neutrophils play an important role in acute lung injury, while CD18-independent neutrophil transmigration pathways have also been reported in acid-aspiration pneumonia animal models. However, the involvement of IL-17A and ß1 integrin still remains unclear. The ß1 integrin subfamily integrin α9ß1 has been shown to be expressed on human neutrophils and to mediate adhesion to extracellular matrix proteins including the vascular cell adhesion molecule-1. OBJECTIVES: To elucidate the possible involvement of ß1 integrin subfamily and IL-17A in aspiration pneumonia. METHODS: We analyzed the expression levels of CD11b, CD18 and integrin α9ß1 in circulating neutrophils and serum concentration of IL-17A, IL-22 and IL-23 in elderly aspiration pneumonia patients (n = 32, 14 males and 18 females, 78.8 ± 3.9 years old) at 2 time points (on the day of admission before starting antibiotics and the day after finishing antibiotics) and compared the results with those of a control group (n = 30, 13 males and 17 females, 76.1 ± 3.4 years old). RESULTS: Recombinant IL-17A stimulated integrin α9ß1 and CD11b expression levels in healthy human neutrophils in vitro. The expression levels of integrin α9ß1 and CD11b in circulating neutrophils were significantly higher in pneumonia patients compared with the controls. In addition, serum IL-17A concentration was significantly increased in pneumonia patients. Integrin α9ß1 levels positively correlated with serum IL-17A and CD18 expression levels. CONCLUSIONS: These findings suggest a potential role of integrin α9ß1 expressed in neutrophils and elevated serum IL-17A in extravasation of neutrophils in cases of aspiration pneumonia.

Evaluation of the efficacy and safety of biapenem against pneumonia in the elderly and a study on its pharmacokinetics.

Although biapenem is used in the treatment of pneumonia, the clinical data on elderly patients are yet insufficient. Therefore, the purpose of this study was evaluating the efficacy and safety of biapenem against pneumonia in the elderly and its pharmacokinetics. The subjects were patients 65 years of age or older with pneumonia. Biapenem (300 mg) was administered once to three times per day. For some cases, the drug concentrations in plasma were measured chronologically. The clinical efficacy was evaluated in reference to the improvement in subjective symptoms and objective opinion. The primary outcome was efficacy rate at the end of treatment. Biapenem was effective in 17 of 20 subject cases (85.0 %). Regarding safety, although 4 cases experienced hepatic dysfunction and 1 case had nausea, these effects were not severe in all cases and administration was continued. There was no deterioration of renal function associated with biapenem. In 13 cases in which the trough value of biapenem was measured, there were no unacceptable side effects and the trough values were generally low. It is believed that biapenem (300 mg once to three times a day), even when taken by elderly people, does not accumulate and that the dosage is safe and appropriate. The changes in the predicted concentrations calculated with the pharmacokinetic-pharmacodynamic (PK-PD) software, which is based on previously reported population pharmacokinetic parameters, and those in the measured concentrations approximately matched. It is useful to plan biapenem administration using the PK-PD software when performing antibiotic chemical treatment.

Efficacy and safety of piperacillin/tazobactam versus biapenem in late elderly patients with nursing- and healthcare-associated pneumonia.

Pneumonia is associated with an extremely high mortality rate in patients of late elderly age. Piperacillin/tazobactam and carbapenems are drugs of first choice for hospitalized patients with potentially resistant bacteria. We compared the efficacy and safety of piperacillin/tazobactam and biapenem. Among elderly patients with nursing- and healthcare-associated pneumonia, we extracted 53 patients treated with piperacillin/tazobactam and 53 patients treated with biapenem who were matched for sex, age, and severity of pneumonia. The average age was more than 80 years; most of the patients were middle- to oldest old in age. Although clinical efficacy was equally good, patients in the piperacillin/tazobactam group achieved significantly faster improvements on chest X-ray and body temperature on day 7. However, in the piperacillin/tazobactam group, nephrotoxicity frequently led to a need for a reduction in the dose or complete discontinuation of treatment. The average age of patients who developed significant nephrotoxicity was high, at 83.2 years. The biapenem group exhibited significantly better continuation of treatment than the piperacillin/tazobactam group. Toxicity profiles were different between the two groups. Hepatic toxicity was significantly higher in the biapenem group, whereas nephrotoxicity was significantly more common in the piperacillin/tazobactam group. Rate of decrease in bacteria was equally good between the two groups. Providing careful follow-up and conducting more detailed examinations, including studies to determine optimal dose and timing of administration, are necessary for the treatment of late elderly patients with numerous underlying diseases and potential organ dysfunctions.

Comparison of hemagglutination inhibition assay and enzyme immunoassay for determination of mumps and rubella immune status in health care personnel.

BACKGROUND: Screening tests are available to determine immunity to vaccine-preventable diseases, such as mumps and rubella. We aimed to define better assay for detecting immune status of health care personnel to vaccine-preventable diseases. METHODS: Mumps and rubella antibodies of health care personnel at Shimane University Hospital were examined by hemagglutination inhibition assay (HI), comparing with those by enzyme immunoassay (EIA). RESULTS: A total of 910 sera from health care personnel were tested. There was poor correlation between HI and EIA in detecting mumps antibodies with correlation coefficient values (r) = 0.190 (P < 0.001), but in rubella antibodies HI and EIA were relatively well correlated (r = 0.930, P < 0.001). Seropositivity rate of HI versus EIA was found to be 65.7 versus 93.2, and 89.5 versus 86.5% for mumps and rubella, respectively. As compared with EIA, HI identified sixfold larger seronegative subjects in mumps. Moreover, in mumps, 88.8% of seronegative subjects detected by HI were seropositive by EIA, while 3.7% of seropositive subjects detected by HI were seronegative by EIA. In rubella, 2.1% of seronegative subjects detected by HI were seropositive by EIA, and 1.7% of seropositive by HI was seronegative by EIA. CONCLUSION: Considerable difference between HI and EIA in determining immune status of health care personnel to mumps and rubella suggests beneficial use of EIA for the identification of accurate susceptible personnel who subsequently undergo an effective vaccination programs. Seroprevalence survey of health care personnel by using appropriate assay is essential for prevention and infection control strategies in health care settings.

Nedaplatin and irinotecan for patients with recurrent small cell lung cancer.

BACKGROUND: No standard second-line combination chemotherapy has yet been established for patients with recurrent small cell lung cancer (RSCLC). METHODS: Patients with RSCLC were treated with nedaplatin (NP) at 50 mg/m2 and irinotecan (CPT) at 50 mg/m2 on days 1 and 8 every 4 weeks for four cycles. RESULTS: The clinical outcomes of 12 patients (9 male and 3 female; age range 48-76 years, median 62 years) were retrospectively analyzed. Seven of the patients showed sensitive relapse. Two patients had a performance status of 2. Nine of the patients were able to receive 4 to 6 courses of NP and CPT chemotherapy. Grade 3 or 4 anemia, neutropenia and thrombocytopenia occurred in 25.0%, 50.0% and 41.7% of patients, respectively. There were no grade 3 or 4 non-hematologic toxicities except for febrile neutropenia in 1 patient. There was no treatment-related death. Nine patients achieved PR, and the objective response rate was 75.0%. The median survival time was 11.1 months (range 4.8 to 31.3+ months) and the 1-year survival rate was 50.0%. CONCLUSION: NP and CPT in combination are effective and safe for patients with RSCLC.

[A case of acute hypersensitivity pneumonia in a worker at a feather duvet factory].

A 44-year-old woman was admitted to our hospital because of a 15-month history of exertional dyspnea, nonproductive cough and fever. Thoracic high-resolution computed tomography (HRCT) showed centrilobular ground-glass opacities distributed in bilateral lung fields. She had worked at a down quilt factory and had been exposed to a large amount of feathers for 5 years. A peripheral lymphocyte proliferation test by positive was positive for pigeon serum. We diagnosed bird-related hypersensitivity pneumonia. After quitting her job, improvement of her clinical symptoms and chest imaging findings were observed and she has been free of relapse.

[A case of germ-cell tumor of the mediastinum].

An 18-year-old man complaining of chest pain was admitted to our hospital. Contrast-enhanced chest computed tomography (CT) showed an anterior mediastinal tumor with patchy enhanced lesions in the peripheral and poorly-enhanced central areas. His serum alpha fetoprotein (AFP) level was high. FDG-PET imaging indicated intense FDG uptake in the mediastinal tumor (SUVmax was 11.2), but no other abnormal FDG uptake, including in his testes, was detected. CT-guided needle biopsy revealed necrotizing tissue, including immature cartilage-like tissue. Based on these clinical features, we diagnosed mixed-type germ cell tumor originating from the mediastinum. Bleomycin, etoposide and cisplatin combination chemotherapy was administered every 3 weeks, for 4 cycles. His serum AFP level declined during the treatment course, and the mediastinal tumor decreased in size. After 4 cycles of chemotherapy, the residual tumor was resected completely and no viable cells were detected in the resected tumor. Tumor recurrence has not been detected for more than 9 months after surgery without adjuvant chemotherapy at the time of writing.

[A case of pulmonary malignant lymphoma with endobronchial involvement with repeated improvement or progress of atelectasis].

A 68-year-old woman, presented to the emergency department with dry cough and increased shortness of breath. Her chest X-ray showed complete atelectasis of the right upper lobe. Her chest examination was significant for diffuse wheezing, and she was treated with corticosteroids. Fourteen hours after her arrival, wheezing and atelectasis on the chest X-ray disappeared. However, 10 days after admission, her chest X-ray showed atelectasis of the right lower lobe, and right middle and lower lobes atelectasis on 17 days, then became complete atelectasis of the lung on 22 days after admission. Bronchoscopic findings showed severe stenosis of the right upper lobe bronchus and truncus intermedius. Pathologic examination of the transbronchoscopic biopsy specimen showed diffuse large B-cell lymphoma. We diagnosed primary pulmonary malignant lymphoma because she had no extrapulmonary diseases. An extremely rare case of pulmonary malignant lymphoma with endobronchial involvement in which the site of atelectasis changed rapidly was reported.

Up-regulated integrinα4ß1 on systemic lymphocytes and serum IL-17A in interstitial pneumonia.

BACKGROUND AND AIMS: In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrinα4ß1 on leukocytes has previously been reported in animal models. Although the integrinα4ß1 expression level is known to be up-regulated by inflammatory cytokines, the involvement of interleukin (IL)-17A is unclear. The purpose of this study is to address the possible involvement of integrinα4ß1 on circulating lymphocytes and its correlation with serum IL-17A in interstitial lung diseases (ILDs). METHODS: We measured the expression levels of integrinα4ß1 on peripheral lymphocytes and the serum concentration of IL-17A and IL-23 in subjects with ILDs (n = 27; 14 males and 13 females, 66.7 ± 7.8 years old) and control subjects (n = 10; 5 males and 5 females, 66.6 ± 4.6 years old). RESULTS: Recombinant IL-17A up-regulated expression levels of integrinα4ß1 on healthy human lymphocytes in an in vitro experiment. Expression levels of integrinα4ß1 were significantly higher in those with acute hypersensitivity pneumonitis (HP) and non-specific IP (NSIP) compared with control. Serum IL-17A concentration was also significantly increased in acute HP and NSIP subjects compared with control. And IL-17A concentration positively correlated with integrinα4ß1 expression level (P < 0.05). Serum IL-23 was below the minimal detectable level in all subjects. CONCLUSIONS: These findings suggest that up-regulated levels of integrinα4ß1 on systemic lymphocytes and elevated serum IL-17A might be involved in the extravasation of lymphocytes in IP.

Multiple logistic regression analysis of risk factors in elderly pneumonia patients: QTc interval prolongation as a prognostic factor.

BACKGROUND: Acute pneumonia is a serious problem in the elderly and various risk factors have already been reported, but the involvement of QTc interval prolongation remains uncertain. The aim of this study was to elucidate the prognostic factors for the development of pneumonia in elderly patients and to study the possible involvement of QTc interval prolongation. METHODS: The subjects were 249 hospitalized pneumonia patients more than 65 years old in Aki-Ohta Hospital from January 2010 to December 2013. Community-acquired pneumonia patients and nursing care and healthcare-associated pneumonia patients were included in the study. The pneumonia severity index, vital signs, blood chemistry data and ECG findings were retrospectively compared using multiple logistic regression analysis. RESULTS: 39 patients died within 30 days from onset. The clinical features related to poor prognosis were: advanced age, past history of cerebral vascular disease and/or diabetes mellitus, decreased serum albumin level, higher CURB-65 or PORT index scores and QTc interval prolongation. Patients showing a prolonged QTc interval had a higher mortality than those with a normal QTc interval. A prolonged QTc interval was not related to serum calcium concentration and/or treatment with QTc prolongation drug, clarithromycin or azithromycin, but related to age, lower albumin concentration and past history of diabetes mellitus. CONCLUSIONS: These findings suggest potential prognostic factors for pneumonia in elderly patients, including a prolonged QTc interval (> 0.44 seconds).

Association of EPAS1 gene rs4953354 polymorphism with susceptibility to lung adenocarcinoma in female Japanese non-smokers.

INTRODUCTION: Hypoxia-inducible factor-2α (also called endothelial periodic acid-Schiff domain protein 1 [EPAS1]) seems to play an important role in some carcinogenesis, though there is no information on the relationship between single nucleotide polymorphism of EPAS1 and lung cancer development. The aim of this study was to explore a possible association of the EPAS1 gene rs4953354 polymorphism with susceptibility to lung cancer. METHODS: A case-control study of 346 patients with non-small-cell lung carcinoma (adenocarcinoma = 249, squamous cell carcinoma = 97) and 247 healthy control subjects was carried out. A/G polymorphism within an intron 2 of the EPAS1 (rs4953354) was determined by direct sequencing. RESULTS: A frequency of lung adenocarcinoma patients with a minor allele G (A/G or G/G genotype) at the rs4953354 was much higher than that of controls (odds ratio, 1.800; 95% confidence interval, 1.161-2.791; p = 0.008). This association was more evident when analyzed using female never-smokers (odds ratio, 3.31; 95% confidence interval, 1.21-9.01; p = 0.017). Mutations in epidermal growth factor receptor tended to be frequent in patients with G allele at the rs4953354, compared with those with other genotypes. CONCLUSION: The EPAS1 rs4953354 may be a potentially susceptible marker for development of lung adenocarcinoma, especially in female never-smokers.

Immunohistochemical comparison of biomarker expression in biopsy and surgical specimens of non-small cell lung cancer.

BACKGROUND: Single tumors may show heterogeneity, and it is unclear whether biomarker expression in surgical and diagnostic biopsy samples correlates. MATERIALS AND METHODS: We retrospectively identified lung cancer patients who were diagnosed by biopsy and underwent surgery between January 2007 and October 2010 at the Shimane University Hospital, Shimane, Japan. Thirty-two patients were identified. The expression of four predictive biomarkers was assessed, namely excision repair cross-complementing gene 1 (ERCC1), ribonucleotide diphosphate reductase M1 (RRM1), thymidylate synthase (TS), and class III beta-tubulin (BT). We also compared immunohistochemical staining in diagnostic biopsy and corresponding resected surgical samples. RESULTS: Moderate correlation was seen between the expression of ERCC1, RRM1, TS, and BT in the biopsy and surgical specimens, with r values of 0.512 (p=0.003), 0.411 (p=0.020), 0.475 (p=0.006), and 0.404 (p=0.027), respectively. CONCLUSION: Assessment of biopsy samples with immunohistochemical staining is a feasible and reliable method for use in clinical decision making.

Periaortitis associated with anti-neutrophil cytoplasmic antibodies induced by bevacizumab combination therapy.

Drug-induced vessel vasculitis is a rare complication of chemotherapy. In particular, few reports have investigated drug-induced large vessel vasculitis. We herein report the case of a 57-year-old woman with advanced lung adenocarcinoma who developed perinuclear anti-neutrophil cytoplastic antibodies (p-ANCA)-positive periaortitis induced by bevacizumab combination chemotherapy. With the increasing use of combination therapy with bevacizumab, the incidence of vascular complications will potentially increase. A noninfectious fever occurring during chemotherapy might be a sign of vasculitis; therefore, we must ensure that possible periaortitis is not overlooked.

Comparative analysis of a complement fixation assay and enzyme immunoassay to determine the seroprevalence of measles and varicella in a survey of healthcare workers.

OBJECTIVE: Seroprevalence surveys of healthcare workers for vaccine-preventable diseases, including measles and varicella, are essential for disease prevention and infection control programmes. The purpose of this study was to compare the complement fixation (CF) assay and an enzyme immunoassay (EIA) to determine the prevalence of immunoglobulin G antibodies directed against measles and varicella viruses in healthcare workers. METHODS: Antimeasles and antivaricella antibody titres were measured simultaneously in serum samples from healthcare workers employed at a Japanese university hospital, using the CF assay and an EIA. RESULTS: Serum samples were obtained from 898 healthcare workers. Seropositivity rates determined using the CF assay and EIA were 67.8% versus 94.0%, respectively, for measles, and 83.2% versus 97.6% for varicella. Compared with EIA, a nine- and 22-fold higher number of seronegative subjects was identified by the CF assay for measles and varicella, respectively. CONCLUSION: Differences between the CF assay and EIA in detecting seronegative or seropositive healthcare workers for measles and varicella suggest that undertaking a seroprevalence survey using an EIA, rather than a CF assay, would more accurately determine susceptibility to vaccine-preventable diseases, in healthcare settings.

Cyclooxygenase 2 1195G > A polymorphism is associated with chronic obstructive pulmonary disease in Japanese and Chinese patients.

BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed during airway inflammation in chronic obstructive pulmonary disease (COPD) patients. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to COPD. We investigated the association between COX-2 (-765G > C, -1195G > A) polymorphisms and COPD susceptibility in Japanese and Chinese patients. METHODS: COX-2 genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism in 230 COPD patients (103 Japanese and 127 Chinese) and 273 healthy controls (129 Japanese and 144 Chinese). RESULTS: The frequency of -1195AA homozygote was significantly higher than the controls in Chinese COPD (adjusted OR = 2.43, 95%CI 1.14 - 4.19), Japanese COPD (adjusted OR = 2.25, 95%CI 1.06 - 4.76) and combined COPD groups (adjusted OR = 2.26, 95%CI 1.34 - 3.99). There was no difference in COX-2 -765G > C polymorphism between COPD and control groups in either Japanese or Chinese, while more Chinese individuals carried the -765C allele than Japanese in both groups (15.3% vs. 2.9% in COPD, 18.8% vs. 5.5% in control). Chinese individuals with the haplotype -765G:-1195A were at higher risk for COPD (adjusted OR = 1.93, 95%CI 1.05 - 3.55). CONCLUSIONS: The COX-2 -1195AA genotype is associated with increased risk for COPD in both Japanese and Chinese individuals. Although COX-2 -765G > C polymorphism was not associated with COPD in either ethnic group, the -765C allele frequency was higher in Chinese than Japanese and haplotype -765G-1195A may confer susceptibility to COPD in Chinese.

Phase I clinical and pharmacokinetic study of bi-weekly carboplatin/paclitaxel chemotherapy in elderly patients with advanced non-small cell lung cancer.

AIM: We evaluated the pharmacokinetics and quality of life of elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with bi-weekly carboplatin and paclitaxel chemotherapy, and determined the maximum tolerated dose (MTD) of this treatment. PATIENTS AND METHODS: Eligible patients had histologically- or cytologically-proven inoperable NSCLC, age of 70 years or older, no prior treatment, and Eastern Cooperative Oncology Group performance status 0-2. Paclitaxel was administered in combination with carboplatin under a bi-weekly schedule. We determined the plasma concentrations of both drugs during therapy. RESULTS: The median patient age was 80 years. Using carboplatin at AUC 3, the MTD of paclitaxel was 100 mg/m(2). Both hematological and non-hematological toxicities were mostly mild and manageable. Although paclitaxel is predominantly metabolized in the liver, clearance was decreased in patients with lower estimated glomerular filtration rate. CONCLUSION: Bi-weekly treatment, as described here, is feasible for elderly patients as a conventional regimen, particularly in the outpatient setting, due to its lower toxicity.

Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma.

BACKGROUND: Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases. PATIENTS AND METHODS: We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations. RESULTS: SMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations. CONCLUSIONS: SMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.

Stromal micropapillary pattern predominant lung adenocarcinoma--a report of two cases.

Generally, adenocarcinomas with micropapillary pattern, featuring small papillary tufts lacking a central fibrovascular core, are thought to have poor prognosis. This pattern has been described in various organs. However, tumor cells with micropapillary pattern of lung adenocarcinoma are more often seen to float within alveolar spaces (aerogenous micropapillary pattern, AMP) than in fibrotic stroma like other organs (stromal micropapillary pattern, SMP) and SMP predominant lung adenocarcinoma (SMPPLA) has not been well described yet. We presented two cases of SMPPLA which were found in the last four years. Both the cases showed more than 50% of SMP in the tumor area. The majority of the stromal micropapillary clusters expressed MUC1 and epithelial membrane antigen along the outer surface of cell membrane. On the other hand, connective tissues surrounding stromal micropapillary clusters showed no reactivity for epithelial markers (thyroid transcription factor-1 and cytokeratin) or endothelial marker (D2-40 and CD34). It means clusters of SMP do not exist within air space or lymphatic or vessel lumens. The tumors with SMP often presented lymphatic permeation and vessel invasion, and intriguingly, one of the two cases showed metastasis to the mediastinal lymph node. Additionally, both the cases showed EGFR point mutations of exon 21. These results suggest that SMPPLA might be associated with poor prognosis and effective for EGFR tyrosine kinase inhibitors.