An adult patient with congenital pulmonary airway malformation and an esophageal cyst.

Combined occurrence of both congenital pulmonary airway malformation (CPAM) and esophageal cyst is rare and its diagnosis requires a carefully pathologic examination. Differential diagnoses include malignant neoplasms of pulmonary origin, pulmonary inflammatory pseudotumor, bronchogenic cysts and other congenital lesions of esophagus and lung. This paper presented a rare case report of a 31-year-old adult male with combined type III CPAM and an esophageal cyst. The patient was misdiagnosed and treated for pneumonia and tuberculosis before being admitted to our hospital. To eliminate symptoms and make an accurate diagnosis, the patient received a right upper lobectomy and a complete excision of the cyst lesion via thoracotomy. The patient remained uneventful during 1-year follow-up observation.

Cavernous sinus cavernous hemangioma: imaging features and therapeutic effect of Gamma Knife radiosurgery.

OBJECT: To investigate the imaging features of cavernous sinus cavernous hemangioma (CSCH) and evaluate the therapeutic effect of Gamma Knife radiosurgery (GKRS) in treatment of CSCH. METHODS AND MATERIALS: Fifteen patients with CSCH treated by GKRS in our institute, including 6 males and 9 females, age range 20-77 years old, were analyzed retrospectively. Three of them were given craniotomies as the initial therapy. All cases had performed conventional and contrast-enhanced MRI and 5 patients underwent dynamic enhanced MRI preoperatively. In 6 cases, the multi-directional continuous data of axial, coronal and sagittal enhanced MRI were acquired. Three cases performed digital subtraction angiography (DSA) simultaneously. The diagnoses of lesions were determined mainly depending on typical imaging features. In 3 patients, the diagnoses of CSCH were confirmed histopathologically. The radiation dosimetry was done with a goal of conformal and selective coverage of the lesion with a 50% prescription isodose line. The mean marginal dose constituted 13.4 Gy (range 10-16 Gy). After GKRS was performed, all patients were arranged regular clinical and MRI follow-up every 6 months during the first 12 months, and once per year thereafter. RESULTS: On MRI, the lesions were typically demonstrated as iso/hypo-intensities on T1WI and remarkable hyper-intensities on T2WI, and apparent homogeneous enhancement. The phenomenon of dynamic enhancement was found in 11 cases. The progressive enhancing process from heterogeneous to uniform was displayed in the 5 patients performed same-slice dynamic MRI, including imaging characteristics of 'edge to center' enhancement in 2 case. In the other 6 cases, the delayed homogeneous enhancement of lesion was observed. Ten patients obtained radiological follow-up results after GKRS. Reviewing the follow-up data of 8 patients during the period of 3-6 months, the lesions were apparently shrunk in 5 patients with shrinkage rate of 20.8-46.8%. In 4 patients with imaging follow-up during the period of 6-12 months, the lesions of 3 patients were remarkably shrunk with shrinkage rate of 53.5-81.7%. Four patients had imaging follow-up data over 12 months, and all their lesion sizes were reduced with shrinkage rate of 19-83.6%. The clinical presentations of all patients after GKRS were followed up during the period of 1-30 months. In 7 of 9 cases with headache, the symptom was improved; in 5 of 6 cases, facial hypesthesia was improved; in 6 of 9 cases with visual impairments, the visions were markedly improved; and in 8 cases with preoperative diplopia, the symptoms were all resolved. CONCLUSION: Although bright hyper-intensities on T2WI and significant homogeneous enhancement on contrast-enhanced T1WI are considered as typical imaging characteristics of CSCH, the dynamic process of progressive delayed enhancement on contrast-enhanced MR is more persuasive in diagnosis. According to our study, GKRS could be chosen as an effective and safe alternative treatment for CSCH. We consider that using relatively low marginal dose may get better effects in tumor shrinkage and protection of cranial nerves.

[A clinicopathologic and prognosis study of Epstein-Barr virus positive diffuse large B-cell lymphoma in west-southern China].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype, and the prognosis related factors of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) in west-southern China. METHODS: There were 42 cases of EBV+ DLBCL in a total 586 DLBCL, the clinical and pathologic profiles of these patients were evaluated. Immunohistochemical study and in situ hybridization (ISH) of EBER1/2 were performed on formalin fixed tissues by tissue chips. The prognosis related factors were analyzed. RESULTS: The median age of these 42 EBV+ DLBCL patients was 62.5 years. The male-to-female ratio was 2.23 : 1. The site of occurrence included lymph node (69.05%) and spleen, stomach, tonsil, nasal cavity and nasopharynx. The mostly common initial clinical presentations were non-specific symptoms, such as lymphadenopathy, splenomegaly, hepatomegaly, fever, and fatigue. Morphologically, the majority (90.48%, 38/42) were pleomorphic subtypes and only 4 cases (9.52%) were simplex subtypes. Immunophenotype showed non-GCB type of DLBCL was predominance (83.33%, 35/42) by Hans classification. The expression of CD30, CD5, BCL-2, P53 and NF-kappaB/ P65 were 52.38% (22/42), 54.76% (23/42), 54.76% (23/42), 87.5% (35/40) and 0% (0/40) respectively. Follow-up data was available in 23 (54.76%) patients, 14 (60.87%) patients died of the tumor. 5-years overall survival was 16.5%. The median survival time was 40 months. The expression of BCL-2, increased LDH level and starry-sky morphologic character were associated with a poor prognosis. CONCLUSION: EBV positive DLBCL is not uncommon. Most lesions locate in lymph nodes. Pleomorphic histologic subtype is predominant. The tumor has worse prognosis with increased LDH level, starry-sky morphologic character and BCL-2 expression.

Downregulation of ribosomal protein S6 inhibits the growth of non-small cell lung cancer by inducing cell cycle arrest, rather than apoptosis.

Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis.

Thymic epithelial tumors: a clinicopathologic study of 249 cases from a single institution.

The WHO histological classification for thymic epithelial tumors of 2004 edition is widely used, but its prognostic value is still controversial. In the present study we collected 249 Chinese patients with thymic epithelial tumors from West China Hospital of Sichuan University since 1999-2009 to assess the prognosis relating to tumor stages, histological classifications, MG and adjuvant therapy. There were 18 cases of type A (7.2%), 97 of type AB (39.0%), 22 of type B1 (8.8%), 63 of type B2 (25.3%), 16 of type B3 (6.5%) thymomas and 33 of thymic carcinomas (13.3%). According to the Massaoka staging, there were 107 patients in stage I (43%), 73 patients in stage II (29.3%), 50 patients in stage III (20.1%) and 19 in stage IV (7.6%). 101 patients (40.6%) complicated with MG, the incidence of MG was highest in type B3 thymomas, then in B2, none of thymic carcinomas complicated with MG. Cox regression analysis showed the Masaoka stage was the most important prognostic factor. Besides of staging, WHO histological classification was also an independent prognostic factor. The age, gender, MG and adjuvant therapy have no significant influence to the prognosis of the patients.

The potential interaction of MARCKS-related peptide and diltiazem on acrolein-induced airway mucus hypersecretion in rats.

UNLABELLED: Airway mucus hypersecretion is recognized as a pathophysiological feature of airway inflammation. Ca2+ entry and myristoylated alanine-rich C kinase substrate translocation are considered as important factors in such process. To investigate the potential interaction of myristoylated alanine-rich C kinase substrate (MARCKS)-related peptide and diltiazem on acrolein-induced airway mucus hypersecretion in rats, rat model of airway mucus hypersecretion was established by inhalation of acrolein on 12 consecutive days. MARCKS-related peptide, diltiazem, saline or the combination (MARCKS-related peptide+diltiazem) was intratracheally administered respectively. The rats were received pilocarpine to stimulate mucus release before sacrifices. The expression of Mucin5ac in bronchoalveolar lavage fluid (BALF) was measured by ELISA. Intracellular Muc5ac level was detected by immunohistochemical staining and western-blot. Muc5ac mRNA in lung was analyzed by RT-PCR. RESULTS: Instillation of MARCKS-related peptide attenuated the release of Muc5ac in BALF induced by acrolein(p<0.05). Diltiazem alone had no effect on mucus hypersecretion induced by acrolein. However, the release of Muc5ac in BALF was further reduced when challenged with simultaneous instillation with MARCKS-related peptide and diltiazem, compared with MARCKS-related peptide alone (p<0.05). The intracellular level of Muc5ac in lung was increased when treated with MARCKS-related peptide alone or MARCKS-related peptide plus diltiazem (p<0.05). Nevertheless, diltiazem alone did not take effect as above. CONCLUSIONS: In the model of airway mucus hypersecretion induced by acrolein, MARCKS-related peptide attenuated mucus secretion and the inhibitory effect was enhanced by diltiazem, which may be due to a further diminution of the intracellular free calcium concentration and retention of mucin within epithelial goblet cells.

Pulmonary sclerosing hemangioma: a unique epithelial neoplasm of the lung (report of 26 cases).

BACKGROUND: Pulmonary sclerosing hemangioma (SH) is an uncommon tumor. The aim of this study was to identify the origin of pulmonary SH and summarize its clinicopathologic features. METHODS: Data of 26 cases of pulmonary SH were collected and reviewed, including their clinical symptoms, chest radiological examinations, treatments, and pathological findings. RESULTS: Female patients of pulmonary SH were markedly frequent (n=23, 88.46%). Solitary mass or nodule in the lung fields was the most common manifestation (n=24, 92.31%), especially in the right middle lobe (n=9, 34.62%). There were two kinds of tumor cells: lining cells and round cells. All tumors contained a mixture of papillary, solid, sclerotic, and hemorrhagic patterns. Immunohistochemistry with a variable number of antibodies was performed for some cases. All of the detected specimens revealed strong reaction of lining cells with epithelial markers, such as thyroid transcription factor-1 (TTF-1), epithelial membrane antigen (EMA), cytokeratin (CK), pancytokeratin (PCK), and cytokeratin 7 (CK-7), while round cells were positive with TTF-1 and EMA. Until the end of last contact, none of the patients died or suffered from the recurrence of the disease after surgical treatment. CONCLUSIONS: Pulmonary SH is a unique neoplasm of the lung with a characteristic solitary mass or nodule. Pulmonary epithelium might be the primary origin of the tumor cells.

[Expressions and significances of CRABPII and E-FABP in non-small cell lung cancer].

BACKGROUND: The cellular retinoic acid-binding protein II (CRABPII) and epidermal fatty acid-binding protein (E-FABP) both serving as the transport protein of retinoic acid (RA), through RA signal transduction pathway, commit the cell to opposite fate, apoptosis or survival. The aim of this study is to investigate the expression of CRABPII and E-FABP and significance in non-small cell lung cancer (NSCLC) and their lymph node metastases with tissue microarray technique. METHODS: CRABPII and E-FABP proteins were detected in 54 normal lung tissues, 287 primary NSCLC tissues and 112 lymph node metastatic tissues by SP method of immunohistochemical staining. RESULTS: The expression level of CRABPII in the primary lesions was relevant to the gender of NSCLC patients, the metastasis and TNM staging of NSCLC (P<0.05), while the expression level of E-FABP was related to the grading and metastasis of NSCLC (P<0.05). The positive expression rate of E-FABP in NSCLC primary lesion was remarkably higher than that in adjacent normal lung tissues and lymph node metastases, respectively (P<0.05). The expression level of E-FABP had a recognizable advantage over that of CRABPII in NSCLC primary lesions (P<0.05). The differential expressions between CRABPII and E-FABP was correlated with the tumor size, grading, metastasis, TNM staging of NSCLC (P<0.05). The larger the tumor was and the later the TNM staging was, along with cancer metastasis, the more likely the expression of E-FABP would dominate. The expression of CRABPII and difference expression between CRABPII and E-FABP were closely related to the prognosis of NSCLC patients based on Kaplan-Meier survival analysis. CONCLUSIONS: E-FABP showed high exp ression in NSCLC, and the increased E-FABP expression may involved in the occurrence and development of NSCLC. CRABPII might have a negative effect in NSCLC progression, and its expression was negatively related to the prognosis of NSCLC patients.

Early lung cancer detection using the self-evaluation scoring questionnaire and chest digital radiography: a 3-year follow-up study in China.

The standard definition of high-risk individuals for lung cancer was not uniform and the value of chest digital radiography (DR) in lung cancer screening was still unproven. The aim of this study was to assess whether the original questionnaire named as "Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer" combined with DR examinations could detect early stage of lung cancer effectively. The Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer had been designed in previous studies. Subjects with scores over 116 points were regarded as high-risk individuals and underwent the current DR scans at least once a year from 2007 to 2009. Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary hilus and atelectasis, were considered to be positive and subjected to further special examinations. Efficacy of the scoring questionnaire combined with DR scans was estimated by 3-year results. Among 1,537 subjects, 13, 11, and 7 were diagnosed with lung cancer in the first, second, and third year, respectively, indicating the detection rate of 2.02 % (31/1,537). In addition, 77.42 % (24/31) of the patients were in stage I and 51.61 % (16/31) were adenocarcinomas. For the 31 cases, 28 were defined as detected cancers, while the other three were interval ones, only accounting for 0.20 % (3/1,504) of individuals with negative judgments. The protocol of Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer combined with DR scans is a cost-effective and safe approach to detect early stage of lung cancer.

[Expression and significance of Snail and Claudin-3 in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Epithelial-mesenchymal transition (EMT) is considered to be one of the major molecular mechanisms inducing tumor invasion and metastasis. The loss of epithelial cell polarity is a hallmark of the EMT process. Epithelial markers such as Claudin are lost in EMT. Snail is a major transcription factor governing EMT. Recent studies about the mechanism of tumor invasion and metastasis has proven that Snail could enhance the ability of many tumors' invasiveness. The aim of this study is to investigate the expression of Snail and Claudin-3 in non-small cell lung cancer (NSCLC) and its metastatic lymph node with tissue microarray technique, and to explore clinical significance of these two molecules expression in NSCLC. METHODS: Snail and Claudin-3 proteins were detected in cases of 59 adjacent normal lung tissues, 302 cases of primary NSCLC and 57 cases of lymph node metastatic tissues by MaxVision and EnVision method of immunohistochemical staining respectively. RESULTS: The expression of Snail in adjacent normal lung tissues, NSCLC primary foci and metastatic lymph node appeared upward tendency (P<0.05), and the expression of Claudin-3 in adjacent normal lung tissues, NSCLC primary foci and metastatic lymph node appeared weakened (P<0.05). Further more, expression 1evel of Snail and Claudin-3 proteins in NSCLC were related to the histological type (P<0.05). The Spearman correlation analysis showed that the expression of Snail and Claudin-3 was negatively correlated (r=-0.178, P=0.002). Kaplan-Meier survival analysis indicated that factors such as the tumor size, histological type, grading, metastasis, TNM staging, and difference expression between two proteins were associated with the postoperative survival rate of NSCLC patients (P<0.05). Multivariate analysis using Cox regression model identified that the tumor size, histological type, grading, metastasis and TNM staging were independent prognostic factors of NSCLC patients (P<0.05). CONCLUSIONS: Snail and Claudin-3 may play important roles in invasion and metastasis in NSCLC, So might be employed to evaluate the prognosis of NSCLC patients.

[Expressions and significance of TIMP-3 and mtp53 in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Tissue inhibitor of metalloproteinase-3 (TIMP-3) can regulate tumor infiltration and metastasis through multiple channels and is likely associated with mutant-type p53 (mtp53). This study detected the expressions of TIMP-3 and mtp53 in non-small cell lung cancer (NSCLC) and lymph node metastasis using tissue microarray and evaluated their significance. METHODS: TIMP-3 and mtp53 expressions were detected in 288 cases of NSCLC (NSCLC group), 106 cases of metastatic carcinoma in lymph nodes (metastasis group), and 24 cases of benign lesions in the bronchial mucosa epithelium (control group) by immunohistochemical staining (LSAB and Elivision). RESULTS: The expression of TIMP-3 in the NSCLC and metastasis groups was lower than that in the control group (P<0.001), but the reverse was true for the expression of mtp53 (P<0.001). TIMP-3 and mtp53 expressions differed between NSCLC with (P=0.015) and without (P=0.030) lymph node metastasis. TIMP-3 expression correlated with NSCLC grade (P=0.030), whereas mtp53 expression correlated with TNM stage (P=0.016) and NSCLC histological type (P=0.004). Moreover, the expressions of TIMP-3 and mtp53 were negative in NSCLC cases (P=0.008) and correlated with patient survival (P=0.011 and P=0.003, respectively). CONCLUSIONS: Low expression of TIMP-3 and high expression of mtp53 in NSCLC can promote tumor metastasis and inhibit each other. TIMP-3 and mtp53 are promising targets for studying the metastatic mechanism of NSCLC.

[An analysis of the clinicopathological features and misdiagnosis of 16 adults pulmonary sequestration].

OBJECTIVE: To explore the clinicopathological features of adult pulmonary sequestration and summarize the misdiagnosis experiences. METHODS: Data of 16 cases of adult pulmonary sequestration (18 years), who were confirmed by surgery and biopsy in our hospital were collected and reviewed. RESULTS: The median age of all the patients was 38.5 years. The female seemed to be more likely to suffer from adult pulmonary sequestration (n = 12) with cough to be the most frequent symptom (n = 9). CT scans revealed most of the lesions were located in the left lower lobes of the lungs (n = 9). Half of the lesions were characterized by pulmonary cyst-like changes and/or multiple cystic bronchiectasis (n = 8), followed by soft tissue mass in or out of the lung fields (n = 7). Enhanced CT scans showed abnormal arteries from the systemic circulation. Only two cases were diagnosed as pulmonary sequestration correctly in the primary diagnosis. The remaining were mostly misdiagnosed as pulmonary cyst-like changes with bronchiectasis (n = 6) or tumors (n = 6). According to the findings during surgery, 13 cases were intralobar pulmonary sequestrations; 3 cases were extralobars, whose tissues were all detected dysplasia and chronic inflammatory by histopathological examinations. CONCLUSIONS: The misdiagnosis rate of pulmonary sequestration is high because of its non-specific clinical symptoms. Since it is characterized by abnormal arteries and pulmonary dysplasia, enhanced CT scans should be used as a preferred screening method for suspected cases, especially for those middleaged patients with cystic or mass-like lesions in the left lower lobes of the lungs.

Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

Design and application of a self-evaluation questionnaire for individuals at a high-risk of lung cancer.

OBJECTIVE: The purpose of this study was to establish a comprehensive evaluation system to assess the risk factors of lung cancer for the general population. METHODS: With the method of evidence-based medicine, risk factors of lung cancer were identified and their risk assignments were calculated to design the Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer. Studies including more than 10 000 subjects were carried the out to confirm the questionnaire's value. RESULTS: The questionnaire consisted of 15 risk factors and their risk assignments, such as sex, age, smoking, female passive smoking, previous illness histories, exposure to harmful gases, mental depression and genetic susceptibility. In the population application, data from 30 lung cancer patients revealed its desired reliability and validity. The next pre-investigation, including 94 patients and 252 controls, confirmed its differentiating power, and encouraged a much larger-scale survey with 2161 subjects to determine the threshold (T) to identify high-risk individuals, the threshold was 116 points. According to this criterion, 1537 high-risk volunteers and 6556 controls were recruited to participate in a 3-year follow-up study from 2007 to 2009. There were 31 cases of lung cancer detected in the high-risk group, with a detection rate of 2.02%, significantly higher than that of the controls (5/6556, 0.08%), indicating an excellent predictive value of the questionnaire. CONCLUSIONS: The Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer was a good means for evaluating the risks of lung cancer.

[clinicopathological analysis of pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue].

BACKGROUND AND OBJECTIVE: As a rare disease, pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT), is often misdiagnosed. The aim of this study is to summarize the clinical and pathological features of this disease and improve the awareness of doctors. METHODS: Seven cases (female 5, male 2) diagnosed of PMZL-MALT in West China Hospital between November 2008 and November 2010, were analyzed retrospectively, including their symptoms, radiological findings, pathological examinations, treatment and prognosis. RESULTS: The median age of the patients were 62 years old (range 34-79 years). Six patients suffered from cough and sputum. Pulmonary consolidation was the most frequent manifestation, leading a misdiagnosis of pneumonia with CT examinations. Pathological diagnosis was obtained via fiberoptic bronchoscopy in six patients and percutaneous pulmonary biopsy for the rest one. In the seven cases, immunohistochemical results showed CD20(+), CD79a(+), while CD3 epsilon(-), CD5(-), CyclinD1(-), CD10(-), Bcl-2(-) and CD30(-). Additionally, the expression of Ki-67 was below 10%. Further PCR analysis showed evidence of immunoglobulin heavy chain gene rearrangement in tissues from six subjects. Based on the disease location and patients' wishes, compared with two cases just receiving symptomatic treatments, the other five ones took in chemotherapies. CONCLUSION: Since there were no specific clinical features for patients of PMZL-MALT, histopathological examination was the only effective means to confirm the diagnosis.

[A clinicopathological analysis of pulmonary lymphangioleiomyomatosis].

BACKGROUND AND OBJECTIVE: Pulmonary lymphangioleiomyomatosis (PLAM) is a rare tumor with unique clinicopathological features. The aim of this study is to investigate the clinicopathological features, the diagnosis and differential diagnosis of pulmonary lymphangioleiomyomatosis. METHODS: Three cases of PLAM were analyzed by light microscopy, immunohistochemistry and their clinical data, and the relative literatures were reviewed. RESULTS: Three cases of patients suffered from PLAM were the women in their reproductive aged, from 27 years to 45 years (mean 37.7 years), two cases of the HRCT showed bilateral diffuse cystic airspaces changed, and one case was the pneumothorax. The histopathological examination revealed the tumor was composed of the variably sized cystic spaces are lined by plaque-like or nodular aggregates of endothelial cells and the hyperplasia, smooth-muscle-like spindle cells which was along with the bronchi and the vessels. The immunohistochemistry showed that Des, Caldes, SMA, MSA, HMB-45, CD63, Vim, ER and PR were positive in the hyperplasia spindle cells, and there was no expression of MRAT-1. The FVIII, CD34 were positive in the capillary endothelial cells, and the D2-40 was positive in the lymphatic vessels. All the patients were alive without the recrudescence of the PLAM since the diagnosis, about 3 months to 25 months, and there was no LAM in their other systems. CONCLUSIONS: The most significant histopathological feature of pulmonary lymphangioleiomyomatosis was the progressive invasion of smooth muscle cells into the lymphatic vessels, and the blood vessels. The majority of the cases occur in the lungs of the women in the predominantly premenopausal and middle-age. It is a poor prognosis due to the progressive respiratory failure.

Activation of mammalian target of rapamycin pathway confers adverse outcome in nonsmall cell lung carcinoma.

BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis. RESULTS: Compared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage. CONCLUSIONS: This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC.

[Pleuropulmonary blastoma: a clinicopathological analysis].

BACKGROUND AND OBJECTIVE: Pleuropulmonary blastoma (PPB) is a rare malignant tumor with unique clinicopathological features. The aim of this study is to investigate the clinicopathological features, the diagnosis and differential diagnosis of pleuropulmonary blastoma. METHODS: Five cases of PPB were analyzed by light microscopy, immunohistochemistry and their clinical data, and the relative literatures were reviewed. RESULTS: Five cases of patients suffered from PPB were aged from 21 to 47 months (mean 32.8 months). Most of the masses were located in the thoracic cavities and 4 cases accompanied with pleural effusions. Histologically, these tumors included 1 case of type I PPB which showed pure cystic architecture; 2 cases were type II PPB which showed cystic and solid masses accompanied with rhabdomyoblastic differentiation and nodules of cartilage; the other 2 cases were type III PPB and characterized by absolute solid masses with anaplastic undifferentiated sarcomatous components. Immunohistochemical studies showed that tumor cells were positive for Vimentin and some for Desmin and Myogenin, the nodules of cartilage were positive for S-100. The tumor cells were negative for PCK, EMA and CD99. CONCLUSION: Pleuropulmonary blastoma is a rare and highly aggressive malignancy arising in the lung and pleural of infancy and early childhood. The type I, II and III PPB have unique clinicopathological features respectively. This kind of tumor should be distinguished from some benign and malignant diseases such as congenital cystic adenomatoid malformation (CCAM) and embryonal rhabdomyosarcoma.

The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer.

BACKGROUND: Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. METHODS: Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0). RESULTS: The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time. CONCLUSIONS: The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.

Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters.

BACKGROUND: Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-beta1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. METHODS: Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction. RESULTS: Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-beta1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs. CONCLUSIONS: These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-beta1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers.