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Showing papers on "Large cell published in 2012"


Journal ArticleDOI
TL;DR: The finding of B cl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.
Abstract: Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

441 citations


Journal ArticleDOI
TL;DR: In this article, the p40 antibody was compared to p63 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas, adenocarcinomas, and large cell lymphomas.

338 citations


Journal ArticleDOI
TL;DR: It is revealed that both NRF2 and p62 are independent prognostic factors for NSCLC, and the prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenOCarcinomas and squamous cell carcinoma.
Abstract: p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non-small-cell lung cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same cohort. The expression of NRF2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma (n = 72), squamous cell carcinoma (n = 31), and large cell carcinoma (n = 6). Accumulation of NRF2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF2 did not correlate with each other, but both were associated with worse lung cancer-specific survival (P = 0.0003 for NRF2; P = 0.0130 for p62). NRF2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma (P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF2 and p62 were both independent factors predicting worse lung cancer-specific survival (P < 0.0001 for NRF2 and P = 0.04 for p62). This study revealed that both NRF2 and p62 are independent prognostic factors for NSCLC. The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma.

180 citations


Journal ArticleDOI
TL;DR: It is concluded that carcinoids and high grade NE lung carcinomas are separate biological entities and do not comprise one spectrum of pulmonary NETs, implying the need to reconsider both diagnostic as well as therapeutic approaches for these different groups of malignancies.

160 citations


Journal ArticleDOI
TL;DR: It is concluded that the clinical behavior of ALCL associated with breast implants is heterogeneous, and patients who present with effusion without a distinct mass have an indolent disease course, similar to CD30+ lymphoproliferative disorder of skin.
Abstract: We report 13 cases of anaplastic large cell lymphoma (ALCL) associated with breast implants. Patient age ranged from 39 to 68 years, and the interval from implant to ALCL was 4 to 29 years. All tumors were composed of large, pleomorphic cells that were CD30 and ALK1, and all 7 cases assessed had monoclonal T-cell receptor γ-chain rearrangements. Two patient subgroups were identified. Ten patients presented with effusion surrounded by fibrous capsule without a grossly identifiable tumor mass. Nine patients had stage I and 1 had stage II disease. Eight patients underwent implant removal and capsulectomy. Four patients received chemotherapy and 4 radiation therapy. All patients were alive without disease at last follow-up. A second subgroup of 3 patients had effusion and a distinct mass adjacent to the implant. One patient had stage I and 2 stage II disease. One patient had a 3-year history of lymphomatoid papulosis, and 1 patient had a 1-year history of CD30 T-cell lymphoma adjacent to the breast before the diagnosis of ALCL associated with breast implant. Two patients received chemotherapy and 1 radiation therapy. Two patients died 2 and 12 years after diagnosis, respectively. We conclude that the clinical behavior of ALCL associated with breast implants is heterogeneous. Patients who present with effusion without a distinct mass have an indolent disease course, similar to CD30 lymphoproliferative disorder of skin. In contrast, patients who present with a distinct mass may have advanced stage or possibly systemic disease and have a poorer prognosis.

146 citations


Journal ArticleDOI
15 May 2012-PLOS ONE
TL;DR: Evidence is presented that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer and support the notion thatSOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe.
Abstract: Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2, and NOTCH1 was detected in side population (SP) cells than in non-side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline-inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2, and NOTCH1 in xenografted NOD/SCID mice. By using the RNA-Seq method, an additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer.

145 citations


Journal ArticleDOI
31 Jul 2012-Cancers
TL;DR: Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting and the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies.
Abstract: Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1-G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

124 citations


Journal ArticleDOI
TL;DR: Results suggest that extrathoracic synchronous solitary metastasis of pN0 adenocarcinoma may achieve long-term survival in the case of lung resection with or without metastasis resection.
Abstract: OBJECTIVES: Patients with extrathoracic synchronous solitary metastasis and non-small cell lung cancer (NSCLC) are rare. The effectiveness of both tumour sites resection is difficult to evaluate because of the high variability among clinical studies. We reviewed our experience regarding the management and prognosis of these patients. METHODS: The charts of 4668 patients who underwent lung cancer surgery from 1983 to 2006 were retrospectively reviewed. We analysed the epidemiology, treatment, pathology and prognostic characteristics of those with extrathoracic synchronous solitary metastasis amenable to lung cancer surgery on a curative intend. RESULTS: There were 94 patients (sex ratio M/F 3.2/1, mean age 56 years). Surgery included pneumonectomy (n= 27), lobectomy (n= 65) and exploratory thoracotomy (n= 2). Pathology revealed adenocarcinomas (n= 57), squamous cell carcinoma (n= 20), large cell carcinoma (n= 14) and other NSCLC histology (n= 3). Lymphatic extension was N0 (n= 46), N1 (n= 17) and N2 (n= 31). Metastasis involved the brain (n= 57), adrenal gland (n= 12), bone (n= 14), liver (n= 5) and skin (n= 6). Sixty-nine metastases were resected. Five-year survival rate was 16% (median 13 months). Induction therapy, adenocarcinoma, N0 staging and lobectomy were criteria of better prognosis, but metastasis resection was not. CONCLUSIONS: These results suggest that extrathoracic synchronous solitary metastasis of pN0 adenocarcinoma may achieve longterm survival in the case of lung resection with or without metastasis resection. This pattern may reflect a specific tumour biology whose solitary metastasis benefits both from surgical or non-surgical treatment.

77 citations


Journal ArticleDOI
TL;DR: The prognosis for patients with either primary or secondary lymphomatous heart involvement is usually poor; late diagnosis is one of the major factors affecting outcome.
Abstract: Lymphoma of the heart and pericardium is usually present as one aspect of disseminated disease and rarely occurs as a primary malignancy. It accounts for 1.3% of primary cardiac tumors and 0.5% of extranodal lymphomas. Cardiac lymphomas are most commonly diffuse large cell lymphomas and frequently manifest as an ill-defined, infiltrative mass. Atrial location is typical; the right atrium is most often affected. Pericardial thickening or effusion is often a common early feature of disease. Infiltration of atrial or ventricular walls with extension along epicardial surfaces is also a notable feature. At computed tomography, the attenuation of cardiac lymphoma may be similar to or lower than that of normal myocardium. At magnetic resonance imaging, it has variable signal intensity and contrast enhancement. Clinical manifestations may include pericardial effusion, cardiac arrhythmias, and a variety of nonspecific electrocardiographic abnormalities, notably first- to third-degree atrioventricular block. Treatment most commonly includes anthracycline-based chemotherapy and anti-CD20 treatment. Chemotherapy has been used alone or combined with radiation therapy. Palliative surgery has been performed, mainly for tumor debulking. The prognosis for patients with either primary or secondary lymphomatous heart involvement is usually poor; late diagnosis is one of the major factors affecting outcome.

75 citations


Journal ArticleDOI
TL;DR: The present data obtained using various histological types of human lung cancer cell lines in vitro illustrate the cytostatic nature of metformin and its cytoprotective properties against cisplatin.
Abstract: The oral antidiabetic agent metformin has anticancer properties, probably via adenosine monophosphate-activated protein kinase activation. In the present study, growth inhibition was assessed by a clonogenic and by a cell survival assay, apoptosis induction was assessed by Hoechst staining and caspase activities and cell cycle alteration after exposure to metformin, and the interaction of metformin with cisplatin in vitro were elucidated in four human lung cancer cell lines representing squamous, adeno-, large cell and small cell carcinoma. Clonogenicity and cell proliferation were inhibited by metformin in all the cell lines examined. This inhibitory effect was not specific to cancer cells because it was also observed in a non-transformed human mesothelial cell line and in mouse fibroblast cell lines. Inhibition of clonogenicity was observed only when the cells were exposed to metformin for a long period, (10 days) and the surviving fraction, obtained after inhibiting proliferation by increasing the dose, reached a plateau at approximately 0.1-0.3, indicating the cytostatic characteristics of metformin. Metformin induced significant apoptosis only in the small cell carcinoma cell line. A tendency of cell cycle accumulation at the G0/G1 phase was observed in all four cell lines. Cisplatin, in a dose-dependent manner, severely antagonized the growth inhibitory effect of metformin, and even reversed the effect in three cell lines but not in the adenocarcinoma cell line. The present data obtained using various histological types of human lung cancer cell lines in vitro illustrate the cytostatic nature of metformin and its cytoprotective properties against cisplatin.

65 citations


Journal ArticleDOI
TL;DR: Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers, and there is a need for prospective studies because this population is frequently excluded from participating in cancer trials.

Journal ArticleDOI
TL;DR: These cases highlight the importance of assessing HHV8 in an anaplastic tumor that arises in a human immunodeficiency virus-positive patient and further contributes to the limited literature currently available for extracavitary PEL.

Journal ArticleDOI
TL;DR: Lung cancer survival rates in Spain are poor, with better prognosis in women, especially among patients aged under 55 years at diagnosis, or those with small cell carcinoma, and the role played by histologic type is evaluated.

Journal ArticleDOI
TL;DR: Novel evidence is provided that decreases in miR-96 could represent a mechanism underlying the aberrant expression of ALK in cancer cells, and these effects were associated with reduced proliferation, colony formation, and migration of AlK-expressing cancer cells.
Abstract: Anaplastic lymphoma kinase (ALK) constitutes a part of the oncogenic fusion proteins nucleophosmin-ALK and echinoderm microtubule–associated protein like 4–ALK, which are aberrantly expressed in a subset of T-cell anaplastic large-cell lymphoma and non–small-cell lung cancer, respectively. The expression of mutated, constitutively active ALK also occurs in a subset of neuroblastoma tumors. ALK is believed to play an important role in promoting tumor survival. Nevertheless, the mechanisms underlying the expression of ALK in cancer cells are not completely known. MicroRNA (miR) has been implicated in the regulation of the expression of both oncogenes and tumor suppressor genes. We tested the hypothesis that the expression of ALK could be regulated by miR. Three Internet-based algorithms identified miR-96 to potentially bind with the ALK 3′-untranslated region. Notably, miR-96 levels were markedly decreased in ALK-expressing cancer cell lines and primary human tumors compared with their normal cellular and tissue counterparts. Transfection of the cell lines with miR-96 decreased levels of the different forms of ALK protein, without significant effects on ALK mRNA. Furthermore, miR-96 decreased the phosphorylation of ALK target proteins, including Akt, STAT3, JNK, and type I insulin-like growth factor receptor, and it down-regulated JunB. These effects were associated with reduced proliferation, colony formation, and migration of ALK-expressing cancer cells. These data provide novel evidence that decreases in miR-96 could represent a mechanism underlying the aberrant expression of ALK in cancer cells.

Journal ArticleDOI
TL;DR: Napsin-A immunoreactivity has the potential to misguide a pathologist to conclude a metastasis from renal, thyroid, or endometrial carcinoma as a primary lung adenocarcinoma, therefore, when there is a need to rule out lung metastases from other organs, implementation of other biologically specific markers should be considered.
Abstract: BACKGROUND Distinguishing between primary lung adenocarcinoma and metastatic adenocarcinoma of lung before planning patient treatment is clinically important. Immunohistochemical markers play an important role in classification of primary lung tumors and are an effective method for separating metastatic tumors from primary pulmonary carcinoma. In this study, we evaluated the expression of Napsin-A in primary pulmonary carcinoma and some cases of nonpulmonary adenocarcinoma. MATERIALS AND METHODS The Napsin-A immunohistochemical evaluation was carried out using surgical specimens from 18 cases of adenocarcinoma, 19 cases of squamous cell carcinoma, 2 cases of large cell carcinoma, 1 case of bronchoalveolar carcinoma of lung, as well as 33 cases of renal cell carcinoma, 30 cases of thyroid neoplasm, 31 cases of colonic carcinoma, 31 cases of breast carcinoma, and 30 cases of endometrial adenocarcinoma. RESULTS For the primary lung carcinoma cases, all 18 cases of adenocarcinoma, 2 of the large cell carcinomas, and the 1 bronchioloalveolar carcinoma case were positive for Napsin-A. For the thyroid tumors, Napsin-A was positive in 14 cases of papillary carcinoma. Napsin-A was positive for 87.5% of papillary renal cell carcinoma cases and in 29.4% of clear cell carcinoma cases and for 1 chromophobe renal cell carcinoma case. Three out of 30 endometrial adenocarcinomas showed Napsin-A reactivity. All squamous cell carcinoma cases and adenocarcinomas of colon and breast were negative for Napsin-A. CONCLUSIONS Napsin-A is a useful marker for differentiating primary lung adenocarcinoma from squamous cell carcinoma. However, Napsin-A immunoreactivity has the potential to misguide a pathologist to conclude a metastasis from renal, thyroid, or endometrial carcinoma as a primary lung adenocarcinoma. Therefore, when there is a need to rule out lung metastasis from other organs, implementation of other biologically specific markers should be considered.

Journal ArticleDOI
TL;DR: High-level ERBB2 amplification occurs in a small fraction of lung cancers with a strong propensity to high-grade adenocarcinomas, andeterogeneity of amplification may limit the utility of anti-HER2 therapy in some of these tumors.

Journal ArticleDOI
TL;DR: The pathological and clinical details of recently described and selected unusual variants of UC are reported, relating to large nested and nested variant of UC, large cell undifferentiated carcinoma, lymphoepithelioma-like carcinomas, osteoclast rich undifferentiate carcinoma and pleomorphic giant cell carcinoma.

Journal ArticleDOI
TL;DR: Thymic neuroendocrine tumors carry a poor prognosis and the results showed that a vast majority of carcinoids in the thymus correspond to ACs, indicating that typical carcinoid is a very rare entity.
Abstract: Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available. To date, only a few studies have reported a substantial number of cases of NEC.1-5 The current evaluation of thymic neuroendocrine tumors is dependent on criteria for doing primary pulmonary neuroendocrine tumors.6 According to the World Health Organization (WHO), they are classified into four histological types: typical carcinoid (TC), atypical carcinoid (AC), small cell neuroendocrine cell carcinoma (SCNEC), and large cell neuroendocrine cell carcinoma (LCNEC).6 Most series have used the term "carcinoid" to describe these tumors. Some previous studies indicate that carcinoid tumors arising in the thymus may show a more aggressive behavior than their pulmonary counterparts.6 In recent years, attempts have been made to validate tumor grading and the range of clinical behavior.7-9 Still, however, little is known about the classification of thymic neuroendocrine tumors and their clinical behavior because of their rarity. In this study, we retrospectively reviewed 21 cases of surgically resected thymic NECs and evaluated their pathologic and clinical features.

Book
23 Oct 2012
TL;DR: The occurrence of lALD demonstrates the importance of competent immunosurveillance in the development of lymphoid neoplasias, which may have therapeutic relevance too.
Abstract: The incidence of malignant lymphomas is significantly higher in patients who have congenital or acquired immunodeficiencies Although there are some differences between these immunodeficiency-associated lymphoproliferative disorders (lALD), they share several features: a tendency to present in extranodal sites, particularly the central nervous system and gastrointestinal tract, rapid clinical progression when untreated, diffuse large cell histology, B-cell origin and association with the Epstein-Barr virus (EBV) In the presence of disturbed T-cell function EBV may induce not only prolonged proliferation but also transformation of B-cells In patients with primary, congenital immunodeficiency the incidence of lALD ranges from 07% for patients with X-linked agammaglobulinemia to 12–15% in patients with ataxia telangiectasia In patients with post-transplant lymphoproliferative disorders (PT-LPD) the incidence varies from 05% after bone marrow transplantation to 10% after heart-lung transplantation PT-LPD are often characterized by a polymorphic cell population Recent studies identified three categories: plasmacytic hyperplasia, poly morphic lymphoproliferation and B-cell non-Hodgkin’s lymphoma (NHL) The plasmacytic hyperplasias are of polyclonal composition, while polymorphic lymphoproliferations and NHL are monoclonal The precise risk of lymphoma development in HIV infection is not defined, but estimates suggest a prevalence of 3–4% HIV-related NHLs are divisible by site of manifestation into systemic, primary central nervous system and body-cavity lymphomas, and by pathology into Burkitfs and Burkitt’s-like lymphoma, and diffuse large cell lymphoma (DLCL) In about 90% of cases these lymphomas are of monoclonal B-cell composition Recent experiences suggest a link between therapy with immunosuppressive drugs (methotrexate, azathioprine, cyclophospamide, etc) and development of lALD, best supported by the increased rate of lALD in patients with rheumatoid arthritis who receive methotrexate therapy The occurrence of lALD demonstrates the importance of competent immunosurveillance in the development of lymphoid neoplasias, which may have therapeutic relevance too

Journal ArticleDOI
TL;DR: It is hypothesized that primary breast neuroendocrine carcinoma differentiates from the epithelial cells during the carcinogenesis process; the prognosis of non-small cell primary NECB seems to improve as the amount of mucinous component increases in the tumor specimen.
Abstract: Primary neuroendocrine cancer of the breast (NECB) is an extremely rare tumor. In 2003, the World Health Organization (WHO) recognized this category with three well-described subtypes: small cell, large cell, and carcinoid-like carcinoma; very few peer-review publications based on the WHO definition were encountered in the literature, and we conducted a literature search to investigate the reported incidence, diagnosis, prognosis, hormone receptor status, and treatment options for this rare tumor. Confirming the breast as an origin of neuroendocrine tumor represents a challenge. The diagnosis is mainly dependent on the exclusion of other extra-mammary organs based on clinical, radiological, and pathological data. Except for the very rare type small cell carcinoma, estrogen and progesterone receptors were reported to be expressed in 90 and 83 % of NECB, respectively. It is hypothesized that primary breast neuroendocrine carcinoma differentiates from the epithelial cells during the carcinogenesis process; the prognosis of non-small cell primary NECB seems to improve as the amount of mucinous component increases in the tumor specimen. Management similar to interventions utilized to manage the usual ductal-type carcinoma has been attempted in the past, such as chemotherapy and hormonal therapy; however, due to the rarity of the tumor, none of the published studies are randomized nor do they have a large number of patients. Additionally, none of reports analyzed NECB based on its distinct subtypes. These limitations make recommendations largely based on anecdotal and small observatory studies and call for the need for further research in this extremely rare tumor.

Journal ArticleDOI
TL;DR: The study confirmed the continuity between f-PTCL and AITL and found Bcl-6 expression in f- PTCL was statistically associated with the characteristics of AIT l, except for pathologic characteristics.
Abstract: We examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma, follicular variant (f-PTCL), and compared these findings with angioimmunoblastic T-cell lymphoma (AITL) to determine whether they were identical to the spectrum of changes seen in AITL and how each of the findings in f-PTCL were related to the characteristics of AITL. Almost all f-PTCL cases showed pathologic characteristics of AITL and immunohistochemical positivities in lymphoma cells for CD4, CD10, Bcl-6, PD-1, and CXCL13. Except for pathologic characteristics, clinicopathologic findings in f-PTCL had few significant differences from AITL. The positive rate for Bcl-6 expression in neoplastic cells was significantly associated with the frequency of polymorphic infiltrates, vascular proliferation, B-immunoblasts, clear cells, Epstein-Barr virus-positive lymphocytes, hepatosplenomegaly, and skin rash. Our study confirmed the continuity between f-PTCL and AITL. Moreover, Bcl-6 expression in f-PTCL was statistically associated with the characteristics of AITL.

Journal ArticleDOI
30 Oct 2012-DARU
TL;DR: The cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines were found.
Abstract: Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT) assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells), and propidium iodide (for necrotic cells) dyes were employed. Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

Journal ArticleDOI
TL;DR: A patient with large-cell carcinoma of the lung is presented, in which cancer cells generate large amounts of GM-CSF leading to a leukemoid reaction with prominent hypereosinophilia and potentially involved in autocrine tumor stimulation.

Journal ArticleDOI
TL;DR: The results suggest that radiologically assessed response to EGFR TKI in NSCLC is related to loss of tumor cellularity and reduced tumor cell proliferation, but residual viable tumor cells may persist even after prolonged treatment.

Journal ArticleDOI
TL;DR: With CCRT, acute pulmonary toxicity of grade III or more developed in 50% of patients with stage III NSCLC, who also had radiological features of tumor cavitation, which is unclear given the high risk of a tumor abscess.

Journal ArticleDOI
TL;DR: When laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.
Abstract: Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC) of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR) images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.

Journal ArticleDOI
TL;DR: The cytologic findings of intrathyroidal epithelial thymoma/carcinoma showing thymus‐like differentiation (ITET/CASTLE) are described in detail and its differential diagnoses are discussed.
Abstract: The purpose of this article is to describe the cytologic findings of intrathyroidal epithelial thymoma/carcinoma showing thymus-like differentiation (ITET/CASTLE) in detail and discuss its differential diagnoses. We examined cytologic specimens taken from eight ITET/CASTLE cases, who underwent fine needle aspiration. Cytologic features of ITET/CASTLE include (1) hypercellularity, (2) large cell clusters without papillary or follicular pattern, (3) round or spindle tumor cells with distinct nucleoli and cell border, (4) few keratinized cells and intracytoplasmic lumina (ICL), and (5) lymphocytic background. The differential diagnoses included poorly differentiated carcinoma, metastatic lymphoepithelioma, squamous cell carcinoma, and mucoepidermoid carcinoma. The presence of individual keratinizing cells and ICL and the location of the tumor may be helpful in indicating ITET/CASTLE.

Journal ArticleDOI
TL;DR: The presence of sarcoidal reactions within regional lymph nodes of patients with non-small cell lung carcinoma predicts a lower rate of disease recurrence after definitive surgical resection, suggesting antitumor immunity is achieved.

Journal ArticleDOI
TL;DR: Cutaneous metastases from lung cancer remain a poor prognostic feature, but skin biopsy might be helpful to establish the histological type of tumour, and thus help with therapeutic decision‐making.
Abstract: Lung carcinoma is one of the most frequent sources of skin metastases in male patients. Our objective was to analyse the clinical and pathological features of 30 patients with skin metastases from lung carcinoma. Cutaneous biopsies codified as 'skin metastasis from lung carcinoma' during 1988-2009 at Bellvitge Hospital (Barcelona, Spain) were reviewed. The histological types of 30 lung carcinomas (29 men, 1 woman) were squamous cell carcinoma (10 cases), undifferentiated carcinoma (7), adenocarcinoma (6), small cell carcinoma (5) and large cell carcinoma (2). The most frequent clinical presentation was as a solitary nodule (16 cases), and the most frequent site was the head (13 cases). Cutaneous metastases were present at the time of diagnosis of the lung primary tumour in 66% of cases. Skin biopsy might be helpful to establish the histological type of tumour, and thus help with therapeutic decision-making. Cutaneous metastases from lung cancer remain a poor prognostic feature.

Journal ArticleDOI
TL;DR: The data show that simultaneous Hsp90 inhibition and irradiation may induce cell type-specific radiosensitization as well as cytotoxicity against tumor cells.