Malignant Mesothelioma in Body Fluids - with Special Reference to Differential Diagnosis from Metastatic Adenocarcinoma

Background : Malignant mesothelioma (MM) is a rare malignant neoplasm occurring in pleura, pericardium, and peritoneum. The differential diagnosis between MM and metastatic adenocarcinoma (MA) causes diagnostic, staging, and therapeutic dilemmas. Herein, we investigated characteristic cytologic features of MM. Methods : Cytologic specimens of MM (n=10), MA (n=25) and reactive mesothelial hyperplasia (n=10) were retrieved and reviewed from archival materials in the Department of Pathology, Seoul National University Bundang Hospital from May 2003 to July 2008. Results : MM showed tumor cell clusters and singly scattered malignant tumor cells forming single cell populations with sparse reactive benign mesothelial cells. In contrast, MA showed distinct two cell populations of tumor cell clusters and scattered reactive mesothelial cells. Furthermore, MM frequently exhibited a characteristic long chain-like arrangement (hand-in-hand appearance) and intercellular windows, which were rarely evident in MA. Variable nuclear size, relatively consistent nuclear-cytoplasmic ratio, i or multi-nucleation, and lacy cytoplasmic borders were also frequently observed in MM. Conclusions : Differential diagnosis of MM from MA in body fluids is possible based on meticulous examination of certain cytologic parameters, which could have significant implications in staging and treatment.Kao S, 2009, J THORAC ONCOL, V4, P920Klebe S, 2009, PATHOLOGY, V41, P140, DOI 10.1080/00313020802579250LEE HJ, 2009, LUNG CANC IN PRESSXU X, 2009, J THORAC ON IN PRESSZervos MD, 2008, CURR OPIN PULM MED, V14, P303Mimura T, 2007, CANCER, V109, P933, DOI 10.1002/cncr.22477Yaziji H, 2006, MODERN PATHOL, V19, P514, DOI 10.1038/modpathol.3800534Soini Y, 2006, J CLIN PATHOL, V59, P250, DOI 10.1136/jcp.2005.028589Muller AM, 2006, PATHOBIOLOGY, V73, P50, DOI 10.1159/000093091DUGGAN MA, 2006, PATHOL CASE REV, V11, P65BHATTI T, 2006, PATHOL CASE REV, V11, P67FILIE AC, 2006, PATHOL CASE REV, V11, P74JAIN R, 2006, PATHOL CASE REV, V11, P92TRAVIS WD, 2004, HLTH ORG CLASSIFICAT, P128GREENE FL, 2002, AJCC CANC STAGING MA, P167RENSHAW A, 1999, CHEST, V111, P106MalamouMitsi VD, 1996, DIAGN CYTOPATHOL, V15, P197PEDIO G, 1988, EXP CELL BIOL, V56, P211

Risk of recurrence in surgically resected stage I adenocarcinoma of the lung: histopathologic and immunohistochemical analysis

STUDY OBJECTIVES: Stage I adenocarcinoma of the lung is the most common type of lung cancer. A better understanding of the histopathology and molecular biology of lung cancer might improve the capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I adenocarcinoma. METHODS: Fifty-five patients at the Seoul National University Bundang Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. RESULTS: Multivariate analysis demonstrated that necrosis, lymphatic vessel invasion, E-cadherin, p53, and Ki-67 emerged as independent prognostic factors of recurrence. When patients were grouped according to low or high risk according to the number of factors involved, the difference in disease-free survival between these groups was statistically significant. CONCLUSIONS: In resected stage I adenocarcinoma, necrosis, lymphatic vessel invasion, E-cadherin, and p53 have been identified as independent predictors of disease-free survival

Otologic Manifestation in IgG4-Related Systemic Disease

IgG4-related systemic disease, including autoimmune pancreatitis, is a multi-organ disorder characterized by elevated serum immunoglobulin G4 (IgG4) concentration and IgG4-positive plasma cell infiltration. We report a case of a 66-year-old woman with IgG4-related hearing disorder, presenting with fluctuating mixed hearing loss with middle ear effusion. The serum IgG4 level was elevated and pathological examination revealed dense infiltration of IgG4-positive lymphocyte in the renal parenchyma, lung tissue and lacrimal gland. With intravenous methylprednisolone at a dose of 60 mg daily, improvement of hearing loss were observed. No recurrence was observed for 6 months with mainternance of prednisolone and methotrexate

Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade

Background : Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors. Methods : 19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%). Results : In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6 +/- 4.2%), AC (n=7, 20.0 +/- 4.9%), LCNEC (n=13, 60.0 +/- 21.1%), and SCC (n= 6, 74.2 +/- 16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6 +/- 21.0%) (p=0.000). Conclusions: The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.This work was supported by grant no 02-2008-029 from the SNUBH Research Fund and partly supported by the Korean Science & Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center at Seoul National University College of Medicine.Song YS, 2008, LUNG CANCER, V61, P54, DOI 10.1016/j.lungcan.2007.11.012Nguyen XC, 2007, EUR J RADIOL, V62, P214, DOI 10.1016/j.ejrad.2006.12.008Khandani AH, 2007, NUCL MED COMMUN, V28, P173Chung JH, 2004, J NUCL MED, V45, P999TRAVIS WD, 2004, WHO INT HISTOLOGICALKalir T, 2002, CANCER, V94, P1078, DOI 10.1002/cncr.10280Wong CYO, 2001, EUR J NUCL MED, V28, P1702Wang BY, 2000, CANCER, V88, P2774Brown RS, 1999, J NUCL MED, V40, P556Ito T, 1998, MODERN PATHOL, V11, P437Travis WD, 1998, HUM PATHOL, V29, P272Baer SC, 1997, J AM ACAD DERMATOL, V37, P575Younes M, 1997, CANCER, V80, P1046Voldstedlund M, 1997, APMIS, V105, P537Haber RS, 1997, THYROID, V7, P363Younes M, 1997, CANCER EPIDEM BIOMAR, V6, P303Younes M, 1996, CLIN CANCER RES, V2, P1151Younes M, 1996, CANCER RES, V56, P1164Younes M, 1995, ANTICANCER RES, V15, P2895NAGASE Y, 1995, J UROLOGY, V153, P798MELLANEN P, 1994, INT J CANCER, V56, P622BROWN RS, 1993, CANCER, V72, P2979TAKATA K, 1992, CELL TISSUE RES, V267, P407PESSIN JE, 1992, ANNU REV PHYSIOL, V54, P911PARDRIDGE WM, 1990, J BIOL CHEM, V265, P18035ISSELBAC.KJ, 1972, NEW ENGL J MED, V286, P929

Epidermal Growth Factor Receptor Mutation and Pathologic-Radiologic Correlation Between Multiple Lung Nodules with Ground-Glass Opacity Differentiates Multicentric Origin from Intrapulmonary Spread

IntroductionNo standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread.MethodsTwenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18–21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients.ResultsHigh frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change.ConclusionsThis study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO

Giant Cell Tumor of Soft Tissue: a Case with Atypical US and MRI Findings

We report the case of a giant cell tumor with diffuse interstitial hemorrhaging and unusually prominent cystic components in the soft tissue of the thigh which has not been reported previously. Magnetic resonance image (MRI), showed signal intensity typical of a giant cell tumor. However, because of its conspicuous large well-circumscribed cystic components, the differential diagnoses, based on the image findings from an ultrasonography (US) and MRI, were complicated epidermoid cyst, cystic change of a neurogenic tumor, and a parasitic cyst

Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung

Background Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression. Methods HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed. Results HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501). Conclusions Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression