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Pathology
was was and and
seen in 9 (12.9%) of 70 cases in bronchial lavage. Disagreement in 10 (20.8%) of the 48 TTNA diagnoses. None of the 5 large-cell 6 adenosuamous carci-noma diagnoses displayed a preoperative postoperative agreement. Conclusion: Non-small cell carcinomas are known to exhibit different characteristics according to the cell types. In the diagnostic methods used for cases in which histological material is available, agreement between preoperative and postoperative cell types is high as compared to cytological examination. The investigation shows that histological examination is preferable in the diagnosis of bronchial carcinoma. ~-~
Clinicopathological correlation o f expression of MCM2 in
patients with non-small cell lung cancer (NSCLC) N. Ramnath, D. Tan, F. Hernandez, A. Beck, G. Loewen, J. Huberman, W. Burhans, C. Nwogul T. Anderson, G. Bepler. Departments of
Medicine, Pathology, Cancer Genetics, and Surgery, Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA DNA replication is controlled by origin licensing. This requires a complex of proteins that include ORC as well as cdc6 and MCM. MCM2 is one the components of a licensed origin. Upon initiation of DNA replication, origins become unlicensed until the cell actively reenters Gl-phase. MCM2 is absent in quiescent cells and in those undergoing differentiation (G0-phase). It thus can serve as a specific marker for cells in active cell cycle. In malignant lesions an inverse association between the expression of origin licensing proteins and the degree of tumor differentiation has been shown. There is also a clear contrast between normal and neoplastic tissue. Normal tissue shows positivity by immunohistochemistry (IHC) for MCM2 only in the proliferating compartment, such as the basal layer of the epidermis or the germinal center of lymph nodes. In contrast, neoplasms show a diffuse and often striking increase in the intensity of nuclear staining as well as an absolute increase in the number of stained nuclei, suggesting active proliferation. We reasoned that studying the expression in malignant lesions may give us useful prognostic information. We preformed IHC for MCM2 on 250 pathological specimens of patients with NSCLC seen at RPCI over a 4-year period. All specimens were graded independently by two different readers on a scale from 14. Germinal centers of normal lymph nodes were used as internal positive controls. To investigate clinical associations, a chart review of all patients with available pathological specimens was performed. Dates of death were confirmed using the social security death index database. Primary study objectives are associations between MCM2 staining and patient survival and best response to therapy. Secondary objectives are associations with disease stage and tumor histology. Data analysis is ongoing, and results will be presented at the meeting.
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Large cell neuroendocrine carcinoma: A poor prognostic entity
H. Takei 1, H. Asamura 1, K. Suzuki 1, H. Kondo 1, R. Tsuchiya 1, T. Niki 2, T, Yamada 2, Y. Matsuno 2. 1Division of Thoracic Surgery,
National Cancer Center Hospital; 2pathology Division, National Cancer Center Research Institute, Tokyo, Japan Background: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a newly recognized clinicopathologic entity. The clinical characteristics and appropriate treatment of patients with LCNEC are yet to be defined. Materials and Methods: The prognosis and clinical characteristics of 52 patients with LCNEC were retrospectively studied. The histologic diagnosis as LCNEC was established according to the description in WHO/IASLC histological classification of lung tumors, They comprised of 2.5% of all the patients undergoing resection for non-small cell carcinoma during the same period at the National Cancer Center Hospital, Tokyo. The median age of 52 patients was 67 years (range: 37-63). There were 45 men and 7 women (m/f ratio: 6.4). Results: Stage distribution was as follows: IA, 9; IB, 14; IIA, 2; liB, 6; IliA, 12; IIIB, 8; IV, 1. Overall 5-year survival of all patients was
35%. Five-year survival of the stage I, II, IliA, IIIB-IV were 41%, 38%, 14%, and 38%, respectively. Twenty patients were dead of disease, 4 are alive with disease. The site of the first documented recurrence was Iocoregional in 9 (39%), distant metastases in 12 (52%), and both simultaneously in 2. Locoregional lymph node recurrences were observed frequently. All the recurrences were found within 2 years after surgery. The level of serum neuron-specific enolase (NSE) was measured in 23 patients, of which the elevation was seen in 4 patients. Despite pre- or postoperative chemotherapy in 5 patients, tumor recurrence was observed in 4 patients. Conclusion: In terms of prognosis, LCNEC was distinctly differentiated from "non-small cell carcinomas" in which LCNEC had been classified. The prognosis of LCNEC was a remarkably poor even in early stage disease. Especially the prognosis of the stage I disease of LCNEC was poorer than the same stage of "non-smaU cell carcinoma". Because of extremely poor prognosis and aggressive nature of this tumor, LCNEC should be recognized as one of the most poor prognostic subgroups, and therefore, novel therapeutic approach is necessary
~Multistep
carcinogenesis in Bronchiolo-alveolar
carcinomas of the Lungs M. Yamasaki 1,2, Y. Takeshima 1, S. Fujii 1, K. Inai 1. 1Second
Departmant of Pathology, Hiroshima University School of Medicine; 2Second Departmant of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan Purpose and Method: Bronchioloalveolar carcinoma (BAC) is one type of lung adenocarcinoma showing the growth along alveolar wall, and it has been pointed out the prognosis is different according to the presence of central scar. We divided BAC into two types, that is sclerosing BAC (SBAC) with central scar and non-sclerosing BAC (NSBAC) without central scar, and attempted to examine the difference of genetic alterations with comparison to those of atypical adenomatous hyperplasia (AAH). The entered cases were 39 SBAC and 19 NSBAC, of which tumors were measured less than 3 cm in the maximum diameter, as well as 20 cases of AAH. On detecting loss of heterozygosity (LOH), the microsatellite markers, D3S1234 and D3S1300 on 3p, IFNA and D9S144 on 9p, and TP53 on 17p were used. Using PCR-SSCP analysis and direct sequencing, point mutation of p53 gene at exons 5-8 was also examined. Results and Conclusion: At TP53 locus, 1 (6%) of 18 informative cases of AAH, 2 (11%) of 19 informative cases of NSBAC and 14 (36%) of 39 informative cases of SBAC showed LOH. The frequency of LOH at TP53 locus showed significant difference between NSBAC and SBAC (p = 0.0367), and statistical rank-difference correlation among AAH, NSBAC and SBAC (p = 0.0044). As to chromosome 3p and 9p, no statistical difference of LOH among AAH, NSBAC and SBAC was shown. Mutation of p53 gene was shown in 3 (16%) of 19 NSBAC cases and in 12 (33%) of 36 SBAC cases, while no mutation was seen in AAH cases. The frequency of p53 point mutation cases of SBAC was higher than that of NSBAC, and therefore, significant statistical rank-difference correlation of p53 mutation was detected among AAH, NSBAC and SBAC (p = 0.0026). These findings suggested that the genetic alterations of chromosome 17p related to the different prognosis between SBAC and NSBAC, and the process of multistep carcinogenesis from AAH through NSBAC to SBAC might occur in some cases of adenocarcinoma.
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Endoscopic ultrasonography vs intraoperative biopsy Sensitivity, specificity and results o f fine needle aspiration cytology
L. Welker, E. Vollmer 1, M. Claussen, D. Branscheid, H. Magnussen.
Krankenhaus Grosshansdoff,, D-22927 Grosshansdorf,; I Experimentelle und Klinische Pathologie, Forschungsinstitut Borstel, D-23845 Borstel, Germany In this retrospective study we determined the diagnostic yield of fine needle cytological investigation (FNC) in the diagnosis of lung tumors
Pathology by comparing aspiration material obtained endoscopically through ultrasonography (EUS) with aspiration material obtained intra-operatively (lOB). In 225 patients studied between 1/97 and 12/99, a total of 243 cytological findings and pest-operative histological diagnoses were compared. No complications arose from both procedures. In EUS, 4 and in lOB, 5 samples did not allow a firm decision. In 174 samples, malignancy was confirmed histologically, and in 60 samples benign lesions were recognized. EUS showed a specificity of 98%, a sensitivity of 79% and a diagnostic accuracy of 85%, whereas lOB showed values of 100, 93 and 95%, respectively; the table shows the corresponding numbers.
Histology
EUS benign
malignant
lOB benign
malignant
benign malignant
38 5
1 23
20 9
1 137
We conclude that the loss in information in EUS owing to inevitable technical factors is about 10% as compared to lOB. Furthermore, the results on lOB underline that FNC per se is as reliable as histology. Supported by LVA - Freie und Hansestadt Hamburg
~-3--~A case of collision tumor: Malignant fibrous histiocytoma with pulmonary adenocarcinoma K. Yamada, T. Yarita, Y. Koide, S. Tsukamoto, G. Kimitsuka, H. Yamakawa, H. Kato I . Dept. of Surgery and Pathology, Yarita
Hospital, Ichihara; 1First Dept. of Surgery, Tokyo Medical University, Tokyo, Japan Few cases were reported of malignant fibrous histiocytoma (MFH) with pulmonary adenocarcinoma. A 70-year old man was referred to our hospital for further examination of an abnormal chest X-ray shadow. But his chest X-ray on mass survey had already showed a coin lesion in the left upper field two years ago. TBLB performed at OPD revealed adenocarcinoma. So he was admitted to our hospital and left pneumonectomy was performed. The resected tumor was consisted of two different nodules, sarcomatous nodule in the peripheral side and adenocarcinomatous nodule in the central side. Sarcomatous component was clearly capsuled and was mostly denatured to necrotic tissue. Immunohistochemical examination suggested that these two nodules, malignant fibrous histiocytoma and adenocarcinoma, existed independently and collided with each other. This case is presented herein followed by a review of the literature.
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Usefulness of immunohistochemistry for surfactant protein-A in lung cancer cells
W.B. Weynand, H.C. Hermans, L.O. Lesur, P.T. Pieters. Department
of Pathology, Cliniques Universitaires Saint-Luc, Brussels; Industrial Toxicology and Occupationa/ Medicine Unit, Cliniques Universitaires Saint-Luc, Brussels; Pneumology Unit, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium, Pu/monary Research Unit, University of Sherbrooke, Quebec, Canada Surfactant protein-A (SP-A) is found at the lung level in normal type II pneumocytes and Clara cells and, outside the lung, in serosal mesothelial cells and type A and B synoviocytes. Lung adenocarcinoma (AC) and, in less extent, squamous and large cell lung carcinoma express SP-A as can be demonstrated by immunohistochemistry. In metastatic lung adenocarcinoma, this expression is absent. SP-A gene transcript has been retrieved from pleural fluid cells only in cases of primary lung AC. The usefulness of the immunohistochemical detection of SP-A to identify tumor cells in pleural fluids is still questioning. Immnuohistochemical analysis was performed on 14 non-malignant pleural fluids (4 transudates and 10 exudates), 19 metastatic pleurat fluids (9 primary lung AC, 10 non pulmonary AC derived from the
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breast, stomach, pancreas, kidney, biliary duct and ovary) and on 10 surgical biopsies from pulmonary squamous carcinoma (SqC). We used a commercial polyclonat anti-SP-A antibody (Rabbit anti-human SP-A, Chemicon International Inc, Temecula, CA, USA) and another one (gift of O. Lesur). Using the Chemicon antibody, 9 out of 9 lung AC pleural fluids, 10 out of 10 non-pulmonary AC pleural fluids, and 9 out of 10 SqC were positive for SP-A. To identify primary lung AC in pleural fluids, sensitivity was 100% and specificity 0%. Using the antibody of O. Lesur, macrophages were detected in 6 out of 14 non-malignant pleural fluids whereas malignant cells were positive for SP-A in 4 out of 9 primary lung AC pleural fluids and 6 out of 10 non-pulmonary AC pleurat fluids. Sensitivity and specificity were respectively 52 and 100% to differentiate malignant from non-maignant pleural fluids. We conclude that search for SP-A positivity is a specific method to detect malignant cells in pleural fluids but it is not a suitable test to distinguish between histologic subtypes of pulmonary carcinomatous cells.
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expression of peanut agglutinin binding carbohydrate(s) correlates with nodal involvement in human lung adenocarcinoma
H. Suzuki, "12 Kawaguchi 1, M. Higuchi, Y. Shio, K. Fujiu, R. Kanno, A. Ohishi 2, M. Gotoh. First Dept. of Surgery; I Second Dept. of
Pathology, Fukushima Medical University; 2Fukushima Red Cross Hospital, Fukushima, Japan Background: Nodal involvement is an important event in lung cancer progression. The establishment of predictive marker for nodal status is important to successful treatment and understanding the mechanism. In the previous Conference we reported that the binding capabilities of cancers with certain lectins were closely correlated with several kinds of clinicopathologic variables including nodal status. Peanut agglutinin (PNA) lectin binding property of tumor cells showed the most significant correlation with nodal involvement. This study was undertaken to ensure the previous findings by adding recent prospective cases and also to isolate the PNA binding proteins in the tumor cells. Materials and Methods: Primary lung adenocaroinomas, surgically resected from 164 patients, were analysed for correlation between several clinicopathologic parameters and expression of PNA binding carbohydrates. Expression of the carbohydrates was detected by histochemistry using biotin-labeled PNA lectin. Carbohydrate binding proteins were investigated by SDS-PAGE electrophoresis followed by Western blotting in two cases. Results: Expression of PNA binding carbohydrates was highly correlated nodal involvement (p = 0.0003) and lymphatic vessel invasion (p = 0.0249). Previously there was no correlation with lymphatic vessel invasion However, there was no significant correlation with age, sex, tumor size, blood vessel invasion, differentiation, pleural invasion or five-years survival rates as previous noted. SDS-PAGE electrophoresis and Western blotting demonstrated several PNA binding proteins ranged from over 30 KDa to 200 KDa. Conclusion: The result of this study suggest that expression of PNA binding carbohydrates could be a valuable marker for lymphatic vessel invasion as well as nodal involvement in human lung adenocarcinomas who may be candidates for some adjuvant therapy.
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Pathological and clinical investigation of pulmonary atypical adenomatous hyperplasia and its association with primary lung adenocarcinoma
A.D. Chapman 1, D. Thetford 2, K.M. Kerr1. Departments of 1Pathology;
2Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen, UK Atypical Adenomatous Hyperplasia (AAH) has been suggested as the adenoma in an adenomacarcinoma sequence in the lung periphery. We undertook a systematic, prospective search from 1989-1998 for AAH in lungs resected for cancer. AAH lesions were found in 70 patients in total and in 67 of 554 patients (12.1%) with primary lung carcinoma (9.2% in male patients and 19.0% in females). AAH was noted in lungs bearing adenocarcinoma (23.2%) more frequently than with