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R. Langfort



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    P1.15 - Poster Session 1 - Thymoma (ID 189)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P1.15-007 - Characteristics of thymomas diagnosed in National Tuberculosis and Lung Diseases Research Institute in Warsaw (Poland) (ID 2682)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      There were 152 thymomas diagnosed in Pathology Department of National Tuberculosis and Lung Diseases Research Institute from 1999 to the beginning of 2013. We performed a clinico-pathologic analyze of this rare group of neoplasms.

      Methods
      The diagnosis was establish on the investigation of totally resected tumors (126 cases) or small biopsied material (26). WHO histological classification of thymic tumors (2004) and Masaoka staging system were applied. The informations about patients age and gender, symptoms, other neoplasms, death and recurrence were collected.

      Results
      There were 86 (57%) women (median age 59 years) and 66 (43%) men (median age 54 years) in analyzed group. Myasthenic symptoms accompanied 50 (33%) tumors, 1 patient suffered from superior vena cava syndrom, the rest (101, 66%) was asymptomatic. In 6 (4%) patient another cancer was discovered: lung (3), renal (1), thyroid (1) and laryngeal (1) carcinoma. 147 thymomas were radiologically described as „mediastinal tumor”, 4 - „mediastinal cyst” and 1 thymoma on CT-scan was treated as mediastinal lymph node. Microscopic analysis revealed 9 (6%) type A thymoma, 42 (28%) AB, 27 (18%) B1, 16 (11%) B2, 4 (3%) B3, 4 (3%) micronodular, 2 (1%) metaplastic, 2 (1%) sclerosing and 1 (less then 1%) microscopic. 4 tumors were almost totally necrotized and the type could not be established, in 3 cases the specimen was to small to recognized the type. 38 (25%) tumors showed combined morphology composed of different types of thymomas, 1 tumor consisted of AB type and carcinoid. The most frequent combined thymomas were B2B3 (19) and B1B2 (8) types. The most histologic types appeared equally in both genders. B2B3 tumors concerned two times more frequent male patients and AB, B1 and micronodular were more common in women. Median age fell from micronodular type (78,5 years) followed by A (63 years), AB (58 years), B1 (55 years), B2 (52,5 years) and B3 (48 years). The tumors were usually in the 2nd stage. 18 (12%) patients died, 92 (60%) are still alive. The data were not available in 42 (28%) cases. The interval from resection to death was 1 month to 10 years. Histological types of thymomas diagnosed in patients who died included B1 (5 cases), AB (3), A (2), B2 (1) and 3 combined thymomas. The most tumors were in the 2nd stage. Recurrence occurred in 8 (5%) patients. Recurrent tumors appeared from 2 to 11 years after resection (median interval 8 years). The tumors were classified as B2 (2 cases), B2B3 (2), B1B2 (1), AB/B3 (1), AB/micronodular (1). The type was not determined in one case. Thymomas were in all stages except the 1st.

      Conclusion
      The thymomas appear mainly in 6th decade, more often in women. The most frequent histological type is AB and the tumors are usually microinvasive (the 2nd stage). High percentage of tumors has combined morphology. Recurrence can occur in any type of thymoma even considered as well-predicting but time to the progression often exceeds 5 years, so the tumors require long-term observations.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-011 - Bronchopulmonary carcinoid tumor (BPC) - is it time to change microscopic criteria of diagnosis? (ID 2269)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      The distinction between typical (TC) and atypical carcinoids (AC) is currently based on histologic criteria reported by Travis and al., then accepted by WHO classification and widely used today. The crucial microscopic features that distinguish TC from AC are mitotic activity and necrosis. TC has fewer than 2 mitotic figures/2mm[2 ], whereas AC has 2 to 10 mitoses/2mm[2] and/or small foci of necrosis. The aim was to analyze the microscopic features and immunohistochemical (IHC) profile of TCs and ACs, and to identify the other pathological criteria that could be simple, and reproducible, as well as helpful in daily practice of surgical pathology and usefulness in differentiation between both of them.

      Methods
      We retrospectively collected 236 cases of resected BPC from 1998 to 2011 at National Tuberculosis and Lung Diseases Research Institute. All tumors were reclassified according to the 2004 WHO classification. The clinicopathological features were correlated and survival analysis were performed. We evaluated size and location of tumors (central or peripheral), depth of bronchial invasion, destruction of bronchial cartilage, tumor invasiveness, the infiltrative growth of the adjacent normal architecture, presence of pleural, perineural and vascular invasion. We also assessed cellular atypia, growth pattern, cellular morphology, especially oncocytic and clear cell, as well as spindle-cell components. The expression of a range of antigens including markers of epithelial differentiation (cytokeratins: AE1/AE3 and 19, TTF-1, napsin A), neuroendocrine markers (chromogranin A, synaptophysin, NCAM/CD56), peptide products (calcitonin, serotonin) and antigens involved in cell proliferation and death (Ki-67, p53, Bcl-2, CD117) were studied.

      Results
      After reclassification, 8 cases were diagnosed as LCNEC, 102 tumors (44,7%) were classified as TC and 126 (55,3%) as AC. Most tumors are localized centrally (73,7%) and occurred in females (69%). AC were larger than TC (2,54 vs 1,9 cm). Solid and insular pattern, medium and high cellular atypia, oncocytic component, centrally located tumors with cartilage destruction, invasion of peribronchial tissue and/or adjacent lung parenchyma correlated with AC. Mitotic activity was one of most accurate method of diagnosis TC and AC but more advantageous would be increasing a number of mitoses figures to 2 for TC and to ≥3/2mm[2] for AC. AC more often revealed positive reaction with CK19 and higher cellular index for p53. Routinely staining for proliferative index (PI) with Ki-67 is recommended, for TC ≤4% and for AC >4%. Immunoreactivity of broad-spectrum cytokeratin was observed in 95% cases, more then 50% showed „dot-like“ reactivity. Peripherally located tumors were distinctly different morphologically and IHC than centrally carcinoids. Peripherally tumors were smaller (1,9 vs 2,4cm), usually not-well demarcated, with solid or insular pattern and spindle-cell component as well as fibrosis. In contrast to centrally tumors, they showed expression of TTF-1, serotonin and Bcl-2 but sparsely CK19.

      Conclusion
      The following pathological features should be evaluated in diagnosis of AC: localization, the infiltrative growth, solid and insular pattern, high grade atypia, oncocytic and spindle-cell components, mitotic figures and IP (Ki-67). We proposed for TC 0-2 mitosis/2mm[2] and PI ≤4%, for AC ≥3 mitosis/2mm[2] and PI >4% and/or foci of necrosis.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-030 - Surgical treatment of bronchopulmonary carcinoid tumors - a single institution experience (ID 2319)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      Bronchopulmonary carcinoid (BPC) comprise about 2-5% of lung tumors. BPC are malignant neoplasms with indolent course. Surgical treatment is the gold standard therapy.

      Methods
      We present our experience of 228 patients treated surgically for typical (TC) and atypical carcinoid (AC) from1998 to 2011 in National Tuberculosis and Lung Diseases Research Institute. We tried to determine the variables influencing the long-term survival of patients with BPC. Among 4467 patients, treated surgically for non-small cell carcinoma, BPC encompassed 5,1%. All cases were reviewed and classified according to the latest WHO classification (2004). The clinical course and survival analysis were performed.

      Results
      The number of BPC during last 14 years gradually growth, from 13,4 cases per year between 1998-2004 to 19,1 cases between 2005-2011. 102 cases (44,7%) were classified as TC and 126 (55,3%) as AC. There were 158 females (69%) and 70 men (31%) and the mean age was 52 ys. Men were significantly younger then females (49 vs 53). Symptoms were present in 143 patients, the most commonly were cough (31%), respiratory tract infection (31%), then haemoptysis (18%), dyspnoe (12%) and atelectasis (3,5%). No patients showed a carcinoid syndrome. There were no correlation between smoking status and BPC. Most of the tumors were central (73,7%), the remaining were peripheral. The mean diameter of BPC was 2,25cm (range 0,6-7,0cm). AC were significantly larger (2,54 vs 1,9) and centrally located were also larger the peripheral. Surgical treatment consisted of: 146 standard lobectomies (64%), 19 pneumonectomies (8%), 23 bilobectomies (10%), 23 sleeve lobectomies (10%), 2 sleeve-pneumonectomies (1%), 7 anatomic segmentectomies (3%), 2 wedge resections (1%), 6 – bronchoplastic procedures without lung resection (2,6%). Radical mediastinal lymphadenectomy was added in all cases exept 1. Involvement of lymph nodes was present in 35 cases (15,4%), N1 -22 (9,7%) and N2 – 13(5,7%). Infiltration of bronchial or vessel margin (R1) was revealed in 8 cases. The postoperative TNM stage contained IA (50%) disease, IB (31%), IIA (10%), IIB (2,6%), IIIA (6,1%), IV (0,4%). The stages IB, IIIA and IV more often related to AC. Four patients died in short time after operation (0,2 -2 months). Three of them were after pneumonectomies, one – sleeve-lobiectomie. In most cases tumor was localized centrally. The mean follow-up time for all patients was 69,3 months (range 0,2-172), with 204 still alive. Four patient died of tumor progression (3 from A, 1 from TC), remaining 8 patients from other causes, from 12 – the cause of death was unknown. Lymph nodes metastasis were seen in 5 cases (20,8%). Overall, 5, 10 and 14-years survival for TC was respectively 95%, 92,1% and 90,2%, for AC – 93%, 90,6% and 88,9%.

      Conclusion
      BPC demonstrate gradual growth during last years. Lung carcinoids are tumors with an excellent prognosis in most cases, even in the presence of metastases in lymph nodes and positive surgical margin (bronchial or vessel). Histologic subtypes did not infleunce on survival. Surgery currently represents the best treatment with good results and long survival but long-time observation is necessary.

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    P3.15 - Poster Session 3 - Thymoma (ID 192)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 2
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      P3.15-001 - Primary mediastinal tumors: epidemiological analysis of 12-years observations. (ID 1234)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      Primary mediastinal tumors (PMT) can be neoplastic or non-neoplastic lesions and originate mostly from thymus. We investigated epidemiology of these tumors and took into consideration age and gender of patients, histologic type of tumor and number of cases per year.

      Methods
      1615 cases clinico-radiologically defined as „mediastinal tumor” and diagnosed in National Tuberculosis and Lung Diseases Research Institute in Warsaw from the half of 1999 to the beginning of 2013 was analyzed. The diagnosis was establish by examination of totally resected tumor or biopsy specimens gained by mediastinoscopy or EBUS. WHO (2004) histological classification of tumors were applied to analysis.

      Results
      Material was obtained from 853 (53%) women (median age 49 years) and 762 (47%) men (median age 53 years). 375 metastatic carcinomas and 217 non-diagnostic cases were excluded from further examination as not „primary tumor”. There were 298 cases (27% of all PMT) of non-neoplastic thymic changes, 282 (26%) lymphomas, 147 (14%) thymomas, 64 (6%) neurogenic neoplasms, 44 (4%) thymic carcinomas, 44 (4%) thyroid lesions, 41 (4%) germ cell tumors, 39 (4%) cysts and 125 (12%) other tumors. Non-neoplastic thymic changes were dominated by follicular hyperplasia (249, 84%) and was observed mostly in women in 2nd - 4th decade. They constituted the most frequent PMT in women. Over half of all lymphomas (51%) were classical Hodgkin lymphoma, followed by primary mediastinal lymphoma (28%). Both types occurred mainly in young women ( the 3rd - 4th decade). The second peak of incidence in late life characteristic for Hodgkin lymphoma was not observed. Lymphomas were the most common PMT in men. The most frequent types of thymomas were AB (28%), B1 (17%) and B2 (11%). 25% of all tumors was classified as „combined”. Thymomas occurred more common in women (56%). Median age was 57 years. Neurogenic neoplasms were mostly schwannomas (58%), neurofibromas and ganglioneuromas (each 16%). The tumors were diagnosed more often in middle aged (3rd - 6th decade) female patients. Median age in thymic carcinomas were 58 years. They appeared almost equally in both genders. Group of thyroid lesions include retrosternal nodular goiter (80%), thyroid carcinomas (18%) and one thyroid lipoadenoma (2%). They occurred three times more often in women. Peak of incidence fell on the 6th decade. Germ cell tumors concerned mostly young men (M:F = 5:1) beneath 30 years old. There was no gender predylection among patients with mediastinal cysts. Median age was 52 years. The cysts were usually of thymic origin. The group of other tumors comprised sarcomas, haemangiomas, pleural lesions and enlarged mediastinal lymph nodes with granulomatous or reactive changes.

      Conclusion
      Both number of cases of all mediastinal tumors and percentage of PMT showed growing tendency from 2000 to 2012. The most frequent PMT in women are non-neoplastic thymic lesions (hyperplasias), followed by lymphomas, thymomas, neurogenic neoplasms and thyroid changes. In men, lymphomas are the most common, then are non-neoplastic thymic changes, thymomas, germ cell tumors, neurogenic neoplasms and cysts.

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      P3.15-002 - Can D2-40 antibody help in identifying B2 thymomas? Preliminary observations. (ID 2292)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      WHO histological classification of thymic tumors (2004) distinguishes five main histologic types of thymomas: A, AB, B1, B2 and B3 and several special types. The classification is not easy and the diagnosis is not reproducible, because thymomas are heterogeneous and often include several different components or the components of borderline types. The evaluation is very subjective and more objective criteria should be found. D2-40 is a monoclonal antibody that recognizes podoplanin expressed by lymphatic vessel endothelium, mesothelial cells, germ cell tumors and stromal cells of lymphoid tissue. Some authors observed, that expression of podoplanin is a prognostic factor in thymomas but is less important in histological typing of the tumor.

      Methods
      30 thymomas were examined immunohistochemically by reaction with D2-40 antibody. Morphology of tumors was established according to WHO histological classification of thymic tumors (2004), stage was based on criteria of Masaoka staging system. Reaction was assessed only in epithelial cells as positive or negative, membranous or cytoplasmic. When the recognition of epithelial cells was problematic, AE1AE3 antibody was involved. Normal thymic tissue remnants, lymphatic vessels or lymphoid stroma with reactive lymphoid follicles were treated as positive internal control of reaction.

      Results
      The group of thymomas consisted of type A - 3 cases, AB - 4, B1 - 5, B2 - 9, B3 - 2, 4 combined thymomas: B2B3 - 3 cases, B1B2 - 1 and 3 cases of special types: 2 micronodular and 1 metaplastic thymoma. The tumors were staged as I in 4 cases, II - 17, III - 3 and IV - 3 cases. Podoplanin was expressed in 1 (33%) type A, 1 (25%) AB, 3 (60%) B1, 9 (100%) B2, 0 (0%) B3, 3 (100%) B2B3, 1 (100%) B1B2, 0 (0%) micronodular and 1 (100%) metaplastic type. B2 and B1 types, B2B3 and B1B2 thymomas showed membranous reaction, other types (A, AB and metaplastic) - cytoplasmic. The intensity of reaction was diverse from inconspicuous to distinct but usually weaker than observed in internal control. Median area of tumor that expressed podoplanin ranged between 0 and 40%: A - 0%, AB - 0%, B1 - 1.5%, B2 - 30%, B3 - 0%, B2B3 - 40%, B1B2 - 20%, micronodular - 0% and metaplastic - 2%. 3/4 (75%) tumors in stage I, 8/17 (47%) tumors in stage II, 2/3 (67%) tumors in stage III and 3/3 (100%) tumors in stage IV (100%) revealed positive reaction. Median positive area of tumor was 17,5 % for stage I, 1% for stage II, 2% for stage III and 17% for stage IV.

      Conclusion
      Our preliminary observations revealed that positive membranous reaction with D2-40 present in epithelial cells that concerns over 20% of tumor area strongly suggests B2 component. The reaction can facilitate the recognition of this high-grade thymoma. Positive reaction in lymphoid stroma or thymic remnants should not be treated as diagnostic, but can be useful as a positive internal control of reaction. Cytoplasmic reaction is not characteristic for B2 type. We did not observed any relationship between D2-40 expression and stage of tumor.

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 2
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      P3.18-011 - Prognostic value of blood and lymphatic vessels embolism (pV, pL) in early stage lung cancer (IA, IB). (ID 2309)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      Stage of lung cancer (TNM) is most valuable prognostic factor. Most of patient in IA and IB stage survive 5 years, but in 10% of them the relapse of the disease is noticed. Therefore identifying the negative prognostic factors is crucial. The neoplastic emboli in blood and lymphatic vessels seem to be one of them.

      Methods
      The retrospective analysis of lung cancer patients operated on from 2002 thru 2006 at our institution was done. In all patient included into the study group the IA or IB stage was diagnosed and the neoplastic emboli in both blood and lymphatic vessels of the tumor were found. The survival rate in this group was compared with those without such findings. Among 1648 patient operated on between 2002 and 2006 564 were classified as IA or IB (pN0) stage (after rejecting 22 of them due to R1). Among 271 pts during microscopic detection neoplastic emboli in blood or lymphatic vessels were found. The analyzed group consisted of 208 women and 356 men. The stage IA was established in 212 pts, including 115 in pT1a, 97 in pT1b. Stage IB was diagnosed in 352 pts (pT2a) among whom 149 have infiltration of parenchymal pleura detected. All of them underwent the radical resection – all surgical margins were negative. The pathological examination revealed adenocarcinoma in 230 pts, squamous cell lung cancer in 203 pts, large cell lung cancer in 30, carcinoid in 80 pts and other kind of NSCLC in remaining 21 pts.

      Results
      5-year survival rates recorded were as follow – in stage IA 79,9% and 74,1% in pT1A pT1b respectively, in stage IB (pT2a) 59,9%. The presence of neoplastic emboli in blood and lymphatic vessels of tumor correlated with poorer prognosis of survival (V=0 L=0 – 72%, V=1 L=0 63,3%, V=0 L=1 64,7%, V=1 L=1 58,1%).

      Conclusion
      Therefore we concluded that such finding should be considered a negative prognostic factor and ought to be recorded in every pathology report.

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      P3.18-013 - Diffuse idiopathic pulmonary neuroendocrine hyperplasia and pulmonary carcinoid tumors - own experiences (ID 2675)

      09:30 - 09:30  |  Author(s): R. Langfort

      • Abstract

      Background
      Pulmonary neuroendocrine cells hyperplasia may be either reactive and idiopathic type. The latter is defined as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and sometimes precedes and coexists with carcinoids. According to the WHO lung tumor classification, DIPNECH is considered a form of preinvasive lung lesion. The available data regarding this rare condition are very limited. We would like to present our own experience with DIPNECH and carcinoid tumors, describe the pathologic features and immunohistochemical profile of both processes and to evaluate the frequency of DIPNECH and carcinoid tumors.

      Methods
      The cohort study group consisted of 229 patients diagnosed with carcinoid tumors who underwent surgery at the National Tuberculosis and Lung Diseases Research Institute between 1998-2011. We evaluated all microscopic samples from main tumor and adjacent, as well as peripheral parenchyma of the lung. When features of neuroendocrine cell proliferation were found, immunohistochemical reaction were done using markers of epithelial differentiation (cytokeratins, TTF-1, Napsin A), neuroendocrine antigens (chromogranin A, synaptophysin, NCAM/CD56). The cell proliferation index with Ki-67 and expression of CD117 were estimated.

      Results
      DIPNECH was confirmed in 15 patients, 14 females and 1 male with an average age 65,2 (range 32 – 79 ys). In 7 cases, carcinoid tumors were found in more than one focus, both typical (TC) and atypical (AC) carcinoid. The lesions exhibited a diameter with an average size of 1,9 (range from 0,6 to 3,0 cm). In one patient, apart from TC and AC, numerous foci of sclerosing haemangioma were found. Three patients had a history of cancer surgery (mastectomy, kidney resection, and hemicolectomy). In all cases, no metastases of primary tumors were evident. Almost all of the diagnosed carcinoid tumors, except one, were located peripherally, with mainly spindle-cell morphology, solid and/or insular pattern and foci of fibrosis. In 1 case, one of the tumorlet infiltrated the pleura but it did not extend beyond its margins. In all patients, the neureondocrine cells, tumorlets and carcinoid tumors displayed intensive positive reactions to neuroendocrine markers. Silimilarly, a positive reaction to cytokeratin was confirmed but in the most cases (73%) it was semi-intensive or weak. In all cases the expression of TTF-1 was positive but in the most cases weak. No positive reaction to napsin A and CD117 was detected. The proliferation index in DIPNECH was 1-2%, but in carcinoid depended of subtype of tumor, for TC was lower than 4%, for AC higher than 4%. Bcl-2 was evident in 9 DIPNECH and carcinoid tumor. Serotonin expression was found in 8 carcinoid tumors. 13 patients were alive at the end of follow-up, there were no information about 2 cases.

      Conclusion
      DIPNECH is a rare condition predominantly connected with carcinoid tumors, both TC and AC. Immunohistochemical profile is similar to peripherally located carcinoids. We suppose that there are biological differences between central and peripheral carcinoids, in that the latter stain more frequently with TTF-1, serotonin and Bcl-2. Peripheral are more often spindled in morphology and seen in cases that present with DIPNECH.