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D. Giedronowicz



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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): D. Giedronowicz

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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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): D. Giedronowicz

      • 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: 1
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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): D. Giedronowicz

      • 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.