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Teh-Ying Chou



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    MTE02 - Update on WHO Classification and Staging of Lung Cancer (Ticketed Session) (ID 812)

    • Event: WCLC 2018
    • Type: Meet the Expert Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 07:00 - 08:00, Room 203 BD
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      MTE02.02 - Update on WHO Classification and Staging of Lung Cancer (Now Available) (ID 11549)

      07:30 - 08:00  |  Presenting Author(s): Teh-Ying Chou

      • Abstract
      • Presentation
      • Slides

      Abstract

      Squamous cell carcinoma comprises approximately 20% of lung cancer cases and is classified into keratinizing, non-keratinizing and basaloid types (1,2,3). The p40 (or p63) immunohistochemical stain is helpful in diagnosing squamous cell carcinoma, if keratinization of the tumor cells is not appreciable.

      Neuroendocrine tumors comprises of four categories: small cell carcinoma, large cell carcinoma, typical carcinoid and atypical carcinoid (1), with variable degrees of malignant potential. Small cell carcinoma comprises approximately 14% of lung cancer cases and is further categorized into small cell carcinoma and combined small cell carcinoma (1,4,5). The tumor is composed of densely packed small-size tumor cells with scant cytoplasm, finely granular chromatin, and absence of distinct nucleoli. Mitotic figures and apoptotic bodies are frequently seen. Nuclear molding and smearing may be observed. Rosette formation and peripheral palisading, characteristics of neuroendocrine tumors, are consistently found. Large cell neuroendocrine carcinoma has the cytological morphology of large cell carcinoma and the growth pattern of neuroendocrine tumor. Both small cell carcinoma and large cell neuroendocrine carcinoma are high grade tumors. Carcinoid tumors are usually centrally located with endobronchial growth and are further divided into two categories: typical carcinoid (intermediate grade) and atypical carcinoid (low grade).

      Adenosquamous carcinoma is rare and comprises 0.4-4% of lung cancer cases (1,6,7). Presence of both adenocarcinoma and squamous cell carcinoma components and each component comprising more than 10% is required.

      Sarcomatoid carcinoma comprises less than 1% of lung cancer cases and is further subcategorized into pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma (1,8). Given the marked histological heterogeneity, sarcomatoid carcinoma need to be thoroughly sampled before the final diagnoses are made.

      Salivary gland-type carcinomas include mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, arising from the salivary-type glands of the bronchial mucosa (1).

      In summary, the major types of lung carcinomas are outlined in Figure 1.

      180629 histology lung cancer classification.jpg

      References:

      1. William D. Travis EB, Allen P. Burke, Alexander Marx, Andrew G. Nicholson (Eds.). WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart (4th Edition). 4 ed: IARC: Lyon; 2015.

      2. Tomashefski JF, Jr., Connors AF, Jr., Rosenthal ES, Hsiue IL. Peripheral vs central squamous cell carcinoma of the lung. A comparison of clinical features, histopathology, and survival. Archives of pathology & laboratory medicine. 1990;114(5):468-74.

      3. Funai K, Yokose T, Ishii G, Araki K, Yoshida J, Nishimura M, et al. Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. The American journal of surgical pathology. 2003;27(7):978-84.

      4. Fraire AE, Johnson EH, Yesner R, Zhang XB, Spjut HJ, Greenberg SD. Prognostic significance of histopathologic subtype and stage in small cell lung cancer. Hum Pathol. 1992;23(5):520-8.

      5. Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Combined small-cell and non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1989;7(5):607-12.

      6. Fitzgibbons PL, Kern WH. Adenosquamous carcinoma of the lung: a clinical and pathologic study of seven cases. Hum Pathol. 1985;16(5):463-6.

      7. Ishida T, Kaneko S, Yokoyama H, Inoue T, Sugio K, Sugimachi K. Adenosquamous carcinoma of the lung. Clinicopathologic and immunohistochemical features. Am J Clin Pathol. 1992;97(5):678-85.

      8. Travis WD. Sarcomatoid neoplasms of the lung and pleura. Archives of pathology & laboratory medicine. 2010;134(11):1645-58

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    OA03 - Advances in Lung Cancer Pathology (ID 897)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 205 BD
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      OA03.03 - Phase 2B of Blueprint PD-L1 Immunohistochemistry Assay Comparability Study (Now Available) (ID 14530)

      10:50 - 11:00  |  Author(s): Teh-Ying Chou

      • Abstract
      • Presentation
      • Slides

      Background
      PD-L1 immunohistochemistry (IHC) has been established as companion or complementary diagnostic assays, each developed as predictive biomarker for specific anti PD1/PD-L1 immunotherapies. The Blueprint (BP) phase 1 comparability study demonstrated that three PD-L1 assays (28-8, 22C3, SP263) showed comparable analytical performance for assessment of PD-L1 expression on tumor cells (TPS), while the SP-142 PD-L1 assay appeared to stain a lower percentage of tumor cells when compared to the other assays. The first part of BP phase 2 (BP2A) re-affirmed these findings in a larger cohort of ‘real life’ specimens scored by 24 experienced pulmonary pathologists, and also showed that the 73-10 assay developed for avelumab showed greater sensitivity than all other assays to detect PD-L1 on tumour cells. BP2A also demonstrated generally excellent inter-observer agreement for tumor cell PD-L1 scoring using both glass slides and digital images, with slightly lesser agreement for the cytology samples included in the study cohort. Inter-observer agreement for immune cell scoring on glass or digital slides was poor. Phase 2B of Blueprint (BP2B) aimed to compare PD-L1 scoring on triplet samples representing large tumor resection blocks, small biopsy samples and fine needle aspirate cell blocks prepared from the same tumor. a9ded1e5ce5d75814730bb4caaf49419 Method
      Triplet samples of large resected tumor block, small biopsy sample and fine needle aspirate cell block (the latter two taken from the resected tumour specimen) were gathered from 31 resected primary lung cancers (17 adenocarcinomas, 12 squamous cell carcinomas, and 2 large cell carcinomas). Sections from all 93 blocks were stained with the pharmDx 28-8 and 22C3, the FDA-approved SP142 and SP263, or clinical trial associated 73-10 PD-L1 assays, in a CLIA-approved immunohistochemistry laboratory. All H&E and PD-L1 IHC slides were scanned and digital images were used to score all cases by the same 24 pathologists involved in BP2A. As before, tumor cells PD-L1 staining were scored as continuous variable and into 7 cut-off-defined categories, as used in various immune checkpoint inhibitor trials. Immune cells were not scored. 4c3880bb027f159e801041b1021e88e8 Result
      The data reaffirm the relative comparability of 28-8, 22C3 and SP263 assays across the range of scores; SP142 assay scores were lower, those for 73-10 higher. Inter-observer agreement between readers ranged from moderate to near perfect (Kappa-Fleiss (K-F) scores generally >0.7); best overall agreement was on aspirates. Overall, the agreement between scores on the different sample types from the same tumor was good (most K-F scores >0.7); aspirates showed no significant difference from biopsy samples or whole surgical blocks. In contrast to biopsies and surgical blocks, scores could, however, not be rendered in about 14% of aspirate sections. 8eea62084ca7e541d918e823422bd82e Conclusion
      The results of BP2B confirms earlier results and also demonstrate comparable performance for fine needle aspirates in those cases where TPS scores were possible. 6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-12 - EGFR Mutation Status in Squamous Cell Carcinoma or Non-Small Cell Carcinoma Favor Squamous Cell Carcinoma Diagnosed from Small Lung Biopsies (ID 13154)

      16:45 - 18:00  |  Author(s): Teh-Ying Chou

      • Abstract

      Background

      Epidermal growth factor receptor (EGFR) mutation testing is strongly recommended in non-small cell lung cancer (NSCLC) patients with adenocarcinoma subtypes, or patients with mixed-type tumors containing adenocarcinomatous components. However, in clinical practice, patients showing squamous cell carcinoma (SqCC) morphology on small biopsies cannot be ruled out to have an adenocarcinomatous component elsewhere in the lesion due to sampling bias. Therefore, EGFR mutation testing may have been neglected in such circumstances, which would affect the clinical management of patients. In this study, we sought to examine the frequency of EGFR mutations in lung cancer patients with SqCC or Non-Small Cell Carcinoma (NSCC) favor SqCC diagnosed from small biopsies. The correlation between EGFR mutation status and clinicopathological characteristics was also evaluated.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      One hundred and forty-eight patients diagnosed as SqCC or NSCC favor SqCC from small lung biopsies were enrolled. All of these cases were histologically confirmed by evaluating cellular morphology using hematoxylin-eosin (HE) staining and TTF1, p40 or CK5/6 expression using immunohistochemistry. EGFR mutations were examined using real-time PCR based assay.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 148 small biopsy cases, 135 (91.2%) were diagnosed as SqCC while 13 (8.8%) were NSCC favor SqCC. Approximately 8.8% (13/148) of all cases were found to have EGFR mutations, including 7 (53.8%) L858R mutation, 4 (30.8%) exon 19 deletion, and 2 (15.4%) cases with coexistent L858R and T790M mutations. EGFR mutation-positive cases accounted for 5.2% (7/135) in SqCC, 46.2% (6/13) in NSCC favor SqCC, and 83.3% (10/12) of all these cases were never smokers. The multivariate analysis showed that EGFR mutations were more prevalent in non-smokers than those in smokers (83.3% versus 16.7%, p = 0.03) and in patients diagnosed as NSCC favor SqCC than in those diagnosed as SqCC (46.2% versus 5.2%, p = 0.002). In addition, 4 out of 13 EGFR mutation-positive patients with SqCC or NSCC favor SqCC morphology were eventually diagnosed as adenosquamous carcinoma after further undergoing surgical resection.

      8eea62084ca7e541d918e823422bd82e Conclusion

      To the best of our knowledge, this is the first study directly addressing the importance of EGFR mutation testing in lung cancer patients with SqCC or NSCC favor SqCC diagnosed from small biopsies. Our findings suggest that EGFR mutation testing should not be excluded in such populations, especially in never-smokers, or patients with NSCC favor SqCC subtypes.

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