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K. Hiroshima
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-021 - Reproducibility of Comprehensive Histologic Assessment and Refining Histologic Criteria in P Staging of Multiple Tumour Nodules (ID 5365)
14:30 - 14:30 | Author(s): K. Hiroshima
- Abstract
Background:
Multiple tumor nodules (MTNs) are being encountered, with increasing frequency with the 8[th] TNM staging system recommending classification as separate primary lung cancers (SPLC) or intrapulmonary metastases (IM). Pathological staging requires assessment of morphological features, with criteria of Martini and Melamed supplanted by comprehensive histologic assessment of tumour type, predominant pattern, other histologic patterns and cytologic features. With publication of the 2015 WHO classification of lung tumours, we assessed the reproducibility of comprehensive histologic assessment and also sought to identify the most useful histological features.
Methods:
We conducted an online survey in which pathologists reviewed a sequential cohort of resected multifocal tumours to determine whether they were SPLC, IM, or a combination. Specific histological features for each nodule were entered into the database by the observing pathologist (tumour type, predominant adenocarcinoma pattern, and histological features including presence of lepidic growth, intra-alveolar cell clusters, cell size, mitotic rate, nuclear pleomorphism, nucleolar size and pleomorphism, nuclear inclusions, necrosis pattern, vascular invasion, mucin content, keratinization, clear cell change, cytoplasmic granules¸ lymphocytosis, macrophage response, acute inflammation and emperipolesis). Results were statistically analyzed for concordance with submitting diagnosis (gold standard) and among pathologists. Consistency of each feature was correlated with final determination of SPLC vs. IM status (p staging) by chi square analysis and Fisher exact test.
Results:
Seventeen pathologists evaluated 126 tumors from 48 patients. Kappa score on overall assessment of primary v. metastatic status was 0.60. There was good agreement as measured by Cohen’s Kappa (0.64, p<0.0001) between WHO histological patterns in individual cases with SPLC or IM status but proportions for histology and SPT or IM status were not identical (McNemar's test, p<0.0001) and additional histological features were assessed. There was marked variation in p values among the specific histological features. The strongest correlations (<0.05) between p staging status and histological features were with nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intra-alveolar clusters and necrosis pattern. Correlation between lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization and emperipolesis did not reach a p value of 0.05.
Conclusion:
Comprehensive histologic assessment shows good reproducibility between practicing lung pathologists. In addition to main tumour type and predominant patterns, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate appear to be useful in distinguishing between SPLC and IM.
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-013 - BAP1 Immunostaining and FISH Analysis of p16 Help Making Distinction among Subtypes of Mesothelioma (ID 4681)
14:30 - 14:30 | Author(s): K. Hiroshima
- Abstract
Background:
Distinction between mesothelioma and reactive mesothelial proliferation is difficult because of morphological overlap between mesothelioma cells and reactive mesothelial cells. It is often difficult to draw the line between epithelioid mesothelioma and biphasic mesothelioma with atypical stromal proliferation. However, separation of biphasic mesothelioma from epithelioid mesothelioma is important because therapeutic option and prognosis is different between two subtypes of mesothelioma.
Methods:
We collected 143 cases with malignant mesotheliomas (83 epithelioid, 22 biphasic and 38 sarcomatoid) and 33 cases with reactive mesothelial proliferation. Immunostaining was performed with anti-BAP1 antibody. Fluorescence in situ hybridization (FISH) analysis was performed with BAP1 probe and with p16 probe. BAP1 loss and deletion of p16 was separately analyzed in 19 biphasic mesotheliomas.
Results:
We analyzed 76 cases with BAP1 immunostaining, 87 cases with p16 FISH, and 37 cases with BAP1 FISH. BAP1 loss with immunohistochemistry was observed in 55% of epithelioid and 37% of biphasic mesotheliomas, but not in sarcomatoid mesotheliomas. Homozygous deletion (HD) of BAP1 was observed in 50% of epithelioid and 11% of biphasic mesotheliomas, but not in sarcomatoid mesotheliomas. HD of p16 was observed in 64% of epithelioid, 91% of biphasic, and 100% of sarcomatoid mesotheliomas. Concordance of BAP1 loss and HD of p16 between epithelioid and sarcomatoid components of 19 biphasic mesotheliomas was 100%. Four of epithelioid mesotheliomas were difficult to differentiate from biphasic mesothelioma with histology alone because of florid proliferation of atypical stromal cells; however, BAP1 loss and HD of p16 were not observed in atypical stromal proliferation and diagnosis of epithelioid mesothelioma could be made. There was a significant difference in overall survival according to histologic subtype (epithelioid 24M, biphasic 15M, sarcomatoid 4.5M). Mesotheliomas with loss of BAP1 expression showed increased survival (20M vs 8M) and HD of p16 showed poor survival (9.5M vs 28M). However, if only epithelioid cases were analyzed, there was no trend toward increased survival with BAP1 loss (24M vs 22M) while HD of p16 still showed poor survival (17M vs 28M).
Conclusion:
Most of biphasic mesotheliomas and all sarcomatoid mesotheliomas harbor HD of p16. BAP1 loss and HD of BAP1 are observed in epithelioid and biphasic mesotheliomas, but not in sarcomatoid mesotheliomas. BAP1 immunostaining and FISH analysis of p16 help making distinction between epithelioid and biphasic mesothelioma as well as between benign and malignant mesothelial proliferation. p16 is a prognostic factor for patients with epithelioid mesothelioma, but BAP1 is not.
