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. 2020 Jul 5;12(7):1800.
doi: 10.3390/cancers12071800.

Digital Pathology and PD-L1 Testing in Non Small Cell Lung Cancer: A Workshop Record

Fabio Pagni  1 , Umberto Malapelle  2 , Claudio Doglioni  3 , Gabriella Fontanini  4 , Filippo Fraggetta  5 , Paolo Graziano  6 , Antonio Marchetti  7 , Elena Guerini Rocco  8   9 , Pasquale Pisapia  2 , Elena V Vigliar  2 , Fiamma Buttitta  7 , Marta Jaconi  1 , Nicola Fusco  8   9 , Massimo Barberis  8   9 , Giancarlo Troncone  2
Affiliations

Digital Pathology and PD-L1 Testing in Non Small Cell Lung Cancer: A Workshop Record

Fabio Pagni et al. Cancers (Basel). .

Abstract

A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1-49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement (p = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.

Keywords: NSCLC; PD-L1; immunotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Negative cases. Exemplificative false positive background in macrophages and inflammatory cells in a lung biopsy. Case n. 10 (original magnification 10×, 22c3): PDL1 TPS < 1%; look at the background staining in macrophages peritumoral cells. CASE n. 22 (10×, 22c3): PDL1 TPS < 1%; the application of a careful magnification rule allows to classify as macrophages this group of PD-L1 strong positive cells.
Figure 2
Figure 2
Intermediate and strong positive cases. Case n. 37 (10×, SP263): PD-L1 TPS > 50%; heterogeneous PD-L1 expression throughout the same tumor, with areas only showing faint background staining in non-neoplastic cells (bottom row, left) along with areas characterized by strong and complete membrane staining in the cancerous elements (bottom row, right). A challenging decision was jointly obtained to decide the exact threshold. Case n. 14 (10×, 22c3): PD-L1 TPS > 50%; all participants correctly ascribed this case to the ‘strong expression’ category due to the diffuse presence of PD-L1 staining in the tumor cells. Case n. 51 (10×, SP263): PD-L1 TPS 1–49%; heterogeneous PD-L1 expression with strong staining cells closely intermixed with faintly staining or negative cells. Case n. 33 (10×, 22C3): PD-L1 TPS 1–49%; a few of the neoplastic elements from this poorly differentiated adenocarcinoma showed a moderate membrane staining with the antibody, so this case was classified as an example of ‘intermediate expression’.
Figure 2
Figure 2
Intermediate and strong positive cases. Case n. 37 (10×, SP263): PD-L1 TPS > 50%; heterogeneous PD-L1 expression throughout the same tumor, with areas only showing faint background staining in non-neoplastic cells (bottom row, left) along with areas characterized by strong and complete membrane staining in the cancerous elements (bottom row, right). A challenging decision was jointly obtained to decide the exact threshold. Case n. 14 (10×, 22c3): PD-L1 TPS > 50%; all participants correctly ascribed this case to the ‘strong expression’ category due to the diffuse presence of PD-L1 staining in the tumor cells. Case n. 51 (10×, SP263): PD-L1 TPS 1–49%; heterogeneous PD-L1 expression with strong staining cells closely intermixed with faintly staining or negative cells. Case n. 33 (10×, 22C3): PD-L1 TPS 1–49%; a few of the neoplastic elements from this poorly differentiated adenocarcinoma showed a moderate membrane staining with the antibody, so this case was classified as an example of ‘intermediate expression’.
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