Probe-based confocal laser endomicroscopy for pleural malignancies diagnosis

Olivier Bonhomme, Vincent Heinen, Nancy Detrembleur, Jean-Louis Corhay, Renaud Louis, Bernard Duysinx, Olivier Bonhomme, Vincent Heinen, Nancy Detrembleur, Jean-Louis Corhay, Renaud Louis, Bernard Duysinx

Abstract

Background and objective: Probe based confocal laser endomicroscopy (pCLE) is an optical imaging technique allowing live tissue imaging at a cellular level. Currently, this tool remains experimental. Two studies regarding pleural disease have been published and suggest that pCLE could be valuable for pleural disease investigations. However, normal and malignant pleural pCLE features remain unknown. Therefore, we conducted a prospective trial of pCLE during medical thoracoscopy to study and describe the malignant and benign pleural pCLE features.

Methods: Every patient >18 years referred to our department for medical thoracoscopy was eligible. Medical thoracoscopy was performed under sedation, allowing spontaneous breathing. Five millilitres of fluorescein (10%) was intravenously administrated 5 min before image acquisition. The pCLE was introduced through the working channel of the thoracoscope and gently placed on the parietal pleura to record videos. Afterwards, biopsies were performed on the corresponding sites. Malignant and benign pleural pCLE features were precisely described and compared using 11 preselected criteria.

Results: A total of 62 patients were included in the analysis including 36 benign and 26 malignant pleura. Among our preselected criteria, 'abnormal tissue architecture' and 'dysplastic vessels' were strongly associated with malignancies (100% and 85% ss, 721% and 74% sp, respectively) whereas, the 'full chia seeds sign' and 'cell shape homogeneity' were associated with benignity (36% and 56% ss, 100% and 70% sp, respectively). No study-related adverse events occurred.

Conclusion: Benign and malignant pleural involvement have clearly distinct pCLE features.

Trial registration: ClinicalTrials.gov NCT03805971.

Keywords: medical thoracoscopy; pleural carcinomatosis; pleuroscopy; probe-based confocal laser endomicroscopy.

© 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

Figures

Figure 1
Figure 1
Normal probe‐based confocal laser endomicroscopy (pCLE) features of the parietal pleura (see the pleural pCLE description in the Results section for more details). (A) The pCLE image and the histological section (haematoxylin and eosin (HE)) show fibroadipose connective tissue of the pleura with adipocytes (crosses) and connective fibres (arrows). (B) The histological (HE) section and the pCLE image show striated muscular fibres (crosses). (C) The pCLE image shows the normal mesothelium (‘full chia seed sign’). The histological section (HE) shows a normal pleura. The arrow shows where the pCLE is positioned (perpendicularly to the mesothelial surface) to give the pCLE image. The triangle lies in the sub‐mesothelial connective tissue and the cross highlights the adipocytes (which are not presented on this pCLE image). (D) The pCLE image shows the pleural vascularization and some mesothelial cells. The histological (HE) section shows pleural vessels (arrows) lying in the pleural adipose tissue (cross).
Figure 2
Figure 2
Illustrations of the significant probe‐based confocal laser endomicroscopy (pCLE) features for pleural investigation. (A) pCLE gently applied on the parietal pleura (thoracoscopic view). (B, B′) Abnormal pleural architecture with cells of different size, shape and infiltration by glands (arrows) and cell clusters (lung metastatic adenocarcinoma). Haematoxylin and eosin (HE) staining for the histological section. (C, C′) The pCLE image shows dysplastic tortuous vessels (arrows) in a patient with metastatic lung adenocarcinoma. The histological section (HE) shows tortuous pleural vessels (arrows) within the pleural connective tissue infiltrated by inflammatory cells. (D, D′) The pCLE image shows a dysplastic vessel with patent fluorescein leaks (arrows) in a patient with pleural infiltration by a large B cell lymphoma. The histological section (HE) shows a haemorrhagic suffusion (crosses) in the pleural connective tissue (triangle for adipocytes) infiltrated by malignant B cells (arrow). (E, E′) The histological section (HE) shows a pleura (blue arrows are for the mesothelial layer) infiltrated by malignant cells taking an epithelioid architecture (epithelioid mesothelioma) (yellow arrows). The pCLE image highlights the epithelioid (aberrant) architecture and identifies some cell clusters (arrows). The full chia seed sign is illustrated in Figure 1 with the normal pleural pCLE features.

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