Summary
In situ stages of malignancy have been characterised in various neoplasms. Mesothelioma in situ (MIS) has been a controversial diagnosis, lacking clear diagnostic criteria and understanding
as to whether it is truly a premalignant lesion in the progression of malignant mesothelioma
(MM). Originally understood as a concept and defined as atypical mesothelial proliferation
in the presence of invasion, it has now been suggested that loss of nuclear labelling
for BRCA1-associated protein-1 (BAP1) in flat, non-invasive mesothelial lesions can
define MIS. This study aimed to characterise BAP1 expression in a cohort of 19 patients
diagnosed with MIS (either pure MIS, n=3, or MIS-predominant invasive MM, n=16) and to compare survival between MIS, MIS-predominant MM and MM (n=114) in order to gain insight into the characteristics of MIS. We defined pure MIS
as any architectural pattern of surface mesothelial cells with loss of BAP1 in the
absence of invasion, but in specimens with superficial stromal invasion we also accepted
the original definition of cytologically and architecturally atypical mesothelial
proliferation, in the absence of inflammatory features, with or without loss of BAP1.
We observed that MIS associated with minimal invasion was associated with significantly
improved survival compared to MM (8 months vs 22 months). This suggests that MIS is
indeed a precursor to MM and that these cases represent earlier stage disease. Loss
of BAP1 was present in 60% of mesotheliomas with invasion, so not all early cases
can be detected by BAP1 loss, but our study provides evidence that BAP1 loss may be
an early molecular alteration in MM pathogenesis in patients that have loss of BAP1.
We confirm that BAP1 loss can be useful for diagnosis of pure MIS in surgical specimens,
permitting earlier diagnosis. However, identification of a predominant MIS component
with minimal invasion has prognostic and conceptual implications. Whilst no approved
therapy is available for MIS, close follow up of patients with BAP1 mutation in mesothelial
cells and/or diagnosis of MIS is required to monitor for disease progression and potentially
investigate earlier treatment interventions.
Key words
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Article info
Publication history
Published online: August 20, 2020
Accepted:
June 25,
2020
Received in revised form:
June 17,
2020
Received:
January 23,
2020
Identification
Copyright
© 2020 Published by Elsevier B.V. on behalf of Royal College of Pathologists of Australasia.
