The BrainNet Europe consortium assessed the
reproducibility in the assignment of the type of frontotemporal
lobar degeneration (FTLD) with TAR DNA-binding
protein (TDP) 43 following current recommendations. The
agreement rates were influenced by the immunohistochemical
(IHC) method and by the classification strategy followed.
p62-IHC staining yielded good uniform quality of
stains, but the most reliable results were obtained implementing
specific Abs directed against the hallmark protein
TDP43. Both assessment of the type and the extent of lesions
were influenced by the Abs and by the quality of stain.
Assessment of the extent of the lesions yielded poor results
repeatedly; thus, the extent of pathology should not be used
in diagnostic consensus criteria. Whilst 31 neuropathologists
typed 30 FTLD-TDP cases, inter-rater agreement ranged
from 19 to 100 per cent, being highest when applying
phosphorylated TDP43/IHC. The agreement was highest
when designating Type C or Type A/B. In contrast, there was
a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist,
independent of his/her familiarity with FTLDTDP
pathology, can identify a TDP43-positive FTLD case.
The goal should be to state a Type (A, B, C, D) or a mixture of
Types (A/B, A/C or B/C). Neuropathologists, other clinicians
and researchers should be aware of the pitfalls whilst
doing so. Agreement can be reached in an inter-laboratory
setting regarding Type C cases with thick and long neurites,
whereas the differentiation between Types A and B may be
more troublesome.