Dementia lacking distinctive histology (DLDH) revisited

• DOI: 10.1007/s00401-006-0123-3
• Publication Date: 2006-08-09T07:03:22Z
• Authors: Ian R. A. Mackenzie; Jing Shi; Catherine L. Shaw; Daniel DuPlessis; David Neary; Julie S. Snowden; David M. A. Mann
• Keywords: Adult; Male; Ubiquitin; tau Proteins; Middle Aged; Immunohistochemistry; United Kingdom; 3. Good health; Cohort Studies; Diagnosis, Differential; 03 medical and health sciences; 0302 clinical medicine; Humans; Dementia; Female; Diagnostic Errors; Aged

Although immunohistochemistry has helped to classify the histology of frontotemporal lobar degeneration (FTLD), there have been many cases, described in the literature as showing "dementia lacking distinctive histology" (DLDH), in which this technique has failed to disclose signature pathological changes. Using an automated procedure we have repeated immunostaining for ubiquitin protein (UBQ) in 41 patients with FTLD, 25 of whom were previously considered, on the basis of UBQ immunostaining performed in Manchester, UK, to show FTLD-ubiquitin (FTLD-U) histology and 16 described as DLDH. Both the quality and amount of UBQ immunoreactive (UBQ-ir) pathology (neurites and intraneuronal cytoplasmic inclusions) was significantly increased using the newer staining method. Although the original histological diagnosis was confirmed in the 25 cases previously classified as FTLD-U, the median UBQ score for slides stained in Vancouver increased significantly compared to those stained in Manchester. More importantly, however, some degree of UBQ-ir changes was now disclosed in 13 of the 16 cases previously classified as DLDH and these were now classed as definite or probable FTLD-U. Of the remaining three DLDH cases, clinical diagnostic uncertainties could have explained the lack of specific pathology in two instances. Hence, we conclude that DLDH is a very rare disorder, and that lack of sensitivity for UBQ immunostaining is likely responsible for the failure to disclose this pathology and to provide a diagnosis of FTLD-U.