Ubiquitinated cytokeratin inclusions in lichen amyloidosus: An immunohistochemical analysis

Abstract

Eosinophilic hyaline inclusions were consistently seen in the perinuclear cytoplasm of suprabasal keratinocytes in lichen amyloidosus. The inclusions, negative with amyloid staining, were immunoreactive for ubiquitin and cytokeratin, and ultrastructurally showed aggregations of fine filaments of two sizes (central thin and peripheral thick). The thin filaments were the main component in the upper epidermal layer. Four monoclonal antibodies (AE1, AE3, KL1 and CAM5.2) and one antiserum (WSS) were used for characterizing cytokeratin expression. The AE1 antibody normally stained the basal cells, but in lichen amyloidosus basal staining mostly disappeared. Instead, groups of suprabasal keratinocytes were labeled, with AE1-reactive inclusions distributed therein. In contrast, the KL1 antibody, showing suprabasal staining, failed to react with the inclusions. The inclusions were weakly reactive with the AE3 and WSS antibodies, which stained all keratinocytes. The CAM5.2 antibody was unreactive. The subepidermal amyloid deposits were negative with all the antibodies. The inclusions were ubiquitinated especially in the granular layer. Immunoelectron microscopy disclosed that ubiquitin was more densely localized in the thin filaments than in the thick ones. This indicated that cytokeratin expression and metabolism are altered in the affected epidermis, and that ubiquitin functions in the process of degradation of abnormal cytokeratin filaments.

Expression of fetal cytokeratins in epidermai cells and colloid bodies in lichen planus*

“…An alteration in tbe epidermal cytokeratin pattern bas also been found in lichen amyloidosiis. Akamatsu and colleages detected immunobistochemically (by MAb AEl) basal cytokeratins in suprabasal cells (33). As far as our findings are concerned, we were intrigued by tbe fact tbat tbe cytokeratin profile in LP includes botb accelerated differentiation by tbe expression of suprabasa!…”

Keratins Turn over by Ubiquitination in a Phosphorylation-Modulated Fashion

“…Ubiquitination and degradation may be coupled or uncoupled since degradation requires an active proteasome. Examples of uncoupling that apply to most if not all IF proteins are the codecoration of Ub and IF proteins as reported in several cytoplasmic deposits in association with a number of diseases (e.g., Lowe et al, 1988;Ohta et al, 1988;Akamatsu et al, 1995). One potential explanation is that the inclusion-associated diseases result in states whereby the proteasome capacity is exceeded (Johnston et al, 1998) or inhibited, with subsequent accumulation of ubiquitinated proteins within aggresomes.…”

Hyaline Inclusion Acanthoma

“…Eosinophilic hyaline inclusions have also been described in the cytoplasm of epidermal keratinocytes in lichen amyloidosis. 15 Of note, the cytoplasmic inclusions in lichen amyloidosis are morphologically different than the common EHI of cutaneous neoplasms because they are irregular in shape and immunoreactive for ubiquitin, reminiscent of Mallory bodies in liver diseases such as steatohepatitis. Finally, in 2003, Philip LeBoit presented an unusual case of dull pink globules in a seborrheic keratosis, 16 analogous to Kamino bodies in Spitz nevus.…”

“…By electron microscopy, the intracytoplasmic hyaline inclusions in lichen amyloidosis are composed of a central core of thin filaments and thick filaments in the periphery. 15 These filaments are believed to represent ubiquitinated keratin complexes and possibly play a role in the formation of amyloid deposit in the dermis of this condition. When comparing with the nature of EHI of the above discussed pathologic entities, the EHI in the current lesion seem distinctly different.…”