Cutaneous Amyloidosis: Mass Spectrometry Based Proteomic Analysis Reveals Diverse Etiology Associated with Unique Histopathological Features
Melanie C Bois, Jason D Theis, Julie A Vrana, Carilyn N Wieland, Lori A Erickson, Karen L Grogg, Paul J Kurtin, Ahmet Dogan. Mayo Clinic, Rochester, MN
Background: Amyloidosis is caused by extracellular protein deposition in a physical format resistant to physiological degradation. It can involve any organ including the skin, and is classified based on the type of protein that constitutes the amyloid deposits. Accurate classification is essential as treatment varies widely depending on the type of amyloid present. While the pathogenesis of amyloidosis is well characterized, there is little information about the types of amyloid that involve the skin, and whether these types produce histologically recognizable patterns of deposition. In this study, using mass spectrometry based proteomic analysis (MS), we describe the detailed pathogenesis and histopathology of cutaneous amyloidosis.
Design: Biopsies of 45 cases of cutaneous amyloidosis were identified from the surgical pathology practice at Mayo Clinic. The histological pattern of amyloid deposition and associated pathological features in the adjacent skin was recorded. In each case amyloid deposits were characterized by MS, and immunohistochemistry for high molecular weight (HMW) keratins (Clone 34Beta12E) was performed. In cases with prominent plasma cells (n=17), in situ hybridization for immunoglobulin kappa and lambda light chain was performed.
Results: MS analysis identified a diverse etiology including immunoglobulins (AL, n=21 cases, 12 kappa, 9 lambda), HMW keratin (AKer, n=13 cases, keratins 5 and 14), insulin (AIns, n=3), transthyretin (ATTR, n=3), beta-2-microglobulin (AB2M, n=1), and other (n=4). Immunohistochemistry for HMW keratins was positive in all cases of AKer but negative for other cases. In situ hybridization identified light chain restricted plasma cells in AL (11/13). AKer cases were characterized by papillary dermis involvement (13/13) and epidermal hyperplasia/hyperkeratosis (10/13), AL by diffuse or nodular dermal involvement (21/21), epidermal atrophy (15/21) and plasmacytic infiltrate (16/21), ATTR by vascular involvement and AIns by deep dermal and subcutaneous involvement.
Conclusions: 1. The etiology of cutaneous amyloidosis most commonly includes the subtypes AL, AKer, ATTR and AIns.
2. Different types of amyloid have characteristic histological patterns and associations.
3. Most cases of cutaneous AL are caused by a subtle underlying plasma cell neoplasm.
4. Careful histopathological examination with typing MS is required for accurate classification and management of cutaneous amyloidosis.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 182, Tuesday Morning