Skin and soft tissue manifestations in amyloid light-chain amyloidosis
Year: 2025
Type: article
Study design: Case Report
Abstract: Amyloidosis is a group of protein misfolding disorders characterized by extracellular deposition of insoluble polymeric protein fibrils that lead to organ dysfunction. Any organ may be involved, with the predominant involvement of the heart, kidney, peripheral or autonomic nerves, liver, and soft tissue. Clinical features depend on the organs involved. Diagnosis is often delayed due to rarity of the disease, its myriad manifestations, and presentation to different medical specialties.[1] Here, we describe a patient having amyloid light-chain (AL) amyloidosis and who had florid skin manifestations with tell-tale signs of amyloidosis. A 74-year-old woman with comorbidities of hypertension, ischemic heart disease, and rheumatoid arthritis presented with paresthesia of the distal extremities, swelling of legs, pain and decrease in movement of both shoulders, fatigue on exertion, yellowish patches around the mouth, and difficulty in swallowing for two years duration. On examination, we observed multiple yellowish patches around the mouth, tragus of both ears, anterior neck and web spaces of hands with an enlarged, mobility restricted tongue [Figure 1a-d]. She had pallor, pedal edema with restricted movement of both shoulders and rounded swelling in the left shoulder region (shoulder pad sign, Figure 1e and f). MRI of the left shoulder showed a poorly circumscribed expansile soft tissue mass. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) showed non FDG avid periarticular soft tissue deposits in bilateral shoulders causing erosion of joint surfaces [Figure 1h]. A lesion biopsy showed amyloid deposition with apple green birefringence on Congo Red stain. Lab evaluation showed Hb level of 13 g/dl, WBC at 7.76 × 109/L, platelet at 406 × 109/L, creatinine level at 0.82 mg/dl, albumin at 3.67 g/dl, β2 microglobulin at 3.99 mg/dl, calcium at 12.01 mg/dl, NTProBNP of 6283 (0–300 pg/ml), Trop T at 0.078 (0–37), 24-hour urinary protein at 99.4 mg. No M-band was detected. Serum free light-chain (sFLC) assay showed increased chains (κ = 20.58 mg/L, λ = 1788.69 mg/L). The bone marrow was hypercellular with increased clonal plasma cells (15%) and without any amyloid deposit. Fluorescence in situ hybridization (FISH) was negative for Immunoglobulin heavy chain (IgH) translocation. 2D echo showed hypokinetic inferior wall with left ventricular ejection fraction (LVEF) of 50%. She was diagnosed with AL amyloidosis of revised Mayo Clinic (2012) stage IV. After discussion about treatment options, including daratumumab, she was started on Bortezomib- cyclophosphamide dexamethasone (VCD) chemotherapy.Figure 1: Images of skin and soft tissue changes in amyloidosis. Picture (a-d) Skin findings in a case of amyloidosis. Yellowish patches, which are amyloid deposits, are seen in the perioral region and in front of the neck (a), both hands in the first web spaces (b). The enlarged tongue (macroglossia), with yellowish amyloid deposition in the undersurface of the tongue, causes restricted movement (c and d). Picture (e and f) Amyloid infiltration of the periarticular region in the left shoulder producing classical “shoulder pad sign”, which is pathognomonic of AL amyloidosis (f). Gross pedal edema causing difficulty in movement (f). Picture (g) 12-lead ECG of the patient showing low voltage in limb leads, q waves in leads III, aVF, V1, V2. Picture (h) CT image showing multiple ill-defined periarticular soft tissue deposits in the bilateral shoulder joint, causing erosion of adjacent joint surfacesIn AL amyloidosis, a small plasma cell clone produces monoclonal light chains that deposit as amyloid fibrils and exert organ toxicity. We describe this case because of florid amyloid features and for emphasizing the need for early diagnosis for optimal outcomes. Systemic treatment targets the underlying clone and should be risk-adapted to rapidly administer the most effective and safely tolerable therapy. Treatment depends upon Autologous stem cell transplant (ASCT) eligibility. For those not eligible, chemotherapy with bortezomib backbone-CyBorD or BMDex has been the standard of treatment. t(11;14) has a worse outcome with bortezomib, while gain 1(q21) is associated with poorer response to melphalan. In the current era, daratumumab and CyBorD combination has emerged as a very effective treatment option and is considered the standard of care based on the Andromeda study.[2,3] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient and relative have given their consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Indian Journal of Cancer
Institution: Tata Memorial Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4410456299