Cutaneous AL-Type Amyloidomas as a Variant of Primary Cutaneous Marginal Zone Lymphoma: A Series of 30 Patients.

Abstract: AL-amyloidomas, particularly those primarily localized to the skin, present diagnostic and clinical challenges. They predominantly arise from immunoglobulin light chains, often due to plasma cell proliferation. The relationship between this entity, AL-amyloidomas, and primary cutaneous marginal zone lymphoma remains a subject of scientific debate. We conducted a retrospective, multicenter observational study, including 30 patients diagnosed with AL-amyloidomas. Demographic data, clinical manifestations, and histopathologic findings were reviewed. Various diagnostic techniques, such as light chain restriction, immunohistochemical analysis, polymerase chain reaction-based clonality testing, and next-generation sequencing, were used to further delineate the nature of these lesions. The cohort consisted of 12 men and 18 women, with a median age of 64.7 years. The most common clinical presentation involved plaques and nodules on the extremities and face. Histopathologically, monoclonal plasma cell infiltrates and amyloid deposits in the dermis and subcutis were observed. Most patients exhibited lambda light chain restriction. Molecular analysis revealed the presence of gene mutations in SPEN and TNFRSF13B in 1 patient. No cases progressed to systemic disease. Sjögren syndrome was the most frequently associated comorbidity. Our findings suggest that cutaneous AL-amyloidomas are indolent lesions and may represent a variant of primary cutaneous marginal zone lymphoma. These lesions exhibit distinct histopathologic features, such as amyloid deposition, and have a favorable prognosis with minimal risk of progression to systemic amyloidosis. This study supports the hypothesis that AL-amyloidomas are part of the broader spectrum of indolent B-cell lymphomas.