Primary amyloidosis of the breast excised using an oncoplastic reduction approach.

We present a case of surgical removal of primary amyloidosis of the breast utilizing an oncoplastic reduction pattern technique. Primary amyloidosis of the breast is a very rare benign disease characterized by accumulation of insoluble amyloid protein. Biopsy is required for definitive diagnosis, and surgical removal of the mass with clear margins is the main treatment for primary amyloidosis. Oncoplastic reduction pattern technique allows for removal of large breast lesions and correction of the resulting defect by combining the extirpative principles of surgical oncology with the aesthetic principles of breast reduction surgery.

The Challenges in Chemotherapy and Stem Cell Transplantation for Light-Chain Amyloidosis.

Light-chain (AL) amyloidosis is a systemic syndrome characterized by progressive organ dysfunction leading to organ failure and death. The heart is the most commonly involved organ and the leading determinant of short- and long-term survival. Pathogenic free light chains, fragments of intact immunoglobulins, are the amyloidogenic proteins and are secreted by clonal bone marrow plasma cells. The goal of therapy is to cut off the supply of these light chains to allow organ recovery. Therapies for AL amyloidosis are based on therapies used to treat multiple myeloma, which is a more common plasma cell disorder. However, because patients with AL amyloidosis have organ dysfunction, including multiorgan involvement, they generally have poor treatment tolerance and increased treatment toxicity. Unfortunately, the consequences of toxicity and difficulty in tolerating treatment may result in a fatal outcome. Therefore, treatment should balance the goal of achieving a rapid and meaningful reduction in the circulating light chains while maximizing patient safety. This approach is best achieved by a multidisciplinary approach involving related medical disciplines. This review describes the challenges of managing patients with AL amyloidosis and provides a guide for physicians with a specific focus on cardiac management. We address the role of autologous stem cell transplantation vs standard-intensity therapies in a risk-adapted approach and discuss the management of commonly encountered toxicities. Guidance on response assessment, including organ response, is provided. With expansion in treatment options, we anticipate continuous improvement in outcome for this disease. Nonetheless, early diagnosis remains the best approach to improve disease burden and outcome.

Orbital AL amyloid.

Amyloidosis and lymphoma localized to the ocular adnexa are rare, and their presentation may resemble more common inflammatory conditions such as autoimmune disease or infection, which can protract diagnostic evaluation and delay eventual therapy. In a patient with recalcitrant facial and tooth pain and ophthalmoplegia, evaluation should include careful histopathologic analysis of biopsy specimens. We report a case of orbital AL amyloidosis associated with localized lymphoma that presented with intractable dental pain and progressed to bilateral complete ophthalmoplegia.

Prognostic value of novel imaging parameters derived from standard cardiovascular magnetic resonance in high risk patients with systemic light chain amyloidosis.

BACKGROUND: The differentiated assessment of functional parameters besides morphological changes is essential for the evaluation of prognosis in systemic immunoglobulin light chain (AL) amyloidosis. METHODS: Seventy-four subjects with AL amyloidosis and presence of late gadolinium enhancement (LGE) pattern typical for cardiac amyloidosis were analyzed. Long axis strain (LAS) and myocardial contraction fraction (MCF), as well as morphological and functional markers, were measured. The primary endpoint was death, while death and heart transplantation served as a composite secondary endpoint. RESULTS: After a median follow-up of 41 months, 29 out of 74 patients died and 10 received a heart transplant. Left ventricular (LV) functional parameters were reduced in patients, who met the composite endpoint (LV ejection fraction 51% vs. 61%, LAS - 6.9% vs - 10%, GLS - 12% vs - 15% and MCF 42% vs. 69%; p <  0.001 for all). In unadjusted univariate analysis, LAS (HR = 1.05, p <  0.001) and MCF (HR = 0.96, p <  0.001) were associated with reduced transplant-free survival. Kaplan-Meier analyses showed a significantly lower event-free survival in patients with reduced MCF. MCF and LAS performed best to identify high risk patients for secondary endpoint (Log-rank test p <  0.001) in a combined model. Using sequential Cox regression analysis, the addition of LAS and MCF to LV ejection fraction led to a significant increase in the predictive power of the model (χ2 (df = 1) = 28.2, p <  0.001). CONCLUSIONS: LAS and MCF as routinely available and robust CMR-derived parameters predict outcome in LGE positive AL amyloidosis. Patients with impaired LV function in combination with reduced LAS and MCF are at the highest risk for death and heart transplantation.

Morphological and primary structural consistency of fibrils from different AA patients (common variant).

Aims: To test the hypothesis that the fibril morphology and the fibril protein primary structure are conserved across different patients suffering from the common variant of systemic Amyloid A (AA) amyloidosis. Methods: Amyloid fibrils were extracted from the renal tissue of four patients. The fibril morphology was analysed in negatively stained samples with transmission electron microscopy (TEM). The fibril protein identity and fragment length were determined by using mass spectrometry. Results: The fibrils show a consistent morphology in all four patients and exhibit an average width of ∼9.6 nm and an average pitch of ∼112 nm. All fibrils are composed of polypeptide chains that can be assigned to human serum amyloid A (SAA) 1.1 protein. All fragments lack the N-terminal arginine residue and are C-terminally truncated. Differences exist concerning the exact C-terminal cleavage site. The most prominent cleavage site occurs at residues 64-67. Conclusions: Our data demonstrate that AA amyloid fibrils are consistent at the level of the protein primary structure and fibril morphology in the four analysed patients.

[Amyloidosis in larynx].

Localised laryngeal amyloidosis is a rare tumour of the upper respiratory tract, which is characterised by extra-cellular accumulation of proteinaceous material in the submucosa. The aetiology is still unclear. This is a case report of localised multifocal amyloidosis located to larynx and rhinopharynx. A 50-year-old women with a history of progressive dysphonia and dyspnoea underwent ear-nose-throat and haematological investigation with no signs of systemic involvement. The amyloid deposits in larynx were effectively treated with laser resection in general anaesthesia and regular follow-up.

Isolated Light Chain Amyloidosis Involving the Parotid Gland: A Case Report.

Amyloidosis in the parotid gland is rare and is usually associated with systemic amyloidosis. Localized amyloidosis in the parotid gland is extremely rare. We present a case of localized light chain amyloidosis of the parotid gland without systemic involvement. A 70-year-old woman presented with an asymptomatic swelling of the right parotid region. The findings of a physical examination, hematologic and biochemical investigations, imaging, and cytology were inconclusive. The patient underwent an extracapsular dissection of the right parotid gland. Histologic analysis showed that the tissue of the right parotid gland mostly consisted of amyloid deposition. The amyloid stained with antibodies to lambda light chains. Additional investigations showed no systemic involvement. The patient is asymptomatic 5 months after surgery. Clinicians should be aware of the possibility of localized amyloid light chain amyloidosis in the parotid gland, especially if magnetic resonance imaging, computed tomography imaging, and ultrasound findings are inconclusive, and they should recognize, evaluate, and treat it accordingly.

[Heart transplantation in AL amyloidosis]. / Livräddande behandling vid hjärtamyloidos av AL-typ - Hjärttransplantation med efterföljande autolog stamcellstransplantation kan ge goda resultat.

Amyloidosis is a disease complex characterized by the deposition of protein fibrils in various tissues, which leads to structural and functional derangement of the affected organ. There are different types of amyloidosis categorized on the basis of the type of protein fibrils deposited. Cardiac involvement has been predominantly noted in amyloid light chain (AL) amyloidosis and is the major prognostic determinant and influences the therapeutic strategy.  In AL amyloidosis, heart transplantation is generally not recommended because of a high risk of recurrence in the transplanted heart and poor survival rate. However, a favourable outcome can be achieved if heart transplantation is followed by an autologous stem cell transplantation (ASCT). We describe our experience from the two first patients with AL amyloidosis treated with heart transplantation and subsequent ASCT at Sahlgrenska University Hospital.

Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis.

BACKGROUND: To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. METHODS: Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. RESULTS: We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p < 0.0001). AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ2 = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ2 = 6.2, p = 0.01). CONCLUSION: In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

Anterior Aortic Plane Systolic Excursion: A Novel Indicator of Transplant-Free Survival in Systemic Light-Chain Amyloidosis.

BACKGROUND: Anterior aortic plane systolic excursion (AAPSE) was evaluated in the present pilot study as a novel echocardiographic indicator of transplant-free survival in patients with systemic light-chain amyloidosis. METHODS: Eighty-nine patients with light-chain amyloidosis were included in the post-hoc analysis. A subgroup of 54 patients with biopsy-proven cardiac amyloid infiltration were compared with 41 healthy individuals to evaluate the discriminative ability of echocardiographic findings. AAPSE is defined as the systolic excursion of the anterior aortic margin. To quantify AAPSE, the M-mode cursor was placed on the aortic valve plane in parasternal long-axis view at end-diastole. Index echocardiography had been performed before chemotherapy. Median follow-up duration was 2.4 years. The primary combined end point was heart transplantation or overall death. RESULTS: Mean AAPSE was 14 ± 2 mm in healthy individuals (mean age=57 ± 10 years; 56% men; BMI=25 ± 4 kg/m2). AAPSE < 11 mm separated patients from age-, gender-, and BMI-matched control subjects with 93% sensitivity and 97% specificity. Median transplant-free survival of patients with AAPSE < 5 mm was 0.7 versus 4.8 years (P = .0001). AAPSE was an independent indicator of transplant-free survival in multivariate Cox regression (echocardiographic model: hazard ratio=0.72 [P = .03]; biomarker model: hazard ratio=0.62 [P = .0001]). Sequential regression analysis suggested incremental power of AAPSE as a marker of transplant-free survival. An ejection fraction-based model with an overall χ2 value of 22.8 was improved by the addition of log NT-proBNP (χ2 = 32.6, P < .005), troponin-T (χ2 = 39.6, P < .01), and AAPSE (χ2 = 54.0, P < .0001). CONCLUSIONS: AAPSE is suggested as an indicator of transplant-free survival in patients with systemic light-chain amyloidosis. AAPSE provided significant incremental value to established staging models.

Opciones de tratamiento para amiloidosis hepática / Treatment options for hepatic amyloidosis

CONTEXTO: La amiloidosis sistémica primaria ocurre en alrededor del 8 por millón de personas por año. La edad media al momento del diagnóstico es de 64 años, pero se puede presentar a cualquier edad. La relación hombre-mujer es de casi 2:1. Todas las estrategias actuales de manejo incluyen la destrucción de las células plasmáticas responsables de la síntesis de cadena ligera de inmunoglobulina. El objetivo de la terapia incluye la eliminación de las cadenas proteicas ligeras con plegamiento erróneo lo más pronto posible para evitar su toxicidad y el tratamiento de soporte para el o los órganos afectados. TRATAMIENTO: El tratamiento de elección es melfalán en altas dosis más trasplante autólogo de células madre (SCT). Sin embargo este tratamiento no está indicado en pacientes con alguno de los siguientes criterios: Contraindicaciones absolutas: -Insuficiencia cardíaca congestiva; -Bilirrubina total >3.0 mg/dL; - Fracción de eyección evaluada por ecocardiografía <30%. Contraindicaciones relativas: -Creatinina sérica < 2.0 mg/dL; -Engrosamiento del tabique interventricular <15mm; -Edad >60 años; -Más de dos órganos involucrados. En pacientes con amiloidosis AL que no son candidatos para terapia de remplazo autólogo con células madre se sugiere considerar el uso de melfalán asociado a dexametasona en altas dosis en lugar de la asociación melfalán más prednisona. La combinación de melfalán y dexametasona tiene el historial más largo con resultados de 5 años de seguimiento y es considerado como la principal opción para el tratamiento de terapia pacientes con amiloidosis AL que no son candidatos para terapia de remplazo autólogo con células madre. Algunos estudios no encontraron diferencias significativas en la sobrevida y tasas de remisión entre melfalán+SCT versus melfalán+dexametasona. RESULTADOS DE LA BÚSQUEDA: Documentos selecionados: 10. Recomendaciones y nivel de evidencia (GRADE): En pacientes con amiloidosis AL que no son candidatos para terapia de remplazo autólogo con células madre se sugiere considerar el uso de melfalán asociado a dexametasona en altas dosis en lugar de la asociación melfalán más prednisona. El trasplante hepático no debe considerarse como una opción de primera línea para el tratamiento de amiloidosis AL. CONCLUSIÓN: El pronóstico para los pacientes con amiloidosis primaria AL (es decir, cadena ligera de inmunoglobulina) después del tratamiento es dependiente del impacto de la terapia en la supresión de la síntesis de inmunoglobulina de cadena ligera. En los pacientes que alcanzan una respuesta completa al tratamiento, la supervivencia a los 7 años se aproxima al 80%. Para los pacientes que logran una reducción del 50% en el tratamiento a los 7 años, la supervivencia es del 57%. Para los pacientes que no han podido demostrar una respuesta con el uso de terapias de rescate apropiadas, la supervivencia es del 30%.