Double Trouble: A Case of Biopsy Proven ATTR and AL Cardiac Amyloid

Introduction Amyloid light chain (AL) and transthyretin amyloidosis (ATTR) account for >95% of all cardiac amyloidosis (CA) cases. The different CA subtypes may have overlapping clinical presentation necessitating further testing and investigation. Determination of CA subtype is critical, as management varies depending on the nature and source of the amyloidogenic protein. We present a very rare case of concomitant clinical and histology proven AL and ATTR amyloidosis. Case A 51-year-old Caucasian male with history of carpal tunnel syndrome, spinal stenosis and bicep tendon rupture initially presented to our clinic with shortness of breath. Initial evaluation included a transthoracic echocardiogram that demonstrated normal left ventricular systolic function and severe concentric left ventricular hypertrophy (interventricular septal wall diameter end diastole 1.92cm, posterior wall thickness end diastole 1.9cm) raising suspicion for amyloidosis. Technetium99m pyrophosphate (99mTc-PYP) scan showed a semi-quantitative visual score of grade 0 and no uptake on SPECT/CT. Cardiac MRI exhibited diffuse patchy mid wall late gadolinium enhancement and elevated extracellular volume (62%). Laboratory work-up included Hs-TNT 21ng/L, NT proBNP 1711pg/mL, kappa light chain 18.8mg/L, lambda light chain 219.2mg/L, FLC difference 199.8mg/L, K/L ratio 0.09 and immunofixation revealed a poorly defined region of restricted mobility in the lambda lane. Bone marrow biopsy (BMx) showed a lambda restricted plasma cell neoplasm representing 10% of marrow cellularity but no evident amyloid deposition. Fluorescence in situ hybridization results were normal. Right ventricular endomyocardial biopsy (EMBx) was performed for further assessment which demonstrated amorphous material strongly positive with thioflavin-S staining and immunohistochemistry observed amyloid deposits positive for lambda light chains. Laser capture microdissection coupled to mass spectrometry (LCM-MS) showed relatively equal abundance of lambda immunoglobulin light chains and transthyretin deposition. Genetic testing was negative, indicating wild type ATTR. AL amyloid treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone was initiated with plan to eventually start tafamidis in the future. Discussion This case highlights a rare but clinically relevant concurrent presence of two different types of amyloidosis in the same patient. There can be overlap in the clinical presentation of these amyloid subtypes. Proceeding with simultaneous 99mTc-PYP and hematologic work-up is highly recommended in all patients when amyloid is suspected to adequately investigate this disease. If initial work-up is suggestive of both AL and ATTR amyloidosis, histopathological investigation with EMBx and BMx is warranted. Utilization of LCM-MS provides more accurate amyloid tissue typing with high sensitivity and specificity. With an increasing number of treatment options for patients with CA, providers should perform a thorough and complete diagnostic work-up to ensure appropriate management is provided.