心臟類澱粉沉積症之臨床病理特性與免疫化學染色分析

Abstract

心臟類澱粉沉積症為不正常的類澱粉蛋白沉積在心臟上，可能導致心律不整、心肌病變、心衰竭等，是心因性猝死的原因之一，具有法醫學上的重要性。依照 沉積的類澱粉蛋白種類可進行分型，最常見的兩種類型是輕鏈蛋白類澱粉沉積 (AL) 與運甲狀腺素蛋白類澱粉沉積 (ATTR)，其中ATTR又可依TTR基因是否有突變分為突變型 (ATTRv) 與非突變型 (ATTRwt)。 本研究回溯收集臺大醫院2002年到2024年共72例診斷為心臟類澱粉沉積症之病理檢體進行分析。統計結果顯示AL初始症狀常是心衰竭或全身性症狀，症狀出現至確診歷時較短，除了影響心臟，也會影響腎臟、骨頭，病患預後較差；ATTR初始症狀常是神經學相關症狀，症狀出現至確診歷時較久，除了影響心臟，較常影響神經系統，病患預後相對較好。 使用免疫化學染色進行類澱粉分型正確的比例為81%。TTR抗體之敏感度與特異度是92.5%與90.6%；κ light chain抗體分別為62.5%與95.2%；λ light chain 抗體則是95.8%與80.9%。AL個案因輕鏈固有性質可能導致偽陰性，或者顯現 非特異性背景染色；TTR抗體雖然敏感性高，但也有交叉反應導致偽陽性的問題。判讀免疫染色結果時應比對剛果紅染色範圍作為參考，另外加上陽性TTR對照組與陰性light chain對照組，有助於增加染色判讀之信心。 總結而言，雖然單純使用免疫染色無法百分之百正確分型心臟類澱粉沉積症，但綜合臨床資訊判斷後，免疫染色法仍不失為一種便宜、容易進行的分型方法。

Cardiac amyloidosis is characterized by the abnormal deposition of amyloid proteins in the heart, which can lead to arrhythmia, cardiomyopathies, heart failure, and is one of the causes of sudden cardiac death, holding significant importance in forensic medicine. Cardiac amyloidosis can be categorized based on the type of amyloid protein, with the most common types being light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), the latter further categorized into mutant (ATTRv) and wild-type (ATTRwt) based on the status of TTR gene mutation. This study retrospectively analyzed 72 pathological specimens diagnosed as cardiac amyloidosis at National Taiwan University Hospital from 2002 to 2024. Statistical analysis revealed that initial symptoms of AL often manifest as heart failure or systemic symptoms, with a shorter duration from symptom onset to diagnosis. Besides affecting the heart, AL can also impact the kidneys, bones, and bone marrow, resulting in poorer prognosis. On the other hand, initial symptoms of ATTR typically involve neurological manifestations, with a longer duration from symptom onset to diagnosis. Apart from cardiac involvement, ATTR more commonly affects the nervous system, leading to relatively better prognosis. Using immunohistochemical staining for classifying cardiac amyloidosis, the correct classification rate was 81%. The sensitivity and specificity of TTR antibody were 92.5% and 90.6%, respectively; for κ light chain antibody, they were 62.5% and 95.2%, respectively; and for λ light chain antibody, they were 95.8% and 80.9%, respectively. In AL cases, the inherent properties of light chains may result in false negativity or non-specific background staining. Although TTR antibody has high sensitivity, it also shows cross-reactivity with light chain amyloidosis that can lead to false positivity. When interpreting immunohistochemical staining results, the Congo red staining area should be used as a reference. Additionally, including external positive TTR controls and negative light chain controls should aid in the interpretation of the results. In conclusion, although immunohistochemical staining alone may not achieve 100% accuracy in classifying cardiac amyloidosis, it remains a cost-effective and easily accessible method when integrated with clinical information for classification.