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- 2009-8-11日病例讨论
| 以下是引用mjma在2009-8-25 7:25:00的发言： Systemic amyloidosis (not the rare localized, idiopathic and asymptomatic forms such as seen in seminal vesicles/vasa deferentia and brain/leptomeninges) is not difficult to diagnose on histology once the deposits are significant in amount. However, when the disease is at early stage and deposits are scant, light microscopy may be false negative and it may take a good electron microscopist to detect it. These are particularly important for nerve and renal biopsies. On another note, the standard of patient care nowadays require at least an attempt to classify the amyloid found at the biochemical level. This, as pointed out by many, is no simple feat. Some experts prefer immunohistochemistry, while others prefer immunofluorescence. Still others insist on other esoteric biochemical assays. Only very rare medical centers where researchers focusing on amyloidosis exist have available a broad panel of antibodies to detect/identify various possible amyloidogenic proteins/peptides. Even so, there are always rare new amyloidogenic peptides that go unidentified. For any routine lab that handles renal biopsy, the incidence of amyloidosis is so low that having such an antibody panel is never cost-effective. This is a difficult gap for pathologists in practice to overcome. |
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淀粉样蛋白肾病 is a good thought based on the light microscopy. GBM毛刷状结构 highly suggests 淀粉样蛋白肾病. Congo red stain should demonstrate apple green birefringence under polarizer. But if the amyloid deposits are small, Congo red stain may not be sensitive enough to show the positivity. Immunofluorescence (IF) microscopy is not very helpful. Sometimes it is confusing. This is my personal experience. Some institutions claim that IF is the technique of choice for detection of amyloid derived from immunoglobulin light and heavy chains. In my lab, kappa and lambda light chain stains are lousy and difficult to interpret. I don't have amyloid panel for immunohistochemical stains. Nephrologists never push me to do the subclassification of amyloid.
Electron microscope is an important tool in diagnosis of renal amyloidosis. The fibrillary deposits must be present. The diameter of the amyloid fibril should be approximately 10 nm. It may be very similar with the fibrils seen in fibrillary glomerulonephritis (GN). The size of the fibril in fibrillary GN is approximately 20 nm. In real life, their measurements could be overlapped. The fibrils in fibrillary GN are not Congophilic. I often rely on Congo red stain to separate these two entities.
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本帖最后由 于 2009-08-25 02:45:00 编辑
I also use 高锰酸钾氧化 to classify amyloid. Most cases will become negative after 高锰酸钾氧化. I start to worry its reliability. Do you (Dr. Geng) use AL amyloid control or any controls?
No matter what I called in my report, our nephrologists will order urine tests and serology to detect Bence-Jones protein. Once they see light chains, they will also refer patients to hematologists.
Some laboratories use panel of antibodies to classify amyloid. I am considering it. The problem is that I have only about a handful of cases (amyloidosis) a year. The lab manager may think it is not cost effective to have these antibodies in the automated stainer.
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Systemic amyloidosis (not the rare localized, idiopathic and asymptomatic forms such as seen in seminal vesicles/vasa deferentia and brain/leptomeninges) is not difficult to diagnose on histology once the deposits are significant in amount. However, when the disease is at early stage and deposits are scant, light microscopy may be false negative and it may take a good electron microscopist to detect it. These are particularly important for nerve and renal biopsies. On another note, the standard of patient care nowadays require at least an attempt to classify the amyloid found at the biochemical level. This, as pointed out by many, is no simple feat. Some experts prefer immunohistochemistry, while others prefer immunofluorescence. Still others insist on other esoteric biochemical assays. Only very rare medical centers where researchers focusing on amyloidosis exist have available a broad panel of antibodies to detect/identify various possible amyloidogenic proteins/peptides. Even so, there are always rare new amyloidogenic peptides that go unidentified. For any routine lab that handles renal biopsy, the incidence of amyloidosis is so low that having such an antibody panel is never cost-effective. This is a difficult gap for pathologists in practice to overcome.
聞道有先後,術業有專攻
非常感谢QU老师和马老师的精彩点评，国内比较好的肾脏病研究所在肾淀粉样变性诊断中，先用刚果红染色阳性明确为淀粉样物质沉积后，用高锰酸钾预处理，AL型仍阳性，AA型转为阴性，但这只是较粗略的，仅供参考，不能作为确诊的依据，如高锰酸钾处理后转阴，用免疫组化抗AA蛋白抗体阳性，结合临床，诊断为AA型淀粉样变性，高锰酸钾处理后仍阳性的，行单克隆抗κ和λ检测，如为阳性，则诊断为AL型淀粉样变性，如为阴性，则需进一步检查是否为遗传性淀粉样变性。
正如QU老师所说的，我们每年遇到的淀粉样变性病例很少，暂时还没有购买这些抗体，所以只能粗略的分型，在高锰酸钾预处理的实验中，我们还没有AA型淀粉样病例（这个病例是我们遇到的第二例淀粉样变性），所以没法做阴性对照。
