To the Editor.—I read with interest the excellent review of “An Organ System-Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology” in the March 2020 issue of the Archives of Pathology & Laboratory Medicine by Giannini and Nast.1 The number of amyloid types and their relevance to diagnostic pathology and patient management will no doubt continue to increase, as they continuously have over the years. Although the review focused specifically on surgical pathology, my experience with cases I see in consultation and discussions with colleagues is that it is not uncommon to see amyloid-related processes in hematoma and brain biopsy specimens handled by surgical pathologists in general practice, even in large medical centers and academic centers where a neuropathologist is not available. As such, I would like to bring to the attention of the readers a few points in this context.
Cerebral amyloidoma is a rare, focal, mass-forming amyloid light chain deposition associated with clonal B-cell population without systemic disease.2 Otherwise, beta-amyloid (Aβ) is the most common type of amyloid seen in the brain.3 Autopsy pathology and detailed discussions aside for the sake of this correspondence on practical diagnostic issues, the typical scenario is the identification of Aβ in the walls of the blood vessels in the background of blood clot (Figure 1), leading to the diagnosis of Aβ-cerebral amyloid angiopathy (Aβ-CAA), the most common type of CAA, originally described as congophilic angiopathy. The hemorrhage is typically lobar/hemispheric, rather than basal ganglionic, thalamic, or pontine hemorrhage of hypertension, and can be multiple metachronously or synchronously, drawing attention to their suspected nature. CAA4 is a common cause of cerebral hemorrhage in those older than 60 years of age. Its prevalence increases with age. Rare hereditary forms are also present. If there are small fragments of gray matter admixed in the blood clot, it is possible to identify the plaque pathology (Figure 1). Although the diagnosis of Alzheimer disease requires a more in-depth examination of the brain, many unsuspected patients can be brought to clinical attention, with a direction for future care for the survivors and their families. Two relatively recently characterized pathologic processes involving Aβ in the brain are CAA-related inflammation and Aβ-related angiitis.5 Their clinicopathologic and radiologic features are different from primary central nervous system vasculitis and pure CAA, and can be biopsied because of suspected vasculitis or their focal radiologic findings. CAA-related inflammation is an inflammatory reaction around the blood vessels containing Aβ, but without vascular destruction (Figure 2), whereas Aβ-related angiitis results in a vasculitis picture, with destruction of the blood vessel.
These Aβ pathologies are limited to the central nervous system, but with significant and frequently catastrophic consequences. Their immunohistochemical identification in otherwise mundane or unremarkable-appearing specimens can result in drastic changes in management, as well as in the lives of their families. Although no definitive treatment is available, immunomodulatory therapies and management to prevent cerebrovascular accidents can be beneficial. Immunohistochemistry for Aβ, if not available in-house, can be performed as a tech-only service in commercial laboratories and is easy to interpret without major technical issues.
The author has no relevant financial interest in the products or companies described in this article.