Amyloidosis of the Lung

Abstract

Context.—Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To date, 31 fibril proteins have been identified in humans, and it is now recommended that amyloidoses be named after these fibril proteins. Based on this classification scheme, the most common forms of amyloidosis include systemic AL (formerly primary), systemic AA (formerly secondary), systemic wild-type ATTR (formerly age-related or senile systemic), and systemic hereditary ATTR amyloidosis (formerly familial amyloid polyneuropathy). Three different clinicopathologic forms of amyloidosis can be seen in the lungs: diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis, and tracheobronchial amyloidosis. Objective.—To clarify the relationship between the fibril protein–based amyloidosis classification system and the clinicopathologic forms of pulmonary amyloidosis and to provide a useful guide for diagnosing these entities for the practicing pathologist. Data Sources.—This is a narrative review based on PubMed searches and the authors' own experiences. Conclusions.—Diffuse alveolar-septal amyloidosis is usually caused by systemic AL amyloidosis, whereas nodular pulmonary amyloidosis and tracheobronchial amyloidosis usually represent localized AL amyloidosis. However, these generalized scenarios cannot always be applied to individual cases. Because the treatment options for amyloidosis are dependent on the fibril protein–based classifications and whether the process is systemic or localized, the workup of new clinically relevant cases should include amyloid subtyping (preferably with mass spectrometry–based proteomic analysis) and further clinical investigation.

Pleural amyloidosis imitating pleural malignancy

“…The most common pulmonary manifestation is amyloid deposition in small pulmonary artery branches, usually an incidental finding at autopsy in elderly patients (so-called ‘senile amyloid’) and generally of no clinical significance, but occasionally extensive vascular deposition is associated with pulmonary hypertension. Amyloid can also produce single or multiple nodules, which are sometimes a manifestation of an underlying myeloma; and diffuse septal amyloid, where amyloid is laid down along alveolar walls, producing a physiologic, imaging, and at first glance, pathologic impression of an interstitial lung disease [1].…”

The Lung in Dysregulated States of Humoral Immunity

“…More frequently primitive, amyloidosis may be associated with another disease. AL amyloidosis (immunoglobulinic or “primary” amyloidosis) is by far the leading type of amyloidosis in the respiratory system, while AA amyloidosis is much rarer [115,116]. AL amyloidosis is most commonly found in a context of plasma cell disorder, while 5% concern B-cell lymphoma.…”

“…AL amyloidosis is most commonly found in a context of plasma cell disorder, while 5% concern B-cell lymphoma. All structures of the respiratory system may be affected: airways, parenchyma, pleura, intrathoracic lymph nodes, and vessels [116,117]. Lesion distribution varies according to the localized or nonlocalized nature of amyloidosis and its subtype (Table 3) [118].…”

“…Cystic lesions are uncommon and often associated with nodules [155]. The mean age at diagnosis is 67 years, and the male/female ratio is 3:2 [116,126,156]. …”

“…Systemic amyloidosis involves several organs with high IgM paraprotein and underlying Waldenström macroglobulinemia [170,171,172]. While usually AL, localized parenchymal amyloidosis may be AA, wild-type ATTR, mixed AB2M/AL amyloidosis and, exceptionally, senile [116]. …”