The pathology of ionizing radiation as defined by morphologic patterns

Abstract

This article presents a brief description of the effects of ionizing radiation in human tissues, as seen by the Pathologist. The lesions that occur in multiple organ/tissues will be discussed, dividing them into those that affect (a) the parenchyma or epithelia, (b) the stromal elements, and (c) the blood vessels. Since not all lesions fit into these patterns, the exceptions will be described as characteristic organ lesions. Unless specified otherwise the alterations presented are those that result from electromagnetic radiation (x-rays and gamma rays) as used for clinical radiation therapy. Most of the material presented will be delayed injury (i.e. months-to-years after exposure). The epithelial/parenchymal lesions include atrophy, necrosis, metaplasia, cellular atypia, dysplasia, and neoplasia. The common stromal lesions--the best recognized by pathologists--include fibrosis, fibrinous exudates, necrosis (with a paucity of cellular inflammatory exudates), and atypical fibroblasts. The vascular lesions are quite consistent: most often they affect the microvessels (capillaries, sinusoids) producing lethal and sublethal damage to the endothelial cells, with capillary rupture or thrombosis. Medium-size vessels show neointimal proliferation, fibrinoid necrosis, thrombosis, or acute arteritis. Damage in large vessels is less common; it occurs more in arteries than in veins and includes neointimal proliferation, atheromatosis, thrombosis and rupture (a dramatic complication). Some of the characteristic organ lesions are veno-occlusive liver disease, acute radiation pneumonitis, permanent bone marrow hypoplasia or aplasia, and colitis cystica profunda. Neoplasms are a well-recognized delayed complication of radiation and will not be described in detail. It is important to remember that there are no pathognomonic features of injuries produced by ionizing radiation. Nonetheless, although not specific individually, the combined features are characteristic enough to be recognized.

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“…Particularly microvessels are extremely sensitive to IR: irradiation often results in a rupture of the capillaries, thrombosis, and telangiectasia (27). In small-sized arteries (having a thin muscular wall and measuring up to 100 lm in external diameter), IR causes a neointimal proliferation, thrombosis, fibrinoid necrosis, and acute arthritis, whereas larger blood vessels (ample lumen and thick muscular wall, >500 lm external diameter) seem to be less affected (27).…”

“…In small-sized arteries (having a thin muscular wall and measuring up to 100 lm in external diameter), IR causes a neointimal proliferation, thrombosis, fibrinoid necrosis, and acute arthritis, whereas larger blood vessels (ample lumen and thick muscular wall, >500 lm external diameter) seem to be less affected (27). Interestingly, ECs of various organs differ in their sensitivity to IR: in vitro studies show that, for example, sinusoidal EC of the liver are highly radioresistant, whereas microvascular EC of the skin are rather radiosensitive (62).…”

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“…In large vessels as femoral artery, the first changes may include myointimal proliferation, thrombosis and rupture, while arterial fibrosis, stenosis and accelerated local atherosclerosis appear later (7,8). These arteries are less often affected than the smaller vessels, due to their large lumen and thick wall, made of relatively radioresistant cells (9). These changes leading to the thickening of the endothelium and fibrosis induce the narrowing of the arterial lumen, favoring thrombus formation, embolization, or occlusion (10).…”

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“…In general, radiation-induced vessel changes are predominantly confi ned to small-and medium-sized arteries and not equally distributed within a defi ned volume of irradiation, but rather focally despite radiation exposure of all small vessels in the same way. In contrast, large arteries and veins are less often affected by irradiation than the smaller vessels (Fajardo 2005 ).In summary, the following radiation-induced main effects can be detected either based on histologic or clinical examinations in the arterial system: • Initially, functional disorder of the vessel innervation and release of cytokines which lead to arterial vessel dilatation ( skin erythema ) -a typical early effect occurring during and shortly after irradiation (see Sect. 5.2 ).…”

“…In this context, the radiosensitivity of tissues depends both on inherent characteristics of cells, with the most important being the cell division rate and degree of differentiation, and on conditional factors including treatment parameters such as type of radiation, mode of delivery, total dose, and fractionation. Consequently, multipotent or pluripotent cells with a high mitotic rate and a long mitotic future are the most radiosensitive (Rubin and Casarett 1968 ).The predominant radiation-induced late effects are characterized by the following:• Atrophy of epithelial tissues including parenchymal and glandular organs • Fibrosis of stromal tissues • Sclerosis of blood vessels (Fajardo 2005 ) These general parenchymal reactions will be described in detail in the following sections. …”