Pathology Of Radiation Injury

Introduction

No single pathognomonic or specific morphologic feature characterizes radiation injury.

Pathologic changes seen in human tissues after radiation exposure:

Epithelial Changes after Radiation Exposure

Atrophy

  • Common
  • Progressive loss of number and volume of epithelial cells
  • Can be seen in any organ with epithelial lining:
    • Skin
    • Subcutaneous tissue
    • Gastrointestinal system
      • More sensitive
    • Genitourinary organs
      • Prostate
        • Reduction in number and size of acini
    • Respiratory tract
    • Breast
    • Salivary glands
  • Distribution is focal and random
  • Can be associated with fibrous tissue replacement months after exposure

Necrosis and Ulceration

  • Usually after atrophic changes
  • Sharply demarcated mucosal ulcers
  • Mucosal necrosis
    • Denudation of the epithelium with an ulcer base consisting of mixed inflammatory cells, necrotic debris, and granulation tissue, extending to the submucosa
  • Adjacent to the ulcer —> Submucosal fibrosis
  • Necrosis and Ulceration usually together.
  • Necrosis without ulceration is an uncommon manifestation of delayed radiation injury, except in the central nervous system where it can be seen in the white matter of the cerebral hemispheres.

Metaplasia

Metaplasia is the reversible replacement of a differentiated cell with another mature differentiated cell type.

Squamous metaplasia of benign prostatic ducts and urothelium is a common finding after radiation therapy.

Epithelial Atypia

  • Cytologic atypia is common
  • Radiation-associated epithelial atypia
    • Often observed in prostate, breast, bladder, lungs, salivary glands, and squamous mucosa of the head & neck.
  • May be misinterpreted as malignant disease
  • Significantly enlarged nuclei with dense “smudgy” appearance, cells with normal to low nuclear/cytoplasm ratio, and well-preserved tissue architecture, despite cellular pleomorphism

Dysplasia

  • Usually occurs in squamous lining
  • Premalignant alteration
  • Increased nucleus-to-cytoplasm ratio
  • Hyperchromasia
  • Irregular nuclear contours
  • Prominent nucleoli
  • Atypical mitoses
  • Loss of normal architecture

Stromal Changes

Fibrosis

  • Delayed radiation injury
    • Skin
      • Basiphilic acellular irregular reticular material/matrix
    • Head and neck
    • Breast
      • Mammary stromal fibrosis
      • Hyalinizing, inhomogeneous, acellular, and eosinophilic collagen deposition superimposed on mammary lobular unit atrophy
    • GU
    • GI
      • Extensive submucosal and, occasionally, transmural fibrosis
      • Circumferential submucosal fibrosis + thickened walls ==> luminal narrowing —> risk for obstruction
    • RARE in Lens and CNS
  • Dependent on dose and time from exposure
  • Within the radiation field
  • Hyalinizing
  • Acellular acidophilic collagen

Atypical Fibroblasts

  • Also called radiation fibroblasts
    • GI
    • Resp tract
    • Urinary
    • Skin
    • Soft tissue
    • Breast
  • Angulated basophilic cytoplasm (“swallow tail”), enlarged and hyperchromatic nuclei with no mitotic activity, cytomegaly
  • A reactive and benign reparative phenomenon and therefore have also been observed in association with acute and chronic inflammation.
  • Non-specific

Stromal Necrosis

  • Rare
  • Delayed
  • Any organ where stroma is present
  • Fat necrosis of the breast

Vascular Changes

  • Late vascular damage ==> Decreased perfusion ==> tissue ischemia, necrosis, ulceration, and fibrosis
  • Endothelial cells are the most radiation-sensitive in vascular structure
  • Intimal hyperplasia
  • Vascular wall fibrosis.

Capillaries

  • Most frequently affected
    • As they mainly composed of endothelial cells
  • Thrombosis
  • Obstruction
  • Capillary destruction
  • Telangiectasia
  • Hematuria

Arterioles

  • Arterioles damage in:
    • GI
    • Skin
    • Brain

Morphology:

  • Swollen endothelial cells
  • Hyperchromatic smudged nuclei
  • Endothelial cell proliferation
  • Indistinct smooth muscle cell borders
  • Thickening and hyalinization of the tunica media

Small and Medium-Sized Arteries

  • Cytologic atypia in endothelial cells
    • Nuclear enlargement with hyperchromatic and pyknotic nuclei that protrude “hobnail-like” into the vascular lumen
    • Random medial wall necrosis
    • Mural thickening with hyalinization
  • Occasionally, foamy or vacuolated macrophages within the vascular wall of small arterioles are identified

Three distinct changes:

  1. Intimal fibrosis
    • Concentric or Eccentric
    • Mild intimal cell atypia ==> vascular luminal narrowing ==> vascular occlusion
  2. Transmural healed necrosis
    • ==> segmental wall fibrosis + organizing thrombus & prominent perivascular fibrosis
  3. Intimal plaque formation with foamy macrophages.

Large Arteries and Veins

  • Not frequently observed
  • The venous segments of the vascular tree are the least affected by ionizing radiation

Pathologic Findings in Specific Organs

Heart and Great Vessels

  • Pericarditis
  • Pericardial effusion
    • Fibrosis and exudates
    • Used to be the most common* Myocardial fibrosis
  • CAD
    • the most common
  • Similar to those of atherosclerosis

Lung

Acute radiation pneumonitis (ARP)

  • Increased number of macrophages in alveolar spaces
  • Mixed chronic inflammatory infiltration
  • Fibroblasts in the alveolar septa
  • Type II pneumocyte hyperplasia
    • With variable degree of associated atypia
  • Hyaline membranes (homogenous, acellular, and eosinophilic material), lining the alveolar septa.
  • Similar to diffuse alveolar injury

Pulmonary fibrosis (PF)

  • Months or years after the development of ARP
  • Alveolar septa fibrosis
  • Diffuse fibrotic areas, or scarred tissue replacing alveolar spaces
  • Bronchiolitis obliterans
  • Unlike ARP, PF is observed as a sharply demarcated fibrous lesion within the previously irradiated site.

Liver

  • Venoocclusive disease (VOD)
    • Involves the central veins and afferent sinusoids of the lobules in the irradiated parenchyma
    • VOD is sharply limited to the exposed area
    • After chemotherapy, a more diffuse VOD is seen

Kidneys

  • Radiation-induced nephropathy:
    • Tubular atrophy
    • Stromal fibrosis
    • Diffuse glomerular sclerosis
    • Vascular intimal proliferation with foamy cells
    • Arteriolar narrowing