Breast malignant, males, children
Miscellaneous
Treatment effect - Radiation therapy

Author: Emily S. Reisenbichler, M.D. (see Authors page)

Revised: 26 July 2017, last major update July 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Radiation therapy effects breast

Related topics: Atypical or benign vascular lesion, post radiation
Cite this page: Treatment effect - Radiation therapy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignanttreatmenteffectradiation.html. Accessed July 26th, 2017.
Definition / general
  • Whole breast irradiation primarily occurs following breast conserving surgery for breast carcinoma
  • Also patients with Hodgkin lymphoma receiving mediastinal radiation with secondary breast exposure to radiation
  • Radiation can also be delivered intraoperatively to the surgical cavity after removing the tumor but prior to closing the wound
Essential features
  • Effects of radiation on skin, such as changes in vascularity, pigmentation and fibrosis, may be induced acutely or as a latent reaction years after radiation (Clin Cosmet Investig Dermatol 2016;9:473)
  • Increased risk of secondary radiation induced sarcomas, most commonly angiosarcoma, with an incidence of 0.03 - 0.2% and average latency period of 10 years (Cases J 2008;1:313) (see also Breast angiosarcoma)
  • Radiation may induce cytologic changes in normal breast tissue that can mimic atrophy, recurrent carcinoma or sarcoma
Clinical features
  • In acute stages, breast skin may become pink or red and peel, as with a sunburn, followed by thickening of the skin in later stages
  • Firmness of the breast may result from fibrosis
  • Lactation may still occur after pregnancy in at least 50% of women who have undergone prior radiation therapy, but production is reduced
  • Lactation is unaffected in the contralateral, untreated breast (Expert Rev Anticancer Ther 2013;13:159)
  • Radiation may induce bullous pemphigoid in the skin (Dermatol Online J 2016;22:13030)
  • In patients undergoing immediate reconstructive surgery, volume loss and fat necrosis may occur due to post mastectomy radiation; however it has not resulted in higher rates of revision surgery in the radiated breast (Ann Plast Surg 2013;71:149)
Radiology description
  • Mammographic changes following radiation therapy include increased breast density and skin thickening, both of which are more common following whole breast radiotherapy than with intraoperative radiotherapy (Eur J Surg Oncol 2014;40:163)
Case reports
Microscopic (histologic) description
  • Giant tumor cells with bizarre nuclear changes (J Clin Pathol 1990;43:152), naked nuclei and abnormal mitotic figures
  • Extensive tumor necrosis demarcated by thick fibrous walls (when radiating tumor prior to surgery)
  • Changes in nonneoplastic breast take place primarily in the terminal duct lobular unit and include atypia, lobular sclerosis and atrophy (may distort lobular architecture and obscure myoepithelial cells, Hum Pathol 1984;15:545)
  • Intimal thickening in small muscular arteries (Radiother Oncol 2009;92:477) and fat necrosis, but usually no mitotic activity or loss of polarity
  • Epithelial atypia in larger ducts ranges from mild to severe but proliferation of the epithelium is generally seen only with mild cytologic atypia (Am J Surg Pathol 2004;28:47)
  • Atypical stromal fibroblasts
  • Changes do not regress over time (Am J Surg Pathol 2004;28:47)
Microscopic (histologic) images

Images hosted on PathOut server:

Thickened basement membranes

Atypical stromal fibroblasts

LCIS unchanged by
radiation compared
to atrophic
normal glands

Collagenization of
intralobular stroma and
glandular atrophy (AFIP)

Images hosted on other servers:

Large stromal
fibroblasts may
also occur in
nonirradiated tissue

Atypia in normal duct

Atypia within normal lobule

Fat necrosis post iridium implant

Vessel shows
reduplicated elastic
lamina and intimal
thickening (elastin stain)

Fig. 1 Edematous lobules
with atypia of some
epithelial cells

Fig. 2 Edematous lobules
with atypia of some
epithelial cells

Atrophic lobules
with atypia of some
epithelial cells

Atypical stromal cells,
lymphocytic infiltrate
and increased collagen
bundles
Differential diagnosis
  • Recurrent carcinoma (invasive or in situ): cells should be keratin positive and demonstrate similar histologic grade and receptor profile as the previous carcinoma
    • Atypical stromal fibroblasts will be keratin negative
    • Cytologic atypia in a lobule secondary to radiation will typically not fill and distend lumina or demonstrate necrosis and mitotic activity (features suggestive of recurrent high grade DCIS)
  • Sarcoma (radiation induced or primary): radiation induced sarcomas typically present as mass forming lesions rather than microscopic atypical stromal cells seen post radiation
    • Primary sarcoma of the breast would likely be a component of a malignant phyllodes and therefore demonstrate other features of a fibroepithelial lesion
Board review question #1
    Which statement about distinguishing radiation induced changes in benign breast tissue from recurrent carcinoma is true?

  1. Cytologically atypical cells scattered in the stroma that are estrogen receptor and keratin positive likely represent fibroblasts with radiation induced atypia.
  2. If the radiation took place more than 10 years previously, any atypia must represent recurrent malignancy.
  3. Low grade cytologic atypia is not seen in benign lobules secondary to radiation effect.
  4. Necrosis in proliferative ductal epithelium with high grade cytologic atypia is indicative of carcinoma in situ.
  5. Proliferative epithelium with high grade cytologic atypia is commonly seen secondary to radiation effect.
Board review answer #1
D. Radiation may induce cytologic atypia of any degree from low to high, but proliferation of epithelium takes place secondary to radiation generally with only low grade atypia. Necrosis, mitoses and proliferative epithelium with high grade atypia together are suggestive of carcinoma rather than radiation atypia. Changes secondary to radiation do not regress over time and can be seen for more than 10 years following radiation therapy. Atypical, post radiation stromal fibroblasts should not be keratin or estrogen receptor positive. This staining pattern is more in keeping with recurrent invasive carcinoma.