Iatrogenic Changes

Key Facts

Etiology/Pathogenesis

Pathologic changes occur in breast due to prior surgery, radiation therapy, and medical treatment
Treatment-related changes are important to recognize

Clinical Issues

Excisions after core needle biopsy must document prior biopsy site
Biopsy site changes must be correlated with prior clinical history and treatment
Recurrent carcinomas should be distinguished from new primary carcinomas
Tumors caused by treatment should be recognized
- Biopsy-associated fibromatosis
- Radiation-associated sarcoma
- Radiation-associated carcinoma
- Implant-associated lymphoma
- Fibroadenomas associated with cyclosporine
- Carcinomas associated with hormone replacement therapy
Iatrogenic changes can mimic malignancy
- Squamous metaplasia
- Radiation atypia
- Epithelial displacement
- Degenerating skeletal muscle
- Neuromas

Image Findings

Top Differential Diagnoses

This patient has a history of breast cancer. The prior excisional site caused retraction of the skin

. A subsequent cancer

is located at a different site and is likely a new primary.

This is a recurrent invasive carcinoma

at the site of a prior excision for cancer

. Therefore, this is most likely a treatment-resistant cancer and is associated with a very poor prognosis.

TERMINOLOGY

Definitions

Pathologic changes in breast due to prior treatment (surgery, radiation, or medical treatment)

ETIOLOGY/PATHOGENESIS

Treatment-related Changes

Breast is unusual organ in that entire organ is typically not removed and multiple surgical procedures are often performed over short period of time
- Thus, recent biopsy sites and excisional sites as well as older excisional sites are common findings in breast specimens
Medical treatments and radiation therapy can also result in pathologic changes
Recognition of changes associated with prior treatment is important to understand relationship of breast lesions to these prior procedures and to avoid misinterpretation of iatrogenic changes as malignancy

Documentation of Removal of Targeted Lesion

Indication of Important Clinical History

Results of any prior excision should be available
- Interpretation of residual lesions may be altered with respect to prior history
If there is prior history of cancer, patient may have received treatment
- Radiation therapy can cause nuclear atypia
- These changes could be mistaken for neoplasia if pathologist is unaware of this history

Recurrence vs. New Primary Invasive Cancers

Recurrent invasive cancers have poor prognosis as they are treatment resistant
- These cancers usually occur at site of original cancer
- New primary carcinomas have a better prognosis as they may be sensitive to treatment
Prior biopsy sites can sometimes be recognized by dense fibrosis &&/or suture material
- If present, it is important to document location of 2nd carcinoma with respect to 1st

Treatment-associated Tumors

Some types of treatment can cause tumors
Fibromatosis associated with surgery (or breast implant)
- May occur at site of prior surgery
Radiation-associated sarcoma
- Most commonly, angiosarcoma of skin after radiation therapy for breast carcinoma
Radiation-associated carcinoma
- Occurs in women undergoing radiation to breasts during late teens and early 20s
  - Radiation at later ages does not markedly increase cancer risk
Implant-associated lymphoma
- Very rare form of T-cell lymphoma has been reported in ˜ 30 cases of women with breast implants
- Lymphoma is found in a seroma cavity surrounding implant
Cyclosporine-associated fibroadenomas
- Renal transplant patients treated with cyclosporine may develop fibroadenomas
- Fibroadenomas can regress when cyclosporine is withdrawn
Hormone replacement treatment-related carcinomas
- Women taking hormonal therapy after menopause are at increased risk for estrogen receptor-positive cancers
- It is unknown if estrogen acts as a carcinogen to cause cancers or if it stimulates growth (and therefore detection) of already existing carcinomas

IMAGE FINDINGS

Mammographic Findings

Prior surgical sites generally have an irregular appearance
- May be difficult to detect recurrent carcinoma
Radiodense debris can be present due to surgical procedure (e.g., metallic fragments)
Associated fat necrosis can calcify
For excisional sites, skin scar will be present

MACROSCOPIC FEATURES

Core Needle Biopsy Sites

Site usually has small central area of hemorrhage (˜ 0.5 cm) surrounded by ill-defined area of firm tissue and fat necrosis
Clip is very small (1-2 mm) but may be seen with careful examination
Some clip deployment systems place gelatin foam pledgets within biopsy site
- These are often color and shape of rice
  - May be mistaken for calcifications or papilloma
  - Usually fall out of tissue
- Some systems use larger rectangular-shaped gel
  - May be surrounded by pseudocapsule with minimal inflammatory response
  - If gel falls out of tissue, site can be difficult to identify
If core biopsy was of small invasive carcinoma, size of carcinoma may be difficult to ascertain grossly
- Correlation with imaging studies prior to biopsy may be necessary to determine best size for AJCC T classification

Excisional Sites

There is generally bleeding at center of excisional site and loss of tissue
Surrounding tissue is firm but not hard and may extend for several millimeters into surrounding breast
Fat necrosis appears as chalky white or yellowish streaks
Residual invasive cancer may be present as areas hard to palpation adjacent to cavity

MICROSCOPIC PATHOLOGY

Core Needle Biopsy Sites

Usually linear track of fibrosis with increased cellularity and hemosiderin-laden macrophages
If gelatin foam pledgets are present, they appear as acellular amphophilic material in center of biopsy site
- There is chronic inflammatory response with giant cells around gelatin

Recent Excisional Sites

Usually easily identified due to fibrosis, hemorrhage, fat necrosis, and chronic inflammation
Cautery artifact is often present due to common use of electrocautery (e.g., Bovie^TM) to excise breast tissue
- Electric field is generated in tissue
- Cells and nuclei become elongated due to electrical potential across the cell membrane
- Tissue with extensive cauterization loses recognizable histologic features and antigenicity
- Other types of heat (e.g., ultrasonic coagulation or ablation) result in coagulative necrosis
Suture material is often present
- Biodegradable suture (“catgut” suture) is monofilament made of strands of collagen
- Usually ovoid in shape and brightly eosinophilic
- Sutures are resorbed by exuberant chronic inflammatory infiltrate with foreign body giant cells
- Collagen can have jagged edges, and elongated nuclei may be present
  - May be mistaken for heterotopic bone formation
- Polyfilament sutures may also be present
Seromas and postoperative infections are possible complications