Iatrogenic Changes

Iatrogenic Changes

This patient has a history of breast cancer. The prior excisional site caused retraction of the skin image. A subsequent cancer image is located at a different site and is likely a new primary.

This is a recurrent invasive carcinoma image at the site of a prior excision for cancer image. Therefore, this is most likely a treatment-resistant cancer and is associated with a very poor prognosis.



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


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

  • Excisions after core needle biopsy must include prior biopsy site

    • Specimen radiography should document removal of any residual lesion &&/or clips marking site

    • In some cases, clip may not have been deployed at site of lesion

    • In other cases, clip may be lost if biopsy site is transected during procedure

    • Histologic findings of core biopsy site must be documented

      • However, if excision occurs > 1 month after biopsy, inflammatory changes may have resolved

  • Margin excisions should include a portion of prior biopsy cavity

  • Biopsy site changes at margin may indicate incomplete removal of a 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


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


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


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., BovieTM) 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

Remote Excisional Sites

Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Iatrogenic Changes

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