Breast

Breast cancer

Inflammatory


Editorial Board Member: Kristen E. Muller, D.O.
Deputy Editor-in-Chief: Gary Tozbikian, M.D.
Kiran Manjee, M.D.
Julie M. Jorns, M.D.

Last author update: 21 March 2023
Last staff update: 21 March 2023

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PubMed Search: Inflammatory carcinoma breast

Kiran Manjee, M.D.
Julie M. Jorns, M.D.
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Cite this page: Manjee K, Jorns JM. Inflammatory. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantinflamcar.html. Accessed November 29th, 2024.
Definition / general
  • Clinicopathologic entity characterized by rapid onset (≤ 6 months) and enlarged, erythematous and edematous (peau d’orange) breast due to dermal plugging of lymphatic vessels by tumor (Breast Cancer Res 2005;7:52)
  • Involvement of dermal lymphatics alone without the classic clinical presentation is not considered inflammatory carcinoma
Essential features
  • Clinical presentation of breast cancer with dermal lymphatic involvement
    • Breast skin with erythema and edema occupying at least 33% of the breast is required to make the diagnosis
    • Must be of rapid onset; duration of symptoms of ≤ 6 months
ICD coding
  • ICD-O: 8530/3 - inflammatory carcinoma
  • ICD-10: C50.9 - malignant neoplasm of breast of unspecified site
  • ICD-11: 2C62 - inflammatory carcinoma of the breast
Epidemiology
Sites
  • Breast, breast skin (dermal lymphatics)
Pathophysiology
  • Tumor microemboli in the lymphatic spaces causes obstruction that leads to the clinical presentation of peau d’orange appearance
  • E-cadherin accumulation / overexpression within tumor emboli (Anticancer Res 2010;30:3903)
Etiology
  • No association with inherited genetic mutation
  • No association with family history
Clinical features
  • Rapid onset of erythema, edema, induration, warmth and tenderness of the breast skin (Ann Oncol 2011;22:515)
  • Patients may have a history of being diagnosed with mastitis that does not respond to at least 1 week of antibiotics (Ann Oncol 2011;22:515)
  • Erythema occupying at least 33% of the breast (Ann Oncol 2011;22:515)
  • Duration of history < 6 months (Ann Oncol 2011;22:515)
  • May or may not have a breast mass, typically not palpable due to rapid spread to lymphatics and distant sites but low volume of invasive carcinoma in breast
Diagnosis
  • At least 2 skin punch biopsies between 2 - 8 mm of the most prominent area of skin discoloration (Ann Oncol 2011;22:515)
Radiology description
Radiology images

Contributed by Kiran Manjee, M.D. and Julie M. Jorns, M.D.
Skin thickening and mass

Skin thickening and mass

Prognostic factors
  • Previous studies have reported poor survival rates; however, this may be due to advanced stage at presentation and delayed diagnosis
  • 2010 - 2015 Surveillance, Epidemiology and End Results (SEER) database showed similar breast cancer specific survival in patients with inflammatory breast cancer and stage T4 noninflammatory breast cancer (BMC Cancer 2021;21:138)
  • 2010 - 2011 SEER data showed worse outcomes in hormone receptor positive / HER2 negative and triple negative breast cancer compared with triple positive and hormone receptor negative / HER2 positive subtypes (J Cancer Res Clin Oncol 2017;143:161)
  • Use of neoadjuvant therapy has improved survival rates
  • Histologic subtype does not impact survival (PLoS One 2016;11:e0145534)
  • 50% of patients with complete pathological response will subsequently recur
  • Overall 5 year survival rate is 41% (Cancer.Net: Breast Cancer - Inflammatory: Statistics [Accessed 27 December 2022])
    • 5 year survival with regional lymph node involvement is 56%
    • 5 year survival with distant metastasis is 19%
  • p53 status is not evaluated routinely but positive staining (≥ 10%) was associated with decreased response to chemotherapy (n = 59) (Clin Cancer Res 2004;10:6215)
Case reports
Treatment
  • Multidisciplinary team approach is critical
  • Neoadjuvant chemotherapy, mastectomy with lymph node dissection, radiation therapy and adjuvant endocrine therapy if indicated (Ann Oncol 2011;22:515)
  • If there is a good clinical response to neoadjuvant chemotherapy, some may be able to safely undergo breast conserving therapy instead of a mastectomy (Gland Surg 2018;7:520)
Clinical images

Contributed by Amanda L. Kong, M.D., M.S. and Mark R. Wick, M.D.
Erythema and edema

Erythema and edema

Discoloration

Discoloration

Gross description
  • Skin findings and mass lesions are usually not present after neoadjuvant therapy
Microscopic (histologic) description
  • Presence of tumor cells in dermal lymphovascular spaces
  • Tumor cells or lymphatic spaces may be scant and therefore assessment at multiple levels is recommended
  • It is not a specific histological subtype
    • Most associated invasive carcinoma is high grade invasive ductal carcinoma, no special type; however, other types of breast cancers can present as inflammatory carcinoma (PLoS One 2016;11:e0145534)
  • Ductal carcinoma in situ is often absent
  • Classified as T4d in AJCC cancer staging
  • T stage does not change following neoadjuvant therapy (ypT4d)
Microscopic (histologic) images

Contributed by Kiran Manjee, M.D., Julie M. Jorns, M.D., Weijie Li, M.D. and AFIP
Dilated lymphatics Dilated lymphatics

Dilated lymphatics

Dermal lymphovascular invasion Dermal lymphovascular invasion

Dermal lymphovascular invasion

Dermal lymphovascular invasion Dermal lymphovascular invasion

Dermal lymphovascular invasion


Dermal lymphovascular invasion

Dermal lymphovascular invasion

HER2 / neu HER2 / neu

HER2 / neu

Locally advanced breast cancer Locally advanced breast cancer Locally advanced breast cancer

Locally advanced breast cancer


Skin punch biopsy

Infiltrative nests

Tumor emboli

Tumor in dermal lymphatics

Tumor in dermal lymphatics

Virtual slides

Images hosted on other servers:
Breast, inflammatory carcinoma

Inflammatory breast carcinoma

Positive stains
Negative stains
Sample pathology report
  • Skin, left breast, punch biopsy:
    • Positive for high grade mammary (ductal) carcinoma within dermal lymphovascular spaces
    • Comment: Immunohistochemistry shows carcinoma to be:
      • GATA3 (subset, moderate) positive, supporting breast origin
      • Estrogen receptor (< 1%) negative
      • Progesterone receptor (< 1%) negative
      • HER2 / neu (0) negative for overexpression
Differential diagnosis
  • Invasive carcinoma involving dermis:
    • CD31 / ERG negative
    • Lack of clear intralymphatic space involvement
  • Ductal carcinoma in situ (DCIS):
    • Tumor clusters within myoepithelial lined spaces
  • Infection (mastitis, cellulitis, abscess):
    • More common in lactating women or in those with history of recent trauma or surgery
    • Responds to antibiotic treatment
  • Radiation dermatitis:
    • Clinical history of radiation
    • Benign biopsies
  • Other causes of edema (lymphatic obstruction or surgical removal, congestive heart failure):
    • Clinical history of medical condition, surgery, travel (parasitic infections)
    • Benign biopsies
  • Locally advanced carcinoma with skin involvement:
    • Skin changes may be present due to dermal lymphatic involvement but clinical history is of longer duration (> 6 months), often with palpable mass
    • Histologically bulky invasive carcinoma is present alongside lymphovascular space involvement
  • Metastatic neoplasms from other sites:
    • Unusual histology for breast
    • Immunohistochemistry can help differentiate
Board review style question #1

A middle aged woman presents with rapid onset (< 6 months) of breast skin thickening and discoloration. A punch biopsy is done and the patient is diagnosed with inflammatory breast cancer. She undergoes neoadjuvant chemotherapy and subsequent mastectomy reveals focal ductal carcinoma in situ (DCIS) but no residual invasive or metastatic carcinoma. How would she be staged?

  1. ypTX
  2. ypT0
  3. ypTis
  4. ypT4d
Board review style answer #1
D. ypT4d. In inflammatory breast cancer, the T stage is classified as T4d and does not change after neoadjuvant chemotherapy.

Comment Here

Reference: Inflammatory
Board review style question #2
What feature best distinguishes inflammatory breast carcinoma from locally advanced breast cancer?

  1. Mammographic mass
  2. Peau d’orange
  3. Skin thickening and discoloration < 6 months
  4. Tumor emboli within lymphatic spaces
Board review style answer #2
C. Skin thickening and discoloration < 6 months. Inflammatory breast cancer is defined as breast cancer with rapid onset of clinical symptoms of skin thickening and discoloration / erythema involving at least 33% of the breast. There is frequent peau d’orange and tumor emboli within lymphatic spaces on skin punch biopsy; however, these findings are not necessary to make the diagnosis of inflammatory breast cancer nor are they unique to inflammatory breast cancer as they can also be seen in locally advanced breast cancer. A mass may or may not be seen on mammogram as in inflammatory breast cancer tumor quickly spreads to lymphatics (and beyond) and mammography has lower sensitivity in this setting.

Comment Here

Reference: Inflammatory
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