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Surgical Pathology Criteria
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Inflammatory Carcinoma of the Breast

Definition

  • Breast carcinoma with dermal lymphatic involvement

Diagnostic Criteria

  • Carcinoma must involve dermal lymphatics
    • Parenchymal peritumoral lymphatic involvement is not sufficient
    • Dermal invasion without lymphatic involvement is not sufficient
  • Marked lymphocytic and plasmacytic reaction may be present
    • Inflammation not required
    • Perivascular lymphocytic aggregates should lead to careful examination for carcinoma emboli
  • Clinical evidence of cutaneous erythema and edema are typically present
    • Not required for the diagnosis
  • Same poor prognosis applies to above changes associated with primary or recurrent breast carcinoma
    • If associated with a recurrent breast carcinoma the term "Secondary Inflammatory Carcinoma" may be applied
  • The term "Inflammatory Carcinoma" is sometimes applied to dermal lymphatic involvement by metastatic carcinomas of other sites to any dermal location

Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: May 1, 2006

Supplemental studies

Immunohistology

  • Immunohistochemical staining of lymphatic endothelium may be helpful
    • Positive markers CD31, CD34, D2-40
      • CD34 also stains dendritic interstitial cells that frequently surround nests of carcinoma
    • Close inspection on H&E is usually definitive
  • Keratin stain may be useful to highlight carcinoma in dermis
  • Inflammatory carcinoma is typically
    • E-cadherin positive
    • Estrogen receptor negative
    • MIB1 high
    • MUC1 positive
    • ERBB2 positive

Differential Diagnosis

Infiltrating Carcinoma with Angio-lymphatic Invasion

  • Inflammatory carcinoma requires dermal lymphatic involvement
  • Peri-tumoral lymphatic involvement does not qualify

 

Non-vascular Dermal Involvement by Carcinoma

  • Inflammatory carcinoma requires dermal lymphatic involvement

 

Invasive Micropapillary Carcinoma

  • Inflammatory carcinoma requires dermal lymphatic involvement
  • Micropapillary carcinoma is typically parenchymal but may extend to the dermis
    • Spaces surrounding carcinoma clusters are not vascular
    • (Micropapillary carcinoma in the dermis with lymphatic involvement would qualify)

Clinical

  • Worse prognosis than locally advanced, non-inflammatory carcinoma
    • Median survival 2.9 years
  • Some improved survival with aggressive combination of surgery, radiation and chemotherapy
  • Classic clinical appearance is "peu d'orange" due to local dermal edema
    • Although classic, this appearance is not required for the diagnosis

Grading / Staging / Report

Grading

  • Therapy and behavior are determined by stage in inflammatory carcinoma but conventional grading can be performed
  • The underlying carcinoma is usually high grade

  • Bloom-Scarff-Richardson grading scheme is most widely used
  • Total score and each of the three components should be reported
  • Based on invasive area only
Tubule formation Score
>75% tubules 1
10-75% tubules 2
<10% tubules 3

 

Nuclear pleomorphism (most anaplastic area) Score
Small, regular, uniform nuclei, uniform chromatin 1
Moderate varibility in size and shape, vesicular, with visible nucleoli 2
Marked variation, vesicular, often with multiple nucleoli 3

 

Mitotic figure count per 10 40x fields (depends on area of field, see key below) Score
0.096 mm2 0.12 mm2 0.16 mm2 0.27 mm2 0.31 mm2
0-3 0-4 0-5 0-9 0-11 1
4-7 5-8 6-10 10-19 12-22 2
>7 >8 >10 >19 >22 3
  • Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece: 0.096 mm2
  • AO with 10x eyepiece: 0.12 mm2
  • Nikon or Olympus with 10x eyepiece: 0.16 mm2
  • Leitz Ortholux: 0.27 mm2
  • Leitz Diaplan: 0.31 mm2
  • Mitotic count figures based on original data presented for Leitz Ortholux by Elston and Ellis 1991, with modifications based on pubished and measured areas of view
  • Evaluate regions of most active growth, usually in cellular areas at periphery
  • We employ strict criteria for identification of mitotic figures
Sum of above three components Overall grade
3-5 points Grade I (well differentiated)
6-7 points Grade II (moderately differentiated)
8-9 points Grade III (poorly differentiated)

Staging

  • Inflammatory carcinoma is definitionally stage T4d
  • Edema (including peau d'orange) in the absence of histologically defined inflammatory carcinoma is definitionally T4b

  • TNM staging is the most widely used scheme for breast carcinomas but is not universally employed
  • Critical staging criteria for regional lymph nodes
    • Isolated tumor cell clusters
      • Usually identified by immunohistochemistry
        • Term also applies if cells identified by close examination of H&E stain
      • No cluster may be greater than 0.2 mm
      • Multiple such clusters may be present in the same or other nodes
    • Micrometastasis
        • Greater than 0.2 mm, none greater than 2.0 mm
    • Metastasis
      • At least one carcinoma focus over 2.0 mm
        • If one node qualifies as >2.0 mm, count all other nodes even with smaller foci as involved
      • Critical numbers of involved nodes: 1-3, 4-9 and 10 and over
    • Note extranodal extension

Report

  • The report should use the term Inflammatory Carcinoma and describe dermal lymphatic involvement

  • Excisions: the following are important elements that must be addressed in the report for infiltrative breast carcinomas
    • Grade
      • Total score and individual components
    • Size of neoplasm
      • Give 3 dimensions or greatest dimension
      • Critical cutoffs occur at 0.5 cm and at 2 cm
    • Margins of resection
      • Measure and report the actual distance of both invasive and in situ carcinoma
    • Angiolymphatic invasion
      • Indicate if confined to tumor mass, outside tumor mass or in dermis
    • (Extensive DCIS is not currently felt to be a significant predictor of behavior)
    • Results of special studies performed for diagnosis
    • Results of prognostic special studies performed
      • ER, PR, Proliferation marker, Her2neu
      • If studies were performed on a prior specimen, refer to that report and give results
  • Needle or core biopsies
    • Provisional grade may be given but may defer to excision for definitive grade
    • Presence of absence of angiolymphatic invasion
    • Results of special studies performed for diagnosis
    • Results of prognostic special studies if performed
      • ER, PR, Proliferation marker, Her2neu
      • State if studies are deferred for a later excision specimen
  • Regional lymph nodes
    • Report findings as described above

Lists

Infiltrating Breast Carcinomas

Bibliography

  • Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005 Jul 6;97(13):966-75.
  • Charafe-Jauffret E, Tarpin C, Bardou VJ, Bertucci F, Ginestier C, Braud AC, Puig B, Geneix J, Hassoun J, Birnbaum D, Jacquemier J, Viens P. Immunophenotypic analysis of inflammatory breast cancers: identification of an 'inflammatory signature'. J Pathol. 2004 Mar;202(3):265-73.
  • Liauw SL, Benda RK, Morris CG, Mendenhall NP. Inflammatory breast carcinoma: outcomes with trimodality therapy for nonmetastatic disease. Cancer. 2004 Mar 1;100(5):920-8.
  • Galmarini CM, Garbovesky C, Galmarini D, Galmarini FC. Clinical outcome and prognosis of patients with inflammatory breast cancer. Am J Clin Oncol. 2002 Apr;25(2):172-7.
  • Henderson MA, McBride CM. Secondary inflammatory breast cancer: treatment options. South Med J. 1988 Dec;81(12):1512-7.
  • Ueno NT, Buzdar AU, Singletary SE, Ames FC, McNeese MD, Holmes FA, Theriault RL, Strom EA, Wasaff BJ, Asmar L, Frye D, Hortobagyi GN. Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer Center. Cancer Chemother Pharmacol. 1997;40(4):321-9.
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