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Surgical Pathology Criteria

Infiltrating Ductal Carcinoma of the Breast (Carcinoma of No Special Type)


  • Invasive adenocarcinoma demonstrating differentiation characteristic of breast ductal cells
    • Includes all carcinomas not designated as an otherwise recognizable type

Diagnostic Criteria

  • Irregular infiltration of stroma
  • Variable ductal formation by infiltrating cells
  • Wide range of cytologic atypia and mitotic rates
  • Typical cases express e-cadherin
  • Myoepithelial cells absent in invasive areas
  • Infiltrating carcinoma should be separated from DCIS with minimal stromal invasion (microinvasion)

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
Last update: December 30, 2008

Supplemental studies


  • Demonstration of myoepithelial cells can confirm the in situ nature of a process while their absence supports invasion
    • We prefer to use both p63 and calponin on problematic cases
    • A variety of markers have been used for myoepithelial cells:
    Marker Sensitivity Specificity
    Calponin Excellent Very good
    p63 Excellent Excellent
    Smooth muscle myosin heavy chain Good Excellent
    CD10 (CALLA) Good Good
    High molecular weight cytokeratin Very good Poor
    Maspin Good Poor
    S100 Good Very poor
    Actin Good Very poor
  • E-cadherin appears to be a sensitive marker of ductal differentiation vs lobular differentiation; its utility in borderline lesions is currently uncertain

  • Immunologic markers useful for identification of breast carcinoma
  • GCDFP15 (BRST2) Estrogen Receptor Progesterone Receptor PAX8
    Infiltrating ductal carcinoma 60-70% 75% 50-60% 0%
    Infiltrating lobular carcinoma 60-70% >95% 80% 0%
    Lung adenocarcinoma 0-1% <5% <5% 0%
    Ovarian adenocarcinoma 1-5% 50-100% 40-90% 90-100%
    Endometrioid adenocarcinoma negative 70% 70%  
    GI adenocarcinoma negative <5% 1-10% 0%
    Pancreatic adenocarcinoma negative negative 0-5% 0%
    Cholangiocarcinoma negative negative 30%  
    Thyroid carcinoma negative 20% 30% 100%
  • Sweat gland and salivary gland neoplasms may also be positive for GCDFP15, ER and PR
  • Prostatic adenocarcinoma may be positive for GCDFP15

  • CK7 and CK20 do not distinguish breast from lung adenocarcinomas but may help in the distinction from ovary, pancreas, bile duct and GI carcinomas.

    CK7 and CK20 expression in carcinomas

    CK7+20+ CK7-20+
    Ovary mucinous 90% Colorectal adeno 80%
    Transitional cell 65% Merkel cell 70%
    Pancreas adeno 65% Gastric adeno 35%
    Cholangio 65%  
    Gastric adeno 40%  
    Excluded tumors 5% or less Carcinoid; Germ cell; Esoph squam; Head/neck squam; Hepato-cellular; Lung small cell & squam; Ovary non-mucinous; Renal adeno Excluded tumors 5% or less Breast; Carcinoid lung; Cholangio; Esoph squam; Germ cell; Lung all types; Hepato-cellular; Ovary; Pancreas adeno; Renal adeno; Transitional cell; Uterus endometrioid
    CK7+20- CK7-20-
    Ovary non-mucinous 100% Adrenal 100%
    Thyroid (all 3 types) 100% Seminoma & Yolk Sac 95%
    Breast 90% Prostate 85%
    Lung adeno 90% Hepatocellular 80%
    Uterus endometrioid 85% Renal adeno 80%
    Embryonal 80% Carcinoid intestinal & lung 80%
    Mesothelioma 65% Lung small cell & squam 75%
    Transitional cell 35% Esoph squam 70%
    Pancreas adeno 30% Head/neck squam 70%
    Cholangio 30% Mesothelioma 35%
    Excluded tumors 5% or less Colorectal adeno; Ovary mucinous; Yolk Sac; Seminoma Excluded tumors 5% or less Breast; Cholangio; Lung adeno; Ovary; Pancreas adeno
  • Derived from Chu PG, Weiss LM. Histopathology 2002, 40:403-439 and other sources

Prognostic/Therapeutic Markers

  • Estrogen receptor (ER) and progesterone receptor (PR) are important markers for directing therapy and determining prognosis
    • Current consensus is that any level of positivity should be reported as positive
  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for cases borderline by one procedure

Genetic analysis

  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline cases

Differential Diagnosis

Infiltrating Ductal Carcinoma Infiltrating Lobular Carcinoma
Infiltration in cords of varying thickness Single file infltration
May form ductal structures No duct formation
E-cadherin positive E-cadherin negative
The utility of E-cadherin in borderline cases is currently uncertain


Infiltrating Ductal Carcinoma Sclerosing Adenosis
Infiltrating Circumscribed, nodular
Myoepithelial cells absent Myoepithelial cells present


Infiltrating Ductal Carcinoma Microglandular Adenosis
Infiltrating Nodular or diffuse
Variable and irregular duct formation Uniformly round ducts
Empty lumens Eosinophilic secretion usually present in lumens
EMA positive EMA negative
Basement membrane absent Basement membrane variable
Both may have rounded non-branching ducts with a single layer of cells, lacking myoepithelial cells


Infiltrating Ductal Carcinoma Radial Scar
Cells may show various levels of atypia Cytologically bland cells
No myoepithelial cells Myoepithelial cells present
Frequent infiltration of fat by naked tubules No bare infiltration of fat
May show various infiltrative patterns Stellate configuration


Tubular Carcinoma Grade I Infiltrating Ductal Carcinoma, NOS
Stellate infiltration Irregular infiltration
90% tubules May have >10% ribbons or cords
Infrequent branching Frequent budding and branching
Single layer of cells May show stratification
Uniform chromatin Slightly irregular chromatin
Nucleoli inconspicuous Nucleoli may be prominent
  • A continuum exists between tubular carcinoma and well differentiated (Grade I) infiltrating ductal carcinoma
  • It is probable that a small (under 2.0 cm) well differentiated infiltrating ductal carcinoma will have a prognosis similar to that of tubular carcinoma so the distinction may not be critical
  • Grade II and III carcinomas are excluded by definition from tubular carcinoma.

    Breast vs. other origin in carcinoma of unknown primary


    • The most important prognostic indicators are nodal status, grade and size
      • See Grading/Staging/Report link at left for guidelines on reporting prognostic factors
    • Inflammatory carcinoma (defined as dermal lymphatic involvement has a dismal prognosis
    • Involvement of the nipple by Paget disease has no clinical significance if the underlying carcinoma is identified and standard prognostic factors evaluated

    Grading / Staging / Report


    • 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)


    • 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


    • 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


    Infiltrating Breast Carcinomas


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    • Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002 May;40(5):403-39.
    • Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT. Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989 Mar;20(3):281-7.
    • Anscher MS, Jones P, Prosnitz LR, Blackstock W, Hebert M, Reddick R, Tucker A, Dodge R, Leight G Jr, Iglehart JD, et al. Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy. Ann Surg. 1993 Jul;218(1):22-8.
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    • Fisher ER, Gregorio RM, Redmond C, Kim WS, Fisher B. Pathologic findings from the national surgical adjuvant breast project. (Protocol no. 4). III. The significance of extranodal extension of axillary metastases. Am J Clin Pathol. 1976 Apr;65(4):439-44.
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    • Rosner D, Lane WW. Should all patients with node-negative breast cancer receive adjuvant therapy? Identifying additional subsets of low-risk patients who are highly curable by surgery alone. Cancer. 1991 Oct 1;68(7):1482-94.
    • Schnitt SJ, Abner A, Gelman R, Connolly JL, Recht A, Duda RB, Eberlein TJ, Mayzel K, Silver B, Harris JR. The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy. Cancer. 1994 Sep 15;74(6):1746-51.
    • Smitt MC, Nowels KW, Zdeblick MJ, Jeffrey S, Carlson RW, Stockdale FE, Goffinet DR. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer. 1995 Jul 15;76(2):259-67.
    • Silverstein MJ, Gierson ED, Waisman JR, Senofsky GM, Colburn WJ, Gamagami P. Axillary lymph node dissection for T1a breast carcinoma. Is it indicated? Cancer. 1994 Feb 1;73(3):664-7.
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    • Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008 Oct;32(10):1566-71.
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