Stanford School of Medicine
use browser back button to return

Surgical Pathology Criteria
http://surgpathcriteria.stanford.edu/

Ductal Carcinoma in Situ of the Breast

Definition

  • A lesion composed of neoplastic ductal cells, without stromal invasion

Diagnostic Criteria

  • Low and intermediate grade DCIS require cytologic, architectural and size criteria to be met
  • High grade DCIS requires only cytologic criteria
  • Link below to separate pages for each grade for complete criteria or select Grading at left for summary
    • Low grade
      • Round, regular to mildly irregular nuclei up to 2-3x the size of a RBC
      • No comedo necrosis
    • Intermediate grade
      • Round, regular to mildly irregular nuclei up to 2-3x the size of a RBC
      • Substantial comedo necrosis
    • High grade
      • Pleomorphic nuclei >3x the size of a RBC
      • Substantial comedo necrosis usually present, not required
  • Usual architectural types (see detailed descriptions on the various grades, links above)
    • Useful for recognition and description but grade is more clinically useful
    • Cribriform
    • Micropapillary
    • Solid (mosaic, microacinar)
    • Comedo
  • Special types
  • Criteria for minimal stromal invasion

     

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

    Original posting:: October 14, 2006

    Low Grade Ductal Carcinoma In Situ

    Diagnostic Criteria (Van Nuys)

    • Dilated ducts completely filled with uniform cells
      • No streaming of cells
      • No cells with elongate nuclei perpendicular to the basement membrane
    • All the following criteria must be met : cytologic, architectural, size and must lack tumor cell (comedo) necrosis
      • Exactly the same criteria as intermediate grade DCIS except for the lack of necrosis
      • Lesions that fulfill some but not all criteria are designated atypical ductal hyperplasia
    • Uniform nuclei 2-3x size of a RBC (10-15 microns)
      • Nuclei round to oval, regular, evenly dispersed chromatin
        • At most, mildly irregular, minimally pleomorphic
      • Nuclei stand apart, do not overlap
      • Nucleoli if present are inconspicuous
      • Mitotic figures sparse to absent
        • Abnormal forms rare
    • Usual architectural types (may be pure or mixed)
      • Cribriform
        • Dilated ducts filled with monotonous cells
        • Cleanly punched out spaces with resultant "Roman arches"
      • Micropapillary
        • Dilated ducts lined by monotonous cells
        • Small finger-like or club-shaped protuberances with bulbous ends extending into the lumen
      • Solid
        • Dilated ducts filled by sheets of monotonous cells
        • Cells may be arranged around small acini
    • Variant architectural types
    • Involved focus must be over 2 mm
      • Must involve at least two ducts
      • If under 2mm, designate as atypical ductal hyperplasia

    Intermediate Grade Ductal Carcinoma In Situ

    Diagnostic Criteria (Van Nuys)

    • Dilated ducts completely filled with uniform cells
      • No streaming of cells
      • No cells with elongate nuclei perpendicular to the basement membrane
    • All the following criteria must be met : cytologic, architectural, size and must show substantial tumor cell (comedo) necrosis
      • Exactly the same criteria as low grade DCIS except for the presence of necrosis
      • Lesions that fulfill some but not all criteria are designated atypical ductal hyperplasia
    • Uniform nuclei 2-3x size of a RBC (10-15 microns)
      • Nuclei round to oval, regular, evenly dispersed chromatin
        • At most, mildly irregular, minimally pleomorphic
      • Nuclei stand apart, do not overlap
      • Nucleoli if present are inconspicuous
      • Mitotic figures sparse to absent
        • Abnormal forms rare
    • Usual architectural types (may be pure or mixed)
      • Cribriform
        • Dilated ducts filled with monotonous cells
        • Cleanly punched out spaces with resultant "Roman arches"
      • Micropapillary
        • Dilated ducts lined by monotonous cells
        • Small finger-like or club-shaped protuberances with bulbous ends extending into the lumen
      • Solid
        • Dilated ducts filled by sheets of monotonous cells
        • Cells may be arranged around small acini
    • Variant architectural types
    • Involved focus must be over 2 mm
      • Must involve at least two ducts
      • If under 2mm, designate as atypical ductal hyperplasia

    High Grade Ductal Carcinoma In Situ

    Diagnostic Criteria (Van Nuys)

    Variant: Apocrine Ductal Carcinoma In Situ

    Diagnostic Criteria

    • Abundant eosinophilic apocrine cytoplasm
    • Same criteria as usual DCIS except that usual nuclear size criteria cannot be used as nuclei in apocrine metaplasia are typically large
    • Special nuclear size criteria based on comparison to benign apocrine metaplastic cells
      • Low and intermediate grades: up to 4x size of benign apocrine nuclei, at most slight pleomorphism
      • High grade: at least 5x size of benign apocrine nuclei, pleomorphism
        • Necrosis is almost always present
    • Low grade apocrine DCIS must also have architectural features of usual low grade DCIS
      • May be less well developed
    • No known significance for apocrine DCIS beyond that for usual DCIS

    Variant: Cystic Hypersecretory Ductal Carcinoma In Situ

    Diagnostic Criteria

    • Cells with pattern of low grade DCIS line large dilated ducts filled with eosinophilic secretion

    Variant: Ductal Carcinoma In Situ Associated with Mucocele-like Lesion

    Diagnostic Criteria

    • Typical DCIS with duct rupture and pools of mucin spilled into stroma
      • Must not have cells floating in mucin
    • Distinguish from following
      • Invasive mucinous carcinoma has mucin in contact with stroma with cells floating in mucin
      • Mucinous DCIS has extracellular mucin but spaces are all lined by epithelium
        • No mucin in contact with stroma
      • Mucocele-like lesion (NOS) lacks DCIS component

    Variant: Endocrine Ductal Carcinoma In Situ

    Alternate Name

    • Neuroendocrine ductal carcinoma in situ

    Diagnostic Criteria

    • Over half of the cells must be chromogranin or synaptophysin positive
    • Usually papillary or solid archictecture
      • May be spindled
      • May have microacini or rosettes
    • Regular round nuclei, stippled chromatin
    • Frequently has extracellular mucin
    • May be associated with papillomas
    • Associated invasive carcinoma usually mucinous or neuroendocrine

    Variant: Mucinous Ductal Carcinoma In Situ

    Diagnostic Criteria

    • Extracellular mucin present within a duct involved by DCIS
    • Epithelium must line all the spaces, separating mucin from stroma
    • Distinguish from following:
      • Invasive mucinous carcinoma has mucin in direct contact with stroma with cells floating in it
      • DCIS with associated mucocele-like lesion has duct ruputure with an area of mucin spilled into stroma
        • No cells should be floating in the mucin pools in the stroma

    Variant: Papillary Ductal Carcinoma In Situ

    Also known as intracystic papillary carcinoma when it is within a large space

    Diagnostic Criteria

    • Large dilated duct or cystic space
    • Four main patterns
      • Cribriform DCIS
        • Resembles ordinary cribriform DCIS on papillary stalks
        • May arise in a papilloma
          • If <3 mm or involves <30% of papilloma, diagnose as atypical ductal hyperplasia
        • Myoepithelial cells should not be present in cribriform areas but may be present along stalks
      • Tall hyperchromatic or stratified spindle cell
        • Lined by single population of tall cells
        • Elongate hyperchromatic stratified or pseudostratified nuclei perpendicular to stalk
        • Complex arborizing thin, delicate fibrovascular stalks
        • Myoepithelial cells are not typically present on the stalks
        • May have nuclear clearing
      • Compact columnar
        • Lined by uniform population of often columnar cells
        • Fine, evenly distributed chromatin
      • Transitional cell
        • Resembles low grade transitional cell carcinoma
    • High grade cytology rare
    • Mitotic figures may be seen
      • They are rare in papillomas over age 40
    • Necrosis may be seen
      • It is rare in papillomas over age 40
    • Myoepithelial cells often cannot be demonstrated around the outside of papillary DCIS; however, papillary DCIS is not clinically an invasive carcinoma
    • Invasion, when it occurs, is typically low grade infiltrating ductal or very rarely invasive papillary

    Variant: Pure Micropapillary Ductal Carcinoma In Situ

    Diagnostic Criteria

    • Dilated ducts lined by stratified population of monotonous cells
    • Small finger-like or club shaped protuberances with bulbous ends
      • May form arches
    • Cells must be the same from base to tips
    • When pure it is frequently multifocreported cases al and multicentric
      • Based on small numbers of
      • Clinical significance is not known
      • Some surgeons consider this to be an indication for mastectomy
        • Be certain that the pattern is pure before reporting as such
    • Usually low grade but may be high grade
    • No special significance if mixed with usual cribriform pattern
    • Not related to invasive micropapillary carcinoma

    Minimal Stromal Invasion

    Definition: Extension of cancer cells beyond the basment membrane into the adjacent tissue with no focus more than 0.1 cm in greatest dimension (AJCC T1mic)

    Diagnostic Criteria

    • Multiple foci are not added together for evaluation of the size criterion
    • Calponin and p63 stains can be useful
    • Focus should be outside the lobular unit or immediate periductal area
      • If cells are present in these areas, designate as "scattered cells in perilobular or periductal area"
        • Note in report that they do not meet the criteria for minimal stromal invasion
        • Note that their clinical significance is unknown
    • Significance
      • Less than 5% chance of metastases
      • Nearly 100% survival
    • We avoid the term "microinvasion" because of its varying definitions

    Supplemental studies

    Immunohistology

    • 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

    • Myoepithelial cells often cannot be demonstrated around the outside of papillary DCIS; however, papillary DCIS is not clinically an invasive carcinoma
    • Endocrine DCIS is defined as >50% of cells reactive with chromogranin or synaptophysin

    Differential Diagnosis

    Low Grade DCIS vs. Atypical Ductal Hyperplasia (ADH)

    • Low grade DCIS requires all of the following
      • Complete filling of ducts by cells with uniform round nuclei without substantial overlap
      • No streaming of cells
      • No columnar cell population
      • Sharply punched out cribriform spaces, microacini or bulbous papillae
        • Solid low grade DCIS is rare but must be excluded before using this feature to diagnose ADH
      • Size over 2-3 mm and involvement of at least two ducts
    • If any one of the above features are lacking, designate as ADH

    Ductal vs. Lobular may be a problem in pagetoid or complete involvement of ducts by LCIS, in solid low grade DCIS, or in lobular involvement by DCIS cells (cancerization of lobules)
    DCIS LCIS
    Cohesive Non-cohesive
    May show moderate to marked pleomorphism Mild to moderate pleomorphism
    No pagetoid involvement of ducts May show pagetoid pattern in ducts
    May show irregular or partial involvement of acini Uniform involvment of acini
    Frequent cribriform or micropapillary pattern No cribriform spaces or micropapillae
    Frequently amphophilic cytoplasm Cytoplasm usually clear to eosinophilic
    E-cadherin positive E-cadherin negative
    Indeterminate cases will be encountered and should be treated as DCIS (excision with clear margins)

    Papillary DCIS Intraductal Papilloma
    Thin, delicate fibrovascular stalks Broad, hyalinized stalks
    Myoepithelial cells restricted to stalk lining Myoepithelial cells integral part of lesion
    No proliferation in stalk stroma Adenosis-like ductal proliferation in hyalinized stroma
    Necrosis may be present Necrosis rare over age 40
    Mitotic figures may be present Mitotic figures rare over age 40

    DCIS vs. Invasive Carcinoma

    • In the context of an invasive pattern, the lack of myoepithelial cells supports a diagnosis of invasion
    • See definition of minimally invasive carcinoma
    • 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

    Cribriform Ductal Carcinoma In Situ Collagenous Spherulosis
    May have intralumenal mucin but lacks fibrillar or laminated appearance Frequently fibrillar or laminated spherules
    Myoepithelial component restricted to peripheral layer of duct Myoepithelial cells surround spherules
    Nuclei slightly enlarged compared to normal (2-3 times larger than RBC) Nuclei identical in size and appearance to normal

    A number of low grade or benign lesions are characterized by pools of mucin
    Mucinous DCIS Extracellular, intralumenal mucin in a duct lined by DCIS, no mucin in contact with stroma
    DCIS with mucocele-like lesion Typical DCIS with discrete areas of rupture resulting in mucin pools in stroma, no groups of cells floating in mucin
    ADH with mucocele-like lesion Some but not all features required for diagnosis of DCIS with discrete areas of rupture resulting in mucin pools in stroma, no groups of cells floating in mucin
    Mucocele-like lesion Pools of mucin in stroma variably lined by bland epithelium, usually no groups of cells floating in mucin (if present they are normal ductal cells and are not complex), almost always a microscopic lesion
    Mucinous carcinoma Mucin in contact with stroma, neoplastic cells floating in mucin
    Nodular mucinosis Nodules of stromal mucin, no epithelial component, subareolar

    Micropapillary Ductal Carcinoma In Situ Gynecomastia-like Lesion of Female Breast
    Micropapillae have bulbous, expanded ends Micropapillae have thin tips, wider base
    Uniform cells throughout Smaller cells at top
    Hyperchromatic throughout Hyperchromatic at top, not base
    Often associated with other DCIS patterns Often associated with other hyperplastic patterns

    Low Grade Ductal Carcinoma In Situ and Atypical Ductal Hyperplasia Columnar Cell Change / Hyperplasia
    Architectural complexity manifested by a) partial or complete filling of ducts or b) arcades or micropapillary formations Essentially a flat lesion, lacks architectural complexity
    Low grade nuclear atypia present (except some cases of ADH that have architectural complexity) Cytologically bland

    Low Grade Ductal Carcinoma In Situ and Atypical Ductal Hyperplasia Flat Epithelial Atypia
    Architectural complexity manifested by a) partial or complete filling of ducts or b) arcades or micropapillary formations Lacks architectural complexity
    All three have low grade nuclear atypia, except for some cases of ADH, which must have architectural complexity

    High Grade Ductal Carcinoma In Situ Flat Epithelial Atypia
    Grade III nuclear atypia Low grade nuclear atypia
    Frequent comedonecrosis Lacks comedonecrosis

    Clinical

    • DCIS is considered a precursor of invasive carcinoma, and as such, complete resection is recommended

    Relative risk for development of invasive breast carcinoma

    • No increased risk
      • Non-proliferative fibrocystic change
      • Fibroadenoma
      • Solitary papilloma
    • Slightly increased risk (1.5 to 2 times)
      • Proliferative fibrocystic change
      • Usual ductal hyperplasia
      • Sclerosing adenosis (florid)
      • Radial scar
      • Complex fibroadenoma (approximately 3 times risk)
    • Moderately increased risk (4 to 5 times)
      • Atypical ductal hyperplasia (no family history)
      • Atypical lobular hyperplasia
    • High risk (8 to 10 times)
      • Ductal carcinoma in situ, low grade
      • Lobular carcinoma in situ
      • Atypical ductal hyperplasia, if history of carcinoma in primary relatives
    • Very high risk (precise level not known)
      • Ductal carcinoma in situ, high grade

    Grading / Staging / Report

    • We use the following grading criteria (Van Nuys)
      • Low grade DCIS
        • Nuclei 2-3x the size of a RBC (10-15 microns)
        • Nuclei oval, round, regular, evenly dispersed chromatin up to mildly irregular and minimally pleomorphic
        • Nucleoi, if present, small and indistinct
      • Intermediate grade DCIS
        • Same nuclear features as Low Grade
        • Substantial tumor cell (comedo) necrosis present
      • High grade DCIS
        • Nuclei >3x the size of a RBC (>15 microns)
        • Nuclei pleomorphic with clumped chromatin
        • Nucleoli prominent, enlarged
        • Necrosis almost universal, lumenal

       

    • Staging not applicable
    • The surgical pathology report should contain or address the following:
      • Type of resection or biopsy and location
      • Type of DCIS
      • Grade of DCIS
      • Size of lesion
      • Distance to closest margin
      • Presence of calcifications if they were the reason for the biopsy
      • Results of any supplementary studies performed

    Lists

    Types and Variants of DCIS

    Intraductal and Intralobular Proliferative Lesions

    Bibliography

    • Holland R, Peterse JL, Millis RR, Eusebi V, et al. Ductal carcinoma in situ: A proposal for a new classification. Sem in Diagn Pathol. 1994;11:167-80.
    • Kamel OW, Kempson RL, Hendrickson MR. In situ proliferative epithelial lesions of the breast. Pathology. 1992;1(1):65-102.
    • Lagios MD, Margolin FR, Westdahl PR, Rose MR. Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence. Cancer. 1989;63(4):618-24.
    • Lagios MD. Heterogeneity of duct carcinoma in situ (DCIS): relationship of grade and subtype analysis to local recurrence and risk of invasive transformation. Cancer Lett. 1995;90(1):97-102.
    • Millis RR. Classification of ductal carcinoma in situ of the breast. Adv Anat Pathol. 1996;3:114-29.
    • Page DL, Dupont WD, Rogers LW, Landenberger M. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer. 1982;49(4):751-8.
    • Recommendations for the reporting of breast carcinoma. Association of Directors of Anatomic and Surgical Pathology. Am J Clin Pathol. 1995;104(6):614-9.
    • Scott MA, Lagios MD, Axelsson K, Rogers LW, Anderson TJ, Page DL. Ductal carcinoma in situ of the breast: reproducibility of histological subtype analysis. Hum Pathol. 1997;28(8):967-73.
    • Silverstein MJ, Lagios MD, Craig PH, Waisman JR, Lewinsky BS, Colburn WJ, Poller DN. A prognostic index for ductal carcinoma in situ of the breast. Cancer. 1996;77(11):2267-74.
    • Acs G, Lawton TJ, Rebbeck TR, LiVolsi VA, Zhang PJ. Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J Clin Pathol. 2001 Jan;115(1):85-98.
    • Goldstein NS, Bassi D, Watts JC, Layfield LJ, Yaziji H, Gown AM. E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast. Implications for the interpretation of problematic lesions. Am J Clin Pathol. 2001 Apr;115(4):534-42.
    • Jacobs TW, Pliss N, Kouria G, Schnitt SJ. Carcinomas in situ of the breast with indeterminate features: role of E-cadherin staining in categorization. Am J Surg Pathol. 2001 Feb;25(2):229-36.
    • Maluf HM, Swanson PE, Koerner FC. Solid low-grade in situ carcinoma of the breast: role of associated lesions and E-cadherin in differential diagnosis. Am J Surg Pathol. 2001 Feb;25(2):237-44.
    • Bobrow LG, Happerfield LC, Gregory WM, Springall RD, Millis RR. The classification of ductal carcinoma in situ and its association with biological markers. Semin Diagn Pathol. 1994 Aug;11(3):199-207.
    • Lagios MD. Duct carcinoma in situ: biological implications for clinical practice. Semin Oncol. 1996 Feb;23(1 Suppl 2):6-11. Review.
    • Page DL, Simpson JF. Ductal carcinoma in situ--the focus for prevention, screening, and breast conservation in breast cancer. N Engl J Med. 1999 May 13;340(19):1499-500.
    • Page DL, Dupont WD, Rogers LW, Jensen RA, Schuyler PA. Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer. 1995 Oct 1;76(7):1197-200.
    • Patchefsky AS, Schwartz GF, Finkelstein SD, Prestipino A, Sohn SE, Singer JS, Feig SA. Heterogeneity of intraductal carcinoma of the breast. Cancer. 1989 Feb 15;63(4):731-41.
    • Bellamy CO, McDonald C, Salter DM, Chetty U, Anderson TJ. Noninvasive ductal carcinoma of the breast: the relevance of histologic categorization. Hum Pathol. 1993 Jan;24(1):16-23.
    • Leal C, Henrique R, Monteiro P, Lopes C, Bento MJ, De Sousa CP, Lopes P, Olson S, Silva MD, Page DL. Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers. Hum Pathol. 2001 May;32(5):487-93.
    • Lefkowitz M, Lefkowitz W, Wargotz ES. Intraductal (intracystic) papillary carcinoma of the breast and its variants: a clinicopathological study of 77 cases. Hum Pathol. 1994 Aug;25(8):802-9.
    • Maluf HM, Koerner FC. Solid papillary carcinoma of the breast. A form of intraductal carcinoma with endocrine differentiation frequently associated with mucinous carcinoma. Am J Surg Pathol. 1995 Nov;19(11):1237-44.
    • Mann GB, Port ER, Rizza C, Tan LK, Borgen PI, Van Zee KJ. Six-year follow-up of patients with microinvasive, T1a, and T1b breast carcinoma. Ann Surg Oncol. 1999 Sep;6(6):591-8.
    • Padmore RF, Fowble B, Hoffman J, Rosser C, Hanlon A, Patchefsky AS. Microinvasive breast carcinoma: clinicopathologic analysis of a single institution experience. Cancer. 2000 Mar 15;88(6):1403-9.
    • Yaziji H, Gown AM, Sneige N. Detection of stromal invasion in breast cancer: the myoepithelial markers. Adv Anat Pathol. 2000 Mar;7(2):100-9.
    • Prasad ML, Osborne MP, Giri DD, Hoda SA. Microinvasive carcinoma (T1mic) of the breast: clinicopathologic profile of 21 cases. Am J Surg Pathol. 2000 Mar;24(3):422-8.
    • Rosner D, Lane WW, Penetrante R. Ductal carcinoma in situ with microinvasion. A curable entity using surgery alone without need for adjuvant therapy. Cancer. 1991 Mar 15;67(6):1498-503.
    • Zavotsky J, Hansen N, Brennan MB, Turner RR, Giuliano AE. Lymph node metastasis from ductal carcinoma in situ with microinvasion. Cancer. 1999 Jun 1;85(11):2439-43.
    • Cross AS, Azzopardi JG, Krausz T, van Noorden S, Polak JM. A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in-situ of the breast. Histopathology. 1985 Jan;9(1):21-37.
    • Tsang WY, Chan JK. Endocrine ductal carcinoma in situ (E-DCIS) of the breast: a form of low-grade DCIS with distinctive clinicopathologic and biologic characteristics. Am J Surg Pathol. 1996 Aug;20(8):921-43.
Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
© 2005  Stanford University School of Medicine