Virchows Archiv

, Volume 444, Issue 4, pp 340–344 | Cite as

Assessment of lesions coexisting with various grades of ductal intraepithelial neoplasia of the breast

Original Article


Ductal intraepithelial neoplasia (DIN) is descriptive of in situ breast lesions from usual ductal hyperplasia (UDH) to advanced ductal carcinoma in situ (DCIS). A total of 2628 cases of DIN diagnosed at the Armed Forces Institute of Pathology were separated based on their grade. These were assessed for the presence of invasive carcinoma (ductal or lobular) and lobular intraepithelial neoplasia (LIN) grades 1–3. The frequency of invasive cancer (ductal and lobular) appearing with DIN increased with increasing DIN grade from 2% in low-risk DIN (UDH) to 37% in DIN 2–3 (DCIS grades 2–3). The frequency of these invasive carcinomas, which were either lobular or displayed lobular features, however, decreased with increasing grade of DIN with a peak of 28% in DIN 1-flat type, (flat epithelial atypia) to a low of 2% in DIN 3. Likewise, the frequency of LIN appearing with DIN decreased as the grade of DIN increased, with a peak of 26% in DIN 1-flat type to a low of 9% in DIN 3. Lower-grade LIN 1 comprised 14% of the LIN in low-risk DIN cases, but only 4% of the LIN seen in DIN 3 cases. Conversely, higher-grade LIN 3 comprised only 6% of the LIN seen in low-risk DIN cases, while accounting for 15% of the LIN in DIN 3 cases. The frequency of invasive carcinoma in DIN 1 ranged from 4% in quantitatively limited DIN 1 less than or equal to 2 mm (atypical ductal hyperplasia) to 27% among the more abundant DIN 1 greater than 2 mm (DCIS grade 1). The frequency of LIN associated with DIN 1 less than or equal to 2 mm was 13.4%, and the frequency of LIN associated with DIN 1 greater than 2 mm was 16.6% when there was no DIN 1-flat type present. However, the frequency of the LIN seen in combination with DIN 1-flat type was reduced by 50% as the quantity of DIN exceeded 2 mm. Based on this retrospective analysis of DIN, we noted that: (1) invasive carcinoma is most frequently associated with the higher grades of DIN; (2) the grade of LIN parallels the grade of coexisting DIN; (3) a relationship exists between DIN 1-flat type and the occurrence of LIN and (4) this relationship in association with DIN less than or equal to 2 mm is not maintained in DIN greater than 2 mm.


Breast Ductal intraepithelial neoplasia Flat epithelial atypia Ductal carcinoma in situ Lobular intraepithelial neoplasia Atypical ductal hyperplasia Invasive ductal carcinoma Invasive lobular carcinoma 


  1. 1.
    Bratthauer GL, Tavassoli FA (2002) Lobular intraepithelial neoplasia: previously unexplored aspects assessed in 775 cases and their clinical implications. Virchows Arch 440:134–138CrossRefPubMedGoogle Scholar
  2. 2.
    Bratthauer GL, Moinfar F, Stamatakos M, Mezzetti TP, Shekitka KM, Man YG, Tavassoli FA (2002) Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasms. Hum Pathol 33:620–627CrossRefPubMedGoogle Scholar
  3. 3.
    Brogi E, Oyama T, Koerner FC (2001) Atypical cystic lobules in patients with lobular neoplasia. Int J Surg Pathol 9:201–206PubMedGoogle Scholar
  4. 4.
    Dupont WD, Page DL (1985) Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312:146–151PubMedGoogle Scholar
  5. 5.
    Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL, Hayes DF, Edge SB, Lichter A, Schnitt SJ (2000) Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124:966–978PubMedGoogle Scholar
  6. 6.
    Page DL, Kidd TE Jr, Dupont WD, Simpson JF, Rogers LW (1991) Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 22:1232–1239PubMedGoogle Scholar
  7. 7.
    Rosen PP, Kosloff C, Lieberman PH, Adair F, Braun DW Jr (1978) Lobular carcinoma in situ of the breast. Detailed analysis of 99 patients with average follow-up of 24 years. Am J Surg Pathol 2:225–251PubMedGoogle Scholar
  8. 8.
    Tavassoli FA (1999) Pathology of the breast, 2nd edn. Appleton and Lange, Norwalk, CT, pp 205–323Google Scholar
  9. 9.
    Tavassoli FA (2001) Ductal intraepithelial neoplasia of the breast. Virchows Arch 438:221–227CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Gynecologic and Breast PathologyArmed Forces Institute of PathologyWashington USA
  2. 2.Yale University School of MedicineDepartment of PathologyNew HavenUSA

Personalised recommendations