Virchows Archiv

, Volume 447, Issue 1, pp 1–8 | Cite as

DCIS, cytokeratins, and the theory of the sick lobe

  • Tibor TotEmail author
Review Article


We postulate that ductal carcinoma in situ (DCIS), and consequently breast carcinoma in general, is a lobar disease, as the simultaneously or asynchronously appearing, often multiple, in situ tumor foci are localized within a single lobe. Although the whole lobe is sick, carrying some form of genetic instability, the malignant transformation of the epithelial cells may appear localized to a part or different parts of the sick lobe at the same time or with varying time difference. It may be confined to terminal ductal lobular units (TDLUs), to ducts or both. The malignant transformation is often associated with aberrant branching and/or aberrant lobularization within the sick lobe. Involvement of a single individual TDLU or of a group of adjacent TDLUs generates a unifocal lesion. Multifocal lesions appear if distant TDLUs are involved. Diffuse growth pattern in DCIS indicates involvement of the larger ducts. The extent of the involved area in multifocal or diffuse cases varies considerably. Diffuse growth pattern with or without evidence of aberrant arborisation within the sick lobe seems to characterize a subgroup of DCIS with unfavourable prognosis. In this paper, we discuss the anatomical, embryological and pathological background of the theory of the sick lobe and present supporting evidence from modern radiological breast imaging, long-term follow-up studies and from our own series of 108 DCIS cases.


Breast Ductal carcinoma in situ Cytokeratins Neoplasia Hypothesis 


  1. 1.
    Andersen JA, Blichert-Toft M, Dyreborg U (1987) In situ carcinomas of the breast. Types, growth pattern, diagnosis, and treatment. Eur J Surg Oncol 13:105–111PubMedGoogle Scholar
  2. 2.
    Bartek J, Bartkova J, Taylor-Papadimitriou J (1990) Keratin 19 expression in the adult and developing mammary gland. Histochem J 22:537–544CrossRefPubMedGoogle Scholar
  3. 3.
    Cady B, Michaelson JS (2001) The life-sparing potential of mammographic screening. Cancer 91:1724–1731CrossRefPubMedGoogle Scholar
  4. 4.
    Chen HH, Thurfjell E, Duffy SW, Tabar L (1998) Evaluation by Markov chain model of a non-randomised breast cancer screening programme in women aged under 50 years in Sweden. J Epidemiol Community Health 52:329–335PubMedGoogle Scholar
  5. 5.
    Cooper AP (1840) On the anatomy of the breast. Longmans, LondonGoogle Scholar
  6. 6.
    Duffy SW, Chen HH, Tabar L, Day NE (1995) Estimation of mean sojourn time in breast cancer screening using Markov chain model of both entry to and exit from the preclinical detectable phase. Stat Med 14:1531–1543PubMedGoogle Scholar
  7. 7.
    Duffy SW, Chen HH, Tabar L, Fagerberg G, Paci E (1996) Sojourn time, sensitivity and positive predictive value of mammographic screening for breast cancer in women aged 40–49. Int J Epidemiol 25:1139–1145PubMedGoogle Scholar
  8. 8.
    Egan RI (1982) Multicentric breast carcinomas: clinical-radiographic-pathologic whole organ studies and 10-year survival. Cancer 49:1123–1130PubMedGoogle Scholar
  9. 9.
    Faverly DRG, Burgers L, Bult P, Holland R (1994) Three dimensional imaging of mammary ductal carcinoma in situ: clinical implications. Semin Diagn Pathol 11:193–198PubMedGoogle Scholar
  10. 10.
    Gallager HS, Martin JE (1969) The study of mammary carcinoma by mammography and whole organ sectioning. Cancer 23:855–873PubMedGoogle Scholar
  11. 11.
    Going JJ, Moffat DF (2004) Escaping from Flatland: clinical and biological aspects of human mammary duct anatomy in three dimensions. J Pathol 203:538–544CrossRefPubMedGoogle Scholar
  12. 12.
    Holland R, Velling SH, Mravunac M, Hendricks JH (1985) Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast conserving surgery. Cancer 56:979–990Google Scholar
  13. 13.
    Jackson PA, Merchant W, McCormick CJ, Cook MG (1994) A comparison of large block macrosectioning and conventional techniques in breast pathology. Virchows Arch 425:243–248CrossRefPubMedGoogle Scholar
  14. 14.
    Jahkola T, Toivonen T, Nordling S, von Snitten K, Virtanen I (1998) Expression of Tenascin C in intraductal carcinoma of human breast: relationship to invasion. Eur J Cancer 34:1687–1692Google Scholar
  15. 15.
    Jolicoeur F, Gaboury LA, Oligny LL (2003) Basal cells of second trimester fetal breasts: immunohistochemical study of myoepithelial precursors. Pediatr Dev Pathol 6:398–413CrossRefPubMedGoogle Scholar
  16. 16.
    Lindgren A, Holmberg L, Thurfjell E (1997) The influence of mammography screening on the pathological panorama of breast cancer. APMIS 105:62–70PubMedGoogle Scholar
  17. 17.
    Longacre TA, Bartow SA (1986) A correlative morphologic study of human breast and endometrium in menstrual cycle. Am J Surg Pathol 10(6):382–393PubMedGoogle Scholar
  18. 18.
    Love SM, Barsky SH (2004) Anatomy of the nipple and breast ducts revisited. Cancer 1001:1947–1957CrossRefGoogle Scholar
  19. 19.
    Mai, KT, Yazdi HM, Burns BF, Perkins DG (2000) Pattern of distribution of intraductal and infiltrating ductal carcinoma: a three-dimensional study using serial coronal giant sections of the breast. Hum Pathol 31:464–474CrossRefPubMedGoogle Scholar
  20. 20.
    Neubauer H, Li M, Kuehne-Heid R, Schneider A, Kaiser WA (2003) High grade and non-high grade ductal carcinoma in situ on dynamic MR mammography: characteristic findings for signal increase and morphological pattern of enhancement. Br J Radiol 76:3–12CrossRefPubMedGoogle Scholar
  21. 21.
    Nishimura S, Takahashi K, Gomi N, Tada K, Makita M, Tada T, Iwase T, Yoshimoto M, Akiyma F, Sakamoto G, Kasumi F (2004) What is the predictor for invasion in non-palpable breast cancer with microcalcifications? Breast Cancer 11:49–54PubMedGoogle Scholar
  22. 22.
    Ohtake T, Abe R, Kimijima I, Fukushima T, Tsuchiya A, Hoshi K, Wahasa H (1995) Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems. Cancer 76:32–45PubMedGoogle Scholar
  23. 23.
    Otterbach F, Bankfalvi A, Bergner S, Decker T, Kreck R, Boecker W (2000) Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology 37:232–240CrossRefPubMedGoogle Scholar
  24. 24.
    Ottesen GL, Graversen HP, Blichert-Toft M, Christensen IJ, Andersen JA (2000) Carcinoma in situ of the female breast. 10 year follow-up results of a prospective nationwide study. Breast Cancer Res Treat 62:192–210CrossRefGoogle Scholar
  25. 25.
    Page DL, Rogers LW, Schuyler PA, Dupont WD, Jensen RA (2002) The natural history of ductal carcinoma in situ of the breast. In: Silverstein MJ (ed) Ductal carcinoma in situ of the breast. Lippincott, Philadelphia, pp 17–21Google Scholar
  26. 26.
    Ringberg A, Idvall I, Fernö M et al (2000) Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast. Eur J Surg Oncol 26:444–451Google Scholar
  27. 27.
    Rosen PP (2001) Rosens’s breast pathology. Lippincott, Philadelphia, pp 300–301Google Scholar
  28. 28.
    Sakakura T, Ishihara A, Yatani R (1991) Tenascin in mammary gland development: from embryogenesis till carcinogenesis. Cancer Treat Res 53:383–400PubMedGoogle Scholar
  29. 29.
    Tabár L, Chen HH, Duffy SW, Yen MF, Chiang CF, Dean PB, Smith RA (2000) A novel method for prediction of long-term outcome of women with T1a, T1b, and 10–14 mm invasive breast cancers: a prospective study. Lancet 355:429–433PubMedGoogle Scholar
  30. 30.
    Tabár L, Chen HT, Yen MFA, Tot T, Tung TH, Chen LS, Chiu YH, Duffy SW, Smith RA (2004) Mammographic tumor features can predict long-term outcomes reliably in women with 1–14-mm invasive carcinoma. Cancer 101:1745–1759CrossRefPubMedGoogle Scholar
  31. 31.
    Tabár L, Tot T, Dean PB (2005) Breast cancer: the art and science of early detection with mammography. Perception, interpretation, histopathologic correlation. Thieme, Stuttgart, pp 405–438Google Scholar
  32. 32.
    Tot T, Tabár L, Dean PB (2000) The pressing need for better mammographic-pathologic correlation of many variations in normal breast anatomy. Virchows Arch 437:338–344CrossRefPubMedGoogle Scholar
  33. 33.
    Tot T, Tabár L, Dean PB (2002) Practical breast pathology. Thieme, Stuttgart, pp 116–123Google Scholar
  34. 34.
    Tot T (2005) Correlating the ground truth of mammographic histology with the success or failure of imaging. Technol Cancer Res Treat 4(1):23–28PubMedGoogle Scholar
  35. 35.
    Vogel PM, Georgiade NG, Fetter BF, Vogel FS, McCarty KS Jr (1981) The correlation of histologic changes in the human breast with the menstrual cycle. Am J Pathol 104:23–34PubMedGoogle Scholar
  36. 36.
    Wellings SR, Jensen HM, Marcum RG (1975) An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst 55:231–273PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of PathologyCentral HospitalFalunSweden

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