Top

Published in:

01-06-2008 | Review and Perspective

Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?

Authors: Gulisa Turashvili, Malcolm Hayes, Blake Gilks, Peter Watson, Samuel Aparicio

Published in: Virchows Archiv | Issue 6/2008

Abstract

Columnar cell lesions (CCLs) are one of the most common abnormalities in the adult female human breast, characterized by the presence of columnar-shaped epithelial cells lining enlarged terminal-duct lobular units. CCLs are being seen increasingly in core biopsies taken for the non-palpable calcifications. The increased incidence may reflect improved delineation and recognition of CCLs by pathologists or a true increase in incidence related to biological and/or environmental factors. Columnar cell-like lesions have been described under a variety of names such as blunt duct adenosis, flat epithelial atypia, and ductal intraepithelial neoplasia type DIN1a. The current histologic classification used by some pathologists divides them into simple columnar cell change and columnar cell hyperplasia, both of which can occur with or without atypia. Columnar cells lack mature luminal or basal/myoepithelial phenotype markers, but they are usually positive for estrogen receptor-α. The cellular origin of CCLs and their possible relationship to either expansion or metaplasia of a preexisting normal cell phenotype remains unclear. CCLs are frequently associated with lobular and ductal in situ tumors and invasive lobular and tubular carcinomas. The relationship and natural history of CCLs to invasive ductal carcinoma is enigmatic, but they may prove of clinical relevance when detected by screening mammography.

Abdel-Fatah TM, Powe DG, Hodi Z, Lee AH, Reis-Filho JS, Ellis IO (2007) High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma. Am J Surg Pathol 31:417–426PubMedCrossRef

Azzopardi JG, Ahmed A, Millis RR (1979) Problems in breast pathology. Major Probl Pathol 11:i–xvi, 1–466PubMed

Berg WA (2004) Image-guided breast biopsy and management of high-risk lesions. Radiol Clin North Am 42:935–946, viiPubMedCrossRef

Bibeau F, Chateau MC, Masson B (2003) Management of non-palpable breast lesions with vacuum-assisted large core needle biopsies (Mammotome). Experience with 560 procedures at the Val d’Aurelle Center. Ann Pathol 23:582–592PubMed

Bijker N, Peterse JL, Duchateau L, Julien JP, Fentiman IS, Duval C, Di Palma S, Simony-Lafontaine J, de Mascarel I, van de Vijver MJ (2001) Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853. J Clin Oncol 19:2263–2271PubMed

Bloodgood J (1906) Senile parenchymatous hypertrophy of female breast. Its relation to cyst formation and carcinoma. Surg Gynecol Obstet 3:721–730

Bonnett M, Wallis T, Rossmann M, Pernick NL, Bouwman D, Carolin KA, Visscher D (2003) Histopathologic analysis of atypical lesions in image-guided core breast biopsies. Mod Pathol 16:154–160PubMedCrossRef

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ (2007) Mammographic density and the risk and detection of breast cancer. N Engl J Med 356:227–236PubMedCrossRef

Boyd NF, Martin LJ, Yaffe MJ, Minkin S (2006) Mammographic density: a hormonally responsive risk factor for breast cancer. J Br Menopause Soc 12:186–193PubMedCrossRef

10.

Brogi E, Oyama T, Koerner FC (2001) Atypical cystic lobules in patients with lobular neoplasia. Int J Surg Pathol 9:201–206PubMedCrossRef

11.

Collins LC, Achacoso NA, Nekhlyudov L, Fletcher SW, Haque R, Quesenberry CP Jr., Alshak NS, Puligandla B, Brodsky GL, Schnitt SJ, Habel LA (2007) Clinical and pathologic features of ductal carcinoma in situ associated with the presence of flat epithelial atypia: an analysis of 543 patients. Mod Pathol 20:1149–1155PubMedCrossRef

12.

Coyne JD (2004) Columnar cell hyperplasia with intraluminal crystalloids and features of a mucocoele-like lesion. Histopathology 44:401–403PubMedCrossRef

13.

Dabbs DJ, Carter G, Fudge M, Peng Y, Swalsky P, Finkelstein S (2006) Molecular alterations in columnar cell lesions of the breast. Mod Pathol 19:344–349PubMedCrossRef

14.

Dauplat MM, Penault-Llorca F (2004) Classification of preinvasive breast and carcinoma in situ: doubts, controversies, and proposal for new categorizations. Bull Cancer 91(Suppl 4):S205–S210PubMed

15.

David N, Labbe-Devilliers C, Moreau D, Loussouarn D, Campion L (2006) Diagnosis of flat epithelial atypia (FEA) after stereotactic vacuum-assisted biopsy (VAB) of the breast: what is the best management: systematic surgery for all or follow-up? J Radiol 87:1671–1677PubMedCrossRef

16.

de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, Vincent-Salomon A, Soubeyran I, Picot V, Coindre JM, Mauriac L (2007) Epithelial atypia in biopsies performed for microcalcifications practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up. Virchows Arch 451:1–10PubMedCrossRef

17.

De Potter CR, Foschini MP, Schelfhout AM, Schroeter CA, Eusebi V (1993) Immunohistochemical study of neu protein overexpression in clinging in situ duct carcinoma of the breast. Virchows Arch A Pathol Anat Histopathol 422:375–380PubMedCrossRef

18.

Dessauvagie BF, Zhao W, Heel-Miller KA, Harvey J, Bentel JM (2007) Characterization of columnar cell lesions of the breast: immunophenotypic analysis of columnar alteration of lobules with prominent apical snouts and secretions. Hum Pathol 38:284–292PubMedCrossRef

19.

Eusebi V, Damiani S, Losi L, Millis RR (1997) Apocrine differentiation in breast epithelium. Adv Anat Pathol 4:139–155CrossRef

20.

Eusebi V, Feudale E, Foschini MP, Micheli A, Conti A, Riva C, Di Palma S, Rilke F (1994) Long-term follow-up of in situ carcinoma of the breast. Semin Diagn Pathol 11:223–235PubMed

21.

Eusebi V, Foschini MP, Cook MG, Berrino F, Azzopardi JG (1989) Long-term follow-up of in situ carcinoma of the breast with special emphasis on clinging carcinoma. Semin Diagn Pathol 6:165–173PubMed

22.

Falkenberry SS, Legare RD (2002) Risk factors for breast cancer. Obstet Gynecol Clin North Am 29:159–172PubMedCrossRef

23.

Feeley L, Quinn CM (2008) Columnar cell lesions of the breast. Histopathology 52:11–19PubMed

24.

Foote FW, Stewart FW (1945) Comparative studies of cancerous versus noncancerous breasts. Ann Surg 121:197–222PubMed

25.

Foschini MP, Flamminio F, Miglio R, Calo DG, Cucchi MC, Masetti R, Eusebi V (2007) The impact of large sections on the study of in situ and invasive duct carcinoma of the breast. Hum Pathol 38:1736–1743PubMedCrossRef

26.

Fraser JL, Raza S, Chorny K, Connolly JL, Schnitt SJ (1998) Columnar alteration with prominent apical snouts and secretions: a spectrum of changes frequently present in breast biopsies performed for microcalcifications. Am J Surg Pathol 22:1521–1527PubMedCrossRef

27.

Fritzsche FR, Dietel M, Kristiansen G (2006) Flat epithelial neoplasia and other columnar cell lesions of the breast. Pathologe 27:381–386PubMedCrossRef

28.

Goldstein NS, Kestin LJ, Vicini FA (2007) Monomorphic epithelial proliferations: characterization and evidence suggesting they are the pool of partially transformed lesions from which some invasive carcinomas arise. Am J Clin Pathol 128:1023–1034PubMedCrossRef

29.

Goldstein NS, O’Malley BA (1997) Cancerization of small ectatic ducts of the breast by ductal carcinoma in situ cells with apocrine snouts: a lesion associated with tubular carcinoma. Am J Clin Pathol 107:561–566PubMed

30.

Gopalan A, Hoda SA (2005) Columnar cell hyperplasia and lobular carcinoma in situ coexisting in the same duct. Breast J 11:210PubMedCrossRef

31.

Guerra-Wallace MM, Christensen WN, White RL Jr (2004) A retrospective study of columnar alteration with prominent apical snouts and secretions and the association with cancer. Am J Surg 188:395–398PubMedCrossRef

32.

Harris GC (2007) Bs14 update on in situ proliferations of the breast. ANZ J Surg 77(Suppl 1):A3CrossRef

33.

Ho BC, Tan PH (2005) Flat epithelial atypia: concepts and controversies of an intraductal lesion of the breast. Pathology 37:105–111PubMedCrossRef

34.

Hoda SA, Chung SM, Gopalan A (2003) Evolving entities and changing concepts in breast pathology. Breast Cancer 10:294–300PubMed

35.

Hulka BS, Moorman PG (2001) Breast cancer: hormones and other risk factors. Maturitas 38:103–113, discussion 113–106PubMedCrossRef

36.

Jacobs TW, Connolly JL, Schnitt SJ (2002) Nonmalignant lesions in breast core needle biopsies: to excise or not to excise? Am J Surg Pathol 26:1095–1110PubMedCrossRef

37.

Kim MJ, Kim EK, Oh KK, Park BW, Kim H (2006) Columnar cell lesions of the breast: mammographic and US features. Eur J Radiol 60:264–269PubMedCrossRef

38.

Koerner FC, Oyama T, Maluf H (2001) Morphological observations regarding the origins of atypical cystic lobules (low-grade clinging carcinoma of flat type). Virchows Arch 439:523–530PubMed

39.

Laden F, Hunter DJ (1998) Environmental risk factors and female breast cancer. Annu Rev Public Health 19:101–123PubMedCrossRef

40.

Lanyi M, Citoler P (1981) The differential diagnosis of microcalcification. Micro-cyst (blunt duct) adenosis (author’s transl). Rofo 134:225–231PubMed

41.

Lee S, Medina D, Tsimelzon A, Mohsin SK, Mao S, Wu Y, Allred DC (2007) Alterations of gene expression in the development of early hyperplastic precursors of breast cancer. Am J Pathol 171:252–262PubMedCrossRef

42.

Lee S, Mohsin SK, Mao S, Hilsenbeck SG, Medina D, Allred DC (2006) Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer. Breast Cancer Res 8:R6PubMedCrossRef

43.

Leibl S, Regitnig P, Moinfar F (2007) Flat epithelial atypia (DIN 1a, atypical columnar change): an underdiagnosed entity very frequently coexisting with lobular neoplasia. Histopathology 50:859–865PubMedCrossRef

44.

Luna-More S, Weil B, Bautista D, Garrido E, Florez P, Martinez C (2004) Bcl-2 protein in normal, hyperplastic and neoplastic breast tissues. A metabolite of the putative stem-cell subpopulation of the mammary gland. Histol Histopathol 19:457–463PubMed

45.

Martel M, Barron-Rodriguez P, Tolgay Ocal I, Dotto J, Tavassoli FA (2007) Flat DIN 1 (flat epithelial atypia) on core needle biopsy: 63 cases identified retrospectively among 1,751 core biopsies performed over an 8-year period (1992–1999). Virchows Arch 451:883–891PubMedCrossRef

46.

Martin AM, Weber BL (2000) Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 92:1126–1135PubMedCrossRef

47.

McLaren BK, Gobbi H, Schuyler PA, Olson SJ, Parl FF, Dupont WD, Page DL (2005) Immunohistochemical expression of estrogen receptor in enlarged lobular units with columnar alteration in benign breast biopsies: a nested case-control study. Am J Surg Pathol 29:105–108PubMedCrossRef

48.

Mills SE, Fechner RE (1980) Focal pregnancy-like change of the breast. Diagn Gynecol Obstet 2:67–70PubMed

49.

Mitchell G, Antoniou AC, Warren R, Peock S, Brown J, Davies R, Mattison J, Cook M, Warsi I, Evans DG, Eccles D, Douglas F, Paterson J, Hodgson S, Izatt L, Cole T, Burgess L, Eeles R, Easton DF (2006) Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res 66:1866–1872PubMedCrossRef

50.

Moinfar F (2007) Essentials of diagnostic breast pathology: a practical approach. Springer, Heidelberg

51.

Moinfar F, Man YG, Bratthauer GL, Ratschek M, Tavassoli FA (2000) Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type (“clinging ductal carcinoma in situ”): a simulator of normal mammary epithelium. Cancer 88:2072–2081PubMedCrossRef

52.

Nasser SM (2004) Columnar cell lesions: current classification and controversies. Semin Diagn Pathol 21:18–24PubMedCrossRef

53.

Noel JC, Fayt I, Fernandez-Aguilar S, Buxant F, Boutemy R (2006) Proliferating activity in columnar cell lesions of the breast. Virchows Arch 449:617–621PubMedCrossRef

54.

O’Malley FP, Mohsin SK, Badve S, Bose S, Collins LC, Ennis M, Kleer CG, Pinder SE, Schnitt SJ (2006) Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast. Mod Pathol 19:172–179PubMedCrossRef

55.

Otterbach F, Bankfalvi A, Bergner S, Decker T, Krech R, Boecker W (2000) Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology 37:232–240PubMedCrossRef

56.

Oyama T, Iijima K, Takei H, Horiguchi J, Iino Y, Nakajima T, Koerner F (2000) Atypical cystic lobule of the breast: an early stage of low-grade ductal carcinoma in-situ. Breast Cancer 7:326–331PubMedCrossRef

57.

Page DL, Kasami M, Jensen RA (1996) Hypersecretory hyperplasia with atypia in breast biopsies. Pathol Case Rev 1:36–40CrossRef

58.

Pinder SE, Provenzano E, Reis-Filho JS (2007) Lobular in situ neoplasia and columnar cell lesions: diagnosis in breast core biopsies and implications for management. Pathology 39:208–216PubMedCrossRef

59.

Pinder SE, Reis-Filho JS (2007) Non-operative breast pathology: columnar cell lesions. J Clin Pathol 60:1307–1312PubMedCrossRef

60.

Rosen P (2001) Rosen’s breast pathology. Lippincott Williams & Wilkins, Philadelphia

61.

Rosen PP (1999) Columnar cell hyperplasia is associated with lobular carcinoma in situ and tubular carcinoma. Am J Surg Pathol 23:1561PubMedCrossRef

62.

Sahoo S, Recant WM (2005) Triad of columnar cell alteration, lobular carcinoma in situ, and tubular carcinoma of the breast. Breast J 11:140–142PubMedCrossRef

63.

Schnitt SJ (2003) The diagnosis and management of pre-invasive breast disease: flat epithelial atypia–classification, pathologic features and clinical significance. Breast Cancer Res 5:263–268PubMedCrossRef

64.

Schnitt SJ, Vincent-Salomon A (2003) Columnar cell lesions of the breast. Adv Anat Pathol 10:113–124PubMedCrossRef

65.

Sewell CW (2004) Pathology of high-risk breast lesions and ductal carcinoma in situ. Radiol Clin North Am 42:821–830PubMedCrossRef

66.

Simooka H, Oyama T, Sano T, Horiguchi J, Nakajima T (2004) Immunohistochemical analysis of 14–3–3 sigma and related proteins in hyperplastic and neoplastic breast lesions, with particular reference to early carcinogenesis. Pathol Int 54:595–602PubMedCrossRef

67.

Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Sloane JP, Hanby A, Pinder SE, Lee AH, Humphreys S, Ellis IO, Lakhani SR (2005) Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol 29:734–746PubMedCrossRef

68.

Tan PH, Ho BC, Selvarajan S, Yap WM, Hanby A (2005) Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility? J Clin Pathol 58:705–709PubMedCrossRef

69.

Tavassoli FA (2001) Ductal intraepithelial neoplasia of the breast. Virchows Arch 438:221–227PubMedCrossRef

70.

Tavassoli FA (1999) Pathology of the breast. McGraw-Hill Professional, New York

71.

Tavassoli FA, Purcell AP, Bratthauer GL, Man Y (1996) Androgen receptor expression along with loss of bcl-2, ER, and PR expression in benign and malignant apocrine lesions of the breast: implication for therapy. Breast J 2:261–269CrossRef

72.

Topal NB, Ayhan S, Topal U, Bilgin T (2006) Effects of hormone replacement therapy regimens on mammographic breast density: the role of progestins. J Obstet Gynaecol Res 32:305–308PubMedCrossRef

73.

Tot T (2007) The theory of the sick breast lobe and the possible consequences. Int J Surg Pathol 15:369–375PubMedCrossRef

74.

Tremblay G, Deschenes J, Alpert L, Quenneville LA (2005) Overexpression of estrogen receptors in columnar cell change and in unfolding breast lobules. Breast J 11:326–332PubMedCrossRef

75.

Viale G (2005) Histopathology of primary breast cancer 2005. Breast 14:487–492PubMedCrossRef

76.

Vincent-Salomon A (2003) Columnar lesions: a frequent diagnosis in breast pathology!. Ann Pathol 23:593–596PubMed

77.

Warren J (1905) The surgeon and the pathologist: A plea for reciprocity as illustrated by the consideration of the classification and treatment of benign tumors of the breast. JAMA 45:149–165

78.

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 55:231–273PubMed

79.

WHO (2003) World Health Organization classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. IARC, Lyon, France

Title: Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?
Authors: Gulisa Turashvili
Malcolm Hayes
Blake Gilks
Peter Watson
Samuel Aparicio
Publication date: 01-06-2008
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 6/2008
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-008-0609-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2008

Perivascular epithelioid cell tumor of the rib

Letter to the editor

The case of the purple colon

Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer

The sub-cellular localization globotriaosylceramide in Fabry disease

Morphological variability of lymphohistiocytic variant of anaplastic large cell lymphoma (former lymphohistiocytic lymphoma according to the Kiel classification)