Paget's disease of the breast pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4];Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[5]

Overview

On gross pathology, eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration of the nipple, and inversion of the nipple are characteristic findings of Paget's disease of the breast. Eczema changes of the nipple-areolar complex are said to occur due to invasion of the overlying epidermis by malignant (Paget) cells. The commonly accepted hypothesis is that most cases of Paget's disease of the breast originate from in situ or invasive ductal carcinoma of the underlying breast tissue. On microscopic histopathological analysis, epidermal Paget cells which are malignant glandular epithelial cells organized in groups with nest-like patterns or gland-like structures and are preferably located in the epidermal basal layer characteristic of Paget's disease of the breast.On gross pathology nipple and areola show eczematoid, erythematous, moist or crusted lesions, with or without fine scaling, infiltration of the nipple, and inversion of the nipple are characteristic findings of Paget's disease of the breast.Immunohistochemistry is very useful in Paget's disease of the breast for differential diagnoses and histogenesis. The overexpression of the low molecular weight cytokeratins, notably CK7, and lack of expression of high molecular weight cytokeratins, such as CK10, CK14 and CK20 are observed in 98-100% of Paget's disease of the breast.

Pathophysiology

  • The pathogenesis of Paget’s disease of the breast still remains controversial.
  • The commonly accepted hypothesis is that most cases of Paget's disease of the breast originate from in situ or invasive ductal carcinoma of the underlying breast tissue.This is supported by two different theories:[1][2]
  • Epidermotropic theory
  • Intraepidermal transformation theory

Epidermotropic Theory


Intraepidermal transformation theory

Gross Pathology

Paget's disease of the nipple[6]

Microscopic pathology

Paget's disease micrography[11]

Immunohistochemistry

Immunohistochemical marker Positivity
Oncoproteins
Her 2 80-100%
Her 1 0-13%
Her 3 0-57%
Her 4 0-79%
Cyclin D1 8-100%
Bcl-2 14%
Tumor suppressors
P16 90%
pRB 67%
p53 13-62%
Steroid hormone receptors
ER 10-41%
PR 0-25%
AR 71-88%
Intermediate filaments
Cam 5.2 70-100%
CK7 98-100%
CK 5/6 0-2%
CK 5/8 100%
CK 8/18 98%
CK19 100%
Vimentin 45%
Glycoproteins
MUC 1 Almost 100%
MUC2 0-50%
MUC3 75%
MUC4 10%
MUC5AC 0-50%
MUC6 0-40%
MUC7 7%
MUC8 4%
CEA 20-56%
GCDFP-15 48-57%
Other proteins
Claudin 2 32%
Claudin 3 100%
Claudin 4 100%
Claudin 5 50%
NY-BR1 75%
S100 25%

References

  1. 1.0 1.1 Subramanian, Ashok; Birch, Hilary; McAvinchey, Rita; Stacey-Clear, Adam (2007). "Pagets disease of uncertain origin: case report". International Seminars in Surgical Oncology. 4 (1): 12. doi:10.1186/1477-7800-4-12. ISSN 1477-7800.
  2. 2.0 2.1 2.2 2.3 Lopes Filho, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo (2015). "Mammary and extramammary Paget's disease". Anais Brasileiros de Dermatologia. 90 (2): 225–231. doi:10.1590/abd1806-4841.20153189. ISSN 1806-4841.
  3. 3.0 3.1 Sakorafas, G.H.; Blanchard, K.; Sarr, M.G.; Farley, D.R. (2001). "Paget's disease of the breast". Cancer Treatment Reviews. 27 (1): 9–18. doi:10.1053/ctrv.2000.0203. ISSN 0305-7372.
  4. Morandi, Luca; Pession, Annalisa; Marucci, Gian Luca; Foschini, Maria Pia; Pruneri, Giancarlo; Viale, Giuseppe; Eusebi, Vincenzo (2003). "Intraepidermal cells of paget's carcinoma of the breast can be genetically different from those of the underlying carcinoma". Human Pathology. 34 (12): 1321–1330. doi:10.1016/S0046-8177(03)00405-2. ISSN 0046-8177.
  5. Nofech-Mozes, Sharon; Hanna, Wedad (2009). "Toker Cells Revisited". The Breast Journal. 15 (4): 394–398. doi:10.1111/j.1524-4741.2009.00743.x. ISSN 1075-122X.
  6. 6.0 6.1 Image courtesy of Dr Garth Kruger. Radiopaedia (original file [1]). [http://radiopaedia.org/licence Creative Commons BY-SA-NC
  7. 7.0 7.1 Serour, F.; Birkenfeld, S.; Amsterdam, E.; Krispin, M.; Treshchan, O. (1988). "Paget's disease of the male breast". Cancer. 62 (3): 601–605. doi:10.1002/1097-0142(19880801)62:3<601::AID-CNCR2820620326>3.0.CO;2-7. ISSN 0008-543X.
  8. 8.0 8.1 Lloyd, J (2000). "Mammary and extramammary Paget's disease". Journal of Clinical Pathology. 53 (10): 742–749. doi:10.1136/jcp.53.10.742. ISSN 0021-9746.
  9. Kanitakis, J (2007). "Mammary and extramammary Paget's disease". Journal of the European Academy of Dermatology and Venereology. 0 (0): 070328074210008–???. doi:10.1111/j.1468-3083.2007.02154.x. ISSN 0926-9959.
  10. Guitera, P.; Scolyer, R.A.; Gill, M.; Akita, H.; Arima, M.; Yokoyama, Y.; Matsunaga, K.; Longo, C.; Bassoli, S.; Bencini, P.L.; Giannotti, R.; Pellacani, G.; Alessi-Fox, C.; Dalrymple, C. (2013). "Reflectance confocal microscopy for diagnosis of mammary and extramammary Paget's disease". Journal of the European Academy of Dermatology and Venereology. 27 (1): e24–e29. doi:10.1111/j.1468-3083.2011.04423.x. ISSN 0926-9959.
  11. Paget's disease of the breast. [2] (original file [3])
  12. Ellis, Patricia E; MacLean, Allan B; Crow, Julie C; Wong Te Fong, L F; Rolfe, Kerstin J; Perrett, Christopher W (2009). "Expression of cyclin D1 and retinoblastoma protein in Paget’s disease of the vulva and breast: an immunohistochemical study of 108 cases". Histopathology. 55 (6): 709–715. doi:10.1111/j.1365-2559.2009.03434.x. ISSN 0309-0167. C1 control character in |title= at position 61 (help)
  13. Sandoval-Leon, Ana C.; Drews-Elger, Katherine; Gomez-Fernandez, Carmen R.; Yepes, Monica M.; Lippman, Marc E. (2013). "Paget's disease of the nipple". Breast Cancer Research and Treatment. 141 (1): 1–12. doi:10.1007/s10549-013-2661-4. ISSN 0167-6806.
  14. Fu W, Lobocki CA, Silberberg BK, Chelladurai M, Young SC (July 2001). "Molecular markers in Paget disease of the breast". J Surg Oncol. 77 (3): 171–8. PMID 11455553.
  15. Karakas C (2011). "Paget's disease of the breast". J Carcinog. 10: 31. doi:10.4103/1477-3163.90676. PMC 3263015. PMID 22279416.
  16. Sek, Piotr; Zawrocki, Antoni; Biernat, Wojciech; Piekarski, Janusz H (2010). "HER2 molecular subtype is a dominant subtype of mammary Paget's cells. An immunohistochemical study". Histopathology. 57 (4): 564–571. doi:10.1111/j.1365-2559.2010.03665.x. ISSN 0309-0167.
  17. Mori O, Hachisuka H, Nakano S, Sasai Y, Shiku H (August 1990). "Expression of ras p21 in mammary and extramammary Paget's disease". Arch. Pathol. Lab. Med. 114 (8): 858–61. PMID 1695839.
  18. Kanitakis J, Thivolet J, Claudy A (1993). "p53 protein expression in mammary and extramammary Paget's disease". Anticancer Res. 13 (6B): 2429–33. PMID 8135479.
  19. Ellis PE, Fong LF, Rolfe KJ, Crow JC, Reid WM, Davidson T, MacLean AB, Perrett CW (August 2002). "The role of p53 and Ki67 in Paget's disease of the vulva and the breast". Gynecol. Oncol. 86 (2): 150–6. PMID 12144821.
  20. Smith KJ, Tuur S, Corvette D, Lupton GP, Skelton HG (November 1997). "Cytokeratin 7 staining in mammary and extramammary Paget's disease". Mod. Pathol. 10 (11): 1069–74. PMID 9388055.

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