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

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  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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  6. 6.0 6.1 Image courtesy of Dr Garth Kruger. Radiopaedia (original file [1]). [http://radiopaedia.org/licence Creative Commons BY-SA-NC
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  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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  11. Paget's disease of the breast. [2] (original file [3])
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  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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

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