Mammary Paget Disease Clinical Presentation

  • Author: Carly A Elston; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Oct 27, 2011
 

History

Patients with mammary Paget disease (PD) present with a relatively long history of an eczematous skin lesion or persistent dermatitis in the nipple and adjacent areas. Eczematous skin lesions are associated with several symptoms, including the following:

  • Erythema
  • Scaling
  • Itching
  • Burning sensation
  • Ulceration
  • Oozing with serosanguineous discharge
  • Bleeding
  • Some combination of the above symptoms

Early symptoms and signs of mammary PD include the following:

  • Excoriation from itching
  • Resolution and recurrence of small vesicles within the skin lesion

Symptoms of pain, itching, and a burning sensation prompt patients to seek medical attention.

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Physical Examination

Scaly, erythematous, crusty, and thickened plaques on the nipple, spreading to the surrounding areolar areas, are typical (see the images below). Axillary PD can arise from underlying axillary accessory breast tissue.[11]

Biopsy-proven Paget disease involving nipple of 56Biopsy-proven Paget disease involving nipple of 56-year-old woman. Patient noted erythematous, swollen, enlarged nipple with focal ulceration and oozing; occasional serosanguineous discharge and bleeding were present. Patient was later found to have palpable breast mass and mammography results positive for subareolar microcalcification; no auxiliary lymphadenopathy was found. Patient was treated by simple mastectomy. At 5-year follow-up, she was alive, without recurrent or metastatic tumor. Mammary Paget disease (PD) affecting 48-year-old wMammary Paget disease (PD) affecting 48-year-old woman. Patient had experienced prolonged history of chronic eczematous dermatitis of nipple and areolar area for several years. Lesion did not respond to topical treatment, and it progressively distorted nipple with expansion into surrounding skin. Note markedly scaly, crusted, and deformed nipple with thickened, irregularly outlined adjacent nipple-areola complex. Excisional biopsy confirmed diagnosis of mammary PD. Patient developed infiltrating ductal carcinoma of underlying breast tissue with axillary lymph metastasis. She was treated by mastectomy and radiation. No metastatic tumor was noted in axillary lymph node. Patient was alive and well 3 years after treatment.

An erythematous patch in mammary PD is usually sharply demarcated and infiltrated (unlike eczematous dermatitis). Retraction of the nipple or the presence of palpable nodules indicates an underlying breast cancer. Serosanguineous discharge from the nipple may be present. Lesion size ranges from 3 mm to 15 cm in diameter; the mean size is 2.8 cm in diameter. Nipple invagination is sometimes seen (see the image below).

Nipple invagination, deformed nipple-areola compleNipple invagination, deformed nipple-areola complex, marked erythema, and alternating hyperpigmentation and hypopigmentation noted in adjacent skin of breast in 65-year-old woman with biopsy-proven Paget disease. Note focal scaling of previous biopsy site. Nipple changes were associated with intraductal carcinoma of breast. Patient was treated by conservative excision of lesion and lumpectomy for in situ carcinoma. No recurrence or metastatic disease was noted at 6-year follow-up.

Nipple changes are associated with an underlying carcinoma of the breast (ie, in situ, infiltrating ductal carcinoma) in more than 98% of patients; as many as two thirds of patients have a palpable breast tumor.

Unilateral involvement is the rule; however, bilateral mammary PD has occasionally been reported.[12] Rare cases of female patients with PD of supernumerary nipples have been reported.[13]

Pigmented mammary PD and pigmented extramammary PD are rare clinical entities in both males and females. These diseases may mimic malignant melanoma both clinically and histopathologically. They may also mimic melanoma on dermatoscopic examination.[14] In pigmented lesions of PD, increased numbers of benign melanocytes are present, which may interfere with the correct diagnosis of PD, resulting in misinterpretation of this condition as malignant melanoma.[15]

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Contributor Information and Disclosures
Author

Carly A Elston  The Commonwealth Medical College

Disclosure: Nothing to disclose.

Coauthor(s)

Grace F Kao, MD  Clinical Professor of Dermatopathology, Department of Dermatology, University of Maryland School of Medicine and George Washington University Medical School; Director, Dermatopathology Section, Department of Pathology and Laboratory Medicine, Veterans Affairs Maryland Healthcare System, Baltimore, Maryland

Grace F Kao, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and International Society of Dermatopathology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Mary Farley, MD Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center

Disclosure: Nothing to disclose.

Marjan Garmyn, MD, PhD Professor, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium; Chair and Adjunct Head, Department of Dermatology, University of Leuven, Belgium

Disclosure: Nothing to disclose.

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

References

  1. Valdes EK, Feldman SM. Paget's disease of the breast. Breast J. Jan-Feb 2006;12(1):83. [Medline].

  2. Muir R. Further observation on Paget's disease of the nipple. J Pathol Bacteriol. 1939;49:299.

  3. Marucci G, Betts CM, Golouh R, Peterse JL, Foschini MP, Eusebi V. Toker cells are probably precursors of Paget cell carcinoma: a morphological and ultrastructural description. Virchows Arch. Aug 2002;441(2):117-23. [Medline].

  4. Toker C. Clear cells of the nipple epidermis. Cancer. Mar 1970;25(3):601-10. [Medline].

  5. Kuan SF, Montag AG, Hart J, Krausz T, Recant W. Differential expression of mucin genes in mammary and extramammary Paget's disease. Am J Surg Pathol. Dec 2001;25(12):1469-77. [Medline].

  6. Morandi L, Pession A, Marucci GL, et al. Intraepidermal cells of Paget's carcinoma of the breast can be genetically different from those of the underlying carcinoma. Hum Pathol. Dec 2003;34(12):1321-30. [Medline].

  7. Schelfhout VR, Coene ED, Delaey B, Thys S, Page DL, De Potter CR. Pathogenesis of Paget's disease: epidermal heregulin-alpha, motility factor, and the HER receptor family. J Natl Cancer Inst. Apr 19 2000;92(8):622-8. [Medline].

  8. Ellis PE, Cano SD, Fear M, et al. Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast. Mod Pathol. Oct 2008;21(10):1192-9. [Medline].

  9. Kao GF, Graham JH, Helwig EB. Paget's disease of the ectopic breast with an underlying intraductal carcinoma: report of a case. J Cutan Pathol. Feb 1986;13(1):59-66. [Medline].

  10. Osteen R. Paget's disease of the nipple. In: Harris J, Hellman S, Henderson JC, eds. Breast Diseases. 2nd ed. Philadelphia, Pa: JB Lippincott; 1991:797-803.

  11. El Khoury M, Lalonde L, David J, Issa-Chergui B, Peloquin L, Trop I. Paget's disease of the axilla arising from an underlying accessory mammary tissue. Clin Radiol. Jun 2011;66(6):575-7. [Medline].

  12. Sahoo S, Green I, Rosen PP. Bilateral paget disease of the nipple associated with lobular carcinoma in situ. Arch Pathol Lab Med. Jan 2002;126(1):90-2. [Medline].

  13. Martin VG, Pellettiere EV, Gress D, Miller AW. Paget's disease in an adolescent arising in a supernumerary nipple. J Cutan Pathol. Jun 1994;21(3):283-6. [Medline].

  14. Yanagishita T, Tamada Y, Tanaka M, Kasugai C, Takahashi E, Matsumoto Y, et al. Pigmented mammary Paget disease mimicking melanoma on dermatoscopy. J Am Acad Dermatol. Jun 2011;64(6):e114-6. [Medline].

  15. Petersson F, Ivan D, Kazakov DV, Michal M, Prieto VG. Pigmented Paget disease--a diagnostic pitfall mimicking melanoma. Am J Dermatopathol. May 2009;31(3):223-6. [Medline].

  16. Morrogh M, Morris EA, Liberman L, Van Zee K, Cody HS 3rd, King TA. MRI identifies otherwise occult disease in select patients with Paget disease of the nipple. J Am Coll Surg. Feb 2008;206(2):316-21. [Medline].

  17. Requena L, Sangueza M, Sangueza OP, Kutzner H. Pigmented mammary Paget disease and pigmented epidermotropic metastases from breast carcinoma. Am J Dermatopathol. Jun 2002;24(3):189-98. [Medline].

  18. Lee EA, Kim HS, Kim HO, Park YM. Pigmented mammary paget disease with reticulated features: a rare variant of mammary paget disease. Ann Dermatol. Feb 2011;23(1):73-5. [Medline]. [Full Text].

  19. Lundquist K, Kohler S, Rouse RV. Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. Am J Surg Pathol. Feb 1999;23(2):212-9. [Medline].

  20. Nardelli AA, Stafinski T, Menon D. Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review. BMC Dermatol. Jun 15 2011;11:13. [Medline]. [Full Text].

 
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Schematic diagram of female breast depicting widely accepted concept of pathogenesis of mammary Paget disease. Malignant Paget cells are derived from luminal lactiferous ductal epithelium (A) of breast tissue with retrograde extension of cancerous Paget cells into epidermis of overlying nipple (B). Enlarged circle shows details that reveal thickening both of lining epithelium of breast duct and of nipple skin.
Biopsy-proven Paget disease involving nipple of 56-year-old woman. Patient noted erythematous, swollen, enlarged nipple with focal ulceration and oozing; occasional serosanguineous discharge and bleeding were present. Patient was later found to have palpable breast mass and mammography results positive for subareolar microcalcification; no auxiliary lymphadenopathy was found. Patient was treated by simple mastectomy. At 5-year follow-up, she was alive, without recurrent or metastatic tumor.
Mammary Paget disease (PD) affecting 48-year-old woman. Patient had experienced prolonged history of chronic eczematous dermatitis of nipple and areolar area for several years. Lesion did not respond to topical treatment, and it progressively distorted nipple with expansion into surrounding skin. Note markedly scaly, crusted, and deformed nipple with thickened, irregularly outlined adjacent nipple-areola complex. Excisional biopsy confirmed diagnosis of mammary PD. Patient developed infiltrating ductal carcinoma of underlying breast tissue with axillary lymph metastasis. She was treated by mastectomy and radiation. No metastatic tumor was noted in axillary lymph node. Patient was alive and well 3 years after treatment.
Nipple invagination, deformed nipple-areola complex, marked erythema, and alternating hyperpigmentation and hypopigmentation noted in adjacent skin of breast in 65-year-old woman with biopsy-proven Paget disease. Note focal scaling of previous biopsy site. Nipple changes were associated with intraductal carcinoma of breast. Patient was treated by conservative excision of lesion and lumpectomy for in situ carcinoma. No recurrence or metastatic disease was noted at 6-year follow-up.
Photomicrograph of malignant melanoma in situ of skin displays prominent intraepidermal pagetoid spread. Note that melanoma cells are present in all layers of epidermis, mostly in single units. Cytoplasm of melanoma cells is vacuolated. Moderate upper dermal chronic inflammatory infiltrate is present (hematoxylin-eosin, original magnification ×250). S-100 protein and homatropine methylbromide immunostains are positive in melanoma cells, whereas carcinoembryonic antigen is negative. No epithelial mucin is seen in these tumor cells.
Photomicrograph of mammary Paget disease lesion. Note nests of malignant Paget cells predominantly involving lower layers of epidermis. Cytoplasm of tumor cells contains abundant pale-staining, granular, mucinous material. Occasional small glandular structures can be seen within malignant cell nests (hematoxylin-eosin, ×100).
Composite photomicrograph of mammary Paget disease depicting nests, islands, and individual tumor cells in epidermis (left; hematoxylin-eosin, ×250), along with tumor cells stained positive for carcinoembryonic antigen (CEA) (right; immunostain with anti-CEA, ×250).
Low-power view of transmission electron micrograph displaying malignant Paget cells in lower layer of epidermis. Note large Paget cell containing ovoid nucleus (N), scanty nuclear chromatin, large nucleolus, and abundant pale-staining cytoplasm with smooth and rough endoplasmic reticulum (arrow), scattered enlarged mitochondria, free ribosomes, and lysosomes. No desmosomal attachments are seen between Paget cells and adjacent keratinocytes. Tonofilaments are seen in keratinocytes (uranyl acetate and lead citrate, ×5,500).
Cytoplasm of malignant Paget cell is packed with numerous rounded, membrane-bound mucin granules with various electron densities (uranyl acetate and lead citrate, ×12,000.)
Photomicrograph of intraductal carcinoma of breast underneath Paget disease of nipple in 56-year-old woman. Note expansion of ductal lumen, which is filled with irregularly sized tumor cells of ductal epithelial origin. Nuclear hyperchromatism and gland-in-gland (cribriform) pattern are evident. Tumor was detected by positive mammogram result depicting focus of microcalcification beneath nipple.
 
 
 
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