Paget's disease of the breast differential diagnosis: Difference between revisions

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{{CMG}};{{AE}} {{Preeti}}
{{CMG}};{{AE}} {{Preeti}}
==Overview==
==Overview==
Due to close similarity with many skin lesions, the diagnosis of Mammary Paget’s Diseas may be delayed or many cases can be misdiagnosed. Paget's disease of the breast must be differentiated from [[atopic dermatitis]], [[eczema]], [[psoriasis]], [[Melanoma|malignant melanoma]], [[Bowen's disease]], [[basal cell carcinoma]], and pagetoid dyskeratosis.
Due to close similarity with many skin lesions, the diagnosis of Mammary Paget’s Diseas may be delayed or many cases can be misdiagnosed. [[Immunohistochemical]] staining for [[cytokeratin]], [[epithelial membrane antigen]] (EMA) and [[c-erb-B2]] [[oncoprotein]] is useful for the differential diagnosis. Toker cells found in the [[epidermis]] of the [[nipple]], close to the opening of [[Lactiferous duct|lactiferous ducts]], along the basal layer of the [[epidermis]], are [[Morphological computation|morphological]] and [[Immunohistochemistry|immunohistochemical]] similar to [[Mammary gland|mammary]] Paget's cells. In contrast to Paget's cells which are strongly associated with both [[Ki-67]] and Her-2/c-erbB-2 and these markers are mostly used to distinguish Paget's cells from Toker cells. In case of [[Atypical cells|atypical]] Toker cells a combination of [[CD138]] and [[p53]] is very helpful in distinguishing these atypical cells from Paget's cells. Paget's disease of the breast must be differentiated from [[atopic dermatitis]], [[eczema]], [[psoriasis]], [[Melanoma|malignant melanoma]], [[Bowen's disease]], [[basal cell carcinoma]], [[Intraductal papilloma|benign intraductal papilloma]], [[Nevoid hyperkeratosis|nevoid hyperkeratosis of the nipple and areola]]  (NHNA), squamous metaplasia of lactiferous ducts (SMOLD)/  [[Zuska's disease]] and pagetoid dyskeratosis.


==Differential Diagnosis==
==Differential Diagnosis==
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*[[Bowen’s disease]]
*[[Bowen’s disease]]
*[[Basal cell carcinoma|Superficial basal cell carcinoma]]
*[[Basal cell carcinoma|Superficial basal cell carcinoma]]
*Squamous metaplasia of lactiferous ducts (SMOLD)/  [[Zuska's disease]]
*[[Intraductal papilloma|Benign intraductal papilloma]]
*[[Intraductal papilloma|Benign intraductal papilloma]]
*[[Nevoid hyperkeratosis|Nevoid hyperkeratosis of the nipple and areola]]  (NHNA)
*Pagetoid dyskeratosis
*Pagetoid dyskeratosis
*[[Mastitis]]
*[[Mastitis]]
*[[Breast abcess]]
*[[Breast abscess|Breast abcess]]


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Revision as of 16:08, 14 March 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]

Overview

Due to close similarity with many skin lesions, the diagnosis of Mammary Paget’s Diseas may be delayed or many cases can be misdiagnosed. Immunohistochemical staining for cytokeratin, epithelial membrane antigen (EMA) and c-erb-B2 oncoprotein is useful for the differential diagnosis. Toker cells found in the epidermis of the nipple, close to the opening of lactiferous ducts, along the basal layer of the epidermis, are morphological and immunohistochemical similar to mammary Paget's cells. In contrast to Paget's cells which are strongly associated with both Ki-67 and Her-2/c-erbB-2 and these markers are mostly used to distinguish Paget's cells from Toker cells. In case of atypical Toker cells a combination of CD138 and p53 is very helpful in distinguishing these atypical cells from Paget's cells. Paget's disease of the breast must be differentiated from atopic dermatitis, eczema, psoriasis, malignant melanoma, Bowen's disease, basal cell carcinoma, benign intraductal papilloma, nevoid hyperkeratosis of the nipple and areola (NHNA), squamous metaplasia of lactiferous ducts (SMOLD)/ Zuska's disease and pagetoid dyskeratosis.

Differential Diagnosis


Paget's disease of the breast is often confused with

Diseases Benign or Malignant Etiology Clinical manifestations Histopathology Gold Standard Associated factors
Symptoms Physical examination
Rash Nipple Discharge Erythema Mastalgia Breast Exam Other
Paget's disease of the breast[7][8] Most the patients have underlying breast cancer. + + ±
  • Usually unilateral nipple is effected
Atopic dermatitis

(Eczema)[9][10]

N/A
  • Clinical examination
Erosive adenomatosis of the nipple[11][12] + + Biopsy: Shows absence of cytological atypia
Allergic contact dermatitis[13] + N/A
Psoriasis[14][15]
  • Well-circumscribed, pink papules and symmetrically distributed cutaneous plaques with silvery scales.
+ + N/A Auspitz's sign (pinpoint bleeding) Risk factors include
Malignant melanoma[4]
  • A lesion with ABCD
    • Asymmetry
    • Border irregularity
    • Color variation
    • Diameter changes
  • Bleeding from the lesion.
± N/A
  • Pigmented lesion with:
  • Asymmetry
  • Irregular borders
  • Variegated color
  • Diameter >6 mm
  • Nests of atypical melanocytes with asymmetry, poor circumscription of varying sizes and shapes
  • Present in the lower epidermis and dermis
  • Complete full-thickness excisional biopsy of suspicious lesions with 1 to 3 mm margin of normal skin.
  • S-100 is used to differentiate Paget's disease from melanoma. But, since 18-25% of Paget's are S-100 positive, at least two melanoma markers, such as HMB-45, S-100, or Melan-A should be used.
Bowen’s disease[4] + N/A
  • Presence of dotted and/or glomerular vessels
  • White to yellowish surface scales
  • Red-yellowish background
  • Clinical examination
  • Slow growth over the years
Superficial basal cell carcinoma[16][17] + N/A
  • Superficial fine telangiectasia
  • Shiny white to red, translucent or opaque structureless areas
  • Multiple small erosions.
Squamous metaplasia of lactiferous ducts (SMOLD)/ Zuska's disease[18][19] + +
Lactiferous duct ectasia / Plasma cell mastitis / Comedomastitis[20] Nipple retraction + Thick nipple discharge. Ultrasound:
Nipple Adenoma / Papillary adenoma of the nipple[21] ± +
  • Multiple small palpable masses below
  • Usually unilateral nipple is effected
Nevoid hyperkeratosis of the nipple and areola (NHNA) [22][23] Slow growing bluish-brown verrucous thickening of the nipple or areola.
  • Usually bilateral nipple is effected
Benign Toker cell hyperplasia[6][1][24]
  • Normal components of the nipple skin
  • Appears similar to paget cells.
Normal nipple- areolar complex Normal breast examination. N/A
  • Toker cells are immunoreactive for cytokeratin 7 and CAM5.2 but are not positive for HER2- neu.
Breast abscess[25][26]
  • Complication of lactational mastitis in 14% of cases
  • Common among African-American women, heavy smokers and obese patients.
± + +
  • Associated symptoms of fever, nausea, vomiting.
  • Resolve after drainage/antibiotic therapy.

Ultrasound:

  • Fluid collection
Mondors disease[27][28][29][30] Superficial phlebitis and periphlebitis of the superficial vein. Red linear cord running from the lateral margin of the breast attached to the overlying skin. + +
  • Red tender cord which may last up to 4-8 weeks before spontaneously remitting leaving a puckered groove along the breast.
  • N/A–
  • Predominantly seen in middle-aged women but is also seen in men.
  • May indicate breast cancer.
Mastitis[31][32]
  • Localized erythema, warmth, swelling, and pain.
± + ±
  • Associated symptoms of fever, chills, or rigor may be present.
  • Resolve after drainage/antibiotic therapy

Breast parenchymainflammation:

Ultrasound:

  • Ill-defined area with hyperechogenicity with inflamed fat lobules
  • Skin thickening.
History of lactation including difficulty in breastfeeding, breast engorgement, or erosion of nipples.
Inflammatory Breast Cancer[33][34]
  • Localized erythema, warmth, swelling, and pain.
+ +
  • Usually unilateral

References

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  2. Lundquist K, Kohler S, Rouse RV (1999). "Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells". Am J Surg Pathol. 23 (2): 212–9. PMID 9989849.
  3. Mitchell, Sonya; Lachica, Roberto; Randall, M. Barry; Beech, Derrick J. (2006). "Paget's Disease of the Breast Areola Mimicking Cutaneous Melanoma". The Breast Journal. 12 (3): 233–236. doi:10.1111/j.1075-122X.2006.00247.x. ISSN 1075-122X.
  4. 4.0 4.1 4.2 Reed W, Oppedal BR, Eeg Larsen T (1990). "Immunohistology is valuable in distinguishing between Paget's disease, Bowen's disease and superficial spreading malignant melanoma". Histopathology. 16 (6): 583–8. PMID 1695889.
  5. Toker C (1970). "Clear cells of the nipple epidermis". Cancer. 25 (3): 601–10. PMID 4313654.
  6. 6.0 6.1 Di Tommaso, Luca; Franchi, Giada; Destro, Annarita; Broglia, Fabiana; Minuti, Francesco; Rahal, Daoud; Roncalli, Massimo (2008). "Toker cells of the breast. Morphological and immunohistochemical characterization of 40 cases". Human Pathology. 39 (9): 1295–1300. doi:10.1016/j.humpath.2008.01.018. ISSN 0046-8177.
  7. Gaspari, Eleonora; Ricci, Aurora; Liberto, Valeria; Scarano, Angela Lia; Fornari, Maria; Simonetti, Giovanni (2013). "An Unusual Case of Mammary Paget's Disease Diagnosed Using Dynamic Contrast-Enhanced MRI". Case Reports in Radiology. 2013: 1–5. doi:10.1155/2013/206235. ISSN 2090-6862.
  8. 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.
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  12. Lewis HM, Ovitz ML, Golitz LE (October 1976). "Erosive adenomatosis of the nipple". Arch Dermatol. 112 (10): 1427–8. PMID 962337.
  13. Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF (2009). "Allergic and irritant contact dermatitis". Eur J Dermatol. 19 (4): 325–32. doi:10.1684/ejd.2009.0686. PMID 19447733.
  14. Ljosaa TM, Rustoen T, Mörk C, Stubhaug A, Miaskowski C, Paul SM, Wahl AK (2010). "Skin pain and discomfort in psoriasis: an exploratory study of symptom prevalence and characteristics". Acta Derm. Venereol. 90 (1): 39–45. doi:10.2340/00015555-0764. PMID 20107724.
  15. Naldi L, Parazzini F, Brevi A, Peserico A, Veller Fornasa C, Grosso G, Rossi E, Marinaro P, Polenghi MM, Finzi A (September 1992). "Family history, smoking habits, alcohol consumption and risk of psoriasis". Br. J. Dermatol. 127 (3): 212–7. PMID 1390163.
  16. Yamamoto H, Ito Y, Hayashi T, Urano N, Kato T, Kimura Y, Tanigawa T, Endo W, Kurokawa E, Kikkawa N, Taniguchi H (2001). "A case of basal cell carcinoma of the nipple and areola with intraductal spread". Breast Cancer. 8 (3): 229–33. PMID 11668245.
  17. Ulanja MB, Taha ME, Al-Mashhadani AA, Al-Tekreeti MM, Elliot C, Ambika S (2018). "Basal Cell Carcinoma of the Female Breast Masquerading as Invasive Primary Breast Carcinoma: An Uncommon Presentation Site". Case Rep Oncol Med. 2018: 5302185. doi:10.1155/2018/5302185. PMC 6051126. PMID 30057838.
  18. Gollapalli V, Liao J, Dudakovic A, Sugg SL, Scott-Conner CE, Weigel RJ (July 2010). "Risk factors for development and recurrence of primary breast abscesses". J. Am. Coll. Surg. 211 (1): 41–8. doi:10.1016/j.jamcollsurg.2010.04.007. PMID 20610247.
  19. Meguid MM, Oler A, Numann PJ, Khan S (October 1995). "Pathogenesis-based treatment of recurring subareolar breast abscesses". Surgery. 118 (4): 775–82. PMID 7570336.
  20. Schwartz GF (1982). "Benign neoplasms and "inflammations" of the breast". Clin Obstet Gynecol. 25 (2): 373–85. PMID 6286199.
  21. Spohn, Gina P.; Trotter, Shannon C.; Tozbikian, Gary; Povoski, Stephen P. (2016). "Nipple adenoma in a female patient presenting with persistent erythema of the right nipple skin: case report, review of the literature, clinical implications, and relevancy to health care providers who evaluate and treat patients with dermatologic conditions of the breast skin". BMC Dermatology. 16 (1). doi:10.1186/s12895-016-0041-6. ISSN 1471-5945.
  22. Mazzella C, Costa C, Fabbrocini G, Marangi GF, Russo D, Merolla F, Scalvenzi M (November 2016). "Nevoid hyperkeratosis of the nipple mimicking a pigmented basal cell carcinoma". JAAD Case Rep. 2 (6): 500–501. doi:10.1016/j.jdcr.2016.09.007. PMC 5161776. PMID 28004028.
  23. Ghanadan A, Balighi K, Khezri S, Kamyabhesari K (September 2013). "Nevoid Hyperkeratosis of the Nipple and/or Areola: Treatment with Topical Steroid". Indian J Dermatol. 58 (5): 408. doi:10.4103/0019-5154.117347. PMC 3778809. PMID 24082214.
  24. Park, Sanghui; Suh, Yeon-Lim (2009). "Useful immunohistochemical markers for distinguishing Paget cells from Toker cells". Pathology. 41 (7): 640–644. doi:10.3109/00313020903273092. ISSN 0031-3025.
  25. D'Alfonso TM, Ginter PS, Shin SJ (2015). "A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples". J Pathol Transl Med. 49 (4): 279–87. doi:10.4132/jptm.2015.06.11. PMC 4508565. PMID 26095437.
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  31. Kvist LJ, Larsson BW, Hall-Lord ML, Steen A, Schalén C (April 2008). "The role of bacteria in lactational mastitis and some considerations of the use of antibiotic treatment". Int Breastfeed J. 3: 6. doi:10.1186/1746-4358-3-6. PMC 2322959. PMID 18394188.
  32. Foxman B, D'Arcy H, Gillespie B, Bobo JK, Schwartz K (January 2002). "Lactation mastitis: occurrence and medical management among 946 breastfeeding women in the United States". Am. J. Epidemiol. 155 (2): 103–14. PMID 11790672.
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  34. Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA, Dirix LY, Levine PH, Lucci A, Krishnamurthy S, Robertson FM, Woodward WA, Yang WT, Ueno NT, Cristofanilli M (March 2011). "International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment". Ann. Oncol. 22 (3): 515–23. doi:10.1093/annonc/mdq345. PMC 3105293. PMID 20603440.