PAGETS DISEASE OF THE BREAST
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Named after the observations of Sir James Paget.
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Characterized by proliferation of malignant glandular epithelial cells within the squamous epithelium of the nipple
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Associated with invasive and insitu carcinoma breast
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Epidemiology
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Incidence – 1- 4% of all breast carcinomas
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Age – 20 – 90 years (20% – 30% of patients are post-menopausal)
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Pathogenesis – Two hypothesis
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Mostly accepted hypothesis: Local migration of underlying carcinoma cells into lactiferous ducts or extension of DCIS from the underlying ducts
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If there is no underlying carcinoma or DCIS ‘toker cells’ are hypothesized as precursor for this lesion
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Location: nipple and or areola region and may extend into adjacent breast skin
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Clinical presentation and Gross appearance of nipple
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Normal appearance
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Erythematous
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Eczematous with weeping (Discharging serosanguinous fluid) – most common presentation
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Crusting
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May present as pigmented macule resembling melanoma
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Microscopy
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Squamous epithelium of nipple shows paget cells
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Paget cells: Adenocarcinoma type cells with pleomorphic nuclei, prominent nucleoli and abundant clear cytoplasm containing PAS positive diastase resistant mucin vacuoles.
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Paget cells can be present as small clusters or single cells or rarely as gland formation at dermoepidermal junction
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Paget cells may phagocytose melanin, mimicking melanocytes. These cells may be admixed with non-neoplastic melanocytes which are markedly increased.
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Underlying lactiferous ducts often contain Duct cell carcinoma – in situ (DCIS) (24 – 43%)
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Lesion is associated with high grade invasive carcinoma (53 – 64%)
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Overlying epithelium of nipple shows varying degrees of hyperplasia, hyperkeratosis, inflammation and ulceration
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Paget cells may invade dermis ( in 4 – 8% of cases of mammary pagets disease). In the dermis invading cells should resemble paget cells and should be separate from underlying carcinoma
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Diagnosis is by cytological examination of the exudates or nipple biopsy
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- Immunohistochemistry
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Paget cells are positive for
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Low molecular weight keratins (CK7 and CAM5.2)
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Her 2 (80 -90%)
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ER and PR (30% to 40% of cases)
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Variable expression is seen in
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CEA
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EMA
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S-100
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GCDFP-15
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p53
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GATA 3
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Rarely Paget cells can be negative for CK7
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Differential diagnosis
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Squamous cell carcinoma –
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Negative for Her 2 and low molecular weight keratin
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Positive for high molecular weight keratins
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Melanoma –
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Positive for S-100, HMB 45, SOX 10, Melan A
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Negative for keratins
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Toker cells
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These cells are similar to Paget cells having clear cytoplasm, but does not have pleomorphism
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They are positive for CK7, and CAM5.2 and negative with Her2 and ER positive
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Staging –
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Pagets disease is considered a Tis
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If underlying carcinoma is present, then the stage of underlying tumor is considered
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Paget disease: Tissue lined by keratinized stratified squamous epithelium with few clusters and individually dispersed tumor cells having clear cytoplasm and pleomorphic nuclei. Underlying stroma shows lymphocytic infiltrate and congested blood vessels (H&E,X100)
Paget disease: Tissue lined by keratinized stratified squamous epithelium with few clusters and individually dispersed tumor cells having clear cytoplasm and pleomorphic nuclei. Underlying stroma shows lymphocytic infiltrate and congested blood vessels. One foci shows lymphovascular tumor emboli (H&E,X100)
Pagets disease: Stratified squamous epithelium with pagets cells having vacuolated cytoplasm and atypical nuclei. Underlying stroma shows congested blood vessels and chronic inflammatory cell (H&E,X100)
Pagets disease: Stratified squamous epithelium with pagets cells having vacuolated cytoplasm and atypical nuclei. Underlying stroma shows congested blood vessels and chronic inflammatory cell (H&E,X100)
Pagets disease: Stratified squamous epithelium with pagets cells having vacuolated cytoplasm and atypical nuclei. Underlying stroma shows congested blood vessels (H&E,X400)
Pagets disease: Stratified squamous epithelium with pagets cells having vacuolated cytoplasm and atypical nuclei. Some of them show prominent nucleoli.(H&E,X400)
Pagets disease: Stratified squamous epithelium with pagets cells having vacuolated cytoplasm and pleomorphic nuclei (H&E,X400).
Invasive Paget disease: Tissue lined by stratified squamous epithelium with paget cells. underlying dermis shows nests of polygonal paget cells having clear cytoplasm and pleomorphic nuclei. Interstitial stroma shows chronic inflammatory cells and congested blood vessels (H&E,X50)
Invasive Paget disease: Ulcerated tissue covered by fibrinous exudate and inflammatory cells. Dermis shows clusters and individually dispersed paget cells. Interstitial tissue shows chronic inflammatory cells and congested blood vessels (H&E,X50)
Invasive Paget disease: Tissue lined by stratified squamous epithelium with paget cells. underlying dermis shows nests of polygonal paget cells having clear cytoplasm and pleomorphic nuclei. Interstitial stroma shows chronic inflammatory cells and congested blood vessels (H&E,X100)
Invasive Paget disease: Ulcerated tissue covered by fibrinous exudate and inflammatory cells. Dermis shows clusters and individually dispersed paget cells. Interstitial tissue shows chronic inflammatory cells and congested blood vessels (H&E,X100)
Invasive Paget disease: Tissue lined by stratified squamous epithelium with paget cells. underlying dermis shows nests of polygonal paget cells having clear cytoplasm and pleomorphic nuclei. Interstitial stroma shows chronic inflammatory cells and congested blood vessels (H&E,X100)
Invasive Paget disease: Dermis with clusters and individually dispersed polygonal paget cells having clear cytoplasm and pleomorphic nuclei. Interstitial stroma shows chronic inflammatory cells and congested blood vessels (H&E,X100)
Invasive Paget disease: Dermis with clusters and individually dispersed polygonal paget cells having clear cytoplasm and pleomorphic hyperchromatic nuclei. Interstitial stroma shows chronic inflammatory cells and congested blood vessels (H&E,X400)