OUTLINE

• INTRODUCTION
• PATHOLOGY
• CLINICAL PRESENTATION
• DIFFENTIAL DIAGNOSIS
• INVESTIGATIONS
• TREATMENT
• PROGNOSIS
• CONCLUSION
INTRODUCTION
• It is ductal carcinoma-in-situ which spreads within the duct, reaches
the nipple, and infiltrates the epidermis of the nipple, areola and
surrounding skin with resulting inflammatory reaction crusting and
scaling.

• Sir James Paget, 1874 a British surgeon and pathologist, He described

‘an eczematous change in the skin of the nipple preceding an
underlying mammary cancer’.
• It is rare, accounting for 0.7–4.9% of breast malignancies
• Peaked in 1985 and have steadily decreased from 1.31 to 0.64 per
100 000
• 90% is invasive ductal carcinoma, 70% shows mass underneath nipple
and areola.
PATHOLOGY
• The epithelium shows two characteristic findings;
1. Pagetoid cells are present – the sine qua non of Paget's disease of
the breast. These are large, round or oval cells with enlarged
pleomorphic and hyperchromatic nuclei, prominent nucleoli and
abundant, clear, pale cytoplasm.
2. Reactive changes in the epidermis and dermis, such as lymphocytic
infiltration and angiogenesis, are also seen, giving rise to the
hyperaemic, exudative appearance characteristic of Paget's disease
of the breast
PATHOGENESIS
• Theories;
1. One suggests that Pagetoid cells are keratinocytes that have undergone
malignant transformation. According to this theory, Paget's disease of the
breast represents an in situ carcinoma of the skin. This theory is supported
by the observation that, often, overlying skin changes and underlying
malignancy are discontinuous.
2. Cells migrate along basement membranes and enter the epidermis and
dermis of the nipple–areola complex. Pagetoid cells and underlying
carcinomas demonstrate similar immunohistochemical staining patterns,
supporting this theory that it is cells from the cancer that migrate.
CLINICAL PRESENTATION
1. First symptom is burning and itching sensation; lymphocytic
infiltration and angiogenesis.
2. Dermatological changes; crusty, erythematous flaking, and
irregular, raised, scaly skin lesions may develop.
3. The spread is from the nipple to the areola and then to surrounding
skin( cf. eczema)
4. As the disease progresses, bleeding, ulceration and destruction of
the nipple– areola complex occur.
5. In Up to 70% of patients with Pagetoid changes of the nipple, an
underlying malignancy is palpable
• NB; Nipple discharge is rare and is usually a result of advanced local
disease, rather than a consequence of Paget's disease.
• Rarely, the underlying malignancy tethers the nipple–areola complex
or adjacent skin, causing retractions and deformity of the natural
contour of the breast.
DIFFERENTIAL DIAGNOSIS
• ECZEMA
• MELANOMA
• TUBERCULOSIS
INVESTIGATION
• GOALS;
• Confirmation that the cutaneous disease is Paget's and
• The detection of the underlying malignancy.
1. BIOPSY; punch, excisional. Full-thickness biopsy is required.
• Histology; Pagetoid cells.
• Immunohistochemistry; these cells stain for CK7, CAM-5.2, AE1/AE3 and
S100. They do not stain for HMB-45 or keratins, differentiating them from
melanoma
• Almost 90% of Paget's cells are HER-2 positive.
2. IMAGING;
• bilateral mammography and ultrasound are the initial steps in the imaging
work-up.
• If a lesion is seen, it is investigated in standard fashion.
• However, the sensitivity of mammography is limited; in one series,
mammography detected only 32% of underlying carcinomas.

• Breast MRI; for clinically and mammographically occult malignancies.

• Morrogh et al. showed that MRI demonstrated the extent of occult
disease in six of seven patients, thereby guiding surgical planning and
the decision whether to pursue total mastectomy or breast
conservation
TREATMENT
• Surgery is the mainstay of treatment for Paget's disease of the breast
– except for patients with significant comorbidities.
• OPTIONS
• BREAST CONSERVATION WITH POST-OPERATIVE RADIOTHERAPY
• MODIFIED RADICAL MASTECTOMY
• The factors which determine the type of treatment are;
1. The presence of ipsilateral carcinoma
2. The location of the carcinoma
CENTRAL SEGMENTECTOMY;
• In the absence of an identifiable tumour within the breast, paget’s
disease is considered to be ductal carcinoma-in-situ of the nipple-
areolar region and can be treated with excision alone or excision and
radiotherapay
• Associated ipsilateral breast carcinoma can be treated with a central
segmentectomy rather than a mastectomy if there are no
contraindications to breast conservation therapy(Kawase et al 2005)
• The tumour is identifiable, confine to the central breast –beneath the
nipple areola.
• Frozen section shows negative margin
• Adjuvant radiotherapy available. (50Gy)
• MODIFIED RADICAL MASTECTOMY;
• When cancer is distance from nipple-areola complex
• Axillary involvement
• NB; axillary staging with SLNB is performed when invasive cancer is
present. Or if mastectomy is under taken without a diagnosis of
invasive cancer.
BREAST CONSERVATIVE MANAGEMENT
•ALGORITHM
PROGNOSIS

The underlying malignancy and the treatment thereof determine the

prognosis of patients with Paget's disease of the breast.
REFERENCES