🧟‍♀️Paget's Disease

Question 1

What is Paget’s Disease?

Answer 1

A rare type of cancer of nipple–areola complex that is often associated with an underlying in situ or invasive carcinoma.

An eczematous change in the skin of the nipple due to Paget’s cells (large cells with pale/clear cytoplasm and prominent nucleoli) in the epidermis of the nipple.

Question 2

Epidemiology of Paget’s disease

Answer 2

• < 5% of breast malignancy
• > 95% have underlying malignancy
  • 90% invasive
  • 10% DCIS
  • almost 1/2 clinically and MMG undetectable
• Most commonly in post-menopausal women, often during the sixth decade of life (mean age 57 years).

Question 3

Pathogenesis of Paget’s disease

Answer 3

• Malignant cells invade across the epithelial-epidermal junction and enter the epidermis of the nipple, breaking the normal epidermal barrier thus allowing fluid to be extruded onto the nipple
• Pathological Hallmark: malignant, intraepithelial adenocarcinoma cells (Paget cells) occurring singly or in small groups within the epidermis of the nipple
• In-situ malignant transformation theory → Paget’s cells (intra epithelial adeno Carcinoma cells) arise from the transformed malignant keratinocytes (Toker cells) of nipple itself.
• Epidermotropic Migratory theory → ductal cancer cells migrate along the basement membrane of ducts into nipple epidermis

Question 4

Presentation of Paget’s disease

Answer 4

History: - Pain, burning, itching and change in sensation of the nipple and areola.

On examination:
- Thickened, sometimes pigmented, eczematoid, erythematous weeping or crusted lesion with irregular borders.
- There is often associated erythema and scaling of nipple with nipple retraction, deformity and discharge.
- Advanced lesions present as a round, ovoid or polycylic eczema-like plaque with a pink or red hue but it is sharply demarcated from the adjacent normal skin. This may result in ulceration and destruction of the nipple–areola complex with serous and bloody discharge.
- Paget’s lesions are almost unilateral and very rarely bilateral.

Inflammatory component may be improved by topical treatment, a result that masks the underlying condition and this may cause delay in diagnosis.

Question 5

Difference between Paget’s and eczema?

Answer 5

• Paget’s → confined to the nipple, may also be widespread. But tends to begin from nipple and spread outwards
• Eczema → starts at the areolar

Question 6

Investigation for Paget’s disease

Answer 6

Triple assessment

• Hx & PE, Risk factor assessment for breast cancer
• Due to the multicentricity of Paget’s disease, it is important to evaluate the entire breast, even if a subareolar tumor is noted on physical examination

MMG - skin, nipple and areola thickening, nipple retraction, subareolar or more diffuse microcalcifications and a discrete mass or masses or architectural distortion.

US breast and axilla - parenchymal heterogeneousness, hypoechoic areas, discrete masses, skin thickening or dilated ducts.

MRI breast → if no lesion seen on other modalities. Abnormal nipple enhancement, thickening of the nipple–areola complex, an associated enhancing DCIS or invasive tumor, or a combination of these, even when clinically unsuspected.

Scrap cytology / if presence of concurrent breast lesion,

CNB / Wedge Biopsy / Punch Biopsy of the nipple - diagnostic

Full thickness biopsy of nipple and areola - when a patient has nipple–areola skin changes, may show pagetoid cells (large, pale staining cell with normal or oval nuclei and large nuclei located between the normal keratinocyte of nipple epidermis).

Immunohistochemistry - Paget’s cells express CK7, CAM5.2 and EMA.

Question 7

Staging for Paget’s disease

Answer 7

If no associated invasive breast cancer or DCIS, Paget disease classified as Tis.

According to the TNM staging system for breast cancer, the T category in cases of Paget disease of the nipple is determined by the characteristics of the underlying tumor:

Paget disease with DCIS only:
Since ductal carcinoma in situ (DCIS) is a noninvasive (in situ) lesion, when Paget disease is associated solely with DCIS (or LCIS), it is classified as Tis (carcinoma in situ).

Paget disease with invasive breast cancer:
When there is an invasive component, the T stage is based on the size and extent of the invasive tumor itself. In other words, the presence of Paget disease does not alter the staging of the invasive carcinoma. For example, if the invasive tumor measures 1.5 cm, it would be classified as T1c; if it’s larger (e.g., 3 cm), it might be T2, and so on.

In summary, Paget disease of the nipple with DCIS is staged as Tis, whereas if invasive carcinoma is present, the tumor is staged (T1–T3, etc.) according to its size and extent.

Example Staging Scenarios
- Paget’s disease with no underlying mass and no lymph node involvement → Stage 0 (Tis, N0, M0)

• Paget’s disease with a 3 cm underlying tumor, no lymph node involvement → Stage IIA (T2, N0, M0)
• Paget’s disease with a 2 cm tumor and 4 positive axillary nodes→ Stage IIIA (T2, N2, M0)
• Paget’s disease with distant metastasis to the lungs → Stage IV (any T, any N, M1)

Paget’s disease + invasive component is staged based on the invasive tumor size (T1–T3), unless there is extensive skin involvement (ulceration, nodules, or >1/3 of breast skin), in which case it becomes T4b.

💡 Example Scenarios:
Paget’s + 1.5 cm invasive ductal carcinoma
➤ T1c (tumor >1–2 cm), regardless of Paget’s.

Paget’s + underlying 4.5 cm invasive tumor with skin ulceration
➤ T4b (due to ulceration, not just Paget’s).

Question 8

Surgical Management of Paget’s disease

Answer 8

~~~

```Surgical

For Invasive ca, Without DCIS

• Mastectomy (excise till pectoralis fascia) + SLNB for diffuse disease or disease away from nipple.
• Central WLE + SLNB → when disease localized to subareolar area or NAC
  
  • ± RT → depends on full HPE report

With DCIS ( no palpable lesion)

• Central WLE → if DCIS localized + RT (evidence is lacking due to rarity of the disease)
• Mastectomy if extensive DCIS

No role for Tamoxifen.

Many patients with Paget disease of breast and a palpable mass are not the candidates for BCT because of the remarkable distance between the primary tumor and the nipple-areolar complex.

If there is no underlying mass, Still there is a higher chance that there is some underlying lesion is present likely DCIS.
The chances of underlying invasive cancer range from 25 to 33 percent.

Question 9

Prognosis of Paget’s disease

Answer 9

Prognosis of the underlying cancer is not altered by the presence of Paget’s disease of the nipple
- Palpable mass –> most have IDC & axillary nodal involvement = 5yr survival 37-43%
- No palpable mass –> most have DCIS = 5yr survival 90-100%