Paget’s disease of the Breast

Paget’s disease of the breast or nipple is an eczematous condition involving the nipple and areolar skin, which is histologically characterized by the presence of malignant cells interspersed within the keratinocytes of the epidermis (cells of the skin). In approximately 90% of cases, the condition is associated with an in situ or invasive breast carcinoma.

Symptoms:

  • Chronic eczematous lesion involving the nipple (most common presentation) [highlighted in the image]
  • Nipple erythema or ulceration
  • Nipple inversion
  • Nipple discharge
  • Pruritus
  • As many as 40% of women have a palpable mass on presentation, and some may present with enlarged axillary lymph nodes.
Ulceration of the nipple

Ulceration of the nipple

Imaging:

90% patients who present with an underlying breast lump along with Paget’s have abnormal findings on mammography but only 50% patients who present with Paegt’s without a breast lump show mammographic abnormalities. Magnetic resonance imaging (MRI) is increasingly being used, particularly in cases without a palpable mass. MRI is particularly useful to establish extent of disease in patients in which breast-conserving surgery is being contemplated.

Pathology: The hallmark of Paget’s is the presence of neoplastic cells within the epidermis that show abundant clear cytoplasm and tend to spread individually in between the native keratinocytes (Image). They tend to display prominent nucleoli and frequent mitoses. In addition, they commonly show intracytoplasmic mucin-filled vacuoles, which are stained with a periodic-acid-Schiff or mucicarmine stain.

Paget cells seen in the epidermis

Paget cells seen in the epidermis

Paget cells are usually positive for markers of breast epithelium differentiation like:

  • Cytokeratin 7
  • CAM 5.2
  • Low-molecular-weight cytokeratins (negative for high-molecular-weight cytokeratins)
  • Vast majority of cases show strong overexpression of the HER2/neu proteinion of the gene
  • Positive for mucin
  • 18-20% of Paget’s cells express S100 protein but contrary to melanoma cells, HMB45 is consistently negative.

Toker cells are immunophenotypically similar to Paget cells, sharing expression of cytokeratin 7 and CAM 5.2, absence of high-molecular-weight cytokeratin expression, and negative S100- and HMB45-expression. They differ in the negative expression of mucin, HER2/neu, and epithelial membrane antigen. The similarities between Toker and Paget cells have suggested that the former may represent the cell that undergoes malignant transformation in the initial phases of PD. Toker cells can be present in normal patients as well.

The most accepted explanation for the development of PD is that Paget cells result from the migration of cells from the underlying adenocarcinoma through the epidermis, the so-called epidermotropic theory. This theory is supported by the existence of an underlying carcinoma in about 90% of cases of PD, which usually shares phenotypic similarities with Paget cells.

 

Differential Diagnosis:

  • Eczema – tends to be bilateral and responds to topical steroids
  • Nipple adenoma

Diagnosis: 

  • Wedge biopsy
  • Punch biopsy

Management: Management of PD depends on the underlying breast lump. Traditionally, the surgical procedure of choice has been a mastectomy but there are numerous studies which show that breast conservation surgery can be carried out in patients with PD. Prognosis in PD is largely determined by the underlying breast tumor.

 

Source: 1. Bland & Copeland – The Breast. 4th Edition 2. Michael Sabel – Essentials of Breast Surgery

39 fibroadenomas removed using just two incisions!!

Yesterday, we performed a marathon fibroadenoma surgery, where we removed 39 fibroadenomas from both the breasts (19 from the right breast and 20 from the left) just by making one incision in each breast. We used a crescent incision in both the breasts and comfortably removed fibroadenomas measuring as big as 5-6 cms through that incision. The entire procedure lasted 2 hours and the patient was discharged the same day.

Although the smaller fibroadenomas could have been left behind (because they are not malignant) but the patient was very apprehensive about them and wanted all of them removed. The importance of the single incision (periareolar crescent) is that it makes the end cosmetic result quite good. I am sharing some intra-operative pictures in this post. Will update the post-operative and follow-up pictures soon.

Marking of the crescent incision.

Marking of the crescent incision.

 Fibroadenomas marked along with the incision. Smaller lesions were not marked.


Fibroadenomas marked along with the incision. Smaller lesions were not marked.

 

6x7 cm fibroadenoma removed through the incision

6×7 cm fibroadenoma removed through the incision

 

5x5 cm lesion removed through the left breast

5×5 cm lesion removed through the left breast

 

Starting the closure. Will share the post-op and follow up pictures soon

Starting the closure. Will share the post-op and follow up pictures soon

Palbociclib – A novel drug for metastatic breast cancer

The issue which has been lingering on in the Breast cancer community in the last few days has been the significant clinical benefit shown by Palbociclib in patients with advanced breast cancer in a phase 2 clinical trial. The results of the PALOMA-1 trial were discussed in a recently concluded meeting of the American Association for Cancer Research.

Palbociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 and it inhibits cell proliferation and cellular DNA synthesis by preventing cell-cycle progression from G1 to S phase. In simple terms, it prevents cell division.

In the trial, patients were randomly assigned to the combination of daily palbociclib 125 mg for 3 weeks followed by 1 week off plus continuous daily letrozole 2.5 mg, or to daily letrozole. Treatment continued until disease progression, unacceptable toxicity, or withdrawal from the study, and tumors were assessed every 2 months.

Patients with hormone receptor positive metastatic breast cancer, demonstrated a significantly better progression-free survival as compared to patients receiving only hormonal treatment. The progression-free survival was significantly better with palbociclib plus letrozole than with letrozole alone (20.2 vs 10.2 months; hazard ratio [HR], 0.488; BP = .0004).

Although there was a positive trend seen in the overall survival analysis as well but the survival data was not mature enough to be shared currently.

The drug was well tolerated and the most common adverse effects were neutropenia, leukopenia, fatigue, and anemia.

Although some people are claiming that this drug will turn out to be the next standard of care in metastatic breast cancer, others share a more guarded opinion. There have been quite a few drugs which have shown promise in phase 2 trials but have not performed well in subsequent phase three trials.

The phase 3 trial (PALOMA-2) is currently underway and only time will tell whether Palbociclib is really beneficial or not.

The other issues which Indian patients & doctors need to consider are:

1. Cost & availability of the drug in India; cost/ benefit ratio

2. Overall survival benefit