Paget’s disease with intraductal spread

Fig. 4. Paget’s cells spread into the lactiferous ducts in the deeper portions of the breast(hematoxylin and eosin stain; original magnification × 40). Bar = 160 µm.

fered formalin and embedded in paraffin wax. The
histlogical sections were stained with hematoxylin
and eosin, periodic acid-Schiff (PAS) and elastic
van Gieson (EVG) methods to distinguish lactiferous ducts from blood vessels.
Histologically, a large number of Paget’s cellswith abundant clear cytoplasms and large nucleoli
were present in the nipple epidermis (Fig. 2). PAS
staining showed granular bodies in the cytoplasmsof a few Paget’s cells. The cells were distributed in
proximal lactiferous ducts underlying the nipple(Fig. 3). Furthermore, extensive intraductal spreadsof Paget’s cells were found at several branches ofthe lactiferous ducts in the deeper breast (Fig. 4).
There was no invasive carcinoma. All the axillary
lymph nodes showed no metastatic tumor.
She remained free from any signs of relapse
for 2 years after the operation. The current form
implies there was a relapse after 2 years.

Discussion
Mammary Paget’s disease occupies 2% of all breast
cancers (Lloyd et al., 2000). The disease does not
grow from the nipple epidermis but from the underlying breast carcinoma, which develops secondarily
because of spreads due to the extension or migration of malignant cells from underlying breast carcinoma.
Intraductal spread of Paget’s cells with theflow, either continuous or discontinuous, has beenreported (Rosai, 1996). Mai and coworkers (May,1999; Mai et al., 1999) reported the discontinuous
pattern of intraductal tumor spread identified in thefoci of carcinoma in deep breast tissues. They suggested 3 possible mechanisms of this discontinuous
pattern of tumor spread: i) tumor cell migration, ii)
tumor implantation and iii) multifocal carcinogenesis that most likely affects progenitors of ductal
cells in the duct.
In the past, radical or modified mastectomy
was the mainstream choice for the surgical treat-47

K. Araki et al.

2 Japanese Breast Cancer Society, The. General rules
for clinical and pathological recording of breast cancer. 14th ed. Tokyo: 2000. p. 12–14.
3 Kothari AS, Beechey-Newman N, Hamed H,Fentiman IS, D’Arrigo Bandy AM, Ryder K. Paget
disease of the nipple: a multifocal manifestation ofhigher-risk disease. Cancer 2002;95:1–7.
4 LIoyd J, Flanagan AM. Mammary and extramammary Paget’s disease. J Clin Pathol 2000;53:742–749.
5 Mai KT. Morphological evidence for field effect asa mechanism for tumor spread in mammary Paget’s
disease. Histopathology 1999;35:567–576.
6 Mai KT, Yazdi M, Perkins DG. Mammary Paget’s
disease: evidence of diverse origin of the diseasewith a subgroup of Paget’s disease developing fromthe superficial portion of lactiferous duct and a discontinuous pattern of tumor spread. Pathol Int 1999;
49:956–961.
7 Pierce LJ, Haffty BG, Solin LJ, McCormick B,Vicini FA, Wazer DE, et al. The conservative management of Paget’s disease of the breast with radiotherapy. Cancer 1997;80:1065–1072.
8 Rosai J. Ackerman’s surgical pathology. 8th ed. St.
Louis: Mosby; 1996.

ment of mammary Paget’s disease. Recently,breast conservative therapy (excision of the nipple/areola complex) has been performed for mostpatients (Pierce et al., 1997). However, there are norandomized trials that provide a specific basis to theselection of an ideal treatment for this condition.
Preoperative procedures including ultrasonography, mammography and MRI are uncertain in diagnosing underlying tumors or intraductal spread of
Paget’s cells which might be overlooked even after
careful sectioning of the resected breast (Dixon etal., 1991; Kothari et al., 2002). Kothari et al. (2002)
reported that cone excision of the nipple resulted inincomplete excision in approximately 75% of mammary Paget’s disease patients. Mammary Paget’sdisease with extensive intraductal spread seems tobe a nonsuitable candidate for breast conservative
therapy. Therefore, breast conservative therapy for
mammary Paget’s disease should be treated as aconsideration for possible intraductal spread.

References
Received April 14, 2003; accepted May 26, 2003

1 Dixon AR, Galea MH, Ellis IO, Elston CW, Blaweg
RW. Paget disease of the nipple. Br J Surg 1991;78:722–723.

Corresponding author: Kunio Araki, MD48