Virchows Archiv

, Volume 449, Issue 4, pp 484–488

Sebaceous carcinoma of the breast: case report and review of the literature

Authors

    • Department of Pathology and Oncology, School of MedicineUniversity of Occupational and Environmental Health
  • Yuji Takamatsu
    • Department of SurgeryKyushu Rosai Hospital
  • Yutaka Hirano
    • Department of SurgeryKyushu Rosai Hospital
  • Hironobu Maeda
    • Department of RadiologyKyushu Rosai Hospital
  • Tetsuo Hamada
    • Department of Surgical PathologyKyushu Rosai Hospital
Case Report

DOI: 10.1007/s00428-006-0264-8

Cite this article as:
Hisaoka, M., Takamatsu, Y., Hirano, Y. et al. Virchows Arch (2006) 449: 484. doi:10.1007/s00428-006-0264-8

Abstract

Sebaceous differentiation has been described in only limited examples of benign and malignant epithelial lesions of the breast. We report a rare case of mammary sebaceous carcinoma to further delineate its morphologic features. Microscopically, the tumor, arising in the right mammary gland of a 63-year-old woman, was composed of well-defined solid sheets or lobules of atypical epithelial cells including many large pale or clear cells with often scalloped nuclei and coarsely vacuolated cytoplasm, in which abundant lipid droplets were identified with oil-red-O staining. Immunohistochemical expressions of cytokeratin, epithelial membrane antigen, and receptors of estrogen and progesterone were detected, whereas GCDFP-15, S-100 protein, vimentin, α-smooth muscle actin, p63, androgen receptor, and the HER2/neu protein were not expressed. Besides, a subset of the tumor cells co-expressed synaptophysin, neurofilament, and PGP9.5, suggesting neuroendocrine differentiation that is a hitherto undescribed phenomenon in the mammary tumors with sebaceous features. This case would expand the morphologic diversity of carcinoma of the breast.

Keywords

BreastCarcinomaSebaceousNeuroendocrine

Introduction

Despite some morphologic and developmental links between the mammary gland and skin appendages, sebaceous differentiation is only rarely encountered in benign or malignant epithelial lesions of the mammary gland. Although mammary sebaceous carcinoma was first described as a variant of lipid-secreting carcinoma by van Bogaert and Maldgue in 1977 [15], the recent WHO classification for breast tumors has recognized it as a distinct subtype of invasive breast carcinomas [13]. The number of well-documented cases is still limited [68, 12, 16], and we feel that recognition of such a peculiar type of carcinoma is generally poor in this anatomical location. In this report, we describe clinicopathologic features of a case of sebaceous carcinoma of the breast to broaden our knowledge of a morphologic variety of mammary carcinoma.

Case report

A 63-year-old woman was noticed to have a lump in the right breast during a medical checkup. An ultrasonographic examination revealed a hypoechoic mass with an irregular margin in the upper central aspect of the breast. Mammographically, an opaque mass measuring about 2 cm in size without calcification was identified in the right breast (Fig. 1). Fine needle aspiration cytology strongly suggested invasive ductal carcinoma. Laboratory data on admission were not remarkable, and the serum levels of CEA and CA15-3 were within normal limits. A muscle-preserving radical mastectomy with a regional lymph node dissection was performed.
https://static-content.springer.com/image/art%3A10.1007%2Fs00428-006-0264-8/MediaObjects/428_2006_264_Fig1_HTML.jpg
Fig. 1

Craniocaudal mammogram of the right breast shows a well-circumscribed opaque mass lesion

Materials and methods

The specimen was routinely processed for microscopic, histochemical, and immunohistochemical examinations. Briefly, histological slides of the formalin-fixed, paraffin-embedded tumor tissue were deparaffinized and stained with hematoxylin-eosin, periodic acid-Schiff (PAS), and mucicarmine. The Grimelius argyrophil technique and immunohistochemistry using the following primary antibodies and a labeled polymeric secondary antibody (EnVision system; DAKO Cytomation, Kyoto, Japan) with or without appropriate antigen retrieval were also performed: anti-cytokeratin (AE1/AE3, 1:50, DAKO Cytomation), anti-epithelial membrane antigen (E29, 1:100, DAKO Cytomation), anti-vimentin (V9, 1:30, DAKO Cytomation), anti-α-smooth muscle actin (1A4, 1:150, DAKO Cytomation), anti-S-100 protein (polyclonal, 1:200, DAKO Cytomation), anti-p63 (4A4, 1:30, DAKO Cytomation), anti-synaptophysin (SY38, 1:100, DAKO Cytomation), anti-neurofilament (DA2/FNP7/RMdO20.11, 1:50, Zymed, South San Francisco, CA, USA), anti-chromogranin A (CAK-A3, 1:100, DAKO Cytomation), anti-PGP9.5 (13C4/31A3, 1:400, UltraClone, Isle of Wight, UK), anti-carcinoembryonic antigen (II-7, 1:200, DAKO Cytomation), anti-GCDFP-15 (23A3, 1:50, Novocastra, Newcastle-upon-Tyne, UK), anti-estrogen receptor (1D5, 1:50, DAKO Cytomation), anti-progesterone receptor (1A6, 1:50, Immunotech, Marseille, France), anti-androgen receptor (AR441, 1:50, DAKO Cytomation), anti-HER2/neu (polyclonal, prediluted, DAKO Cytomation), and anti-Ki-67 (MIB-1, 1:50, DAKO Cytomation). Frozen sections were prepared from the formalin-fixed wet tumor tissue and stained with oil-red-O.

Results

Macroscopically, the tumor, measuring 2×1.8×1.5 cm in diameter, was well-demarcated and had the white or grayish cut surface with a firm consistency. The lesion had no connection to the overlying skin or the nipple.

Histologically, the tumor was made up of solid sheets or lobules of a proliferation of polygonal atypical epithelial cells possessing round hyperchromatic or vesicular nuclei, small nucleoli, and eosinophilic fine granular cytoplasm (Fig. 2a). The lobules frequently contained or were partially replaced by large epithelial cells with ample clear, multivacuolated cytoplasm and irregular or often scalloped nuclei (Fig. 2b). An overt ductal structure or squamous or apocrine differentiation was absent. Mitotic figures were readily encountered (more than 10/10 HPF). Although mild stromal invasion of the tumor cells was focally noted, the lesion was almost confined to the mammary gland without intraductal components or necrotic areas. Many tumor cells, particularly multivacuolated cells, had abundant oil-red-O-positive lipid droplets in the cytoplasm (Fig. 2c), whereas they were negatively stained with PAS or mucicarmine staining. Approximately two thirds of the tumor consisted of vacuolated cells with lipid droplets. The Grimelius staining failed to demonstrate darkly granulated, argyrophilic tumor cells. A metastatic deposit was identified in one of the nine axillary lymph nodes examined microscopically.
https://static-content.springer.com/image/art%3A10.1007%2Fs00428-006-0264-8/MediaObjects/428_2006_264_Fig2_HTML.jpg
Fig. 2

a In a low-power view, the tumor shows a well-delineated, solid sheet-like or lobular configuration (hematoxyline and eosin, ×20). b The lobules are made up predominantly of large clear or multivacuolated cells admixed with minor non-vacuolated epithelial cells (hematoxyline and eosin, ×400). c Abundant intracytoplasmic neutral lipids are demonstrated in many tumor cells (oil-red-O staining, ×200). d Diffuse membranous and bubbly cytoplasmic expression of epithelial membrane antigen is seen (immunohistochemistry, ×200). e Some of the tumor cells, mostly of a non-vacuolated phenotype, are positive for synaptophysin (immunohistochemistry, ×400). f Nuclear immunoreactivity to estrogen receptor is seen in the vast majority of tumor cells (immunohistochemistry, ×100)

Immunohistochemically, the tumor cells including large multivacuolated cells were positive for cytokeratin and epithelial membrane antigen (Fig. 2d). Synaptophysin, neurofilament, and PGP9.5 were co-expressed in a subset of the tumor cells mostly lacking vacuolated cytoplasm (Fig. 2e). In addition, the vast majority of tumor cells were positive for the receptors of estrogen and progesterone (Fig. 2f). MIB-1 labeling index was approximately 38%. Other immunohistochemical markers examined were essentially negative.

Discussion

Based on the clinicopathologic findings, the current tumor is analogous to those previously reported as mammary carcinoma with sebaceous differentiation or sebaceous carcinoma of the breast [6, 7, 12, 15, 16]. As the initial identification as a variant of lipid-secreting carcinoma [15], sebaceous differentiation has been rarely described in variable morphologic types of mammary carcinoma, such as infiltrating (or invasive) ductal carcinoma, adenoid cystic carcinoma, and a carcinoma with ductal, myoepithelial and squamous elements [6, 7, 12, 14, 16]. In addition, a single case of sebaceous gland metaplasia in intraductal papilloma has been recently described [3]. Another case, also recorded as sebaceous carcinoma of the breast with Muir–Torre syndrome, does not appear to represent a mammary carcinoma, but indeed a cutaneous sebaceous carcinoma because of its dermal localization [8].

The number of previously documented cases with such a peculiar mammary carcinoma with sebaceous differentiation is still very small, and their detailed clinicopathologic information is available in only four examples (Table 1) [6, 7, 12, 16]. According to the reported cases including ours, four of the five patients were women with ages ranging from 45 to 74 years. The lesions were frequently recognized as palpable masses more often in the right breast than in the left, and the size of the tumors ranged from 2.5 to 7.5 cm in diameter. The patients were treated with a simple or modified radical mastectomy and a regional lymph node dissection. The cases except for ours had no lymph node metastasis at surgery. One case, however, developed distant metastases involving the skin and bones and underwent chemotherapy [16], suggesting that a mammary sebaceous carcinoma is a potentially more aggressive phenotype than presumed previously [12]. Thus, a careful follow-up survey is mandatory in any case with mammary sebaceous carcinoma.
Table 1

Summarized clinicopathologic features of reported sebaceous carcinomas of the breast

Author (year/ref. no.)

Age/ gender

Side

Size

Lymph node metastasis

Histologic feature

Outcome (follow-up period)

Prescott et al. (1992/[7])

74/F

Right

5×4.5×4 cm

Invasive ductal carcinoma with squamous and myoepithelial components

NED (6 m)

Mazzella et al. (1995/[6])

55/M

Left

5×4×4 cm

Infiltrating ductal carcinoma with intraductal components

NED (10 m)

Tavassoli (1999/[12])

46/F

Right

7.5 cm

Carcinoma with squamous morules

No information

Varga et al. (2000/[16])

45/F

Right

2.5 cm

Invasive ductal carcinoma with intraductal components

Skin and bone metastases (10 years)

Hisaoka et al. (current case)

71/F

Right

2.5×2×1.5 cm+

+ (1 of 9 nodes)

Invasive carcinoma

Recent case

Microscopically, the carcinoma is essentially characterized by a lobular or nested growth pattern of tumor cells variably admixed with those displaying sebaceous differentiation [12, 13]. In contrast to the previously reported carcinomas with sebaceous differentiation [6, 7, 12, 14], our case showed distinct, well-delineated solid and lobular structures without other histologic elements such as squamous and myoepithelial cells or in situ (or intraductal) components. In addition to such a histologic appearance [9], immunohistochemical expressions of cytokeratin and epithelial membrane antigen are conformed to the features of sebaceous carcinoma arising in other anatomical locations such as the skin and the ocular adnexa [1, 11, 16]. However, the status of sex steroid hormone receptors in the mammary lesions appears somewhat different; mammary sebaceous carcinoma tends to express progesterone and/or estrogen receptors, but not that of androgen [6, 12, 16], whereas androgen has been suggested to be a dominant sex hormone influencing a cutaneous counterpart [2, 4]. In the three cases analyzed, a percentage of Ki-67-positive tumor cells was relatively high and ranged from 16 to 38% [12, 16].

The extent of the sebaceous morphology differed among the reported cases [6, 7, 12, 14, 16], and the criteria of mammary sebaceous carcinoma seem ambiguous at this point [12, 13]. Because a non-sebaceous component may display diverse morphologic features, the appellation of sebaceous carcinoma might be suitable for lesions with a prominent sebaceous appearance (e.g., at least half of tumor cells).

It is notable that the current case was immunohistochemically positive for some neuroendocrine markers such as synaptophysin and neurofilament, even if the positivity was confined to cells that were non-vacuolated and non-argyrophilic. The neuroendocrine phenotype is a hitherto undescribed feature in sebaceous carcinoma of the breast or at other sites, although a carcinoid-like trabecular or ribbon-like growth pattern of cells may be seen in subsets of extraocular sebaceous carcinoma and sebaceoma [5]. This phenomenon might represent aberrant or divergent differentiation that may be also encountered in non-sebaceous mammary carcinomas such as mucinous carcinoma and non-mucinous solid carcinoma [10, 13].

Because of the lack of overexpression of the HER2/neu protein in the current case or in the case examined by Varga et al. [16], the protein cannot yet be a molecular therapeutic target for this type of mammary carcinoma.

Copyright information

© Springer-Verlag 2006