Sebaceous carcinoma of the breast: case report and review of the literature
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- Hisaoka, M., Takamatsu, Y., Hirano, Y. et al. Virchows Arch (2006) 449: 484. doi:10.1007/s00428-006-0264-8
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.
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 , the recent WHO classification for breast tumors has recognized it as a distinct subtype of invasive breast carcinomas . The number of well-documented cases is still limited [6–8, 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.
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.
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.
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.
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 , 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 . 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 .
Summarized clinicopathologic features of reported sebaceous carcinomas of the breast
Author (year/ref. no.)
Lymph node metastasis
Outcome (follow-up period)
Prescott et al. (1992/)
Invasive ductal carcinoma with squamous and myoepithelial components
NED (6 m)
Mazzella et al. (1995/)
Infiltrating ductal carcinoma with intraductal components
NED (10 m)
Carcinoma with squamous morules
Varga et al. (2000/)
Invasive ductal carcinoma with intraductal components
Skin and bone metastases (10 years)
Hisaoka et al. (current case)
+ (1 of 9 nodes)
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 , 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 . 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. , the protein cannot yet be a molecular therapeutic target for this type of mammary carcinoma.