Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Sebaceous Carcinoma of the Breast

  • Zsuzsanna VargaEmail author
  • Linda Moskovszky
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4761-1

Synonyms

Definition

Infiltrative growing carcinomas of the breast exhibiting sebaceous cell differentiation in at least 50% of the invasive tumor cells. In order to classify a breast tumor as such, an extramammary tumor especially carcinomas arising from the skin adnexal structures must be excluded clinically or immunohistochemically (Acosta et al. 2018; Maia and Amendoeira 2018; Martin et al. 2017).

Clinical Features

  • Incidence

    This type of breast tumor is exceedingly rare, accounting less than 1% of all breast carcinomas. Until now, 18 cases were reported in the literature, most of them fulfilling the complete criteria for a sebaceous breast carcinoma, and some were described as invasive breast cancer with sebaceous differentiation. Difficulties in recognizing this entity requires precise knowledge and recognition of the specialized additional cell type within the infiltrating tumor cells (Acosta et al. 2018; Maia and Amendoeira 2018; Sakai et al. 2018; Martin et al. 2017; Yamamoto et al. 2017; Švajdler et al. 2015; Wachter et al. 2014; Carlucci et al. 2012; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Propeck et al. 2000; Tavassoli and Norris 1986; van Bogaert and Maldague 1977).

  • Age

    Based on the available literature data, sebaceous breast carcinoma presents a wide range of age, between 25 and 84 years at initial diagnosis with a mean age of 59.16 years, with most patients being postmenopausal (Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000).

  • Sex

    Almost exclusively female patients were reported in the literature so far. In one earlier paper, a male patient with a large sebaceous carcinoma in the breast area was described; however this tumor as described in this paper represents a skin adnexal tumor rather as a primary breast carcinoma (Acosta et al. 2018; Maia and Amendoeira 2018; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Ascari-Raccagni et al. 2011).

  • Site

    There is no site-specific predilection for this tumor type. Both breasts are equally involved (Acosta et al. 2018; Maia and Amendoeira 2018; Martin et al. 2017).

  • Treatment

    Depending on the pathological stage and grade of the tumor under consideration of the presence or absence of the predictive markers as estrogen and progesterone receptors and Her2 status, the current recommendation to surgery and chemo- and radiotherapy is analogous to breast cancer independently from the subtype (Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000).

  • Outcome

    Follow-up is available in most reported cases. Based on this information and on the limited number of cases, sebaceous breast carcinoma tends to present with metastatic disease (as skin, eyelid, and disseminated bone metastases) in about a third of the cases (Maia and Amendoeira 2018; Martin et al. 2017; Švajdler et al. 2015; Carlucci et al. 2012; Müller et al. 2011; Varga et al. 2000). Death due to metastatic disease has been described in four patients. Seven of eighteen patients presented with positive nodal status at initial diagnosis (Maia and Amendoeira 2018; Švajdler et al. 2015; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006). Tumor stage is variable, and reported tumor sizes vary between 12 and 120 mm (mean size 35.9 mm) (Acosta et al. 2018; Maia and Amendoeira 2018; Sakai et al. 2018; Martin et al. 2017; Yamamoto et al. 2017; Švajdler et al. 2015; Wachter et al. 2014; Carlucci et al. 2012; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Propeck et al. 2000; Tavassoli and Norris 1986; van Bogaert and Maldague 1977).

Macroscopy

Sebaceous carcinomas usually present with a palpable mass in the breast, as noted above in a third of the cases with nodular lesions within the metastatic site. It has been reported that sebaceous carcinomas exhibit a yellowish whitish cut surface and a multilobulated tumor contour with sharp borders (Acosta et al. 2018; Maia and Amendoeira 2018; Sakai et al. 2018; Martin et al. 2017; Yamamoto et al. 2017; Švajdler et al. 2015; Wachter et al. 2014; Carlucci et al. 2012; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Propeck et al. 2000; Tavassoli and Norris 1986; van Bogaert and Maldague 1977).

Microscopy

Tumor with sebaceous differentiation often has a background of an infiltrating carcinoma of ductal type, which exhibits sharp borders toward the tumor periphery. According to the 2012 WHO classification on breast tumors, it was defined that at least 50% of the whole tumor mass containing large tumor cells with coarse or bubbly vacuolated tumor cells resembling sebaceous cells of the skin appendix need to be present for this diagnosis (Acosta et al. 2018; Maia and Amendoeira 2018). These cells may show variable stain with fat stains (as Sudan black or Oil Red O) and usually remain negative at the PAS stain. Intermingled among the sebaceous cells, there are usually another cell components found (as of spindle, squamous, or ovoid morphology). A few studies conducted electron microscopy showing non-membrane-bound empty vacuoles corresponding to lipid droplets of different sizes (Sakai et al. 2018; Varga et al., 2000). Grading in the reported cases is G2 or G3; until now there is no case reported with good differentiated (G1) morphology (Acosta et al. 2018; Maia and Amendoeira 2018; Sakai et al. 2018; Martin et al. 2017; Yamamoto et al. 2017; Švajdler et al. 2015; Wachter et al. 2014; Carlucci et al. 2012; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Propeck et al. 2000).

Immunophenotype

Most studies confirm that sebaceous cells are usually strongly positive for keratins, EMA, and adipophilin. Recent cases reports could additionally show GATA 3 and AR positivity in the sebaceous cells. Three cases analyzed mismatch repair proteins showing preserved epitopes without any selective loss. Interestingly, GCDFP-15 and S100 are consequently negative in the sebaceous cells. One case was shown to exhibit neuroendocrine differentiation by synaptophysin positivity (Acosta et al. 2018; Maia and Amendoeira 2018; Sakai et al. 2018; Martin et al. 2017; Yamamoto et al. 2017; Švajdler et al. 2015; Wachter et al. 2014; Carlucci et al. 2012; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Propeck et al. 2000).

Predictive markers were tested in a large subset of reported cases; most cases are hormone receptor positive and HER2 negative, and three cases were triple negative and two cases HER2 positive (Acosta et al. 2018; Maia and Amendoeira 2018; Sakai et al. 2018; Martin et al. 2017; Yamamoto et al. 2017; Švajdler et al. 2015; Wachter et al. 2014; Carlucci et al. 2012; Müller et al. 2011; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000; Propeck et al. 2000).

Molecular Features

No established molecular features are known currently. One reported case had a BRCA2 germ line mutation; one additional case occurred within the scope of the Muir-Torre syndrome, an autosomal dominant inherited disease with variable penetrance and exhibiting at least one sebaceous gland tumor and one additional malignancy (Acosta et al. 2018; Propeck et al. 2000) (Figs. 1, 2, and 3).
Fig. 1

Low-power appearance of a sebaceous carcinoma. The tumor exhibits several large cells with pale cytoplasm with coarse and bubbly vacuolated tumor cells (HE stain, low magnification)

Fig. 2

High-power appearance of a sebaceous carcinoma, large tumor cells with pale, coarse, and bubbly vacuolated cytoplasm (HE stain, high magnification)

Fig. 3

High-power appearance of a sebaceous carcinoma, large tumor cells with pale, coarse, and bubbly vacuolated cytoplasm (HE stain, high magnification)

Differential Diagnosis

The main differential diagnosis encompasses a primary skin adnexal tumor with sebaceous morphology. The presence of in situ components (DCIS, LN) in the tumor and the lack of connection to the skin of the breast are useful features, which favor a primary sebaceous breast carcinoma. Additionally, the use of immunohistochemistry (especially a positive AR reaction and the negativity for S100 and GCDFP-15 can support breast origin) (Table 1).
Table 1

Summary of reported cases

Publication

Number of cases

Age (years)

Tumor size (in mm)

Nodal status

Histological grade

ER/PR

HER2

IHC positive

IHC negative

other

Follow-up

Acosta (2018)

1

51

20 mm

pNO

2

+/+

Neg

AR

MMRP

 

BRCA2+

NA

Maia (2018)

2(1)

65

70 mm

pN1(1/2)

NA

Neg/neg

Neg

AR

MMRP

GATA 3

  

Died 9 months after initial diagnosis

Maia (2018)

2

71

37 mm

pNO

NA

+/neg

Neg

GATA3

MMRP

AR

 

100 months uneventful

Sakai 2018

1

74

23 mm

NA

G2

+/+

Neg

AR

GATA3

Adipophylin

Mammoglobin

 

NA

Martin 2017

1

59

NA

NA

G2

+/+

Neg

EMA

CK7

CAM2

  

Eyelid metastasis 2 years after initial diagnosis

Yamamoto 2017

1

80

35 mm

NA

NA

Neg/neg

Neg

EMA

BerEp4

Adipophylin

AR

 

NA

Svajdler 2015

4(1)

65

16 mm

pN1(1/1)

G3

+/+

Neg

EMA

S100

 

27 months uneventful

Svajdler 2015

(2)

61

17 mm

pN1(2/5)

G3

Neg/neg

Neg

EMA

  

Died after 28 months

Svajdler 2015

3

66

30 mm

pN1(1/10)

G2

+/+

Neg

 

GCDFP-15

EMA

S100

 

70 months uneventful

Svajdler 2015

4

25

NA

NA

G3

+/+

Neg

EMA

S100

GCDFP-15

 

75 months uneventful

Wachter 2014

1

53

12 mm

pNO

G3

+/+

Neg

GATA3

MMRP

  

NA

Carlucci 2012

1

84

120 mm

NA

NA

Neg/neg

IHC score 3+

EMA

GCDFP-15

S100

AR

 

Metastases 10 years after initial diagnosis

Müller 2011

1

61

NA

pN3(18/19)

G2

+/+

Neg

EMA

CEA Adipophylin

 

Skin metastases 5 years after initial diagnosis

Muakami 2009

1

50

24 mm

pN1

NA

Neg/neg

IHC score 3+

AR

EMA

Adipophylin

GCDFP-15 S100

 

NA

Hisaoka 2006

1

63

20 mm

pN1(1/9)

NA

+/+

Neg

EMA

Synaptophysin

Lipid stains

GCDFP-15

Vimentin

AR

P63

SMA

S100

 

NA

Varga 2000

1

45

25 mm

NA

G2

+/+

Neg

EMA +

S100

Vimentin

CEA

 

Skin and disseminated bone métastases 8 years after initial diagnosis

Propeck 1999

1

46

15 mm

NA

NA

NA

NA

  

Muir-Torre syndrome

6 months uneventful

Tawassoli 1986

1

46

75 mm

NA

NA

NA

NA

   

NA

Van Bogaert 1977

3

NA

NA

NA

NA

NA

NA

   

NA

Abbreviations: ER estrogen receptors, PR progesterone receptors, HER2 epidermal growth factor 2 receptors, AR androgen receptors, EMA epithelial membrane antigen, MMRP mismatch repair protein, IHC immunohistochemistry, BRCA breast cancer, CEA carcinoembryonic antigen, GCDFP-15 gross cystic disease fluid protein 15, SMA smooth muscle actin, NA not available

Further differential diagnosis is the different types of breast cancers; especially the spectrum of primary clear cell carcinomas needs to be excluded. Apocrine breast carcinoma, lipid-rich breast carcinoma, and glycogen-rich breast carcinoma are in the differential diagnosis. Morphology (large lipid droplets, water-clear cytoplasm, or eosinophilic cytoplasm) and positive special stains (granular PAS stain and large fatty droplets with Sudan Black and Oil Red O) favor another type of clear cell breast carcinoma. Expansive growth in a lobular pattern and the presence of a dual neoplastic cell population of larger sebaceous cells and smaller cells of different type are suggestive of a sebaceous carcinoma (Acosta et al. 2018; Maia and Amendoeira 2018; Murakami et al. 2009; Hisaoka et al. 2006; Varga et al. 2000).

References

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Institute of Pathology and Molecular PathologyUniversity Hospital ZurichZurichSwitzerland