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J Zhejiang Univ Sci B. 2008 February; 9(2): 109–113.
PMCID: PMC2225492

Primary leiomyosarcoma of the nipple-areola complex: Report of a case and review of literature


Primary leiomyosarcoma of the nipple-areola complex is extremely rare. Less than ten such cases have been reported in English literature so far. Herein we describe a 52-year-old female presenting with a 1.5 cm×1.1 cm×0.7 cm nodular lesion over her left nipple, and leiomyosarcoma was proved by pathological examination of the excised specimen. Positron emitted tomogram (PET) revealed no abnormal signal other than the primary site. Microscopically, this poorly circumscribed tumor was composed of interlacing bundles of smooth muscle cells with bizarre and pleomorphic nuclei, as well as prominent nucleoli. Its mitotic count was up to 7 mitoses per 10 high power fields (HPF). Immunohistochemical study of tumor cells revealed positive stain for α-smooth muscle actin and vimentin; and negative for cytokeratin, CD34 and S-100. Left simple mastectomy was undertaken and no residual mass lesion was noted on the resected specimen. Related literatures about the diagnosis and treatment for breast leiomyosarcoma will be presented here.

Keywords: Breast, Leiomyosarcoma, Mastectomy


Sarcomas of the breast account for less than 0.1% of all malignant tumors of the breast. Leiomyosarcomas belong to a less common subgroup (5% to 10%) of sarcomas of the breast (Adem et al., 2004; Hussien et al., 2001; Munitiz et al., 2004). There were only 27 cases being reported in English literature (Abd El All, 2006; Gupta, 2007; Jayaram et al., 2005; Munitiz et al., 2004; Vu et al., 2006). Leiomyosarcoma of the nipple-areola complex is even rarer. Herein a patient whose nipple nodular lesion was confirmed as leiomyosarcoma will be presented, and as well its diagnosis and treatment in previous literature will be discussed.


A 52 year-old female patient has been noted with a slowly growing lump over the left nipple area since three months ago. Breast ultrasound revealed a lobulated lesion 1.5 cm in diameter in the 2 o’clock direction of the periareolar region. Excisional biopsy was performed. Grossly, the excised tumor was firm in consistency, and showed a white tan whorling cut surface, with an irregular tumor border. Microscopically, it shows a poorly circumscribed nodular mass composed of interlacing fascicles of spindle cells located in the dermis, separated from the overlying epidermis by a thin Grenz zone (Figs.(Figs.11 and and2).2). The spindle cells exhibited cigar-shaped nuclei with blunt ends and eosinophilic cytoplasm. Moderate nuclear atypia was noted (Fig.(Fig.3).3). The mitotic count was 7 mitoses per 10 high power fields (HPF) in the most active area. Necrosis and hemorrhage are absent. Immunohistochemically, the tumor cells were diffusely and strongly positive for α-smooth muscle actin (Fig.(Fig.4)4) and vimentin, while negative for cytokeratin, CD34 and S-100 protein.

Fig. 1Fig. 1
Under low magnification, a nodular tumorous lesion is noted in the dermis of the nipple-areola complex. (a) H & E, ×40; (b) H & E, ×100
Fig. 2
Intermediate magnification shows densely cellular tumor composed of interlacing fascicles of spindle cells (H & E, ×200)
Fig. 3
The tumor cells are characterized by cigar-shaped nuclei with blunt ends, moderate nuclear atypia, moderate amount of eosinophilic cytoplasm. Mitotic figure can be seen (H & E, ×400)
Fig. 4
The immunohistochemical stains for α-smooth muscle actin are diffusely and strongly positive in the tumor cells (H & E, ×400)

She was admitted to our ward for further evaluation and treatment. A series of surveys including whole body positron-emitted tomography (PET) revealed no other malignant lesions. Therefore, she underwent left simple mastectomy without axillary lymph node dissection. The pathological report revealed no residual tumor in the resected specimen. The post-operative course was uneventful and she was discharged 4 d after operation and underwent regular follow-up at our clinic.


Leiomyosarcoma is not rare among soft tissue tumors. It can exist in any part of the body. However, its most common primary sites are the uterus, retroperitoneum, subcutaneous tissues and gastrointestinal tract (Cohen et al., 2007; Insabato et al., 2004; Szekely et al., 2001). Leiomyosarcomas of the breast are extremely rare, either primary (Abd El All, 2006; Adem et al., 2004; Gupta, 2007; Hussien et al., 2001; Jayaram et al., 2005; Munitiz et al., 2004; Vu et al., 2006) or metastatic from other sites (Lin et al., 2003; Taillibert et al., 2000). The smooth muscle component might be originated from the blood vessels and sarcomatous change is usually from leiomyoma or other spindle cell tumors (Szekely et al., 2001). Our presented case should be regarded as primary leiomyosarcoma of the breast since there was no other primary focus being found after a series of surveys including PET scan.

The nipple-areola complex is a circular area of skin that exhibits increased pigmentation and contains numerous sensory nerve endings. The tip of the nipple contains 15 to 20 orifices of lactiferous ducts which are surrounded by a stroma rich in circular and longitudinal smooth muscle bundles, collagen and elastic fibers. The periphery of the nipple-areola complex also contains pilosebaceous units and hair. Therefore, the initial pathologic differential diagnoses should include tumors of both mammary and cutaneous origins. The differential diagnoses and their histological and immunohistochemical features are listed in Table Table11.

Table 1
The initial differential diagnoses and their histological and immunohistochemical features

The strong and diffuse cytoplasmic expression of α-smooth muscle actin in this case, in additional to the typical cellular morphology, indicates smooth muscle origin of this tumor. According to the previously published cases of mammary, cutaneous and nipple-areola tumors, Ragsdale (1997)’s minimal criteria for cutaneous leiomyosarcomas, and the WHO classification of breast tumors (Tavassoli and Devilee, 2003), the presence of mitosis, nuclear atypia of various degree depending on differentiation, and hypercellularity are the most important criteria to designate a smooth muscle tumor as sarcoma. Tumor necrosis is not required for the diagnosis of malignancy.

Primary leiomyosarcoma of nipple-areola complex is rare. Table Table22 illustrates the cases reported in English literature (Lonsdale and Widdison, 1992; Markaki et al., 2003; Uğraş et al., 1997). Histologically, the nipple-areola complex is cutaneous tissue composed of epidermis and dermis. However, in contrast to skin of other sites, it also contains lactiferous ducts that connect to the mammary parenchyma. Table Table33 summarizes the clinical features, the treatment and outcome of primary leiomyosarcoma at the nipple-areola complex, the skin of other sites and the mammary parenchyma that reported in literature (Choy et al., 2006; Holst et al., 2002; Lonsdale and Widdison, 1992; Markaki et al., 2003; Uğraş et al., 1997). Tumors of these various sites had similar cytological and architectural characteristics. However, for primary cutaneous leiomyosarcoma, treatment recommendations include a wide local excision with a 3- to 5-cm margin, including subcutaneous tissue and fascia; while mastectomy, including simple and modified radical mastectomy, is the most common treatment for breast leiomyosarcoma. Due to few cases of primary leiomyosarcoma of nipple-areola complex reported in literature so far, there is no general agreement on whether to treat them as cutaneous or mammary tumors, and the need of adjuvant radio-chemotherapy. An analysis of more cases with a longer follow-up duration is necessary to develop an optimum mode of treatment for leiomyosarcomas at this specific site.

Table 2
Review of cases of primary leiomyosarcomas of the nipple-areola region
Table 3
Summary of the clinical features of primary leiomyosarcoma of various sites reported in literature


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Articles from Journal of Zhejiang University. Science. B are provided here courtesy of Zhejiang University Press