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

Primary leiomyosarcoma of the nipple-areola complex: Report of a case and review of literature 1 first-author 1 2 corresp ‡Corresponding Author ‡Corresponding Author †E-mail:luh572001@yahoo.com.tw †E-mail:luh572001@yahoo.com.tw luh572001@yahoo.com.tw 3 Department of Pathology, Taichung Hospital, Executive Yuan Department of Health, Taichung 401, Taiwan, China Department of Pathology, Taichung Hospital, Executive Yuan Department of Health, Taichung 401, Taiwan, China Department of Surgery, Chung-Shan Medical University and Hospital, Taichung 402, Taiwan, China Department of Surgery, Chung-Shan Medical University and Hospital, Taichung 402, Taiwan, China Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan, China Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan, China 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. Breast Leiomyosarcoma Mastectomy INTRODUCTION 1 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 2004 ; Hussien et al., 2001 2001 ; Munitiz et al., 2004 2004 ). There were only 27 cases being reported in English literature (Abd El All, 2006 2006 ; Gupta, 2007 2007 ; Jayaram et al., 2005 2005 ; Munitiz et al., 2004 2004 ; Vu et al., 2006 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. CASE REPORT 1 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. 1 1 and 2 2 ). The spindle cells exhibited cigar-shaped nuclei with blunt ends and eosinophilic cytoplasm. Moderate nuclear atypia was noted (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. 4 4 ) and vimentin, while negative for cytokeratin, CD34 and S-100 protein. 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. DISCUSSION 1 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 2007 ; Insabato et al., 2004 2004 ; Szekely et al., 2001 2001 ). Leiomyosarcomas of the breast are extremely rare, either primary (Abd El All, 2006 2006 ; Adem et al., 2004 2004 ; Gupta, 2007 2007 ; Hussien et al., 2001 2001 ; Jayaram et al., 2005 2005 ; Munitiz et al., 2004 2004 ; Vu et al., 2006 2006 ) or metastatic from other sites (Lin et al., 2003 2003 ; Taillibert et al., 2000 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 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 1 1 . Diagnoses Histological features Immunohistochemical features Leiomyoma Interlacing bundles of bland spindle cells with eosinophilic cytoplasm and blunt-ended, cigar-shaped, vesicular nuclei. Necrosis and mitosis are absent Diffusely and strongly positive for α-smooth muscle actin Dermatofibrosarcoma protuberans Fairly uniform spindle cells with elongated nuclei showing little pleomorphism and pale cytoplasm, arranged in storiform or “rush mat” pattern Usually diffusely positive for CD34, negative for S-100, desmin and α-smooth muscle actin Leiomyosarcoma Infiltrative tumor composed of interlacing bundles of cells with eosinophilic cytoplasm and blunt-ended, cigar-shaped, often vesicular nuclei. Varied cytological pleomorphism Diffusely positive for α-smooth muscle actin, desmin and h-caldesmon, negative for S-100 and CD34 Malignant peripheral nerve sheath tumors Alternating myxoid and cellular areas containing irregular interlacing bundles of spindle cells with scanty pale cytoplasm and wavy, hyperchromatic, variably pleomorphic nuclei. Myxoid change, hyaline nodule and perivascular whorling may be present 50% of these tumors are S-100 positive, negative for α-smooth muscle actin Malignant phyllodes tumor Epithelial slits and hypercellular stroma showing marked overgrowth of spindle cells. Prominent nuclear pleomorphism, mitotic count over 10 per 10 HPF and infiltrative tumor border Spindle cells are positive for vimentin and negative or only focally positive for α-smooth muscle actin. Positive staining for CD117 was reported Malignant fibrous histiocytoma Prominently pleomorphic cells arranged in storiform pattern. Bizarre multinucleated giant cells, and a mononuclear inflammatory cell infiltrate with foamy macrophages are often present. Most represent extension from deep soft tissue Negative for α-smooth muscle actin Sarcomatoid carcinoma A tumor composed of markedly atypical spindle and pleomorphic epithelial cells, necrosis, and numerous atypical mitotic figures Pleomorphic spindle cells are positive for cytokeratin, negative for α-smooth muscle actin Spindle cell malignant melanoma Groups of spindle cells exhibiting variable pigmentation and pleomorphism Stain positively for S-100 protein and HMB45, negative for α-smooth muscle actin 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 1997 )’s minimal criteria for cutaneous leiomyosarcomas, and the WHO classification of breast tumors (Tavassoli and Devilee, 2003 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 2 2 illustrates the cases reported in English literature (Lonsdale and Widdison, 1992 1992 ; Markaki et al., 2003 2003 ; Uğraş et al., 1997 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 3 3 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 2006 ; Holst et al., 2002 2002 ; Lonsdale and Widdison, 1992 1992 ; Markaki et al., 2003 2003 ; Uğraş et al., 1997 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. All the references are from Uğraş et al.( 1997 1997 ) NET: No evidence of tumor; r: Recurrence Reference * * Site Age/sex Size (cm) Mitoses Treatment Follow-up Crocker and Murad, 1969 Right, above the nipple 51/male 5 Common Radical mastectomy – Pardo-Mindan et al., 1974 Left, near the nipple 49/female 7 16/10 HPF Simple mastectomy Alive at 6 months, NET Hemandez, 1978 Left, involving nipple 53/male 4 15/10 HPF Modified radical mastectomy Alive at 1 year and 2 months, NET Yatsuka et al., 1984 Left, beneath the nipple 56/female 1.5 21/10 HPF Radical mastectomy Alive at 4 years and 7 months, NET 3 Nielsen, 1984 3 Right, edge of the areola 3 24/female 1.5 (1962) r 2/10 HPF Excision in 1960, 1962 3 Died 20 years later with metastases to brain, skin, thyroid gland, and kidneys 1 (1965) r 8/10 HPF Excision 2 (1966) r 14/10 HPF Excision and simple mastectomy 2 Lonsdale et al., 1992 2 Left, areola 2 60/female 2 10/10 HPF Excision with 1 cm safe margin 2 Alive at 3 months, post-mastectomy, NET 4.5 (18 months later) r Excision with subsequent mastectomy Uğraş et al., 1995 Right, under areola 47/female 2 3/10 HPF Total excision and subcutaneous simple mastectomy Alive at 1 year and 6 months, NET The present case described in this article Left, involving nipple-areola complex 52/female 1.5 7/10 HPF Excision (July, 2007) and subsequent total mastectomy and regional lymph node dissection Alive Clinical presentation Treatment Outcome Leiomyosarcoma of nipple-areola complex More common in female. Solitary slow-growing nodular lesion. May be asymptomatic. Possible origins: smooth muscle bundles surrounding lactiferous ducts, arrector pili muscle at periphery of areola Excision, simple, modified radical or radical mastectomy 2 of the 7 tumors listed above recurred, 1 metastasized Leiomyosarcoma of skin other than nipple-areola complex More common in men. Peak incidence: the sixth decade. Usually presents as a solitary nodule or plaque on the extensor surfaces of extremities and less commonly on the scalp and trunk. May be painful or asymptomatic. Grow insidiously. Possible origins: arrector pili muscle in the dermis or genital dartos muscle Wide local excision with a 3- to 5-cm safe margin Local recurrence rates: 30%~50%, rarely metastasize Leiomyosarcoma of mammary parenchyma More common in female. Average age: 52 years. Slow-growing solitary well-defined nodule. May be asymptomatic. 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