Primary Leiomyosarcoma of the Breast: A Successful Surgical Treatment in a 45-Year-Old Woman

Background

Primary breast sarcoma is a rare tumor type that originates from mesenchymal tissue [1]. Breast sarcomas account for less than 1% of all breast tumors, and tend to affect mostly postmenopausal women [2]. Primary leiomyosarcoma (LMS) of the breast is even more rarely observed and has not been fully studied [1]. Therefore, treatment protocols for breast sarcomas are mainly based on what we know about soft-tissue sarcomas [2].

Surgery with adequate margins remains the best treatment choice. There is also emerging evidence to support use of neoadjuvant chemotherapy for treatment of metastatic disease, but the results remain inconclusive [3].

Leiomyosarcoma is one of the most common subtypes of soft-tissue sarcomas (STS), comprising up to 10–20% of all sarcomas. Classically, LMS originate directly from the smooth muscle cells or from the precursor mesenchymal stem cells that eventually differentiate into smooth muscle cells [4].

There is no definite identifiable causative factor for LMS. Prior history of radiotherapy (RT), which is one of the most significant risk factors for developing STS, can also lead to the development of LMS [5]. Patients with genetic syndromes like hereditary retinoblastoma (RB1 gene deletion) and Li-Fraumeni syndrome (mutation in the TP53 gene) can develop LMS, amongst other STS [6]

Leiomyosarcomas typically have better prognosis than other types of breast sarcomas [1]. However, more studies are needed to understand the true survival rate for this rare malignancy [7].

There are several published case reports on primary breast LMS. One of the first cases of primary breast LMS was presented by Amaadour et al in 2013, reporting the case of a 44-year-old patient with primary LMS of the breast rapidly increasing in size, which progressed on chemotherapy with distant appearance of a cutaneous abdominal nodule. Tumor progression was observed despite the provided cycles of chemotherapy [2]. A recent report by Horton et al presented a case of primary LMS in a 61-year-old woman successfully treated with lumpectomy and breast reduction surgery [8].

This report is of a 45-year-old woman with a primary leiomyosarcoma of the breast, successfully treated by surgical excision.

Case Report

A 45-year-old woman first noticed a 5-cm lump in her right breast in December 2016. In the following months, the lump increased in size, leading to tightening of the skin in that area, with no nipple retraction, nor palpable axillary or supraclavicular lymphadenopathy. Ultrasonography (US) was performed in March 2017 and revealed a well-circumscribed mass 5.0×4.5 cm in size, located in the upper outer quadrant of the right breast. It was initially recognized as fibroadenoma, but a core-needle biopsy result was consistent with a malignancy. Subsequently, segmental resection of the breast was performed and histological examination of the specimen revealed sarcoma. On immunohistochemical examination, the tumor cells were positive for smooth muscle actin (SMA) and vimentin, and negative for desmin, pan cytokeratin (panCK), epithelial membrane antigen (EMA), estrogen receptor (ER), progesterone receptor (PR), and cluster of differentiation (CD) 117. The Ki 67 index was 15–20%. A further 9 cycles of chemotherapy with Gemcitabine was unsuccessful and there was significant tumor growth.

The patient presented to our hospital in February 2018 with a tumor mass and burst of pain associated with it. Physical examination revealed a tender 10-cm mass in the upper outer quadrant of the right breast, with significant skin thickening and skin invasion (Figure 1). Chest computed tomography (CT) revealed an upper outer-quadrant mass 9.3×8.7×10.5 cm in size with lateral invasion of the pectoralis minor and pectoralis major.

Following evaluation, right mastectomy was recommended. However, the patient only presented for the surgery in May 2018, with the evidence of additional tumor growth. Subsequent chest CT revealed an upper outer-quadrant mass 18.0×18.0×15.0 cm in size with invasion of both pectoralis muscles and enlarged axillary lymph nodes (Figure 2). The patient underwent total right breast mastectomy, total excision of the pectoralis minor muscle, partial excision of pectoral major muscle, and axillary lymph node dissection on May 23, 2018.

Pathological assessment revealed a necrotic mass 21.0×16.0×12.0 cm in size with invasion into the overlying breast skin and pectoralis major muscle. Two out of 20 excised lymph nodes revealed tumor growth. The mass was resected with clear margins (Figure 3). Microscopically the tumor was well-circumscribed, well-encapsulated, composed of spindle cells arranged as intersecting long fascicles in a collagenous background consistent with leiomyosarcoma (Figures 4, 5).

The patient was discharged 7 days after the surgery, and no further treatment was advised. Five-year follow-up with physical exam, mammography, ultrasonography of the breast with regional lymph nodes, chest and abdominal CT with contrast, and pelvis (magnetic resonance imaging) MRI did not show any signs of local recurrence or distant metastasis. Long-term follow-up is planned.

Discussion

This case report vividly illustrates the example of a patient with rapidly growing chemotherapy-resistant breast LMS, which was initially misdiagnosed as fibroadenoma.

Sarcomas are a very heterogenous tumor type. They originate from mesenchymal tissue and can arise anywhere in the body. Breast sarcomas are rare entities responsible for less than 1% of breast malignancies [1]. Sarcomas often affect middle-aged women in their 5th or 6th decade of life (the mean age is around 56 years), and manifests as a slowly-growing mass [2]. According to published studies, the duration of symptoms varies from a few weeks to several years [2]. There are many histological subtypes of breast sarcoma and they are generally named based on the corresponding tissue of origin, such as angiosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma [1].

Leiomyosarcoma of the breast primarily originates from the muscle wall of blood vessels or from the smooth muscle of the nipple [2,9]. This type of tumor is very rare, and information about them mainly comes from case reports or small retrospective studies. Preoperative diagnosis is extremely challenging since histological and immunohistochemical evaluations are essential to establish proper diagnosis [10,11]. Initially, LMS are often mistaken for fibroadenomas, as in our case. Histologically, leiomyosarcoma is characterized by spindle-shaped cells with pleomorphic, hyperchromatic, and elongated nuclei; eosinophilic cytoplasm; large nucleoli; and significant mitoses [2,12,13]. Definitive diagnosis is established through immunohistochemistry, which generally points to the muscle origin, staining positive for desmin, vimentin, and muscle-specific actin, while excluding epithelial origin with negative keratin, epithelial membrane antigen, myoglobin, and S-100 [1,9,12].

Differential diagnoses include leiomyoma, spindle cell myoepithelioma, and spindle cell sarcomatoid carcinomas [2]. In contrast to leiomyosarcoma, leiomyoma does not show evidence of atypia and mitosis [8]. Malignant myoepithelioma often does not show significant atypia; however, an epithelioid cell population may be found, which is not found in leiomyosarcoma [7]. Other tumors are often positive for cytokeratins or immunoreact with epithelial markers such as Cytokeratin 7 or SMA, which are negative in case of LMS [2].

Leiomyosarcoma of the breast is often described as a well-circumscribed mass, with tendency for skin and muscle invasion. Although pain and overlying skin changes are rare, cutaneous tissue may be involved, resulting in thickening of the breast [4]. Areolar changes and nipple discharge are usually absent [1]. The tumor is believed to spread hematogenously [1,2,9]. Several studies reported metastatic spread to lungs, liver, and bones [1,9]. Lymph node involvement is extremely uncommon [2,3,9]. The study by Fong et al that involved 1772 cases of soft-tissue sarcomas showed only a 2.6% rate of lymph nodal involvement [14]. Lamyman et al demonstrated that soft-tissue leiomyosarcoma of the extremities results in metastatic spread to lymph nodes in 7% of cases [15]. To the best of our knowledge, the present study is the first to demonstrate malignant spread to the lymph nodes from breast LMS. Routine lymph nodal resection and sentinel node biopsy, however, are not recommended, since it has no effect on patient survival [15]. Axillary lymph nodes should be evaluated only if suspicious based on the assessment or imaging [3].

Horton et al presented a case of breast LMS in which breast reduction surgery and postlumpectomy therapy prevented cancer recurrence. Unfortunately, this type of treatment is only appropriate for patients with small tumor-to-breast ratio [8]. In comparison with the case report presented by Horton, in our patient had a huge tumor that was a contraindication to breast-conserving surgery and required mastectomy. LMS often reaches a large size and can deform the mammary gland. Like the case presented by Amaadour et al, our patient also had a huge, rapidly growing tumor resistant to chemotherapy, but unlike Amaadour et al, we were able to perform surgery and save the patient’s life [16].

Treatment protocols for breast sarcomas generally come from research on other soft-tissue sarcomas. Surgical excision with wide margins of at least 1 cm is generally considered the best treatment option [1]. Margins status is known to be the most important factor in disease recurrence [1,10]. There is ongoing discussion regarding use of RT and chemotherapy for treatment of LMS. Adjuvant RT is often advised if the tumor was resected with positive margins, if dealing with large tumors (>5 cm) or high-grade sarcomas [1,3]. A few reports have discussed the use of neoadjuvant chemotherapy in case of extensive disease [1,3], but the response rate varies greatly, and prolonging the surgery for chemotherapy is often not advised [1].

Complete survival analysis for breast sarcomas is challenging to conduct due limited available data. The overall prognosis of breast sarcomas is known to be poorer than for other breast cancers [3]. Leiomyosarcomas tend to have a favorable prognosis [9]. According to Amberger et al, 5-year survival rates are 64%, 36%, and 14% for localized, regional, and distant disease, respectively [9]. Recurrence and metastatic spread are possible even long after (15 to 20 years) disease eradication [2]. Therefore, long-term follow-up is important.

Conclusions

Our case highlights the importance of proper follow-up and necessity of wide excision surgery with negative margins for breast LMS, and has shown the importance of histopathology and immunohistochemistry in the diagnosis of primary spindle cell malignant tumors of the breast. Primary LMS of the breast should be excised with an adequate excision margin to reduce the risk of recurrence and improve patient outcomes.