Primary leiomyosarcoma of the breast: A case report and literature review

Abstract

Introduction

Primary leiomyosarcoma is an uncommon form of stromal breast sarcoma. Approximately 73 cases have been documented in English-language literature to date. To our knowledge, this is the first report from Indonesia of an adolescent female with primary leiomyosarcoma of the breast.

Case presentation

A 30-year-old Southeast Asian female presented with a tumor in her left breast. Clinical examination revealed a 12 × 8-centimeter tumor. The supraclavicular, subclavicular, and axillary lymphadenopathy were not palpable. An ultrasound revealed a Breast Imaging Reporting and Data System category 5. Abdominal ultrasonography and chest x-ray were normal, as were blood chemistry and routine blood tests. A wide excision with a surgical margin of 2 cm was performed. Pathological investigation identified the mass as a leiomyosarcoma. The pelvis, abdomen, and lung CT scan metastatic workups were negative. The patient is well 8 months post-surgery, with no signs of recurrence.

Clinical discussion

Wide local excision has been the mainstay of treatment for leiomyosarcoma; however, there is no accepted standard of treatment due to the rarity of the disease.

Conclusion

Breast leiomyosarcomas have a more favorable prognosis than other breast neoplasms; however, patients must be closely monitored for recurrence or metastases. While there are no known predictors of outcomes, the margins of the initial surgery, mitotic activity, and atypia cellularity are more indicative of malignancy.

Highlights

• •Primary leiomyosarcoma is an uncommon form of stromal breast sarcoma.
• •To our knowledge, this is the first report in Indonesia of an adolescent female with primary leiomyosarcoma of the breast.
• •A wide excision with a surgical margin of 2 cm was performed.
• •Eight months post-surgery, the patient was well and showed no recurrence.

1. Introduction

Primary leiomyosarcoma is an uncommon form of stromal breast sarcoma and was first reported by Waterworth in 1968 [1], [2]. To our knowledge, this is the first report from Indonesia of an adolescent female with primary leiomyosarcoma of the breast. We report this case according to the Updating Consensus Surgical CAse REport (SCARE) 2020 guidelines [3].

2. Case presentation

A 30-year-old Southeast Asian female was admitted to the hospital's outpatient department complaining of a tumor in her left breast, which had grown gradually over the last 12 months. The patient had no comorbid conditions or family history of breast cancer. Clinical examination revealed a 12 × 8-centimeter tumor in the left breast. The supraclavicular, subclavicular, and axillary lymphadenopathy were not palpable.

Ultrasound of the breast revealed a Breast Imaging Reporting and Data System (BI-RADS) category 5, measuring 12.3 × 7.8 × 4.8 cm. Abdominal ultrasonography and chest x-ray were normal, as were blood chemistry and routine blood tests. A wide excision with a surgical margin of 2 cm was performed.

Pathological investigation identified a tumor made up of fascicles of hyperchromatic spindle cells with marked pleomorphism, >10 mitoses per 10 high-power fields, and atypical nuclei (Fig. 1). Based on immunohistochemistry (IHC) analysis, the tumor cells were positive for the proteins vimentin and desmin but negative for cytokeratin, identifying this mass as a leiomyosarcoma (Fig. 2). The pelvis, abdomen, and lung CT scan metastatic workups were negative. The patient was well 8 months post-surgery, with no signs of recurrence.

Fig. 1.

A) Leiomyosarcoma. Cellular tumors comprised of long intersecting fascicles. Hematoxylin and eosin (HE), 100× magnification. B) Leiomyosarcoma. Spindle cells with eosinophilic cytoplasm, hyperchromatic nuclei, and atypic and moderate nuclear pleomorphism. Mitoses >10 per 10 high-power fields. HE, 400× magnification.

Fig. 2.

A) Desmin expressed in the cytoplasm of tumor cells with moderate intensity. IHC, 400× magnification. B) Vimentin protein expressed in the cytoplasm of tumor cells with strong intensity. IHC, 400× magnification.

3. Discussion

Breast leiomyosarcoma is an uncommon type of cancer with unclear etiology. These tumors may develop from stromal mesenchymal cells or the smooth muscle cells lining blood vessels [4], [5].

Approximately 73 cases have been documented in English-language literature to date. The age of incidence ranges from 18 to 70 years (mean age was 51.24 years; Table 1). Typically, these tumors present as large masses with an average diameter of 4.7 cm (range of 0.3–16 cm). Most patients are female; however, at least 8 cases of leiomyosarcomas in male breasts have been recorded (Table 1).

Table 1.

Literature-reported clinicopathologic characteristics of breast leiomyosarcoma.

No	Author/s (year of publication)	Age (years)	Sex	Side	Size (cm)	Mitoses/10 HPF	Lymph node/vascular invasion (histology)	Treatment	Outcome and follow-up
1	Crocker and Murad (1969) [6]	51	M	R	5	Common	NA	RM	Local recurrence
2	Haagensen (1971) [6], [7]	77	F	L	8	Frequent	NA	SM	Alive, 14 years
3	Pardo-Mindán, Garcia-Julian and Eizaguirre Altuna (1974) [6], [7]	49	F	L	7	16	Yes	SM	Alive, 6 months
4	Barnes and Pietruszka (1977) [6], [7]	55	F	L	3	10	NA	SM	Died 4 years and 4 months later due to basilar artery thrombosis
5	Hernandez (1978) [6], [7]	53	M	L	4	15	No	MRM	Alive, 14 months
6	Chen, Kuo and Hoffmann (1981) [6], [7]	59	F	L	5.6	3	No	SM	Liver metastases after 16 years
7	Callery, Rosen and Kinne (1984) [6], [7]	56	F	NA	2	NA	NA	SM	Alive, 39 months
8	Callery, Rosen and Kinne (1984) [6], [7]	54	F	NA	3	NA	NA	SM	Alive, 53 months
9	Gobardhan (1984) [6], [7]	50	F	L	9	5	NA	MRM	Alive, 2 years
10	Yatsuka et al. (1984) [6], [7]	56	F	L	1.5	21	No	RM	Alive, 4 years
11	Nielsen (1984) [6], [7]	24	F	R	1.5	2	No	Excision	Died, multiple metastases to the layer of the SCALP and lung after 14 years
12	Yamashina (1987) [6], [7]	62	F	L	1	24	NA	RM	Alive, 1 year
13	Arista-Nasr et al. (1989) [6], [7]	50	F	R	4.5	4	NA	Excision	Alive, 6 years
14	Alessi and Sala (1992) [7]	62	M	R	NA	1	NA	Excision	Alive, 6 years
15	Lonsdale and Widdison (1992) [6], [7]	60	F	L	2	10	No	SM	Alive, 3 months
16	Parham et al. (1992) [6], [7]	52	F	L	3	29	NA	SM	Died 4 months later due to lung and cerebral metastases
17	Waterworth et al. (1992) [6], [7]	58	F	L	4	10	No	Excision	Alive, 1 year
18	Boscaino et al. (1994) [6], [7]	56	F	R	2.5	2	No	MRM	Alive, 6 years
19	Boscaino et al. (1994) [6], [7]	45	F	L	2.2	2	No	WLE	Alive, 40 months
20	Falconieri et al. (1997) [6]	83	F	R	6 × 5 × 5.5	20	No	MRM	Alive, 10 months
21	Falconieri et al. (1997) [6]	86	F	R	8 × 7 × 6	11	No	SM	Alive, 8 months
22	Uğraş et al. (1997) [7]	47	F	R	2	3	No	Excision and SM	Alive, 18 months
23	Gupta et al. (2000) [6], [7]	80	F	L	7 × 5	8	No	MRM	Alive, 2 years
24	Hussien et al. (2001) [8]	48	F	R	2	≤12	No	MRM	Alive, 18 months
25	Szekely et al. (2001) [6], [7]	73	F	R	4.5	20–22	No	MRM	Alive, 1 year
26	Kusama et al. (2002) [6], [7]	55	F	L	1	10	No	MRM	Multiple metastases: lung 12 months and lumbar spine 2 years post-MRM
27	Shinto et al. (2002) [6], [7]	59	F	L	12	19	No	MRM	Local recurrence, lung metastases 2 months post-MRM
28	Liang et al. (2003) [7]	25	F	L	4	5	NA	WLE	Alive, 32 months
29	Markaki et al. (2003) [6], [7]	42	F	R	14 × 10 × 4	50	No	MRM	Alive, 3 years
30	Markaki et al. (2003) [6], [7]	65	F	L	5 × 1	10	NA	Excision	Alive, 18 months
31	Jun Wei et al. (2003) [6], [7]	52	F	R	1.5	22	NA	Excision	Alive, 3 months
32	Lee et al. (2004) [6]	44	F	NA	3	6–12	NA	SM	Alive, 13 months
33	Lee et al. (2004) [6]	52	F	NA	4.5	6–12	NA	SM	Alive, 17 months
34	Munitiz et al. (2004) [6], [7]	58	F	R	4	14	No	MRM	Alive, 12 months
35	Stafyla, Gauvin and Farley (2004) [6], [7]	53	F	L	23	NA	No	MRM	Alive, 2 years
36	Jayaram, Jayalakshmi and Yip (2005) [6], [7]	55	F	R	12	40	No	MRM	Local recurrence after 2 months
37	Gupta (2007) [6]	37	F	R	8 × 6	15	No	WLE	Alive, 36 months
38	Ende (2007) [9]	48	F	L	1.2	0	NA	Excision	NA
39	De la Pena and Wapnir (2008) [6], [7]	50	F	L	3.5 × 1.4 × 2.8	Few	NA	SM	Alive, 11 months
40	Wong et al. (2008) [6], [7]	52	F	L	1.5 × 1.1 × 0.7	7	NA	SM	Alive
41	Cobanoglu et al. (2009) [6], [7]	64	F	L	3.6	≤12	No	MRM	Alive, 22 months
42	Boehm et al. (2010) [7]	62	M	R	4.6 × 3.5	4	NA	MRM	Alive, 24 months
43	Kamio (2010) [7]	46	F	L	0.5	2–8	NA	SM	Alive, 8 years 4 months
44	Masannat, Sumrien and Sharaiha (2010) [7]	59	M	R	1.8 × 1.3	NA	NA	SM	Alive, 26 months
45	Sandhya et al. (2010) [7]	54	F	L	7 × 7	6	No	MRM	Alive, 1 year
46	Fujita et al. (2011) [6]	18	F	R	7	10	No	SM	Alive, 5 years
47	Oktay and Fikret (2011) [7]	44	F	L	3.5	Few	NA	Excision	Alive, 12 months
48	Nagao et al. (2011) [10]	61	F	R	3	>10	NA	WLE	Alive, 18 months
49	Karabulut, Akkaya and Moray (2012) [7], [11]	48	F	R	10 × 9 × 6	Frequent	No	MRM	Alive, 1 month
50	Rane, Batra and Saikia (2012) [7]	19	F	L	8	20–25	NA	Excision	Alive, 3 years
51	Pai and Yoon (2013) [7]	46	F	L	7 × 6 × 6.5	>10	NA	MRM	Lung metastases after 3 months
52	Yener and Aksoy (2013) [7]	44	F	L	3.5	Few	NA	Lumpectomy	Alive, 12 months
53	Amaadour et al. (2013) [7]	44	F	R	9.2 × 7.6 × 6	6	NA	Palliative chemotherapy	Died one month later due to metastases in the lung and abdominal wall
54	Basset et al. (2014) [1]	20	F	L	3	High	No	Excision followed by MRM	NA
55	Guedes et al. (2014) [2]	46	F	R	1.6 × 1	3	NA	Excision	Alive, 1 year
56	Agrawal, Garg and Pandey (2015) [12]	40	F	R	9 × 9 × 8	Frequent	Yes	MRM	Alive, 1 year
57	Agrawal, Garg and Pandey (2015) [12]	70	F	L	8 × 7 × 6	NA	No	MRM	Alive, 1 year
58	Sokolovskaya et al. (2014) [7]	58	F	R	15 × 9 × 13	NA	NA	MRM	Multiple bone and lung metastases after 2 years
59	Kim et al. (2015) [13]	51	F	R	4 × 3 × 4	15	NA	Excision	Alive, 5 years
60	Tajima, Koda and Fukayama (2015) [7]	50	F	L	4.8 × 4.5 × 4.2	6	No	MRM	Alive, 6 months
61	M'rabet et al. (2017) [7]	40	F	L	6	NA	No	MRM and RT	Alive, 8 years
62	Arsalane et al. (2017) [14]	68	M	R	8 × 9	9–10	No	MRM	Alive, 9 months
63	Testori et al. (2017) [15]	62	F	L	0.3 × 0.15	Up to 5	No	Breast conservative surgery	NA
64	Singh, Sharma and Goyal (2017) [16]	48	F	R	16 × 10	Numerous	NA	MRM, RT, and CT	Alive
65	Lee and Lee (2018) [7]	49	F	L	6 × 8	≤18	NA	Palliative mastectomy and CT	Lung metastases; died 4 months later due to sudden steep decrease in blood pressure
66	Villegas et al. (2018) [8]	48	M	L	8 × 5	NA	No	SM	Alive, 1 month
67	Amberger et al. (2018) [7]	20	F	L	3	30	No	Excision and MRM	Lung metastases after 3 years
68	Ilyas et al. (2020) [17]	52	F	L	6	2 to 50	Yes	SM	Alive, 1 year
69	Liu et al. (2020) [18]	28	F	L	1.6 × 0.9	10	NA	WLE	Alive, 1 year
70	Kumar et al. (2020) [19]	53	F	R	8 × 6	Frequent	NA	WLE	Multiple metastases (lung, renal, and skeletal)
71	Horton et al. (2020) [20]	61	F	R	1.6	NA	No	WLE	NA
72	Bürger et al. (2020) [21]	54	F	R	3	Up to 3	No	Breast conservative surgery	Alive, 24 months
73	Ely Cheikh et al. (2021) [22]	65	M	Bilateral	7	15	NA	L: WLE; R: SM and RT	Alive, 11 months
74	Present case	30	F	L	12 × 8	>10	No	WLE	Alive, 8 months

Note: cm, centimeter; HPF, high-power fields; F, female; M, male; R, right; L, left; WLE, wide local excision; RM, radical mastectomy; SM, simple mastectomy; MRM, modified radical mastectomy; RT, radiotherapy; CT, chemotherapy; NA, not available; SCALP, Skin, dense Connective tissue, epicranial Aponeurosis, Loose areolar connective tissue and Periosteum.

Breast leiomyosarcomas can be difficult to clinically distinguish from other breast neoplasms as physical examination and imaging findings are frequently similar to those of other malignancies [7]. Clinical lymphadenopathy is relatively uncommon, appearing in <10 % of cases. Involvement of the breast tissue and areola is also uncommon [5]. Ultrasound, mammogram, and other imaging methods are frequently non-specific. These masses are often misidentified as benign etiologies (phyllodes tumors and fibroadenomas); however, they are more frequently confused with other primary breast sarcomas due to their lack of recognizable imaging characteristics [7], [13]. Excisional biopsy or core biopsy findings are necessary for definitive diagnosis [5], [7]. Diagnostic histologic features include interlaced spindle cell bundles, with additional grading determined by the level of mitotic activity, nuclear pleomorphism, and atypia cellularity [16]. IHC analysis is often used to confirm the diagnosis. Leiomyosarcomas will be positive for desmin, smooth muscle actin, and vimentin and negative for epithelial markers, cytokeratin, and S-100 [4], [7], [16]. The usual tumor, nodes, and metastases (TMN) classification for breast malignancy is used for the clinical staging of leiomyosarcomas [7].

The treatment of breast sarcomas follows the same principles as treatments for sarcomas of extremities [4], [19]. Early-stage cases are surgically treated via excision or mastectomy [7]. The patient in this study was treated with wide local excision. A previous study has suggested that a negative margin of at least 3 cm should be achieved for optimal efficacy; however, for breast conservation, 2-centimeter margins can be used [6], [21]. Although axillary node dissection is not required, it is performed in many cases due to an unclear preoperative diagnosis or the presence of clinically palpable nodes [15], [21]. According to the literature, the prognosis is unaffected by the primary tumor size or the type of excision (mastectomy or local excision) [17].

Following surgical excision, radiotherapy is advised for local control. Adjuvant radiation following breast-conserving resection has been shown to improve local control of disease-free survival and recurrence, especially if the resection margin is inadequate [22]. Chemotherapy may be indicated for tumors larger than 5 cm, high-grade tumors, or advanced cancer. However, it is unknown if treatment would be beneficial or have any effect on morbidity and mortality. Anthracyclines have become known as the first-line chemotherapy, with a combination of the addition of ifosfamide [7].

Hematogenous spread is the most common metastasis associated with leiomyosarcomas [7]. Distant hematogenous metastases to the bone, liver, lungs, central nervous system, and spine are reported in approximately 25 % of cases and are commonly discovered after a latent period of 15–20 years [11], [16]. For example, a study reported a patient who presented with liver metastasis 16 years after a simple mastectomy [16]. According to a study, the disease-free survival rate at 5 years is 33 % to 52 %, the 5-year overall survival rate ranges from 50 % to 66 %, and a major predictor of survival is the margins of the first surgery [8]. In the current case, there was no recurrence after an eight months follow-up, and the treatment was well tolerated.

4. Conclusion

Breast leiomyosarcomas have more favorable prognoses than other breast neoplasms. There are no known outcome predictors; however, the margins of the initial surgery, mitotic activity, and atypia cellularity can be indicative of malignancy. The most common form of treatment is excision or mastectomy without axillary lymphadenectomy.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Provenance and peer review

Not commissioned, externally peer reviewed.

Ethical approval

The study is exempt from ethical approval in our institution.

Funding

None.

CRediT authorship contribution statement

Rina Masadah, Faradilla Anwar, Berti Julian Nelwan, and Muhammad Faruk: study concept, and therapy for this patient. Rina Masadah and Muhammad Faruk: Data collection, Writing-Original draft preparation. Rina Masadah, Faradilla Anwar, Berti Julian Nelwan, and Muhammad Faruk: Editing, Writing. All authors read and approved the final manuscript.

Guarantor

Rina Masadah.

Research registration number

N/A.

Declaration of competing interest

None.