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Leiomyosarcoma of the breast: A case report and review of the literature about therapeutic management
The Breast 20 (2011) 389e393
Contents lists available at ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Review
Leiomyosarcoma of the breast: A case report and review of the literature about therapeutic management Noriko Fujita a, c, *, Ryo Kimura a, Jun Yamamura a, Kenji Akazawa a, Tsutomu Kasugai b, Fumine Tsukamoto a a b c
Department of Breast and Endocrine Surgery, Osaka Kosei-Nenkin Hospital, Japan Department of Pathology, Osaka Kosei-Nenkin Hospital, Japan Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 May 2010 Received in revised form 28 September 2010 Accepted 17 March 2011
We experienced a leiomyosarcoma of the breast in an 18-year-old female. No specific treatment has been established. In order to clarify appropriate therapeutic management methods, the limited data available from our and previous case reports were assessed. A leiomyosarcoma of the breast must be excised with a negative margin. If the tumor size is large and an adequate margin, greater than 3-cm margin around the excised tumor, is not achieved due to anatomical constraints, radiotherapy may be indicated. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Leiomyosarcoma Breast Surgery Therapeutic management
Introduction A leiomyosarcoma of the breast is exceedingly rare. Up to now only 44 cases of genuine leiomyosarcoma of the breast have been documented in the literature,1e38 and no specific treatment has been established. We experienced a case of an 18-year-old female with a leiomyosarcoma of the breast, and attempted to clarify appropriate therapeutic management methods based on the limited data available from those case reports.
Case report An 18-year-old female patient with no prior medical problems presented with a slowly growing tumor in the center of the right breast. The tumor had enlarged rapidly in the prior eight months. Her mother had breast cancer at age 40. A fine needle aspiration biopsy demonstrated no malignant findings in the cytological features. However, the tumor was, grossly, thought to be malignant. Thus, she was introduced to our hospital for further examination in order to ascertain the histological findings, and definitive treatment. * Corresponding author. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: þ81 6 6879 3772; fax: þ81 6 6879 3779. E-mail address: [email protected] (N. Fujita). 0960-9776/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2011.03.001
Physical examination showed an elastic-hard tumor, 7.2 6.8 cm in size with a well-defined mass, in her right breast. The skin was invaded and the nipple was dimpling. No axillary lymph nodes were palpable. No other findings on her general physical examination were remarkable. Her laboratory data and the values of tumor markers, including CEA 1 ng/ml and CA15-3 5.5 U/ ml, were within normal limits. The mass appeared to be lobulated on ultrasonography. A Computed tomography showed a phyllodeshaped high density area in her right breast, and showed no metastasis in the whole body, including the bilateral lung, liver and axillary lymph node (Fig. 1(a)). Magnetic resonance imaging showed a phyllode-shaped hyper-intensity mass on enhanced imaging in her right breast, and showed that deep fascia was not involved (Fig. 1(b)). Ultrasound-guided vacuum-assisted breast biopsy revealed spindle cells in the histological findings (Fig. 2(a)). Based on the results in those examinations, the preoperative diagnosis of leiomyosarcoma in the right breast was obtained. A simple mastectomy with sentinel lymph node biopsy was selected. The surgical specimen from the tumor was hard in consistency and whitish-gray in color; necrosis was identified. The tumor was an elastic-hard tumor, 7.0 cm in size. Hematoxylin and eosin staining showed many bundles of spindle cells under low magnification, and showed necrosis in the tumor and polymorphic cells with occasional mitotic activity under high magnification. Mitotic figures were frequently observed and averaged six per ten high power fields (Fig. 2(b)). Immunohistochemical staining
Fig. 1. (a) Computed tomography showed a phyllode-shaped high density area on the breast, and also showed no metastasis of the bilateral lungs, liver and axillary lymph node. (b) Magnetic resonance imaging showed a phyllode-shaped hyper-intensity mass on enhanced imaging, and showed that deep fascia was not involved.
Fig. 2. (a) Ultrasound-guided vacuum-assisted breast biopsy showed spindle cells by hematoxylin and eosin staining (H & E 100). (b) Higher magnification showed nuclear atypia and mitotic figures (H & E 400). (c) Higher magnification showed Mib-1LI 10% (400). (d) Enzyme-antibody stain using antibody against a-smooth muscle actin was positive (400). (e) Immunohistochemical study of desmin was positive (400).
N. Fujita et al. / The Breast 20 (2011) 389e393
391
Table 1 Review of cases of primary leiomyosarcoma of the breast. Author
Year Sex Age Side Location Size (cm)
Mitosis
Treatment
Meta
Crocker and Murad1 Haagensen2 Pardo-Mindan3 Barnes4
1969 1971 1974 1977
M F F F
51 77 49 55
R L L L
E AC E
5 8 7 3
common very frequent 16/10 HPF 10/10 HPF
radical mastectomy mastectomy simple mastectomy simple mastectomy
NET NET NET NET
Hernandez5
1978 M
53
L
E
4
15/10 HPF
NET
Chen Callery7 Callery Yatsuka8 Gobardhan9
1981 1984 1984 1984 1984
F F F F F
59 56 54 56 50
L
CD
3/10 HPF
L L
E D
5.6 2 3 1.5 9
hepatic metastasis NET NET NET NET
alive, alive, alive, alive, alive,
Nielsen10
1984 F
24
R
E
1.5(1962)r, 1 (1965) r, 2 (1966) r
2/10 HPF, 8/10 HPF, 14/10 HPF
modified radical mastectomy simple mastectomy simple mastectomy simple mastectomy radical mastectomy modified radical mastectomy excision in 1960. 1962 excision, excision and simple mastectomy
alive, 14 years alive, 6 months died 4 years 4 months later with basilar arterythrombosis alive, 1 year 2 months
died 20 years later
Yamashina11 Arista-Nasr12
1987 F 1989 F
62 50
L R
B
11/10 HPF 4/10 HPF
simple mastectomy local excision
Parham13
1992 F
52
L
CD
2.5 4.5 (1980), 2.3 (1986) r 3
29/10 HPF
mastectomy
1992 F
60
L
E
Waterworth15
1992 F
58
L
C
2, 4 (18 10/10 HPF months later) 4 10/10 HPF
local recurrence & systemic recurrence (brain, skin, thyroid, kidney) NET local recurrence, no metastasis local & systemic recurrence, (brain, lung) local recurrence
Wei16
1993 F
36
R
C
4
Boscaino
1994 F
56
R
C
2.5 / 4
Boscaino
1994 F
45
L
D
1.9 / 2.2
Levy18 Falconieri19 Falconieri Ugras20
1995 1997 1997 1997
F F F F
35 83 86 47
R R R R
D E E E
4 6 8 2
Gonzalez-Palacios21 1998 F 2000 F Gupta22
62 80
L L
C AC
3 6.5
Szekely23 Kusama24
2001 F 2002 F
73 55
R L
B C
4.8 0.5
Shinto25
2002 F
59
L
CDEAB
12
wide local excision with level 2 axillary LN sampling modified radical mastectomy 2/10 HPF excise (1981) / radical mastectomy (1984) 2/10 HPF biopsy (1985) / wide local excision (1989) 2/10 HPF simple mastectomy 20/10 HPF radical mastectomy 11/10 HPF simple mastectomy 3/10 HPF subcutaneous simple mastectomy 10/10 HPF simple mastectomy 5e8/10 HPF mastectomy with axillary clearance 20e22/10 HPF mastectomy few excisions (1996, 1997) / simple mastectomy (1998) 19/10 HPF simple mastectomy
Jun Wei26 Markaki27
2003 F 2003 F
52 42
R R
B
4 14
22/10 HPF 50/10 HPF
Markaki
2003 F
65
L
5,2
10/10 HPF
Liang28 Adem29 Adem Jayaram30
2003 2004 2004 2004
F F F F
25 67 55 55
L
C
5/10 HPF
R
BD
4 2 4 12
2004 F
44
3
6e12/10 HPF
2004 F
52
4.5
6e12/10 HPF
2004 F
53
L
CDEAB
23
2004 F
58
R
C
4
14/10 HPF
Gupta Vu and Knudson35 De la Pena36 Wong37 Cobanoglu38
2006 2006 2008 2008 2009
F F F F F
37
R
D
15/10 HPF
50 52 64
L L L
C C C
8 23 3.2 1.5 3.5
present report
2010 F
18
R
EABCD
7.2
10/10 HPF
6
Lonsdale
14
17
Lee
31
Lee Stafyla32 33
Munitiz
34
NET: No evidence of tumor. HPF: High power field.
21/10 HPF 5/10 HPF
7/10 HPF 12/10 HPF
excise / mastectomy
excision wide modified radical mastectomy excision not major surgery excision excision mastectomy modified radical mastectomy partial or simple mastectomy partial or simple mastectomy modified radical mastectomy modified radical mastectomy wide lumpectomy mastectomy mastectomy mastectomy modified radical mastectomy simple mastectomy
NET systemic recurrence (brain, bone), left breast local recurrence / NET local recurrence
Final follow up
15 years 39 months 53 months 4 years 7 months 2 years
alive, 2 years 2 months alive, 6 years 4 months alive, 6 months alive, 3 months, post-mastectomy alive, 1 year died 14 months later alive, 9 years (3 þ 6)
NET NET NET NET
alive, 40 months,post wide local excision alive, 6 months alive, 10 months alive, 8 months alive, 1 year 6 months
NET NET
alive, 17 years alive, 2 years
NET alive, 1 year 2local recurrence, systemic alive, 4 years 8 months metastasis (lung, bone) with lung bone metastasis local & systemic alive, 8 months recurrence (lung) NET alive, 3 months NET alive, 3 years NET
alive, 18 months
NET alive, 32 months local & systemic recurrence died 7 months later systemic recurrence died 77 months later local recurrence NET
alive, 13 months
NET
alive, 17 months
NET
alive, 2 years
NET
alive, 1 year
NET NET NET NET NET
alive, alive, alive, alive, alive,
NET
alive, 5 years
36 months 10 months 11 months 4 days 22 months
392
N. Fujita et al. / The Breast 20 (2011) 389e393
was positive for a-smooth muscle actin, vimentin, desmin but not for S-protein (Fig. 2 (cee)). No sentinel node metastasis was found. We made the diagnosis of leiomyosarcoma according to the WHO classification. We determined that the grade and stage of the tumor was T2N0M0 and Grade 2 based on the AJCC staging system. Pathological assessment revealed that the width of surgical margin was greater than 3-cm. At five years after surgery, this patient had shown no evidence of local recurrence or metastases. Discussion A leiomyosarcoma of the breast is exceedingly rare disease. Up to now only 45 cases of genuine leiomyosarcoma of the breast, including this patient, have been documented in the literature (Table 1).1e38 No specific treatment has been established. Thus, we attempted to clarify appropriate therapeutic management methods for affected patients based on the limited data available from our and previous case reports. The basis of the treatment is surgery, either local excision or mastectomy (simple or modified radical mastectomy). Local excisions were performed in 1210,12,14,15,17,24,26e29,34 cases. Of those, six patients10,14,17,24,29 had a tumor sized less than 3 cm, of which five10,14,17,24 had local recurrence following resection because of an inadequate margin. In the six12,15,26e28,34 patients with a tumor sized 3 cm or greater, only one12 had local recurrence following resection, in whom, the excision left a 5-mm margin of mammary tissue, which was thought to be inadequate. Mastectomies were performed in 331e9,11,13,16,18e23,25,27,29e33,35e38 cases including our report. Of those cases, five7,8,11,20,37 had a tumor sized less than 3 cm, no case had local and systemic recurrence. In 28 patients with a tumor sized 3 cm or greater, six6,13,16,25,29,30 had local or systemic metastasis. In two13,25 of those recurred six patients, one underwent an open surgical biopsy for the differential diagnosis and the other underwent a simple mastectomy as a benign phyllodes tumor, which was 7.3 12.0 8.0 cm in size. We think that the margins were not adequate in those two cases. The other four16,25,29,30 case reports did not provide detailed descriptions about the clinical courses or operative findings. It appears that the type of surgical excision, whether excisional biopsy, simple mastectomy, or modified radical mastectomy, does not affect prognosis as long as the tumor is excised with an adequate margin. In the present case, we performed a simple mastectomy and the width of the margin was obtained at least 3 cm. We hoped to recommend an adequate margin width around the excised tumor based on the previous case reports. However, we could not clarify the margin width in those studies due to lack of descriptions, as only a few papers stated concrete widths. For example, local recurrence occurred in a 1-cm margin in a case,14 while did not occur in a 2-cm margin in another case.28 And local recurrence did not occur in the width of the margin obtained, in mastectomy procedures, at least 3 cm.9 In addition, in a patient with a tumor sized less than 3 cm, a 2-cm margin is considered necessary when planning breast-conserving surgery. A leiomyosarcoma tends to develop local recurrence. Accordingly, we recommend a greater than 3-cm margin as an adequate margin. In addition, an axillary lymph node dissection was performed in 151,5,8,9,15,16,19,22,23,25,27,30,32,33,38 of the 45 cases. None were reported to have axillary lymph node metastasis. Thus, it is unlikely that axillary node dissection affords benefit. In the present case, we were uneasy about the exact histological diagnosis due to the rarity of the disease. Accordingly, we wanted to confirm that there was no lymph node metastasis by performing a sentinel node biopsy. A few of the reports noted about adjuvant therapy used in cases of leiomyosarcoma of the breast. Three patients24,29,30 were offered
chemotherapy. However, one patient had multiple lung metastases and local recurrence developed at 12 months after surgery in spite of chemotherapy with vincristine, adriamycin, cyclophosphamide, and dacarbazine.24 Another had local recurrence after two cycles of adriamycin.30 The third case did not provide detailed descriptions.29 We found only three case reports applied for radiotherapy to treat leiomyosarcoma of the breast.30,32,35 In two of those,32,35 a wide excision was not possible due to anatomical constraints. The third reported local recurrence after surgery. Good results were obtained in those three cases. Radiotherapy is a well-established treatment used to reduce local recurrence of leiomyosarcomas in other lesions of the body.39 Accordingly, post operative radiotherapy may be indicated for cases with leiomyosarcoma of the breast. Where a wide excision is not possible due to anatomical constraints, a planned marginal excision plus radiotherapy may be an appropriate means of achieving tumor control. In conclusion, a leiomyosarcoma of the breast must be excised with a negative margin in order to obtain good results. If the tumor size is large and an adequate margin, greater than 3-cm margin around the excised tumor, is not achieved due to anatomical constraints, radiotherapy may be indicated.
Acknowledgments We are indebted to Nobuaki Hirata, MD, for his thoughtful suggestions during the manuscript preparation.
References 1. Crocker DJ, Murad TM. Ultrastructure of fibrosarcoma in a male breast. Cancer 1969;23:891e9. 2. Haagensen CD. Nonepithelial neoplasms of the breast. Diseases of the Breast. Revised 2nd ed. Philadelphia: W.B.Saunders; 1971. pp299epp300. 3. Pardo-Mindan J, Garcia-Julian G, Eizaguirre Altuna M. Leiomyosarcoma of the breast. Report of a case. Am J Clin Pathol 1974;62:477e80. 4. Barnes L, Pietruszka M. Sarcomas of the breast. A clinicopathologic analysis of ten cases. Cancer 1977;40:1577e85. 5. Hernandez FJ. Leiomyosarcoma of male breast originating in the nipple. Am J Surg Pathol 1978;2:299e304. 6. Chen KT, Kuo TT, Hoffmann KD. Leiomyosarcoma of the breast: a case of long survival and late hepatic metastasis. Cancer 1981;1(47):1883e6. 7. Callery CD, Rosen PP, Kinne DW. Sarcoma of the breast. A study of 32 patients with reappraisal of classification and therapy. Ann Surg 1985;201:527e32. 8. Yatsuka K, Mihara S, Isobe M, Edakuni S, Takeoka A, Kakegawa T, et al. Leiomyosarcoma of the breast e a case report and an electron microscopic study. Jpn J Surg 1984;14:494e8. 9. Gobardhan AB. Primary leiomyosarcoma of the breast. Neth J Surg 1984;36: 116e8. 10. Nielsen BB. Leiomyosarcoma of the breast with late dissemination. Virchows Arch A Pathol Anat Histopathol 1984;403:241e5. 11. Yamashina M. Primary leiomyosarcoma in the breast. Jpn J Clin Oncol 1987; 17:71e7. 12. Arista-Nasr J, Gonzalez-Gomez I, Angeles-Angeles A, Illanes-Baz E, BrandtBrandt H, Larriva-Sahd J. Primary recurrent leiomyosarcoma of the breast. Case report with ultrastructural and immunohistochemical study and review of the literature. Am J Clin Pathol 1989;92:500e5. 13. Parham DM, Robertson AJ, Hussein KA, Davidson AI. Leiomyosarcoma of the breast; cytological and histological features, with a review of the literature. Cytopathology 1992;3:245e52. 14. Lonsdale RN, Widdison A. Leiomyosarcoma of the nipple. Histopathology 1992;20:537e9. 15. Waterworth PD, Gompertz RHK, Hennessy C, Henry JA, Lennard TWJ. Primary leiomyosarcoma of the breast. Br J Surg 1992;79:169e70. 16. Wei CH, Wan CY, Chen A, Tseng HH. Epithelioid leiomyosarcoma of the breast: report of a case. J Formos Med Assoc 1993;92:379e81. 17. Boscaino A, Ferrara G, Orabona P, Donofrio V, Staibano S, De Rosa G. Smooth muscle tumors of the breast: clinicopathologic features of two cases. Tumori 1994;80:241e5. 18. Levy RD, Degiannis E, Obers V, Saadia R. Leiomyosarcoma of the breast. A case report. S Afr J Surg 1995;33(15e7) (discussion 17e18). 19. Falconieri G, Della Libera D, Zanconati F, Bittesini L. Leiomyosarcoma of the female breast: report of two new cases and a review of the literature. Am J Clin Pathol 1997;108:19e25.
N. Fujita et al. / The Breast 20 (2011) 389e393 20. Ugras S, Dilek ON, Karaayvaz M, Dilek H, Peker O, Barut I. Primary leiomyosarcoma of the breast. Jpn J Surg 1997;27:1082e5. 21. Gonzalez-Palacios F. Leiomyosarcoma of the female breast. Am J Clin Pathol 1998;109:650e1. 22. Gupta RK, Kenwright D, Naran S, Lallu S, Fauck R. Fine needle aspiration cytodiagnosis of leiomyosarcoma of the breast. A case report. Acta Cytol 2000 NoveDec;44:1101e5. 23. Szekely E, Madaras L, Kulka J, Jaray B, Nagy L. Leiomyosarcoma of the female breast. Pathol Oncol Res 2001;7:151e3. 24. Kusama R, Fujimori M, Hama Y, Shingu K, Ito K, Mochizuki Y, et al. Stromal sarcoma of the breast with leiomyosarcomatous pattern. Pathol Int 2002 Aug;52:534e9. 25. Shinto O, Yashiro M, Yamada N, Matsuoka T, Ohira M, Ishikawa T, et al. Primary leiomyosarcoma of the breast: report of a case. Surg Today 2002;32:716e9. 26. Jun Wei X, Hiotis K, Garcia R, Hummel Levine P. Leiomyosarcoma of the breast: a difficult diagnosis on fine-needle aspiration biopsy. Diagn Cytopathol 2003;29:172e8. 27. Markaki S, Sotiropoulou M, Hanioti C, Lazaris D. Leiomyosarcoma of the breast. A clinicopathologic and immunohistochemical study. Eur J Obstet Gynecol Reprod Biol 2003;106:233e6. 28. Liang WC, Sickle-Santanello BJ, Nims TA, Accetta PA. Primary leiomyosarcoma of the breast: a case report with review of the literature. Breast J 2003;9(6):494e6. 29. Adem C, Reynolds C, Ingle JN, Nascimento AG. Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature. Br J Cancer 2004;91:237e41.
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30. Jayaram G, Jayalakshmi P, Yip CH. Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features. Acta Cytol 2005;49:656e60. 31. Lee J, Li S, Torbenson M, Liu QZ, Lind S, Mulvihill JJ, et al. Leiomyosarcoma of the breast: a pathologic and comparative genomic hybridization study of two cases. Cancer Genet Cytogenet 2004;149:53e7. 32. Stafyla VK, Gauvin JM, Farley DR. A 53-year-old woman with a leiomyosarcoma of the breast. Curr Surg 2004;61:572e5. 33. Munitiz V, Rios A, Canovas J, Ferri B, Sola J, Canovas P, et al. Primitive leiomyosarcoma of the breast: case report and review of the literature. Breast 2004;13:72e6. 34. Gupta RK. Needle aspiration cytology and immunohistologic findings in a case of leiomyosarcoma of the breast. Diagn Cytopathol 2007;35:254e6. 35. Vu LT, Luce J, Knudson MM. Image of the montheleiomyosarcoma of the breast. Arch Surg 2006 Dec;141:1263e4. 36. De la Pena J, Wapnir I. Leiomyosarcoma of the breast in a patient with a 10year-history of cyclophosphamide exposure: a case report. Cases J 2008;7(1):301. 37. Wong LC, Huang PC, Luh SP, Huang CS. Primary leiomyosarcoma of the nippleareola complex: report of a case and review of literature. J Zhejiang Univ Sci B 2008;9:109e13. 38. Cobanoglu B, Sezer M, Karabulut P, Ozer S, Murat A. Primary leiomyosarcoma of the breast. Breast J 2009;15:423e5. 39. Suit HD, Mankin HJ, Wood WC, Gebhardt MC, Harmon DC, Rosenberg A, et al. Treatment of the patient with stage M0 soft tissue sarcoma. JCO 1988;6:854e62.
Contents lists available at ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Review
Leiomyosarcoma of the breast: A case report and review of the literature about therapeutic management Noriko Fujita a, c, *, Ryo Kimura a, Jun Yamamura a, Kenji Akazawa a, Tsutomu Kasugai b, Fumine Tsukamoto a a b c
Department of Breast and Endocrine Surgery, Osaka Kosei-Nenkin Hospital, Japan Department of Pathology, Osaka Kosei-Nenkin Hospital, Japan Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 May 2010 Received in revised form 28 September 2010 Accepted 17 March 2011
We experienced a leiomyosarcoma of the breast in an 18-year-old female. No specific treatment has been established. In order to clarify appropriate therapeutic management methods, the limited data available from our and previous case reports were assessed. A leiomyosarcoma of the breast must be excised with a negative margin. If the tumor size is large and an adequate margin, greater than 3-cm margin around the excised tumor, is not achieved due to anatomical constraints, radiotherapy may be indicated. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Leiomyosarcoma Breast Surgery Therapeutic management
Introduction A leiomyosarcoma of the breast is exceedingly rare. Up to now only 44 cases of genuine leiomyosarcoma of the breast have been documented in the literature,1e38 and no specific treatment has been established. We experienced a case of an 18-year-old female with a leiomyosarcoma of the breast, and attempted to clarify appropriate therapeutic management methods based on the limited data available from those case reports.
Case report An 18-year-old female patient with no prior medical problems presented with a slowly growing tumor in the center of the right breast. The tumor had enlarged rapidly in the prior eight months. Her mother had breast cancer at age 40. A fine needle aspiration biopsy demonstrated no malignant findings in the cytological features. However, the tumor was, grossly, thought to be malignant. Thus, she was introduced to our hospital for further examination in order to ascertain the histological findings, and definitive treatment. * Corresponding author. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: þ81 6 6879 3772; fax: þ81 6 6879 3779. E-mail address: [email protected] (N. Fujita). 0960-9776/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2011.03.001
Physical examination showed an elastic-hard tumor, 7.2 6.8 cm in size with a well-defined mass, in her right breast. The skin was invaded and the nipple was dimpling. No axillary lymph nodes were palpable. No other findings on her general physical examination were remarkable. Her laboratory data and the values of tumor markers, including CEA 1 ng/ml and CA15-3 5.5 U/ ml, were within normal limits. The mass appeared to be lobulated on ultrasonography. A Computed tomography showed a phyllodeshaped high density area in her right breast, and showed no metastasis in the whole body, including the bilateral lung, liver and axillary lymph node (Fig. 1(a)). Magnetic resonance imaging showed a phyllode-shaped hyper-intensity mass on enhanced imaging in her right breast, and showed that deep fascia was not involved (Fig. 1(b)). Ultrasound-guided vacuum-assisted breast biopsy revealed spindle cells in the histological findings (Fig. 2(a)). Based on the results in those examinations, the preoperative diagnosis of leiomyosarcoma in the right breast was obtained. A simple mastectomy with sentinel lymph node biopsy was selected. The surgical specimen from the tumor was hard in consistency and whitish-gray in color; necrosis was identified. The tumor was an elastic-hard tumor, 7.0 cm in size. Hematoxylin and eosin staining showed many bundles of spindle cells under low magnification, and showed necrosis in the tumor and polymorphic cells with occasional mitotic activity under high magnification. Mitotic figures were frequently observed and averaged six per ten high power fields (Fig. 2(b)). Immunohistochemical staining
Fig. 1. (a) Computed tomography showed a phyllode-shaped high density area on the breast, and also showed no metastasis of the bilateral lungs, liver and axillary lymph node. (b) Magnetic resonance imaging showed a phyllode-shaped hyper-intensity mass on enhanced imaging, and showed that deep fascia was not involved.
Fig. 2. (a) Ultrasound-guided vacuum-assisted breast biopsy showed spindle cells by hematoxylin and eosin staining (H & E 100). (b) Higher magnification showed nuclear atypia and mitotic figures (H & E 400). (c) Higher magnification showed Mib-1LI 10% (400). (d) Enzyme-antibody stain using antibody against a-smooth muscle actin was positive (400). (e) Immunohistochemical study of desmin was positive (400).
N. Fujita et al. / The Breast 20 (2011) 389e393
391
Table 1 Review of cases of primary leiomyosarcoma of the breast. Author
Year Sex Age Side Location Size (cm)
Mitosis
Treatment
Meta
Crocker and Murad1 Haagensen2 Pardo-Mindan3 Barnes4
1969 1971 1974 1977
M F F F
51 77 49 55
R L L L
E AC E
5 8 7 3
common very frequent 16/10 HPF 10/10 HPF
radical mastectomy mastectomy simple mastectomy simple mastectomy
NET NET NET NET
Hernandez5
1978 M
53
L
E
4
15/10 HPF
NET
Chen Callery7 Callery Yatsuka8 Gobardhan9
1981 1984 1984 1984 1984
F F F F F
59 56 54 56 50
L
CD
3/10 HPF
L L
E D
5.6 2 3 1.5 9
hepatic metastasis NET NET NET NET
alive, alive, alive, alive, alive,
Nielsen10
1984 F
24
R
E
1.5(1962)r, 1 (1965) r, 2 (1966) r
2/10 HPF, 8/10 HPF, 14/10 HPF
modified radical mastectomy simple mastectomy simple mastectomy simple mastectomy radical mastectomy modified radical mastectomy excision in 1960. 1962 excision, excision and simple mastectomy
alive, 14 years alive, 6 months died 4 years 4 months later with basilar arterythrombosis alive, 1 year 2 months
died 20 years later
Yamashina11 Arista-Nasr12
1987 F 1989 F
62 50
L R
B
11/10 HPF 4/10 HPF
simple mastectomy local excision
Parham13
1992 F
52
L
CD
2.5 4.5 (1980), 2.3 (1986) r 3
29/10 HPF
mastectomy
1992 F
60
L
E
Waterworth15
1992 F
58
L
C
2, 4 (18 10/10 HPF months later) 4 10/10 HPF
local recurrence & systemic recurrence (brain, skin, thyroid, kidney) NET local recurrence, no metastasis local & systemic recurrence, (brain, lung) local recurrence
Wei16
1993 F
36
R
C
4
Boscaino
1994 F
56
R
C
2.5 / 4
Boscaino
1994 F
45
L
D
1.9 / 2.2
Levy18 Falconieri19 Falconieri Ugras20
1995 1997 1997 1997
F F F F
35 83 86 47
R R R R
D E E E
4 6 8 2
Gonzalez-Palacios21 1998 F 2000 F Gupta22
62 80
L L
C AC
3 6.5
Szekely23 Kusama24
2001 F 2002 F
73 55
R L
B C
4.8 0.5
Shinto25
2002 F
59
L
CDEAB
12
wide local excision with level 2 axillary LN sampling modified radical mastectomy 2/10 HPF excise (1981) / radical mastectomy (1984) 2/10 HPF biopsy (1985) / wide local excision (1989) 2/10 HPF simple mastectomy 20/10 HPF radical mastectomy 11/10 HPF simple mastectomy 3/10 HPF subcutaneous simple mastectomy 10/10 HPF simple mastectomy 5e8/10 HPF mastectomy with axillary clearance 20e22/10 HPF mastectomy few excisions (1996, 1997) / simple mastectomy (1998) 19/10 HPF simple mastectomy
Jun Wei26 Markaki27
2003 F 2003 F
52 42
R R
B
4 14
22/10 HPF 50/10 HPF
Markaki
2003 F
65
L
5,2
10/10 HPF
Liang28 Adem29 Adem Jayaram30
2003 2004 2004 2004
F F F F
25 67 55 55
L
C
5/10 HPF
R
BD
4 2 4 12
2004 F
44
3
6e12/10 HPF
2004 F
52
4.5
6e12/10 HPF
2004 F
53
L
CDEAB
23
2004 F
58
R
C
4
14/10 HPF
Gupta Vu and Knudson35 De la Pena36 Wong37 Cobanoglu38
2006 2006 2008 2008 2009
F F F F F
37
R
D
15/10 HPF
50 52 64
L L L
C C C
8 23 3.2 1.5 3.5
present report
2010 F
18
R
EABCD
7.2
10/10 HPF
6
Lonsdale
14
17
Lee
31
Lee Stafyla32 33
Munitiz
34
NET: No evidence of tumor. HPF: High power field.
21/10 HPF 5/10 HPF
7/10 HPF 12/10 HPF
excise / mastectomy
excision wide modified radical mastectomy excision not major surgery excision excision mastectomy modified radical mastectomy partial or simple mastectomy partial or simple mastectomy modified radical mastectomy modified radical mastectomy wide lumpectomy mastectomy mastectomy mastectomy modified radical mastectomy simple mastectomy
NET systemic recurrence (brain, bone), left breast local recurrence / NET local recurrence
Final follow up
15 years 39 months 53 months 4 years 7 months 2 years
alive, 2 years 2 months alive, 6 years 4 months alive, 6 months alive, 3 months, post-mastectomy alive, 1 year died 14 months later alive, 9 years (3 þ 6)
NET NET NET NET
alive, 40 months,post wide local excision alive, 6 months alive, 10 months alive, 8 months alive, 1 year 6 months
NET NET
alive, 17 years alive, 2 years
NET alive, 1 year 2local recurrence, systemic alive, 4 years 8 months metastasis (lung, bone) with lung bone metastasis local & systemic alive, 8 months recurrence (lung) NET alive, 3 months NET alive, 3 years NET
alive, 18 months
NET alive, 32 months local & systemic recurrence died 7 months later systemic recurrence died 77 months later local recurrence NET
alive, 13 months
NET
alive, 17 months
NET
alive, 2 years
NET
alive, 1 year
NET NET NET NET NET
alive, alive, alive, alive, alive,
NET
alive, 5 years
36 months 10 months 11 months 4 days 22 months
392
N. Fujita et al. / The Breast 20 (2011) 389e393
was positive for a-smooth muscle actin, vimentin, desmin but not for S-protein (Fig. 2 (cee)). No sentinel node metastasis was found. We made the diagnosis of leiomyosarcoma according to the WHO classification. We determined that the grade and stage of the tumor was T2N0M0 and Grade 2 based on the AJCC staging system. Pathological assessment revealed that the width of surgical margin was greater than 3-cm. At five years after surgery, this patient had shown no evidence of local recurrence or metastases. Discussion A leiomyosarcoma of the breast is exceedingly rare disease. Up to now only 45 cases of genuine leiomyosarcoma of the breast, including this patient, have been documented in the literature (Table 1).1e38 No specific treatment has been established. Thus, we attempted to clarify appropriate therapeutic management methods for affected patients based on the limited data available from our and previous case reports. The basis of the treatment is surgery, either local excision or mastectomy (simple or modified radical mastectomy). Local excisions were performed in 1210,12,14,15,17,24,26e29,34 cases. Of those, six patients10,14,17,24,29 had a tumor sized less than 3 cm, of which five10,14,17,24 had local recurrence following resection because of an inadequate margin. In the six12,15,26e28,34 patients with a tumor sized 3 cm or greater, only one12 had local recurrence following resection, in whom, the excision left a 5-mm margin of mammary tissue, which was thought to be inadequate. Mastectomies were performed in 331e9,11,13,16,18e23,25,27,29e33,35e38 cases including our report. Of those cases, five7,8,11,20,37 had a tumor sized less than 3 cm, no case had local and systemic recurrence. In 28 patients with a tumor sized 3 cm or greater, six6,13,16,25,29,30 had local or systemic metastasis. In two13,25 of those recurred six patients, one underwent an open surgical biopsy for the differential diagnosis and the other underwent a simple mastectomy as a benign phyllodes tumor, which was 7.3 12.0 8.0 cm in size. We think that the margins were not adequate in those two cases. The other four16,25,29,30 case reports did not provide detailed descriptions about the clinical courses or operative findings. It appears that the type of surgical excision, whether excisional biopsy, simple mastectomy, or modified radical mastectomy, does not affect prognosis as long as the tumor is excised with an adequate margin. In the present case, we performed a simple mastectomy and the width of the margin was obtained at least 3 cm. We hoped to recommend an adequate margin width around the excised tumor based on the previous case reports. However, we could not clarify the margin width in those studies due to lack of descriptions, as only a few papers stated concrete widths. For example, local recurrence occurred in a 1-cm margin in a case,14 while did not occur in a 2-cm margin in another case.28 And local recurrence did not occur in the width of the margin obtained, in mastectomy procedures, at least 3 cm.9 In addition, in a patient with a tumor sized less than 3 cm, a 2-cm margin is considered necessary when planning breast-conserving surgery. A leiomyosarcoma tends to develop local recurrence. Accordingly, we recommend a greater than 3-cm margin as an adequate margin. In addition, an axillary lymph node dissection was performed in 151,5,8,9,15,16,19,22,23,25,27,30,32,33,38 of the 45 cases. None were reported to have axillary lymph node metastasis. Thus, it is unlikely that axillary node dissection affords benefit. In the present case, we were uneasy about the exact histological diagnosis due to the rarity of the disease. Accordingly, we wanted to confirm that there was no lymph node metastasis by performing a sentinel node biopsy. A few of the reports noted about adjuvant therapy used in cases of leiomyosarcoma of the breast. Three patients24,29,30 were offered
chemotherapy. However, one patient had multiple lung metastases and local recurrence developed at 12 months after surgery in spite of chemotherapy with vincristine, adriamycin, cyclophosphamide, and dacarbazine.24 Another had local recurrence after two cycles of adriamycin.30 The third case did not provide detailed descriptions.29 We found only three case reports applied for radiotherapy to treat leiomyosarcoma of the breast.30,32,35 In two of those,32,35 a wide excision was not possible due to anatomical constraints. The third reported local recurrence after surgery. Good results were obtained in those three cases. Radiotherapy is a well-established treatment used to reduce local recurrence of leiomyosarcomas in other lesions of the body.39 Accordingly, post operative radiotherapy may be indicated for cases with leiomyosarcoma of the breast. Where a wide excision is not possible due to anatomical constraints, a planned marginal excision plus radiotherapy may be an appropriate means of achieving tumor control. In conclusion, a leiomyosarcoma of the breast must be excised with a negative margin in order to obtain good results. If the tumor size is large and an adequate margin, greater than 3-cm margin around the excised tumor, is not achieved due to anatomical constraints, radiotherapy may be indicated.
Acknowledgments We are indebted to Nobuaki Hirata, MD, for his thoughtful suggestions during the manuscript preparation.
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