- Email: [email protected]
Primary leiomyosarcoma of bone: a report on three patients
Clinical Imaging 32 (2008) 321 – 325
Primary leiomyosarcoma of bone: a report on three patients Hakan Atalar a,⁎, Cuneyd Gunay a , Yusuf Yildiz b , Yener Saglik b a
Department of Orthopaedic Surgery and Traumatology, Fatih University, Alparslan Turkes Caddesi No. 57, 06510 Emek/Ankara, Turkey b Department of Orthopaedic Surgery and Traumatology, Ankara University, Sihhiye PK 06100, Ankara, Turkey Received 5 August 2007; accepted 20 October 2007
Abstract Primary leiomyosarcoma of bone is a rare aggressive tumor that occurs mainly in older people. It resembles other malignancies clinically and radiologically, and differential diagnosis is based on histopathology, including immunohistochemistry. If leiomyosarcoma is found in bone, the possibility that it is a metastasis from a distant tumor should be investigated. The treatment is surgical excision with wide margins. Here we present three patients who had primary leiomyosarcoma of radius, ilium, and femur, respectively, and who were treated surgically. © 2008 Elsevier Inc. All rights reserved. Keywords: Bone neoplasms; Leiomyosarcoma; Diagnostic imaging; Differential diagnosis
1. Introduction Leiomyosarcoma is a spindle cell malignant neoplasm with smooth muscle differentiation, and in extragnathic bones, it rarely occurs as a primary tumor [1]. Pain is the presenting symptom in most patients with this disease. The tumor generally affects older people [1]. Radiologically, leiomyosarcoma appears as an osteolytic lesion with aggressive features, such as endosteal scalloping, permeation, poor definition of margins, and lack of sclerosis [2]. Radiological differential diagnosis includes other aggressive bone tumors such as malignant lymphoma, plasmacytoma, and malignant fibrous histiocytoma of bone [2]. Either immunohistochemistry or electron microscopy is necessary for a definitive diagnosis of leiomyosarcoma [1,3]. Histopathologically, leiomyosarcoma may be misdiagnosed as malignant fibrous histiocytoma, fibrosarcoma, malignant spindle cell sarcoma, or inflammatory myofibroblastic tumor of bone [1,4–7].
⁎ Corresponding author. Alparslan Turkes Caddesi No. 57 06510, Emek/Ankara, Turkey. Tel.: +90 312 212 62 62; fax: +90 312 215 36 14. E-mail address: [email protected] (H. Atalar). 0899-7071/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2007.10.022
Metastases to the lung occur in approximately 50% of patients with leiomyosarcoma within 5 years [2]. Neoadjuvant and adjuvant chemotherapy have not provided an improved prognosis, and radiotherapy has not been shown to be effective in treating leiomyosarcoma [2]. Wide excision is the mainstay of treatment. In this article, we describe three patients who had primary leiomyosarcoma of bone and discuss the relevant literature. Consent for publication was obtained from Patient 1 and Patient 3 themselves and from the nearest relative of Patient 2. 2. Patient 1 A 60-year-old male presented with a 3-month history of pain and mass at his right distal radius. He had no history of trauma. Physical examination revealed an immobile tender mass 2 × 3 cm in size. He had no palpable lymphadenopathy. His past medical history was unremarkable. A plain radiograph showed an ill-defined, permeative lytic lesion and cortical thinning (Fig. 1A, B). Magnetic resonance imaging revealed a lesion 6 cm in length at the distal radius, with invasion of the bone and surrounding soft tissues (Fig. 1C). Computed tomography showed no lesions in the thorax or abdomen.
322
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
Fig. 1. In Patient 1, (A) anteroposterior and (B) lateral radiographs revealed an ill-defined, permeative lytic lesion and cortical thinning in the right radius. (C) In Patient 1, this coronal magnetic resonance image with protein density-weighted inversion recovery shows a hyperintense lesion in the distal radius with invasion of the soft tissues medially and laterally. (D) In Patient 1, parallel arrays of atypical spindle cells having elongated nuclei with blunted ends are visible on this light-microscopy image. Mitotic figures are readily seen. Neither osteoid nor chondroid is present. Tumor cells demonstrate strong reactivity for α SMA and desmin (hematoxylin–eosin, 400×). (E) In Patient 1, due to osteomyelitis, there was no union between the carpal bones and the fibular graft, and destruction of the carpal bones was also apparent.
An incisional biopsy was performed for diagnosis. Macroscopically, the tumor was grey in color. Lightmicroscopy examination revealed proliferation of spindle cells with elongated nuclei. Each cell contained abundant acidophilic cytoplasm. Tumor cells demonstrated strong reactivity for α smooth muscle actin (SMA), desmin, and vimentin (Fig. 1D). A diagnosis of high-grade leiomyosarcoma was made. Surgical resection was performed with a margin of at least 2 mm around the tumor, and the bone defect was filled with a vascularized fibular bone graft. Adjuvant chemotherapy (ifosfamide and Adriamycin) and radiotherapy (total 5000 cGy) were applied. At 4 months after surgery, osteomyelitis
developed (Fig. 1E). Antibiotics and hyperbaric oxygen therapy were tried for 8 months but were unsuccessful, and below-elbow amputation was performed. In the 19 months since the initial diagnosis, computed tomography at 6-month intervals has shown no pulmonary metastases. In the 7 months since the amputation, there has been no local recurrence of the tumor or osteomyelitis.
3. Patient 2 A 57-year-old female presented with a 6-month history of pain and mass in her right groin. Her medical history was
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
unremarkable. A plain radiograph of the pelvis revealed an ill-defined, destructive, lytic lesion at the right ilium and an associated soft tissue mass (Fig. 2A). Magnetic resonance imaging revealed a lesion 20 × 10 × 16 cm in size, with invasion of the ilium and surrounding soft tissue (Fig. 2B). There was neither metastasis nor lymphadenopathy on chest and abdominal computed tomography. An incisional biopsy revealed high-grade leiomyosarcoma. Preoperative chemotherapy was performed with ifosfamide and Adriamycin, but imaging methods revealed no effect on the size of the mass. An anterior flap external hemipelvectomy was performed with a negative margin of at
323
least 1.3 mm. Pathological examination demonstrated large areas of necrosis in the mass. Postoperative chemotherapy (ifosfamide, Adriamycin) and radiation therapy (total 5800 cGy) were provided. At 18 months after surgery, local recurrence and pulmonary metastases developed. The patient died 4 months later while continuing chemotherapy. 4. Patient 3 A 59-year-old male patient presented with pathological fracture of the right femur. The patient said he had experienced pain in the distal right thigh for the past 4 months. He had no palpable lymphadenopathy. A plain radiograph of the distal femur showed an osteolytic lesion with pathological fracture (Fig. 3A). Magnetic resonance imaging likewise showed pathological fracture, with a lesion 11 cm in length invading the distal femur and the surrounding soft tissues (Fig. 3B, C). Pulmonary and abdominal computed tomography images were normal. An incisional biopsy revealed high-grade leiomyosarcoma. The patient received neoadjuvant chemotherapy (ifosfamide, Adriamycin), but imaging methods demonstrated no change in the size of the lesion. A midfemoral amputation was performed. Microscopic examination of surgical specimens revealed no necrosis in the tumor. In 15 months of postoperative follow-up, there has been no evidence of metastasis or local recurrence. 5. Discussion
Fig. 2. (A) In Patient 2, a plain radiograph showed destruction of the right ilium and a soft tissue mass. (B) In Patient 2, this postcontrast coronal T1weighted magnetic resonance image shows invasion of the ilium and areas of necrosis within the lesion.
Leiomyosarcoma is a malignant soft-tissue tumor arising from smooth muscle. Primary leiomyosarcoma of bone is very rare, and its etiology is unclear [8]. The histological features of leiomyosarcoma of bone are the same as those of leiomyosarcoma found in other tissues. There are two main hypotheses about the origin of primary leiomyosarcoma of bone; the first is that it arises from vascular smooth muscle, and the second is that it arises from an intermediate cellular form capable of smooth muscle differentiation [1]. Patients with primary leiomyosarcoma of bone generally present with pain and sometimes with mass. Both genders are equally affected [1,3]. Different age groups may be affected by this tumor, but it generally occurs in older patients [1]. When the tumor originates in extragnathic bones, the most common sites of origin are epiphyseal or metaphyseal locations in the femur or tibia; pelvic origins are rare [3,9,10]. The radius is also an unusual location for this tumor [1]. Some patients may present with pathological fractures [9]. If bone and soft tissue together are affected by this tumor, it may be difficult to decide which one is the tissue of origin. If the amount of tumor tissue is greater in the bone than in the soft tissue, the tumor may be considered to have arisen in the bone [1]. We therefore considered the leiomyosarcomas in
324
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
Fig. 3. (A) In Patient 3, this preoperative plain radiograph showed pathological fracture, destructive changes, and sclerosis at the fracture region in the distal femur. (B) In Patient 3, this preoperative sagittal T1-weighted magnetic resonance image showed a lesion invading the epiphysis and metaphysis of the femur and protruding from the fracture region in a posterosuperior direction. (C) In Patient 3, this postcontrast coronal T1-weighted magnetic resonance image shows the fracture and invasion of bone and soft tissue.
our patients to be primary bone tumors, in spite of the additional soft tissue involvement. Primary extraosseous leiomyosarcoma may metastasize to bone [3]. The gastrointestinal tract and uterus should be investigated in this context since they are the most common tissues of origin [1]. In leiomyosarcoma metastases to bone, the bone lesions are generally less than 4 cm in length [11], whereas primary lesions are generally more than 7 cm in length [12]. If there is no extraosseous primary tumor, a diagnosis of primary leiomyosarcoma of bone can be made. Primary leiomyosarcoma of bone can metastasize to other tissues, the most frequent being the lungs, followed by the lumbar spine and liver [3,11]. Metastases to the adrenal gland, kidney, and lymph nodes also rarely occur [11]. In our patients, preoperative chest and whole-abdomen computerized tomography was performed to look for extraosseous lesions. On plain radiographs, leiomyosarcoma of bone generally shows an indistinct tumor margin, osteolysis, endosteal erosion, cortical breakthrough, and a permeative pattern; soft tissue invasion may also be present [11]. The lack of a sclerotic margin is also characteristic of this tumor; however, perilesional sclerosis may be seen on plain radiographs in low-grade primary leiomyosarcoma [9]. In our Patient 3, the radiograph showed sclerosis at the fracture site (Fig. 3A). Since other aggressive neoplasms in bone can have a similar appearance, plain radiographs alone are insufficient for making a differential diagnosis. On imaging studies, the lack of matrix in long-bone lesions raises the diagnostic possibility of lymphoma, plasmacytoma, malignant fibrous histiocytoma, fibrosarcoma of bone, inflammatory myofibroblastic tumor, osteomyelitis, and Ewing sarcoma [2].
On magnetic resonance imaging, leiomyosarcoma is isointense to muscle on T1 images and gives heterogeneous high signal intensity on T2 images [3,12]. In relation to fat, the tumor can give hypo- or isointensity on conventional and fast spin-echo sequences [12]. Gadolinium injection usually gives enhancement in the tumor's periphery [11,12]. In Figs. 2B and 3C, extensive contrast enhancement is visible. Rarely, spoke-wheel-like enhancement may occur due to central tumor necrosis and/or septa [11]. In our Patient 2, postcontrast T1-weighted images revealed areas of necrosis within the lesion (Fig. 2B). In all three patients, tumors were hypointense relative to fluid on T2-weighted images. Light microscopy of leiomyosarcoma shows proliferation of atypical spindle cells and elongated nuclei with blunted ends [3]. Microscopic evidence of necrosis has been encountered in 30% of patients [1]. In all three of our patients, spindle cells were focally arranged in fascicles with eosinophilic cytoplasm. Areas of necrosis were seen in Patient 2. All three tumors were histologically high grade [7]. For definitive diagnosis of leiomyosarcoma, either immunohistochemistry or electron microscopy is necessary [1,3]. Immunohistochemical tests useful for this tumor include α SMA, vimentin, desmin, common muscle actin, and low-molecular-weight keratin [1]. In our patients, the reactivity for α SMA was positive, as was reactivity for desmin, a marker of myogenic differentiation. Immunohistochemical staining for vimentin was also positive in all three patients. In the differential diagnosis, fibrosarcoma and malignant fibrous histiocytoma can be ruled out via immunohistochemistry because both of these tumors lack the expression of muscle markers [1]. Distinguishing between leiomyosarcoma and myofibrosarcoma may be
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
difficult, however, because both tumors show immunoreactivity for SMA and, to a lesser extent, desmin [1]. On electron microscopy, the cells composing myofibrosarcoma usually have a well-developed, variably dilated, branching rough endoplasmic reticulum, and the parallel arrays of microfilaments are thin and generally restricted to the ectoplasm. A collagenous stroma also is usually more commonly seen in myofibrosarcoma. In contrast, in leiomyosarcoma, the rough endoplasmic reticulum is inconspicuous, whereas microfilaments with interspersed fusiform densities are found in all regions of the cytoplasm [1]. Fibroblastic osteosarcoma should also be considered in the differential diagnosis. Histopathological increased calcifications point to osteosarcoma. Wide excision with adequate normal tissue surrounding the tumor is the mainstay of treatment for leiomyosarcoma. In two of our patients (Patients 1 and 2), a wide surgical margin was not possible due to the local anatomy. Surgical treatment is particularly effective in patients with low-grade tumors [1]. Neoadjuvant and adjuvant chemotherapy have not provided an improved prognosis; the efficacy of radiotherapy in treating leiomyosarcoma has not been shown [2]. For Patients 2 and 3, we used preoperative chemotherapy. In both patients, this had no effect on tumor dimensions. Because our patients' tumors were high grade, we tried adjuvant chemotherapy and radiotherapy in two (Patients 1 and 2). Although we achieved a tumor-free margin in two patients (Patients 1 and 2), one of these (Patient 2) developed local recurrence and died due to pulmonary metastases. In Patient 3, midfemoral amputation was performed as a definitive treatment, and the patient continues to have no evidence of disease 15 months after the operation.
6. Conclusion Primary leiomyosarcoma in extragnathic bones is a rare condition, and for its diagnosis, the presence of extraosseous primary lesions should be ruled out. The efficacy of pre-
325
operative and postoperative radiation or chemotherapy is not clear in the treatment of this tumor. Surgery is currently the best method of treatment. However, obtaining a wide surgical margin may be difficult, and amputation may be necessary for high-grade tumors in the extremities when there is soft tissue involvement. References [1] Antonescu CR, Erlandson RA, Huvos AG. Primary leiomyosarcoma of bone: a clinicopathologic, immunohistochemical, and ultrastructural study of 33 patients and a literature review. Am J Surg Pathol 1997;21: 1281–94. [2] Endo K, Takahashi M, Matsui Y, Hasegawa T, Yasui N. Minimally Invasive Taskforce of the American Association of Hip and Knee Surgeons. Bone tumor of the distal femur in a 67-year-old woman. Clin Orthop 2005;440:262–8. [3] Goto T, Ishida T, Motoi N, Yokokura S, Kawano H, Yamamoto A, Matsuda K, Yamamoto M. Primary leiomyosarcoma of the femur. J Orthop Sci 2002;7:267–73. [4] Angervall L, Berlin O, Kindblom LG, Stener B. Primary leiomyosarcoma of bone: a study of five cases. Cancer 1980;46:1270–9. [5] Wang TY, Erlandson RA, Marcove RC, Huvos AG. Primary leiomyosarcoma of bone. Arch Pathol Lab Med 1980;104:100–4. [6] Sciot R, Dal Cin P, Fletcher CD, Hernandez JM, Garcia JL, Samson I, Ramos L, Brys P, Van Damme B, Van den Berghe H. Inflammatory myofibroblastic tumor of bone: report of two cases with evidence of clonal chromosomal changes. Am J Surg Pathol 1997;21:1166–72. [7] Enzinger FM, Weiss SW. Leiomyosarcoma. In: Enzinger FM, Weiss SW, editors. Soft tissue tumors. 3rd ed. St. Louis: Mosby, 1995. p. 491–510. [8] Miura K, Hatori M, Hosaka M, Kokubun S, Watanabe M, Ehara S. Primary leiomyosarcoma with the invasion into the intertrabecular space of bone: a case report and the review of the literatures. Clin Imaging 2001;25:209–14. [9] Berlin O, Angervall L, Kindblom LG, Berlin IC, Stener B. Primary leiomyosarcoma of bone. A clinical, radiographic, pathologic-anatomic and prognostic study of 16 cases. Skeletal Radiol 1987;16:364–76. [10] Takami KM, Ishida T, Ieguchi M, Kuniyoshi Y, Wakasa K, Sakurai M. Primary leiomyosarcoma or leiomyoma of the pubic bone? A case report. Int Orthop 1994;18:248–51. [11] Shen SH, Steinbach LS, Wang SF, Chen WY, Chen WM, Chang CY. Primary leiomyosarcoma of bone. Skeletal Radiol 2001;30:600–3. [12] Sundaram M, Akduman I, White LM, McDonald DJ, Kandel R, Janney C. Primary leiomyosarcoma of bone. AJR Am J Roentgenol 1999;172:771–6.
Primary leiomyosarcoma of bone: a report on three patients Hakan Atalar a,⁎, Cuneyd Gunay a , Yusuf Yildiz b , Yener Saglik b a
Department of Orthopaedic Surgery and Traumatology, Fatih University, Alparslan Turkes Caddesi No. 57, 06510 Emek/Ankara, Turkey b Department of Orthopaedic Surgery and Traumatology, Ankara University, Sihhiye PK 06100, Ankara, Turkey Received 5 August 2007; accepted 20 October 2007
Abstract Primary leiomyosarcoma of bone is a rare aggressive tumor that occurs mainly in older people. It resembles other malignancies clinically and radiologically, and differential diagnosis is based on histopathology, including immunohistochemistry. If leiomyosarcoma is found in bone, the possibility that it is a metastasis from a distant tumor should be investigated. The treatment is surgical excision with wide margins. Here we present three patients who had primary leiomyosarcoma of radius, ilium, and femur, respectively, and who were treated surgically. © 2008 Elsevier Inc. All rights reserved. Keywords: Bone neoplasms; Leiomyosarcoma; Diagnostic imaging; Differential diagnosis
1. Introduction Leiomyosarcoma is a spindle cell malignant neoplasm with smooth muscle differentiation, and in extragnathic bones, it rarely occurs as a primary tumor [1]. Pain is the presenting symptom in most patients with this disease. The tumor generally affects older people [1]. Radiologically, leiomyosarcoma appears as an osteolytic lesion with aggressive features, such as endosteal scalloping, permeation, poor definition of margins, and lack of sclerosis [2]. Radiological differential diagnosis includes other aggressive bone tumors such as malignant lymphoma, plasmacytoma, and malignant fibrous histiocytoma of bone [2]. Either immunohistochemistry or electron microscopy is necessary for a definitive diagnosis of leiomyosarcoma [1,3]. Histopathologically, leiomyosarcoma may be misdiagnosed as malignant fibrous histiocytoma, fibrosarcoma, malignant spindle cell sarcoma, or inflammatory myofibroblastic tumor of bone [1,4–7].
⁎ Corresponding author. Alparslan Turkes Caddesi No. 57 06510, Emek/Ankara, Turkey. Tel.: +90 312 212 62 62; fax: +90 312 215 36 14. E-mail address: [email protected] (H. Atalar). 0899-7071/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2007.10.022
Metastases to the lung occur in approximately 50% of patients with leiomyosarcoma within 5 years [2]. Neoadjuvant and adjuvant chemotherapy have not provided an improved prognosis, and radiotherapy has not been shown to be effective in treating leiomyosarcoma [2]. Wide excision is the mainstay of treatment. In this article, we describe three patients who had primary leiomyosarcoma of bone and discuss the relevant literature. Consent for publication was obtained from Patient 1 and Patient 3 themselves and from the nearest relative of Patient 2. 2. Patient 1 A 60-year-old male presented with a 3-month history of pain and mass at his right distal radius. He had no history of trauma. Physical examination revealed an immobile tender mass 2 × 3 cm in size. He had no palpable lymphadenopathy. His past medical history was unremarkable. A plain radiograph showed an ill-defined, permeative lytic lesion and cortical thinning (Fig. 1A, B). Magnetic resonance imaging revealed a lesion 6 cm in length at the distal radius, with invasion of the bone and surrounding soft tissues (Fig. 1C). Computed tomography showed no lesions in the thorax or abdomen.
322
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
Fig. 1. In Patient 1, (A) anteroposterior and (B) lateral radiographs revealed an ill-defined, permeative lytic lesion and cortical thinning in the right radius. (C) In Patient 1, this coronal magnetic resonance image with protein density-weighted inversion recovery shows a hyperintense lesion in the distal radius with invasion of the soft tissues medially and laterally. (D) In Patient 1, parallel arrays of atypical spindle cells having elongated nuclei with blunted ends are visible on this light-microscopy image. Mitotic figures are readily seen. Neither osteoid nor chondroid is present. Tumor cells demonstrate strong reactivity for α SMA and desmin (hematoxylin–eosin, 400×). (E) In Patient 1, due to osteomyelitis, there was no union between the carpal bones and the fibular graft, and destruction of the carpal bones was also apparent.
An incisional biopsy was performed for diagnosis. Macroscopically, the tumor was grey in color. Lightmicroscopy examination revealed proliferation of spindle cells with elongated nuclei. Each cell contained abundant acidophilic cytoplasm. Tumor cells demonstrated strong reactivity for α smooth muscle actin (SMA), desmin, and vimentin (Fig. 1D). A diagnosis of high-grade leiomyosarcoma was made. Surgical resection was performed with a margin of at least 2 mm around the tumor, and the bone defect was filled with a vascularized fibular bone graft. Adjuvant chemotherapy (ifosfamide and Adriamycin) and radiotherapy (total 5000 cGy) were applied. At 4 months after surgery, osteomyelitis
developed (Fig. 1E). Antibiotics and hyperbaric oxygen therapy were tried for 8 months but were unsuccessful, and below-elbow amputation was performed. In the 19 months since the initial diagnosis, computed tomography at 6-month intervals has shown no pulmonary metastases. In the 7 months since the amputation, there has been no local recurrence of the tumor or osteomyelitis.
3. Patient 2 A 57-year-old female presented with a 6-month history of pain and mass in her right groin. Her medical history was
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
unremarkable. A plain radiograph of the pelvis revealed an ill-defined, destructive, lytic lesion at the right ilium and an associated soft tissue mass (Fig. 2A). Magnetic resonance imaging revealed a lesion 20 × 10 × 16 cm in size, with invasion of the ilium and surrounding soft tissue (Fig. 2B). There was neither metastasis nor lymphadenopathy on chest and abdominal computed tomography. An incisional biopsy revealed high-grade leiomyosarcoma. Preoperative chemotherapy was performed with ifosfamide and Adriamycin, but imaging methods revealed no effect on the size of the mass. An anterior flap external hemipelvectomy was performed with a negative margin of at
323
least 1.3 mm. Pathological examination demonstrated large areas of necrosis in the mass. Postoperative chemotherapy (ifosfamide, Adriamycin) and radiation therapy (total 5800 cGy) were provided. At 18 months after surgery, local recurrence and pulmonary metastases developed. The patient died 4 months later while continuing chemotherapy. 4. Patient 3 A 59-year-old male patient presented with pathological fracture of the right femur. The patient said he had experienced pain in the distal right thigh for the past 4 months. He had no palpable lymphadenopathy. A plain radiograph of the distal femur showed an osteolytic lesion with pathological fracture (Fig. 3A). Magnetic resonance imaging likewise showed pathological fracture, with a lesion 11 cm in length invading the distal femur and the surrounding soft tissues (Fig. 3B, C). Pulmonary and abdominal computed tomography images were normal. An incisional biopsy revealed high-grade leiomyosarcoma. The patient received neoadjuvant chemotherapy (ifosfamide, Adriamycin), but imaging methods demonstrated no change in the size of the lesion. A midfemoral amputation was performed. Microscopic examination of surgical specimens revealed no necrosis in the tumor. In 15 months of postoperative follow-up, there has been no evidence of metastasis or local recurrence. 5. Discussion
Fig. 2. (A) In Patient 2, a plain radiograph showed destruction of the right ilium and a soft tissue mass. (B) In Patient 2, this postcontrast coronal T1weighted magnetic resonance image shows invasion of the ilium and areas of necrosis within the lesion.
Leiomyosarcoma is a malignant soft-tissue tumor arising from smooth muscle. Primary leiomyosarcoma of bone is very rare, and its etiology is unclear [8]. The histological features of leiomyosarcoma of bone are the same as those of leiomyosarcoma found in other tissues. There are two main hypotheses about the origin of primary leiomyosarcoma of bone; the first is that it arises from vascular smooth muscle, and the second is that it arises from an intermediate cellular form capable of smooth muscle differentiation [1]. Patients with primary leiomyosarcoma of bone generally present with pain and sometimes with mass. Both genders are equally affected [1,3]. Different age groups may be affected by this tumor, but it generally occurs in older patients [1]. When the tumor originates in extragnathic bones, the most common sites of origin are epiphyseal or metaphyseal locations in the femur or tibia; pelvic origins are rare [3,9,10]. The radius is also an unusual location for this tumor [1]. Some patients may present with pathological fractures [9]. If bone and soft tissue together are affected by this tumor, it may be difficult to decide which one is the tissue of origin. If the amount of tumor tissue is greater in the bone than in the soft tissue, the tumor may be considered to have arisen in the bone [1]. We therefore considered the leiomyosarcomas in
324
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
Fig. 3. (A) In Patient 3, this preoperative plain radiograph showed pathological fracture, destructive changes, and sclerosis at the fracture region in the distal femur. (B) In Patient 3, this preoperative sagittal T1-weighted magnetic resonance image showed a lesion invading the epiphysis and metaphysis of the femur and protruding from the fracture region in a posterosuperior direction. (C) In Patient 3, this postcontrast coronal T1-weighted magnetic resonance image shows the fracture and invasion of bone and soft tissue.
our patients to be primary bone tumors, in spite of the additional soft tissue involvement. Primary extraosseous leiomyosarcoma may metastasize to bone [3]. The gastrointestinal tract and uterus should be investigated in this context since they are the most common tissues of origin [1]. In leiomyosarcoma metastases to bone, the bone lesions are generally less than 4 cm in length [11], whereas primary lesions are generally more than 7 cm in length [12]. If there is no extraosseous primary tumor, a diagnosis of primary leiomyosarcoma of bone can be made. Primary leiomyosarcoma of bone can metastasize to other tissues, the most frequent being the lungs, followed by the lumbar spine and liver [3,11]. Metastases to the adrenal gland, kidney, and lymph nodes also rarely occur [11]. In our patients, preoperative chest and whole-abdomen computerized tomography was performed to look for extraosseous lesions. On plain radiographs, leiomyosarcoma of bone generally shows an indistinct tumor margin, osteolysis, endosteal erosion, cortical breakthrough, and a permeative pattern; soft tissue invasion may also be present [11]. The lack of a sclerotic margin is also characteristic of this tumor; however, perilesional sclerosis may be seen on plain radiographs in low-grade primary leiomyosarcoma [9]. In our Patient 3, the radiograph showed sclerosis at the fracture site (Fig. 3A). Since other aggressive neoplasms in bone can have a similar appearance, plain radiographs alone are insufficient for making a differential diagnosis. On imaging studies, the lack of matrix in long-bone lesions raises the diagnostic possibility of lymphoma, plasmacytoma, malignant fibrous histiocytoma, fibrosarcoma of bone, inflammatory myofibroblastic tumor, osteomyelitis, and Ewing sarcoma [2].
On magnetic resonance imaging, leiomyosarcoma is isointense to muscle on T1 images and gives heterogeneous high signal intensity on T2 images [3,12]. In relation to fat, the tumor can give hypo- or isointensity on conventional and fast spin-echo sequences [12]. Gadolinium injection usually gives enhancement in the tumor's periphery [11,12]. In Figs. 2B and 3C, extensive contrast enhancement is visible. Rarely, spoke-wheel-like enhancement may occur due to central tumor necrosis and/or septa [11]. In our Patient 2, postcontrast T1-weighted images revealed areas of necrosis within the lesion (Fig. 2B). In all three patients, tumors were hypointense relative to fluid on T2-weighted images. Light microscopy of leiomyosarcoma shows proliferation of atypical spindle cells and elongated nuclei with blunted ends [3]. Microscopic evidence of necrosis has been encountered in 30% of patients [1]. In all three of our patients, spindle cells were focally arranged in fascicles with eosinophilic cytoplasm. Areas of necrosis were seen in Patient 2. All three tumors were histologically high grade [7]. For definitive diagnosis of leiomyosarcoma, either immunohistochemistry or electron microscopy is necessary [1,3]. Immunohistochemical tests useful for this tumor include α SMA, vimentin, desmin, common muscle actin, and low-molecular-weight keratin [1]. In our patients, the reactivity for α SMA was positive, as was reactivity for desmin, a marker of myogenic differentiation. Immunohistochemical staining for vimentin was also positive in all three patients. In the differential diagnosis, fibrosarcoma and malignant fibrous histiocytoma can be ruled out via immunohistochemistry because both of these tumors lack the expression of muscle markers [1]. Distinguishing between leiomyosarcoma and myofibrosarcoma may be
H. Atalar et al. / Clinical Imaging 32 (2008) 321–325
difficult, however, because both tumors show immunoreactivity for SMA and, to a lesser extent, desmin [1]. On electron microscopy, the cells composing myofibrosarcoma usually have a well-developed, variably dilated, branching rough endoplasmic reticulum, and the parallel arrays of microfilaments are thin and generally restricted to the ectoplasm. A collagenous stroma also is usually more commonly seen in myofibrosarcoma. In contrast, in leiomyosarcoma, the rough endoplasmic reticulum is inconspicuous, whereas microfilaments with interspersed fusiform densities are found in all regions of the cytoplasm [1]. Fibroblastic osteosarcoma should also be considered in the differential diagnosis. Histopathological increased calcifications point to osteosarcoma. Wide excision with adequate normal tissue surrounding the tumor is the mainstay of treatment for leiomyosarcoma. In two of our patients (Patients 1 and 2), a wide surgical margin was not possible due to the local anatomy. Surgical treatment is particularly effective in patients with low-grade tumors [1]. Neoadjuvant and adjuvant chemotherapy have not provided an improved prognosis; the efficacy of radiotherapy in treating leiomyosarcoma has not been shown [2]. For Patients 2 and 3, we used preoperative chemotherapy. In both patients, this had no effect on tumor dimensions. Because our patients' tumors were high grade, we tried adjuvant chemotherapy and radiotherapy in two (Patients 1 and 2). Although we achieved a tumor-free margin in two patients (Patients 1 and 2), one of these (Patient 2) developed local recurrence and died due to pulmonary metastases. In Patient 3, midfemoral amputation was performed as a definitive treatment, and the patient continues to have no evidence of disease 15 months after the operation.
6. Conclusion Primary leiomyosarcoma in extragnathic bones is a rare condition, and for its diagnosis, the presence of extraosseous primary lesions should be ruled out. The efficacy of pre-
325
operative and postoperative radiation or chemotherapy is not clear in the treatment of this tumor. Surgery is currently the best method of treatment. However, obtaining a wide surgical margin may be difficult, and amputation may be necessary for high-grade tumors in the extremities when there is soft tissue involvement. References [1] Antonescu CR, Erlandson RA, Huvos AG. Primary leiomyosarcoma of bone: a clinicopathologic, immunohistochemical, and ultrastructural study of 33 patients and a literature review. Am J Surg Pathol 1997;21: 1281–94. [2] Endo K, Takahashi M, Matsui Y, Hasegawa T, Yasui N. Minimally Invasive Taskforce of the American Association of Hip and Knee Surgeons. Bone tumor of the distal femur in a 67-year-old woman. Clin Orthop 2005;440:262–8. [3] Goto T, Ishida T, Motoi N, Yokokura S, Kawano H, Yamamoto A, Matsuda K, Yamamoto M. Primary leiomyosarcoma of the femur. J Orthop Sci 2002;7:267–73. [4] Angervall L, Berlin O, Kindblom LG, Stener B. Primary leiomyosarcoma of bone: a study of five cases. Cancer 1980;46:1270–9. [5] Wang TY, Erlandson RA, Marcove RC, Huvos AG. Primary leiomyosarcoma of bone. Arch Pathol Lab Med 1980;104:100–4. [6] Sciot R, Dal Cin P, Fletcher CD, Hernandez JM, Garcia JL, Samson I, Ramos L, Brys P, Van Damme B, Van den Berghe H. Inflammatory myofibroblastic tumor of bone: report of two cases with evidence of clonal chromosomal changes. Am J Surg Pathol 1997;21:1166–72. [7] Enzinger FM, Weiss SW. Leiomyosarcoma. In: Enzinger FM, Weiss SW, editors. Soft tissue tumors. 3rd ed. St. Louis: Mosby, 1995. p. 491–510. [8] Miura K, Hatori M, Hosaka M, Kokubun S, Watanabe M, Ehara S. Primary leiomyosarcoma with the invasion into the intertrabecular space of bone: a case report and the review of the literatures. Clin Imaging 2001;25:209–14. [9] Berlin O, Angervall L, Kindblom LG, Berlin IC, Stener B. Primary leiomyosarcoma of bone. A clinical, radiographic, pathologic-anatomic and prognostic study of 16 cases. Skeletal Radiol 1987;16:364–76. [10] Takami KM, Ishida T, Ieguchi M, Kuniyoshi Y, Wakasa K, Sakurai M. Primary leiomyosarcoma or leiomyoma of the pubic bone? A case report. Int Orthop 1994;18:248–51. [11] Shen SH, Steinbach LS, Wang SF, Chen WY, Chen WM, Chang CY. Primary leiomyosarcoma of bone. Skeletal Radiol 2001;30:600–3. [12] Sundaram M, Akduman I, White LM, McDonald DJ, Kandel R, Janney C. Primary leiomyosarcoma of bone. AJR Am J Roentgenol 1999;172:771–6.