Primary leiomyosarcoma of bone is a very rare malignancy, consisting of predominantly spindle cell neoplasm exhibiting smooth muscle differentiation thought to originate from either the smooth muscle cells of blood vessels or the mesenchymal myofibroblasts in bone (2). When one encounters a confirmed leiomyosarcoma involving a bone, exclusion of a metastasis from uterus or gastrointestinal tract is a prerequisite. In a review of the literature, Fornasier and Paley found 10 reported cases of metastatic leiomyosarcoma, mostly from the uterus, initially presenting as a skeletal metastasis. Interestingly, the metastases were often to osseous sites that are uncommon for primary leiomyosarcoma such as the skull, spine, and scapula (5).
Since the first case reported by Evans and Sanerkin in 1965 (6), approximately 100 accumulative skeletal leiomyosarcomas have been reported in 1999 (excluding the gnathic bones) (2). Patients' age ranges from 9 to 80 years with an average age of 44.4 years (3). The tumor is rare before 20 years of age. Males are affected slightly more often than females. The usual complaint is pain that may be from several weeks' to 3 years' duration. Long bone of the body are the most common site (femur, tibia, and humerus take up to three quarters). The rest of the cases involve jaw bone, axial skeleton, and phalanx (2).
The typical radiographic appearance is that of a nonspecific but malignant-appearing lytic defect located in the metaphyseal portion of the bone, often with extension into the diaphysis or the epiphysis. The tumor has ill-defined margins and ranges from 2 to 12 cm in greatest dimension. The cortex is frequently destroyed and periosteal reaction is seen in about half of cases. Leiomyosarcoma of bone does not have a typical radiographic appearance and can mimic any other primary or secondary malignant tumor (3).
Grossly, the neoplasm presents as a gray, white, or tan cut surface with focal areas of necrosis. Most cases exhibit soft tissue extension. Compared to leiomyomas, tumors are softer, fleshy, gray-yellow, usually solitary, with irregular margins, and sometimes with hemorrhage and necrosis.
The microscopic appearance is similar to that of soft tissue leiomyosarcoma. Typically, there are interweaving fascicles of spindle cells having prominent eosinophilic, fibrillary cytoplasm. A nonspecific storiform pattern may be present, and the background stroma is variably collagenized. Occasionally, the neoplastic cells are more rounded, with pale to clear cytoplasm. Mitotic figures range from 1 to 35 per 10 high-power fields. Unlike soft tissue leiomyosarcoma, ubiquitous osteoclast-like giant cells are common, usually interspersed in the neoplastic stroma. The histologic analysis showed that the osseous leiomyosarcoma are most commonly of the classic type, followed by epithelioid, myxoid, and pleomorphic variants (3).
Ultrastructurally, the findings are characteristic for smooth muscle differentiation such as intracytoplasmic thin, actin-sized filaments with dense bodies arranged in bundles parallel to the longitudinal axis of the cell. Pinocytotic vesicles are prominent. Immunohistochemically, the cells stain with antibodies directed against muscle specific actin and, less often, desmin. Positivity for cytokeratin varies from widely scattered cells to more extensive staining.
The differential diagnoses of skeletal leiomyosarcomas include fibrosarcomas, malignant fibrous histiocytomas, malignant hemangiopericytoma, epithelioid angiosarcoma, epithelioid hemagnioendothelioma, and spindle cell carcinomas. Immunostaining for muscle specific actin or desmin usually helps to confirm the diagnosis (4). The presence of occasional cytokeratin positivity in leiomyosarcomas mandates the use of a panel of immunohistochemical markers. In the event of equivocal immunohistochemical stains, electron microscopy will aid in differentiating epithelial cells from smooth muscle.
About 50 percent of patients with skeletal leiomyosarcoma die of tumor, mainly due to pulmonary metastases. Widespread metastases, including cutaneous involvement, also have been reported. Amputation is the mainstay of therapy. Radiation may relieve pain at metastatic sites, but the role of chemotherapy is currently undetermined.
Primary leiomyosarcoma of bone is a very rare neoplasm. We report a new case with a brief review of literature. The current case is a 43-year-old lady with remote history of uterine leiomyoma for which hysterectomy was performed 13 years prior to current admission. The archive slides from outside hospital were reviewed, and showed an ordinary leiomyoma with no evidence of malignancy. The pathological examination of hemipelvectomy specimen revealed a low-grade leiomyosarcoma that originated from the left iliac wing. The immunoreactivity of Ki67 nuclear antigen, which associated with cell proliferation, is found throughout the cell cycle (G1, S, G2, M phases). However, it is absent in resting (G0) cells (7, 8). The studies of nuclear antigen Ki67 expression in archive material of uterine leiomyoma and current iliac leiomyosarcoma from this patient show a marked difference in nuclear staining. Indirectly, the findings support the fact that the two neoplasms of smooth muscle derivation occurred in different organs are not histogenetically related. Complete excision of the tumor was achieved with free surgical margins. Patient recovered from the operation smoothly and underwent rehabilitation therapy without adjuvant therapy for the tumor. At the time of this report, patient appeared to be free of disease.
Contributed by Wen-Wei Chung, MD, PhD, Remigio M. Gregorio, MD.