CEREBELLAR METASTASIS OF UTERINE LEIOMYOSARCOMA.
Follow-up CT scans designated the presence of residual tumour, measuring 2 cm in maximum diameter, while additionally displayed abundant metastatic foci both in the lungs and in the abdominal cavity. Adjuvant radiotherapy was introduced. The patient died of cardiopulmonary arrest 6 weeks after the removal of the metastatic tumor.
Leiomyosarcoma has been defined by the World Health Organization of Tumors as a malignant neoplasm composed of cells demonstrating smooth muscle differentiation and accounts for 25-36% of all sarcomas of the uterus and slightly over 1% of all uterine malignancies. The prognosis chiefly depends upon the extent of spread, and the overall 5-year survival rates extend from 15-25% (21). This aggressive biological behavior is associated to its strong tendency of recurrence, local spread and more often hematogenous dissemination. In fact, the majority of the patients recur within 2 years from diagnosis and about 90% show distant relapses alone or in combination with pelvic recurrences (6). Most frequent sites are the lungs, the peritoneal cavity and the liver. The metastatic potential is interpreted by its location within the myometrium, which enables the early vascular invasion. In addition, certain characteristics of the neoplasm, such as tumor size larger than 3cm, mitotic count >5MF/10HPF, moderate to severe nuclear atypia, coagulative necrosis and epithelioid cell type, serve as predisposing factors for the development of metastasis (10).
Thorough review of the literature (including case reports and autopsy series) revealed 22 documented cases of brain and skull metastasis from uterine leiomyosarcoma (2-3, 5-10, 12-14, 16-20, 22-24, 26). In decreasing order of frequency, the most common intracranial sites were the cerebrum (15 cases), skull (4), pons (1), sphenoid sinus (1) and cerebellum (1). The age, the time interval between the uterine leiomyosarcoma diagnosis and the confirmation of metastasis and the survival time were not available in all subjects. Moreover, several cases were included in autopsy series, without specifying if the primary tumour was a leiomyosarcoma or another malignant mesenchymal neoplasm of the uterus. Albeit, it should be noted that: (i) the patient mean age was 51.1 years (range 35-72 years); (ii) the mean time interval between the initial diagnosis of the primary tumour and the detection of the intracranial lesion was 37.83 months (range 3-116 months); and (iii) the mean survival of the patients after resection of the metastatic tumor was 12.13 months (range 3 days-36 months). The majority of brain metastases were supratentorial, mainly in frontal and parietal lobes. The most frequently applied treatment was neurosurgical resection followed by adjuvant radiotherapy. This combination has improved the survival time; conservative management conferred only 4 months.
Of particular importance is the fact that most patients developed pulmonary metastases. This phenomenon is well recognized in patients with metastases of sarcoma to the brain and has served as a theory suggesting that the uterine malignancy is disseminated hematogenously to the central nervous system (CNS) after lung invasion by pulmonary arterial circulation (4). A second possible route for metastasis is the paravertebral venous system.
Hematogenous spread of sarcoma to the CNS is quite uncommon. Alveolar soft-part sarcoma, fibrosarcoma, leiomyosarcoma, osteosarcoma, malignant fibrous histiocytoma and rhabdomyosarcoma encompass the most frequent sarcoma types which metastasize to the brain (5, 18). Cerebellar metastases comprise approximately 15% of all CNS metastatic lesions in patients with systemic cancer, with the lung, breast and gastrointestinal tract being the most common primary sites. Metastatic sarcomas to the cerebellum are extremely rare. In fact, only 4 case reports have been previously published, including two osteosarcomas, one Ewing sarcoma and one uterine leiomyosarcoma (1-2, 11, 15).
The main symptoms which accompany metastatic lesions are severe headache, gait disturbance and motor deficit. Cerebellar metastases are associated with worse prognosis than metastases in cerebral hemispheres due to obstructive hydrocephalus and brain stem compression. Neurosurgical removal of the lesion, followed by radiation therapy, is regarded as the most pertinent treatment for metastases to the cerebellum, regardless of the primary tumour histology (25). To our knowledge, this is the second reported case of an uterine leiomyosarcoma metastatic to cerebellum, suggesting that hematogenous dissemination of this tumor plays a key role in the course of the disease, CNS metastasis is associated with dismal prognosis and stressing the importance of including this entity in the complete differential diagnosis of CNS lesions occurring in female oncologic patients.
Contributed by Ioannis Venizelos, Eleftherios Anagnostou, Thomas Papathomas, Vasilios Spandos, Dimitrios Marinopoulos, Parmenion Tsitsopoulos, Christos Tsonidis