Childs Nerv Syst (2002) 18:648–651 DOI 10.1007/s00381-002-0628-6
Gianni Bisogno Jelena Roganovic Modesto Carli Giovanni Scarzello Milena Calderone Roberto Faggin Giorgio Perilongo
Received: 13 May 2002 Published online: 15 August 2002 © Springer-Verlag 2002 G. Bisogno (✉) · M. Carli · G. Perilongo Hematology/Oncology Division, Department of Pediatrics, Via Giustiniani, 3, 35128 Padua, Italy e-mail:
[email protected] Tel.: +39-049-8211481 Fax: +39-049-8213510 J. Roganovic Hematology/Oncology Division, Department of Pediatrics, Rijeka, Croatia G. Scarzello Radiotherapy Division, Hospital of Padua, Padua, Italy M. Calderone Neuroradiology Service, Hospital of Padua, Padua, Italy R. Faggin Unit of Pediatric Neurosurgery, Department of Pediatrics, Via Giustiniani, 3, 35128 Padua, Italy
C A S E R E P O RT
Primary intracranial fibrosarcoma
Abstract Introduction: Primary fibrosarcomas of the brain are very rare tumors, so that information regarding the treatment is scarce. We report the contributions that different therapeutic options made to the treatment of a child with one of these aggressive tumors. Case report: A 13year-old boy underwent a complete resection of a left temporo-parietal mass that had been diagnosed as a fibrosarcoma by two independent pathologists. Adjuvant chemotherapy with vincristine, actinomycin-D, ifosfamide and Adriamycin was started, but after 3 months tumor relapse was evident. The boy subsequently received radiation therapy during which there was evidence of progressive tumor shrinkage. A second surgery was performed 6 months after radiotherapy and a small enhancing lesion, revealed to be gliosis,
Introduction Primary intracranial sarcomas are rare tumors, accounting for up to 1.5–2% of all central nervous system neoplasms [2, 7]. Together with malignant fibrous histiocytomas, fibrosarcomas appear to constitute one of the most common histologies that have been described [6, 7]. It is supposed that cerebral fibrosarcomas originate from fibroblastic elements within the brain parenchyma or its meningeal coverings [3]. The tumor mass is usually located supratentorially, often in a superficial position, adherent to the dura mater. There are no distinctive clinical features. Prognosis is generally regarded as being
was resected. The child remains alive and well 44 months after diagnosis. Conclusion: Our experience supports the importance of total resection followed by radiation therapy, and radiotherapy should be started as soon as possible after surgical resection, rather than administering chemotherapy first. Keywords Fibrosarcoma · Intracranial sarcoma
very poor, despite radical surgery and radiotherapy, while the role of chemotherapy is still unclear. In this report we describe the contributions that different therapeutic options made to the treatment of a child with a primary intracranial fibrosarcoma.
Case report A 13-year-old boy presented to the local hospital with a 4-day history of progressive headache. One day prior to admission the boy complained of right arm paresthesia and vomiting. Previous medical and family histories were unremarkable. Axial computed tomography (CT) scans obtained with and without contrast demon-
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Fig. 1 Round, well-circumscribed 4×4-cm temporal-parietal mass, hypointense in the axial T1-weighted images (A), and hyperintense in the T2-weighted (B) and T1 postcontrast ones (D). The lesion appears as a hypointense lesion on the noncontrast CT scan (C)
Fig. 2A–D Postsurgical head CT scan with and without contrast, showing complete removal of the neoplastic lesion
strated a 4×4-cm inhomogeneous, well-circumscribed enhancing mass in the left temporo-parietal site (Fig. 1C). The patient was subsequently referred to our clinic for further evaluation and treatment. Neurological examination revealed nuchal rigidity and hyperreflexia of the right upper extremity, and the plantar responses were flexor on the right. There was also an initial bilateral papilledema. Magnetic resonance imaging (MRI) confirmed the CT finding. A T1-weighted sagittal image delineated a gadolinium-enhanced left temporo-parietal mass with compression of the occipital horn and a minimal perilesional edema. A T2-weighted axial image demonstrated an inhomogeneous hyperintense corresponding to the T1 enhancing region (Fig. 1A, B, D). The neurological imaging findings led to a clinical diagnosis of an extra-axial tumor, such as meningioma. The patient underwent a left parietal craniotomy that disclosed a whitish tumor of hard consistency presenting at the surface. The tumor was not encapsulated but was relatively well demarcated, and was completely resected. A postoperative CT scan performed within 24 h of surgery showed no residual tumor (Fig. 2). The postsurgical period was uneventful. The histological diagnosis was fibrosarcoma. Hematoxylin and eosin sections showed a highly cellular malignant tumor, made up of sheets of spindle-shaped cells in a fascicular pattern with nuclear pleomorphism. The highly malignant nature of the tumor was also reflected by a high mitotic rate (>10 mitoses per high-power field). No areas of necrosis were observed. Immunohistochemical studies demonstrated positivity for vimentin, which was indicative of a fibrosarcoma. In
contrast, glial fibrillary acidic protein (GFAP), S100, cytokeratin, epithelial membrane antigen (EMA), desmin, muscle actin, and CD34 were negative. Ki-67 proliferation index in the specimens was 30%. There was no sharp demarcation between the neoplastic cells and surrounding brain tissue. The histological diagnosis was independently confirmed by the Italian Panel for Soft Tissue Sarcoma and by a reference neuropathologist. In order to exclude the possibility that the cerebral lesion might have been a metastasis, a chest X-ray and a CT scan of the chest and abdomen were carried out, but no extracerebral disease was documented. Similarly, the postoperative contrast-enhanced spinal MRI and the cerebrospinal fluid cytology examination were negative. After the confirmation of the histopathological and immunohistochemical findings, the patient was referred for adjuvant chemotherapy according to the Italian protocol for soft tissue sarcoma, RMS 96. The child was to receive two courses of VAIA: vincristine 1.5 mg/m2 on day 1 of weeks 1, 2, 3, 4, and 7; actinomycin-D 1.5 mg/m2 on day 1 of weeks 1 and 7; ifosfamide 3 g/m2 on days 1 and 2 of weeks 1, 4, and 7; Adriamycin 40 mg/m2 on days 1 and 2 of week 4. The patient was followed up using MRI studies. After the first 3 months of chemotherapy an enhancing 1×1-cm nodule appeared within the tumor bed (Fig. 3A). This finding was interpreted as a tumor recurrence. The boy subsequently underwent radiation therapy up to a total dose of 5760 cGy in 32 daily fractions of 180 cGy; the target volume encompassed the T2-weighted image with 1.5 cm and was covered by two local oblique, wedge-filtered, tailored beams. The follow-up MRI, performed 1 month after the
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Fig. 3 A Postcontrast T1-weighted axial imaging showing an enhancing lesion within the surgical bed, read as being a local recurrence. B Same images 2 months after completion of radiotherapy showing a significant reduction of the previously documented enhancing lesion
completion of the radiation treatment, showed a reduction of the tumor. The patient did well clinically. Repeated MRI 1 month later (7.5 months after presentation) showed a further decrease in the size of the tumor (Fig. 3B). In order to clarify the nature of the lesion, the patient underwent another surgical operation 6 months after the irradiation. Histological findings led to a diagnosis of reactive gliosis. Forty-four months after the diagnosis the boy is well and shows no evidence of disease.
Discussion Primary fibrosarcomas of the brain are very rare tumors. Previous investigators found an incidence ranging from 0.5% to 2.7%, with an average of 1.5%, of all central nervous system neoplasms [4]. On the other hand, more recent studies suggested a very low incidence with 1 out of 402 children reported by Tomita and Gonzales-Crussi [7] and only 1 fibrosarcoma out of 25,000 brain tumors reported by Paulus et al. [6]. This is presumably due to the improvement in the diagnostic tools that has led to an increased recognition of other histological types. Moreover, due to a change in the classification systems, sarcomas previously classified as fibrosarcomas are nowadays diagnosed differently, in particular as being malignant fibrous histiocytoma [6]. Intracranial sarcomas are found in patients of all ages, although a greater number of young patients were reported in older studies. These tumors are not associated with any typical clinical history or findings that would be helpful in distinguishing sarcomas from other central nervous system neoplasms [4]. Information regarding the treatment of choice is still inconclusive and limited due to its scarcity. In our patient, the diagnosis of primary intracranial sarcoma was established based on a systemic tumor survey and morphological and immunohistochemical stud-
ies. The morphological features of spindle cells in a fascicular pattern and the prominent vimentin positivity confirmed the diagnosis. The high cellularity and high mitotic rate indicated that the tumor was a high-grade fibrosarcoma. Sarcomatous transformation from a pre-existing brain neoplasm such as meningioma or a glial tumor was excluded by the negativity of tumor cells for EMA and GFAP, respectively. We planned to treat our patient using a combined multimodality approach, but the tumor seemed to have recurred despite a grossly complete surgery and multiagent chemotherapy. However, it is possible that radiotherapy has cured this child. A poor prognosis is reported for patients with primary intracranial fibrosarcomas. In 1984 Tomita and Gonzales-Crussi [7] reviewed 18 children with primary CNS sarcomas, including a series of 9 patients reported by Christensen and Lara [1]: only 5 were alive 8 months to 12 years from diagnosis. Six children died postoperatively and 7 because of the tumor, 2–36 months after diagnosis (median 7 months). Four out of the 5 patients who were still alive had undergone total resection on diagnosis, 9 received radiotherapy, and none were treated using chemotherapy. In the past two decades more than 20 cases of primary cerebral fibrosarcomas that were not secondary to radiotherapy have been reported [3, 5, 6, 7]. However, only 1 pediatric patient has been described [7]. This was a 6month-old boy with a right temporal superficial mass who was well 10 years after diagnosis, following a subtotal resection and radiotherapy (45 Gy). Three more patients were still alive with no evidence of disease, but only 1 can be considered a long-term survivor, with 8.3 years of follow-up. Local recurrence was very common in these patients, even after total surgical resection. Time to recurrence or progression varied from 2 months to 5 years but most patients relapsed within 1 year of diagnosis. Radiotherapy has been part of the treatment in nearly all patients, with doses ranging from 35 to 60 Gy, while adjuvant chemotherapy has been administered in 1 patient, after initial resection, and in 2 patients at recurrence, without any evidence of activity. In conclusion, the prognosis of patients with intracranial fibrosarcomas has not improved in the last two decades, despite improvements in surgical procedures. Our experience supports the importance of total resection followed by radiation therapy, and radiotherapy should be started as soon as possible after surgical resection, rather than administering chemotherapy first. Acknowledgements This work was supported in part by a grant from the Fondazione Città della Speranza.
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