Medical and Pediatric Oncology 32:57–59 (1999) MISLEADING LEADS Vertebra Plana Due to a Ewing Tumor L. Kager, MD,1 A. Zoubek, MD,1 R. Kotz, MD,2 G. Amann, MD,3 P. Wiesbauer, MD,1 W. Dobrowsky, MD,4 and H. Gadner, MD1* Key words: vertebra plana; Langerhans cell histiocytosis; Ewing tumor; multimodal therapy INTRODUCTION The radiological diagnosis ‘‘vertebra plana’’ indicates the most severe degree of compression of the vertebral body . The collapse of the vertebral body can be caused by various pathologic conditions. However, the most common cause in children is Langerhans cell histiocytosis (LCH) . Localized LCH of the bone is a benign and often spontaneous regressing disorder. In typical vertebra plana, biopsy confirmation of the presumptive diagnosis has been considered unnecessary by some . Our experience with a child with vertebra plana of the third cervical vertebra due to a Ewing tumor is relevant and illuminating. CASE REPORT The patient was an 8-year-old girl with neck pain of 2 months duration who was first admitted to another hospital. Physical examination demonstrated a tenderness to percussion in the neck, but no neurological deficit. Plain films of the cervical spine revealed a typical vertebra plana of C3 (Fig. 1). The most likely diagnosis was LCH of the spine and therefore no biopsy was performed. Treatment with analgesic drugs and rest initially resolved her complaints. Four months later, the girl was referred to our hospital with rapid progressive tetraparesis. Magnetic resonance imaging (MRI) of the cervical spine revealed a collapsed C3 vertebral body and a large intraspinal (C1–C4) mass (Fig. 2). A fine-needle biopsy was performed and revealed an MIC-2/CD99 positive, EWS/ Fli-1 rearranged small blue round cell tumor without neural differentiation, compatible with the diagnosis of a Ewing tumor. Extensive examination showed no other tumor sites. Chemotherapy according to the EICESS 92 protocol  and radiotherapy were immediately started and neurological function improved quickly. After five cycles (EVAIA) of a combination of etoposide, vincristine, ifosamide, and alternating doxorubicin and dactinomycin and accelerated fractionated radiation of the third cervical vertebral body with 54 Gy, an impressive reduction in tumor size was noted by MRI. Four months after diag© 1999 Wiley-Liss, Inc. nosis, tumor resection by a ventral approach was performed. The third cervical vertebral body was resected, followed by anterior fusion with autologous iliac crest bone graft and plating. She then underwent resection 4 months later by a posterior approach with laminectomy at C3 and removal of the posterior elements close to the vertebral arteries on both sides. Posterior spinal fusion from C2 to C4 was accomplished with bone grafts anchored by sublaminar wires (Fig. 3). Neither resected specimen showed any viable tumor cells. The girl was then treated with 7 cycles of EVAIA over 10 months. Currently, she is 6 years off therapy and in good general condition with no evidence of disease and without neurological deficits. DISCUSSION In 1925, Calvé  reported two children with radiologically detected flattened vertebral bodies and suggested aseptic necrosis of the involved bones as the cause. Buchman  suggested the term ‘‘vertebra plana’’ for lesions characterized by a) total collapse of only one vertebra, b) no involvement of the intervertebral disc, c) the intravertebral space at least one third wider than normal, and d) increased density of the involved vertebra. Later on it was proven histopathologically that acquired vertebra plana in children was in most cases a manifestation of LCH [2,3]. Less common causes include trauma , metabolic and endocrine disorders , infectious diseases , myofibromatosis , aneurysmal bone cyst , neurofibromatosis , hemangiomas , and malignancies. Among the malignant disorders, osteosarcoma , lymphoma , neuroblastoma , leukemia , rhabdo1 St. Anna Children’s Hospital, Vienna, Austria 2 Department of Orthopedics, University of Vienna, Vienna, Austria 3 Department of Pathology, University of Vienna, Vienna, Austria 4 Department of Radiotherapy, University of Vienna, Vienna, Austria *Correspondence to: H. Gadner, Professor of Pediatrics, St. Anna Children’s Hospital, Kinderspitalgasse 6, A-1090 Vienna, Austria. Email: Gadner@ccri.univie.ac.at Received 29 June 1998; Accepted 7 July 1998 58 Kager et al. Fig. 1. Conventional tomography of the cervical spine at initial presentation revealed a typical vertebra plana of the third cervical vertebra. Fig. 2. Sagital T1 weighted MRI (after administration of gadolinium-GPTA) four months after initial presentation revealed again the collapsed third cervical vertebra and additionally a large intraspinal (C1–C4) mass. myosarcoma , Hodgkin disease , and four cases of Ewing sarcoma [3,8,11,12] have been described. The few reported cases of vertebra plana caused by malignancies were often initially misdiagnosed as LCH, resulting in a regrettable diagnostic delay [9–12] since early therapeutic interventions are highly desirable. Conventional radiography of vertebra plana is unable to identify the underlying disesase process. MRI, although also nonspecific, offers optimum detection of extraosseous tumor invasion of adjacent tissues; but ultimately a biopsy is needed to establish the diagnosis. Fine-needle sampling often yields inadequate tissue specimens . Some authors therefore recommend open biopsy [8,9]. Ewing tumor is the general term for a group of small round-cell neoplasms that include Ewing sarcoma, extraosseus Ewing sarcoma (EES), and peripheral primitive neuroectodermal tumors (pPNET) . They are biologically characterized by an EWS-gene rearrangement with either FLI-1, ERG, ETV1, E1A-F, or FEV and high expression of the MIC2/CD-99 antigen in at least 95% of tumors. Primary Ewing tumor arising in the vertebral column including the sacrum and paravertebral region is rare. The incidence of primary vertebral involvement in Ewing sarcoma and pPNET is approximately 3% [12,14– 16], paraspinal pPNET occurs in about 5% , and 16 cases of primary spinal epidural EES have been reported . Almost all cases with ET of the spine at presentation suffered from local pain that precedes the diagnosis by 2–8 months [12,16]. Neurological signs and symptoms are reported to be present in 60–80% [12,16]. Almost all Ewing sarcoma patients published in the last two decades were treated by a multimodal approach to achieve local and systemic tumor control [12,16,17]. Systemic chemotherapy is the mainstay of treatment, while the relative roles of surgery and radiotherapy in local tumor control are still evolving. There is a high rate of only partially resectable tumors in primary spinal epidural EES (about 64%) with a high rate of local recurrence . These data suggest that complete surgical removal may play an important role in local tumor control. Our experience does not help to resolve this issue. On the one hand, excision was performed in two steps as described; on the other, no viable tumor cells after chemoradiotherapy could be detected in the resected specimens. Ewing Tumor and Vertebra Plana 59 EES, 63% died at a median 16 months after diagnosis . CONCLUSIONS We conclude that the diagnosis of LCH should not be assumed whenever vertebra plana is detected radiographically. This erroneous diagnosis led to a 4-month delay in instituting appropriate therapy in our patient. Thus, we recommend that when vetebra plana is detected in a child with back pain and when the physical examination elicits additional neurologic signs, the lesion should be regarded as malignant until proven otherwise. Ewing tumor should be included in the differential diagnosis. Rapid diagnostic workup including biopsy is needed. Ewing tumor of the spine is rare, and combined modality treatment, as described in our case, can be effective. REFERENCES Fig. 3. Plain radiograph taken 1 month following excision of C3 and spine stabilization (see text). Radiotherapy has been employed for definitive treatment irradiation or as an adjuvant in doses ranging from 30 to 60 Gy [12,16,17]. Prudence is needed because, using conventional fractionation at doses above 45 Gy, postirradiation myelopathy can occur. Also to be remembered is the 5–10% frequency of second malignancies in irradiated sites within 20 years after treatment . Our patient was treated by an accelerated fractionated schedule and received a total of 54 Gy on the third vertebra. Nonetheless, preoperative irradiation can play an important role when used to improve neurological impairment quickly, as in our case. Pilepich et al.  reported 100% local control and 86% 5-year disease-free survival of 14 patients diagnosed between 1973 and 1977 with Ewing sarcoma of the spine proximal to the sacrum, treated according to the Intergroup Ewing Sarcoma Study protocol. In that study, eight patients with Ewing sarcoma of the sacrococcygeal segments showed local control in 62.5% and a disease free-survival in only 25% of the cases . 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