Ewing sarcomas are characterized as primitive malignant round cell tumors.1 These tumors are diagnosed by neuroectodermal differentiation and by their common histologic and immunohistochemical properties.2 Ewing sarcoma is the second most common malignant bone tumor in adolescents and young adults. It is the fourth most common primary malignant tumor, accounting for about 9% of all malignant tumors of bone. The most common primary bone tumors are multiple myeloma, osteosarcoma, and chondrosarcoma.3
The diaphyses of long bones (eg, femur, tibia, humerus) and flat bones (eg, pelvis, scapula) are the most commonly involved sites. Involvement of bones in the hands and feet is uncommon (3%-5% of reported cases).4 The foot bones most commonly involved include the calcaneus and the metatarsals, in the series by Casadei and colleagues.5
About 90% of Ewing sarcoma cases present before age 20 years (mean age, 13 years).6 Typical presentation is that of localized pain at the involved site. Some patients have systemic symptoms, such as fever, malaise, weight loss, leukocytosis, and increased erythrocyte sedimentation rate (ESR) mimicking infection. Radiographically, Ewing sarcoma appears as a permeative destructive bone lesion with a moth-eaten appearance (almost 76% of cases).7 This is usually associated with lamellated periosteal new bone formation or an “onion skin” appearance. Less commonly, a sunburst configuration with an associated soft-tissue mass can be seen. Computed tomography (CT) and magnetic resonance imaging (MRI) show the osseous extent of the tumor and the presence or absence of the soft-tissue component of the tumor. Radionuclide bone scans show increased technetium-99m methylene diphosphonate accumulation and are typically hot.6
Histopathologically, the tumor is composed of small, uniformly sized cells characterized by an almost clear eosinophilic cytoplasm and very little intercellular matrix. There are lobules and strands divided by prominent septa. Macroscopically, appearance can range from a soft, fleshy solid mass to an almost liquid form, as the lesion does not produce any matrix. At time of surgery, the tumor may have a liquefied component and the appearance of pus.6 Prognostic factors are tumor site in foot and treatment according to the series by Casadei and colleagues.5 Patients with large central tumors, especially in the pelvis, have worse outcomes than patients with distal tumors.8
In this article, we report a case of multifocal Ewing sarcoma involving multiple bones in the foot. Given the multifocal nature of the disease confined to the foot, the initial impression was that of osteomyelitis. We describe the histologic, radiologic, and diagnostic features of the tumor and outline treatment and prognosis. To our knowledge, this is the first report of multifocal Ewing sarcoma involving multiple bones in the foot. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 19-year-old man visited our clinic with the chief complaints of left foot pain and swelling. The pain started 10 months earlier and was followed by swelling. Complaints started after a minor local trauma. The man sought outside medical attention 8 months after pain onset. At his first visit at another institution, an initial radiograph was reported as normal, and all laboratory measures, including complete blood cell count (CBC) differential, ESR, and C-reactive protein (CRP) level, were within normal limits. Under the erroneous diagnosis of infection, the patient was treated with cloxacillin 500 mg 4 times a day for 4 weeks.
The patient’s pain had started 10 months before presentation (2 months after antibiotic therapy was initiated) (Figure 1). Physical examination at our institution revealed a palpable mass on the dorsum of the left foot. Anteroposterior and lateral plain radiographs showed a permeative lytic lesion with cortical destruction in the left calcaneus, navicular, cuboid, and cuneiform bones and in all metatarsal bones except the first (Figure 2). A soft-tissue mass around the involved bones was noted as well. The talus was not involved (Figure 3).
CT showed permeative destruction of left foot bones, including the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first. Invasion through the overlying cortex of the involved bones indicated aggressive biological activity of the tumor (Figure 4). MRI showed a destructive bony lesion of the mentioned bones associated with the soft-tissue mass (Figure 3).
Bone scan showed increased uptake in the involved areas (Figure 5). Chest plain radiographs and CT showed no distant metastasis. An incisional biopsy was performed, and histopathology showed a malignant small round cell tumor, identified as Ewing sarcoma (Figure 6). An immunohistochemistry study demonstrated positive CD99 and negative cytokeratin, leukocyte common antigen, desmin, and synaptophysin.
The patient was started on 4 cycles of adjuvant chemotherapy. Cycles 1 and 3 involved cyclophosphamide 2 g, vincristine 2 g, and doxorubicin 50 mg; cycles 2 and 4 involved ifosfamide 3.5 g and etoposide 200 mg. Tumor shrinkage occurred after chemotherapy. Clinical response to preoperative chemotherapy was documented by a decrease in tumor size at follow-ups. The patient underwent below-knee amputation.