Late recurrence of a tumor of Ewing’s sarcoma family of tumors: report of a case
© Yun et al. 2015
Received: 28 September 2014
Accepted: 9 April 2015
Published: 24 April 2015
A 27-year-old female presented with a history of a right chest wall tumor at 3 years of age. At that time, the tumor was surgically resected and diagnosed as Ewing’s sarcoma (EWS), and postoperative chemoradiotherapy was administered. The patient remained disease-free for 25 years. At age 27, chest computed tomography revealed a mass adjacent to the anterolateral thoracic wall. After surgery, the diagnosis was primitive neuroectodermal tumor (PNET). She died of the disease 10 months later. PNET and EWS were integrated into a single item in the 2002 WHO classification; thus, they are considered clinically and pathologically identical. The morphologic, immunohistochemical, and molecular biological characteristics of both specimens showed that the second tumor was a local recurrence of Ewing’s sarcoma family of tumors (ESFT). Our case is the longest duration local recurrence reported. Long-term recurrences of ESFT and patients with recurrent ESFT have a poor prognosis; thus, long-term follow-up is necessary.
KeywordsEwing’s sarcoma family of tumors Primitive neuroectodermal tumor Late recurrence
Tumors of Ewing’s sarcoma family of tumors (ESFT) are malignant tumors that originate in the central and peripheral nervous systems and soft tissues in children and adolescents. The prognosis is generally poor. However, recent treatment outcomes of ESFT have improved with the use of multimodal therapy . Advances in molecular biology have revealed common chromosomal translocations such as EWS-FLI-1 among Ewing’s sarcoma (Ewing’s sarcoma of the bone and extraosseous Ewing’s sarcoma) and related diseases, such as primitive neuroectodermal tumor (PNET) and Askin’s tumor .
PNET and Ewing’s sarcoma (EWS) were integrated into a single item in the 2002 WHO classification; thus, they are considered clinically and pathologically identical. Late relapses are seldom described. We report a patient with an ESFT who had a recurrence 25 years after initial surgery and postoperative chemoradiation.
As either radiation-induced sarcoma or a local recurrence of EWS was suspected, we performed extirpation of the tumor and chest wall (the left second to the fourth ribs), partial resection of the right lung, and reconstruction of the chest wall (Figure 2b). Intraoperative blood loss was 800 g, and the operation took 4 h and 51 min.
Pathologic findings were identical to those of the original chest wall tumor, with small round cells and extensive necrosis (Figure 2c). The specimen stained positively with antibodies to CD99 (Figure 2d). Immunohistochemical and histochemical staining showed that the tumor was positive for chromogranin, synaptophysin, and neuron-specific enolase and negative for thyroid transcription factor-1, myogenin, and desmin. Fluorescence in situ hybridization analysis using a EWSR1 break-apart probe identified the rearranged EWSR1 gene in both cases. Thus, histopathologically, the tumor was diagnosed as a PNET. Four cycles of VDC (vincristine, doxorubicin, cyclophosphamide) chemotherapy and two cycles of IE (ifosfamide, etoposide) and high-dose L-PAM (melphalan) and radiotherapy of left thigh bone for a total dose of 30 Gy was administered after the second operation. She had recurrences in the right chest wall and upper middle lobe and metastases in the skull, rib, vertebrae, ilium, and thigh bone. She died of carcinomatous lymphangiosis 10 months after the second surgery.
In 1921, James Ewing reported a rare type of sarcoma in children, adolescents, and young adults that is a highly malignant tumor of the bone and soft tissue, composed of small round cells . Separately, Stout et al. reported in 1918 that a PNET is an ulnar nerve-derived small round cell tumor with rosette formation that develops in soft tissues in young individuals . The first small round cell tumor of chest wall origin was reported in a pediatric patient by Askin, and these tumors are referred to as Askin tumors . An Askin tumor is a PNET that develops from the soft tissues of the chest wall in childhood. At that time, our case might have been termed an Askin tumor.
Pathologically, EWS/PNET is composed of small, round, uniform cells with characteristic small-sized rosette formation. These tumors, both with a poor prognosis, were described as separate entities in the small round cell tumor group in the second version of the WHO classification published in 1993. However, with recent improvements in molecular biology, a translocation (11; 22) (q24; q12) specific to both EWS and PNET has been identified, and the EWS-FLI-1 fused gene was identified at the cleavage site of this translocation. They therefore were subsequently integrated into a single item (Ewing’s sarcoma/PNET) in the WHO classification, published in 2007 . The ESFT includes EWS of the bone, extraosseous EWS, and PNET of the bone or soft tissue.
The most useful immunohistologic reagent for the diagnosis of ESFT is the monoclonal antibody CD99, which recognizes a cell surface protein. Specimens stain strongly positive with the CD99 antibody in more than 90% to 95% of cases of reported ESFT.
Chest wall ESFT tumors are rare, have a high rate of local recurrence, and frequently are metastatic at presentation. In a report of 84 thoracic PNET cases by Biswas et al., patient age ranged from 3 to 40 years (mean age = 15 years) and tumor diameter ranged from 1.6 to 20.0 cm (mean diameter = 9.0 cm). It occurred most commonly in the ribs (54%), the scapula (25%), and the chest wall (14%), with a male predominance (70%). Twenty-seven (32%) patients had metastatic disease at diagnosis. An independent prognostic factor for PNET is the presence of metastatic disease . The median relapse-free interval (RFI) after treatment was 17 months (range, 5 to 90 months). In contrast to the dramatic improvement in survival for ESFT, the prognosis after recurrent disease remains poor, especially for patients with a RFI of less than 24 months .
The morphologic, immunohistochemical, and molecular biological characteristics from both specimens supported that the second tumor was a local recurrence of an ESFT. Several prior studies established that the longest time until recurrence of ESFT was 19 years . Our case demonstrates the possibility of very late local recurrence of ESFT.
We report a case of locally recurrent ESFT 25 years after initial treatment. To our knowledge, no case with such late local relapse as our case has been reported to date.
We report a rare case of chest wall ESFT in a 27-year-old female. A right thoracic recurrence was surgically resected 25 years after the primary tumor, but the patient died of the disease 10 months after surgery. Our case suggests that patients with ESFT should undergo lifetime surveillance. Generally, it is difficult to detect recurrence from clinical symptom of the patients. Patients should be under observation using periodical CT, bone scintigraphy, or PET periodically.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
We would like to thank Dr. Masanori Hisaoka (Department of Pathology and Oncology, University of Occupational and Environmental Health, Japan) for the assistance with the pathological diagnosis and for performing the molecular biological analysis of the EWS gene.
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