Primitive neuroectodermal tumors (PNETs) are rare, highly malignant neoplasms consisting of small round cells of neural crest origin (1). PNETs may be further subdivided into central and peripheral PNETs (pPNETs), which arise outside the central and sympathetic nervous system. pPNETs often occur in the soft tissues of thoracopulmonary region (Askin tumor), retroperitoneum and abdomen, and, more rarely, in the bones (1–3). There is no consensus with regard to the guidelines for the treatment of pPNET at present, due to its rare occurrence. As PNET exhibits similarities to Ewing sarcoma, surgical resection followed by adjuvant radiotherapy, as well as multiagent chemotherapy if possible, is considered necessary to improve patient survival. There have been few studies published exclusively on the osseous pPNET (3), particularly regarding its radiological and clinical features. Therefore, the present study aimed to document the radiological and clinical features of osseous pPNET by conducting a retrospective radiological and clinical review of 15 patients with surgically or bioptically confirmed osseous pPNET.

The first case of pPNET, occurring in the ulnar nerve, was reported by Stout in 1918 and the tumor was composed of small round cells, focally arranged as rosettes (4). Ewing reported an undifferentiated, diffuse, small round-cell tumor occurring in the diaphysis of long bones in 1921; that type of tumor was eventually named Ewing's sarcoma (ES) (5). In 1984, Jaffe (6) analyzed the pathological sections of 4 cases that had been diagnosed as bone ES by previous clinical, X-ray and pathological examinations and identifed Homer-Wright rosettes by microscopy and neurospecific enolase (NSE) expression by immunohistochemical staining; thus, these cases were diagnosed as neuroectodermal tumors, rather than ES, and were the first reported cases of osseous pPNET. It was recently demonstrated that pPNET and ES may be further differentiated using characteristics observed on electron microscopic and immunohistochemical examination. For example, neurotubules, neurofilaments and neurosecretory granules may be observed under an electron microscope, whereas O13, CD99, S100-protein, vimentin, chorionic gonadotropin α (CgA) and NSE may be identified by immunohistochemical staining in PNETs (7–12).

The PNETs, a subtype of the family of small round-cell malignancies, are mainly found in the central nervous system (CNS). Rarely, however, PNETs may be found outside the CNS. These pPNETs are most common in the thoracopulmonary region, followed by the abdomen, pelvic cavity and retroperitoneum. Bone is a rare location and, to date, there have been few reports of osseous pPNET in the literature (3). To the best of our knowledge, this is the first English language study exclusively investigating the CT and MRI findings of osseous pPNETs. Osseous pPNETs may occur in any bone in every age group, but mainly affect children and adolescents and exhibit a marginal male predominance. Patients often present with a rapidly enlarging mass and associated compression symptoms (3,12). Consistent with previous reports (9,11), osseous pPNET mainly affected males, adolescents and young adults in the present study (Table II). The 15 patients presented with varying degrees of pain and 11 patients presented with local edema and a progressively growing mass. The tumors were located in the limb bones (7 cases), vertebrae (2 cases), clavicle (2 cases), scapula (1 case), ilium (1 case), maxilla (1 case) and mandible (1 case). It should be noted that pPNETs of the maxilla and mandible are extremely rare. Following a review of the literature, only 16 pPNET cases of the mandible (13) and 13 of the maxilla (14) have been reported.

The CT findings of osseous pPNETs include destructive lesions with a sizeable soft tissue mass and, occasionally, with periosteal reaction (3,13). The soft tissue mass is usually isodense or marginally hypodense compared with normal muscle (1,3,15). When the tumor is smaller, its density is often homogeneous. However, when the tumor is larger, it often exhibits isodensity with patchy hypodense necrotic areas. Tumor calcification is uncommon (11,12). In the present study, 13 of the 15 cases exhibited lytic bone lesions; all 15 cases exhibited surrounding soft tissue mass formation and 5 cases exhibited associated periosteal reaction. In 9 cases the soft tissue mass was heterogeneous, with different sizes of lower-density necrotic areas. Two cases of soft tissue mass exhibited calcification. These findings were consistent with the CT findings of osseous pPNET. Of note, osseous pPNET is a highly invasive malignant tumor and, therefore, it theoretically lacks the time required for calcification or ossification. Thus, the 2 cases exhibiting calcifications may be due to the pressure exerted on normal bone tissue, which may be observed among the CT findings of primary bone lymphoma (formation of sequestra) (16).

On T1WI, the majority of pPNETs are isointense or marginally hyperintense compared with normal muscle, and may contain hyperintense hemorrhagic areas. On T2WI, the majority of pPNETs are heterogeneous iso- or hyperintense. On contrast-enhanced T1WI, the tumor is often homogeneous when it is smaller and heterogeneous when it grows larger and exhibits areas of hemorrhage or necrosis (8,9). In the present study, 11 cases exhibited a surrounding soft tissue mass on MRI. On T1WI, a soft tissue mass exhibiting isointensity (8 cases) or marginal hyperintensity (3 cases) was identified. On T2WI, a soft tissue mass exhibiting heterogeneous iso- or hyperintensity (11 cases) was identified. On contrast-enhanced T1WI, marked heterogeneous enhancement was present in 10 cases and intermediate heterogeneous enhancement in 1 cases. These findings were consistent with those of previous reports (3,4). MRI is a sensitive method for displaying and accurately evaluating the extent of the lesions, evaluating treatment effectiveness and detecting the presence of distant metastases during the follow-up period. The two cases of the present study and those in other literature reports demonstrated that the ability of MRI to detect change is superior to that of CT, even following chemotherapy (11).

pPNETs are often associated with distant metastases and local recurrence following treatment, as well as poor prognosis. The most common recurrence is characterized by localized soft tissue masses and distant metastases, often occurring in the lung, bone, liver, adrenal gland, brain and retroperitoneum (15). In the present study, 1 patient had pulmonary and hepatic metastases at the time of diagnosis, 6 patients developed local recurrence and distant metastasis following surgery during the follow-up period and 4 patients developed distant metastasis following chemotherapy or chemoradiotherapy. A total of 7 patients succumbed to lymph node, pulmonary, hepatic, osseous or meningeal metastasis during the follow-up period.

In conclusion, osseous pPNETs mainly affect males aged <30 years. The patients often present with varying degrees of pain, local edema and a progressively growing mass. The CT findings of osseous pPNET include destructive lesions with a sizeable soft tissue mass and, occasionally, with periosteal reaction. Tumor calcification is uncommon. The MRI findings include aggressive soft tissue mass with isointensity on T1WI and iso- or hyperintensity on T2WI and markedly heterogeneous tumors following enhancement. The CT and MRI findings demonstrated that the tumor originated in the bone marrow cavity and exhibited a bone-centric growth pattern. Although the imaging characteristics of pPNETs may be non-specific, CT and MRI may be useful in delineating the extent of the tumor, identifying distant metastases, predicting resectability and monitoring treatment.