Review of the English-language literature showed that parotid gland as a primary site is a rare event1-4, 6 (Table1). Consistent with previous reports that EOS predominantly occurs in patients older than 40 and a slight predilection for males, all 5 patients were males and median age was 44.8 years old [17-73]. The present case whose age and sex are also in line with the trend reported in the literature. As mentioned above, these 5 cases, together with the cases we reported, show that primary EOS of the parotid gland is an extremely rare. Moreover, there was one case of EOS with giant cell-rich, among them, which was an exceedingly rare variant6.
The presenting signs and symptoms of parotid EOS are progressive swelling of soft tissue masses with pain, occasionally with swelling or tenderness, but it depends on tumor size and location. When the lesion is small and does not have extensive mineralization, it may look quite harmless and may look like a small lymph node. It has been reported that the inducement of EOS might be related to the history of trauma or radiotherapy1, 3, 4. In the Table1, neither radiation nor trauma could have been a documented predisposing factor in the case we report here nor in the other 5 cases. It seems that radiation is not the main factor of parotid EOS.
The most important criterion for the diagnose of this tumor is based on the presence of sarcomatous pleomorphic cells producing an osteoid or bone matrix. Macroscopically, the majority of the tumors are solitary masses with a diameter of 5cm to 10cm3. The tumor size will not become smaller because the parotid region is small, therefore, most of the cases in Table1 (from 1.3cm to 6.2cm) are within that range. The pathological features and IHC phenotype corroborated with those of osteosarcoma. The tumor cells usually presented positivity for Vimentin, Bcl-2, CDK4, and STAB-2. The case we present met 3 of the above diagnostic criteria, however, it is important to note that the IHC results of the 5 cases mentioned above (Table 1) were not specific. To our knowledge, this is the most complete IHC record of EOS in parotid gland so far. Melanocytes and epithelial markers (S-100, pan-cytokeratin, HMB-45, Melan-A) were all negative, thus, melanoma was excluded. Previous studies showed that high-and low-grade EOS expressed MDM2, and STAB-2 positivity in tumor cells was confirmed around the osteoid matrix in some cases with only immature osteoids7. Based on the World Health Organization (WHO) system, the tumor was classified as high-grade (grade 3). Calcification or osteoid matrix is present in approximately 50% of primary lesions3. The lack of calcification in our case was may attributed to acute onset (Fig. 1A). Also, reports indicate EOS different from traditional osteosarcoma with rare calcification, hence, calcification is not specific for EOS1, 3, 5.
Metastatic osteosarcoma should be ruled out during the diagnosis of primary EOS. Radionuclide static bone scan of our patient revealed no tumors in bone and other organs of his body (Fig. 1D). Clinically, the differential diagnosis of EOS has vital significance, specifically from MO3. For parotid EOS, biopsy is the main means to make diagnosis and radiographic examination is essential for early detection of the disease and to plan surgery1-3, 6.
We need more cases to clearly identification of the exact biobehavioral criteria for this disease, to determine the best treatment. Therefore, so far, its treatment is still controversial, referring to the treatment of osteosarcoma or soft tissue sarcoma to a large extent. Conventionally, radical resection is the primary surgical treatment but has no effect on distant metastasis1, 2, 6. One report does suggest surgery and combined a chemotherapy (doxorubicin, cisplatin, and ifosfamide etc.) regimen was used to treat EOS, giving a high survival rate8. For parotid EOS, nevertheless, postoperative chemoradiotherapy have not shown benefits in survival rates to date1-3, 6. Further exploration of the utility of chemoradiotherapy is certainly warranted. The recurrence rate and metastasis rate after EOS was about 70%, with a poor prognosis, and a 5-year survival rate of 25%-77%1, 3, 4. The data in Table1 note that except for one patient’s follow-up information was unavailable, only 1 case were observed to be alive as well as no local recurrence and metastatic disease, the rest all died of disease in the end. In the 4 death cases (including our case), all patients exhibited distant metastases after surgery and 2 developed tumor recurrences. In fact, however, no long-term survivor of primary parotid EOS has ever been reported1, 2, 6. Thus, we suppose that the poor prognosis of parotid EOS may be caused by tumor recurrence and metastasis. Another series showed that tumor size was a vital factor influencing prognosis, on the other hand, histological types and other clinicopathological features demonstrated no significant effect on the prognosis9. There were several limitations in the management of this case. The tumor was not diagnosed at an early stage, the range of the previous operation was small and was an emergency operation, neither of which was the standard treatment plan of EOS. Multiple surgical stress destroyed the homeostasis in the body affecting tumor growth microenvironment. The resulting immunosuppressive effect accelerated the metastasis of the residual tumor and increased the risk of disease progression among patients. As such, the tumor relapses and metastases in a short time. After a definite diagnosis, the tumor was removed by radical resection, followed by doxorubicin or cisplatin-based chemotherapy regimen. During the follow-up for more than one year, we observed no sign of local recurrent tumor.