Discussion
Primary salivary gland tumors are rare in infancy and childhood (1). The incidence of salivary gland tumors in children aged <5 years is extremely rare (1), particularly during infancy (1). In the first decade of life, the incidence of salivary gland tumors is <0.25% (2). The majority of salivary gland tumors in children are non-epithelial neoplasms (8). Hemangioma is the most common salivary gland tumor during the first year of life (6,7).
Sialoblastoma is a rare epithelial neoplasm of salivary gland origin in children (3), with ~50 cases reported in the English literature (5). This tumor may occur during the congenital, neonatal, or childhood periods (9,10). However, the vast majority of the cases are identified at or shortly after birth (5), with a median age at diagnosis of 9.8 months (9). Sialoblastoma exhibits a male predilection of ~2:1. These tumors are mostly found in the parotid and submandibular glands, although involvement of the minor salivary glands has also been reported. The size of tumor is ranging from 1.5 to 15 cm in greatest dimension (5). The majority of the patients clinically present with a slow-growing, painless, subcutaneous mass (8).
Regarding the macroscopic findings, most tumors are multilobulated, firm, tan-pink to yellow masses (8,10). Microscopically, sialoblastomas exhibit the primitive embryonic histological characteristics of salivary gland tissue, together with basaloid epithelial components and a variable amount of stroma (1,10). This tumor consists of variably arranged, tight clusters or clumps of basaloid-like cells in a background of dispersed epithelial and myoepithelial cells, and partially formed ductal and pseudo-ductal spaces separated by thin fibrous bands (8,11). These microscopic characteristics reflect the pre-acinar stage of salivary gland morphogenesis, together with primitive cell masses, forming ducts and pseudo-ductular spaces, without acinar differentiation (3,11).
The differential diagnosis includes adenoid cystic carcinoma and basal cell adenoma. One-third of sialoblastomas exhibit a cribriform growth pattern, which is different from adenoid cystic carcinoma regarding various histological characteristics, including prominent, elongated and branching ductal structures within basaloid cells bulbs, thickened tubules with basaloid cells, and larger basaloid cells with more obvious cytoplasm (12). In contrast to basal cell adenoma, sialoblastoma is composed of more primitive cells that exhibit less prominent peripheral palisading of nuclei, significant cytological atypia and higher mitotic activity, and often infiltrate the surrounding tissue, including vascular, perineural and skeletal muscular invasion.
Immunohistochemical studies have reported that sialoblastoma stains positive for cytokeratin in the ductal cells and for vimentin, smooth muscle actin and S100 in the outer ductal parts (5,11). Solid nests of basaloid cells are focally positive for S100 and vimentin (11). The immunohistochemical results in our case were compatible with previous reports. In addition, our case was also immunohistologically and serologically positive for AFP (11,13). Moreover, immunohistochemical investigation demonstrated positivity for Hep Par-1 in a considerable number of tumor cells.
The presence of anaplasia, neurovascular invasion and necrosis were suggested as adverse prognostic factors (2,6). Other adverse histological characteristics include infiltration of the capsule (12). Sialoblastomas may be histomorphologically divided into two groups, namely favorable and unfavorable groups (10). The characteristics of the favorable group include circumscription and infrequent mitoses (<3–4/10 HPFs) (10), whereas the characteristics of the unfavorable group include anaplasia, frequent mitoses (≥4/10 HPFs), apoptosis, necrosis and a high Ki67 index (10). According to this classification, the pathological findings of our patient were those of the unfavorable group, namely frequent mitoses (50/10 HPFs) and high Ki67 proliferation index (70%).
The pathogenesis of sialoblastoma has not been fully elucidated. It has been suggested that sialoblastoma originates from retained blastema cells in the salivary gland, rather than basal reserve cells. Dysembryonic salivary gland changes have been described adjacent to the tumor, with proliferation of the terminal ductal epithelial bulbs. In tumor chromosome study, the cytogenetic karyotype of sialoblastoma was 47, XX, del(3)(q13),inv(9)(p11q12)c,+?r [5]/46, XX, inv(9)(p11q12)c[41] (14). The aberrations detected in the sialoblastoma (deletion of the long arm of chromosome 3 and ring chromosome formation) are different from those detected in other salivary gland tumors, suggesting that the pathogenetic mechanisms differ between sialoblastoma and other salivary gland neoplasms (14).
A case with a concurrent sialoblastoma associated with hepatoblastoma has been reported (9). Furthermore, there are few reports in the literature documenting the focal expression of AFP in tumor cells. Our patient also demonstrated co-expression of AFP and Hep Par-1 in tumor cells. AFP is an oncofetal antigen that is produced by the fetal liver. These data suggest that there may be an association between hepatic tumorigenesis and the development of sialoblastoma. However, since studies on the association between sialoblastoma and hepatic markers remain scarce, the pathogenesis of sialoblastoma should be further investigated.
The prognosis of sialoblastoma is controversial. Sialoblastoma has a tendency to progress further with local invasion, local recurrence and occasional metastasis (5). In general, in infants and children, sialoblastoma is usually of low-grade malignancy and most cases have a favorable outcome (12). However, although they generally behave benignly, these tumors may be associated with lymphatic metastases (12). Approximately one-third of sialoblastomas develop local recurrence and metastasis (12). Recurrences have been reported as late as 4 years after excision (7) and distant metastases usually involve the lung and lymph nodes (5,12).
Due to the limited number of the cases, definitive treatment guidelines have not yet been established (7,9). Early complete surgical excision remains the cornerstone of the surgical management of sialoblastoma (2,7,9,15), whereas radiotherapy and chemotherapy remain controversial (15). Radiation may play a role in cases with incomplete tumor resection (8). However, since the disease mostly occurs in childhood, the use of radiotherapy may be limited, due to the radiation-related side effects, such as impaired bone growth, abnormal facial structure and mutagenic effects (8,9). Sialoblastoma is likely sensitive to chemotherapy (9), which may be useful in patients with extensive or metastatic tumors, relapsed cases, or inadequate surgical excision of a primary tumor (1,7,9,15). The protocols are usually based on the chemosensitivity, as with other mesenchymal tumors (7). The use of neoadjuvant chemotherapy for locally invasive tumors, rather than extensive, mutilating surgery, has also been suggested (9). The follow-up should be frequent and prolonged. AFP may be a useful marker of tumor response in patients with sialoblastoma.