Desmoplastic small round cell tumor of the parotid gland-report of a rare case and a review of the literature

Desmoplastic small round cell tumor (DSRCT) is rare and a highly aggressive neoplasm that typically involves the soft tissues of the abdomen or pelvis in children or young adults, showing a male predilection. Although it occurs over a wide age range, the peak incidence is in the third decade of life. DSRCT usually shows widespread abdominal serosal involvement, and overall patient survival is poor. On the other hand, extra-abdominal DSRCT is very rare. Previous cases have been reported to arise in the lung [1], pleura [2], paranasal sinuses [3], central nervous system [4], and scalp soft tissue [5] . DSRCT in major salivary glands has been reported, but it is extremely rare. To our knowledge, only 5 cases occurring in the salivary gland have been reported in the English literature [6‐10]. Here, we report a case of a primary parotid gland DSRCT in a 49-year-old man, who is the oldest patient known to have been affected by this tumor, and who has survived for 3 years without recurrence. We also summarize the clinicopathological features of DSRCT in the salivary gland.

DSRCT is an uncommon malignant neoplasm that first described in two boys in 1989 [13]. DSRCT occurs mainly in the abdominal cavity, retroperitoneum, and pelvis, but Gerald et al. reported that 6% of DSRCTs can occur in an extra-abdominal location [14]. Histologically, DSRCT is characterized by various-sized nests composed of small neoplastic cells with a prominent desmoplastic, fibromyxoid, or collagenous stroma. Immunohistochemically, DSRCT shows a distinctive and characteristic pattern of multi-phenotypic differentiation. Tumor cells express proteins associated with epithelial, muscular and neural differentiation. The distinctive dot-like staining pattern of desmin is typical, but a diffuse cytoplasmic pattern has also been described [7], as seen in the present case. Hill et al. reported that nuclear immunoreactivity with C-WT1 antibody, which was observed in this case and is considered attributable to EWSR1-WT1 gene fusion, is useful for differentiating DSRCT from other small blue cell tumors, such as Ewing sarcoma [9]. The variable immunohistochemical reactivity of WT1 protein according to the anti-WT1 antibody employed may be a diagnostic pitfall. Obviously, it is critically important to use C-WT1 antibody for diagnosis of DSRCT, because N-WT1 antibody would give negative results, as was confirmed by the lack of the 5′-regional expression of the WT1 gene in the present case.

The clinicopathological features of salivary gland DSRCT reported previously in the English literatures are summarized in Table 2. All 6 cases, including the present one, occurred in males, and the age at the diagnosis ranged from 5 to 49 years, with a median age of 28 years. Two of these cases occurred in the fifth decade, although DSRCT is generally considered as a differential diagnosis in children or young adults. The tumors ranged in size from 2.7 to 5 cm, with an average of 4.1 cm. Among the six patients, three were still undergoing follow-up, and one had died due to systemic metastasis. Salivary gland DSRCT showed histological features similar to those of abdominal DSRCT. The overall survival in abdominal DSRCT patients is generally poor, despite multimodality therapy [15], According to the present case as well as previous cases, only one among 6 patients with salivary gland DSRCT died due to metastasis. The prognosis of salivary gland DSRCT is unclear because of its rarity, but early detection or complete resection of salivary gland DSRCT might result in better prognosis.

The origin of DSRCT remains unclear. It has been speculated that DSRCTs are derived from mesothelial or submesothelial cells because a vast majority of patients develop DSRCTs in cavities that are lined with mesothelial cells or because tumor cells show immunohistochemical positivity for epithelial and mesenchymal antigens including desmin, and WT-1 [12].

DSRCT is not usually included in the differential diagnosis in primary salivary gland tumors in view of its rarity. Because DSRCT is composed of small nests with cohesive small to medium-sized cells and shows immunoreactivity for epithelial markers, it might be diagnosed as carcinomas, such as small cell carcinoma, poorly differentiated carcinoma, undifferentiated carcinoma, without staining for desmin. Primary small cell carcinoma of the salivary glands is also rare, accounting for approximately 2% of all salivary gland tumors, and most arise in patients 50 years old or more [16]. Positivity for synaptophysin or chromogranin is useful for identification of small cell carcinoma. It is also difficult to rule out poorly differentiated carcinoma or undifferentiated carcinoma, although an abundant desmoplastic or fibromyxoid stroma is an unusual feature in these carcinomas. Therefore, this might be a diagnostic clue for DSRCT. Other differential diagnosis, such as malignant melanoma, metastatic neuroblastoma, or lymphoma, are excluded with positivity for epithelial markers. Merkel cell carcinoma is also the differential diagnosis, but it is excluded with staining for neuroendocrine markers and its characteristic dot-like staining pattern for cytokeratin 20.

Primary non-lymphoid mesenchymal neoplasms of major salivary glands are also rare and account for only 1.9–5% of cases [8]. Most mesenchymal tumors are benign. The most common mesenchymal tumor is lipoma, [8] [17]. Malignant cases are extremely rare [8]. Because of the histological features of small round cell tumors, Ewing sarcoma and rhabdomyosarcoma are also included as differential diagnoses. Positivity for desmin and WT1 nuclear staining in addition to positive epithelial markers strongly favors a diagnosis of DSRCT over that of Ewing sarcoma and rhabdomyosarcoma. Furthermore, molecular biology studies are useful and important in differentiating DSRCT from Ewing sarcoma and rhabdomyosarcoma. In the present case, the tumor nests were composed of not only small-sized cells with a high nuclear/cytoplasmic ratio, but also medium-sized cells with clear cytoplasm. These cells with clear cytoplasm were also described in a previous report [6]. Because both two cell types share the same immunohistochemical profiles in the present case, cells with clear cytoplasm should also be recognized as neoplastic, and not as non-neoplastic bystander cells such as myoepithelial cells.