Pediatr Blood Cancer 2010;55:374–376 BRIEF REPORT How to Manage an Unresectable or Recurrent Sialoblastoma Ebru Tugrul Saribeyoglu, MD,1* Omer Devecioglu, MD,1 Zeynep Karakas, MD,1 Sema Anak, MD,1 Aysegul Unuvar, MD,1 Leyla Agaoglu, MD,1 Aladdin Celik, MD,2 Mine Gulluoglu, MD,3 and Bilge Bilgic, Only 2–5% of all salivary gland tumors occur in children. Sialoblastoma is an extremely rare salivary gland tumor diagnosed at birth or shortly thereafter with significant variability in histological range and clinical course, so that it may be difficult to predict the most appropriate therapy. In cases where surgical removal is not curative or technically feasible, chemotherapy may be attempted. We report herein a patient with progression of a huge partially Key words: MD 3 resected sialoblastoma who was successfully treated with chemotherapy. Systemic chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC) seems to be an effective adjuvant or neoadjuvant treatment option for unresectable or recurrent sialoblastoma. Pediatr Blood Cancer 2010;55:374–376. ß 2010 Wiley-Liss, Inc. embryoma; salivary gland tumors; sialoblastoma INTRODUCTION Sialoblastoma is an extremely rare salivary tumor diagnosed at birth or shortly thereafter with significant variability in histological range and clinical course, so that for an individual case it may be difficult to predict the most appropriate therapy. Fewer than 30 cases of sialoblastoma have been reported in the English literature. This rare epithelial salivary gland tumor arises mainly from the parotid gland. It is usually diagnosed at birth. They are locally infiltrative and can be treated with surgery alone, if a complete surgical resection with tumor free margins can be achieved [1]. Prognosis is determined by the tumor grade as well as the stage at presentation and the extent of resection. In cases where surgical removal is not possible or incomplete, chemotherapy may be attempted. We report a patient with progression of a partially resected sialoblastoma, which was successfully treated with chemotherapy alone. CASE REPORT A 3-day-old male was referred to our clinic with a right lateral face and neck mass measuring 15 cm  10 cm  8 cm with superficial hemorrhage and necrosis (Fig. 1A). After an uneventful pregnancy, he was born spontaneously by vaginal route. The patient’s antenatal ultrasound (US) records were not available since no prenatal follow-up had been performed. Magnetic resonance imaging (MRI) revealed a facial mass located in the region of the right parotid gland and invading the maxilla and adjacent muscles, without evidence of intracranial or intraorbital extension. Heterogeneous and weak contrast enhancement was detected on contrastenhanced images. The radiological appearance of the tumor is a soft tissue mass hypodense to the brain and isodense to muscle (Fig. 1B). During surgery, the mass was necrotic and fragile and found to extend through the adjacent muscles. It was invading the right maxilla and oropharyngeal mucosa and the parotid gland could not be discerned separately from the mass. Parotidectomy and partial tumor resection were performed on the eighth day from the birth, but the size, extent, and invasive character of the tumor made total excision with tumor-free margins impossible; the tumor was resected with microscopic residue. The histopathological examination of the tumor revealed sialoblastoma. S-100 protein, PAS, and DPAS were positive. The proliferation index was 95%. ß 2010 Wiley-Liss, Inc. DOI 10.1002/pbc.22464 Published online 19 April 2010 in Wiley InterScience (www.interscience.wiley.com) In light of the positive surgical margin, chemotherapy was proposed, but the family refused the treatment and the patient was lost to follow-up for 3 months. The child was re-admitted 3 months later and at that time the tumor size was greater than the original presentation. A complete staging examination was performed to rule out any metastasis; a chest CT scan, bone scintigraphy, and lumbar puncture showed no evidence of distant disease or spread to the central nervous system. After obtaining an informed consent from the family, chemotherapy was started when the baby was 312 months old. The chemotherapy regimen (low-dose VAC) consisted of vincristine 0.7 mg/m2/day, actinomycin D at 0.007 mg/kg/day for 5 days, cyclophosphamide 20 mg/kg/day; this course was repeated every 3 weeks. After the initial course of therapy, tumor shrinkage of 70% was clinically and radiologically achieved. After the second course, there was no evidence of disease and the tumor disappeared completely with some cosmetic sequela. However, the patient developed severe veno-occlusive disease (VOD), which was successfully treated with defibrotide. The third course could only be delivered after a delay of 8 weeks. The treatment was well tolerated apart from the VOD. After a total of four courses of VAC, the patient is still in remission for the last 4 years and is doing well. There is some facial soft tissue asymmetry but mandibular growth is normal (Fig. 2). DISCUSSION Only 2–5% of all salivary gland tumors occur in children. Most lesions present after the age of 5 years and there is an increasing incidence over the first two decades of life [1]. Most —————— 1 Department of Pediatric Hematology-Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Surgery, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; 3Department of Pathology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey Conflict of interest: Nothing to report. *Correspondence to: Ebru Tugrul Saribeyoglu, Acibadem University, Buyukdere cad. No: 40 Maslak, 34457, Istanbul. E-mail: ebrusaribeyoglu@gmail.com Received 13 November 2008; Accepted 11 January 2010 Management of Sialoblastoma Fig. 1. The presentation of the patient before treatment. A: The picture shows a huge right lateral face and neck mass. B: CT appearance of the tumor. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] of these tumors originate from the parotid gland, but submandibular, sublingual, or minor salivary glands can also be affected [1,2]. Perinatal, congenital, and neonatal salivary gland tumors are exceptionally rare with about 30 reported cases in the literature. Sialoblastoma is a congenital tumor of the salivary glands arising mainly from the parotid gland and might be locally invasive and potentially malignant. It can also behave aggressively and metastasize, thus requires systemic intervention [3]. Histopatho- Fig. 2. Post-treatment picture of the patient. The tumor disappeared completely after the therapy with some cosmetic sequela. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] Pediatr Blood Cancer DOI 10.1002/pbc 375 logical description of sialoblastoma was initially reported and named as embryoma by Vawter and Tefft in 1966 [4]. This tumor has been called by various names, such as congenital basal cell adenoma, monomorphic adenoma, basal cell adenoma, low-grade basaloid adenocarcinoma, congenital hybrid basal cell adenoma, or adenoid cystic carcinoma [5–8] in the past. However, Taylor [9] defined a universally accepted terminology of sialoblastoma in 1988. The majority of the tumors arise in the parotid gland, the remainder in the submandibular gland [2]. Sialoblastomas can also develop from a pre-existing cutaneous hamartoma [3,10,11]. Som et al. [12] reported that sialoblastomas had low intermediate signal intensity and slightly higher intermediate signal intensity on T1-weighted and T2-weighted MRI images. In this present case, the majority of the lesion was mildly hyperintense on T2-weighted images. In this age group, however, the commonest lesion in the salivary glands, with predilection of the parotids, is hemangioma. But hemangiomas typically show hypervascularity on color Doppler US, uniform and intense enhancement post-contrast injection on CT and MRI, and presence of flow voids on spin-echo MRI [13]. The histopathological description of the sialoblastoma was consolidated by Hsueh and Gonzalez-Crussi in 1992 [14]. Like in our case, immunoperoxidase staining shows the presence of cytokeratin in the ductal cells as well as the positive staining for keratin, vimentin, smooth muscle actin, and S-100 protein in the outermost layer of the ducts to varying degrees. Sialoblastomas are usually locally invasive but distant metastases were also reported [3,15]. There is no uniform approach to the management of sialoblastoma in the literature. If tumor-free margins are obtained, it can be treated with early conservative surgery alone [16,17]. In incompletely resected cases, local invasion can be life threatening [18]. In adult patients with unresectable or recurrent parotid tumors radiation therapy can be considered. But in pediatric patients the potential side effects and inevitable consequences for the mid-face growth limit the use of radiation and surgery remains the treatment of choice [19]. Chemotherapy has been recommended in unresectable, partially resectable, and recurrent cases [3,4,10,14]. The disease recurrence in our patient progressed very rapidly requiring urgent intervention. In the literature, a combination of radiation therapy and chemotherapy (vincristine, doxorubicin, cyclophosphamide alternating with cisplatin, and etoposide for a total of four courses) and SIOP MMT953B protocol (consisting of carboplatin, epirubicin, vincristine, etoposide, ifosfamide, and actinomycin D) were used successfully [3,10]. To avoid the side effects of the radiation therapy we omitted using radiation and treated the patient with only a low-dose VAC chemotherapy regimen. Our goal was to decrease the tumor volume such that a second surgery with free margins could be done. The tumor showed a favorable response to chemotherapy so well that a second surgery was not necessary. VOD was the only major chemotherapyrelated complication. After the resolution of VOD we were able to give the rest of the chemotherapy (two more courses of VAC) without any major problems. In conclusion, the management of this rare tumor is still controversial when complete resection is not possible. Neoadjuvant chemotherapy may therefore be an option to reduce tumor size and diminish the extent of surgery in primarily resectable cases, with the possibility of improved cosmetic results. 376 Saribeyoglu et al. REFERENCES 1. Krolls SO, Trodahll J, Maleers RC. Salivary gland lesions in children. A survey of 430 cases. Cancer 1972;30:459–469. 2. Mostafapour SP, Folz B, Barlow D, et al. Sialoblastoma of the submandibular gland: Report of a case and review of the literature. Case report. 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