Recurrent Unresectable Malignant Granular Cell Tumor With Response to Pazopanib

Abstract

Malignant granular cell tumors (MGCTs) are rare and aggressive variants of granular cell tumors. They usually involve the head and neck region, skin and soft tissues. There are no standard therapeutic guidelines for management; however, surgical resection, whenever feasible, is considered to be first line. We report a patient with recurrent unresectable MGCT of lower lip who responded to pazopanib monotherapy. This drug has been recently approved for the treatment of advanced soft tissue sarcomas. It is a potent oral tyrosine kinase inhibitor and acts on multiple receptors, including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), c-kit, platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR). Due to the overexpression of multiple genes by the tumor and multiple targets of this drug, it is difficult to establish the mechanism of action responsible for disease response.

Antiangiogenics in Malignant Granular Cell Tumors: Review of the Literature

“…Amongst these, 75 articles that fulfilled the above criteria according to their abstract or tittle were identified. After reviewing the full texts of these 75 articles, 10 articles were finally selected (Figure 2) [20][21][22][23][24][25][37][38][39][40]. The most common target systemic therapy used in GCTs according to this review of the literature was pazopanib, (Table 1).…”

“…Five patients had received previous systemic therapy, with limited benefit in terms of progression-free survival while no objective responses were detected. Previous treatments were as follows: three patients received chemotherapy (the different schemes administered were carbo-platin/paclitaxel + cetuximab, gemcitabine/docetaxel, doxorubicin/ifosfamide) [23,24,38] and no responses were reported, one patient received dasatinib progressing after two months, and one patient received smoothened inhibitor, after progression a PI3K inhibitor was administered with disease control lasting nine months [21].…”

“…Some cases reported in the literature have described the use of targeted therapies in malignant GCTs. In particular, there is growing evidence coming from case-reports on the use of pazopanib [20][21][22][23][24][25]. However, currently, there are no recommendations about the preferred systemic therapy for metastatic GCTs.…”

An update on cutaneous granular cell tumours for dermatologists and dermatopathologists

“…Some authors have reported success using the sarcoma treatment pazopanib and some recommend adjuvant radiotherapy. 28,29 Owing to the rarity of malignant GCTs, no randomized clinical trials have been performed. Benign GCTs have an excellent prognosis with complete surgical excision regarded as curative.…”

“…Chemotherapy and adjuvant radiotherapy have a disputed role in treating malignant GCTs and metastatic disease. Some authors have reported success using the sarcoma treatment pazopanib and some recommend adjuvant radiotherapy 28,29 . Owing to the rarity of malignant GCTs, no randomized clinical trials have been performed.…”