Angiosarcoma of the thyroid is a rare and aggressive primary malignant tumor of the thyroid originally reported in patients from the Swiss Alpine region. Diagnosis of this tumor rests mainly on characteristic histopathological features of a malignant vascular tumor supported by immunopositivity for vascular markers e.g., CD31, Factor VIII, and CD34. Its cytological features, however, are not well-defined. We describe a case of primary angiosarcoma of the thyroid in a 48-year-old female, who presented with a rapidly enlarging neck mass associated with compressive symptoms. She had a history of hypothyroidism. The initial fine needle aspiration cytology of the neck mass was negative. She then underwent left hemithyroidectomy. Histologically, the tumor showed poorly differentiated malignant cells with eccentrically-placed nuclei, prominent nucleoli, and intracytoplasmic vacuoles admixed with mixed inflammatory cells. These showed immunopositivity for CD31 but were negative for CD34, Factor VIII, CK5/6, EMA, TTF-1, Thyroglobulin, Calcitonin, Melan A, and Calretinin. A diagnosis of poorly differentiated malignant tumor consistent with angiosarcoma was made. The patient was treated with radiation therapy but developed recurrence of the tumor. Second aspiration cytology of the recurrent tumor yielded hypocellular smears containing singularly dispersed atypical cells having eccentrically-placed nuclei with prominent macronucleoli and intracytoplasmic vacuoles within a background of inflammatory cells, consistent with recurrent angiosarcoma. Chemotherapy was started but she succumbed to the disease 7 months after diagnosis. The cytological, histopathological, immunohistochemical findings, and the clinical course are discussed.
We recently reported the antineovascularization effect of scopoletin on rat aorta and identified its potential anti-angiogenic activity. Scopoletin could be useful as a systemic chemotherapeutic agent against angiogenesis-dependent malignancies if its antitumorigenic activity is investigated and scientifically proven using a suitable human tumor xenograft model. In the present study, bioassay-guided (anti-angiogenesis) phytochemical investigation was conducted on Nicotiana glauca extract which led to the isolation of scopoletin. Further, anti-angiogenic activity of scopoletin was characterized using ex vivo, in vivo and in silico angiogenesis models. Finally, the antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenograft model using athymic nude mice. For the first time, an in vivo anticancer activity of scopoletin was reported and characterized using xenograft models. Scopoletin caused significant suppression of sprouting of microvessels in rat aortic explants with IC50 (median inhibitory concentration) 0.06μM. Scopoletin (100 and 200mg/kg) strongly inhibited (59.72 and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice. In the tumor xenograft model, scopoletin showed remarkable inhibition on tumor growth (34.2 and 94.7% at 100 and 200mg/kg, respectively). Tumor histology revealed drastic reduction of the extent of vascularization. Further, immunostaining of CD31 and NG2 receptors in the histological sections confirmed the antivascular effect of scopoletin in tumor vasculature. In computer modeling, scopoletin showed strong ligand affinity and binding energies toward the following angiogenic factors: protein kinase (ERK1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). These results suggest that the antitumor activity of scopoletin may be due to its strong anti-angiogenic effect, which may be mediated by its effective inhibition of ERK1, VEGF-A, and FGF-2.