it behaves highly aggressive and spreads widely throughout the skin , recurs locally , and metastasizes early .
standard treatment with resection and adjuvant radiotherapy results in local control in approximately 50% of patients at 1 year and median survival is approximately 8 months .
considerable evidence has implicated matrix metalloproteinases ( mmp ) in the degradation of the extracellular matrix ( ecm ) during the metastatic process .
murakami et al .   reported the expression of mmp-2 on subcutaneous angiosarcoma in canine . in human ,
however , there is no english report suggesting the expression of mmp-9 on human angiosarcoma of the skin . in this report
, we describe a case of angiosarcoma in which complete remission was archived with low dose docetaxel and bisphosphonate after the standard treatment of angiosarcoma .
a 78-year - old woman consulted us with a 6-month history of an asymptomatic nodule on her scalp .
her nodule has been surgically resected at a private clinic 3 months before her visit .
two weeks after the resection , skin nodules had suddenly enlarged . on her first visit ,
physical examination revealed a skin - colored nodule with a surgery scar , teleangiectasia and purpura on her scalp ( fig .
histologically , irregular anastomosing vascular channels lined by single layers of enlarged endothelial cells existed between collagen bundles with dense infiltration of lymphocytes ( fig .
immunohistochemical staining revealed that these enlarged endothelial - like cells were strongly positive for cd31 and vimentin , and positive for factor viii and thrombomodulin , and negative for cd34 , s-100 , ck , sma , and desmin .
moreover , these enlarged endothelial - like cells and tumor stromas were positive for mmp-9 ( fig .
we used rabbit polyclonal anti - human mmp-9 antibody ( abcam , tokyo , japan ) at a dilution of 1:100 .
in addition , we employed immunohistochemical staining for 9 cases of angiosarcomas that were histologically diagnosed in our institution , and about 78% ( 7/9 ) cases of angiosarcomas were positive for mmp9 . from these results , we diagnosed this patient as mmp-9-expressing angiosarcoma . positron emission tomography ( pet ) scans showed no evidence of metastases .
then , we administered docetaxel monthly at 40 mg / m body surface area intravenously and weekly with oral administration of 17.5 mg sodium risedronate hydrate .
one and a half years after the surgical treatment , there was no evidence of local recurrence or metastasis .
in our present case , we describe a case of mmp-9-expressing angiosarcoma treated with low - dose docetaxel and bisphosphonate . like paclitaxel
, docetaxel promotes microtubule assembly and inhibits the depolymerization of tubulin , thus stabilizing microtubules , but docetaxel has a higher potency [ 4 , 7 , 8 ] .
however , in studies conducted in europe , docetaxel monotherapy was rather ineffective for soft - tissue sarcoma , including angiosarcoma , and could not be recommended for further use .
mmp-9 is a stromal factor that regulates the mobilization of hematopoietic stem cells from the bone marrow niche by solubilizing the membrane - bound form of c - kitl . because it remodels the extracellular matrix and promotes the sprouting and growth of new blood vessels by making vegf available to the vegfr-2/flk receptor on endothelial cells , mmp-9 is a linchpin in tumor progression .
moreover , recently , several reports revealed the expression of mmp-9 on tumor correlated with the progression or prognosis of several skin tumors such as malignant melanoma , squamous cell carcinoma , basal cell carcinoma , and mycosis fungoides .
in addition , koontz et al .   reported two cases of successful treatment of angiosarcoma with the administration of the anti - vegf antibody bevacizumab along with radiotherapy prior to surgery .
more recently , it was reported that pharmacological inhibition of mmp-9 by amino - bisphosphonate decreased pro - mmp-9 and vegf in the serum and abrogated the induction of immunosuppressive macrophages , myeloid - derived suppressor cells ( mdscs ) , in the tumor microenvironment [ 15 , 16 ] . in aggregate ,
inhibition of mmp-9 by bisphosphonate could be one of the optimal supportive therapies for the treatment of angiosarcoma by inhibiting tumor - induced angiogenesis and by the induction of anti - tumor immunity . in conclusion ,
the combination of docetaxel with bisphosphonate was effective for mmp-9-expressing angiosarcoma and resulted in complete remission after the standard therapy for angiosarcoma .
 we describe a 78-year - old japanese patient with angiosarcoma on the scalp . 
 interestingly , immunohistochemical staining revealed this tumor as positive for matrix metalloproteinase 9 ( mmp-9 ) . 
 after conventional therapy for angiosarcoma with surgical treatment and radiation therapy , we intravenously administered docetaxel at 40 mg / m2 body surface area together with oral administration of 17.5 mg sodium risedronate hydrate . 
 one and a half years after the standard treatment , there was no evidence of local recurrence or metastasis . 
Introduction
Case Report
Discussion