kaposiform hemangioendothelioma ( khe ) is a rare neoplasm of vascular origin typically arising from the skin or soft tissues , and it is more often described in children .
the tumor is composed of irregular lobules of small malformed vessels with sheets of spindle cells and infiltrating nodules .
previously , khe has been compared to other vascular abnormalities such as juvenile hemangiomas , tufted angiomas , capillary hemangiomas , and kaposi sarcoma .
tumor cells typically express endothelial markers , such as cd31 and cd34 . in the largest cohort of patients with khe including 107 cases , the disease occurred in infancy in 93% of cases ; only 11% of patients presented with noncutaneous khe , the majority of them in bone , mediastinum , or retroperitoneum .
khe can be associated with the development of kasabach - merritt phenomenon ( kmp ) in up to 71% of the cases . in this life - threatening syndrome ,
severe thrombocytopenia and hypofibrinogenemia occur as a result of intralesional platelet trapping . despite the locally aggressive behavior and
the potential for lethal complications due to consumptive coagulopathy in the setting of kmp , metastatic spread of khe seldom occurs . here
, we present the case of a patient with khe with several atypical features , namely onset in adulthood , primary presentation in the spleen , and metastatic spread to the liver and bones , with a partial response to treatment with paclitaxel .
a 36-year - old caucasian male presented to the emergency department with acute onset of abdominal pain in the left upper quadrant in november 2012 .
abdominal tenderness in the left upper quadrant was noteworthy . a computed tomography ( ct ) scan revealed a 16  11  24 cm splenic mass with signs of splenic rupture .
exploratory laparotomy was performed with an intraoperative finding of spontaneous splenic rupture and active subcapsular bleeding .
a splenectomy was performed , and the patient was discharged without any additional complications . initial external pathology assessment of the mass indicated a nonspecific vascular proliferation , and the patient started follow - up with his primary care physician .
surveillance ct scans performed in january 2013 revealed enlarged cervical and mediastinal lymph nodes , lytic bone lesions in vertebral bodies , a 1.7-cm peritoneal node , and a punctate lesion in the skullcap .
short - interval imaging repeated in may 2013 detected additional vertebral lesions and multiple hepatic metastases .
the initial recommendation included systemic treatment with gemcitabine and docetaxel , and treatment was started in july 2013 , with significant hematological toxicity , leading to treatment discontinuation .
a pathology review showed endothelial cells with lobular - pattern proliferation ; immunohistochemical staining revealed positivity for vimentin , cd34 , and cd31 and negativity for hhv8 , s-100 , and smooth muscle actin . ki-67
the decision was made to withhold the systemic treatment and periodically repeat the scans every 3 months , since there was no clear evidence of progression .
although the patient remained asymptomatic for 6 months , ct scans showed an increase in the number and volume of hepatic lesions ( fig .
after 18 weeks , restaging ct scans revealed stability of the vertebral lesions and reduction of the hepatic lesions ( table 1 ; fig .
2b ) , consistent with a 40% reduction based on investigator - assessed recist criteria .
paclitaxel was continued until october 2014 ( total of 24 weeks ) , when restaging scans revealed disease progression .
subsequent lines of treatment included oral prednisone , doxorubicin , interferon- , gemcitabine , and ifosfamide , with no radiologic response or clinical benefit .
although the patient remained with mild to moderate symptoms and adequate performance status , the decision was made to offer best supportive care , and the patient was referred to a palliative care service .
after 2 months , the patient had acute onset of thrombocytopenia , hypofibrinogenemia , petechiae , and epistaxis .
one week after the presumptive diagnosis of kmp was made , the patient died due to a major episode of gastrointestinal bleeding .
atypical presentations of khe have been reported in the bones , breast , thymus , thyroid , ductus choledochus , or retroperitoneum .
khe from the spleen has been previously described in a single case by yu and yang , with long - term recurrence - free survival after splenectomy .
the case reported here presents several atypical features , namely the age at onset and the pattern of distant spread .
in addition , kmp was described in 70% of the cases in the largest published cohort of patients with khe , usually in patients with muscle or fascia involvement , retroperitoneal disease , or mediastinal involvement .
described multilevel spinal involvement in a 6-year - old girl with khe that responded to systemic therapy .
due to the rarity of this condition , the optimal management of patients with khe remains unclear , and treatment options are supported by small series and single case reports . whenever feasible , complete surgical resection should be recommended .
however , complete resection is not always possible due to the infiltrative and locally aggressive nature of khe .
medical therapies in the setting of unresectable / metastatic khe aim to decrease the tumor size , revert kmp , and palliate symptoms . corticosteroids are widely used .
a consensus meeting suggested oral prednisolone 2 mg / kg / day as the first - line therapy for infant cases with enlarging , unresectable masses requiring intervention without kmp .
additional responses were seen with vincristine , interferon- , actinomycin d , cyclophosphamide , and sirolimus . based on the lack of prospective data addressing the optimal treatment for khe , extrapolating the experience with the treatment of other vascular tumors was a strategy for the present case .
paclitaxel was recommended in the present case and resulted in partial response after 3 cycles .
this semisynthetic taxane showed clinical benefit in a phase ii trial in patients with angiosarcoma .
interestingly , very low concentrations of paclitaxel proved to inhibit endothelial cell proliferation in an in vitro environment .
had previously described the first evidence of paclitaxel - based chemotherapy in a case of metastatic khe . to the best of our knowledge ,
our report is the second khe case in the literature documenting an objective response after treatment with paclitaxel . in a retrospective analysis from the memorial sloan kettering cancer center , first - line doxorubicin , liposomal doxorubicin , or paclitaxel produced response rates of 2531% , with equivalent overall survivals in patients with angiosarcoma .
molecular therapies may also benefit patients with vascular sarcomas . despite disappointing results in a phase ii study with nonselected patients with sarcomas , sorafenib led to clinically relevant responses in radiation - associated breast angiosarcomas with myc and flt4 amplifications . of note , tyrosine kinase or mtor inhibitors or antiangiogenic agents
were not offered to the present patient since these molecules are not available for routine use in our institution for this indication .
in summary , this case illustrates an unusual presentation of khe with metastatic spread to the liver and bones , in which the patient experienced a partial response to paclitaxel - based chemotherapy . due to the lack of prospective data , we consider reports such as ours of importance for improving the knowledge about this rare and challenging condition .
written informed consent was obtained from the patient for publication of this case report and accompanying images .
 backgroundkaposiform hemangioendothelioma ( khe ) is a rare neoplasm of vascular origin that typically arises from the skin or soft tissues as a solitary tumor . 
 the optimal therapy for this disease is still unknown . 
 we report the case of an adult patient presenting with metastatic khe of the spleen , who had a partial response after treatment with paclitaxel.case presentationa 36-year - old man presented in november 2012 with a nontraumatic rupture of the spleen . 
 a splenectomy was performed , and the pathology was consistent with a nonspecific vascular proliferation . 
 follow - up scans revealed lytic bone lesions and liver metastasis . a biopsy of the liver was performed and confirmed khe . 
 the decision was made to proceed with treatment with gemcitabine and docetaxel , which was discontinued due to myelotoxicity . 
 the patient was then transferred to our institution , and a pathology review supported the diagnosis of metastatic khe . 
 his disease remained stable until february 2014 , when he developed progression in the liver . 
 chemotherapy was restarted with paclitaxel , and a partial response was documented after 3 cycles . unfortunately , disease progression occurred after 24 weeks , and subsequent treatments included prednisone , doxorubicin , interferon- , gemcitabine , and ifosfamide , without any response . 
 the patient developed kasabach - merritt phenomenon and passed away 1 week later due to a major gastrointestinal bleeding.conclusionsthis case report suggests that paclitaxel could be considered as a treatment option for advanced khe , a rare condition for which no standard treatment exists . 
Background
Case Report
Discussion
Conclusions
Statement of Ethics
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