Among fifty-five patients, who were clinically suspicious for vascular tumors, five patients were excluded due to final diagnosis confirmed nonvascular tumors, incomplete data sets and lose follow up. Therefore, 50 patients with confirmed diagnosis of vascular tumors were subsequently enrolled in this study as shown in Figure 1. Medical records of all participating patients were retrospectively reviewed with complete information described in Supplementary Table 1. Patients’ characteristics including age, sex, diagnosis, diagnostic modalities including histopathological examination and imaging studies, size and location of the tumor, treatment strategies and its complications and clinical outcomes are summarized in Table 1.
Among 50 patients with vascular tumors enrolled in this study, most presented at older age with a median age at diagnosis of 11.5 years. Sex was equally distributed with a male to female ratio of 1:1. Hemangioma was the most common diagnosis followed by pyogenic granuloma, KHE with KMP, infantile hepatic hemangioma or liver hemangioendothelioma without KMP and juvenile nasal angiofibroma (JNA), in rank. Histopathological examination was the key diagnostic modality to establish diagnosis with radiological studies required in small numbers of patients whose tumors were inoperable. The reasons for inability to resect the tumors were large hemangiomas at the face and lower extremity for two patients, tumor with KMP-related complications for two patients and multiple infantile hepatic hemangiomas in 1 patient.
The average tumor size was 3.6 cm in the longest diameter located most commonly at the head and neck regions including the scalp, eyelids, face and lips. Most patients presented cutaneous vascular tumors, in which only 10% were noted to have visceral tumors located at the liver, brain, orbit and retroperitoneal regions. Hemorrhagic complication was commonly seen at initial diagnosis followed by poor weight gain, proptosis, feeding intolerance and seizures, in rank.
Among 50 patients with vascular tumors enrolled in this study, radiological studies were essentially required to assist in establishing diagnosis and management plans in almost one half of the patients. The most common radiological modality used in this study was MRI followed by ultrasonography and CT scan, respectively as shown in Table 1. However, 6 in 21 patients required a combination of radiological imaging including CT scan, ultrasonography, Tc 99m-bone scan and MRI. In addition, all vascular tumors with visceral organ involvement (Figure 2), KHE with KMP, JNA and infantile hepatic hemangioma were imaged.
Over 90% of patients enrolled in this study received treatment intervention as shown in Table 1, and most underwent surgical resection of the tumors with no postoperative complications reported. However, three patients who underwent surgery had disease recurrence after partial resection of the tumors, and the remaining patients undergoing surgery remained in complete remission until their last follow-up visits. Medical treatment was administered among three patients (6%). Intravenous vincristine combined with oral prednisolone was delivered to two patients with KHE complicated by KMP resulting in complete resolution of the tumors. One patient received oral prednisolone monotherapy with partial response to treatment. The decision was made to closely observe and monitor clinical status among three patients (6%) whose tumors were inoperable including the scalp hemangioma, large intramuscular hemangioma of the right leg and multiple infantile hepatic hemangiomas. Spontaneous regression until complete resolution of the tumor was noted in one patient; however, another two experienced spontaneous regression with partial resolution of the tumor on their last follow-up visit.
All patients with vascular tumors enrolled in this study did not experience tumor-related mortality. Only one patient, presenting hemangioma at the extremity which was completely excised, died from liver cirrhosis and congestive heart failure due to the underlying biliary atresia status post Kasai operation. In summary, 43 patients (86%) survived without evidence of disease. Six (12%) patients survived with disease including three patients who had disease recurrence after partial resection of the tumors, one who was treated with oral prednisolone with partial response, one with intramuscular hemangioma of the right leg and one with multiple infantile hepatic hemangioma. The last two patients were closely observed clinically as shown in supplementary Table 1.
Kapasiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP)
KMP is a life-threatening condition requiring immediate recognition and management. Two patients of KHE with KMP enrolled in this study received a diagnosis from clinical and laboratory findings combined with radiological studies as described in Table 2. Both cases required multiple platelet and cryoprecipitate transfusions to maintain platelet count as well as fibrinogen level in normal range. In addition, intravenous vincristine and oral prednisolone were administered resulting in complete resolution of the tumors. The first patient was treated with prednisolone 2 mg/kg/day for two weeks and then tapering off at six weeks and vincristine 0.625 mg/kg/day weekly for four weeks then monthly for five months (totaling six months therapy), and the patient could achieve complete remission within eight months after treatment (Figure 3). The second patient was also treated with combined vincristine and prednisolone regimen and could achieve complete resolution within six months after treatment. In addition, both patients survived without evidence of disease recurrence.
Cutaneous versus visceral vascular tumors
The majority of patients enrolled in this study presented cutaneous vascular tumors (90%) while 10% of those experienced visceral involvement. Patient characteristics including age, sex, location of the tumor, size, diagnosis, diagnostic modalities including histopathological examination and imaging studies, treatment strategies and clinical outcomes are summarized in Table 3. However, no significant difference was found regarding sex, treatment modalities and outcomes between the two groups of patients. Interestingly, the median age at diagnosis of patients with cutaneous vascular tumors was significantly older than the age of those with visceral vascular tumors (p-value 0.009). In addition, the mean size of visceral vascular tumors among patients was significantly greater than the size of those with cutaneous vascular tumors (p-value 0.023). Types of cutaneous and visceral vascular tumors also significantly differed, in which hemangioma, pyogenic granulomas and JNA were found mostly among patients with cutaneous vascular tumors with p-value <0.001. Moreover, histopathological examination was mostly performed and served as the main diagnostic modality among patients with cutaneous vascular tumors compared with those with visceral vascular tumors (p-value 0.018).
Influential factors associated with clinical outcomes
Among 50 patients with vascular tumors enrolled in this study, 49 patients survived. Only one patient, in complete remission, died from the complications of underlying biliary atresia. Age at diagnosis, sex, location of the tumor, existing visceral involvement and types of treatment were analyzed and were found not significantly associated with outcomes. However, univariate analysis was performed revealing significant differences of average tumor size between patients who survived with residual disease (8.8±4.64 cm.) and those who survived without disease (2.96±3.37 cm.) with p-value 0.008. In addition, multivariate analysis was subsequently performed affirming that the size of vascular tumor remained an independent risk factor to identify outcome of disease with p-value 0.008 as shown in Table 4 (adjusted odds ratio [OR], 1.359; 95% confidence interval [CI], 1.083-1.707).
Moreover, among 44 particular patients with cutaneous vascular tumors, age at diagnosis, sex and types of treatment were not significant predicting factors for the outcome. However, univariate analysis was performed revealing statistically significant differences of average tumor size between patients who survived with residual disease (9.00±5.15 cm.) and those who survived without disease (2.46±2.73 cm.) with p-value <0.001. In addition, multivariate analysis was subsequently performed affirming that the size of vascular tumor remained an independent risk factor to identify outcome of disease particularly among patients with cutaneous vascular tumors with p-value 0.027 as shown in Table 5 (adjusted OR, 1.487; 95% CI, 1.046-2.116).