Vascular Tumor with Kasabach Merritt Phenomenon Treated with Steroids and Vincristine: A Retrospective Study.

Vascular tumours (VT) with Kasabach-Merritt phenomenon (KMP) are rare and aggressive tumors. In absence of evidence based treatment guidelines, we studied varied presentation and response to therapy with vincristine and steroids in VT with KMP at our center. In this retrospective observational study, infants with a symptomatic/disfiguring rapidly growing VT with features of KMP were included. Demographic, treatment and outcome data was retrieved from patient file. Complete response (CR) was defined as complete clinical regression of VT with normalization of coagulopathy and thrombocytopenia. Partial response (PR) was defined as decrease in size of VT by more than 80%, absence of clinical bleed with normalization of coagulopathy and platelet count > 50,000/cumm. Five infants (2-male, 3-female) with age range (0-7 month) treated with daily prednisolone and weekly vincristine were included. The location of VT was: face (2), hemi-thorax (2) and urinary bladder (1). Four of five infants showed PR within two months; while two of these attained CR to treatment. There were no significant adverse effects over 9-32 (range) month follow-up. Two children (one in PR, one immediately after presentation) succumbed to intra-cranial hemorrhage. Combination therapy of steroids with vincristine is effective and safe in management of VT with KMP.

A case report of primary Kaposiform hemangioendothelioma of the humerus.

To examine the clinicopathological and immunohistochemical features of Kaposiform hemangioendothelioma (KHE) and discuss its differential diagnosis and prognosis. A patient with KHE was examined; the patient's clinical and histopathological features were observed, and the expression levels of CD31, CD34, ERG, D2-40, SMA, GLUT-1, and LANA-1 were assessed. The patient was a four-year-old child with primary KHE of the humerus. She was admitted to the hospital because of pain in the right elbow joint and limited movement for more than 2 years. Imaging revealed Langerhans cell histiocytosis. The child was not diagnosed with Kasabach-Merritt phenomenon (KMP). The tumor consists of multiple hemangiomatous nodules with infiltrative growth separated by fibrous connective tissue. The proliferating hemangiomatoid nodules consisted of crisscrossing short spindle-shaped cell bundles and erythrocyte-containing lacunar or crescentic vessels. Immunohistochemical staining showed that the tumor cells diffusely expressed CD31, CD34, ERG, and other vascular endothelium-derived markers; further, the tumor cells expressed neither GLUT-1 nor LANA-1. The patient's general condition improved after surgical resection. There was no tumor recurrence after more than 8 months of follow-up. Primary KHE of the humerus is a rare vasculogenic tumor. It presents with morphological features that require an accurate differential diagnosis.

A Case of Superficial Kaposiform Hemangioendothelioma Treated with Oral Propranolol Combined with Topical Sirolimus.

Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.

Treatment experience for different risk groups of Kaposiform hemangioendothelioma.

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging. Objective: The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE. Methods: Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data. Results: In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge. Conclusions: Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Coexistence of kaposiform hemangioendothelioma and capillary malformation: More than a coincidence? Two case reports.

The coexistence of kaposiform hemangioendothelioma (KHE) and capillary malformation (CM) is quite rare, and few relevant studies can be found to confirm whether this phenomenon is accidental. We diagnosed and treated two such patients, revealing interesting phenomena associated with the development of vascular diseases. These cases offer the possibility that the coexistence of KHE and CM is not accidental and open up a new field of research related to pediatric vascular tumors and vascular malformations. Personalization and precision are required in the diagnosis and treatment of such patients, and the present findings provide a reliable theoretical and practical basis for further research on the pathogenesis and therapy of patients with multiple vascular diseases.

Sirolimus monotherapy for Kasabach-Merritt phenomenon in a neonate; Case report.

INTRODUCTION AND IMPORTANCE: The Kasabach-Merritt Phenomenon (KMP), characterized by thrombocytopenia and consumptive coagulopathy due to endothelial cell growth in the infantile vascular tumor kaposiform hemangioendothelioma, presents a therapeutic challenge. This case highlights the novel use of sirolimus in a neonate, an approach less explored in this age group. CASE PRESENTATION: A female neonate presented with a right anterior chest mass, progressing to respiratory distress and congestive heart failure. Diagnosed with KMP, she exhibited low platelet count and coagulation abnormalities. Treatment with sirolimus (0.06 mg/day) led to mass reduction, improved bleeding, and a stable tumor after 12 months, without side effects. This case contrasts with existing literature advocating for combination therapy or higher sirolimus concentrations for effective treatment. Yet, our patient achieved favorable outcomes with low-dose monotherapy, suggesting a potentially safer approach in neonates with immature hepatic and renal metabolism. CLINICAL DISCUSSION: This case demonstrates the efficacy of low-dose sirolimus monotherapy in treating KMP in a neonate, challenging current preferences for combination therapies or higher doses. It emphasizes the need for further research into age-specific treatment protocols in KMP, considering the unique metabolic profiles of neonates and infants. CONCLUSION: Sirolimus has demonstrated potential in treating KMP in pediatric patients. While initial results are promising, determining optimal dosages and trough concentrations, especially in neonates and infants, remains essential.

Construction and applications of the EOMA spheroid model of Kaposiform hemangioendothelioma.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare intermediate vascular tumor with unclear pathogenesis. Recently, three dimensional (3D) cell spheroids and organoids have played an indispensable role in the study of many diseases, such as infantile hemangioma and non-involuting congenital hemangiomas. However, few research on KHE are based on the 3D model. This study aims to evaluate the 3D superiority, the similarity with KHE and the ability of drug evaluation of EOMA spheroids as an in vitro 3D KHE model. RESULTS: After two days, relatively uniform morphology and high viability of EOMA spheroids were generated by the rotating cell culture system (RCCS). Through transcriptome analysis, compared with 2D EOMA cells, focal adhesion-related genes such as Itgb4, Flt1, VEGFC, TNXB, LAMA3, VWF, and VEGFD were upregulated in EOMA spheroids. Meanwhile, the EOMA spheroids injected into the subcutaneous showed more obvious KMP than 2D EOMA cells. Furthermore, EOMA spheroids possessed the similar characteristics to the KHE tissues and subcutaneous tumors, such as diagnostic markers (CD31 and LYVE-1), cell proliferation (Ki67), hypoxia (HIF-1α) and cell adhesion (E-cadherin and N-cadherin). Based on the EOMA spheroid model, we discovered that sirolimus, the first-line drug for treating KHE, could inhibit EOMA cell proliferation and downregulate the VEGFC expression. Through the extra addition of VEGFC, the effect of sirolimus on EOMA spheroid could be weakened. CONCLUSION: With a high degree of similarity of the KHE, 3D EOMA spheroids generated by the RCCS can be used as a in vitro model for basic researches of KHE, generating subcutaneous tumors and drug screening.

Adult-onset multifocal kaposiform hemangioendothelioma in the bone marrow, lung, liver, and brain: a case report.

Kaposiform hemangioendothelioma (KHE), a rare form of vascular neoplasm, is typically seen in children. In this paper, we report a unique case of KHE replacing bone marrow tissue mimicking myeloproliferative neoplasm with additional involvement in the lung, liver, and brain in a 60-year-old Caucasian woman. The patient was initially seen in the hematology department for the chief complaint of epigastric pain and anemia. Abdominal magnetic resonance imaging (MRI) revealed mild splenomegaly with iron deposition secondary to extramedullary hematopoiesis. Additional workup was inconclusive. Subsequent bone marrow and lung biopsies eventually revealed bone marrow with extensive grade 3 fibrosis and multiple foci of low-grade vasoformative neoplasm in the lung suggestive of KHE. Although rare, KHE can present as an aggressive disease with indolent behavior in adults and can be distinguished from other vascular malignancies based on histopathology and imaging findings.

How we use angiopoietin-2 in the diagnosis and management of vascular anomalies.

The diagnosis of vascular anomalies remains challenging due to significant clinical heterogeneity and uncertain etiology. Evaluation using biopsy and/or genetic testing for somatic variants is invasive, expensive, and prone to sampling error. There is great need for noninvasive and easily measured blood laboratory biomarkers that can aid not only in diagnosis, but also management of treatments for vascular anomalies. Angiopoietin-2, a circulating blood angiogenic factor, is highly elevated in patients with kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon and kaposiform lymphangiomatosis. Here, we describe our clinical experience using serum angiopoietin-2 as a biomarker for diagnosis and monitoring response to treatment.

Vascular tumors of intermediate malignancy: An update.

The term "hemangioendothelioma" is used for endothelial neoplasms of intermediate malignancy and describes a group of rare neoplasms having biologic behavior falling in between that of the benign hemangiomas and fully malignant angiosarcomas. The hemangioendotheliomas fall into several specific, clinicopathologically and genetically distinct entities, specifically epithelioid hemangioendothelioma, kaposiform hemangioendothelioma, papillary intralymphatic angioendothelioma and retiform hemangioendothelioma (hobnailed hemangioendothelioma), pseudomyogenic hemangioendothelioma, composite hemangioendothelioma, and YAP1::TFE3-fused hemangioendothelioma. The clinical, morphologic, immunohistochemical, and genetic features, and the differential diagnosis of each of these rare entities are discussed in this review.

Kaposiform Hemangioendothelioma with Bone Destruction: A 16-Year Follow-Up Cohort Study of the Clinical Characteristics and Prognosis.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that often occurs in infants and young children. The goal of this study was to analyze the clinical characteristics of KHE patients with bone destruction and provide clinical guidance for diagnosis and treatment. METHODS: We conducted a descriptive cohort study with follow-up from January 2007 to January 2023 to collect demographic information and tumor-related clinical information from KHE patients with bone destruction. RESULTS: A total of 269 KHE patients were included in the study, of whom 70 (26.0%) patients had tumors with bone destruction. The median age at diagnosis of patients with bone destruction was 19.0 months, which was much later than that of patients without bone destruction (P < 0.001). Patients with bone destruction were more likely to have a decreased range of motion (ROM) (P < 0.001). Metaphysis involvement was more likely to occur in the lower limb bones (P = 0.039), and the lower limb bones were more likely to be associated with decreased ROM (P = 0.001). Tumors involving extracompartmental bone were more likely to have decreased ROM (P = 0.003) and exhibit the Kasabach-Merritt phenomenon (P = 0.006). CONCLUSIONS: Based on the rarity and significant heterogeneity of KHE patients with bone destruction, we should give full play to the role of multidisciplinary teams in addressing disease to reduce the long-term complications of KHE with bone destruction and improve the quality of life of patients. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: Level II.

Kaposiform hemangioendothelioma presented with raynaud phenomenon: a case report.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm affecting infants or young children. KHE includes a spectrum of lesions, ranging from small and superficial tumors to large and invasive lesions with Kasabach-Merritt phenomenon (KMP). Currently, no published studies have reported a KHE presenting as thrombocytopenia and Raynaud phenomenon. CASE PRESENTATION: A 2-year-old boy with right hand swelling and thrombocytopenia was admitted to our hospital. His right hand turned swelling and red, even occasionally cyanotic. This condition became worse in response to cool environments and improved with warming, and platelet counts were between 50 ~ 80 × 10^9/L. Physical examination on admission revealed the swelling and frostbite-like rash of the right-hand fingers, and the skin temperature of the right hand was lower than the left. On day 3 of admission, chest CT results showed an irregular mass on the right side of the spine. The puncture biopsy demonstrated positive CD31, D2-40, and FLI1 immunohistochemical staining, but negative GLUT1 staining, confirming the diagnosis of KHE. Furthermore, endothelin-1 (ET1) expression levels significantly increased, and eNOS and A20 expression levels significantly decreased comparing with control patients. The patient received methylprednisolone and sirolimus treatments, and his condition gradually improved during the follow-up. CONCLUSIONS: We reported the first case of KHE presenting with thrombocytopenia and Raynaud phenomenon. The development of Raynaud phenomenon could be associated with increased ET-1 and reduced eNOS and A20 expressions. Careful differential diagnosis of hidden KHE should be considered in children with thrombocytopenia and Raynaud phenomenon.

Medical and interventional therapy of Kasabach-Merritt phenomenon associated with Kaposiform hemangioendothelioma: A case report.

An infant with Kasabach-Merritt Phenomenon (KMP) presented with a giant subcutaneous mass in the right lower limb, severe hypofibrinogenemia, and thrombocytopenia. Glucocorticoids, along with supportive treatments including transfusion of blood products and clotting factors, were administered to reverse fatal disseminated intravascular coagulation and acute hemolysis. The glucocorticoid dose was tapered slowly, and sirolimus was added to treat the hemangiomas. The patient subsequently underwent interventional therapy. After 6 months of medical and interventional therapy, the patient was doing well with a normal platelet count, the tumor volume was markedly reduced, and the primary cutaneous lesion became pale pink. Currently, the patient remains on sirolimus, and no recurrence of thrombocytopenia or further growth of the mass was observed after six months of follow-up.

Kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon in an infant girl.

Key Clinical Message: We report a successful treatment course of an infant with mediastinal Kaposiform hemangioendothelioma. As the current complex of diseases is rare and calls for highly specialized treatment, large prospective studies are lacking. This case provides an example of balanced treatment complicated by Kasabach-Merritt phenomenon, life-threatening infections, and pericardial effusion. Abstract: Kaposiform hemangioendothelioma (KHE) and tufted angioma are vascular benign tumors that can be associated with the rare condition Kasabach-Merritt Phenomenon (KMP). KMP is characterized by consumption coagulopathy with severe thrombocytopenia, hypofibrinogenemia, and elevated D-dimer. We here report successful treatment of a female infant with a mediastinal KHE where treatment was complicated by KMP, life-threatening infections, and pericardial effusion. Due to the absence of randomized clinical trials, there is currently no standardized treatment protocol available for KHE. In our case, the infant was treated successfully with prednisolone, vincristine, and sirolimus.

Kaposiform hemangioendothelioma of the thigh: A case report.

Kaposiform hemangioendothelioma is a rare, locally aggressive or borderline vascular tumor that typically affects infants. It presents as a purpuric cutaneous lesion and may be associated with life-threatening coagulation disorders, such as the Kasabach-Merritt phenomenon. The differential diagnosis can be challenging based on clinical presentation alone. Imaging plays a crucial role in the diagnostic workup, particularly magnetic resonance imaging. We present a case report of a 4-month-old patient with an enlarging vinous cutaneous mass on the thigh and coagulation abnormalities. Magnetic resonance imaging revealed a large, infiltrative, soft-tissue lesion with poorly defined margins and heterogeneous enhancement, that involved all muscle compartments of the thigh and was associated with lymphedema, stranding of the subcutaneous fat and cutaneous thickening. These findings were consistent with kaposiform hemangioendothelioma of the thigh and the diagnosis was confirmed by histopathological characterization.

Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma: a retrospective cohort study.

Introduction: The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation. Methods: The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors. Results: A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis. Conclusion: For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.

Kaposiform hemangioendothelioma of skull base with dura invasion in a pediatric patient: a case report.

Kaposiform hemangioendothelioma is an extremely rare vascular tumor which shows aggressive local growth. We present a case of rapid growing vascular skull tumor with dura invasion in a pediatric patient with neurofibromatosis type 1. A 14-year-old male complained of headache and dizziness for 1 month after minor head trauma. Brain magnetic resonance imaging (MRI) revealed a 5-cm-sized tumor in the left frontotemporal bone with internal hemorrhage and cystic changes. The gross total resection of tumor was done. At the 7-month follow-up, brain MRI revealed a recurrent skull tumor with intracranial dura mass. He underwent second surgery, and the pathologic diagnosis was suggestive of Kaposiform hemangioendothelioma. For this vascular proliferative tumor, mTOR inhibitor was treated for 6 months, and there was the recurred nodular-enhancing mass along the sphenoid ridge. After additional 2 months of medication, the following MRI revealed a decreased nodular-enhancing mass.

Case Report: Kaposiform hemangioendothelioma with PIK3CA mutation successfully treated with sirolimus.

Kaposiform hemangioendothelioma (KHE) is an extremely rare, locally aggressive vascular neoplasm. The etiopathogenesis of KHE is still poorly understood. In the present study, we found a new mutation in KHE (c.685delA, p.Thr229fs). The KHE patient with the PIK3CA mutation showed complete regression after sirolimus treatment. We propose that the presence of the PIK3CA mutation in KHE may correlate with good response to sirolimus.