Case 3 -

Kaposiform Hemangioendothelioma (KHE) with Atypical Features Cheryl Coffin Primary Children's Medical Center Salt Lake City, UT

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Clinical History A seven-month old female presented with a vascular mass on the jaw, multiple capillary hemangiomas on the abdomen and thigh, and a history of thrombocytopenia and anemia. She had previously received a tracheostomy for airway obstruction by a vascular mass, which had not been biopsied. An MRI scan demonstrated an enlarging heterogenous mass involving the soft tissue of the right neck and retropharyngeal space, without skull or intracranial involvement. A variety of treatments had failed, including systemic steroids, interferon, and embolization. Weekly vincristine, intermittent interferon, and intralesional steroids were given. A biopsy was performed two months later. Following the biopsy and continuation of vincristine and interferon, growth stabilized, and the mass became more heterogenous on MRI scan. Platelet count returned to normal following administration of Amicar. Case 3 - Figure 1 - Nodules of cellular vascular tissue are interspersed between bands of fibrous tissue, with occasional irregular empty dilated vessels resembling lymphatic vessels and congested capillary spaces. Case 3 - Figure 2 - A cellular proliferation of spindled and polygonal cells is present with abundant small blood vessels. Case 3 - Figure 3 - Spindled and plump polygonal cells form bundles and fascicles and are interspersed with blood vessels. Case 3 - Figure 4 - Spindled and polygonal cells form a cellular mass with focal accumulation of hemosiderin. The endothelial cells have large vesicular nuclei with small nucleoli and occasional mitotic figures. Diagnosis Kaposiform hemangioendothelioma (KHE) with atypical features. Discussion and Differential Diagnosis This case represents an example of KHE with overlapping features of tufted angioma (TA), probable therapy-related changes, and Kasabach-Merritt syndrome. The biopsy was obtained three months after initiation of therapy with vincristine, interferon, and intralesional steroids. The points for discussion about this case include the pathologic findings, the differential diagnosis and comparative features of KHE and TA, the therapy-related changes, and the Kasabach-Merritt phenomenon. Histologically, the biopsy from the right neck masses revealed fibroadipose tissue and skeletal muscle infiltrated by a lobular mass of vascular tissue separated by bands of fibrous tissue. The fibrous bands contained small and medium-sized, irregularly dilated lymphatic channels. The lobules were composed of tightly packed small capillaries, dilated congested capillaries, pericytes, and spindle cells with focal arrangement into fascicles. In some areas, the vascular nodules formed tufts with a peripheral semilunar blood vessel. The endothelial cells had large vesicular nuclei with small nucleoli and frequent mitotic figures, but no atypical mitoses. No significant cytologic atypia was observed. Hemosiderin was present within the vascular proliferation, especially in spindle cell areas. Immunohistochemical analysis revealed reactivity in the endothelial cells for CD31, CD34, and vascular endothelial growth factor (FLK1). Smooth muscle actin was positive in vessel walls, in bands of fibrous tissue, and in occasional spindle cells. Muscle-specific actin staining had similar pattern, but was less intense. Approximately 20% of nuclei stained for Mib-1 (Ki-67). Factor VIII-related antigen staining was present only within a few endothelial cells in larger vessels. The lesion was interpreted as a KHE with overlapping features of TA. There was no evidence of angiosarcoma or Kaposi sarcoma. The pronounced lobular architecture, fibrosis, and hemosiderin-deposition were attributed partly to treatment effects. KHE is a locally aggressive, non-metastasizing, immature vascular neoplasm characterized by a fascicular spindle cell growth pattern resembling Kaposi sarcoma. Although it most commonly occurs in the retroperitoneum, the skin is a frequent site and it can occur in the head and neck region. KHE typically presents in infancy and the first decade of life. It is rare in adults. Males and females are equally affected. Cutaneous lesions appear as ill-defined violaceous plaques. The major complications of KHE are blood loss and consumptive thrombocytopenia. Gradual, but incomplete regression has been observed. Unlike Kaposi sarcoma, there is no known association with HIV infection or human herpes virus type 8. A nodular architecture with surrounding fibrous tissue containing dilated lymphatic vessels resembling lymphangioma is seen in some examples of KHE. The ill-defined nodules contain a mixture of small round capillary-sized vessels that blend with slit-like vessels. Glomeruliod nests of endothelial cells containing hemosiderin and vascular nodules with semilunar vessels at the periphery may be seen. The spindle cells are usually nonreactive for factor VIII-related antigen, but the lesion is positive for CD34 and CD31 and actin stains focally highlight spindle cells. The differential diagnosis of KHE includes cellular capillary hemangioma (cellular juvenile or infantile hemangioms), TA, spindle cell hemangioendothelioma, and Kaposi sarcoma. Cellular capillary hemangiomas of infancy have a distinct nodular pattern with small capillary-sized vessels and absence of spindle cells, erythrocyte fragmentation, and hemosiderin. TA typically displays a cannonball-pattern of dermal infiltration, but can bear striking histologic similarity to KHE. Both KHE and TA can display a multinodular architecture, dilated lymphatic paces, hemosiderin, and microthrombi occasional cases are encountered with features of both KHE and TA, suggesting a relationship between the two. Spindle cell hemangioendothelioma lacks a lobular architecture, has cavernous areas with papillae and vacuolated cells, and is found with hamartomatous vessels. Kaposi sarcoma has a more uniform pattern of spindling, a prominent peripheral inflammatory infiltrate, and immunohistochemical activity for human herpes virus 8. Consumption coagulopathy, or Kasabach-Merritt syndrome, has been associated with a variety of vascular tumors in childhood including KHE, other hemangiomas, chorangioma, and large vascular malformations. Thrombocytopenia, hypofibrinogenemia, and anemia are typical laboratory abnormalities. Activation of clotting within tumor vessels is the mechanism. Some evidence suggests that this phenomenon is more frequently associated with KHE than other vascular lesions, and there is some controversy about terminology and classification. The clinical, radiologic, and pathologic features of residual vascular lesions following treatment of Kasabach-Merritt syndrome have been reported in 41 patients by Enjolras and colleagues. Pathologically, KHE was more frequent among biopsies taken during the active phase of Kasabach-Merritt syndrome, and TA was more common in specimens from residual lesions. Fibrosis and lymphatic spaces were common in the residual lesions. These changes differ from the involutional changes of capillary hemangiomas. References Allen PW. Three new vascular tumors-tufted angioma, kaposiform infantile hemangioendothelioma, and proliferative cutaneous angiomatosis. Int J Surg Pathol 1994; 2:63-72. Alvarez-Mendoza A, Lourdes TS, Ridaura-Sanz C, et al. 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