Case 3 -
Kaposiform Hemangioendothelioma (KHE) with Atypical Features
Primary Children's Medical Center
Salt Lake City, UT
Click on each slide thumbnail image for an enlarged view
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
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.
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
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.
- 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. Histopathology of vascular lesions found in Kasabach-Merritt syndrome: review based on 13 cases. Pediatr Dev Pathol 2000; 3:556-560.
- Beaubien ER, Ball NJ, Storwick GS. Kaposiform hemangioendothelioma: a locally aggressive vascular tumor. J Am Acad Dermatol 1998; 38:799-802.
- Blei F, Karp N, Rofsky N, et al. Successful multimodal therapy for kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: case report and review of the literature. Pediatr Hematol Oncol 1998; 15:295-305.
- Coffin CM, Dehner LP. Vascular tumors in children and adolescents: a clinicopathologic study of 228 tumors in 222 patients. Pathol Annu 1993; 28:97-120.
- Deb G, Jenkner A, De Sio L, et al. Spindle cell (kaposiform) hemangioendothelioma with Kasabach-Merritt syndrome in an infant: successful treatment with alpha-2A interferon. Med Pediatr Oncol 1997; 28:358-361.
- Enjolras O, Mulliken JB, Wassef M, et al. Residual lesions after Kasabach-Merritt phenomenon in 41 patients. J Am Acad Dermatol 2000; 42:225-35.
- Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas. J Pediatr 1997; 130:631-40.
- Folpe AL, Veikkola T, Valtola R, et al. Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas. Mod Pathol 2000; 13:180-185.
- Hu B, Lachman R, Phillips J, et al. Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D. J Pedatr Hematol Oncol 1998; 20:567-569.
- Lai FMM, To KF, Choi PCL, et al. Kaposiform hemangioendothelioma: five patients with cutaneous lesion and long follow-up. Mod Pathol 2001; 14:1087-1092.
- Lalaji TA, Haller JO, Burgess RJ. A case of head and neck kaposiform hemangioendothelioma simulating a malignancy on imaging. Pediatr Radiol 2001; 31:876-878.
- Mentzel T, Mazzoleni G, Dei Tos A, et al. Kaposiform hemangioendothelioma in adults: clinicopathologic and immunohistochemical analysis of three cases. Am J Clin Pathol 1997; 108:450-455.
- Niedt GW, Greco A, Wieczorek R, et al. Hemangioma with Kaposi's sarcoma-like features: report of two cases. Pedatr Pathol 1989; 9:567-575.
- Sarkar M, Mulliken JB, Kozakewich HPW, et al. Thrombocytopenic coagulopathy (Kasabach-Merritt Phenomenon) is associated with kaposiform hemangioendothelioma and not with common infantile hemangioma. Plast Reconstr Surg 1997; 100:1377-1386.
- Tsang WYW. Kaposiform haemangioendothelioma. In: Fletcher CDM, Unni KK, Mertens F (Eds.), Pathology and Genetics of Tumours of Soft Tissue and Bone. World Health Organization Classification of Tumours. Lyon: IARC Press, 2002. Pages 163-164.
- Tsang WYW, Chan JKC. Kaposi-like infantile hemangioendothelioma a distinctive vascular neoplasm of retroperitoneum. Am J Surg Pathol 1991; 15:982-989.
- Vin-Christian K, McCalmont TH, Frieden IJ. Kaposiform hemangioendothelioma: an aggressive, locally invasive vascular tumor that can mimic hemangioma of infancy. Arch Dermatol 1997; 133:1573-1578.
- Zukerberg LR, Nickoloff BJ, Weiss SW. Kaposiform hemangioendothelioma of infancy and childhood. Am J Surg Pathol 1993; 17:321-328.