Clinical History:
The patient was a 15 year old male who presented with a 3 month history of a painful right thigh mass.
No other associated laboratory abnormalities were noted. Following an incisional biopsy a more extensive
excision was performed. The gross specimen consisted of skin, subcutaneous tissue and an underlying
portion of sartorius muscle. The latter was involved by a partially hemorrhagic infiltrating lesion.
Your sections are taken from the excision specimen.
Case 3 - Figure 3 - Slit-like spaces are present between the spindle cells and some contain red blood cells.
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Case 3 - Figure 4 - Overt vascular formation is present in focal areas of the neoplasm.
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The kaposiform hemangioendothelioma (KHE)1 is a vascular tumor of intermediate malignancy which has been
reported under a number of terms including Kaposi-like hemangioendothelioma2 and hemangioma with
Kaposi-like features. Although these lesions were probably misclassified as juvenile hemangiomas in the
past, there are substantial reasons to consider them distinct from the usual juvenile (cellular)
hemangioma (CH) of infancy and Kaposi's sarcoma (KS).
KHE typically presents during childhood or teenage years as a superficial or deep lesion. Superficial
lesions appear as violaceous plaques which contrast with the red polypoid appearance of classic CH.
Large lesions or those in deep locations may also be associated with consumption coagulopathy and
Kasabach Merritt syndrome which develops in about 50% of patients in our experience. In fact, it now
appears that most cases of Kasabach Merritt syndrome, are associated with KHE and not with ordinary
capillary or cavernous hemangiomas, as was once thought.3 A subset of KHE may be associated with
lymphangiomatosis. Histologically KHE consists of irregular nodular aggregates of tumor often evoking a
dense sclerosis. About two thirds are surrounded by dilated lymphatic vessels. Within the nodules the
tumor modulates between areas resembling a capillary hemangioma and Kaposi's sarcoma. A characteristic
feature of KHE is the presence of glomeruloid nests of rounded cells with abundant eosinophilic
cytoplasm, presumably, endothelium and/or pericytes, which contain fine granules of hemosiderin and
hyaline globules. Red blood cells and fibrin thrombi can be identified between these cells. Atypia and
mitotic activity is usually minimal.
Immunohistochemically the neoplastic endothelium express CD31, CD34 and VEGFR3 but not GLUT1 (an oxygen
transport protein that is strongly expressed in CH). Actin immunostains (SMA) highlight a population of
cells, presumably pericytes, which also participate in these lesions.1,4 The presence of VEGFR3 is a
feature that this tumor has in common with other intermediate vascular tumors of childhood (cf.
Dabska-retiform hemangioendothelioma) whereas the lack of GLUT1 serves to distinguish it from CH. HHV8
which is consistently present in Kaposi's sarcoma, has not been detected in 3 cases of KHE studied by
RT-PCR.4
Although these tumors are far more life threatening than ordinary hemangiomas, morbidity and mortality is
directly linked to the paraneoplastic complications of the disease. In the largest study to date
comprising 21 cases with follow up information, 3 died of disease.4 Two succumbed to Kasabach Merritt
syndrome and 1 to the complications of lymphangiomatosis. Ten patients were alive without residual
disease and 8 were alive with disease. Only 1 patient has developed local soft tissue and regional
lymph node metastasis,4,5 but none has developed distant metastasis. Thus the challenge in these cases
is not only to eradicate the tumor but to support patients who develop life threatening hemorrhage. Some
success has been reported using interferon alpha 2a and multimodality chemotherapy.
The differential diagnosis of these tumors include CH, KS, and acquired tufted hemangioma. CH, usually
presenting shortly after birth, as a rapidly growing red nodules, are composed of more orderly nodular
aggregates of small capillary sized vessels that surround a central feeding vessel. In the early
proliferative stage these vessels are poorly canalized andare mitotically active. With maturation the
vessels become canalized less mitotically active. However, regardless of stage of evolution the cells
consistently express GLUT1 in contrast to KHE. Kaposi's sarcoma, of course, is almost exclusively a
tumor of adults although in Africa the lympadenopathic forms occurs in children. Typically the lesions
consist of uniformly spindled cells surrounded by a chronic inflammatory infiltrate and thick walled
vessels. Virtually all cases are associated with HHV8 and none with Kasabach Merritt syndrome. Acquired
tufted hemangioma is histologically similar to KH and, in fact, may simply represent a variant of KH
presenting as an isolated skin lesion in adults.
References
- Zukerberg, LR, Nickoloff, BJ, Weiss, SW: Kaposiform hemangioendothelioma of infancy and childhood:
an aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis. Am J Surg Pathol
17:321, 1993.
- Tsang, WYW, Chang, JKC: Kaposi-like hemangioendothelioma: a distinctive vascular tumor of the
retroperitoneum. Am J Surg Pathol 15:982, 1991.
- Enjolras, O, Wassef, M, Mazoyer, E et al: Infants with Kasabach Merritt syndrome do not have "true"
hemangiomas. J Pediatr 130:631, 1997.
- Lyons,LL,North PE, Stoler, MH, Folpe, AH, Weiss, SW: Kaposiform hemangioendothelioma (KH) is
histologically, immunohistochemically, and biologically distinct from common (juvenile) hemangioma (JH):
A bi-institutional analysis of 33 cases. Mod Pathol, in press.
- Lai, FM, Allen, PW, Yuen, PM et al: Locally metastasizing vascular tumor: spindle cell,
epithelioid or unclassified hemangioendothelioma. Am J Clin Path 96:660, 1991.
