History
Three year old girl with a recurrent tumour in the left mandibula.
First two diagnosis
were fibromatous tumour and hemangioma.
Pathology
Pieces of firm grayish-white and brownish tissue, measuring about
5cm in aggregates were submitted with a fragmented piece of bone.
Histologically the tissue consisted of skeletal muscle widely invaded
by a solid tumour; this was composed of irregularly shaped nodules
separated by broad fibrous bands. Tumour cells were spindled and
their nuclei elongated or oval. They showed scant cytoplasm with
blurred cell borders. Interspersed were slitlike vascular spaces
filled with fragmented erythrocytes. Occasional intracellular hyaline
globules and fine granular hemosiderin were present. Cellular atypia
was moderate and mitotic figures few. No significant inflammation
was seen. Immunohistochemically the tumour cells were positive
for Vimentin, CD 34, CD 31 and Factor VIII-related antigen, the
latter two with variable intensity and distribution. Silver stain
highlighted the vasoformative character of the lesion.
Discussion
Kaposiform Hemangioendothelioma (KH) is a distinct vascular neoplasm
that, despite its worrisome histology, belongs to the intermediate
malignancy group according to the WHO Classification. It is a
locally invasive tumour, that however has no capacity to metastasize.
There are some reports of involvement of regional lymphnodes,
but it is unclear whether this represents true metastasis or
simply local extension. Long term behaviour, however, remains
undetermined.
KH is rare (just over 60 cases in the literature) and occurs in
childhood and early adolescence; it was recently diagnosed in elderly
persons as well. The distribution varies widely although the more
commonly affected sites are the skin of the trunk and limbs. Only
about 18 % are found in the mediastinum and retroperitoneum; these
often prove to be fatal due to unresectability and the consequent
difficulty in managing the often associated Kasabach- Merritt syndrome
(consumption coagulopathy and severe thrombocytopenia). But even
the skin lesions, which are better amenable to surgical therapy,
require wide local excision because of almost invariable deep soft
tissue involvement! Often, a skin biopsy is not representative.
KH is also known to be associated with lymphangioma/ lymphangiomatosis.
Microscopically, its appearance is somewhere
between that of capillary hemangioma and Kaposi’s sarcoma
(KS). The peripheral portions of the tumour are reminiscent of
a capillary hemangioma (cave!), although they often lack the typical
lobular pattern. The deeper regions show a striking resemblance
to KS with their more immature aspect and spindled neoplastic endothelial
cells forming slitlike vascular spaces. Sometimes these spindle
cells blend with plumper, more rounded endothelial cells growing
in circles and forming so-called „glomeruloid nests“.
These cells have abundant eosinophilic cytoplasm containing occasional
hyaline globules and fine granular hemosiderin. Sometimes vacuolation
is seen similar to that in epitheloid hemangioendothelioma. Broad
fibrous septa separate the tumour cell masses and give this neoplasm
its characteristic nodular pattern. Cellular atypia is usually
minimal, as are mitotic figures; atypical mitoses are not found.
Hemorrhage and necrosis can occur; inflammation is minimal.
Immunohistochemistry is not very
useful in distinguishing this entity from KS. Both
tumours express CD 34 and the usual endothelial markers, like CD31,
F VIII antigen (variable staining) and UEA. Reticulin stain confirms
the vasoformative character of the tumour and Collagen IV can be
very helpful in evaluating the degree of maturity expressed by
the tumour cells.
Differential Diagnosis
The most important one is Kaposi’Sarcoma (KS).
Distinguishing features are, in the first instance, related to
the clinical presentation: KH, in contrast to KS, is a solitary
lesion. KS is very rare in children ( except the lymphadenopathic
form, in Africa ). Despite similar histology, there are some peculiar
morphologic features confined to KH which make the differential
diagnosis easier. These are the lobular growth pattern with broad
fibrous septa and scanty inflammatory infiltrate, deep extension
to the underlying soft tissue and bone and the often concomitant
lymphatic malformation.
The second most important differential diagnosis is the Tufted
Angioma (TA), which can also present clinically with severe bleeding
disturbances. Nevertheless, TA never extends into the deep soft
tissue (especially not beyond the fascia) and has a typical „cannonball“ pattern.
Additionally, it shows the characteristic crescents surrounding
the lobules due to indentation of adjacent thin- walled vessels.
The TA is a benign vascular tumour, which notoriously recurs due
to difficulty of radical resection, but it has never shown locally
aggressive behaviour or distant metastasis.
The therapy of KH is still empiric. It is multimodal and includes
both surgical eradication and medical management of the coagulopathy.
Embolization and transfusions have been used in the management
of the Kasabach-Merritt syndrome. Successful stabilization of this
often fatal condition has only been achieved with the use of Interferon
alpha together with chemotherapeutic agents. Due to the risk of
secondary malignancies, radiotherapy is not recommended and must
only be used as a last resort.
