KHE as a separate pathological entity, distinct from the more common haemangiomatous lesions, was described originally by Zukerberg et al in 1993, as a benign, locally aggressive, vascular tumour of childhood. A lack of both spontaneous involution and distant metastasis are features of all described KHE, though regional lymphadenopathy and local invasion into deeper subcutaneous and muscle planes are also seen (2). It commonly presents as a rapidly enlarging, bluish-red, subcutaneous mass in infants and children, with a known and consistent association with the Kasabach-Merritt syndrome or phenomenon (KMP), characterised by severe thrombocytopenia due to intralesional platelet trapping. In an extensive review of 107 cases by Croteau et al (3), the common presenting features were an enlarging cutaneous lesion, musculoskeletal pain associated with decreased function and thrombocytopenia along with its manifestations. A cutaneous vascular lesion is the commonest symptom, confusing with entities such as tufted angioma, pyogenic granuloma, juvenile haemangioma, vascular malformations and Kaposi sarcoma(KS) as well. Older patients lacking thrombocytopenia were found to have musculoskeletal features in multiple reports, as in our case.
Although widely reported in children, it was first reported in adults by Mentzel et al (4). Several atypical cases of KHE have been since seen in adults, with lesions arising from the thoracic cavity, lateral neck, buttock region (4), tongue (5), tonsil (6), spleen, gastrointestinal tract and the extremities. According to published reports, many features of KHE are vastly different in children and adults. KMP in children with KHE tend to be large, and because of intralesional platelet trapping, cause widespread thrombocytopenic manifestations. A cascade of consumption coagulopathy follows from the interaction of abnormally proliferating endothelium within the KHE and the platelets, secondarily activating the clotting cascade (7). It is inherently refractory to transfused platelets, thus is considered to be a potentially life-threatening disorder. In contrast, lesions in adults tend to be smaller and do not present with KMP presumably due to the size and lack of abnormal epithelium. An empirical size of 8cm has been designated in a review of KHE (8), below which KMP in KHE is usually not observed.
No obvious aetiology for the abnormal angiogenesis and lymph-angiogenesis has been identified (9). KHE is not related to HHV-8 or the more ominous KS. Biopsies are usually not recommended in KHE, given the risk of KMP, but are advised in cases where the diagnosis is doubtful or unusual sites are involved. KHE consists of irregularly infiltrating, compressed vascular spaces, intervening between spindle-shaped endothelial cells. Occasionally the vessels contain erythrocyte and platelet thrombi (10). Dilated discrete lymphatic vessels may also be found. Nuclear atypia and abnormal mitoses are rare. The spindle cells are positive for endothelial cell markers such as CD31, CD34 and ERG but negative for GLUT-1, which is found in infantile haemangiomatous endothelium. The most specific IHC marker, however, is podoplanin, found on the endothelial cells, which harbours co-receptors for platelets (1).
Ultrasound is the modality of choice for small subcutaneous lesions, though MRI is more sensitive. KHE appears ill-defined on MRI, involving multiple tissue planes, with hemosiderin deposits, prominent vessels, fat stranding and remodelling of the underlying bone, with high T2 signal intensity and diffuse early enhancement (11). Osteolytic destruction of surrounding bone, spiculations and flow voids are suggestive, but not characteristic.
A major clinical concern is a differentiation from the more sinister Kaposi sarcoma (KS), which is suspected in the setting of an immunocompromised patient. Periodic acid Schiff (PAS) positivity and better histologic differentiation, in a background of HHV-8 positivity, points to a diagnosis of KS rather than KHE (12).
Aggressive treatment is indicated in cases with catastrophic bleeding, especially when associated with KMP. A host of treatment modalities have been proposed, with fairly consistent success. Surgical excision with a safe margin, embolization, radiation therapy and pharmacologic therapy have all been tried in KHE, with radical surgery generally deemed adequate and definitive (13). Lasers, high dose systemic corticosteroids, interferon-alpha therapy, cryotherapy, vincristine, sirolimus, antiplatelet-antifibrinolytics and propranolol are all indicated, either in combination with surgery or alone, depending upon clinical practice and availability. The long duration of response to medical therapy and lack of reliable treatment guidelines precludes consistent pharmacotherapy in all cases of KHE.
In the case of a first, a sublingual gland KHE without KMP is an atypical diagnosis obtained at an unusual site. The routine excision of the sublingual gland was sufficient in our case without any histopathological evidence of positive margins. However, it is prudent to excise the gland along with an empirical margin for oncological safety, as KHE is considered a potential malignancy of intermediate grade.