Introduction

Kaposiform haemangioendothelioma (KHE) is defined as a locally aggressive vascular neoplasm, characterised by a predominantly Kaposi sarcoma-like fascicular spindle cell growth pattern [17]. The tumour usually occurs in the skin [3, 7, 8, 11, 18, 20] and retroperitoneum [1, 9, 11, 16, 20] of infants and young children, but some adult cases have been described [5, 10]. KHE is often complicated by Kasabach–Merritt phenomenon (KMP), a condition of severe thrombocytopenia and consumptive coagulopathy [1–3, 6, 7, 11, 14, 16, 18–20]. Some cases of KHE are associated with lymphangiomatosis [7, 20]. Unlike juvenile haemangioma, KHE shows no tendency for spontaneous regression [7, 8]. Regional lymph node metastasis is rare, but distant metastasis has not been reported yet [7]. Mortality is mostly due to KMP with life-threatening haemorrhage [7, 14]. We recently encountered a case of KHE with a multifocal presentation and infiltration into the thyroid gland, a hitherto undescribed phenomenon.

Clinical history

A 3-year-old boy presented with three episodes of fever and a right submandibular swelling of 3 cm in diameter, which was due to painless, but firm lymphadenopathies. Since there was no regression of the adenopathies, an excisional biopsy of a right neck lymph node was taken 4 months after the first consultation. Afterwards, the boy was referred to our center. He was in good general condition. Besides the submandibular lymphadenopathies, clinical examination also revealed a slightly elevated violaceous skin lesion as big as a rice-grain, situated left laterally of the mouth (Fig. 1a). There was no trombocytopenia, but still an elevation of the D-dimer level (2,007 μg/l) (normal values 0–500 μg/l), thyroglobulin (43.5 μg/l ) (normal values 0.0–25.0) and LDH (625 U/l) (normal values 240–480 U/l). Imaging revealed a prominent submandibular lymph node group and adenopathies along the right internal jugular vein (Fig. 1b). Furthermore, a lesion in the right thyroid lobe was seen, but could not further be specified on CT scan. Because of the presence of multiple lesions and the possibility of malignancy, a right hemithyroidectomy and a right lymph node dissection of levels I to IV was performed. Preoperatively, there was no connection between the thyroid lesion and the enlarged lymph nodes. During the same surgery, the skin lesion was excised. After the operation, there was a normalisation of the D-dimers (340 μg/l).

Fig. 1
figure 1

a A violaceous skin lesion at the left commissure of the lips. b CT scan: a prominent submandibular lymph node group at the right side

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Materials and methods

The right thyroid lobe, the right neck dissection specimen and the skin lesion were received fresh. A small part of the lesion in the thyroid and the lymph nodes was snap-frozen in liquid-nitrogen-cooled isopentane. The rest of the specimens were fixed in 6% formalin and processed to paraffin. Five-micrometer thick tissue sections were subjected to haematoxylin and eosin. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue, using a three-step indirect peroxidase complex method. The following antibodies were used: CD31 (1:50 dilution, monoclonal, Dako, Glostrup, Denmark), CD34 (1:10 dilution, monoclonal, Becton Dickinson, San Jose, USA), alfa-SMA (1:100 dilution, monoclonal, Dako, Glostrup, Denmark), HHV-8 (1:20 dilution, Novocastra, Newcastle, UK).

Pathological findings

The right thyroid lobe, measuring 2.2×1.5×1 cm, contained an ill-defined lesion of 1.3×0.9×1 cm. The right neck dissection specimen consisted of enlarged lymph nodes along the right jugular vein and next to the right submandibular gland, which was not infiltrated. The skin biopsy measured 0.5×0.5×0.7 cm.

Histopathological examination of the three resected specimens showed the same picture. The tumour was characterised by an infiltrative multilobular spindle cell proliferation. The infiltrative growth pattern caused destruction of the thyroid parenchyma (Fig. 2a) and the lymph node parenchyma (Fig. 2b). The skin biopsy showed that the tumour was situated in the deeper part of the dermis and in the upper part of the subcutis (Fig. 2c). The tumour consisted of nodules of compact spindle cell fascicles with hardly recognisable interspersed vascular spaces. Thin-walled dilated and probably lymphatic vessels were seen in-between and around the nodules (Fig. 3). The spindle cells did not show cytological atypia or nuclear pleomorphism. Mitotic activity was inconspicuous. Convincing microthrombi were very rare, as well as hyaline globules.

Fig. 2
figure 2

a A spindle cell proliferation with destructive infiltration of the thyroid (hematoxylin-eosin stain ×100). b A vascular spindle cell proliferation involving a lymph node (hematoxylin-eosin stain ×100). c A multilobular spindle cell proliferation in dermis and subcutis (hematoxylin-eosin stain ×50)

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Fig. 3
figure 3

Thyroid: a dilated thin-walled vessel encircling a tumour nodule (hematoxylin-eosin stain ×100)

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The tumour showed strong positivity for CD34 (Fig. 4) and CD31. Many SMA-positive spindle cells, presumably pericytes, were present around the vascular spaces. A HHV-8 stain was negative.

Fig. 4
figure 4

Thyroid: an infiltrative CD34-positive proliferation between the thyroid follicles (×100)

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Based on these morphological and immunohistochemical findings, a diagnosis of KHE was made.

Discussion

The term ‘Kaposiform haemangioendothelioma’ was introduced in 1993 by Zukerberg et al. Ever since, fewer than 100 cases have been reported in the literature [1–11, 14–16, 18–20].

KHE usually occurs in early childhood, and often in the first decade of life. KHE mostly involves the skin and the retroperitoneum. The tumour occurs less commonly in the head and neck region [2, 5–7, 15, 20] and in the deep soft tissue of the extremities and the trunk [7, 20]. Rare cases have been described in the mediastinum [7], thymus (one case) [19] and scrotum (one case) [7]. To our knowledge, we present in this paper the first case involving the thyroid.

KHE is often associated with KMP. In our case, there was an elevation of D-dimers, an important marker of consumptive coagulopathy. Therefore, it seems likely that this child showed some evidence of KMP, although platelet count was normal and fibrin thrombi were rare. Yet the recent study of Lyons et al. mentioned that the number of platelet thrombi does not correlate with the presence of KMP [7]. Moreover, normalisation of D-dimers after resection of the lesions proves that the trigger for consumptive coagulopathy has been removed. This trigger has been thought to be related to unique architectural features that favour turbulent blood flow and platelet activation [7]. Absence or presence of KMP is an important prognostic factor, since life-threatening haemorrhage can cause mortality.

Our case illustrates both the nodules of compressed vessels and the ectatic vascular component of KHE. This biphasic pattern has been described before in the literature [1, 7, 9, 11, 15, 20].

In contrast to juvenile haemangioma, KHE shows no tendency to involute. KHE is a locally aggressive tumour, and distant metastasis is not described to date. When reviewing the literature, we found one case of congenital cutaneous multifocal haemangioendothelioma [4]. This report mentions the case of a newborn having multiple cutaneous lesions with the histopathological picture of KHE. All these lesions were confined to the skin. In the present case, we describe KHE in three anatomically distinct and separate lesions. Moreover, we do not have evidence of congenital disease.

Theoretically, one could consider metastatic and aggressive disease because of the separate locations. However, in our case, just as in all earlier described KHEs, there were no histological features of malignancy. In addition, some benign vascular lesions, like the spindle cell haemangioma, can give rise to multiple lesions in the same general area [13]. Finally, another benign vascular tumor, the retiform haemangioendothelioma, occasionally metastasises to the lymph nodes without systemic spread and without aggressive behaviour [12]. In our case, multifocal presentation seems more likely than metastasis from the right thyroid lobe to contralateral lymph nodes only and not to ipsilateral lymph nodes. Obviously, the patient will be followed very closely and only a long-term follow-up will be to disclose the true biologic behaviour. At present, it seems that KHE can be added to the list of vascular tumours with an occasional multifocal presentation.