Pediatric Hematology Oncology Journal 1 (2016) 89e92

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Pediatric Hematology Oncology Journal

journal homepage: https://www.elsevier.com/journals/pediatric-
hematology-oncology-journal/

Management of a Kaposiform haemangioendothelioma of the kidney

with Kasabach-Meritt phenomenon without chemotherapy
Mya Soe Nwe a, *, Marc Weijie Ong b, Joyce Ching Mei Lam a, Kenneth Tou-En Chang c,
Marielle V. Fortier d, Olivia Wijeweera e, Ah Moy Tan a, Amos Hong Pheng Loh b
a
Haematology/Oncology Subspecialties, Department of Pediatric Medicine, KK Women's and Children's Hospital, Singapore
b
Department of Paediatric Surgery, KK Women's and Children's Hospital, Singapore
c
Department of Pathology, KK Women's and Children's Hospital, Singapore
d
Department of Radiology, KK Women's and Children's Hospital, Singapore
e
Department of Anaesthesia, KK Women's and Children's Hospital, Singapore

a r t i c l e i n f o a b s t r a c t

Article history: Kaposiform haemangioendothelioma (KHE) is a benign vascular tumour. While it is not associated with
Received 5 January 2017 distant spread, it can be locally aggressive and associated with Kasabach-Merritt syndrome (KMS). There
Received in revised form were only 2 prior reports of KHE isolated to the kidney, with both having been managed with neo-
22 February 2017
adjuvant chemotherapy. We present a case report of renal KHE in a paediatric patient managed instead
Accepted 6 March 2017
with upfront surgical resection, and discuss the close interdisciplinary diagnostic and management
Available online 29 March 2017
approach undertaken to facilitate this, and the considerations in the approach.
© 2017 Production and hosting by Elsevier B.V. on behalf of Pediatric Hematology Oncology Chapter of
Keywords:
Kaposiform hemangioendothelioma
Indian Academy of Pediatrics. This is an open access article under the CC BY-NC-ND license (http://
Kidney creativecommons.org/licenses/by-nc-nd/4.0/).
Kasabach-Merritt syndrome
Rotational thromboelastography

1. Introduction 2. Case report

Kaposiform hemangioendothelioma (KHE) is a rare vascular
tumour typically seen during childhood. Most cases of KHE involve
superficial and deep tissues of the extremities, while visceral
involvement is less common. Kasabach-Merritt syndrome (KMS),
characterized by profound thrombocytopenia and consumptive
coagulopathy, is a potentially life-threatening complication
commonly associated with KHE. We report a case of KHE occurring
in the kidney in a 5 month old infant with associated KMS, and
successful treatment of renal KHE with upfront surgical resection
without neoadjuvant or adjuvant chemotherapy. This case high-
lights the importance of tight interdisciplinary coordination in the
approach and successful management of a rare paediatric solid
tumour.
* Corresponding author. Haematology/Oncology subspecialties, Department of
Pediatric medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road,
229899, Singapore.
E-mail address: Mya.Soe.Nwe@KKH.com.sg (M.S. Nwe).
Peer review under responsibility of Pediatric Hematology Oncology Chapter of
Indian Academy of Pediatrics.
A 5 month old girl presented to the outpatient general paedi-
atric clinic with a 2 week history of an incidentally-detected left
abdominal mass. She was antenatally well and born at 39 weeks'
gestation with a birth weight of 3.36 kg. Postnatally, the child was
in good health. There were no associated urinary symptoms or
preceding weight loss. On physical examination, there was a bal-
lotable mass over the left upper abdomen. Cardiac, respiratory and
genital examinations were unremarkable. Her spine was normal
with absence of scoliosis and neurological deficits. There was no
hemihypertrophy or petechial rashes.
Computed tomography (CT) of the abdomen and pelvis revealed
a 3.9  6.4  5 cm enhancing lobulated mass in the left retro-
peritoneum adjacent to the left renal hilum, displacing the left
kidney inferiorly and invading the renal parenchyma at the lower
pole. There were no internal calcifications or necrosis within the
mass (Fig. 1). Renal Doppler ultrasound demonstrated marked left
hydronephrosis due to extrinsic compression from the mass. Im-
aging was suspicious for an exophytic renal tumor and less likely a
neuroblastic tumor encasing the renal hilar vessels.
Serum beta-hCG and alpha-fetoprotein, and urinary

http://dx.doi.org/10.1016/j.phoj.2017.03.001
2468-1245/© 2017 Production and hosting by Elsevier B.V. on behalf of Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
90 M.S. Nwe et al. / Pediatric Hematology Oncology Journal 1 (2016) 89e92

vanillylmandelic acid and homovanillic acid were unremarkable.

Hemoglobin level was 8.2 g/dL (range: 12e16 g/dL), white blood
cell count was 12,000/mL (range: 4500e13500/mL) and platelet
count was 23,000/mL (range: 150,000e450,000/mL). This was of
concern for possible bone marrow involvement by tumour. How-
ever, bone marrow aspiration and trephine biopsy showed tri-
lineage marrow with erythoid and megakaryocytic hyperplasia
with no evidence of tumour infiltration.
Haematology input was sought and differentials for peripheral
causes of thrombocytopaenia included immune-mediated thro-
mobocytopenia as a paraneoplastic phenomenon or thrombocy-
topaenia secondary to tumour sequestration. The patient was
started on a trial of intravenous immunoglobulin and 3 doses of
intravenous methylprednisolone. However there was no sustained
response in platelet counts. Platelet trapping secondary to KMS was
suspected, further evidenced by hypofibrinogenemia [fibrinogen
0.40 g/L (normal range 1.80e4.80 g/L)] and elevated markers of Fig. 2. Intraoperative view of highly vascular left retroperitoneal tumor contiguous
coagulation activation [D dimers >32 mg/L (normal range with the medial aspect of the left kidney and adrenal gland, completely encasing the
0.19e0.55 mg/L). This raised the suspicion for a vascular anomaly as left renal hilar vessels isolated on blue and red vessel loops.

the underlying aetiology of the mass. In order to optimize pre-

operative platelet levels, a trial of transfusion with platelet
the intensive care unit postoperatively and extubated the following
concentrate was performed which showed a satisfactory rise in
day.
platelet count to a safe level for surgery, from 25,000/mL to 127,000/
Her platelet trend increased to 292,000/mL by post-operative
mL at 1 hour post transfusion, before decreasing to 22,000/mL by 24
day 2, without further platelet transfusions. Her postoperative
hours post-transfusion. Thus, a left radical nephroureterectomy
course was complicated by gastroparesis and ileus lasting 13 days,
was performed under the cover of continuous platelet and cry-
which was treated conservatively with intravenous erythromycin.
oprecipitate transfusions (Fig. 2).
In view of the histopathological findings, no adjuvant chemo-
Intraoperative rotational thromboelastometry (ROTEM™) was
therapy or interferon alpha was indicated. The patient returned to
used to guide the transfusion of blood products. Intraoperative
her home country and no complications were recorded in subse-
INTEM and FIBTEM reflected the hypofibrinogenemia and a defi-
quent follow-up at 1 year after operation in our hospital.
cient intrinsic pathway. Intravenous tranexamic acid bolus and
Pathological examination of the nephroureterectomy specimen
infusion was administered to minimize blood loss. Other strategies
revealed a lobulated haemorrhagic tumour replacing the renal
employed intraoperatively to minimize blood loss included mild
parenchyma with prominent hydronephrosis (Fig. 3a). Histology
hypotension and maintenance of normothermia via the use of
showed multiple blood-filled lobules of plump spindled tumour
active warming devices. The INTEM and FIBTEM repeated toward
cells forming slit-like anastomosing and complex vascular spaces
the end of surgery showed a robust clot formation with normal clot
(Fig. 3b). The spindled tumour cells had oval nuclei containing
formation time, alpha angle, and maximal amplitude. The imme-
dispersed chromatin and small nucleoli. Occasional fibrin thrombi
diate postoperative haemoglobin was 10.9 g/dL, platelet count of
were noted (Fig. 3c). Immunohistochemical stains showed positive
95  109/L and fibrinogen 4.44 g/L. The patient was transferred to
reactivity for vascular markers CD31 and CD34. D2-40 was positive
in patchy areas indicating lymphatic differentiation (Fig. 3d). There
was negative staining for desmin, GLUT1, CD10 and WT-1. The
histological features and immunophenotype were in keeping with

Fig. 1. Contrast enhanced CT scan demonstrating the exophytic lobulated mass
centered at the left renal hilum, with prominent contrast enhancement and associated
hydronephrosis.
Fig. 3. a. Gross specimen showing lobulated hemorrhagic tumor replacing the renal
parenchyma, b. Photomicrograph (H&E,  20) demonstrating lobulated architecture of
tumor and prominent congestion of vascular spaces, c. Photomicrograph (H&E,  400)
demonstrating complex well canalized to slit-like vascular structures lined by spindled
cells with occasional fibrin thrombi (arrow), d. Immunohistochemical stain with D2-
40 showing patchy reactivity indicating differentiation towards a lymphatic
phenotype.
 M.S. Nwe et al. / Pediatric Hematology Oncology Journal 1 (2016) 89e92
that of kaposiform hemangioendothelioma.
3. Discussion
KHE is a rare vascular neoplasm occurring commonly in infancy
or early childhood, and is associated with lymphangiomatosis and
Kasabach-Merritt syndrome [1]. Pathologically, KHE is a locally
aggressive vascular neoplasm which does not spontaneously
regress nor metastasize, and which involves mostly superficial and
deep soft tissues and rarely, the retroperitoneum, mediastinum,
and internal organs. There was one case report of autopsy finding of
multifocal KHE in multiple visceral organs in 9 days old baby girl
who died of systemic bleeding tendency following disseminated
intravascular coagulation [2]. Over 70% of KHE are associated with
KMS and mostly found in patients with large lesions involving the
retroperitoneum or mediastinum [3]. Most tumours present as
cutaneous, red to purplish masses on the extremities and trunk
with ill-defined borders. Visceral involvement albeit sporadic has
been described, affecting the thymus, thyroid, pancreas, liver,
stomach and kidney [3e7]. KHE bears some morphological
resemblance histologically to Kaposi sarcoma, but is not associated
with Human Herpes Virus-8 infection or HIV infection.
KHE of the kidney is extremely rare. To date, there have only
been 1e2 other reports of KHE involving the kidney reported in the
English literature. The first paper reports a 4 year old girl who
presented with persistent haematuria but no KMS [7]. She received
neoadjuvant vincristine and actinomycin and subsequent ne-
phrectomy. Post-operative interferon alpha was administered and
the patient had no complications 8 years after surgery. Another
paper appears to report on the same girl who received similar
neoadjuvant chemotherapy prior to surgical resection, and
following postoperative interferon alpha, survived to 10 years
without recurrence [8].
This is the first known case of renal KHE associated with KMS.
The various challenges encountered included accurate preoperative
recognition of a rare tumour type, perioperative management of
consumptive thrombocytopaenia and post-operative care involving
multiple paediatric subspecialties. Radiographic imaging demon-
strated a hypervascular lesion with poor margins and hyper-
intensity on MRI T2-weighted images, which are typical
appearances for this tumor [9]. The presence of refractory throm-
bocytopenia in this patient also posed a challenge to both diagnosis
and management. This combination of the radiological and hae-
matologic features raised the suspicion of a vascular tumour with
KMS, making Wilms tumor and neuroblastoma less likely.
The management of KMS in KHE is often difficult and is typically
associated with more aggressive lesions and poorer outcomes [10].
Medical management for tumours associated with KMS have been
reported but with variable outcomes with no demonstration of
superiority of a single therapeutic regimen [11e13]. Despite the
alarmingly low platelet counts often seen in KMS, prophylactic
platelet transfusions have been shown to be of minimal benefit due
to the short half-life and sequestration within the tumour and have
been reported to paradoxically worsen coagulopathy [14]. How-
ever, demonstration of an adequate, though transient response in
platelet counts with adequate platelet transfusions can facilitate
safe and successful surgery of thrombocytopenic patients [15].
For inoperable KHE associated with KMS, first-line therapy with
intravenous vincristine, oral prednisolone or intravenous methyl-
prednisolone is recommended [16]. For inoperable KHE without
KMS that require intervention due to symptoms arising from
enlarging masses, oral prednisolone is the treatment of choice [16].
Recently, consensus-derived treatment plans for complex KHE have
proposed that upfront surgical resection should be considered for
patients with KHE that can be safely and completely excised [16].
91
Nonetheless, certainty of complete removal, access to ROTEM, and
overall morbidity risk should be considered prior to undertaking
such a decision. Arterial embolization can be employed as an
adjunct to surgery to minimize bleeding during resection [17].
Pharmacological management of KHE to reduce tumour burden
and correct coagulopathy is more controversial as it may cause
many side effects or may be ineffective [18]. In our case, with suf-
ficient diagnostic workup and haemostatic measures, upfront sur-
gical resection was a viable approach to managing renal KHE with
KMS. We spared the patient neoadjuvant chemotherapy as com-
plete surgical resection was deemed feasible based on preoperative
imaging, and resection of the tumour was indeed achieved with
clear margins. KMS resolved after radical nephrectomy and the
tumour has shown no recurrence at last follow up, one year after
surgery.
4. Conclusion
While the management of KHE should be individualized, based
on the size of tumour, resectability, presence of functional
compromise, and the presence of accompanying KMS, the diag-
nostic and management approach to a rare tumour like this is
facilitated by close inter-disciplinary consultation. With patho-
gnomonic radiological and haematological features to provide
diagnostic certainty, upfront surgical resection is a feasible option
that can spare the use of chemotherapy in the treatment of this
disease.
Funding source
No specific source of funding was used.
Financial disclosure statement for all authors
The authors have no financial relationships relevant to this
article to disclose.
Conflict of interest
The authors do not have any conflict of interest to declare.
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