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Year : 2021  |  Volume : 58  |  Issue : 4  |  Page : 631--634

Kaposiform hemangioendothelioma of leg: An unusual presentation

Adarsh W Barwad1, Ekta Dhamija2, Venkatesan S Kumar3, Sameer Rastogi4, Asit R Mridha1,  
1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Radiodiagnosis, Dr Bhimrao Ambedkar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
3 Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, India
4 Department of Medical Oncology, Dr Bhimrao Ambedkar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Asit R Mridha
Department of Pathology, All India Institute of Medical Sciences, New Delhi

How to cite this article:
Barwad AW, Dhamija E, Kumar VS, Rastogi S, Mridha AR. Kaposiform hemangioendothelioma of leg: An unusual presentation.Indian J Cancer 2021;58:631-634

How to cite this URL:
Barwad AW, Dhamija E, Kumar VS, Rastogi S, Mridha AR. Kaposiform hemangioendothelioma of leg: An unusual presentation. Indian J Cancer [serial online] 2021 [cited 2022 May 22 ];58:631-634
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Kaposiform hemangioendothelioma (KHE) is an uncommon intermediated grade, vascular tumor, which primarily occurs in infants and children. It is characterized by rapid growth with local extension involving the skin, soft tissues, and even bone.[1] Extremities, joint, chest and abdominal wall, retroperitoneum, head, and neck regions are usually affected. Superficial lesions are common and seen in the skin as an enlarging ill-defined red to purple indurated plaque.[2] Dermal ecchymosis, petechiae around the umbilicus or in the skin, and cutaneous ulceration are other manifestations. KHE may be associated with lymphangiomatosis, thrombocytopenia, and bleeding manifestation leading to Kasabach–Merritt phenomenon (KMP).[2] KHE may rarely involve bone and reminiscent primary bone neoplasm; however, KHE clinically presenting as osteomyelitis has not been described in the English literature.

A 3-year-old boy presented with complaints of gradually increasing swelling in the right leg, low grade, and intermittent fever since 7 months of age. The swelling increased from 3–5 cm to 8–10 cm over the past 2 years. There was no history of trauma, bleeding, or contact with tuberculosis. The child had delayed motor developmental milestones as he could not crawl or stand without support due to the swelling. Physical examination revealed diffuse edema of the right leg and a hard non-tender mass measuring about 10 cm. The overlying skin was unremarkable. Sequential radiographs revealed soft-tissue swelling with ill-defined sclerosis in the proximal right tibia and cortical erosion along the medial aspect of the right fibula (arrow) [Figure 1]a. The lesion progressed to involve the fibula circumferentially and produced lytic sclerotic areas in the tibia [Figure 1]b. Magnetic resonance imaging (MRI) showed a heterogeneous lesion with a low signal intensity in T1-weighted image [Figure 1]c and mixed high and low signal intensity in the T2 fat suppressing sequence [Figure 1]d. The lesion exhibited reticulations within the subcutaneous fat, fatty infiltration within the muscular plane, and an ill-defined plaque-like soft tissue along the muscular fascia on short tau inversion recovery (STIR) sequences [Figure 1]e and [Figure 1]f. There was marked atrophy of the muscles. The radiological differentials were an aggressive neoplasm and infective pathology.{Figure 1}

Complete blood count revealed hemoglobin of 10.7 g/dL (Reference range [RR]: 12-15 g/dL) g/dL with mean corpuscular volume 73 fL (RR: 72-85 fL). Platelet count was 204000 cu/mm3 (RR: 150000-450000/mm3) and total leucocyte count 15900/mm3 (RR: 4000-11000/mm3). The differential leucocyte count showed neutrophils 55 (RR: 40-75), lymphocytes 38 (RR: 25-40), and monocytes 7 (RR: 2-10) percent. Erythrocyte sedimentation rate was 31mm at 1 hour (RR: < 10mm), and C-reactive protein 5.6mg/L (RR: < 3mg/L). Liver and renal function tests were within normal limits. Serum serology for HbsAg, HCV, HIV1, and HIV2 was non-reactive.

A biopsy in a local hospital was non-diagnostic. Surgical debridement was done and antibiotics were given. However, the swelling recurred and low-grade fever persisted. Repeat debridement was performed and a histopathology report was given as an inflammatory lesion. He was shifted to another hospital, where debridement was done again and antibiotics were given but the swelling recurred. Then empiric antituberculosis drugs were administered. There was no response even after 6 months and the patient was referred to a tertiary healthcare institute.

Microscopic sections of submitted paraffin blocks showed irregular, infiltrating nodules of compressed vessels with an intervening dense hyaline stroma. The vessels were highly convoluted and compactly curled producing slit-like spaces and resembling capillary hemangioma [Figure 2]a and [Figure 2]b. A scattered lymphocytic infiltrate was noted within. The spindle cells were immunopositive to CD34, FLI1, and CD31 [Figure 2]c and [Figure 2]d. Histopathology diagnosis was KHE.{Figure 2}

Though vincristine has been a commonly used first-line chemotherapeutic drug in the patients with KHE even in KMP, considering the safety of the drugs, the patient was treated with oral propranolol (0.6 mg/kg twice a day) and prednisone (2 mg/kg). On the 1-month follow-up, there was a slight decrease in the size of the swelling and the child was able to sleep without analgesics. On a 3-month follow-up, the child started crawling and standing without support. Subsequently, he developed Cushingoid features and the steroid doses were tapered. The patient has now been planned for surgery with an exploring possibility of limb salvage. However, due to the COVID-19 pandemic, surgery has been postponed.

The term, KHE, was given by Zukerburg, Nickoloff, and Weiss in 1993 because of its histologic similarities to Kaposi sarcoma (KS).[3] This is a rare locally infiltrative, aggressive, vascular neoplasm, which primarily affects infants and children. Typically, the extremities especially the proximal arms, legs, and the trunk are affected. The lesion manifests as ill-defined superficial indurated violaceous papules, plaque, ecchymotic patches, ulcer, or deep-seated soft-tissue masses. Skin is the most frequently involved organ. A large tumor may be associated with thrombocytopenia and consumption coagulopathy, which is known as KMP.[2] In our case, the lesion affected deeper soft tissue, and bone without any cutaneous manifestation or thrombocytopenia.

Radiography usually shows a locally invasive, well defined, or infiltrative solid lesion involving one or more adjacent organs. MRI shows iso to hyperintensity on T2-weighted images. Ma et al. reported two cases of osseous KHE in a 9-year-old girl and a 5-year-old boy, who presented with pain and swelling in the right distal femur, and episodic pain in the right shoulder, respectively, without cutaneous lesions. In the former patient, tumor involved the distal epiphysis of right femur and radiographs showed circumscribed lytic lesion, mimicking chondroblastoma. The tumor recurred 5 years after the local excision. However, no relapse was observed 15 years after the second excision. Radiographs of the second case showed a honeycomb-like lytic lesion in the cortex and medulla of the proximal humerus including epiphysis. Clinically the differential diagnoses were an enchondroma and a chondroblastoma. No recurrence was observed for about 5 years after the complete excision.[4] In our case, the radiographic findings were suggestive of chronic osteomyelitis versus an aggressive soft tissue tumor.

The microscopic features of KHE resemble KS with the formation of infiltrative nodules of bland-looking spindle-shaped endothelial cells and slit-like vascular channels. The tumor margins are typically irregular and infiltrative, and the endothelial cells are immunoreactive to CD34, CD31, FLI1, and ERG but negative for GLUT1. At the periphery of the lesion, the proliferative capillaries are positive for D240.[2] In the present case, the tumor showed similar classic morphology and immunohistochemistry.

The differential diagnoses of KHE include KS and tufted angioma (TA). KS usually has cutaneous and or mucosal manifestation and occurs due to an infection of endothelial or progenitor cells by Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8). The majority of KS occurs when the patients suffer from concomitant immune deregulation that provides a favorable microenvironment for the hyperproliferation of KSHV infected cells. Infiltration of immune-modulatory cells induces chronic inflammation, which favors angiogenesis. Elderly Mediterranean men are usually affected by the classical KS and present with cutaneous lesions on the lower extremities. Endemic KS is seen in sub-Saharan Africa and is more aggressive than classic KS. Most of the Kaposi sarcomas are epidemic KS or HIV-associated and develop in HIV-infected patients as a disseminated cutaneous disease with or without mucosal involvement. Patients receiving immunomodulatory agents, especially for a solid organ transplant, often develop transplant-associated KS.[5] Histomorphology and immunohistochemistry profiles of KS share many similarities with that of KHE. In this case, there was no skin involvement, and serum serology for HIV was negative.

TA occurs in children and adolescents as erythematous macules and papules, which microscopically show multiple lobulated clusters of capillary-sized vessels in a "cannonball" fashion in the dermis. TA is a benign tumor that is generally located in the dermis; while, KHE is an aggressive, infiltrative tumor and can involve different organs, tissues, subcutaneous fascia, muscle, and skeleton as seen in our case. Both KHE and TA show lymphocytic infiltration and similar immunoprofiles.[6]

KHE is often associated with KMP with thrombocytopenia, consumptive coagulopathy, and localized intravascular coagulation in the tumor. In fact, KHE has a progressive clinical course and develops KMP. Croteau et al. observed that the risk of KMP increases when the tumor infiltrates into the muscle or arises in the retroperitoneum or mediastinum.[7] In our case, KMP was not seen despite such a large size, which is an unusual finding.

Surgical excision is the treatment of choice for KHE. Adjuvant medical therapy is required for the patient associated KMP and the most frequent therapies include systemic corticosteroids and vincristine (VCR), or corticosteroids alone. VCR, rapamycin, and propranolol are considered for second-line management.[8] Some authors also used systemic corticosteroids and urea. Urea injection works as sclerotherapy and is usually given before resection.[2] However, no definite treatment guideline is available for the long-term observation of patients with KHE. Sirolimus has been added as another option for the complicated vascular tumors like KHE with or without KMP.[9] A combined regimen is recommended and monotherapy is usually not indicated. Prognosis is good and recurrences are rare after complete resection. Our patient showed significant improvement with the combination therapy with propranolol and prednisolone. There were functional improvement and reduction of edema.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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