Pancreatic Kaposiform Hemangioendothelioma Not Responding to Sirolimus

Abstract

Background Kaposiform hemangioendothelioma (KHE) is a vascular tumor frequently associated with Kasabach–Merritt phenomenon (KMP), characterized by severe thrombocytopenia and consumptive coagulopathy. Visceral involvement in KHE is rare. In our recent experience, sirolimus has shown to be an effective treatment in cutaneous KHE, becoming indeed the treatment of choice in KMP. We report a case of pancreatic KHE associated with KMP and refractory to sirolimus. Case Report A 4-month-old infant is referred for obstructive jaundice (10 mg/dL conjugated bilirubin) secondary to vascular pancreatic tumor. Magnetic resonance (MR) and immunohistochemistry were compatible with KHE, but the tumor was considered unresectable. We initiated sirolimus (0.8 mg/m 2 /12 h) to treat KMP, and interventional radiology was performed for percutaneous biliary diversion. This procedure prompted KMP (platelets: 51,000/µL). Sirolimus treatment for 7 days showed no effect; therefore, we started our VAT protocol (vincristine/aspirine/ticlopidin) with great response after 10 days (platelets: 3,70,000/µL). Three months later, percutaneous biliary diversion was replaced by a biliary stent. The tumor disappeared leaving fibrosis and dilatation of biliary tract needing hepaticojejunostomy 6 months later. Discussion It is difficult to establish protocols for an unusual presentation of a tumor with different targets. This is a reason collaborative multicenter studies should be performed. Management of obstructive jaundice secondary to a tumor that usually regresses in 10 years is an added challenge; therefore, the management should be led by a multidisciplinary team. Sirolimus treatment in cutaneous KHE has been described as successful in the literature, as well as in our own experience; however, it failed in our first patient with visceral KHE. We need to investigate the different response to pharmacological agents in tumors with similar histopathology, but with visceral involvement.

Efficacy and safety of sirolimus in the treatment of vascular anomalies: A systematic review

“…One prospective nonrandomized study and 17 retrospective studies described the treatment of lymphatic malformations with oral sirolimus. 14,19,26,32,41,48,56,61,[64][65][66][67][68][69][70][71][72][73] The median age was 12.8 years (0-34 years); 20% of patients were younger than 1 year, and 90% were younger than 18 years. Nonspecified decrease in lesion size was reported in 77.8% patients, partial response in 22.2%, complete response in 3.7%, improvement of pleural effusion in 9.9%, decrease of skin exudate and vesicles in 16.5%, and improvement of pain in 4.9%.…”

Curative effect of surgical resection in the treatment of Kaposiform hemangioendothelioma

“…While prednisolone, vincristine and sirolimus showed some effectiveness in decreasing the tumor size 16,17 , can cause side effects such as abdominal pain, elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), opportunistic infection, loss of appetite, etc 18 . Moreover, there are case reports of visceral KHE not responding to sirolimus 19,20 . In addition, for those KHE patients unresponsive to glucocorticoids, propranolol, vincristine or sirolimus treatment, surgical therapy reduced skin petechia and coagulopathy to normal levels.…”

Pancreatic kaposiform hemangioendothelioma complicated by Kasabach–Merritt phenomenon: A rare entity

“…6 Medical therapies for KHE and KMP include systemic steroids, vincristine, inteferon-alpha and aspirin. 7 In cases with associated biliary obstruction, complete surgical resection with a Whipple operation has been reported and there have also been successful attempts at biliary stenting and external drainage (palliative surgery), pending spontaneous tumour regression. 1,6 Historically, angiography and embolisation have been used for the diagnosis and treatment of KHE.…”

“…Mammalian target of rapamycin (mTOR) inhibitors such as sirolimus have proven to be effective in the treatment of cutaneous KHE. 7 Triana et al described a case of pancreatic KHE not responding to sirolimus and suggested the possibility of a different molecular profile compared to the cutaneous form as a result of the resistance to mTOR inhibitors treatment. 7…”