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Advances in dermatology and venereology Acta Dermato-Venereologica
Ramucirumab-induced Multiple Haemangiomas of the Skin : Two Case Reports
Hideyuki KOSUMI 1 , Wataru NISHIE 1 *, Tatsuro SUGAI 1 , 2 , Ellen TOYONAGA 1 , Norihiro YOSHIMOTO 1 , 2 , Hiroyuki NAKAMURA 2 , Ryota HORIBE 3 , Yasuo KITAMURA 3 , Hiroshi NAKATSUMI 4 and Hiroshi SHIMIZU 1
1
Department of Dermatology , Faculty of Medicine and Graduate School of Medicine , Hokkaido University , North 15 West 7 , Kita-ku , Sapporo 060-8638 , Departments of 2 Dermatology and 3 Respiratory Medicine and Allergology , Kushiro City General Hospital , Kushiro and 4 Department of Cancer Chemotherapy , Hokkaido University Hospital Cancer Center , Sapporo , Japan . * E-mail : nishie @ med . hokudai . ac . jp Accepted Dec 20 , 2017 ; Epub ahead of print Dec 20 , 2017
Ramucirumab is a fully human IgG1 monoclonal antibody that selectively binds to the extracellular domain of vascular endothelial growth factor receptor 2 ( VEGFR-2 ). Ramucirumab is mainly used as a second-line treatment for advanced cancers , such as gastric , colorectal and nonsmall-cell lung cancers ( 1 – 4 ). Various adverse events due to ramucirumab have been reported , including hypertension , deep vein thrombosis , headaches , anorexia , vomiting and dyspnoea ( 5 ). Tanibirumab and alacizumab , which are reagents targeting VEGFR-2 , are known to induce haemangiomas as a paradoxical reaction ( 6 , 7 ); however , only 2 cases of multiple haemangiomas associated with ramucirumab have been reported in a phase I study ( CP12-0401 ), and these had no detailed clinical or histopathological descriptions ( 8 ). Moreover , tanibirumab and alacizumab are not commercially available . Therefore , we clinicians have limited opportunity to observe this phenomenon . We report here 2 cases of ramucirumab-induced multiple haemangiomas of the skin .
CASE REPORTS
Case 1 . A 61-year-old woman presented to our department with multiple reddish macules over the body . She was on FOLFIRI ( 5-fluorouracil , leucovorin , irinotecan ) and ramucirumab treatment as a second-line chemotherapy for refractory metastatic caecal adenocarcinoma . Eighteen months earlier , caecal adenocarcinoma with multiple liver metastases had been found and she had received mFOLFOX6 ( oxaliplatin , 5-fluorouracil ( 5-FU ), folic acid ) plus bevacizumab therapy . After 5 cycles of the regimen , she had undergone a right hepatic and caudal lobectomy . New liver metastases were found 5 months after the operation , and mFOLFOX6 plus bevacizumab treatment was re-started . Unfortunately , the metastatic lesion of the liver enlarged and the treatment was changed to FOLFIRI plus ramucirumab . Two months after the treatment , reddish papules developed .
Physical examination revealed numerous reddish papules approximately 2 – 3 mm in diameter on the scalp , neck , trunk and limbs ( Fig . 1a , b ). There was a slightly elevated red macule of 30 × 20 mm on the right shoulder ( Fig . 1a ). Dermoscopy revealed red homogenous globules surrounded by telangiectasia ( Fig . 1c ). Histopathological findings of the skin specimen obtained from a red papule on the neck revealed local proliferation of vascular endothelial cells in the superficial dermis ( Fig . 1d ). Enlarged capillary vessels and fibrosis surrounding the endothelial cells were also observed ( Fig . 1d ). We made a diagnosis of capillary haemangioma , and the other lesions were not removed . The FOLFIRI plus ramucirumab therapy was switched to panitumumab because of severe neutropaenia . Approximately 3 months after discontinuing the treatment , the haemangiomas disappeared gradually ( Fig . 1b ).
Case 2 . A 65-year-old woman presented to our department with slowly growing nodules on the limbs and the face . She had been receiving docetaxel and ramucirumab as a second-line therapy for refractory metastatic lung adenocarcinoma for 2 months . Three years earlier , she had been diagnosed with lung adenocarcinoma with bone metastasis of the right sixth rib and thoracic vertebrae . The patient had received radiation ( total dose : 30 Gy ) to the right rib , and thoracic vertebrae and afatinib was started . One month later , the afatinib was changed to gefitinib due to drug-related ileus . One year later , carboplatin and pemetrexed were started because of metastasis to the skull . Unfortunately , cerebellar metastasis was found after 3 cycles of the regimen , which was
Fig . 1 . Clinical and histopathological characteristics of case 1 . ( a ) Sporadic reddish papules approximately 2 – 3 mm in diameter are seen on the neck and right shoulder ( black arrows ). There is also a slightly elevated red macule measuring 30 × 20 mm on the right shoulder ( white arrow ). ( b ) Three months after the cessation of FOLFIRI ( 5-fluorouracil , leucovorin , irinotecan ) and ramucirumab . Note the haemangioma has spontaneously regressed . ( The lesion of the right neck has been excised .) ( c ) Dermoscopy shows red homogenous globules surrounded by telangiectasia ( arrowheads ). ( d ) The skin specimen of the red papule on the neck shows local proliferation of vascular endothelial cells in the superficial dermis . Enlarged capillary vessels ( arrowheads ) and fibrosis surrounding the endothelial cells are also seen . Scale bar : 200 μm . doi : 10.2340 / 00015555-2869 Acta Derm Venereol 2018 ; 98 : 454 – 455
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica .