Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Letter to the Editor - Observation Letter
doi: 10.4103/ijdvl.IJDVL_184_19
PMID: 32031107

Multiple cherry angiomas and pyogenic granuloma in a patient treated with ramucirumab and paclitaxel

Young Hwan Choi, Hyun Jeong Byun, Jong Hee Lee, Ji-Hye Park
 Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence Address:
Ji-Hye Park
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351
Published: 03-Feb-2020
How to cite this article:
Choi YH, Byun HJ, Lee JH, Park JH. Multiple cherry angiomas and pyogenic granuloma in a patient treated with ramucirumab and paclitaxel. Indian J Dermatol Venereol Leprol 2020;86:199-202
Copyright: (C)2020 Indian Journal of Dermatology, Venereology, and Leprology


Secondary neoplasm may develop as a side effect of chemotherapy.[1],[2],[3] Anticancer drugs reported to cause secondary neoplasm are mainly the classic chemotherapeutic agents, including alkylating agents, possibly caused by the effects of DNA damage and immunosuppression.[2] Recently, there have been reports that newer anticancer drugs, including targeted agents and checkpoint inhibitors, may induce secondary neoplasm, such as vemurafenib-induced squamous cell carcinoma and keratoacanthoma.[3] Ramucirumab, one of the newer anticancer drugs, is a fully-human monoclonal antibody targeting the extracellular domain of vascular endothelial growth factor receptor-2 (VEGFR-2) thereby blocking proangiogenic effects of vascular endothelial growth factor (VEGF).[1],[4],[5],[6] The drug is used for treatment of gastric, colorectal and non-small cell lung cancers.[1],[5],[6] We present a case of two different vascular lesions, cherry angioma and pyogenic granuloma, which occurred after treatment with the newer anticancer drug ramucirumab and classic chemotherapeutic agent paclitaxel.

A 40-year-old man presented with 8 mm sized, reddish, dome-shaped, bleeding nodule on the left parietal region of the scalp [Figure - 1]a. He also reported newly appeared multiple tiny erythematous papules on the face and the neck [Figure - 1]a and [Figure - 1]b. He had history of advanced gastric cancer with metastasis to the omentum, pelvic cavity, and transverse mesocolon treated with capecitabine combined with oxaliplatin. Four months later, due to progression of advanced gastric cancer, capecitabine and oxaliplatin were discontinued. Subsequently, the patient was treated with ramucirumab (8 mg/kg) every two weeks and paclitaxel (80 mg/m2) once a week. Four months after starting the changed regimen, he came to our clinic due to the development of lesions described above. for which he claimed no preceding trauma. We performed excisional biopsy on the scalp lesion. The histopathological findings showed dilated capillary vessel proliferation and lymphohistiocytic infiltration in the dermis with epidermal collarettes [Figure - 2]. The scalp mass was diagnosed as pyogenic granuloma, and multiple reddish papules on the face and the neck were clinically diagnosed as cherry angioma. He opted to treat the multiple cherry angiomas for cosmetic reasons and they were removed with carbon dioxide laser. Ramucirumab and paclitaxel was also discontinued due to progression of advanced gastric cancer. The patient was started on pembrolizumab after stopping ramucirumab. Four months after discontinuation of ramucirumab, there were no new lesions.

Figure 1:
Figure 2:

Angiogenesis is one of the hallmarks of cancer and therapies targeting angiogenesis are integral modalities in cancer treatment.[1],[7] As there is increased expression and secretion of the key angiogenesis regulators VEGF and VEGFR in cancers, several newer anticancer drugs inhibiting this pathway have been developed, one of them is ramucirumab.[1],[7] In the English literature, we found only eight cases which reported vascular lesions following treatment with ramucirumab [Table - 1].[1],[4],[5],[8] Seven of the nine cases reported ramucirumab treatment combined with taxanes.[4],[5],[8] In six of these seven cases, pyogenic granuloma-like vascular lesions developed, while eight cases showed vascular lesions on sun-exposed areas such as head and neck.[4],[5],[8]

Table 1: Vascular lesions following treatment with ramucirumab as reported in the English literature

Although the pathological mechanisms underlying development of vascular lesions by ramucirumab are unknown, somatic gene mutation and paradoxical angiogenesis have been suggested.[1],[7] Lim et al. reported that a single somatic VEGFR-2 precursor mutation, which has been reported in angiosarcoma, was identified in the vascular neoplasms induced by ramucirumab.[1] It is thought that disturbance of the VEGF axis, such as increased plasma levels of placental growth factor, VEGF-C, and VEGF-D in patients receiving the VEGF-A inhibitor bevacizumab or complementary enhancement of non-VEGF-mediated angiogenetic pathways involving fibroblast growth factors, contributes to development of vascular neoplasms.[1],[7]

In seven of the nine cases, ramucirumab was used in combination with taxanes.[4],[5],[8] Paclitaxel has been reported to cause periungual pyogenic granuloma and may inhibit functional cytoskeletons required for cell migration, proliferation, secretion, and capillary-like structure formation in angiogenesis by microtubule stabilization.[9] The researchers reported that pyogenic granuloma may be induced by an imbalance between inhibition of angiogenesis and other proangiogenic factors activated by paclitaxel.[9] Although the pathological mechanisms underlying the attribution of paclitaxel and ramucirumab in developing vascular lesions are unknown, changed pharmacokinetics of paclitaxel by VEGFR-2 inhibitor could be one of the mechanisms.[10] Steins et al. reported that a murine VEGFR-2 inhibitor showed systemic effects in decreasing vasculature in patient-derived xenograft mouse models. In addition, after the administration of paclitaxel, pharmacokinetics of paclitaxel was interfered in VEGFR-2-inhibitor-treated group compared with the control group. 10 As the VEGFR-2 inhibitor alters the pharmacokinetics of paclitaxel resulting in imbalance of angiogenic factors, angiomas and pyogenic granuloma-like vascular lesions have developed in cases treated with ramucirumab combined with taxane.

Furthermore, in eight of the nine cases, vascular lesions developed on the head or the neck.[4],[5],[8] Yano et al. reported that ultraviolet radiation may induce angiogenesis by upregulation of VEGF and downregulation of the endogenous angiogenesis inhibitor thrombospondin-1.[11] We believe that ultraviolet exposure might have contributed to the development of vascular lesions on sun-exposed areas.[11]

Therefore, we suggest that clinicians should be aware of the potential development of various vascular lesions especially on the head and the neck when opting for combination therapy with ramucirumab and taxane.

Declaration of patient consent

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

Lim YH, Odell ID, Ko CJ, Choate KA. Somatic p.T771R KDR (VEGFR2) mutation arising in a sporadic angioma during ramucirumab therapy. JAMA Dermatol 2015;151:1240-3.
[Google Scholar]
Boffetta P, Kaldor JM. Secondary malignancies following cancer chemotherapy. Acta Oncol 1994;33:591-8.
[Google Scholar]
Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 2012;366:207-15.
[Google Scholar]
Kosumi H, Nishie W, Sugai T, Toyonaga E, Yoshimoto N, Nakamura H, et al. Ramucirumab-induced multiple haemangiomas of the skin: Two case reports. Acta Derm Venereol 2018;98:454-5.
[Google Scholar]
Espinosa Lara P, Medina-Puente C, Riquelme Oliveira A, Jiménez-Reyes J. Eruptive cherry angiomas developing in a patient treated with ramucirumab. Acta Oncol 2018;57:709-11.
[Google Scholar]
Vennepureddy A, Singh P, Rastogi R, Atallah JP, Terjanian T. Evolution of ramucirumab in the treatment of cancer – A review of literature. J Oncol Pharm Pract 2017;23:525-39.
[Google Scholar]
Clarke JM, Hurwitz HI. Understanding and targeting resistance to anti-angiogenic therapies. J Gastrointest Oncol 2013;4:253-63.
[Google Scholar]
Watanabe R, Nakano E, Kawazoe A, Kuboki Y, Bando H, Shitara K, et al. Four cases of paradoxical cephalocervical pyogenic granuloma during treatment with paclitaxel and ramucirumab. J Dermatol 2019;46:e178-80.
[Google Scholar]
Paul LJ, Cohen PR. Paclitaxel-associated subungual pyogenic granuloma: Report in a patient with breast cancer receiving paclitaxel and review of drug-induced pyogenic granulomas adjacent to and beneath the nail. J Drugs Dermatol 2012;11:262-8.
[Google Scholar]
Steins A, Ebbing EA, Pistorius MC, Waasdorp C, Krishnadath KK, Medema JP, et al. Systemic effects of angiogenesis inhibition alter pharmacokinetics and intratumoral delivery of nab-paclitaxel. Drug Deliv 2017;24:1801-10.
[Google Scholar]
Yano K, Kadoya K, Kajiya K, Hong YK, Detmar M. Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by upregulation of vascular endothelial growth factor and by downregulation of thrombospondin-1. Br J Dermatol 2005;152:115-21.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections