Multiple Squamous Cell Carcinoma after Vemurafenib Therapy Vemurafenib Tedavisi Sonrası Gelişen Multiple Yassı Hücreli Karsinom
Sinem Çiloğlu1, Alpay Duran1, Şirin Yaşar Pekcan2, Aslı Duran2
1Clinic of Plastic and Reconstructive Surgery, Haydarpaşa Numune Training and Research Hospital, İstanbul, Turkey
2Clinic of Dermatology, Haydarpaşa Numune Training and Research Hospital, İstanbul, Turkey
Correspondence Author/Sorumlu Yazar: Alpay Duran, MD E-mail/E-posta: dr.alpayduran@hotmail.com
DOI: 10.5152/TurkJPlastSurg.2016.2063
Letter to the Editor / Editöre Mektup
Received/Geliş Tarihi: 21.10.2015 Accepted/Kabul Tarihi: 31.08.2016 Dear Editor,
Vemurafenib is a low molecular weight, orally available, inhibitor of oncogenic V600 BRAF serine–threonine kinase. It is effective in the treatment of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600-located melanomas.1 The drug specifically targets tumor cells that harbor activating mutations in BRAF gene, most commonly the substitution of glutamic acid for valine at codon 600 (V600E).
Selective BRAF inhibition therapy is associated with malignant and benign growths. Among these are keratoacanthomas, cutaneous squamous cell carcinomas, warty dyskeratomas, verrucous keratoses, acantholytic dyskeratoses, and widespread eruptions. Recent stud- ies showed that squamous cell carcinoma (SCC) and keratoacanthomas developed in 20%–57% of patients who are on vemurafenib therapy.2,3 Cutaneous malignancies occur more frequently than other kinase inhibitor molecules after vemurafenib therapy.
A 59-year-old female patient was referred to our outpatient clinic due to complaints developing over one month. Patient history showed that she underwent surgery in the neurosurgery ward for malignant melanoma in the right frontotemporal area six years earlier, and while she was undergoing radiotherapy and chemotherapy in her follow-ups, metastatic spots were identified in the frontal lobe and abdomen and bilateral lungs with positron emission tomography–computed tomography and cranial magnetic resonance imaging stud- ies. The patient was initiated on vemurafenib therapy and has been followed up at the oncology clinic for five months. The patient was admitted to our clinic for surgery after punch biopsy performed at the dermatology clinic showed crusted lesions on her scalp 4 months after the therapy was initiated resulted as well-differentiated SCC (Figure 1). The masses located in the scalp vertex, bilateral temporal, and right parietal areas were excised, and surgical repair was performed
with full thickness skin graft. Pathology reports of the excised masses revealed well-differentiated SCC. The patient is still in control by our out- patient clinic.
Keratoacanthomas and squamous cell carcinomas occurring after ve- murafenib treatment are believed to be a result of paradoxical activation of mitogen-activated protein kinase pathway. Vemurafenib, a potent in- hibitor of V600E BRAF, targets tumors containing activating V600E BRAF mutations. In phase I trials, vemurafenib has shown complete or par- tial tumor regression in 81% of patients.4 Decrease in mortality rates by 63% has been reported in patients with metastatic melanoma during the 5-year follow-up. In addition, metastatic melanoma progression-free survival time of patients reportedly increased by 74%.5 Considering the potential for malignant lesions to develop on treatment, awareness of potential adverse effects of this agent is necessary, and a low threshold for biopsy of new growth is recommended. Skin lesions should be eval- uated at baseline and every two months, and patients should be moni- tored for 6 months after treatment. More studies need to be conducted
216
Content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
www.turkjplastsurg.org
Figure 1. Preoperative view of the lesions
for a better understanding of the biological development of secondary neoplasms.
Informed Consent: Written informed consent was obtained from pa- tient who participated in this study.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept – S.Ç.; Design – S.Ç., A.D., Ş.Y.P.; Su- pervision – S.Ç., S.Y.P.; Resources – A.D., Aslı.D.; Materials – A.D., Aslı.D.;
Data Collection and/or Processing – A.D., Aslı.D.; Analysis and/or In- terpretation – S.Ç.; Literature Search – A.D., Aslı.D.; Writing Manuscript – A.D., S.Ç.; Critical Review – S.Ç.
Conflict of Interest: No conflict of interest was declared by the au- thors.
Financial Disclosure: The authors declared that this study has re- ceived no financial support.
Hasta Onamı: Yazılı hasta onamı bu çalışmaya katılan hastadan alın- mıştır.
Hakem Değerlendirmesi: Dış bağımsız.
Yazar Katkıları: Fikir – S.Ç.; Tasarım – S.Ç., A.D., Ş.Y.P.; Denetleme – S.Ç., S.Y.P.; Kaynaklar – A.D., Aslı.D.; Malzemeler – A.D., Aslı.D.; Veri To- planması ve/veya İşlemesi – A.D., Aslı.D.; Analiz ve/veya Yorum – S.Ç.;
Literatür Taraması – A.D., Aslı.D.; Yazıyı Yazan – A.D., S.Ç.; Eleştirel İn- celeme – S.Ç.
Çıkar Çatışması: Yazarlar çıkar çatışması bildirmemişlerdir.
Finansal Destek: Yazarlar bu çalışma için finansal destek almadıklarını beyan etmişlerdir.
REFERENCES
1. Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, et al. Clin- ical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010; 467(7315): 596-9. [Cross- Ref]
2. Chu EY, Wanat KA, Miller CJ, Amaravadi RK, Fecher LA, Brose MS, et al. Diverse cutaneous side effects associated with BRAF in- hibitor therapy: a clinicopathologic study. J Am Acad Dermatol 2012; 67(6): 1265-72. [CrossRef]
3. Sharma A, Shah RS, Illum H, Dowel J. Vemurafenib: targeted inhi- bition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies. Drugs 2012; 72(17): 2207-22.
[CrossRef]
4. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic mela- noma. N Engl J Med. 2010; 363(9): 809-19. [CrossRef]
5. Sullivan RJ, Flaherty KT. BRAF in Melanoma: Pathogenesis, Di- agnosis, Inhibition, and Resistance. J Skin Cancer 2011; 2011:
423239.
Turk J Plast Surg 2016; 24(4): 216-7 Çiloğlu et al / Vemurafenib Therapy
