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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 6  |  Issue : 2  |  Page : 105-108

Nivolumab induced vitiligo-like depigmentation in metastatic acral lentiginous melanoma


1 Department of Dermatology, Command Hospital, Chandimandir, Chandigarh, India
2 Department of Dermatology, AFMC, Pune, Maharashtra, India
3 Department of Pathology, Command Hospital, Kolkata, India

Date of Web Publication19-Dec-2019

Correspondence Address:
Shekhar Neema
Department of Dermatology, AFMC, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/Pigmentinternational.Pigmentinternational_

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  Abstract 


Melanoma is an uncommon malignancy in Indian subcontinent. Dermoscopy of cutaneous metastases of malignant melanoma has been rarely reported. Immune checkpoint inhibitors are increasingly being used for management of metastatic melanoma. They are associated with frequent cutaneous adverse events. Few of the cutaneous adverse events are associated with better prognosis for melanoma. We report a rare case of metastatic acral lentiginous melanoma for rarity of dermoscopic findings of cutaneous metastases and adverse effect due to immune checkpoint inhibitor.

Keywords: dermoscopy, immune checkpoint inhibitors, malignant melanoma, nivolumab, vitiligo-like depigmentation


How to cite this article:
Dabbas D, Neema S, Pathak N. Nivolumab induced vitiligo-like depigmentation in metastatic acral lentiginous melanoma. Pigment Int 2019;6:105-8

How to cite this URL:
Dabbas D, Neema S, Pathak N. Nivolumab induced vitiligo-like depigmentation in metastatic acral lentiginous melanoma. Pigment Int [serial online] 2019 [cited 2020 Oct 26];6:105-8. Available from: https://www.pigmentinternational.com/text.asp?2019/6/2/105/273463




  Introduction Top


Melanoma is malignant proliferation of melanocytes. It accounts for less than 5% of cutaneous malignancies, but accounts for 60% of deaths due to skin cancers.[1] It is also one of the most common cancers in adolescent and young adults. The incidence of melanoma is rising for last 50 years worldwide. It is more common in fair-skinned individuals. India has low incidence of malignant melanoma and cutaneous malignant melanoma forms 0.5% of all malignancies.[2] In Caucasian population, melanoma is more common on the back and shoulders of men and lower legs of women. This may be due to intense and intermittent sun exposure. In Asian population, acral lentiginous melanoma (ALM) is commoner and hidden location of ALM contributes to its poorer prognosis. Prognosis depends on tumor thickness, histologic ulceration, and lymph node involvement.[3] Surgical excision is treatment of choice in patient with early-stage cutaneous melanoma. Sentinel lymph node biopsy and lymph node dissection are also performed in patients who have nodal disease. Advance disease (Stage IV) has poor prognosis with median survival of 6–9 months and 5 years survival rates of less than 20%. With availability of immunotherapy and targeted therapy, prognosis has greatly improved. Targeted therapy for melanoma includes BRAF inhibitors (Vemurafenib), mitogen-activated protein kinase (MEK) inhibitors (Tramatenib), anti-CTLA4 antibody (Ipilimumab), and anti-programmed death receptor (PD-1) agents (Pembrolizumab and Nivolumab). PD-1 blockers are considered first line monotherapy in unresectable melanoma. Nivolumab and pembrolizumab are humanized IgG4 anti-PD1 monoclonal antibody. Nivolumab was approved in December 2014 for treatment of metastatic melanoma. PD-1 inhibitors increase the antitumor response by immune checkpoint inhibition.[4] We hereby report a case of metastatic acral lentiginous melanoma for its rare dermoscopic features of intransit metastases and cutaneous adverse effects of anti-PD1 therapy.


  Case report Top


A 58-year old male, a case of acral lentiginous melanoma, was diagnosed when he was presented with dark colored lesion on plantar aspect of left foot involving fourth and fifth toe. Punch biopsy confirmed diagnosis of melanoma. Ray amputation of fourth and fifth left toe was done. Stage of tumor was determined to be IIc with Breslow thickness of 7 mm [Figure 1]a,b. Clinically there was no lymph node involvement. However, inguinal lymph node dissection was done. All resected margins were free of disease and there was no involvement of lymph nodes. One year later patient had recurrence of disease and he was presented with multiple dark colored lesions involving left lower limb. Evaluation revealed involvement of inguinal lymph nodes and presence of in-transit metastases [Figure 2]. He was diagnosed as metastatic ALM and started on Nivolumab 240 mg iv every 2 weeks. After three cycles, he was presented with cheilitis which was managed symptomatically. Three months after starting therapy, he developed light colored asymptomatic lesions involving face and upper extremities [Figure 3]a,b. Dermatological examination revealed presence of depigmented macules involving face, trunk, and upper limbs. Numerous dark colored nodules involving left lower limb were present. Dermoscopy of these nodules revealed diffuse-homogenous, blue-grey pigmentation without pigment network [Figure 4]a,b. He was diagnosed with vitiligo-like depigmentation resulting from PD-1 inhibitor; he was counselled about effectiveness of treatment and advised to continue same treatment.
Figure 1 (a) Naests of malignant cells seen infiltrating the epidermis with obliteration of dermo-epidermal junction (H&E, 4x). Inset: The cells are highly pleomorphic with prominent eosinophilic nucleoli and abundant granular pigmented cytoplasm showing retraction artifact (H&E, 40x). (b) Ibnfiltration and destruction of the adnexal structures are seen in the deeper dermis (H&E, 4x).

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Figure 2 Amputated fourth and fifth toe. Multiple dark colored nodules involving left lower limb.

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Figure 3 a and 3b Vitiligo-like depigmentation is seen in Figure 3b, 12 weeks after starting nivolumab.

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Figure 4 (a) Daermoscopy of dark colored nodules (intransit metastases) reveals homogenous blue to grey pigmentation (white star) with an incomplete white veil, fine peripheral scaling (thin blue arrow). Subcutaneous nodule shows similar ill-defined bluish hue on dermoscopy (thick blue arrow) (Dermlite DL4 Polarised X20). (b) Hbigher magnification shows diffuse blue grey pigmentation, white veil and fine scaling (white arrow) more clearly (Dermlite DL4 polarised X 50).

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  Discussion Top


Cutaneous malignant melanoma is one of the most aggressive malignancy. Approximately, 16.5% patients develop in-transit, regional, or distant metastases. The frequency of metastases to skin varies from 42% to 57%.[5]

Skin metastases may be first manifestation in 2-8% of cases. Dermoscopic features of cutaneous malignant melanoma are well defined, however melanoma metastases do not have characteristic dermoscopic features. Various patterns that have been described are homogenous diffuse pattern, saccular pattern, vascular pattern, amelanotic pattern, and polymorphic or multi-component pattern.[6] Our patient had homogenous pattern.

PD-1 inhibitors are new group of drugs which belong to class of immune check point inhibitors and are increasingly being used for management of various malignancies. Immune checkpoint inhibitors result in adverse effects, collectively known as immune-related adverse events (irAEs). irAEs can be systemic or cutaneous. Cutaneous adverse effect is seen in as much as 40% patients.[7] Cutaneous adverse effects are common during these drugs and seldom require discontinuation of therapy. Cutaneous adverse effects which have been described as pruritus, non-specific rash, lichenoid reaction, eczema, psoriasiform dermatitis, bullous pemphigoid, and vitiligo. Rash and vitiligo have also been associated with favorable outcome in terms of disease-free survival and antitumor response in melanoma patients.[8] It is important for dermatologists to be aware of these adverse effects and their prompt management can avoid dose reduction or cessation of these life-saving drugs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Garbe C, Leiter U. Melanoma epidemiology and trends. Clin Dermatol 2009;27:3-9.  Back to cited text no. 1
    
2.
Nair MK, Varghese C, Mahadevan S, Cherian T, Joseph F. Cutaneous malignant melanoma-clinical epidemiology and survival. J Indian Med Assoc 1998;96:19-20.  Back to cited text no. 2
    
3.
Erdmann F, Lortet-Tieulent J, Schuz J, Zeeb H, Greinert R, Breitbart EW et al. International trends in the incidence of malignant melanoma 1953-2008—Are recent generations at higher or lower risk? Int J Cancer 2013;132:385-400.  Back to cited text no. 3
    
4.
Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Bastholt L et al. European Dermatology Forum (EDF), European Association of Dermato-Oncology (EADO), European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline − Update 2016. Eur J Cancer 2016; 63:201-17.  Back to cited text no. 4
    
5.
Finn L, Markovic SN, Joseph RW. Therapy for metastatic melanoma: the past, present, and future. BMC Med 2012;2:10-23.  Back to cited text no. 5
    
6.
Rubegni P, Lamberti A, Mandato F, Perotti R, Fimiani M. Dermoscopic patterns of cutaneous melanoma metastases. Int J Dermatol 2014;53:404-12.  Back to cited text no. 6
    
7.
Collins LK, Chapman MS, Carter JB, Samie FH. Cutaneous adverse effects of the immune checkpoint inhibitors. Curr Probl Cancer 2017;41:125-8.  Back to cited text no. 7
    
8.
Nakamura Y, Teramoto Y, Asami Y, Matsuya T, Adachi JI, Nishikawa R, Yamamoto A. Nivolumab therapy for treatment-related vitiligo in a patient with relapsed metastatic melanoma. JAMA Dermatol 2017;153:942-4.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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