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. 2025 Oct 31:llaf482.
doi: 10.1093/ced/llaf482. Online ahead of print.

Vitiligo-like leukoderma following treatment with cyclin-dependent kinase 4/6 inhibitors - analysis of clinicopathologic and immunohistochemical findings

Maya Engler Markowitz  1   2 , Rotem Merose  2   3 , Elena Didkovski  2   4 , Alon Doron  2 , Amit Iton  1   2 , Shir Ben Shitrit  1   2 , Aviv Barzilai  2   5   6 , Einav Nili Gal-Yam  2   7 , Debora Kidron  2   8 , Amir Sonnenblick  2   9 , Igor Snast  1   2 , Daniel Mimouni  1   2 , Shany Sherman  1   2
Affiliations

Vitiligo-like leukoderma following treatment with cyclin-dependent kinase 4/6 inhibitors - analysis of clinicopathologic and immunohistochemical findings

Maya Engler Markowitz et al. Clin Exp Dermatol. .

Abstract

Background: Vitiligo-like leukoderma is a rare cutaneous adverse event associated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. However, its clinicopathological and immunohistochemical profiles remain unclear.

Objectives: To characterize the clinical, pathological, and immunohistochemical features of CDK4/6 inhibitor-induced vitiligo-like leukoderma.

Methods: This retrospective case series describes five female patients with advanced or metastatic breast cancer who developed vitiligo-like leukoderma during CDK4/6 inhibitor therapy. Clinical data and skin biopsies were evaluated, including immunohistochemical analysis of melanocyte markers, cell-cycle protein (p16), and T-cell subsets.

Results: The depigmented lesions appeared primarily in sun-exposed areas. Two patients exhibited an inflammatory phenotype with pruritus and a lichenoid rash. In all patients, the lesions progressed rapidly over several months and then stabilized. This course was maintained regardless of any vitiligo-targeted therapeutic interventions. Histopathological examination revealed complete absence of melanocytes in all biopsies. Three specimens (60%) had inflammatory changes, including lichenoid and perivascular lymphohistiocytic infiltrates, with immunohistochemistry showing a predominance of CD4+ T cells within the infiltrates. Features of chronic actinic damage (epidermal atrophy, orthokeratosis, reactive keratinocytes, dermal solar elastosis) were observed. In two biopsies (40%), there was a patchy distribution of p16 staining within basal and suprabasal keratinocytes. Four patients (80%) demonstrated prolonged (2-4 years) progression-free survival.

Conclusions: CDK4/6 inhibitor-induced vitiligo-like leukoderma appears to be a distinct clinicopathological entity, characterized by a predictable course and stabilization, consistent inflammatory features, and a CD4+-predominant immune profile. These findings suggest a unique pathogenic mechanism, either immune-mediated or associated with actinic damage, that distinguishes this condition from classic vitiligo and Immune checkpoint-inhibitor-induced vitiligo-like leukoderma.

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