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- Presentation
Oncodermatology Rash Patterns and Histopathology in Targeted Therapies and Checkpoint Inhibitors
Description
The speaker, a dermatopathologist at Houston cancer centers, reviewed rapidly evolving oncodermatology with emphasis on targeted therapies and immune checkpoint inhibitors. She noted that skin toxicities are common and often treatment-limiting, making biopsy and clinicopathologic correlation essential. For targeted therapies, she highlighted on-target/off-organ toxicities in skin structures such as hair follicles, nails, and eccrine glands, using nectin-4 antibody-drug conjugate therapy as an example of toxic erythema of chemotherapy with characteristic fold-predominant eruptions and subtle histology including syringosquamous metaplasia and dyskeratosis. She also discussed amivantamab and similar agents, which can cause acneiform eruptions, paronychia, eczema, hypertrichosis, and later neutrophilic or pyoderma gangrenosum-like ulcerations; histology may show neutrophils, plasma cells, and follicular damage, and dapsone can be useful. For checkpoint inhibitors, she reviewed common patterns including eczematous, psoriasiform, lichenoid, bullous pemphigoid, vitiligo, and less commonly granulomatous or classic severe drug eruptions. She stressed that histology is often subtler than the clinical presentation, mixed spongiotic/psoriasiform or lichenoid patterns are common, and emerging markers such as IL-13 and IL-36 may help predict response to biologics like dupilumab or risankizumab. Overall, the talk emphasized using pathology to identify the likely culprit drug, guide management, and help decide whether cancer therapy can continue, be held, or be switched.
View moreConclusions
- Cutaneous adverse events from modern cancer therapies are increasingly common and clinically important, often affecting treatment continuation as much as skin symptoms themselves.
- Histopathology is essential for distinguishing targeted-therapy toxicity from checkpoint-inhibitor eruptions, especially when patients are receiving combination regimens.
- Many drug eruptions show overlapping and mixed patterns rather than classic textbook appearances, so dermatopathologic diagnoses should be descriptive and correlated with the clinical setting.
- Targeted therapies can produce on-target, off-organ toxicities in skin appendages and epithelium, with patterns such as toxic erythema of chemotherapy, acneiform eruptions, and neutrophilic or pustular disease.
- Enfortumab vedotin commonly causes toxic erythema of chemotherapy–like eruptions with characteristic eccrine/follicular involvement and dyskeratotic changes that may help confirm the diagnosis.
- Amivantamab and similar EGFR/MET-directed agents can produce prominent acneiform, periungual, hypertrichotic, and neutrophilic/ulcerative toxicities that may require different management such as dapsone or steroids.
- Checkpoint inhibitor eruptions frequently include eczematous, psoriasiform, lichenoid, and bullous pemphigoid–like patterns, and these reactions can be managed with biologics while often allowing rechallenge.
- Spongiosis is a recurring microscopic theme across several immune-related eruptions and may reflect a shared cytokine biology that could guide treatment choices such as dupilumab or IL-17/IL-23 blockade.
- Clinicopathologic communication is critical because subtle microscopic findings can understate the severity of the clinical rash and can influence which drug is blamed and whether therapy is held, reduced, or continued.
- New translational markers such as IL-13 and IL-36 may eventually help predict rash subtype or treatment response, but current management still relies heavily on careful pattern recognition and integrated interpretation.
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