Skin cancer in chronic graft-versus-host disease
cGVHD-associated skin cancer; HSCT skin cancer; "post-transplant cutaneous malignancy" in haematopoietic stem-cell transplant recipients
Allogeneic haematopoietic stem-cell transplant (allo-HSCT) recipients have a substantially elevated lifetime risk of cutaneous malignancy — particularly when complicated by chronic graft-versus-host disease (cGVHD). The risk is driven by a combination of (1) prolonged systemic immunosuppression to manage cGVHD; (2) the chronic immune dysregulation of cGVHD itself; (3) chronic inflammation and fibrosis in sclerodermatoid cGVHD skin (Marjolin-spectrum); (4) prior conditioning chemoradiotherapy; (5) viral co-infection (HPV, EBV, KSHV); and (6) post-HSCT exposure to voriconazole — the long-term azole antifungal that has been independently associated with cSCC risk. Standardised cumulative incidence estimates suggest 5–10% develop cutaneous SCC by 10 years post-transplant, and the risk continues to rise lifelong. Surveillance, photoprotection, voriconazole minimisation, and aggressive surgical management of any new skin lesion are the cornerstones of care, paralleling the management approach for solid-organ-transplant recipients (see monograph).
Cancer risk in HSCT recipients
- Cutaneous SCC — relative risk 5–20× general population; cumulative incidence 5–10% by 10 years post-transplant.
- Cutaneous BCC — relative risk 2–5×; cumulative incidence 10–20% by 10 years.
- Cutaneous melanoma — modestly increased (~2×).
- Kaposi sarcoma — over-represented in HSCT recipients with prolonged immunosuppression and HHV-8 reactivation.
- Other skin cancers — Merkel cell carcinoma, lymphoma, sweat-gland carcinomas — case reports.
- Risk amplified by:
- Chronic GVHD — particularly sclerodermatoid; chronic inflammation, scarring and fibrosis create a Marjolin-spectrum substrate for cSCC.
- Voriconazole exposure — independent risk factor for cSCC; cumulative dose-dependent; consider switching to alternative antifungal (posaconazole, isavuconazole) where possible after 6+ months.
- Prior conditioning chemoradiotherapy — particularly total body irradiation.
- Prolonged systemic immunosuppression for cGVHD (corticosteroids, calcineurin inhibitors, mycophenolate, ruxolitinib, sirolimus).
- Viral co-infection — HPV, EBV.
- Smoking, UV exposure, fair skin.
Chronic graft-versus-host disease — cutaneous features
- cGVHD develops in 30–70% of allogeneic HSCT recipients.
- Cutaneous manifestations:
- Lichen planus-like cGVHD — early; violaceous flat-topped papules with Wickham striae; oral involvement.
- Sclerodermatoid cGVHD — late; scleroderma-like skin thickening, hypopigmentation / hyperpigmentation, joint contractures; the principal Marjolin-spectrum substrate.
- Lichen sclerosus-like cGVHD — atrophic white plaques; vulval / penile involvement; itself an SCC substrate.
- Eczematoid cGVHD — generalised eczematous eruption.
- Mucosal cGVHD (oral, ocular, vulval, anal) is also an SCC substrate; oral SCC risk is substantially elevated in chronic oral GVHD.
Clinical presentation of skin cancer in cGVHD
- Cutaneous SCC may arise:
- Within sclerodermatoid cGVHD plaques as Marjolin-spectrum lesions (chronic ulcer, induration, exophytic mass).
- On photodamaged sun-exposed skin in the context of UV exposure + immunosuppression.
- In oral mucosa with chronic oral GVHD.
- In vulval / penile / anal mucosa with chronic genital GVHD.
- Behaviour is more aggressive than in immunocompetent patients — frequent multifocality, faster growth, higher metastatic risk (similar to solid-organ-transplant recipients).
- Multiple synchronous and metachronous tumours common.
Management
- Multidisciplinary care — haematology / HSCT team, dermatology, plastic surgery, ENT / oral medicine, gynaecology, oncology; lifelong.
- Skin / mucosal surveillance:
- Annual full skin examination from 1 year post-HSCT (6-monthly if previous skin cancer or severe cGVHD).
- Annual oral examination by ENT / oral medicine for patients with oral cGVHD.
- Annual gynaecology / vulval examination for women with vulval cGVHD.
- Lower threshold for biopsy of any new or changing lesion (particularly any new ulceration / induration in a chronic cGVHD plaque).
- Photoprotection — broad-spectrum SPF 50+ daily, sun-protective clothing.
- Voriconazole minimisation — switch to posaconazole / isavuconazole / liposomal amphotericin where possible after the first 6 months post-transplant; particularly in cSCC-prone patients.
- Optimise cGVHD control — extracorporeal photopheresis, ruxolitinib, sirolimus, mycophenolate; minimise corticosteroid exposure.
- Skin cancer treatment:
- Excisional surgery is the cornerstone.
- Mohs micrographic surgery for facial / functionally important sites.
- Adjuvant radiotherapy for incomplete margins, perineural invasion or nodal disease.
- Cemiplimab (NICE TA802) for advanced / metastatic cSCC unsuitable for surgery / RT — caution in HSCT recipients with cGVHD; PD-1 blockade can flare GVHD; multidisciplinary discussion.
- Field treatment with 5-FU, imiquimod, PDT for AKs.
- HPV vaccination for HSCT recipients (per BHIVA / vaccination guidelines).
- Smoking cessation.
References
- Curtis RE et al. Solid cancers after bone marrow transplantation. N Engl J Med; 1997.
- Williams KM et al. Voriconazole-associated cutaneous malignancy — review. Clin Infect Dis; 2014.
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