Chronic graft-versus-host disease (cGvHD) is a significant complication of allogeneic hematopoietic cell transplantation (HCT). The skin is frequently affected and common findings include lichenoid papules, sclerodermatous thickening or lichen planus-like striae of the oral mucosa. We describe a patient with an unusual presentation of cGvHD.
A 68-year-old woman with a history of secondary acute myeloid leukemia underwent non-myeloablative HLA-matched allogeneic HCT five years ago with subsequent long-term immunosuppressive therapy. She was admitted to Massachusetts General Hospital for surgical resection of a 3.0 × 3.0 cm nodular scaly verrucous lesion with central ulceration on the left anterior tibial surface that had grown larger over a period of three months and was suspicious for squamous cell carcinoma. The patient underwent excision of this lesion with full-thickness skin grafting. The biopsy showed hyperkeratosis and hypergranulosis with prominent lymphovascular dilatation in the superficial dermis on low power (). At higher power (), there were dyskeratotic cells scattered throughout the epidermis, occasionally with adjacent lymphocytes (satellite cell necrosis). The superficial dermis showed a mixed inflammatory infiltrate which included eosinophils and rare plasma cells as well as lymphocytes at the dermal-epidermal interface and deeper in the dermis. The dermis further showed a sclerodermoid reaction with prominent fibrosis and fibrin deposition in a perivascular distribution around ectatic vessels. There was no evidence of dysplastic epithelial cells, increased mitotic activity or invasion of the underlying stroma, excluding a diagnosis of squamous cell carcinoma.
Figure 1. Low power magnification of biopsy showing hyperkeratosis and hypergranulosis with prominent lymphovascular dilatation in the superficial dermis.
Figure 2. A higher power view illustrating dyskeratotic cells scattered throughout the epidermis with occasional adjacent lymphocytes.
The histopathology was consistent with cGvHD and mycophenolate mofetil was added to her immunosuppressive regimen that included methylprednisolone and cyclosporine. Her cGvHD was stable throughout 18 months of follow-up.
Cutaneous cGvHD commonly presents with a lichenoid or sclerodermatous appearance. In a recent study, 70% of patients with cGvHD showed lichenoid and 26% showed sclerodermoid lesions [Citation1–3]. Lichenoid lesions involve the epidermis and histologically appear as moderate vacuolar degenerations of the basal cell layer, epidermal apoptosis, and perivascular lymphohistiocytic infiltrates. Clinically, these cutaneous lesions are indistinguishable from lichen planus. Violaceous flat-topped papules varying in size from 1 to 10 mm can appear grouped, linear, annular, or disseminated. Sclerodermoid cGvHD appears as confluent areas of dermal sclerotic plaques with overlying scales. If layers deeper than the dermis are affected, the plaques are bound down, and cannot be moved over the underlying structures. The severity of the disease parallels the depth of dermal, subcutaneous, or fascial sclerotic changes [Citation4]. Decreased joint mobility, ulcerations on acral and pressure sites, permanent hair loss, and xerostomia may also occur. Risk factors for secondary malignant neoplasms after HCT include previous chemotherapy and ionizing radiation, as well as immune deficiency due to incomplete or late immune system recovery and immunosuppressive medications. Graft-versus-host reactions can increase the risk of certain malignancies including post-transplant lymphoid neoplasms [Citation5], non-melanoma skin cancers [Citation6], squamous cell carcinomas [Citation7], and cervical dysplasia [Citation8], particularly when cGvHD is treated with long-term immunosuppression. While patients on immunosuppressive therapies have increased incidence of certain malignancies, our case illustrates that, in patients undergoing allogenic HCT, unusual skin lesions that clinically resemble squamous cell carcinoma should always include GvHD in the differential diagnosis. This will facilitate early and appropriate treatment.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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