Abstract
BackgroundSorafenib is an oral multikinase inhibitor that targets Raf serine/threonine receptor tyrosine kinases and inhibits tumor cell growth and angiogenesis. Cutaneous toxicities of sorafenib are common, including cutaneous eruptions (such as truncal erythema and seborrheic-dermatitis-like changes) and hand–foot syndrome. Keratoacanthomas and squamous cell carcinomas have been reported previously; however, we report a case of multiple eruptive keratoacanthomas in the form of Grzybowski syndrome after initiation of sorafenib.Case presentationWe report a 63-year-old Caucasian male who developed multiple cutaneous eruptive keratoacanthomas after starting sorafenib 400 mg twice daily. He had a known history of hepatitis-C-related cirrhosis and hepatocellular carcinoma, and previously had actinic keratosis and skin squamous cell carcinoma excision. Approximately two and a half months after starting sorafenib, the patient initially developed two lesions, one on each forearm, and after excision, these lesions demonstrated histological features of squamous cell carcinoma. One month later, the patient presented with approximately 48 new skin lesions of varying size on the back, bilateral upper limbs, and face requiring excisional biopsy of a large number of these lesions. Histopathology showed eruptive invasive keratoacanthomas (Grzybowski syndrome). Sorafenib was temporarily stopped and subsequently restarted at a lower dose. Acitretin 25 mg daily was commenced after few weeks, and no further keratoacanthomas developed during his treatment.ConclusionsWe report a unique case of sorafenib-associated Grzybowski syndrome. Temporary interruption and dose reduction of sorafenib and use of acitretin appeared to prevent further development of keratoacanthomas.
Highlights
Sorafenib is an oral multikinase inhibitor that targets Raf serine/threonine receptor tyrosine kinases and inhibits tumor cell growth and angiogenesis
We report a unique case of sorafenib-associated Grzybowski syndrome
Case presentation A 63-year-old Caucasian male with known hepatocellular carcinoma presented with multiple cutaneous eruptive keratoacanthomas approximately three and half months after starting sorafenib 400 mg twice daily
Summary
Sorafenib is an oral small-molecule antineoplastic agent targeting multiple protein kinases and has been approved for the treatment of metastatic renal cell carcinoma and hepatocellular carcinoma. The patient initially developed two hyperkeratotic erythematous nodules on the right and left forearm (approximately two and half months after starting sorafenib) with rapid growth over 1–2 months These lesions were assessed as keratoacanthomas; both lesions were excised with clear margins, and histology. One month later (three and half months after starting sorafenib), the patient presented with approximately 48 new skin lesions of varying size on the left ear lobe (Figure 1), left lateral cheek, right side of the nose, central back, left shoulder, left arm and forearm (Figure 2), right wrist, right arm, and forearm These lesions appeared on sun-damaged skin and clinically correlated with multiple keratoacanthomas, appearing as multiple, firm, rounded nodules with central crateriform architecture and rapid growth over a month. Sorafenib and acitretin were discontinued 2 weeks before his death
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