Squamous Cell Carcinoma Within Advanced Basal Cell Carcinoma During Vismodegib Treatment: Importance of Serial Biopsy
In a report in JAMA Dermatology, Zhu et al discuss two cases in which clinically significant squamous cell carcinoma was found within the tumor bed of locally advanced basal cell carcinoma during vismodegib (Erivedge) treatment for basal cell carcinoma. In one, basal cell carcinoma tumor shrinkage in response to vismodegib revealed the squamous cell carcinoma; in another, biopsy prompted by tumor progression during vismodegib treatment revealed the squamous cell carcinoma. These cases underline the importance of repeat biopsy in such circumstances.
Squamous Cell Carcinoma Revealed by Tumor Shrinkage
The first case was a patient with locally advanced basal cell carcinoma who had dramatic tumor shrinkage after starting vismodegib. After 4 months, the patient had enlargement of a discrete 0.5 × 0.7–cm hyperkeratotic papule within the basal cell carcinoma tumor bed.
A pretreatment photograph showed that the papule was likely present but smaller prior to vismodegib treatment. Biopsy showed invasive acantholytic squamous cell carcinoma with no abnormal basaloid cells.
The squamous cell carcinoma was resected by Mohs surgery. The patient continued vismodegib during and after surgery, with subsequent complete response of the surrounding basal cell carcinoma.
Squamous Cell Carcinoma Identified After Tumor Progression
The second case was a patient with Gorlin syndrome who initially presented with a 15-cm locally advanced nodular basal cell carcinoma on the vertex of the scalp extending to the dura. The basal cell carcinoma had recurred after previous treatment with photodynamic therapy and radiation. Vismodegib treatment resulted in shrinkage of the tumor to 11 cm after 3 months and stable disease over the next 2.5 years.
Magnetic resonance imaging then showed tumor progression. Biopsy of two areas of the tumor showed atypical pleiomorphic spindle cell proliferation; immunohistochemical analysis showing positive staining for cytokeratin 5/6 and p63, supporting a diagnosis of keratinocytic neoplasm. Further immunohistochemical analysis ruled out atypical fibroxanthoma, melanoma, and leiomyosarcoma, supporting a diagnosis of invasive squamous cell carcinoma with a spindle cell subtype. There were no abnormal basaloid cells in the biopsy specimens.
The tumor was surgically resected, and examination showed discontinuous distribution of spindled cells with significant atypia and mitoses, with these areas being interspersed with nodular infiltrative basal cell carcinoma. Findings were consistent with dedifferentiation of a predominantly basal cell carcinoma tumor into discontinuous areas of spindle cell squamous cell carcinoma.
The authors noted that in their experience, response of basal cell carcinoma to vismodegib is evident by 3 months after starting treatment. Thus, they recommended, “[N]ew or persistent ulcerations, nodules, or erythema in the locally advanced basal cell carcinoma tumor bed should prompt a biopsy after this time.”
They concluded, “These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in two clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non–basal cell histologic characteristics is critical to institution of effective therapy.”
Anne Lynn S. Chang, MD, of Stanford University School of Medicine, is the corresponding author for the JAMA Dermatology article.
Dr. Chang has been a clinical investigator for studies sponsored by Lilly, Infinity, Genentech, and Novartis.
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