Merkel Cell Carcinoma with a Suppressor of Fused (SUFU) Mutation: Case Report and Potential Therapeutic Implications

Abstract

Introduction: Merkel cell carcinoma is a neuroendocrine malignancy. Suppressor of fused (SUFU) is a tumor suppressor oncogene that participates in the Hedgehog (Hh) signaling pathway. The aim of the study was to describe a patient whose Merkel cell carcinoma demonstrated a SUFU genomic alteration.

Case study: The Hh signaling pathway is involved in the pathogenesis of several tumors, including nevoid basal cell carcinoma syndrome that is associated with an alteration of the patched-1 (PTCH1) gene. Targeted molecular therapy against smoothened (SMO) with vismodegib has been shown to be an effective therapeutic intervention for patients with PTCH-1 mutation. The reported patient was presented with metastatic Merkel cell carcinoma. Analysis of his tumor, using a next-generation sequencing-based assay, demonstrated a genomic aberration of SUFU protein, a component of the Hh signaling pathway that acts downstream to SMO and, therefore, is unlikely to be responsive to vismodegib. Of interest, arsenic trioxide or bromo and extra C-terminal inhibitors impact signals downstream to SUFU, making this aberration conceivably druggable. His tumor has initially been managed with chemotherapy (carboplatin and etoposide) and subsequent radiation therapy is planned.

Conclusion: The pathogenesis of Merkel cell carcinoma is multifactorial, and related to ultraviolet radiation exposure, immunosuppression, and Merkel cell polyomavirus. We report a patient with a mutation in SUFU, a potentially actionable component of the Hh signaling pathway.

Fig. 1

Distant (a) and closer (b) views with ink demarcating the borders of the primary Merkel cell carcinoma on the left buttock nodule of a 66-year-old man

Fig. 2

Gross examination of the punch biopsy specimen shows a cylindrical piece of tissue secured using the 4-mm circular blade and several blood-tinged yellowish-white lobules of tumor (morphologically mimicking adipose tissue). These were expressed through the hole created during the biopsy after applying firm pressure to the tumor

Fig. 3

Tumor is present at the base of the punch biopsy specimen. It is in the deep dermis and extends into the subcutaneous tissue [hematoxylin and eosin, ×2]

Fig. 4

Distant (a) and closer (b) views of hematoxylin and eosin stained sections show the blue small cell tumor that extends from the deep dermis into the subcutaneous tissue [hematoxylin and eosin; a = ×4, b = ×20]

Fig. 5

The tumor shows positive staining for cytokeratin 20 (a), CD56 (b) and synaptophysin (c) [immunoperoxidase: cytokeratin 20, a = ×40; CD56, b = ×40; synaptophysin, c = ×40]