Histopathology of Basal Cell Carcinoma After Treatment With Vismogedib

February 2019 | Volume 18 | Issue 2 | Original Article | 136 | Copyright © 2019

Jennifer C. Tang MD,a Larry Buckel MD,B C. William Hanke MDa

aLaser and Skin Surgery Center of Indiana, Carmel, IN bCAMP Laboratory, Indianapolis, IN

Abstract

Background: Vismodegib used in the treatment of metastatic basal cell carcinoma (BCC) or locally advanced, recurrent BCC not amenable to surgery or radiation leads to various clinical changes. Objective: Aim was to elucidate the histopathology that corresponds to tumor involution observed with vismodegib therapy. Methods: Retrospective case series of patients treated with vismodegib between May 2012 and April 2017 with intra- or post-treatment biopsy. Results: 42 biopsy specimens and 4 Mohs frozen sections were analyzed. Necrosis, fibrosis, and increased plasma cells were common features. Limitations: Single center study. Conclusion: The histologic findings of BCCs treated with vismodegib correlate with clinical response. J Drugs Dermatol. 2019;18(2):136-138.

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INTRODUCTION

Non-melanoma skin cancer (NMSC) is the most common cancer, with basal cell carcinoma (BCC) as the most prevalent subtype. It is estimated that there were more than 5.4 million incident cases of NMSC and more than 2.3 million procedures performed to treat them in 2012 in the United States.1 Vismodegib is the first in class of Hedgehog pathway inhibitors approved for treatment of metastatic BCC, or locally advanced BCC that has recurred after surgery or is not amenable to surgery or radiation. Treatment with vismodegib leads to various clinical changes. The aim of this study was to elucidate the histopathology that corresponds to tumor involution observed with vismodegib therapy.

METHODS

The study was a retrospective case series of patients treated with vismodegib between May 2012 and April 2017 at a single center. Patients were included only if intra- or post-treatment biopsy was performed. The paraffin and frozen specimens were selected and reviewed by three investigators (JCT, LB, and CWH). Common histologic patterns were recorded.

RESULTS

Twenty-one distinct patients were treated with vismodegib from May 2012 to April 2017. Five patients were excluded due to no intra- or post-treatment pathology specimen. In the 16 patients included, there were 42 biopsy specimens and 4 Mohs frozen sections. The mean vismodegib treatment duration was 98 days (range, 36-263 days). The timing of pathology specimen obtained ranged from during treatment up to 882 days post treatment. Necrosis was observed in several specimens both during and after vismodegib treatment. Five biopsy specimens obtained from 3 patients demonstrated necrosis en masse with pyknotic nuclei, karryorhexis, neutrophils, and amorphous, eosinophilic hyalinization (Figure 1). Three of the 5 biopsies were performed during treatment and 2 of the 5 were collected 35 days after treatment. In 1 patient, Mohs micrographic surgery was performed 53 days after biopsy and did not reveal necrosis.Fibrosis and scar were seen in 12 specimens. These biopsies were collected both during and up to 287 days after vismodegib therapy. The 4 cases of scar during therapy were in patients who had been on treatment for an extended period, range of 117 to 263 days. Scar developed even in patients treated for short periods of 36-37 days. The scar response was sustained in two patients for 258 and 287 days after discontinuation of vismodegib therapy without histologic evidence of BCC recurrence. The scar tissue was unique such that there were increased fibroblasts in a haphazard array similar to a dermatofibroma rather than fibroblasts parallel to collagen bundles in typical mature scars (Figure 2).Increased plasma cells were present in 6 specimens (Figure 3). The pathology specimens were obtained between 67-387 days after vismodegib therapy. The biopsy locations included the cheek, nose, chest, and scalp. One of the 5 specimens was a Mohs micrographic stage that revealed persistent plasma cell infiltrate 53 days after initial biopsy.

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