Multiple keratin granulomata: A potential histologic clue to cutaneous squamous cell carcinoma responding to programmed cell death protein 1 inhibitor therapy

Abstract

We present histologic features of a locally advanced cutaneous squamous cell carcinoma (cSCC) treated with the programmed cell death protein-1 (PD-1) antagonist, pembrolizumab, with a partial response. This contributes to a growing body of literature supporting the efficacy of pembrolizumab in treatment of surgically unresectable cSCC. We also provide a detailed description of the histologic features, particularly keratin granulomata with adjacent lymphocytic aggregates and fibrosis, observed in cSCC under treatment with a PD-1 antagonist.histology, immunomodulation, squamous cell carcinoma, tumor-infiltrating lymphocytes 1 | INTRODUCTION Cutaneous squamous cell carcinoma (cSCC) is a common cancer that is effectively treated with surgical excision in most cases. A small percentage of cSCC are too locally extensive for surgery or radiation therapy to achieve complete remission and/or avoid significant cosmetic or functional impairment. Pembrolizumab is a programmed cell death protein 1 (PD-1) antagonist approved by the Food and Drug Administration for advanced or unresectable melanoma, non-small-cell lung cancer, and head and neck squamous cell carcinoma, among others. Prior case reports detail the effective use of off-label pembrolizumab to treat unresectable cSCC. 1-5 A phase II trial is currently evaluating the efficacy of pembrolizumab in adults with recurrent or metastatic cSCC. 6 In this case report, we present a patient with locally advanced cSCC of the left upper lip and columella treated with pembrolizumab, highlighting both its use in the treatment of an advanced cSCC and the unique histologic findings of multiple keratin granulomata with adjacent lymphocytic aggregates and fibrosis. | CASE REPORTA 65-year-old white woman presented with a 5-year history of multiply recurrent left upper lip cSCC (Figure 1). She had been treated previously with (in chronological order) electrodesiccation and curettage, excision with repair, and Mohs micrographic surgery. Biopsy from the upper cutaneous lip at the time of presentation confirmed invasive welldifferentiated squamous cell carcinoma without definitive perineural invasion. The lesion measured 3.3 × 2.8 × 1.9 cm on computerized tomography (CT), extending from the left upper lip to the columella, abutting the maxilla without osseous erosion (Figure 2). The lesion was deemed unresectable due to the high risk of cosmetic and functional impairment. The patient then began a clinical trial of intravenous pembrolizumab at a flat dose of 200 mg every 3 weeks. The infusions were well tolerated without adverse reaction. After 6 months, the lesion showed remarkable clinical improvement and tumor depth on CT had decreased from 1.9 to 0.7 cm along with decreased enhancement and nodularity. Scouting skin biopsies were performed at 4 months to assess histologic response to immunotherapy. A scouting biopsy from the left upper cutaneous lip showed numerous keratin granulomata diffusely within the dermis with associated fibrosis and mixed inflammation, including aggregates of l...

RETRACTED: Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings

“…The extensive granulomatous type of inflammation was seen in the responsive patient (#1) and to a lesser extent in the other two patients. This type of inflammation was also reported in a responsive case of cutaneous SCC [ 16 ]. The incidence of these histological parameters should be further examined in larger groups of OSCC patients treated with pembrolizumab in order to find out any potential associations with clinical outcomes.…”

“…On a biological level, it is expected to find infiltration of the tumor by a remarkable lymphocytic reaction. This has been documented in only a few studies regarding SCC of the skin and non-small cell lung carcinoma (SCC type) and melanoma [15][16][17]20]. Here, we describe a small series of patients with advanced OSCC (one tongue and two mandibular bone), who based on the combined PD-L1 score of >1, were eligible for neoadjuvant treatment with pembrolizumab and were assumedly expected to respond favorably.…”

“…The use of pebrolizumab in oral cancer is relatively new and treatment outcomes have been primarily evaluated by clinical parameters of patients' survival. Histologic changes related to this modality have not been well-documented and usually addressed other types of SCC but not OSCC [15][16][17]. The present brief research aimed to report the histologic findings within the TME in a small series of patients with OSCC following neoadjuvant pembrolizumab.…”

Eligibility criteria for programmed death receptor 1 inhibitors vs. real‐world advice: a retrospective analysis of 69 patients with advanced cutaneous squamous cell carcinoma of the head and neck

“…Contraindications defined absolute were immunosuppression equalling ≥ 10 mg prednisolone, organ transplant other than kidney, and an Eastern Cooperative Oncology Group (ECOG) performance score > 2. Relative contraindications were organ failure, 3 autoimmune disease in the last 5 years, 4 brain metastases, 5 kidney transplant, 6 ECOG performance score = 2, malignancy in the past 5 years (unless treated with curative intent and no recurrence) and tumour location on eyelid or lip 7 …”

“…Relative contraindications were organ failure, 3 autoimmune disease in the last 5 years, 4 brain metastases, 5 kidney transplant, 6 ECOG performance score = 2, malignancy in the past 5 years (unless treated with curative intent and no recurrence) and tumour location on eyelid or lip. 7 …”