Programmed death-ligand 1 expression is associated with fibrosarcomatous transformation of dermatofibrosarcoma protuberans

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a locally invading tumor, characterized by the presence of the collagen type I α 1 (COL1A1)-platelet-derived growth factor (PDGF) β fusion gene. We herein report the case of a 31-year-old man with a history of resection of an abdominal wall DFSP. The patient presented with chest pain and a computed tomography scan revealed a large mass in the posterior mediastinum and another mass in the right lung. The mediastinal mass was a sarcomatous lesion expressing the COL1A1-PDGFβ fusion gene, suggesting that it represented a metastasis of the DFSP following fibrosarcomatous (FS) transformation. Following resection of the mediastinal metastasis and subsequent radiotherapy, the mass in the right lung was also resected. Due to the emergence of pleural and pancreatic tail metastases, the patient was treated with a combination therapy of adriamycin and ifosfamide. After five courses, the disease progressed and the patient was subsequently treated with pazopanib for ~2 months until further progression. Three years after the diagnosis of the mediastinal metastasis of DFSP, the patient was referred to another hospital for palliative care. The expression of programmed cell death 1 ligand (PD-L1) in the primary and metastatic tumors was investigated: PD-L1 expression was detected in the metastasis but not in the primary tumor. Given that the metastatic tumor exhibited FS transformation (DFSP-FS), PD-L1 expression may be induced by FS transformation, contributing to the metastasis through escape from immune surveillance. Further investigation of the PD-L1 pathway in DFSP and DFSP-FS in primary as well as metastatic sites is required to evaluate the clinical efficacy of therapies targeting the PD-L1 signaling cascade.

Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report

“…Several different molecular genetic alterations have been proposed to account for this transformation, including genomic gains of COL1A1-PDGFB , losses of genomic material from 22q, mutations of TP53, activation of the PDGFR-β/Akt/mTOR pathway signaling, and microsatellite instability [ 22 ]. Most recently, single reports have suggested that over-expression of programmed cell death 1 ligand (PD-L1) [ 23 ] and fusion of MAP 3K7CL-ERG [ 24 ] may be implicated in the transformation of conventional DFSP to fibrosarcomatous DFSP. It’s worth noting that both the previously reported two cases of EMILIN2-PDGFD fusion DFSP exhibited a fibrosarcomatous histology and showed homozygous deletion of CDKN2A [ 9 ], which had also been identified in PGDFB -rearranged DFSPs and often observed in cases showing hypercellularity and fibrosarcomatous transformation morphology [ 25 ].…”

Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times

“…The efficacy was very limited but interestingly PD-L1 expression was detected in the metastasis but not in the primary tumor (a locally invading dermatofibrosarcoma). PD-L1 expression was probably induced by the fibrosarcomatous transformation of the initial tumor, contributing to the metastasis through escape from immune surveillance ( 79 ).…”

Dermatofibrosarcoma Protuberans: Update on the Diagnosis and Treatment

“…Loss of p16 expression was demonstrated in 2 of 12 classic DFSP and 2 of 6 FS-DFSP [ 119 ]. Programmed cell death 1 ligand (PD-L1) expression was detected in metastatic FS-DFSP, but not in the primary tumor, suggesting a role of PD-L1 in the metastasis of FS-DFSP [ 123 ]. Since PD-L1 expression in the tumor cells is involved in immune escape from T cell attack [ 124 ], PD-L1 signal pathway may be a potential target for metastatic FS-DFSP.…”