A case of Langerhans cell sarcoma on the scalp: Whole-exome sequencing reveals a role of ultraviolet in the pathogenesis.
Pathol Int
; 70(11): 881-887, 2020 Nov.
Article
en En
| MEDLINE
| ID: mdl-33410565
Langerhans cell sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway-related genes, CDKN2A and TP53 have been reported. Here we present a 70-year-old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD-L1, and the Ki-67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole-exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD-L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Histiocitosis de Células de Langerhans
/
Sarcoma de Células de Langerhans
/
Secuenciación del Exoma
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Aged
/
Humans
/
Male
Idioma:
En
Revista:
Pathol Int
Asunto de la revista:
PATOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Australia