RESUMO
Context: Immune-related adverse events frequently take place after initiation of immune checkpoint inhibitors (ICI) therapy. The thyroid gland is the endocrine organ most commonly affected by ICI therapy, the pathological mechanism is still poorly understood. Case Description: A 60-year old Upper Austrian male melanoma patient under pembrolizumab therapy received thyroidectomy because of a suspicious FDG avid thyroid nodule. Histopathology showed a pattern comparable with thyroiditis de Quervain. The inflammatory process consisted predominantly of T lymphocytes with a dominance of CD4+ T helper cells. In addition CD68+ histiocytes co-expressing PD-L1 were observed. Conclusion: Clusters of perifollicular histiocytes expressing PD-L1 were observed in this case of pembrolizumab induced thyroiditis - probably induced by the former ICI therapy. This finding might indicate the initial target for the breakdown of self tolerance. In context with other data the immunological process seems to be driven by CD3+ lymphocytes infiltrating the thyroid.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/metabolismo , Linfócitos T CD4-Positivos/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Histiócitos/imunologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Glândula Tireoide/patologia , Tireoidite/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Movimento Celular , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Melanoma/complicações , Melanoma/diagnóstico , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/diagnóstico , Glândula Tireoide/imunologia , Tireoidectomia , Tireoidite/etiologiaAssuntos
Necrose Gordurosa , Paniculite , Dermatopatias , Deficiência de alfa 1-Antitripsina , Abscesso , HumanosRESUMO
A patient was diagnosed with leukocyte adhesion deficiency-1. She was born in 1996 and her parents are not known to be related. Her leukocytes expressed less than 2% of the CD18 antigens relative to normal individuals. Molecular analysis revealed that she is a compound heterozygote. She inherited a 27,703bp deletion from her father (g.43201_PTTG1IP:10890del27703), spanning from intron 11 of the gene for the ß2 integrin (ITGB2, CD18, NG_007270.2) to intron 2 of the gene for the Pituitary Tumor-Transforming Gene 1 Interacting Protein (PTTG1IP, NC_000021.8). The maternal allele has a g.23457C>A mutation at position -10 in intron 2 of the ITGB2 gene, resulting in the activation of a cryptic 3' splice site in intron 2 to include 43 intronic nucleotides (r.[59-43_59-1ins;59-10C>A]).
