ABSTRACT
The Hodgkin lymphoma (HL) genomic landscape is hardly known due to the scarcity of tumour cells in the tissue. Liquid biopsy employing circulating tumour DNA (ctDNA) can emerge as an alternative tool for non-invasive genotyping. By using a custom next generation sequencing (NGS) panel in combination with unique molecule identifiers, we aimed to identify somatic variants in the ctDNA of 60 HL at diagnosis. A total of 277 variants were detected in 36 of the 49 samples (73·5%) with a good quality ctDNA sample. The median number of variants detected per patient was five (range 1-23) with a median variant allele frequency of 4·2% (0·84-28%). Genotyping revealed somatic variants in the following genes: SOCS1 (28%), IGLL5 (26%), TNFAIP3 (23%), GNA13 (23%), STAT6 (21%) and B2M (19%). Moreover, several poor prognosis features (high LDH, low serum albumin, B-symptoms, IPI ≥ 3 or at an advanced stage) were related to significantly higher amounts of ctDNA. Variant detection in ctDNA by NGS is a feasible approach to depict the genetic features of HL patients at diagnosis. Our data favour the implementation of liquid biopsy genotyping for the routine evaluation of HL patients.
Subject(s)
DNA, Neoplasm/blood , Genotyping Techniques , Hodgkin Disease/genetics , Liquid Biopsy , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Female , Genotype , High-Throughput Nucleotide Sequencing , Hodgkin Disease/blood , Humans , Male , Middle Aged , Mutation , Prognosis , Prospective Studies , Young AdultABSTRACT
The thrombopoietin receptor agonists (THPO-RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO-RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18-83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5-21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet-count fluctuation (n = 6) and side-effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow-up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet-count fluctuation and side-effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.
Subject(s)
Benzoates/administration & dosage , Benzoates/adverse effects , Hydrazines/administration & dosage , Hydrazines/adverse effects , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Receptors, Fc/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Thrombopoietin/administration & dosage , Thrombopoietin/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Platelet Count , Purpura, Thrombocytopenic, Idiopathic/blood , Receptors, Thrombopoietin/agonists , Retrospective StudiesABSTRACT
Several types of large atypical epithelioid cells can mimic tumoral melanocytes and can therefore be a source of misdiagnosis of melanoma. Megakaryocytes are one of these types, and are not frequently mentioned in the literature. In the current report, we present the case of a 76-year-old man presenting with acute panmyelosis with myelofibrosis. The bone marrow biopsy contained atypical megakaryocytes that expressed S100 in the cytoplasm. We discuss how such aberrant expression could be a source of some diagnostic problems in dermatopathology, including cutaneous melanoma, metastasis of melanoma in bone marrow and metastasis of melanoma in sentinel lymph nodes.
Subject(s)
Megakaryocytes/metabolism , Megakaryocytes/pathology , Primary Myelofibrosis/metabolism , Primary Myelofibrosis/pathology , S100 Proteins/biosynthesis , Aged , Biopsy , Bone Marrow/metabolism , Bone Marrow/pathology , Cytoplasm/metabolism , Diagnosis, Differential , Humans , Male , Primary Myelofibrosis/diagnosisABSTRACT
Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii conorii. Some rare cases present without a rash, and they are known as "spotless." This fact is important; although the mortality rates for MSF are low and generally range from 0% to 3%, the absence of a rash usually leads to a delay in the diagnosis and, therefore, an increase in the rates of morbidity and mortality. Necrosis of the digits is one of the complications of MSF that has occasionally been reported in the literature. However, very few reports have studied the morphological changes seen in the cutaneous necrotic lesions. In this report, we describe the morphological changes found through examining a biopsy taken from a necrotic cutaneous lesion in a 69-year-old man who had been diagnosed with Mediterranean spotless fever due to R. conorii. The main morphological changes included areas of collagen degeneration in the papillary dermis, necrotic eccrine glands, and hypodermal collagen with a smudged homogeneous appearance.
