RESUMO
A man in his 50s presented with sudden onset expressive aphasia and right-sided facial droop after experiencing coryzal symptoms and malaise for 7 days prior to admission. A brain MRI showed a rapidly progressive mass effect across both hemispheres and cerebrospinal fluid analysis revealed neutrophil predominance with raised protein levels. Acute disseminated encephalomyelitis was provisionally diagnosed, and high-dose methylprednisone was initiated.On admission to the high dependency unit, the patient tested positive for COVID-19 and was treated with appropriate therapeutic agents for severe COVID-19. A subsequent brain biopsy confirmed a demyelinating process, strongly indicating a diagnosis of acute haemorrhagic leucoencephalitis when correlated with the presence of severe oedema on imaging. Nine sessions of plasma exchange were provided over 18 days.At the time of writing, the patient has made an excellent recovery. We urge clinicians to consider this diagnosis and these treatment options for an otherwise devastating condition.
Assuntos
COVID-19 , Leucoencefalite Hemorrágica Aguda , Imageamento por Ressonância Magnética , SARS-CoV-2 , Humanos , Masculino , COVID-19/complicações , Pessoa de Meia-Idade , Leucoencefalite Hemorrágica Aguda/diagnóstico , Leucoencefalite Hemorrágica Aguda/etiologia , Troca Plasmática/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes, and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements. Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). Seventy-nine percent harbored pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAFV600E-mutated tumors, gene rearrangement was characterized by psammoma bodies involving the entire lobe (P = .038), follicular predominant or mixed follicular architecture (P = .003), pulmonary metastases (24% vs none, P = .04), and absent classical, so-called "BRAF-like" atypia (P = .014). There was no correlation between the presence of gene rearrangement and recurrence-free survival. Features associated with persistent/recurrent disease included pediatric population (P = .030), gene-rearranged tumors (P = .020), microscopic extrathyroidal extension (P = .009), metastases at presentation (P = .007), and stage II disease (P = .015). We conclude that DS-PTC represents 1.9% of papillary thyroid carcinomas and that actionable gene rearrangements are extremely common in DS-PTC. DS-PTC can be divided into 2 distinct molecular subtypes and all BRAFV600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions.
Assuntos
Carcinoma Papilar , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Adulto Jovem , Humanos , Criança , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Mutação , Receptores Proteína Tirosina Quinases/genéticaRESUMO
Diffuse sclerosing variant (DSV) of papillary thyroid carcinomais a rare form of thyroid cancer that demonstrates more aggressive histopathology than classical papillary thyroid carcinoma (c-PTC); however, if this leads to worse survival is debated. Many DSVs are driven by fusion events which are of recent clinical importance due to the advent of targeted RET inhibitors. A systematic search and meta-analysis of the literature was performed to compare outcomes of disease-specific mortality (DSM), metastatic and recurrent disease and the incidence of fusion events between DSV and c-PTC to July 2022. The Newcastle-Ottawa Quality Assessment studies was used to assess quality. An odds ratio (OR) was utilised to measure outcomes with 95% CIs. The Preferred Reporting Items for Systematic Reviews and Meta-analysis guideline was followed. Seventeen studies were included with 874 DSV patients compared to 76,013 c-PTC patients. DSV patients had worse DSM (OR=2.50, 95% CI 1.39-4.51) and presented with a higher rate of metastatic lymph nodes (OR = 5.85, 95% CI 2.73-12.53) and more distant metastases (OR = 3.83, 95% CI 2.17-6.77). DSV patients had higher odds of recurrent disease (OR = 3.23, 95% CI 2.00-5.23) and overall distant metastasis (OR = 2.70, 95% CI 1.74-4.17). Rates of RET fusion alterations for DSV ranged from 25 to 83%. DSV has a worse prognosis than c-PTC with higher rates of recurrent disease and distant metastasis. The high prevalence of RET fusions offers the potential to improve outcomes for patients with DSV.