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INTRODUCTION: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). CASE PRESENTATION: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18Fluoro-D-glucose positron emission computed tomography (18FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. CONCLUSION: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment.
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Infecções por HIV , Hipercalcemia , Síndrome Inflamatória da Reconstituição Imune , Humanos , Síndrome Inflamatória da Reconstituição Imune/complicações , Hipercalcemia/etiologia , Masculino , Adulto , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnósticoRESUMO
Transcriptome-based molecular subtypes of muscle-invasive bladder cancer (MIBC) have been shown to be both prognostic and predictive, but are not used in routine clinical practice. We aimed to develop a feasible, reverse transcription quantitative polymerase chain reaction (RT-qPCR)-based method for molecular subtyping. First, we defined a 68-gene set covering tumor intrinsic (luminal, basal, squamous, neuronal, epithelial-to-mesenchymal, in situ carcinoma) and stromal (immune, extracellular matrix, p53-like) signatures. Then, classifier methods with this 68-gene panel were developed in silico and validated on public data sets with available subtype class information (MD Anderson [MDA], The Cancer Genome Atlas [TCGA], Lund, Consensus). Finally, expression of the selected 68 genes was determined in 104 frozen tissue samples of our MIBC cohort by RT-qPCR using the TaqMan Array Card platform and samples were classified by our newly developed classifiers. The prognostic value of each subtype classification system and molecular signature scores were assessed. We found that the reduced marker set combined with the developed classifiers were able to reproduce the TCGA II, MDA, Lund and Consensus subtype classification systems with an overlap of 79%, 76%, 69% and 64%, respectively. Importantly, we could successfully classify 96% (100/104) of our MIBC samples by using RT-qPCR. Neuronal and luminal subtypes and low stromal gene expressions were associated with poor survival. In conclusion, we developed a robust and feasible method for the molecular subtyping according to the TCGA II, MDA, Lund and Consensus classifications. Our results suggest that stromal signatures have a superior prognostic value compared to tumor intrinsic signatures and therefore underline the importance of tumor-stroma interaction during the progression of MIBC.
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Genes Neoplásicos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Adulto JovemRESUMO
The current edition of the WHO classification of thyroid tumors (2017) contains a number of very relevant changes with considerable consequences for the diagnostic assessment of thyroid specimens. This applies to both the histomorphological examination of surgical specimens and the preoperative fine needle biopsy (FNB). In addition, molecular pathological examinations are becoming increasingly important in the diagnosis of thyroid tumors. Changes affect practically all areas of thyroid tumor diagnostics. Some of these changes have far-reaching consequences that justify a comprehensive commentary and query of the knowledge acquired in the form of this CME article.
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Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Biópsia por Agulha Fina , Humanos , Neoplasias da Glândula Tireoide/diagnóstico , Organização Mundial da SaúdeRESUMO
We report the case of a 70-year-old female patient with an unclear liver mass after clinical and radiological evaluation. In histopathological evaluation, we diagnosed a hepatic angiomyolipoma, which is a rare entity and belongs to the perivascular epithelioid group of tumours (PEComa). In this report, we illustrate the typical histomorphology, immunohistochemical profile and molecular changes based on the case presentation and discuss and review the current literature on hepatic angiomyolipomas. In addition, typical differential diagnostic problems are highlighted.
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Angiomiolipoma , Neoplasias Hepáticas , Idoso , Angiomiolipoma/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnósticoRESUMO
The onset of radioiodine-refractory thyroid carcinoma (RR-TC) is a negative predictor of survival and has been linked to the presence of BRAFV600E mutations in papillary thyroid cancer. We aimed to identify further genetic alterations associated with RR-TC. Methods: We included 38 patients with papillary thyroid cancer who underwent radioiodine imaging and 18F-FDG PET/CT after total thyroidectomy. The molecular profile was assessed by next-generation sequencing. The time to the onset of RR-TC for different genetic alterations was compared using the log-rank test. Results: The median onset to RR-TC was 0.7 and 19.8 mo in patients with and without, respectively, telomerase reverse transcriptase promoter mutations (P = 0.02) and 1.7 and 19.8 mo in patients with and without, respectively, a tumor protein 53 mutation (P < 0.01). This association was not observed for BRAFV600E mutations (P = 0.49). Conclusion: Our data show a significant association between the onset of RR-TC and mutations in telomerase reverse transcriptase promoter and tumor protein 53, indicating the need for a more extensive diagnostic workup in these patients. Certain genetic changes put patients with thyroid cancer at risk of developing cancer spread that does not respond to radioiodine therapy.
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Carcinoma Papilar , Telomerase , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/radioterapia , Radioisótopos do Iodo/uso terapêutico , Telomerase/genética , Proteínas Proto-Oncogênicas B-raf/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Biomarcadores , MutaçãoRESUMO
Mediastinal tumors present a rather rare phenomenon with a variety of underlying causes. Important differential diagnoses include benign and malignant tumors as well as idiopathic sclerosing mediastinitis and parasitic infection.Here, we present the case of a mediastinal pseudotumor with compression of the superior vena cava in a young adult male who spent several years abroad in Brazil. Clinicians suspected either a mediastinal lymphoma, malignant mesenchymal tumor, teratoma, sarcoidosis, or tuberculosis. Biopsy tissue failed to provide a definite diagnosis. The subsequently resected mediastinal mass showed a necrotizing, granulomatous inflammation with prominent eosinophilia and sclerosis. Membranous structures were detected in the necrotic areas, which presented as collagen bundles ultrastructurally. Therefore, these membranes were proven to be constituents of lipid pseudomembranes. Consequently the lesion shows characteristics of sclerosing mediastinitis next to characteristics of adipose tissue necrosis with lipid pseudomembranes. Parasitic infection could not be proven.
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Neoplasias do Mediastino , Veia Cava Superior , Humanos , Lipídeos , Masculino , Neoplasias do Mediastino/diagnóstico , Mediastinite , Necrose/patologia , Esclerose/diagnóstico , Veia Cava Superior/patologia , Adulto JovemRESUMO
Background and Aims: Acute-on-chronic liver failure (ACLF) is associated with excessive systemic inflammation, cell death, and organ failures. Yet, little is known about the hepatic histopathology of ACLF. Here, we assessed the histopathology and regenerative capacity of the liver in ACLF with or without cirrhosis. Methods: Liver specimens of patients with compensated cirrhosis (N = 37), acute decompensation (N = 40), and ACLF with (N = 18) or without (N = 10) cirrhosis were assessed for morphological features and the pro-regenerative Stat3 pathway. Results: ACLF was associated with high levels of lobular inflammation, tissue necrosis, and apoptosis. In patients with cirrhosis, the percentage of pStat3-positive hepatocytes was increasing with disease severity (3.5%/10.4%/21% for compensated cirrhosis/acute decompensation/cirrhosis-ACLF; P < .001), but lower in noncirrhotic ACLF vs cirrhosis-ACLF (21% vs 13%; P = .02). A distinct pattern of the expression of the proliferation marker Ki-67, a downstream effector marker of pStat3, was observed. Ki-67-positive hepatocytes were more frequent in patients with cirrhosis-ACLF compared to compensated cirrhosis or acute decompensation (4.9% vs 1.3% vs 1.8%; P < .05), but much lower in cirrhosis-ACLF vs noncirrhotic ACLF (4.9% vs 13.5%; P = .01). The ratio of Ki-67-positive to pStat3-positive hepatocytes was lowest in cirrhosis-ACLF and predicted 3-month transplant-free survival accurately (area under the curve = 0.95, P < .00001). Conclusion: Our study identifies hepatic inflammation and Stat3 activation as hallmarks of ACLF. In cirrhosis-ACLF, Stat3 activation does not appear to translate in effective liver regeneration, which is distinct from noncirrhotic ACLF.
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BACKGROUND: Gastritis induced by checkpoint inhibitors (CPI) is a rare but severe drug-related side effect. The reference standard for confirming CPI-associated gastritis (CPI-assGastritis) is histopathological assessment; however, the histopathological features of CPI-assGastritis are not yet adequately defined. MATERIALS AND METHODS: Gastric biopsies of melanoma patients with histopathologically suspected CPI-assGastritis were compared with gastric biopsies of patients with inflammation free gastric mucosa (IFGM), type A, B, and C gastritis with respect to apoptosis count and predominant histopathological features. Immunohistochemical anti-caspase-3 staining was performed to identify apoptosis. Quantification was performed by manually counting the number of apoptotic events per 10 high-power fields (HPF). Clinical symptoms, treatment, and follow-up data of patients with CPI-assGastritis were examined. The nonparametric Mann-Whitney U test was used for statistical testing. RESULTS: Five melanoma patients (three women, two men; median age: 45 years) were treated with PD-1-based CPI. The patients reported epigastric pain, weight loss, nausea, and vomiting. Histologically, the patients with CPI-assGastritis showed a partly lymphocytic, partly granulocytic inflammatory infiltrate. Manual counting of apoptotic cells in biopsy tissue slides stained against caspase 3 revealed a median of 6 apoptotic events/10 HPF (95% CI, 2.75-17.30) in the patients with CPI-assGastritis. Results for the comparison cohort (patients n = 21) were a median of 1 apoptotic event/10 HPF (95% CI, 0.5-4.5) for type-A gastritis (six patients), a median of 2 apoptotic events/10 HPF (95% CI, 0-4.5) for type-B gastritis (five patients), and no apoptosis for IFGM and type-C gastritis (five patients). Patients with CPI-assGastritis had a significantly higher apoptosis count than patients with IFGM (p<0.01), type A (p<0.05), B (p<0.05), and C gastritis (p<0.01). None of the CPI-assGastritis biopsies showed evidence of Helicobacter pylori. All CPI-assGastritis patients responded to systemic treatment with corticosteroids. CONCLUSION: CPI-assGastritis manifests with nonspecific symptoms but histologically shows a high number of apoptotic events, which can best be visualized by anti-caspase-3 immunohistochemistry. This histopathological feature may help to histologically differentiate CPI-assGastritis from other forms of gastritis and inform decision-making regarding its optimal management.