Heart Transplantation as a Treatment Option for Recurrent Myxofibrosarcoma: A Clinical Case.

Myxofibrosarcoma is one of the most rare tumors of the heart. Surgical resection is the principal method of treatment; however, in some cases, radical removal of the tumor is not possible. Here, we present a case of heart transplant in a patient who experienced recurrent myxofibrosarcoma of the left atrium and examine the morphological features of this tumor. A 40-year-old female patient presented for treatment for heart failure of a high functional class. An examination revealed a tumor in the left atrial cavity, which was subsequently surgically removed. Morphological examination revealed an inflammatory myofibroblastic tumor. After 2 years, the patient's tumor recurred. The tumor was removed, and a morphological study again diagnosed myxofibrosarcoma of the heart. A year later, recurrence was again diagnosed. Instrumental examination determined that the tumor had incurred into the mitral valve and possibly spread to the myocardium. Tumor resection was not possible, and the need to perform a heart transplant was determined. The given case contributes to the practical conclusion that heart transplant contributes to an increase in the life expectancy for patients with inoperable cases of cardiac sarcoma.

Comparative Study of the Myocardium of Patients from Four COVID-19 Waves.

BACKGROUND: Few studies have compared COVID-19 patients from different waves. This study aims to conduct a clinical and morphological analysis of patients who died from COVID-19 during four waves. METHODS: The study involved 276 patients who died from COVID-19 during four waves, including 77 patients in the first wave, 119 patients in the second wave, and 78 patients in the third wave. We performed a histological examination of myocardium samples from autopsies and additionally analyzed the samples by PCR. We conducted immunohistochemistry of the myocardium for 21 samples using antibodies against CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, enteroviral VP1, and SARS-CoV-2 spike protein. We also did immunofluorescent staining of three myocardial specimens using VP1/SARS-CoV-2 antibody cocktails. Further, we ran RT-ddPCR analysis for 14 RNA samples extracted from paraffin-embedded myocardium. Electron microscopic studies of the myocardium were also performed for two samples from the fourth wave. RESULTS: Among the 276 cases, active myocarditis was diagnosed in 5% (15/276). Of these cases, 86% of samples expressed VP1, and individual cells contained SARS-CoV-2 spike protein in 22%. Immunofluorescence confirmed the co-localization of VP1 and SARS-CoV-2 spike proteins. ddPCR did not confidently detect SARS-CoV-2 RNA in the myocardium in any myocarditis cases. However, the myocardium sample from wave IV detected a sub-threshold signal of SARS-CoV-2 by qPCR, but myocarditis in this patient was not confirmed. Electron microscopy showed several single particles similar to SARS-CoV-2 virions on the surface of the endothelium of myocardial vessels. A comparison of the cardiovascular complication incidence between three waves revealed that the incidence of hemorrhage (48 vs. 24 vs. 17%), myocardial necrosis (18 vs. 11 vs. 4%), blood clots in the intramural arteries (12 vs. 7 vs. 0%), and myocarditis (19 vs. 1 vs. 6%) decreased over time, and CD8-T-killers appeared. Immunohistochemistry confirmed the presence of endotheliitis in all 21 studied cases. CONCLUSIONS: This study compared myocardial damage in patients who died during three COVID-19 waves and showed a decrease in the incidence of endotheliitis complications (thrombosis, hemorrhage, necrosis) and myocarditis over time. However, the connection between myocarditis and SARS-CoV-2 infection remains unproven.

Differential Morphological Diagnosis of Various Forms of Congenital Hyperinsulinism in Children.

Introduction: Congenital hyperinsulinism (CHI) has diffuse (CHI-D), focal (CHI-F) and atypical (CHI-A) forms. Surgical management depends on preoperative [18F]-DOPA PET/CT and intraoperative morphological differential diagnosis of CHI forms. Objective: to improve differential diagnosis of CHI forms by comparative analysis [18F]-DOPA PET/CT data, as well as cytological, histological and immunohistochemical analysis (CHIA). Materials and Methods: The study included 35 CHI patients aged 3.2 ± 2.0 months; 10 patients who died from congenital heart disease at the age of 3.2 ± 2.9 months (control group). We used PET/CT, CHIA of pancreas with antibodies to ChrA, insulin, Isl1, Nkx2.2, SST, NeuroD1, SSTR2, SSTR5, DR1, DR2, DR5; fluorescence microscopy with NeuroD1/ChrA, Isl1/insulin, insulin/SSTR2, DR2/NeuroD1 cocktails. Results: Intraoperative examination of pancreatic smears showed the presence of large nuclei, on average, in: 14.5 ± 3.5 cells of CHI-F; 8.4 ± 1.1 of CHI-D; and 4.5 ± 0.7 of control group (from 10 fields of view, x400). The percentage of Isl1+ and NeuroD1+endocrinocytes significantly differed from that in the control for all forms of CHI. The percentage of NeuroD1+exocrinocytes was also significantly higher than in the control. The proportion of ChrA+ and DR2+endocrinocytes was higher in CHI-D than in CHI-F, while the proportion of insulin+cells was higher in CHI-A. The number of SST+cells was significantly higher in CHI-D and CHI-F than in CHI-A. Conclusion: For intraoperative differential diagnosis of CHI forms, in addition to frozen sections, quantitative cytological analysis can be used. In quantitative immunohistochemistry, CHI forms differ in the expression of ChrA, insulin, SST and DR2. The development of a NeuroD1 inhibitor would be advisable for targeted therapy of CHI.

Analysis of pituitary adenoma expression patterns suggests a potential role for the NeuroD1 transcription factor in neuroendocrine tumor-targeting therapies.

NeuroD1's roles in the pathogenesis of pituitary adenomas and in the biology of the normal adult pituitary gland have been insufficiently researched. Much of the work investigating its expression patterns has yielded contradictory results. OBJECTIVE: morphological study of NeuroD1 transcription factor expression in different types of pituitary adenomas and in normal adult human pituitary glands. MATERIALS AND METHODS: This study analyzed 48 pituitary adenomas and nine normal pituitary glands. In all cases, immunohistochemical study was performed with antibodies to NeuroD1, 6 hormones of adenohypophysis, Ki-67, and CK7. We used confocal laser scanning microscopy, electron microscopy and electron immunocytochemistry. RESULTS: NeuroD1 expression was detected in all cases of plurihormonal adenomas, mammosomatotropinomas, corticotropinomas, prolactinomas, gonadotropinomas, null-cell pituitary adenomas, and in normal pituitary glands. The average numbers of NeuroD1 expressing cells in normal adenohypophysis specimens were significantly lower than in the adenomas overall (p=0.006). NeuroD1 expression was confirmed by several methods (in prolactinomas, by double stain immunohistochemistry; in mammosomatotropinomas, by double stain immunohistochemistry, confocal laser scanning microscopy, and electron immunocytochemistry; and in somatotropinomas, by electron immunocytochemistry). CONCLUSION: Immunohistochemistry, confocal microscopy, and double label electron immunocytochemistry confirmed NeuroD1's key role in the pathogenesis of pituitary tumors, regardless of their hormonal state. Its expression level in pituitary adenomas is significantly higher than in the normal pituitary gland and has no reliable correlation with any studied hormones or Ki-67. These findings suggest that NeuroD1 should be investigated further as a potential molecular target in tumor-targeting therapies.