Myxoma

AimsCardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue.Methods and resultsTwenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft's in immunodeficient NOD/SCID mice.ConclusionMyxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.

PurposeA clinical feature of myxofibrosarcoma is local recurrence, but knowledge about distant metastasis is sparse. We evaluated the tendency of clinical and histological features of metastasis in myxofibrosarcoma patients.MethodsFifty-eight patients with myxofibrosarcoma were treated in our hospitals, and a total of 16 consecutive patients with distant metastases were included in this retrospective study (9 males and 7 females, with a mean age of 77 years). Because there was no patient complicated by both lung and lymph node metastases, we compared the age, sex, tumor size and location, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade, American Joint Committee on Cancer (AJCC) stage, and times of the first metastasis from the initial examination between the lung and lymph node groups. In addition, we examined factors affecting the prognosis.ResultsThe median follow-up period was 42.9 months (range 8-142). Eleven of 16 patients developed pulmonary metastases. The sites of extra pulmonary metastases were the lymph nodes in 5 patients, bone in 1, subcutaneous in 1, intramuscular in 1, and peritoneum in 1. The median time for patients to develop distant metastases was 17.4 months (range 0-59). The time until the onset of the first metastasis in the lung metastasis group was significantly shorter than in the lymph node group (p ConclusionsNot only lung metastasis but also lymph node metastasis occurs frequently in myxofibrosarcoma patients. Myxofibrosarcoma with lung metastasis is more aggressive than the type with lymph node metastasis.

BackgroundCardiac myxoma is the most common benign cardiac tumor. Brain metastases or multiple cerebral aneurysms are extremely rare, especially for the case of both complications. Brain metastases are usually found at the same time or few months after the diagnosis or surgical removal of cardiac myxoma CASE PRESENTATION: We describe a case of patient, operated for a cardiac myxoma, who presented multiple central nervous system metastases associated, cerebral aneurysms and subsequent intracerebral hemorrhage CONCLUSIONS: The long-term follow-up of the patients with atrial myxoma even after complete surgical excision is recommended, especially for the patient with central nervous system manifestations before atrial myxoma excision.

BackgroundIntramuscular myxoma (IM) is a benign tumor that harbors GNAS missense variants. Distinguishing IM from low-grade myxofibrosarcoma (LGMFS) is challenging due to similarities in imaging and histological features. While molecular analysis aids differentiation, the low number of tumor cells available for DNA extraction necessitates highly accurate detection methods for variant identification. The aim of this study was to delineate molecular characteristics using next-generation sequencing (NGS) and to propose an optimal screening method in a clinical setting to differentiate IM from LGMFS.MaterialsTen IM cases and nine LGMFS cases with extractable DNA from FFPE samples were recruited.ResultsA custom NGS panel-based analysis for GNAS revealed R201C/R201H variants in resected samples of eight cases with IM and in none of the eight cases, excluding one with insufficient sample quality, with LGMFS, and in biopsy samples of both available cases with IM. Additionally, various sequence alterations were detected irrespective of the clinical status (IM, LGMFS, and normal tissue) or sample conditions (resected, biopsy, and relapsed). The detection rate of GNAS-positive IM using other methods (PCR-direct sequencing, fragment signal analysis using restriction digestion and capillary electrophoresis after PCR combined with peptide nucleic acid (PNA) clamping, and PCR-direct sequencing combined with PNA clamping) was calculated as 0.42, 0.83, and 0.75, respectively, while the detection rate for GNAS-negative LGMFS was 1.ConclusionThese findings suggest that fragment signal analysis is a reasonable diagnostic approach for differentiating IM from LGMFS. However, it is important to recognize that the absence of GNAS R201C/R201H variants does not rule out IM.