[Primary cardiac angiosarcoma: a clinicopathological and molecular genetic analysis of thirteen cases].

Objective: To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma (PCAS), and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS. Methods: Thirteen cases of PCAS were collected at Beijing Anzhen Hospital, Capital Medical University from January 2007 to December 2021. The clinicopathological features, diagnosis, differential diagnosis and outcome were retrospectively analyzed. KDR mutation was detected by next-generation sequencing (NGS) and then the expression of KDR (VEGFR2) was determined by immunohistochemistry (IHC), with review of relevant literatures. Results: There were eight males and five females with a mean age of 45 years. The primary tumor was in the right atrium in 10 cases, left atrium in two cases and right ventricle in one case. The histomorphology was mainly poorly differentiated angiosarcoma (11 cases), with highly pleomorphic spindle or round cells in solid sheets, brisk mitotic activity and extensive necrosis. Vascular lumen formation was observed in two cases of high to moderate differentiation, and biphenotypic differentiation was seen in five cases. IHC staining showed CD34, CD31, Fli1, ERG and vimentin were diffusely positive, pan-cytokeratin was positive, Ki-67 index ranged from 3% to 90%, which was positively correlated with the differentiation degree and grade of the PCASs (P<0.05). At the end of follow-up period, one patient was alive, two patients were lost to follow-up, and the remaining 10 patients had an average survival time of 4.6 months. Finally, NGS sequencing was performed on seven samples after screening, and the results showed that KDR and NF1 mutations were both present in three cases. VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS (P>0.05), and it was not related to KDR mutation. Conclusions: PCASs mainly occur in the right atrium, and are mainly poorly differentiated. Ki-67 index is helpful to assess the degree and grade of tumor differentiation. The occurrence and development of PCAS may be related to the pathway involved in KDR mutation, but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS, and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.

[Clinical characteristics and placental pathology analysis of 14 cases of pregnancy with aortic dissection/aortic aneurysm].

Objective: To investigate the pathological changes of placenta in pregnant women with aortic dissection/aneurysm and their relationship with clinical features. Methods: The placental samples of 14 pregnant women with aortic dissection/aneurysm diagnosed from January 2012 to October 2021 and 10 normal placental samples of pregnant women from January 2021 to December 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China were selected. Routine H&E staining and immunohistochemistry were used to analyze the histological features under light microscope. The clinical data were also analyzed. Results: The age of 14 pregnant patients with aortic dissection/aneurysm for placental examination ranged from 22 to 38 years (median, 28 years). The gestational ages ranged from 22 to 39 weeks (median, 34 weeks). The pregnancy of second trimester was noted in 2 cases, and the third trimester in 12 cases. All cases were singleton pregnancy. Seven cases were Stanford type A aortic dissection, 6 cases were Stanford type B aortic dissection, and one case was aortic root aneurysm. Four of the pregnant women underwent aortic dissection surgery after caesarean section, three underwent caesarean section after aortic dissection surgery, and seven underwent both caesarean section and aortic dissection procedures. Among the newborns, 2 cases were full-term birth, and 12 cases were premature birth. Twelve cases had alive newborns, and 2 cases stillbirths. Fetal/placental weight ratio (FPR)<10th percentile was in 5 cases and FPR>90th percentile in one case. Compared with the normal group, accelerated villus maturation and distal villus dysplasia were more frequently found in pregnancy with aortic dissection group (P<0.05). There was no significant difference in villi infarction and decidua vascular lesions between the two groups (P>0.05), nor was there correlation between the type of aortic dissection and distal villus dysplasia and accelerated villus maturation of placentas (P>0.05). The number of villous interstitial blood vessels in the placentas of pregnancy with aortic dissection group was significantly fewer than that in the normal control group (P<0.01). Conclusions: There are considerable pathological changes in the placentas of pregnant women with aortic dissection/aneurysm. The main histological features are accelerated villus maturation and distal villus dysplasia, which are manifestations of villous ischemia and hypoxia, and also a part of the placental pathological manifestations of maternal vascular dysperfusion.

[Clinicopathological characteristics and molecular alterations of primary cardiac leiomyosarcoma: report of five cases].

Objective: To investigate the clinical, pathologic and radiologic features and molecular alterations in patients with primary cardiac leiomyosarcoma (PCLMS). Methods: Five cases of PCLMS were collected in Beijing Anzhen Hospital from January 2016 to December 2020. The clinical, pathologic and radiologic data, and molecular alterations were analyzed, and the patients were followed up. Results: All five patients were female, and had no history of leiomyosarcoma in other parts of the body. The age of patients ranged from 37 to 62 years (median 47 years). The main clinical symptoms were chest pain and dyspnea, one also presented with palpitation and lower limb weakness and one with dizziness. Two tumors were located in the left atrium, two in the right atrium, and one in the right ventricle, and they maximal diameter ranged from 2.5 to 14.0 cm (mean 6.2 cm). The neoplasms presented as medium-echo masses with a broad base in the echocardiography, and as a low-density, solid mass when detected by contrast-enhanced CT. Histologically, two tumors were well-differentiated and three were moderately and poorly differentiated, and two included extensive, loose myxoid stroma. Immunohistochemical staining showed that PCLMS was positive for SMA, desmin, MDM2, and epidermal growth factor receptor. Fluorescence in situ hybridization showed ALK gene rearrangement in two cases, and COL1A1-PDGFB fusion in three cases. All cases received surgical excision and two cases received chemotherapy. Three patients died within 0-11 months (mean survival of 7.7 months) and two patients were alive. Conclusions: PCLMS is a malignant tumor with a high recurrence rate and poor prognosis. These cases may provide useful information to improve the diagnosis and management of PCLMS.

[Pathological diagnosis of Danon disease by endomyocardial biopsy].

Objective To investigate the clinicopathological features and differential diagnosis of Danon disease. Methods: Two cases of Danon disease were selected from Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2019 to December 2019. The clinical history, histological, immunohistochemical, ultrastructural and gene mutation analysis were collected. Results: Both of the patients were male, aged 21 and 19 years old, respectively. They were diagnosed with hypertrophic cardiomyopathy by clinicians. The histologic features of endocardial biopsies were hypertrophy and vacuolar degeneration of cardiomyocytes. Part of cardiomyocytes appeared as intracellular clear areas lacking myofibers. The nuclei were large, irregular and hyperchromatic. And lipofuscin was occasionally observed in the nuclei of cardiomyocytes. Ultrastructural feature of electron microscopic was glycogen accumulation. Genetic analysis identified two lysosome-associated membrane protein-2 (LAMP2) gene mutations. A 1-bp deletion in exon 8 (c.973delC) was found in patient 1, leading to a frame-shift mutation. A 3-bp duplication in exon 5 (c.719_721dupAGC) was found in patient 2, leading to an insertion mutation. Conclusions: Danon disease is a rare disease characterized by hypertrophic cardiomyopathy. It is caused by mutations in the LAMP2 gene. Vacuolar degeneration of cardiomyocytes, glycogen accumulation under electron microscope and the mutation of LAMP2 gene are the critical features of Danon disease. Familiar with its clinicopathological characteristics would be helpful to avoid the misdiagnosis of Danon disease.

[Clinicopathologic study of cardiac myxofibrosarcomas].

Objective: To investigate the clinicopathologic features of cardiac myxofibrosarcomas. Methods: The clinical data, pathomorphologic and immunohistochemical features were evaluated in five cases of cardiac myxofibrosarcoma collected from January 2009 to December 2014, with relevant literature review. Results: Five patients with cardiac myxofibrosarcoma, including four women and one man [age range 39-61 years; mean (50.4±9.0) years] were included. All tumors were broadbased and located mainly in the left atrium, with one case extending through the atrial wall and pericardium to the left lower lung lobe. The morphological grade was low in one case, intermediate in one, and high in three. Using Fédération Nationale des Centres de Lutte Contre le Cancer (FNLCC) grading system, one case was grade 1 and four cases were grade 2. Immunohistochemical analysis revealed diffuse and strong expression for vimentin in all cases. Smooth muscle actin and muscle specific actin were variably expressed. Complete tumor excision was performed in one case, and tumor debulking was performed in the other four cases. Clinical follow-up was available in three cases. One patient with en bloc excision of the tumor mass survived 13 months and the other two with tumor debulking died one month after surgery. Conclusions: The most common location for cardiac myxofibrosarcoma is the left atrium. Some myxofibrosarcoma may be histologically bland and misdiagnosed as myxoma due to histological similarities. Thus caution should be exercised in their microscopic differentiation. Precise imaging, multidisciplinary approach and adequate initial surgery may contribute to improving the clinical outcomes of myxofibrosarcoma.

[Clinical application value of echocardiography combined with genetic testing in fetal cardiac rhabdomyoma].

OBJECTIVE: To investigate the clinical value of echocardiography combined with genetic testing in the fetal cardiac rhabdomyoma. METHODS: Thirty-three fetal cardiac rhabdomyoma cases diagnosed by fetal echocardiogram in Beijing Anzhen Hospital from Jan. 2011 to Oct. 2015 were enrolled in a retrospective analysis. The results of other examination and pregnancy outcomes of them were followed up, the genetic characteristics of cardiac rhabdomyoma were summarized on the basis of pathology and genetics examination results. RESULTS: The pregnancy outcomes: 24 cases were terminated pregnancy, 4 cases were born and 5 cases were lost. The results of ultrasound, pathology and genetic examination were detailed in 8 cases. Pathological examination: the typical characteristics of cardiac rhabdomyoma were found in the 8 cases with cardiac rhabdomyoma. The tumor tissue was composed of irregular and swelling shape of cardiomyocytes, and the cytoplasm was vacuole like, which was characteristic of " spider like cells" through microscopic observation. The geneticdetection results: 7 cases had tuberous sclerosis complex (TSC) gene mutation, TSC gene abnormalities were not detected in 1 case. Among the 7 cases with TSC gene mutations, 6 cases were with TSC2 gene mutation and the other 1 case was with TSC1 gene mutation. The family gene was investigated in the 5 cases, which including 3 cases of TSC gene mutation in mother passed on to the fetus (1 case with family of three generations of genetic) and 2 cases of spontaneous TSC gene mutation in the fetus. CONCLUSIONS: Prenatal echocardiography combined with genetic detection have important clinical significance, which not only can clear if cardiac rhabdomyomas were associated with TSC, but also can clear the TSC gene mutation source. So as to further guide the perinatal management.