Primary cardiac undifferentiated pleomorphic sarcoma is associated with TP53 mutation during lack of MDM2 amplification, and targeted sequencing analysis reveals potentially actionable targets.

Cardiac undifferentiated pleomorphic sarcoma (UPS) is a rare malignancy. Several studies have revealed frequent MDM2, CDK4, PDFGRA, and KIT amplifications and CDKN2A and CDKN2B deletions. Cases lacking the above copy number alterations may harbor alternative driver mutations; however, little is known about such occurrences. This study was conducted to gain further insights into the molecular features of cardiac UPS using targeted sequencing of 560 cancer-related genes, and fluorescence in situ hybridization and immunohistochemistry of MDM2, CDK4, CDKN2A, TP53, and RB1 in 9 cardiac UPS cases. TP53 mutation or CDKN2A deletion was found in cases lacking MDM2 amplification. Further, p53 overexpression was detected in the case with TP53 mutation, while p16 expression was completely lost in the case with CDKN2A homozygous deletion. p16 overexpression was found in cases with MDM2 and CDK4 amplification but without CDKN2A deletion. Immunohistochemistry of MDM2, CDK4, p53, and p16 is expected to be preliminarily used for gene status analysis. As cardiac UPS and intimal sarcomas are merging into a single spectrum, mutation data for 3 cardiac UPS and 9 intimal sarcomas from the literature, as well as data for 5 cardiac UPS in our study were evaluated, and known recurrently mutated cancer driver genes, including PDGFRB, TP53, ALK, PTCH1, RET, ERBB4, JAK3, GATA1, PIK3CG, and RARA, were identified. Several new potentially actionable mutations, including those in RARA, ALK, PTCH1, RET, ROS1, ABL1, and MET, were also found. These findings improve the molecular understanding of this rare malignancy and are expected to provide a basis for developing precision therapeutics for cardiac UPS and intimal sarcomas.

Cardiac fibroma: A clinicopathologic study of a series of 12 cases.

BACKGROUND: Cardiac fibroma (CF) is a rare tumor that has not been widely reported. This study investigated the clinical findings, histologic features, and differential diagnosis of CF. METHODS: A total of 12 CF cases were studied and reviewed using hematoxylin and eosin (H&E), special staining and immunohistochemical staining. The ALK gene was tested in 4 cases of cardiac fibroma with significant inflammatory cells. Clinicopathological data were retrospectively analyzed and followed up. RESULTS: The cases occurred in six males and six females ranging in age from 0.5 to 55 years (median, 5 years). The tumors were grossly single and solid (1-17 cm; mean 5.6 cm). The clinical signs and symptoms depended largely on the location of the tumor. Microscopically, the CFs observed were composed of monomorphic spindle cells and abundant collagen. The spindle cells demonstrated little or no atypia. The histology of CFs in infants and young children showed some differences from those in adults. Infants and young children with fibromas exhibited cellular types with more inflammatory infiltration. All tumors expressed vimentin markers. Eleven of 12 cases (91.7%) were positive for SMA by immunohistochemistry. ALK immunostaining and ALK-FISH tests showed negative results. Follow-up information was available for all patients. The mean postoperative follow-up was at 3 years (range 2 months-8.8 years). All patients were alive with no evidence of disease. CONCLUSIONS: Our study shows that CFs exhibit a wide morphological spectrum of soft tissue tumors with fibroblastic or myofibroblastic differentiation and/or components. Infants and younger pediatric patients with fibromas have tumors that are more hypercellular and more likely to be misdiagnosed with aggressive or malignant lesions than adults. Finally, the data indicate that CF exhibits benign behavior and that local resection is safe and effective.

Primary cardiac synovial sarcoma: a clinicopathological, immunohistochemical, and molecular genetics study of five clinical cases.

BACKGROUND: Primary cardiac synovial sarcoma was an exceedingly rare tumor that less reported. The study investigated the clinicopathologic, immunohistochemical, and molecular features of primary cardiac synovial sarcoma. METHODS: A total of five cardiac synovial sarcoma cases were assessed and reviewed using H&E, immunohistochemical and fluorescence in situ hybridization staining methods. Clinicopathological data were retrospectively analyzed and followed up. RESULTS: The cases occurred in four males and one female ranging in age from 23 to 48 years (mean, 32 years). The tumors were grossly large and solid (7.4-13.7 cm; mean 8.6 cm). Microscopically, clinical cases were biphasic (n = 2) and monophasic (n = 3) types and were diffusely immunoreactive for EMA, vimentin, and BCL-2. All cases demonstrated SS18 rearrangement by fluorescence in situ hybridization staining. Clinically, three patients died within 1 year after surgery, while one patient had bone metastasis and still carried the disease. One last patient underwent a heart transplant and survived without evidence of the disease. CONCLUSION: Cardiac synovial sarcoma was an aggressive tumor whose differentiation may be a continuous and complex morphologic spectrum. SS18 rearrangement demonstration by fluorescence in situ hybridization was decisive in our study for differential diagnosis of cardiac synovial sarcoma and other tumors. Cardiac synovial sarcoma usually endured poor survival rates. Patients in advanced stages may undergo heart transplantation as a means of improving their survival rates.

[Autopsy findings of 19 cases of pulmonary vein abnormalities associated with fetal cardiac anomalies].

OBJECTIVE: To improve the diagnostic accuracy of fetal pulmonary venous abnormalities through the analysis of the fetal pulmonary vein anatomy. METHODS: 234 cases of congenital cardiac abnormalities were detected by echocardiography during pregnancy in An Zhen Hospital, Capital Medical University from May 2010 to August 2015. Autopsy was then performed. The type of fetal pulmonary venous malformation, cardiac abnormalities, systemic venous malformations, and other internal organs deformities were documented. RESULTS: There were ninteen cases of pulmonary venous malformations among the 234 cases of fetal congenital heart disease. These included two cases of congenital pulmonary venous hypoplasia (CPVH) or atresia, four cases of partial anomalous pulmonary venous drainage (PAPVD), seven cases of total anomalous pulmonary venous drainage (TAPVD), five cases of atresia of common pulmonary vein (CPV), one case of congenital pulmonary venous hypoplasia with total anomalous pulmonary venous drainage. There were eleven cases with single ventricle, eight cases with right aortic arch, seven cases with single atrium and six cases with pulmonary valve stenosis. Eleven cases had pulmonary hypoplasia and nine cases had abnormal spleen. CONCLUSIONS: There are many variations in pulmonary venous abnormalities associated with severe and complex cardiac abnormalities and internal organs malformation. Care should be exercised during autopsy examination to look for all branches of the pulmonary vein.

[Immunohistochemical evaluation of mutant p53 protein over-expression in non-mucinous adenocarcinoma in-situ and invasive adenocarcinoma, NOS of lung].

OBJECTIVE: To study the over-expression of mutant p53 protein in non-mucinous adenocarcinoma in-situ (NMAIS) and invasive adenocarcinoma, NOS of lung. METHODS: Immunohistochemical study for p53 protein was performed on 17 cases of NMAIS and 70 cases of invasive adenocarcinoma, NOS of lung. The difference in p53 over-expression between the two tumor subtypes was analyzed. RESULTS: The over-expression of mutant p53 protein was observed in 0 case (0%) of NMAIS and 37 cases (52.9%) of invasive adenocarcinoma, NOS of lung. The difference was of statistical significance (P = 0.000). CONCLUSION: Mutant p53 protein over-expression may play a role in the progression of NMAIS to invasive adenocarcinoma, NOS.