In this retrospective study, we have shown that the subclassification of DLBCL on the basis of the cell of origin continues to have prognostic importance in the rituximab era.

Gastroblastoma is a rare distinctive biphasic tumor of the stomach. The molecular biology of gastroblastoma has not been studied, and no affirmative diagnostic markers have been developed. We retrieved two gastroblastomas from the consultation practices of the authors and performed transcriptome sequencing on formalin-fixed paraffin-embedded tissue. Recurrent predicted fusion genes were validated at genomic and RNA levels. The presence of the fusion gene was confirmed on two additional paraffin-embedded cases of gastroblastoma. Control cases of histologic mimics (biphasic synovial sarcoma, leiomyoma, leiomyosarcoma, desmoid-type fibromatosis, EWSR1-FLI1-positive Ewing sarcoma, Wilms' tumor, gastrointestinal stromal tumor, plexiform fibromyxoma, Sonic hedgehog-type medulloblastomas, and normal gastric mucosa and muscularis propria were also analyzed. The gastroblastomas affected two males and two females aged 9-56 years. Transcriptome sequencing identified recurrent somatic MALAT1-GLI1 fusion genes, which were predicted to retain the key domains of GLI1. The MALAT1-GLI1 fusion gene was validated by break-apart and dual-fusion FISH and RT-PCR. The additional two gastroblastomas were also positive for the MALAT1-GLI1 fusion gene. None of the other control cases harbored MALAT1-GLI1. Overexpression of GLI1 in the cases of gastroblastomas was confirmed at RNA and protein levels. Pathway analysis revealed activation of the Sonic hedgehog pathway in gastroblastoma and gene expression profiling showed that gastroblastomas grouped together and were most similar to Sonic hedgehog-type medulloblastomas. In summary, we have identified an oncogenic MALAT1-GLI1 fusion gene in all cases of gastroblastoma that may serve as a diagnostic biomarker. The fusion gene is predicted to encode a protein that includes the zinc finger domains of GLI1 and results in overexpression of GLI1 protein and activation of the Sonic hedgehog pathway.

No abstract

Aberrant expression of neuroendocrine markers is extremely rare in endothelial neoplasms, with only a single report describing three cases. Although originally classified as conventional angiosarcoma, further assessment of these tumors revealed a strikingly composite morphology composed of retiform and epithelioid elements reminiscent of composite hemangioendothelioma, a rare subtype of hemangioendothelioma. To further investigate these findings, available materials from 11 morphologically distinctive endothelial tumors showing neuroendocrine marker expression were retrieved from our archives. Immunohistochemistry for CD31, CD34, FLI-1, synaptophysin, chromogranin, D2-40, ERG, keratin (OSCAR), and CAMTA1 was performed. Total RNA from five cases were extracted and subjected to whole transcriptome sequencing. Clinical follow-up was obtained. These tumors were found to arise in five males and six females in patients from 9 to 55 years in age (median 47 years). They arose both in superficial (wrist, ankle, scalp, hip, and foot) and deep (periaortic tissues, C5 vertebra, pulmonary vein, and liver) locations. All contained elongated, retiform vascular channels lined by hyperchromatic 'hobnail' endothelial cells and a solid growth of uniform epithelioid cells reminiscent of epithelioid hemangioendothelioma. Hemangioma-like foci also lined by hobnail endothelial cells were frequently present. Mitotic activity was typically <1/10 HPF, and necrosis or areas of conventional angiosarcoma was absent. The results of immunohistochemistry were: CD31 (10/10), FLI-1 (10/10), ERG (9/9), CD34 (5/10), D2-40 (7/10), synaptophysin (11/11), chromogranin A (1/11), CD56 (5/11), keratin (0/11), and CAMTA1 (0/6). Sequencing analysis showed one case with PTBP1-MAML2 and one case with EPC1-PHC2 fusion transcripts; fusion transcripts were not identified in the remaining cases. Follow-up (8 cases) revealed local recurrence in one patient and metastatic spread in four individuals (bone, lung, liver, and brain). One person died of disease. Although the morphological features of these tumors are characteristic of composite hemangioendothelioma, this distinctive subset with neuroendocrine differentiation more often involves deep locations and displays more aggressive behavior than typically described in other cases of composite hemangioendothelioma.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as the diagnostic modality of choice for mass lesions in the pancreas. The objective of the current study was to determine the accuracy and pitfalls of EUS-FNA in the diagnosis of pancreatic lesions in cases that involved follow-up surgical resection. METHODS: Cases of EUS-FNA of pancreatic lesions performed from 2007 to mid-2012 for which subsequent surgical resection was performed were retrieved from the department's database. The accuracy of the cytologic diagnosis was assessed using the histological diagnosis as the gold standard. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. "Neoplastic," "suspicious," and "malignant" were classified as a positive cytologic diagnosis. In one calculation method, "atypical" was also included as a positive cytologic diagnosis whereas in another it was not considered to be a positive cytological result. The cases with a cytologic-histological discrepancy were reviewed to identify sources of errors.RESULTS: A total of 1212 cases from 1104 patients (518 women and 586 men; age range, 18-94 years [average age, 63.5 years]) were identified. Cytologic diagnoses included 52 unsatisfactory, 224 benign, 129 atypical, 140 neoplasm, 35 suspicious, and 632 malignant diagnoses. Of these cases, 397 patients had histological follow-up information available. The sensitivity, specificity, positive predictive value, and negative predictive value were 83.2%, 85.9%, 95.9%, and 56.1%, respectively, with atypical cases excluded from the analysis. When atypical cases were included as a positive cytologic diagnosis, the sensitivity, specificity, positive predictive value, and negative predictive value were 86.7%, 67.9%, 90.7%, and 58.5%, respectively, and were 73.7%, 87.7%, 95.6%, and 48.0%, respectively, when atypical cases were included as a negative cytologic diagnosis. The major difficulty in EUS-FNA cytology was to differentiate pancreatic mucinous neoplasms from contaminants of gastric mucosa. Other pitfalls included differentiating mucinous neoplasm from extensive pancreatic intraepithelial neoplasia, and endocrine tumor from nesidioblastosis versus acinar cell carcinoma or intrapancreatic spleen.CONCLUSIONS: EUS-FNA is a valuable tool for the diagnosis of pancreatic lesions, especially solid malignant tumors.Cytologic-radiological correlation is essential in differentiating pancreatic mucinous neoplasms from gastric mucosa, because the former usually are found to have characteristic features on imaging. Pathologists should be aware of the pitfalls in the cytologic diagnosis of pancreatic lesions that may significantly change the clinical management of the patients.Cancer (Cancer Cytopathol) 2015;123:98-107.