A novel specific genetic translocation in epithelioid hemangioendotelioma, showing a fusion of the WWTR1 and CAMTA1 genes, supports the monoclonality of multifocal epithelioid hemangioendotelioma.

Like other vascular tumors, epithelioid hemangioendothelioma (EHE) is multifocal in approximately 50% of cases, and it is unclear whether the separate lesions represent multifocal disease or metastases. We hypothesized that the identification of an identical WWTR1-CAMTA1 rearrangement in different EHEs from the same patient supports the monoclonal origin of EHE. To test our hypothesis, we undertook a molecular analysis of two multicentric EHEs of the liver, including separate tumor samples from each patient. Matherial and Methods: We retrieved two cases of EHE with available tissue for molecular analysis. In both cases, fluorescence in situ hybridization (FISH) was performed to identify the presence of the WWTR1-CAMTA1 rearrangement to confirm the histologic diagnosis of EHE, as previously described. The reverse transcription-polymerase chain reaction (RT-PCR) products were analyzed by electrophoresis and the RT-PCR–amplified products were sequenced using the Sanger method. Results: FISH analysis revealed signal abnormalities in both WWTR1 and CAMTA1. Combined results confirmed the presence of the t(1;3)(1p36.23;3q25.1) translocation in both cases of EHE. Using RT-PCR analysis, we found that the size of the rearranged bands was identical in the different tumors from each patient. The sequence of the fusion gene confirmed a different WWTR1-CAMTA1 rearrangement in each patient, but an identical WWTR1-CAMTA1 rearrangement in the different lesions from each patient. Discussion: Because of its generally indolent clinical course, EHE is commonly classified as a multifocal, rather than metastatic, disease. In this study, we examined two cases of multifocal liver EHE and found an identical WWTR1-CAMTA1 rearrangement in each lesion from the same patient, but not between the two patients. These findings suggest that multifocal EHE arises from metastasis of the same neoplastic clone rather than from the simultaneous formation of multiple neoplastic clones, which supports the monoclonal origin of multifocal EHE.

Tumori primitivi multipli del polmone. Profilo clinico e biologico in pazienti affetti da neoplasie polmonari multiple. Analisi di elementi clinici e marcatori biologici come possibili fattori di differenziazione dei tumori polmonari multipli

Background: MPLC represents a diagnostic challenge. Topic of the discussion is how to distinguish these patients as a metastatic or a multifocal disease. While in case of the different histology there are less doubt on the opposite in case of same histology is mandatory to investigate on other clinical features to rule out this question. Matherials and Methods: A retrospective review identified all patients treated surgically for a presumed diagnosis of SPLC. Pre-operative staging was obtained with Total CT scan and fluoro-deoxy positron emission tomography and mediastinoscopy. Patients with nodes interest or extra-thoracic location were excluded from this study. Epidermal growth factor receptor (EGFR) expression with complete immunohistochemical analisis was evaluated. Survival was estimated using Kaplan-Meyer method, and clinical features were estimated using a long-rank test or Cox proportional hazards model for categorical and continuous variable, respectively. Results: According to American College Chest Physician, 18 patients underwent to surgical resection for a diagnosis of MPLC. Of these, 8 patients had 3 or more nodules while 10 patients had less than 3 nodules. Pathologic examination demonstrated that 13/18(70%) of patients with multiple histological types was Adenocarcinoma, 2/18(10%) Squamous carcinoma, 2/18(10%) large cell carcinoma and 1/18(5%) Adenosquamosu carcinoma. Expression of EGFR has been evaluated in all nodules: in 7 patients of 18 (38%) the percentage of expression of each nodule resulted different. Conclusions: MPLC represent a multifocal disease where interactions of clinical informations with biological studies reinforce the diagnosis. EGFR could contribute to differentiate the nodules. However, further researches are necessary to validate this hypothesis.