Background: Thymic epithelial tumors (TET) are rare neoplasms with inconsistent treatment strategies.When researching for molecular pathways to find new therapies, the correlation between specific molecular markers and outcome has only rarely been investigated. The aim of this study was to investigate the correlation between survival, metastatic potential and invasiveness of aggressive subtypes of TET and immunohistochemical markers. Methods: Overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and metastasisfree survival (MFS) of patients with WHO type B2/B3 mixed type thymoma (MT), thymoma type B3 (B3) and thymic carcinoma (TC), undergoing surgery [1998][1999][2000][2001][2002][2003][2004][2005][2006][2007][2008][2009][2010][2011][2012][2013] were determined. Tumor specimens were stained using a tissue microarray (TMA) (CD117, CD5, p63, p40, p21, p27, p53, Bcl-2, Ki67, podoplanin, synaptophysin, PTEN and Pax8). Invasive behavior of primary tumors and the presence of extrathoracic metastases were assessed. Results: We found in 23 patients included into this study (four MT, ten B3, nine TC) that (I) p21 expression in the cytoplasm significantly correlated with a decrease of OS (P=0.016), PFS (P=0.034) and MFS (P=0.005); (II) MFS was significantly shorter when the combination of p21-low p27-low p53-high was present (P=0.029); and (III) nuclear p27 (P=0.042), Ki-67 (P=0.024) and podoplanin (P=0.05) expression correlated with the presence of extrathoracic metastases. Conclusions: The main finding of this study is that cytoplasmic p21 expression negatively influences the outcome of malignant TETs and correlates with metastatic activity. Additionally, selected immunohistochemical markers correlate with the distant metastatic potential of TETs. These results may contribute to the stratification of diagnosis and improvement of treatment strategies for thymic malignancies.
Sclerosing epithelioid fibrosarcoma (SEF) is a rare neoplasm arising mostly in limbs and limb girdles, with a high rate of recurrence and a strong tendency to metastasize. This case study is of a 54-year-old woman with an asymptomatic mass in the upper lobe of the left lung detected by PET-CT when staging for Lynch syndrome-associated colon carcinoma. Histology of the resected tumor showed epithelioid cells arranged in nests, partly restiform within a zone of sclerosing fibrosis. Immunohistochemistry was positive for vimentin, epithelial membrane antigen, and S100-protein. Eight months after lung resection, the patient was diagnosed for basal cell carcinoma on her back. At the end of a two year follow-up period, she developed metastases to the mediastinum, vertebrae, ribs, femurs, pelvic bones, kidneys, and one lung, histologically all related to SEF. Here we report the first case of a SEF primarily arising from the lung and discuss it in the context of the current literature.
Background: Advanced unresectable thymic epithelial tumors (TETs) are usually treated with platinum-based chemotherapy, although no randomized trials have been conducted and no clear recommendations on the regimen choice are available. Actually, the modern scenario of TETs treatment has become more complex after the introduction of biological agents, but no clear evidences on the more effective sequence treatment between chemotherapy and target therapy have been stated. Here we investigate the effectiveness of platinum rechallenge in advanced TETs. Method: All the clinical data of patients with advanced/unresectable or metastatic TETs, treated with first line platinum-based chemotherapy at our institution during a 10-year period were retrospectively reviewed, and those who received platinum rechallenge from the third line and beyond, were included in this study. Patients characteristics, disease control rate (DCR), overall survival (OS), progression free survival (PFS) and post-rechallenge (P-Re) OS and PFS were analyzed. Result: Platinum rechallenge was administered in 22 patients, of whom 17 had thymoma and 5 thymic carcinoma. A DCR of 95.4% (stable disease (SD) 63.6%, partial response (PR) 31.8%) was achieved after the first line platinum-based chemotherapy according to RECIST criteria, while a DCR of 81.8% (SD 63.6%, PR 18.1%) was registered after platinum rechallenge. All the responders to first line, were confirmed as responders also to rechallenge, only 3 patients with stable disease to first line, had a progressive disease after rechallenge. The median OS of 122 months was statistically correlated with histotype (p¼0.015) and with the median treatment free interval (TFI) of 18 months (p¼0.019). No statistical correlation has been found between the median P-Re OS of 27 months, the histotype and the TFI. To point out that a statistical correlation between the P-Re PFS of 7 months and the administration of target therapy before rechallenge, has been observed (p¼0.04). Conclusion: Our retrospective analysis showed that platinum rechallenge may be considered a suitable treatment for advanced, heavily pretreated TETs, especially in case of previous response and longer TFI. Moreover, in the light of our results, we assume, as already stated for other solid tumors, that the chemo-resistant clones can be re-sensitized to platinum by target agents. Prospective trials are needed.
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