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Chronic myelomonocytic leukemia (CMML) is a rare clonal hematopoietic disorder that can also involve the skin. The histopathology of these skin lesions is not clearly defined, and few data are available in the literature. To better understand tumoral skin involvements in CMML we carried out an extensive, retrospective clinicopathologic study of 42 cases selected from the database of the French Study Group of Cutaneous Lymphomas. On the basis of clinical data, morphology, and phenotype we identified 4 clinicopathologic profiles representing 4 distinct groups. The first group comprised myelomonocytic cell tumors (n=18), exhibiting a proliferation of granulocytic or monocytic blast cells, which were CD68 and/or MPO positive but negative for dendritic cell markers. The second group comprised mature plasmacytoid dendritic cell tumors (n=16), denoted by a proliferation of mature plasmacytoid dendritic cells, which were CD123, TCL1, and CD303 positive but CD56, CD1a, and S100 negative. The third group comprised blastic plasmacytoid dendritic cell tumors (n=4), characterized by a proliferation of monomorphous medium-sized blast cells, which were CD4, CD56, CD123, TCL1 positive but CD1a and S100 negative. The fourth group consisted of a putatively novel category of tumor that we named blastic indeterminate dendritic cell tumors (n=4), distinguished by a proliferation of large blast cells that not only exhibited monocytic markers but also the dendritic markers CD1a and S100. These 4 groups showed distinctive outcomes. Finally, we showed, by fluorescence in situ hybridization analysis, a clonal link between bone marrow disease and skin lesions in 4 patients. Herein, we have described a novel scheme for pathologists and physicians to handle specific lesions in CMML, which correspond to a spectrum of myelomonocytic and dendritic cell proliferations with different outcomes. A minimal panel of immunohistochemical markers including CD68, CD1a, S100, Langerin, and CD123 is necessary to make the correct classification in this spectrum of cutaneous CMML tumors, in which dendritic cell lineage plays an important role.

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Chordomas are slow-growing malignant neoplasms. Determination of histopathologic prognostic factors using a large cohort study has been limited by their low incidence. In this retrospective study, we investigated the clinical, histopathologic, and immunohistochemical prognostic factors in 287 chordomas from 111 patients assessed by central pathologic review. Expression patterns of a variety of markers, including vascular endothelial growth factor (VEGF), mTOR pathway, c-kit, HER2, epidermal growth factor receptor (EGFR) and STAT3, and KRAS, BRAF, EGFR, and PIK3CA mutations were analyzed. On univariate analysis, the results confirm surgery as the best treatment, as judged by patient progression-free survival (PFS) and overall survival (OS). Proton therapy, the presence of a dedifferentiated component, mitotic figures, and Ki67 and p53 labeling indices correlated with PFS . Necrosis and apoptosis correlated with OS. Based on these findings, we propose a histopathologic grading system that correlates with PFS and OS. On multivariate analysis, extent of resection, tumor grade, and proton therapy were independent prognostic factors of PFS; extent of resection, tumor location, and grade were independent prognostic factors of OS. Based on the expression of EGFR, pSTAT3, VEGF, and mTOR pathway proteins, (in 85.9%, 79.1%, 85.7%, and 46% of chordomas, respectively), and 2 new mutations in the PIK3CA gene, we also provide evidence for potential therapeutic targets.

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti-SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi-allelic inactivating events were found by NGS-based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild-type sequence. We then validated the anti-SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non-meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non-meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker.

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These results underscore an impact of pSTAT3 on the clinical efficacy of anti-EGFR-containing chemotherapy regimens and support the prospective assessment of this biomarker.

BackgroundThe GABARAP family members (GABARAP, GABARAPL1/GEC1 and GABARAPL2 /GATE-16) are involved in the intracellular transport of receptors and the autophagy pathway. We previously reported that GABARAPL1 expression was frequently downregulated in cancer cells while a high GABARAPL1 expression is a good prognosis marker for patients with lymph node-positive breast cancer.MethodsIn this study, we asked using qRT-PCR, western blotting and epigenetic quantification whether the expression of the GABARAP family was regulated in breast cancer by epigenetic modifications.ResultsOur data demonstrated that a specific decrease of GABARAPL1 expression in breast cancers was associated with both DNA methylation and histone deacetylation and that CREB-1 recruitment on GABARAPL1 promoter was required for GABARAPL1 expression.ConclusionsOur work strongly suggests that epigenetic inhibitors and CREB-1 modulators may be used in the future to regulate autophagy in breast cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1761-4) contains supplementary material, which is available to authorized users.