We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in the base of tongue, lung, and nasopharynx were studied. All cases shared a clear cell morphology with hyalinized stroma, presence of mucin and p63 positivity and were initially diagnosed as mucoepidermoid carcinoma but were negative for evidence of any of the expected gene fusions. Anchored multiplex polymerase chain reaction demonstrated a EWSR1-CREM fusion in all 3 cases to confirm a diagnosis of CCC. This finding is biologically justified as CREM and ATF1 both belong to the CREB family of transcription factors. EWSR1-CREM fusions have not been previously reported in CCC and have only rarely been reported in other tumors. We show that the ability to discover novel gene variants with next-generation sequencing-based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.

Glioblastoma multiforme (GBM) represents an extremely chemoresistant tumour type. Here, authors analysed the immunophenotype of GBM tumours by flow cytometry and correlated the immunophenotypic characteristics with sensitivity to chemotherapy. The expression of selected neural and non-neural differentiation markers including A2B5, CD34, CD45, CD56, CD117, CD133, EGFR, GFAP, Her-2/neu, LIFR, nestin, NGFR, Pgp and vimentin was analysed by flow cytometry in eleven GBM (WHO gr.IV) patients. The sensitivity of tumour cells to a panel of chemotherapeutic agents was tested by the MTT assay. All tumours were positive for A2B5, CD56, nestin and vimentin. CD133, EGFR, LIFR, NGFR and Pgp were expressed only by minor tumour cell subpopulations. CD34, CD45, CD117, GFAP and Her-2/neu were constantly negative. Direct correlations were found between the immunophenotypic markers and chemosensitivity: A2B5 vs lomustine (r(2) = 0.642, P = 0.033), CD56 vs cisplatin (r(2) = 0.745, P = 0.013), %Pgp(+) vs vincristine (r(2) = 0.846, P = 0.008), and %NGFR(+) vs daunorubicine (r(2) = 0.672, P = 0.047) and topotecan (r(2) = 0.792, P = 0.011). In contrast, inverse correlations were observed between: EGFR vs paclitaxel (r(2) = -0.676, P = 0.046), CD133 vs dacarbazine (r(2) = -0.636, P = 0.048) and LIFR vs daunorubicine (r(2) = -0.878, P = 0.004). Finally, significant associations were also found among sensitivities to different chemotherapeutic agents and among different immunophenotypic markers. In conclusion, histopathologically identical GBM tumours displayed a marked immunophenotypic heterogeneity. The expression of A2B5, CD56, NGFR and Pgp appeared to be associated with chemoresistance whereas CD133, EGFR and LIFR expression was characteristic of chemosensitive tumours. We suggest that flow cytometric imunophenotypic analysis of GBM may predict chemoresponsiveness and help to identify patients who could potentially benefit from chemotherapy.

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The intravascular variant of diffuse large B-cell lymphoma (IVBL) is a rare form of non-Hodgkin lymphoma that is frequently diagnosed at autopsy because the symptoms are nonspecific or confusing. We report a case of IVBL in a woman with pre-existing myelodysplastic syndrome manifested as a fever of unknown origin, bilateral adrenal enlargement and subsequent development of panhypopituitarism. Lymphomatous infiltration or osteomyelitis of the sella was supposed. Despite antibiotic and corticosteroid therapy the patient died within three months. An intravascular variant of B-cell lymphoma with intravascular collections of lymphomatous cells predominantly localized in the adrenal and pituitary glands was found at autopsy. The association of panhypopituitarism with bilateral adrenal enlargement is uncommon in endocrinological praxis and the occurrence of combined endocrine involvement in a patient with IVBL has not been described in previous literature.

We report a 38-year-old woman with relapsing-remitting multiple sclerosis, treated with subcutaneous injections of interferon beta (IFN-beta)-1b every other day. Disseminated cutaneous lesions were observed after 3 injections. These symptoms reappeared after drug readministration. The histopathological examination of the skin specimens confirmed nonspecific cutaneous lymphocytic vasculitis. The patient's outcome was favorable after corticosteroid placement and discontinuing IFN-beta therapy. Isolated lymphocytic cutaneous vasculitis linked to IFN-beta-1b therapy is suspected as a new association.

28 SummaryWe report the case of a 14-year-old girl who suffered from headache, fatigue, caught and a fever with body temperature up to 40 0 C for a week. The patient had abdominal enlargement and clinical examination showed the hepatomegaly +5 cm. In ELISA assays employing Em2+ antigen, high titres of specific IgG antibodies to Echinococcus multilocularis somatic antigens were found in the serum. Western blot analysis also indicated on presence of alveolar echinococcosis (AE). CT examination showed expansive foci in the right liver lobe and histological examinations of the biopsy after PAS staining confirmed the presence of alveolar echinococcosis. After 320 days of chemotherapy with albendazole, CT revealed progression of parasitic foci and new abscess lesions inside parasitic cysts were detected, with some parts being necrotic. The surgical removing of foci was performed as following -the laparotomic revision, the removal of the right liver lobe with dilatation, reconstruction of v. cavae cum prothesis PTFE in length 12 cm. Three months after the operation, the rest of the patient's left liver lobe had grownup and compensated at least a part of the removed liver.

A rare case of duplicate tumor, osteosarcoma and Ewing's sarcoma, complicated by metachronous pulmonary metastasis in a child is reported. A nine-year-old girl's osteosarcoma was treated by neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Four years later, resection of the chest wall to remove an Ewing's sarcoma had to be performed, followed by chemotherapy and radiotherapy. At the age of 17, the girl underwent a metastasectomy of Ewing's sarcoma metastasis to the lung. Five years later, the patient is free from any recognizable malignant disease. We conclude that after the complete surgical removal of two primary tumors, metastasectomy is an optimal treatment procedure in case of a solitary pulmonary metastasis.

The purpose of this case control study was to evaluate the role of X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genotypes as genetic indicators of susceptibility to breast cancer (BC). We analysed DNA samples from 114 breast cancer patients and 113 control subjects using polymerase chain reaction-restriction fragment length polymorphism. For the single nucleotide polymorphisms in XRCC1 exon 10 (Arg399Gln, G/A) and XPD exon 23 (Lys751Gln, A/C), no remarkable differences for genotype distribution and allele frequencies were observed between BC group and control group in the study. The genotype frequency for homozygote A/A in XPD exon 6 (Arg156Arg, C/A) were significantly different between BC and control groups (P < 0.0001, odds ratio = 2.14; 95% confidence interval 1.44-3.17). The data indicate a possible role for XPD (Arg156Arg, C/A) polymorphisms in BC susceptibility.