Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response.

Pure intraductal carcinoma of the parotid gland: Cytologic findings on FNA sample. Report of one case.

One case of intraductal carcinoma of the parotid gland in a 67-year-old male patient is here introduced. The patient, who had a one-year history of a parotid mass, had undergone ultrasound and MRI examination that disclosed a 13x4x3 mm well delimited nodular mass of the accessory lobe of his left parotid gland. Ultrasound-guided Fine Needle Aspiration (FNA) had been performed by the clinician. The obtained smears showed widespread cellular necrosis in which cellular clusters with moderate and focally severe atypias displayed papillary and cribriform architecture and were admixed with sheets of epithelial cells with less striking nuclear atypias, squamous, or apocrine metaplasia. Histopathological examination disclosed a pure intraductal carcinoma of the parotid gland with classical morphology, which was radically excised. The differential cytological diagnosis of pure intraductal carcinoma of salivary glands may be difficult and comprises mucoepidermoid carcinoma as well as "in situ" carcinomas developping in the context of sclerosing polycystic adenosis, mammary analogue secretory carcinoma (MASC) of the salivary glands and cystic variants of salivary adenocarcinoma NOS (formerly called cystadenocarcinomas).

The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions.

Hurthle cell adenomas and carcinomas, characterized by the presence of oncocytic cells, are unusual thyroid neoplasms, the treatment of which is still controversial. We analyzed specimens from 49 patients with oncocytic cell nodular lesions including 20 adenomas, 19 carcinomas, and 10 hyperplasias for RET/PTC (papillary thyroid carcinoma) activation, which is the most frequent genetic alteration in PTCs. RET/PTC activation was detected in a significant number of cases of Hurthle cell adenomas and carcinomas, but in 0 of 10 patients with hyperplastic nodules. In particular, the RET/PTC1 isoform was found in 7 of 12 adenomas and 4 of 7 carcinomas. These results would indicate that RET/PTC is a genetic event common to papillary carcinomas and to Hurthle cell neoplasias.

Impact of preoperative radiotherapy on survival in locally advanced rectal cancer: an observational population-based study from the South of Switzerland.

Preoperative radiotherapy (RT) followed by surgery is widely accepted in the treatment of locally advanced rectal cancer (LARC). This study aimed to estimate at the population-based level the impact of preoperative RT on overall survival (OS) and cancer-specific survival (CSS) in LARCs diagnosed in Southern Switzerland between 1996 and 2007. All patients with LARC were selected from the Ticino Cancer Registry database. Patients were categorized according to the first administered treatment: preoperative radiotherapy (RT) followed by surgery (RT+) versus surgery (RT-). Clinical-pathological characteristics and 5-year OS and CSS were analysed. Among 384 patients with LARC, 54% underwent preoperative RT, occurring more frequently in the mid-distal part of the rectum compared with the RT- group (74.8 vs. 29.8%, respectively). Both 5-year OS and CSS significantly improved in RT+ patients (OS: 68 vs. 54%, respectively; CSS: 71 vs. 63%, respectively). The adjusted hazard ratio for all death was equal to 0.66 (95% confidence interval: 0.46; 0.97); similarly, the hazard ratio for cancer-specific death was 0.63 (95% confidence interval: 0.39; 0.99). These observational population-based results, after controlling for most important diagnostic and clinical prognostic factors, confirm the benefit of preoperative RT of LARC, even if the magnitude seems greater than expected in clinical trials results. Additional studies are needed, particularly with regard to the possible effect of standardized staging procedure and multidisciplinary discussion on patient outcome.