Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma

Combination therapy with BRAF and MEK inhibitors significantly improves survival in BRAF mutated melanoma patients but is unable to prevent disease recurrence due to the emergence of drug resistance. Cancer stem cells (CSCs) have been involved in these long-term treatment failures. We previously reported in lung cancer that CSCs maintenance is due to altered lipid metabolism and dependent upon Stearoyl-CoA-desaturase (SCD1)-mediated upregulation of YAP and TAZ. On this ground, we investigated the role of SCD1 in melanoma CSCs

Cytological diagnostic features of late breast implant seromas. From reactive to anaplastic large cell lymphoma

Late breast implant seroma may be the presentation of a breast implant-associated anaplastic large cell lymphoma (BI-ALCL), which claims for a prompt recognition. However, BI-ALCL diagnosis on fine-needle aspiration (FNA) might be challenging for pathologists lacking experience with peri-implant breast effusions. Sixty-seven late breast implant seromas collected by FNA from 50 patients were evaluated by Papanicolaou smear stain and immunocytochemistry on cell blocks. A diagnostic algorithm based on the cellular composition, cell morphology and percentage of CD30+ cells was developed. Histological evaluation of the corresponding peri-prosthetic capsules was also performed. Most of the effusions (91% of the samples) were classified as reactive and 9% as BI-ALCL. In the BI-ALCL cases, medium-to-large atypical cells expressing CD30 represented more than 70% of the cellularity, whereas in in the reactive effusions CD30+ elements were extremely rare (<5%) and consisted of non-atypical elements. The reactive effusions were categorized into three patterns: i) acute infiltrate with prominent neutrophilic component (33% of the samples); ii) mixed infiltrate characterized by a variable number of neutrophils, lymphocytes and macrophages (30% of the samples); iii) chronic infiltrate composed predominantly of T lymphocytes or macrophages with only sporadic granulocytes (37% of the samples). The inflammatory cytological patterns were consistent with the histology of the corresponding capsules. Our results indicate that cytological analysis of late breast implant effusions, supported by the knowledge of the heterogeneous cytomorphological spectrum of late seromas, is a valuable approach for the early recognition of BI-ALCL

Raman spectroscopy discriminates malignant follicular lymphoma from benign follicular hyperplasia and from tumour metastasis

Raman spectroscopy is a non-destructive label-free technique providing biochemical tissue fingerprint. The objective of the present work was to test if Raman spectroscopy is a suitable tool to differentiate lymph nodes affected by different conditions, such as reactive follicular hyperplasia (benign), follicular lymphoma (low grade primary tumour), diffuse large B cell lymphoma (high grade primary tumour) and tumour metastasis (secondary tumours). Moreover, we tested its ability to discriminate follicular lymphomas by the tumour grade and the BCL2 protein expression. Lymph nodes collected from 20 patients, who underwent surgery for suspected malignancy, were investigated. Imaging of tissue areas from about 400 µm2 up to 2 mm2 was performed collecting Raman maps containing thousands of spectra. Partial least squares discriminant analysis (PLS-DA) - a bilinear classification method - was used to calculate lymph node classification models, in order to discriminate at first between benign and malignant tissues and successively among cancer types, grades and the BCL2 protein expression. This proof-of-concept study paves the way for the development of clinical optical biopsy tools for lymph node cancer diagnosis, complementary to histopathological assessment

Optimized immunohistochemistry using the D5F3 antibody provides a reliable test for identification of ALK-positive lung adenocarcinomas

We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative. The FISH positive/IHC-positive cases with moderately intense reactivity had the typical clinicopathologic features of ALK-positive patients (younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01; cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In conclusion, our findings indicate that optimized IHC using the D5F3 antibody provides a reliable and inexpensive test for identification of ALK-positive adenocarcinomas. Inclusion of this information in the pathology report at the time of the histological diagnosis might significantly shorten time to treatment

Oncocytic variant of medullary thyroid carcinoma: a rare case of sporadic multifocal and bilateral RET wild-type neoplasm with revision of the literature

Oncocytic variant of medullary thyroid carcinoma (OV-MTC) is a very unusual entity, up to date only 17 cases have been reported in the literature. MTC is a neuro-endocrine malignancy arising from the para-follicular C cells of the thyroid gland. It generally has a slight female predominance and appears as a single lesion. However in the Multiple Endocrine Neoplasia Syndrome 2, linked to the point mutation of RET oncogene, multifocal MTCs may also occur. Herein, we report the case of a 75 years old man with a rare form of sporadic multifocal and bilateral OV-MTC expressing wild-type RET gene. The histological and molecular features of this rare entity are pre sented and discussed with revision of the pertinent literature

HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection

Background: Natural killer (NK) cells provide a major defense against cytomegalovirus (CMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulinlike receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This study assessed whether the KIR and HLA repertoire may influence the risk of developing symptomatic or asymptomatic disease after primary CMV infection in the immunocompetent host. Methods: Sixty immunocompetent patients with primary symptomatic CMV infection were genotyped for KIR and their HLA ligands, along with 60 subjects with a previous asymptomatic infection as controls. Results: The frequency of the homozygous A haplotype (only KIR2DS4 as activating KIR) was higher in symptomatic patients than controls (30% vs 12%, respectively; odds ratio [OR] = 3.24; P =.01). By logistic regression, the risk of developing symptomatic disease was associated with the homozygous A haplotype and the HLABw4T allele. Combining the 2 independent variables, we found that 37 out of 60 (62%) symptomatic patients but only 18 out of 60 (30%) of controls possessed the homozygous A haplotype or the HLABw4T allele with a highly significant OR (OR = 3.75, P <.0005). Conclusions; Immunocompetent subjects carrying the homozygous A haplotype or the HLABw4T allele are at higher risk of developing symptomatic disease after primary CMV infection