Virginie Verkarre

FGF10 Signaling differences between type I pleuropulmonary blastoma and congenital cystic adenomatoid malformation

BackgroundType I pleuropulmonary blastoma (PPB) and congenital cystic adenomatoid malformation of the lung (CCAM) are cystic lung diseases of childhood. Their clinical and radiological presentations are often similar, and pathologic discrimination remains difficult in many cases. As a consequence, type I PPB and CCAM are frequently confused, leading to delayed adequate management for type I PPB. Recent studies have suggested a role for fibroblast growth factor (FGF) 10 signal pathway in CCAM pathogenesis. The objective of our study was to determine whether FGF10 signaling differs between CCAM and type I PPB.MethodsImmunohistochemical studies were performed for expression of FGF10, its receptor FGFR2b, and its inhibitor sonic hedgehog (SHH) in focal type I PPB (n=6), CCAM type I (n=7), CCAM type II (n=7), and control lungs (n=5).ResultsFGF10, FGFR2b, and SHH expressions differed markedly between type I PPB and both types of CCAM. Type I and type II CCAM cystic walls expressed FGF10, FGFR2b, and SHH, whereas staining was absent or poor in type I PBB cystic walls. Expression of FGF10, FGFR2b, and SHH did not differ between CCAM cystic walls and control airway walls.ConclusionsThese findings show that immunohistochemistry with FGF10, FGFR2b, or SHH could be useful in differentiating CCAM from type I PPB, when a child presents with a focal cystic lung lesion. The absence of strong expression of FGF10, FGFR2b, and/or SHH makes the diagnosis of CCAM very doubtful.

Pathological heterogeneity in sporadic synchronous renal tumors: Is the histological concordance predictable?

OBJECTIVE To evaluate the pathological concordance rate of multiple synchronous renal masses (MSRM) presumed to be sporadic and to analyze predictive factors of concordance. MATERIAL AND METHODS We identified from our institutional database patients with sporadic MSRM treated at our center between January 2000 and December 2015. All tumors were reviewed by a dedicated uropathologist. Pathological concordance rate was analyzed regarding clinical characteristics and preoperative imaging. RESULTS We included 112 patients: 50 had unilateral synchronous renal masses and 62 bilateral synchronous renal masses. A total of 291 tumors were analyzed, with an average of 2.6 tumors per patient. Overall, the malignant concordance rate was 91.6%, the pathological concordance rate was 67.3% and the grade concordance rate was 62.5%. In univariate analysis, predictive factors of histological concordance were bilateral synchronous renal masses (odds ratio [OR] = 3.39; 95% CI: 1.06-10.8; P = 0.04), age<60 years (OR = 3.04; 95% CI: 1.2-7.7; P = 0.02) and ≥3 lesions (OR = 2.41; 95% CI: 1.03-5.68; P = 0.04). In multivariate analysis, age<60 remained significantly associated with histological concordance (OR = 3.84; 95% CI: 1.24-11.9; P = 0.02). CONCLUSIONS The histological concordance rate of MSRM is low. Age at diagnosis <60 years, bilateral lesions and ≥3 tumors are predictive factors of histological concordance, but the pathological diagnosis remains difficult to predict. This heterogeneity is important to take into account, particularly when choosing the treatment upon the renal biopsy results from a single lesion.

Sunitinib in kidney cancer: 10 years of experience and development

ABSTRACT Introduction: Sunitinib is a multi-target, anti-angiogenic tyrosine kinase inhibitor and a key molecule in the treatment of metastatic renal cell carcinoma (mRCC). Since it first demonstrated its efficacy ten years ago, overall survival of mRCC has more than doubled, in part due to sunitinib. In most recent years, progress has been made in the comprehension of its mechanism of action and resistance. Areas Covered: In this article, clinical trials involving sunitinib in kidney cancer have been reviewed, defining its different indications in metastatic and localized RCC. The rationale of sunitinib’s efficacy, preclinical trials, past-clinical trials and ongoing clinical trials are summarized. Dose and scheme base are discussed, as the recommended dosage is frequently not well tolerated. Combination therapies appear to be toxic. Novel immunotherapies are changing the landscape of mRCC treatment and challenging sunitinib. Special attention has been paid towards cancer cell biology and immunity involved in treatment response. Expert Commentary: Sunitinib’s place in the therapeutic arsenal is being redefined with the arrival of major challengers. Dosage and scheduling of sunitinib remains a major challenge.

A single-tube, EuroClonality-inspired, TRG clonality multiplex PCR aids management of patients with enteropathic diseases, including from formaldehyde-fixed, paraffin-embedded tissues

Celiac disease is a chronic inflammation of the small intestine with villous atrophy that can become refractory to a gluten-free diet. Two categories of refractory celiac disease can be distinguished by the phenotype of intraepithelial lymphocytes and the status of TRG genes. Their distinction is important because 30% to 50% of type II but only 0% to 14% of type I evolve to an aggressive enteropathy-associated T-cell lymphoma and therefore require intensive treatment. Currently, differential diagnosis integrates immunohistochemistry, immunophenotyping, and TRG clonality analyses, but each has limitations. A single-tube multiplex TRG PCR (ECN) was prospectively compared to an in-house two-tube TRG PCR (N2T) in 73 samples, including 67 cryopreserved intestine tissues. Thirteen formalin-fixed, paraffin-embedded (FFPE) samples were also analyzed retrospectively. The ECN PCR had comparable efficiency to detect major clonal rearrangements in highly infiltrated tissues from T-cell lymphoproliferative disorders and type II refractory celiac disease and to detect the persistence of minor clones in type II refractory celiac disease follow-up samples. The ECN PCR abolished the risk of amplification of false-positive weak clonal rearrangements in cryopreserved specimens and allowed improved detection of clonal rearrangements in DNA from FFPE samples. The ECN PCR allows robust assessment of cryopreserved and FFPE digestive tissues at diagnosis and follow-up of enteropathies with villous atrophy, thus guiding therapeutic management.