Recurrence of a Pheochromocytoma With TNEM127 Mutation Negative on 18F-FDOPA and 18F-FDG but Positive on 123I-MIBG and 68Ga-DOTATOC Imaging.

ABSTRACT: We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18F-FDOPA and 18F-FDG PET/CT scans but strongly positive on 123I-MIBG scintigraphy and on 68Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18F-FDOPA shows very high sensitivity and specificity. However, 18F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68Ga-DOTATOC imaging could be an alternative.

Atypical Presentation of Testicular Adrenal Rest Tumor (TART) Leading to Bilateral Partial Orchiectomy in a 31-Year-Old Adult Revealing Primary Adrenal Insufficiency with CYP11A1 Deficiency.

Adrenogenital syndrome is commonly associated with a deficiency in 21-hydroxylase but can be present in other rare enzymatic blocks. We report here the case of a 31-year-old man who presented with bilateral painful testicle lesions leading to bilateral partial orchiectomy as they were suspected for malignancy. These lesions were finally identified as benign testicle adrenal rest tumors (TARTs), and the patient was actually belatedly diagnosed with primary adrenal insufficiency due to 2 mutations of the CYP11A1 gene encoding the cholesterol side-chain cleavage enzyme (P450scc); the mutations were 940G > A (p.Glu314Lys) and c.1393C > T (p.Arg465Trp). The same mutations were found in his 29-year-old sister, who was then also diagnosed for primary adrenal insufficiency. Deficiency in P450scc is an extremely rare genetic autosomal recessive disorder with around 40 described families in the literature and 30 different mutations. As the diagnosis of delayed onset of P450Scc mutation is difficult, this case illustrates the need for a systematic endocrinological assessment in any case of bilateral testicle lesions, thus avoiding unnecessary surgery.

MET overexpression and activation favors invasiveness in a model of anaplastic thyroid cancer.

In thyroid cancers, MET receptor overexpression has been associated with higher risk of metastatic progression. In this study, it was shown that the anaplastic thyroid cancer (ATC)-derived TTA1 cell line overexpressed MET. By using FISH and relative quantification by qPCR, it was demonstrated that this overexpression resulted from a MET amplification with more than 20 copies. As expected, MET overexpression led to its constitutive activation and upregulated signaling towards the MAPK, PI3K/AKT, STAT3 and NF-κB pathways. Since the usual feature of MET-amplified cell lines is the "MET addiction" for their cell proliferation, the effect of the highly selective ATP competitive MET inhibitor PHA665752 was analyzed. While PHA665752 strongly inhibited the MAPK pathway, it did not reduce cell proliferation in TTA1 cells (IC50 = 4100 nM). This resistance to PHA665752 of the TTA1 cell line was demonstrated to be related to EGFR-MET functional cross-talk and PI3K/AKT and NF-κB signaling. Nevertheless, PHA665752 suppressed the anchorage-independent growth capacity of the TTA1 cell line and reduced cell migration and invasion in a transwell assay. The role of activated MET in these neoplastic properties of the TTA1 cells was also proved with si-MET-RNA targeting. Thus, this work highlights the TTA1 cell line as the first model of MET amplification in an ATC cell line, which leads to MET constitutive activation and underlies its neoplastic properties. Besides being a useful model for MET inhibitors screening, the TTA1 cell line also supports the argument for searching for MET amplification in ATC, as it could have therapeutic implications.

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas.

OBJECTIVES: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. DESIGN: Multicenter retrospective study by members of the French Society of Endocrinology. METHODS: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. RESULTS: The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. DISCUSSION: Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols.