Castleman disease: surgical cure in pediatric patients

Castleman disease is a rare disorder characterized by lymphoid hyperplasia which rarely manifests in children. We present 2 cases which highlight both histologic variants of this disease, and provide suggestions regarding workup and treatment with the goal of making practitioners aware of Castleman disease in the differential diagnosis of a child presenting with vague symptoms.     

Neuroendocrine mechanisms that delay and initiate puberty in higher primates

This paper highlights a series of studies using the male rhesus monkey that has led to a model for the control of the onset of puberty in higher primates. The model proposes that the timing of puberty in these species is governed by the duration of a central brake that, during juvenile development, holds in check the hypothalamic network of gonadotropin-releasing hormone (GnRH) neurons, which, in the adult, drive the pituitary-gonadal axis. The neurobiology of this hypothalamic brake, and the physiological mechanisms that time its application and removal, are incompletely understood. Nevertheless, the pubertal resurgence of pulsatile GnRH release, which terminates the juvenile phase of primate development and triggers the initiation of puberty in man and monkeys, is associated with structural and molecular remodeling of the hypothalamus. A major component of this developmental plasticity appears to involve neuropeptide Y (NPY). NPY inhibits GnRH release, and NPY gene expression in the hypothalamus is elevated during juvenile development when GnRH release is restrained. Since the changes in hypothalamic function and morphology that trigger primate puberty unfold in the absence of gonadal steroid feedback, the possibility is raised that, in addition to activating the pituitary-gonadal axis at this stage of development, they may also contribute directly to the causation of behaviors and affective states that emerge at adolescence.     

Mesenteric panniculitis does not confer an increased risk for cancers: A systematic review and meta-analysis

Background:Mesenteric panniculitis (MP) is a non-specific, localized inflammation at the mesentery of small intestines which often gets detected on computed tomography. An association with malignant neoplasms remains unclear. We performed a systematic review and meta-analysis to examine the association of malignancy with MP.Methods:MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for articles published from inception to 2020 that evaluated the association of malignant neoplasms with MP in comparison with control groups. Using random-effects method, a summary odds ratio (OR) estimate with 95% confidence intervals for malignant neoplasms in MP was estimated.Results:Four case-control studies reporting data on 415 MP patients against 1132 matched-controls met inclusion criteria and were analyzed. The pooled OR for finding a malignant neoplasm in patients with MP was 0.907 (95% CI: 0.688–1.196; P = .489). The heterogeneity was mild and non-significant. Also, there was no heightened risk of any specific type of malignancy with MP. Three more case-series with unmatched-control groups (MP: 282, unmatched-controls: 17,691) were included in a separate analysis where the pooled OR of finding a malignant neoplasm was 2.963 (95% CI: 1.434–6.121; P = .003). There was substantial heterogeneity in this group.Conclusion:This meta-analysis of matched controlled studies proves absence of any significant association of malignant neoplasms with MP. Our study also demonstrates that the putative association of malignancy with MP is mainly driven by uncontrolled studies or case-series.     

Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population

CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.     

Evidence for a physiological role of gonadotropin-releasing hormone (GnRH) or GnRH-like material in the ovary

The possibility that GnRH or a GnRH-like material of ovarian origin may play a physiological role in follicular development was explored in immature hypophysectomized rats by testing whether a potent synthetic antagonist of GnRH action [( N-acetyl-dehydro-Pro1,D-p-chloro-Phe2,D-Trp3,6]GnRH), would potentiate FSH-induced maturation of ovarian follicles to an ovulable stage. Rats were hypophysectomized on day 25 of their life and implanted with a Silastic capsule containing diethylstilbestrol. On day 30, they were started on injections of 10 micrograms NIH FSH-S12 twice daily alone (control) or in combination with 10 micrograms of either native GnRH or GnRH antagonist. On day 35, all rats received 30 IU hCG to trigger ovulation and luteinization of mature follicles. Rats were killed 25.5-28 h later and inspected for number of ova in Fallopian tubes, ovarian weight, number of corpora lutea (CL) on ovarian surface, and appearance of hematoxylin-eosin-stained ovarian slices. In control animals (n = 6), we found some ovulations (mean +/- SEM, 3.2 +/- 1.1/rat), many more CL (16.5 +/- 4.5/rat), and ovarian weights of 37.7 +/- 1.1 mg/rat. In GnRH-treated rats (n = 5), there were no CL formed, no ova were found, and ovarian weights were 16.0 +/- 1.5 mg/rat. In contrast, in GnRH antagonist-treated rats (n = 5), 16.4 +/- 1.6 ova/rat were recovered from the Fallopian tubes, and ovaries contained 20.8 +/- 2.5 CL/rat and weighed 52.7 +/- 3.2 mg/rat. All changes were statistically significant. We conclude that an antagonist of GnRH action is able to potentiate the action of FSH on ovarian follicle development and suggest that it does so by inhibiting the action of an endogenous GnRH or GnRH-like substance that may play a role as a physiological atretic signal.