Shaimaa S. Eissa, Egypt
Children’s Cancer Hospital-Egypt (57357) Pediatric OncologyPresenter of 2 Presentations
GENOTYPE-PHENOTYPE VARIATIONS AND SPECTRUM OF MALIGNANCIES IN PATIENTS WITH NOONAN SYNDROME: A REVIEW OF LITERATURE
Abstract
Background and Aims
Noonan syndrome (NS)the commonest RASopathy, autosomal dominant trait, characterized by short stature, craniofacial dysmorphism, congenital heart defects and susceptibility to cancer. A relationship is suggested between the underlying genotype and the apparent phenotype. The aim of this review is to examine NS’s genotype-phenotype variations and the spectrum of malignancies.
Methods
A review of previously published literature through PubMed database. Articles were chosen if they characterized NS, were available in English and were peer reviewed.
Results
Ninety-three articles met the inclusion criteria. NS was described as the commonest of an inherited overlapping group of disorders collectively known as “RASopathies”. Heterozygous mutations in PTPN11, SOS1, KRAS, NRAS, BRAF, SHOC2, CBL, and others were identified as leading etiologies through abnormal activation of the RAS-MAPK signaling that's also incriminated in oncogenesis. Forty-seven articles described abnormal myelopoiesis, particularly Juvenile Myelo-Monocytic Leukemia (JMML) as the commonest malignancies followed by CNS tumors. Solid tumors as neuroblastoma, chondroma and rhabdomyosarcoma were limited to case reports. The clinical features of NS were described in 21 articles and another 7 detailed its genotypic variations. Genotype-phenotype variabilities were described by many authors. Germline CBL mutations had increased risk of neurological disorders, JMML but lower risk for cardiac defects, growth retardation, and cryptorchidism. NRAS positive NS linked to hyperpigmentation. Neurofibromatosis-Noonan (NFNS) harbor both PTPN11 and neurofibromin mutations were described distinctly.
Conclusions
Available research suggests the relationship between the underlying genotype and the variably expressed phenotype in NS.Mutations in the RAS-MAPK pathway that are potential therapeutic targets,drive oncogenesis and should be molecularly identified in every patient.
UNUSUAL PRESENTATIONS OF HODGKIN LYMPHOMA
Abstract
Background and Aims
Paraneoplastic syndrome(s)(PNSs); A rare phenomenon charcterizes HL occurring months/years before diagnosis-typically an advanced stage with B symptoms-or preceding relapse.Aims:To evaluate the available evidence regarding PNSs in HL.
Methods
A systematic review of literature on paraneoplastic syndromes in HL according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The online database PubMed was searched using wth key words “paraneoplastic syndromes and Hodgkin lymphoma”, “vanishing bile duct syndrome in Hodgkin lymphoma” and “neurological manifestations in Hodgkin lymphoma”. Studies done on humans, published in the last 10 years were included.
Results
112 studies met the inclusion criteria. 23 review articles and 83 case reports were identified. The most common PNSs are the neurologic manifestations including paraneoplastic cerebellar degeneration (PCD),limbic encephalitis,Guillain-Barré syndrome,autonomic neuropathy and motor neuron disease.An immune related phenomenon is the proposed pathogenesis of PNSs supported by the presence of anti-Tr antibodies against Purkinje cells and anti-mGluR5 antibodies in the case of PCD and in HL and limbic encephalopathy (Ophelia syndrome) respectively. The most serious hepatic affection:Vanishing Bile Duct syndrome (VBDS) .Reported cases of toxic epidermal necrolysis, Stevens Johnson syndrome and angiokeratoma corpora diffusum were the most severe dermatologic manifestations. Early initiation of chemotherapy with high dose steroids and IVIG is the mainstay of tratment. Prognosis is unfavorable sometimes fatal as in VBDS progressing to liver cell failure.
Conclusions
The management of PNSs is challenging. Most available evidence is centered on the use of steroids, IVIG concomitantly with chemotherapy based on case reports and case series. Establishing evidence-based guidelines is mandatory to improve outcome.