Prenatal Features of MIRAGE Syndrome-Case Report and Review of the Literature.

MIRAGE syndrome is a recently described congenital condition characterized genetically by heterozygous gain-of-function missense mutations in the growth repressor sterile alpha domain containing 9 (SAMD9) located on the arm of chromosome 7 (7q21.2). The syndrome is rare and is usually diagnosed in newborns and children with myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy, hence the acronym MIRAGE. The aims of this paper are (1) to present fetal ultrasound features in a case where MIRAGE syndrome was diagnosed prenatally and (2) to review the existing literature records on prenatal manifestations of MIRAGE syndrome. In our case, the fetus had severe early fetal growth restriction (FGR) with normal Doppler studies, atypical genitalia, oligohydramnios, and hyperechogenic bowel at the routine mid-gestation anomaly scan. Amniocentesis excluded infections and numeric or structural chromosomal abnormalities while whole exome sequencing (WES) of the fetal genetic material identified the specific mutation. Targeted testing in parents was negative, suggesting the "de novo" mutation in the fetus. We could not identify other specific case reports in the literature on the prenatal diagnosis of MIRAGE syndrome. In cases reported in the literature where the diagnosis of MIRAGE syndrome was achieved postnatally, there are mentions related to the marked FGR on prenatal ultrasound. Severe early-onset FGR with no other apparent cause seems to be a central prenatal feature in these babies, and WES should be offered, especially if there are other structural abnormalities. Prenatal diagnosis of MIRAGE syndrome is possible, allowing for reproductive choices, improved counseling of parents, and better preparation of neonatal care.

Preconceptional Counseling in Women with Hyperthyroidism.

Preconception evaluation of couples wishing to conceive is an important step toward a healthy pregnancy and it is especially important in people with a chronic condition or at genetic risk. The most common endocrine disorders in women at reproductive age are those involving the thyroid gland and it is well recognized that hyperthyroidism (HT), over-function of the thyroid gland, is associated with risks of maternal, fetal, and neonatal complications. The aim of this paper is to review the latest evidence regarding the components of preconception counseling in women with HT that contemplate a pregnancy. We also want to raise awareness among healthcare professionals about the importance of periconceptional counseling in improving pregnancy outcomes and avoid maternal and fetal complications related to thyroid dysfunction. In women with Graves' disease seeking pregnancy, it is essential to discuss all the treatment options along with the associated risks and benefits. Extensive prospective studies are still needed to understand the implications of current recommended strategies for the management of HT in preconception and during pregnancy.

The Significance of CD20 Intensity Variance in Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia.

B-cell precursor acute lyphoblastic leukemia (ALL) is a common pediatric malignancy and patients may have significant benefits from monoclonal antibodies therapy with increased survival rates. Positive CD20 expression is identified in about half of these patients and its presence may serve as a prognostic factor in disease evolution. We performed a retrospective study including 114 patients diagnosed with B-ALL and evaluated the expression of CD20 through flow cytometry at diagnosis and on day 15. Additional immunophenotypic analyses as well as cytogenetic and molecular genetic analyses were also performed. We observed an increase in the mean fluorescence intensity (MFI) of CD20 between diagnosis-1.9 (1.2-3.26) and day 15: 6.17 (2.14-27.4), (p < 0.0001). Furthermore, we assessed that both diagnosis and day 15 CD20 MFI had an impact on RFS and OS, respectively, for cut-off values of >8.08 at diagnosis and >28.65 at day 15. In conclusion, CD20 expression appears to be a poor prognostic feature of B-ALL in pediatric patients. In this study, stratification of the outcome by the intensity of CD20 has implications concerning the allocation to rituximab-based chemotherapy and may offer new, potentially useful information for pediatric patients with B-ALL.

Assessment of peripheral blood cells parameters as a valuable tool in patients with neuroendocrine neoplasms.

OBJECTIVES: Neuroendocrine neoplasms (NENs) are an extremely heterogeneous medical entity, representing a diagnostic and therapeutic challenge. Chronic inflammation, as is the case with other malignancies, plays a crucial role in NEN carcinogenesis. DESIGN: The complete blood count (CBC) is a reliable tool for monitoring patients with cancer. Quantifying the absolute count of neutrophils (N), lymphocytes (L), platelets (P), and the ratios that derive from these parameters (neutrophil-to-lymphocyte ratio - NLR, platelet-to-lymphocyte ratio - PLR, and inflammatory systemic index - SII calculated as N×P/L) proved their prognostic and predictive value in numerous malignancies. MATERIALS AND METHODS: We aimed to investigate the utility of these hematological parameters in 31 patients with NENs of various locations. Our study included the comparative analysis of pre-treatment hematological markers in NEN patients versus 21 age and gender matched healthy individuals. Additionally, for 26 out of the 31 patients included we analyzed and compared the inflammatory markers before and after treatment initiation. RESULTS: The results revealed a statistically significant higher median value of N, NLR, PLR and SII in the NENs group in comparison with the values obtained in the control group and higher values of N, NLR and SII in the pretreatment group. Furthermore, we observed a higher mean value of the post-treatment P in the pancreatic NENs as opposed to the values obtained for other tumor locations. CONCLUSIONS: The current study emphasizes the importance of the evaluation of CBC in the NENs setting thus adding value to prognostic models that can be useful for risk stratification and medical decision-making.

Long-term thyroid disorders in pediatric survivors of hematopoietic stem cell transplantation after chemotherapy-only conditioning.

BACKGROUND: Thyroid dysfunction (TD) was usually described in hematopoietic stem cell transplantation (HSCT) recipients who were given total body irradiation (TBI) in the conditioning regimen. Because previous studies have reported discrepant results regarding the presence of long-term thyroid complications in HSCT survivors following chemotherapy-only conditioning, we investigated the frequency of thyroid abnormalities in a series of children treated with HSCT for different disorders without TBI as part of the conditioning protocol. METHODS: We compared thyroid-stimulating hormone, free thyroxine, total triiodothyronine (TT3), anti-peroxidase (TPO Ab) and anti-thyroglobulin antibodies and thyroid volume z-score in 28 HSCT survivors and 16 healthy subjects matched for age and sex. RESULTS: HSCT recipients had a higher frequency of TD and thyroid complications in total, including TD and euthyroid Hashimoto thyroiditis, compared to the control group. Patients transplanted for Hodgkin lymphoma (HL) were more likely to develop a thyroid complication compared to patients with non-malignant hematologic diseases and leukemia patients. BEAM (carmustine, etoposide, citarabin and melphalan) conditioning compared to busulfan (Bu) and fludarabine (Flu)-based regimens and autologous compared to allogenic grafting were associated with a higher prevalence of TD in our study. HSCT survivors had higher mean serum TT3 levels. A multivariate analysis revealed that autologous (auto)-HSCT recipients had higher mean serum titers of TPO Ab compared to allogenic (allo)-HSCT recipients and controls and the mean thyroid volume z-score was significantly higher in controls compared to auto-/allo-HSCT survivors. CONCLUSIONS: We identified a 35.7% prevalence of thyroid abnormalities, emphasizing the need for a long-term surveillance of thyroid function and morphology even in this group of patients who were not exposed to TBI.

Graves' orbitopathy after allogeneic bone marrow transplantation in a patient with Fanconi anemia - side effect of alemtuzumab therapy?

A few cases of thyroid eye disease following alemtuzumab therapy have been described in patients with multiple sclerosis. Our patient is the first case of Graves' orbitopathy after alemtuzumab conditioning for hematopoietic stem cell transplantation.

Perspectives on the co-treatment with GnRHa in female patients undergoing hematopoietic stem cell transplantation.

Outcomes after hematopoietic stem cell transplantation (HSCT) for patients with both malignant and nonmalignant diseases have improved significantly in recent years. However, the endocrine system is highly susceptible to damage by the high-dose chemotherapy and/or irradiation used in the conditioning regimen before HSCT. Ovarian failure and subsequent infertility are frequent complications that long-term HSCT survivors and their partners face with a negative impact on their QoL. Several meta-analyses of randomized clinical trials showed that gonadotropin-releasing hormone agonist (GnRHa) administration in advance of starting standard chemotherapy decreases the risk of gonadal dysfunction and infertility in cancer patients, but GnRHa use for ovarian protection in HSCT patients is not fully determined. In this review, we are discussing the potential preservation of ovarian function and fertility in pubertal girls/premenopausal women who undergo HSCT using GnRHa in parallel with conditioning chemotherapy, focusing on the current data available and making some special remarks regarding the use of GnRHa.

Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy in acromegalic patient with severe headache.

A 68-year-old female patient was admitted in our clinic with severe frontal bilateral headache, dizziness, depression and cognitive decline in the context of a previously diagnosed acromegaly. She also had high blood pressure, dyslipidemia, secondary diabetes mellitus. Acromegaly was caused by a growth hormone (GH) secreting-pituitary macroadenoma, so a transsphenoidal surgery was performed. The postoperative magnetic resonance imaging (MRI) scan revealed a 20÷22÷25 mm pituitary mass remnant and medical therapy with somatostatin analogues (SSAs) was started. After nine months of treatment with SSAs, she continued having severe headache, the blood pressure was well controlled, but GH secretion was only partially controlled with insulin-like growth factor-1 (IGF-1) level still above the normal value. The MRI scan showed the same pituitary tumor remnant with supra- and parasellar right extension and also multiple fronto-temporo-parietal subcortical lesions that could suggest in the clinical context cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). According to a pregenetic screening tool, the Pescini Scale, the patient had a 19 points score, which is highly suggestive for CADASIL, an inherited cerebrovascular disease due to mutations of the Notch3 gene at the chromosome locus 19p13. In the absence of genetic testing, an alternate way to prove small vessels disease, the skin biopsy, was performed. Electron microscopy showed granular osmiophilic material (GOM) surrounding the vascular smooth muscle cells on that are pathognomonic for the disease. Our report underscores the importance of repeated investigations even in patients with apparently obvious explanations of their condition since they may have multiple diseases with the same presenting clinical signs.

Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

BACKGROUND: A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. CASE PRESENTATION: A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. CONCLUSIONS: The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.