Impact of choroid plexus size in prenatal diagnosis of normal and abnormal closure of fourth ventricle.

OBJECTIVE: To assess the role of the choroid plexus (CP) of the fourth ventricle (4V) in fetuses with an open 4V and a normal cerebellar vermis. METHODS: Two groups of patients were recruited in two fetal medicine referral centers. The prospectively collected control group included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome, recruited in the period between 2019 and 2022. The study group was selected retrospectively by searching our databases to identify all cases with an isolated open 4V and normal anatomy and size of the cerebellar vermis. The inclusion criteria of the study group were: (1) gestational age between 20 and 22 weeks; (2) a brainstem-vermis angle ≥ 18° in the midsagittal plane with an otherwise normal cerebellum and vermis; (3) 4V-CP visible and seen separately from the vermis; (4) absence of other intra- and extracranial anomalies; and (5) available prenatal and/or postnatal magnetic resonance imaging (MRI) data. RESULTS: In 169 cases of the control group, the 4V-CP was seen separately from the cerebellar vermis and was noticed to progressively fill the space caudal to the 4V, between the vermis and brainstem. From 12 to 22 weeks, the surface areas of the vermis and medial portion of the 4V-CP increased progressively with advancing gestation (P < 0.0001). Intra- and interobserver correlation analysis showed good reproducibility for the measurements. Among the cases with an open 4V and a normal vermis, it was retrospectively feasible to visualize the 4V-CP separately from the inferior part of the vermis in 41 fetuses. In five of these cases, the open 4V was due to a small CP. In all 41 fetuses, the diagnosis on MRI was isolated upward rotation of the cerebellar vermis, and no additional anomaly was found. CONCLUSIONS: Closure of the 4V is dependent on the 4V-CP and not only the cerebellar vermis. In fact, a small CP may represent another cause of an open 4V. Therefore, separate visualization of the 4V-CP and cerebellar vermis is crucial to improve discrimination between the different causes of an open 4V at the anomaly scan and its clinical implications. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Position of the choroid plexus of the fourth ventricle in first- and second-trimester fetuses: a novel approach to early diagnosis of cystic posterior fossa anomalies.

OBJECTIVE: To describe the sonographic appearance and position of the choroid plexus of the fourth ventricle (4V-CP) between 12 and 21 weeks' gestation in normal fetuses and in fetuses with Dandy-Walker malformation (DWM) or Blake's pouch cyst (BPC). METHODS: The study population comprised 90 prospectively recruited normal singleton pregnancies and 41 pregnancies identified retrospectively from our institutional database that had a suspected posterior fossa anomaly at 12-13 weeks' gestation based on the ultrasound finding of abnormal hindbrain spaces. In all cases the final diagnosis was confirmed by prenatal and/or postnatal magnetic resonance imaging or postmortem examination. All pregnancies underwent a detailed ultrasound assessment, including a dedicated examination of the posterior fossa, at 12-13 weeks, 15-16 weeks and 20-21 weeks of gestation. Two-dimensional ultrasound images of the midsagittal and coronal views of the brain through the posterior fontanelle and three-dimensional volume datasets were obtained. Multiplanar orthogonal image correlation with volume contrast imaging was used as the reference visualization mode. Two independent operators, blinded to the fetal outcome, were asked to classify the 4V-CP as visible or not visible in both normal and abnormal cases, and to assess if the 4V-CP was positioned inside or outside the cyst in fetuses with DWM and BPC. RESULTS: Of the 41 fetuses with apparently isolated cystic posterior fossa anomaly in the first trimester, eight were diagnosed with DWM, 29 were diagnosed with BPC and four were found to be normal in the second trimester. The position of the 4V-CP differed between DWM, BPC and normal cases in the first- and second-trimester ultrasound examinations. In particular, in normal fetuses, no cyst was present and, in the midsagittal and coronal planes of the posterior fossa, the 4V-CP appeared as an echogenic oval-shaped structure located inside the 4V apparently attached to the cerebellar vermis. In fetuses with DWM, the 4V-CP was not visible in the midsagittal view because it was displaced inferolaterally by the cyst. In contrast, in the coronal view of the posterior brain, the 4V-CP was visualized in all cases with DWM at 12-13 weeks, with a moderate decrease in the visualization rate at 15-16 weeks (87.5%) and at 20-21 weeks (75%). In the coronal view, the 4V-CP was classified as being outside the cyst in all DWM cases at 12-13 weeks and in 87.5% and 75% of cases at 15-16 and 20-21 weeks, respectively. In fetuses with BPC, the 4V-CP was visualized in all cases in both the midsagittal and coronal views at 12-13 weeks and in 100% and 96.6% of cases, respectively, at 15-16 weeks. In the coronal view, the 4V-CP was classified as being inside the cyst in 28 (96.6%), 27 (93.1%) and 25 (86.2%) cases at 12-13, 15-16 and 20-21 weeks, respectively. The medial segment of the 4V-CP was visualized near the inferior part of the vermis. CONCLUSIONS: Our study shows that longitudinal ultrasound assessment of the 4V-CP and its temporal changes from 12 to 21 weeks is feasible. The 4V-CP is located inside the cyst, just below the vermis, in BPC and outside the cyst, inferolaterally displaced and distant from the vermian margin, in DWM, consistent with the pathogenesis of the two conditions. The position of the 4V-CP is a useful sonographic marker that can help differentiate between DWM and BPC as early as in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Epidemiological, clinical and endoscopic features of epistaxis severity and quality of life in Hereditary haemorrhagic telangiectasia: a cross-sectional study.

BACKGROUND: Epistaxis is the main complaint in patients with Hereditary haemorrhagic telangiectasia (HHT). Even though the role of epistaxis in affecting the quality of life (QoL) is well-known, little is known about epidemiological and clinical factors contributing to epistaxis severity and QoL. METHODOLOGY: This is a cross-sectional study, including adult patients with HHT with epistaxis. All patients underwent an otolaryngological evaluation with nasal endoscopy. Epistaxis severity was graded using the FID score, and QoL was evaluated with the Short-Form Health Survey (SF-36). Descriptive statistics were produced for demographic characteristics; the Shapiro-Wilk test was used to test the normal distribution of quantitative variables. Correlation between the quantitative variables was evaluated with Pearson's correlation coefficient. Both univariate and multivariate linear regression models were fitted to find associations between demographic or clinical factors and the FID score or SF-36. RESULTS: A total of 234 patients with HHT were included in the study. The univariate analysis highlighted the association between high blood pressure, septal perforation, nocturnal epistaxis, surgery, blood transfusion, hormonal therapy and both FID score and QoL. Sex, allergic rhinitis and nasal polyposis were neither related to epistaxis severity nor perceived health. CONCLUSIONS: Epistaxis severity and QoL in patients with HHT are influenced by several clinical factors both dependent and independent from HHT. Some of the results are consistent with those already published, but for the first time, we extended the analysis to different clinical parameters, such as endoscopic findings, never assessed before.

FID Score: an effective tool in Hereditary Haemorrhagic Telangiectasia - related epistaxis.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia and epistaxis, that is the most common cause of disability and social impairment. Patient management strictly depends on the severity of this symptom; therefore, it is of paramount importance for the clinicians to effectively grade epistaxis severity. The aim of this report was to validate the Frequency, Intensity and Duration score (FID) for grading epistaxis severity in patients with HHT; we studied repeatability and external validity comparing FID score with Epistaxis Severity Score (ESS). METHODS: This is a descriptive, observational study that included 264 adult HHT patients with epistaxis. Diagnosis of HHT was established with Curacao criteria or positivity at genetic testing. Nosebleed severity was evaluated according to the FID score and the ESS. The first 30 patients were included in the validation of the FID score, which was graded on days 0, 1, 3 and 7. In the remaining 234 patients, a comparison between the ESS and FID score was performed. RESULTS: The statistical analysis performed in order to validate the FID score showed very good agreement between scores calculated on different days; analysis comparing the FID score with the ESS revealed a high correlation between the two grading systems. CONCLUSIONS: The FID score is a quick, easy and precise tool for evaluating HHT-related epistaxis and could be a possible alternative to the ESS. The FID score meets the need for an intuitive and smart grading system that is easy to manage in clinicians’ hands.

Bilateral Striatal Necrosis after Sydenham's Chorea in a 7-Year-Old Boy: A 2-Year Follow-Up.

Child bilateral striatal necrosis (BSN) is a rare and etiologically heterogeneous condition. An association with group A streptococcus (GAS) infection was previously reported in two cases of BSN in infancy and early childhood. We here report on a 7-year-old boy who developed chorea and dystonia 20 days after symptomatic recovery from Sydenham's chorea. Repeated brain magnetic resonance imaging scans, obtained before, soon after the onset of the post-Sydenham symptoms, and 1 year later were consistent with an evolution from bilateral striatal microbleeding to necrosis, and consequently reduced basal ganglia volume and enlargement of the frontal horns. No support was found for other possible autoimmune, infectious, metabolic, toxic or genetic etiologies for BSN. Prednisone treatment was instituted and continued for 1 year. Two years after the onset of the post-Sydenham symptoms, the child, although much improved, still has generalized dystonic-choreic movements. This case confirms and extends into school age, the link between GAS and BSN.

Non-invasive ventilation after surgery in amyotrophic lateral sclerosis.

BACKGROUND: Surgery in patients affected by amyotrophic lateral sclerosis (ALS) presents a particular anesthetic challenge because of the risk of post-operative pulmonary complications. AIMS OF THE STUDY: We report on the use of non-invasive ventilation (NIV) to prevent post-operative pulmonary complications (PPCs) in nine patients affected by ALS enrolled in a phase-1 clinical trial with stem cell transplantation. METHODS: All patients were treated with autologous mesenchymal stem cells implanted into the spinal cord with a surgical procedure. Anesthesia was induced with propofol and maintained with remifentanil and sevoflurane. No muscle relaxant was used. After awakening and regain of spontaneous breathing, patients were tracheally extubated. Non-invasive ventilation through nasal mask was delivered and non-invasive positive pressure ventilation and continuous positive pressure ventilation were started. RESULTS: The average time on NIV after surgery was 3 h and 12 min. All patients regained stable spontaneous breathing after NIV discontinuation and had no episodes of respiratory failure until the following day. CONCLUSIONS: Our case series suggest that the use of NIV after surgery can be a safe strategy to prevent PPCs in patients affected by ALS. The perioperative procedure we chose for these patients appeared safe even in patients with advanced functional stage of the disease.

Pediatric blunt renal trauma with wide fragments dislocation: successful organ saving management by internal stenting and percutaneous perirenal drain.

Children have an high risk of renal damage as a result of blunt trauma. Conservative management is always recommended for lower grades (I to III) but is rather controversial whenever high grade injuries (grade IV and V) are concerned. We describe a case of successful conservative management in grade IV renal injury occurred in a 9-years-old girl with blunt trauma.

Sacral sensory blockade from 27-gauge pencil-point dural puncture epidural analgesia or epidural analgesia in laboring nulliparous parturients: a randomized controlled trial.

BACKGROUND: The dural puncture epidural (DPE) technique has been associated with better sacral analgesia compared with a traditional epidural (EPL) technique in laboring parturients. The aim of this study was to investigate whether DPE with a 27-gauge pencil-point needle compared with a traditional EPL technique produces more rapid bilateral sacral blockade in nulliparous parturients. METHODS: Patients were randomized to a DPE or EPL technique. Epidural analgesia in both groups was initiated with ropivacaine 0.1% and sufentanil 0.5 µg/mL (15 mL) and maintained via programmed intermittent epidural boluses. Analgesic blockade was tested bilaterally beginning 10 min after initiation, and then at predefined intervals until delivery. The presence of an S2 blockade at 20 min was the primary outcome. RESULTS: Among 108 (54 per group) patients enrolled, bilateral sacral (S2) blockade at 20 min was significantly more common in the DPE than in the EPL group [47 (87%) vs. 23 (43%), absolute risk reduction (ARR) 44%, 95% CI 28 to 60; P < 0.001]. Time to a numeric pain rating scale score (0-10 scale) ≤ 3 (20 [20,30] min in both groups, HR 1.15, 95% CI 0.77 to 1.15; P = 0.50), number of rescue doses [0 (0, 1) vs 0 (0, 1); P 0.08], and presence of bilateral S2 blockade at delivery were not significantly different between groups. CONCLUSIONS: The DPE technique with a 27-gauge pencil-point spinal needle more often provides bilateral sacral blockade at 20 min following block initiation compared with the EPL technique. The time to adequate analgesia and need for supplemental analgesia did not appear to differ between techniques.

Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure.

BACKGROUND: As delayed intubation may worsen the outcome of coronavirus disease 2019 (COVID-19) patients treated with continuous positive airway pressure (CPAP), we sought to determine COVID-specific early predictors of CPAP failure. METHODS: In this observational retrospective multicentre study, we included all COVID-19 patients treated with out-of-ICU CPAP, candidates for intubation in case of CPAP failure. From these patients, we collected demographic and clinical data. RESULTS: A total of 397 COVID-19 patients were treated with CPAP for respiratory failure, with the therapeutic goal of providing intubation in case of CPAP failure. Univariable analysis showed that, age, lactate dehydrogenase (LDH) and white cell counts were all significantly lower in patients with successful CPAP treatment compared to those failing it and undergoing subsequent intubation. The percentage changes between baseline and CPAP application in the ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2), PaO2, respiratory rate and ROX index were higher in patients experiencing successful CPAP compared to those failing it. FiO2 and male gender were also significantly associated with intubation. Multivariable analysis adjusting for age, gender, Charlson comorbidity index, percentage change in PaO2/FiO2 or PaO2 and FiO2 separately, lactate, white blood cell count, LDH and C-reactive protein levels led to an area under the curve of 0.818 and confirmed that age, LDH and percentage increase in PaO2/FiO2 are predictors of intubation. CONCLUSIONS: In COVID-19 patients requiring CPAP, age, LDH and percentage change in PaO2/FiO2 after starting CPAP are predictors of intubation.

Cytokine modulators in the treatment of sarcoidosis.

Sarcoidosis is a granulomatous lung disease in which several cytokines play a pivotal pathogenetic role. Steroid-resistant disease can be treated with immunosuppressive drugs, antimalarial therapies and recently with anti-TNFα agents. The use of biological agents for the treatment of sarcoidosis springs from research into the pathogenesis of the disease and also from the experience of rheumatologists with other chronic inflammatory diseases. Rituximab, golimumab and ustekinumab are cytokine modulators, useful in the treatment of immunoinflammatory disorders, for which randomized trials to evaluate safety and efficacy in sarcoidosis are not yet available. Novel anticytokine drugs administered alone or in association may offer a new approach to treatment of the disease. This review focuses on recent advances in anti-TNFα agents and cytokine modulators for the treatment of sarcoidosis and their therapeutic prospects.

Rare localizations of bone sarcoidosis: two case reports and review of the literature.

Sarcoidosis is a multisystem disease of unknown origin. Granulomatous bone involvement has an overall incidence of 1-13%. This incidence is probably underestimated in certain patient series because bone involvement is often asymptomatic. The small bones of hands and feet are the most common localizations, while skull, knee, rib, pelvic and sternal localizations are rarely reported. Here we describe some interesting cases of chronic sarcoidosis with unusual bone localizations observed at our regional referral centre for sarcoidosis. We also review the literature to underline the complexity of the disease, the problem of differential diagnosis with respect to malignancies and the need for appropriate and effective therapy of this rare localization.

Contrast echocardiography for pulmonary arteriovenous malformations screening: does any bubble matter?

AIMS: To evaluate diagnostic accuracy of contrast echocardiography (CE) as compared with CT, for the screening of pulmonary arteriovenous malformations (PAVMs) in hereditary haemorrhagic telangiectasia (HHT); to evaluate the clinical significance of semi-quantitative analysis of a shunt on CE. METHODS AND RESULTS: A blinded prospective study was conducted in 190 consecutive subjects at risk of HHT who underwent screening for PAVMs, including clinical evaluation, pulse oximetry, standard and CE, and chest multirow CT without contrast medium. A semi-quantitative analysis of the shunt size was performed according to the contrast echo opacification of the left-sided chambers: Grade 0, no bubbles; 1, occasional filling with <20 bubbles; 2, moderate filling; 3, complete opacification. The first 100 patients were compared with 100 controls. A total of 119 (63%) patients had positive CE (32.2% Grade 1, 13.1% Grade 2, 11% Grade 3, 6.3% with patent foramen ovale). The overall diagnostic performance of CE was sensitivity 1.00, specificity 0.49, positive predictive value (PPV) 0.32, negative predictive value (NPV) 1.00. The PPV for the different grades was 0.00 for Grade 1, 0.56 for Grade 2, 1.00 for Grade 3; the NPV of Grade 0 was 1.00. A significant correlation was found between the CE grading and the number of PAVM, and complications (P < 0.0001). CONCLUSION: CE is an extremely sensitive procedure for the detection of PAVMs with substantial clinical impact.

A comparison of two protocols for optimal red blood cell depletion using Sepax-2 device for ABO-major incompatible transplantation in adults.

PURPOSE OF THE STUDY: In ABO-incompatible bone marrow transplantation, an efficient depletion of red blood cells (RBC) within the graft is mandatory to avoid adverse events in transplanted patients. Using non therapeutic products, we evaluated the substitution of the standard density gradient-based separation (DGBS) over Ficoll-Paque with the use of an automated procedure intended for buffy coat only (SmartRedux software) introducing modifications within the settings to achieve a drastic reduction of the initial volume of the product. Both methods were conducted on the Sepax-2 device. SAMPLES AND METHODS: RBC depletion rates and CD34+ cells recoveries from eight procedures with SmartRedux software using "in-house" settings (method A) were compared to those obtained from four procedures using NeatCell software, an automated DGBS over Ficoll-Paque (method B). RESULTS: Median erythrocyte depletion of 95,4% (92,7%-99,0%) and 99,8% (99,0%-99,9%) were observed using methods A and B, respectively. Median residual RBC volumes in the final product were 19 mL (4,4 mL-31,2 mL) and 0,7 mL (0,4 mL-4,7 mL), respectively (p = 0,014). CD34+ cells recoveries of 90,9% (62,7%-102,1%) and 78,4% (64,1%-86,2%) were achieved for methods A and B. Median platelet depletion was 16,6% (10%-42,7%) and 89,8% (88,5%-92,4%) using methods A and B, respectively (p = 0,004). Processing duration was shorter using method A (168 ± 29 min) than method B (295 ± 21 min) (p = 0,004). CONCLUSION: Both methods achieved satisfactory erythrocyte depletion and CD34+ recovery. The use of Sepax-2 device in association with SmartRedux software could be extended to efficiently deplete RBC from large-volume BM in a raw instead of DGBS.

Calgranulin B (S100A9) levels in bronchoalveolar lavage fluid of patients with interstitial lung diseases.

Calgranulins are small calcium-binding proteins with several immunological functions involved in inflammatory processes. Calgranulin A is reported to be mainly associated with acute inflammation while calgranulin B seems to play a role in chronic inflammatory disorders. In this study we used a proteomic approach to analyse calgranulin B expression in bronchoalveolar lavage (BAL) from a group of patients with different interstitial lung diseases. Two dimensional electrophoresis analysis of BAL was performed in 11 idiopathic pulmonary fibrosis patients, nine sarcoidosis patients, 11 with systemic sclerosis patients and five healthy controls. Significantly higher (p<0.001) calgranulin B percentage volumes were observed in BAL from IPF patients than controls and other ILD patients. This result sustains the hypothesis that calgranulin B could be involved in chronic lung diseases, probably through increased expression and enhanced activation of alveolar polymorphonuclear cells related to idiopathic pulmonary fibrosis. Quantitative analysis by an easier method applied to a larger population will be necessary to determine whether calgranulin B could be a good marker of disease severity.

Epstein-Barr Virus-Infected Plasma Cells Infiltrate Erosive Oral Lichen Planus.

Epstein-Barr virus (EBV), in addition to its transforming properties, contributes to the pathogenesis of several inflammatory diseases. Here, we investigated its involvement in oral lichen planus (OLP), a common autoimmune-like disease of unknown etiopathogenesis that can display a malignant potential. EBV-infected cells (EBV+ cells) were sought in a large series of clinically representative OLPs ( n = 99) through in situ hybridization to detect small noncoding EBV-encoded RNAs. Overall, our results demonstrated that EBV was commonly found in OLP (74%), with significantly higher frequency (83%) in the erosive form than in the reticular/keratinized type mild form (58%). Strikingly, many erosive OLPs were massively infiltrated by large numbers of EBV+ cells, which could represent a large part of the inflammatory infiltrate. Moreover, the number of EBV+ cells in each OLP section significantly correlated with local inflammatory parameters (OLP activity, infiltrate depth, infiltrate density), suggesting a direct relationship between EBV infection and inflammatory status. Finally, we characterized the nature of the infiltrated EBV+ cells by performing detailed immunohistochemistry profiles ( n = 21). Surprisingly, nearly all EBV+ cells detected in OLP lesions were CD138+ plasma cells (PCs) and more rarely CD20+ B cells. The presence of EBV+ PCs in erosive OLP was associated with profound changes in cytokine expression profile; notably, the expression of key inflammatory factors, such as IL1-ß and IL8, were specifically increased in OLP heavily infiltrated with EBV+ PCs. Moreover, electron microscopy-based experiments showed that EBV+ PCs actively produced EBV viral particles, suggesting possible amplification of EBV infection within the lesion. Our study thus brings conclusive evidence showing that OLP is commonly infiltrated with EBV+ PCs, adding a further puzzling element to OLP pathogenesis, given that PCs are now considered to be major regulatory immune cells involved in several autoimmune diseases (ClinicalTrials.gov NCT02276573).

Bone marrow failure may be caused by chromosome anomalies exerting effects on RUNX1T1 gene.

BACKGROUND: The majority of the cases of bone marrow failure syndromes/aplastic anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The peripheral blood picture is variable, with anaemia, neutropenia and/or thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid leukaemia (AML), as ascertained for all inherited BMFS. We already reported four patients with different forms of BMFS/AA with chromosome anomalies as primary etiologic event: the chromosome changes exerted an effect on specific genes, namely RUNX1, MPL, and FLI1, leading to the disease. RESULTS: We report two further patients with non-hereditary BM failure, with diagnosis of severe aplastic anaemia and pancytopenia caused by two different constitutional structural anomalies involving chromosome 8, and possibly leading to the disorder due to effects on the RUNX1T1 gene, which was hypo-expressed and hyper-expressed, respectively, in the two patients. The chromosome change was unbalanced in one patient, and balanced in the other one. CONCLUSIONS: We analyzed the sequence of events in the pathogenesis of the disease in the two patients, including a number of non-haematological signs present in the one with the unbalanced anomaly. We demonstrated that in these two patients the primary event causing BMFS/AA was the constitutional chromosome anomaly. If we take into account the cohort of 219 patients with a similar diagnosis in whom we made cytogenetic studies in the years 2003-2017, we conclude that cytogenetic investigations were instrumental to reach a diagnosis in 52 of them. We postulate that a chromosome change is the primary cause of BMFS/AA in a not negligible proportion of cases, as it was ascertained in 6 of these patients.

Liver involvement in hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber disease.

Hereditary haemorrhagic telangiectasia is a genetic disease characterised by the presence of teleangiectases virtually involving every organ. Hepatic involvement is represented by a spectrum of vascular abnormalities, which evolve in a continuum from tiny teleangiectases to substantial vascular malformations, potentially with a progressively greater arteriovenous shunt. Liver involvement in hereditary haemorrhagic telangiectasia is almost always asymptomatic; on the other hand, hepatic vascular malformations can induce severe complications, depending on the predominant venous side of the arteriovenous fistulas-high-output cardiac failure in the case of hepatohepatic fistulas, and portal hypertension in the case of hepatoportal fistulas. Doppler sonography can detect and stage hepatic vascular malformations in subjects with hereditary haemorrhagic telangiectasia; according to Doppler sonographic grading, appropriate advice for follow-up and/or therapy can be given.

Meiotic origin of trisomy in neoplasms: evidence in a case of erythroleukaemia.

Trisomic cells in neoplasms may represent abnormal clones originated from a tissue-confined mosaicism, and arise therefore by a meiotic error. We report on a 16-month-old child with erythroleukaemia (AML-M6), whose marrow karyotype at onset was 48,XX,del(13)(q12q14),del(14)(q22q32),+21,+21. The parental origin of the supernumerary chromosomes 21 was investigated by comparing 10 polymorphic loci scattered along the whole chromosome on the patient's marrow and her parents' leukocytes. Three loci were informative for the presence of three alleles, two of which were of maternal origin; two further loci showed a maternal allele of higher intensity. Lymphocytes and skin fibroblasts showed a normal karyotype, and molecular analysis on leukocytes at remission, buccal smear and urinary sediment cells consistently showed only one maternal allele, whereas neonatal blood from Guthrie spot showed two maternal alleles as in the marrow. An accurate clinical re-evaluation confirmed a normal phenotype. Our results indicate that tetrasomy 21 arose from a marrow clone with trisomy 21 of meiotic origin. To the best of our knowledge, this is the first evidence that supernumerary chromosomes in neoplastic clones may in fact be present due to a meiotic error. This demonstrates that a tissue-confined constitutional mosaicism for a trisomy may indeed represent the first event in multistep carcinogenesis.