Introduction: Follicular-derived differentiated thyroid carcinoma (DTC) is the most common endocrine and epithelial malignancy in children. The differences in the clinical and pathological features of pediatric vs. adult DTC could relate to a different genetic profile. Few studies are currently available in this issue, however, and most of them involved a limited number of patients and focused mainly on radiation-exposed populations. Materials and Methods: We considered 59 pediatric patients who underwent surgery for DTC between 2000 and 2017. RET/PTC rearrangement was investigated with fluorescent in situ hybridization and real-time polymerase chain reaction. Sequencing was used to analyze mutations in the BRAF, NRAS, PTEN, PIK3CA genes, and the TERT promoter. The pediatric patients' clinical and molecular features were compared with those of 178 adult patients. Results: In our pediatric sample, male gender and age <15 years coincided with more extensive disease and more frequent lymph node and distant metastases. Compared with adults, the pediatric patients were more likely to have lymph node and distant metastasis, and to need second treatments (p < 0.01). In all, 44% of the pediatric patients were found to carry molecular alterations. RET/PTC rearrangement was confirmed as the most frequent genetic alteration in childhood DTC (24.6%) and correlated with aggressive features. BRAFV600E was only identified in 16% of the pediatric DTCs, while NRASQ61R, NRASQ61K, and TERTC250T mutations were very rare. Conclusions: Pediatric DTC is more aggressive at diagnosis and more likely to recur than its adult counterpart. Unlike the adult disease, point mutations have no key genetic role.
We report the case of a 3-year-old girl admitted to her town emergency department for fever (39°C) associated with diarrhea, generalized edema, oliguria, and drowsiness. The blood test revealed metabolic acidosis, leucocytosis, increased inflammatory markers, anemia, thrombocytopenia, and acute kidney failure. Based on the diagnosis of hemolytic-uremic syndrome, the patient was referred to a third-level children hospital. Assisted ventilation, hemodialysis, and parenteral nutrition were instituted. The blood glucose levels increased above 200 mg/dl with peaks at 500 mg/dl. Islet auto-antibodies were negative and C-peptide was undetectable, thus ruling out the diagnosis of type 1 diabetes. Multiple-daily-injection insulin therapy was then instituted with the following regimen: Detemir 2 U once daily and Aspart 0.5 U if blood glucose >200 mg/dl. Despite the very low insulin dosage, the patient experienced frequent and severe hypoglycemic events during the following 24 h and was therefore switched to sensor-augmented pump therapy. Optimal glucose control was achieved without further hypoglycemic episodes. Moreover, thanks to the possibility to customize insulin therapy hour by hour during the day and the use of a pre-low glucose suspend system, glucose control was maintained even despite the continuous modifications in the nutritional scheme due to the multiple complications that arose during hospitalization. This rare case of post-hemolytic-uremic syndrome diabetes, treated with sensor-augmented therapy from its outbreak, suggests for the first time the potential of this therapeutic strategy in achieving glucose control without significant hypoglycemic episodes in children with secondary forms of diabetes associated with very low insulin requirement.
Early detection of child maltreatment in pediatric emergency department is one of the most important challenges for the Italian and European medical care system. Several interventions have been proposed, but results are often unquantifiable or inadequate to face this problem. We promoted an educational program and built up an interdisciplinary team to improve the identification and management of maltreated children. Aim of this study is to report preliminary results of these interventions. Meetings structured with lecture-based teaching and case-based lessons were focused on identification and management of maltreatment cases. An interdisciplinary team with forensic physicians, dermatologists, orthopedics, radiologists, gynecologists, oculists, psychologists and psychiatrics, was created to manage children with suspected diagnosis of maltreatment. We analysed the characteristics of subjects diagnosed after these interventions and their number was compared with the one in the two previous years. An increased rate of diagnoses of 16.9 % was found. Results of the reported program are encouraging, but many efforts are still mandatory to improve the child maltreatment identification in emergency departments.
Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support.This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC).This was a retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33-56 y) and median follow-up time of 37 months (interquartile range, 15-82 mo).The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P < .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC > CPTC ≫ FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66), and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07-11.11) and 14.96 (95% CI, 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old.This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC ≫ FVPTC, providing important clinical implications for specific variant-based management of PTC.
Background Differentiated thyroid carcinoma is the most common endocrine neoplasm; several studies have shown that individuals perceive the disease as being more severe than it actually is, resulting in a reduced quality of life. The primary aim of this study is to assess the quality of life and perception of illness among patients admitted for radiometabolic therapy, post total thyroidectomy for differentiated thyroid carcinoma. The secondary aim is to identify which patient characteristics are associated with a lower quality of life in order to improve and personalize care. Methods The study was conducted at the UOC of Radiotherapy Veneto Institute of Oncology IOV-IRCCS in Padua, Italy. Three questionnaires were administered: Psychological General Well-Being Index (PGWBI), the Illness Perception Questionnaire (IPQ-R) and the Short Form Survey (SF-12). A descriptive statistics analysis and multiple linear regression models were performed to explore the relationship between some of the variables. Results Significant associations emerged between the type of surgery and higher values on the PGWBI questionnaire (P = 0.022) and the score obtained in the ‘emotional representations’ dimension of the IPQ-R questionnaire (P = 0.028). Pathology staging was statistically significantly (P = 0.026) associated with the score obtained in the dimension ‘identity’; age with the scores obtained in the dimensions ‘emotional representations’ (P = 0.035), ‘personal control’ (P = 0.004), ‘consistency with pathology’ (P < 0.001) and ‘causes’ (P = 0.004). Conclusions There is evidence of moderate distress in psychological well-being and good perception of pathology. There is less understanding of the disease in individuals with stage 3 and 4 thyroid cancer, in those who have undergone total thyroidectomy without lymphadenectomy and who are aged over 60. Physical well-being: limitations in self-care and moderately physically demanding activities. Mental health: more information to patients decreases the degree of stress and promotes ‘positive’ emotions. Physical health status: a long-term activity program, characterized by aerobic exercises to be performed in groups or at home, is useful. This study allows to transpose the results into clinical practice, evaluating the possibility and methods of providing personalized care to patients.
Pituitary metastases are found in about 1% of all pituitary resections. They often derive from breast, lung, and gastroenteric tract adenocarcinomas, very rarely from thyroid carcinoma. Presenting symptoms of thyroid carcinoma metastatic to the pituitary gland are usually chiasmatic with central neurological impairment due to space-occupying expansion in the parasellar region. Hypopituitarism is more often associated with papillary and medullary rather than follicular thyroid carcinoma (FTC). Here we describe a patient with pituitary metastasis from FTC who had hypopituitarism with thyrotropin (TSH) deficiency.A 61-year-old woman, who presented with visual deficits and pain to the right orbit, was found on magnetic resonance imaging to have a large mass involving the pituitary gland. She was found to have pituitary insufficiency based on corticotropin-releasing hormone and TSH-releasing hormone testing. Transnasopharyngeal biopsy of the mass revealed metastases from FTC. After total thyroidectomy, which confirmed widely invasive FTC, the patient underwent external beam radiation therapy of the metastases for progressive neurological symptoms and an increase in orbit pain. Since endogenous TSH production was insufficient, we used recombinant human TSH (rhTSH) as preparation for a series of radioiodine treatments. rhTSH administration, followed by 7.4 GBq of (131)I, was repeated seven times over a 10-year period. This was associated with a marked decrease in serum thyroglobulin levels accompanied by substantial clinical improvement, but after 7 years disease progression occurred.Seven patients with pituitary metastases from FTC have been reported. In all cases, some neurological signs and symptoms related to mass effect were reported, but no pituitary insufficiency was described. This may be the first case of FTC with metastases to the pituitary causing hypopituitarism. It seems likely that management of such cases could be limited to biopsy to confirm thyroid carcinoma, rather than more extensive surgery, and that this could be followed by multiple treatments with rhTSH followed by (131)I.
May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder in the spectrum of myosin heavy chain-related disorders (MYH9-RD), characterized by congenital macrothrombocytopenia and white blood cell inclusions. MHA carries a potential risk of hemorrhagic complications. Bleeding diathesis is usually mild, but sporadic, life-threatening events have been reported. Data regarding the clinical course and outcomes of neonatal MYH9-RD are limited, and specific guidelines on platelet transfusion in asymptomatic patients are lacking. We present monochorionic twins born preterm at 32 weeks of gestation to an MHA mother; both presented with severe thrombocytopenia at birth. Peripheral blood smear demonstrated the presence of macrothrombocytes, and immunofluorescence confirmed the diagnosis of MHA. Close clinical monitoring excluded bleeding complications, and serial hemostatic assessments through a viscoelastic system demonstrated functionally normal primary hemostasis in both patients. Therefore, prophylactic platelet transfusions were avoided. Whole DNA sequencing confirmed the pathogenetic variant of MHA of maternal origin in both twins. Thromboelastography allowed real-time bedside bleeding risk assessment and supported individualized transfusion management in preterm newborns at risk of hemostatic impairment. This report suggests that dynamic and appropriate clotting monitoring may contribute to the more rational use of platelets' transfusions while preserving patients with hemorrhagic complications and potential transfusion-related side effects.
Background: The primary goal of papillary thyroid cancer (PTC) management was to stratify patients at pre- and post-surgical level to identify the small proportion of cases with potentially aggressive disease. Purpose: The aim of our study is to evaluate the possible role of programmed cell death 4 (PDCD4) and BRAF status as prognostic markers in PTC. Patients and methods: We investigate programmed cell death 4 (PDCD4) immunohistochemical expression in 125 consecutive PTCs with median follow-up of 75.3 months (range, 15–98 months) to verify the possible correlation between BRAF status and correlate the classical clinicopathological prognostic factors and PTC outcome with PDCD4 expression. To further support the data, miR-21 expression was tested (by quantitative real-time PCR and in situ hybridization) in a different series of 30 cases (15 PTCs BRAFwt and 15 PTCs BRAFV600E). Moreover, we validated our results using TGCA thyroid carcinoma dataset. Results: We found that 59.8% of the patients showed low-grade PDCD4 nuclear expression and low-grade expression correlated with BRAF V600E. Compared with BRAF 15 wild-type tissue samples, a significant miR-21 up-regulation was associated with BRAF V600E mutations. Low-grade PDCD4 resulted, and was associated with aggressive histological variants, higher cancer size, extra-thyroidal extension, multifocality, lymph-node metastasis and lymph nodal ratio at the diagnosis. Concerning the outcome, the low-grade PDCD4 expression correlated at univariate and multivariate analysis, with lower levels of recurrence-free survival rate (RFS) and with poor outcome. Moreover, there was significant association between BRAF V600E patients with PDCD4 nuclear loss and lower RFS, whilet here was significant association between BRAF wild-type patients with PDCD4 nuclear expression and better outcome. Conclusion: These results showed that PDCD4 could predict PTC outcome and that the sum of PDCD4 and BRAF alterations increases the prognostic power of BRAF mutation alone. Keywords: papillary thyroid cancer, PDCD4, BRAF , outcome
