Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma - case series and literature review.

INTRODUCTION: Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy. MATERIAL AND METHODS: This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results. RESULTS: The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children. CONCLUSIONS: The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.

Adrenocortical carcinoma - 12-year observation period in a single centre. Case report with literature review.

BACKGROUND: Adrenocortical carcinoma (ACC) accounts for 0.2% of childhood malignancies. The most common symptom in children is rapidly progressive androgenization. Herein, we report a case of a patient with symptoms of hypercortisolaemia and androgenization, who was diagnosed with ACC. CASE PRESENTATION: In a 10-year-old patient with ACC the course of the disease was complicated by 3 recurrences. She was treated with surgery, chemo-, and radiotherapy. Currently, 8 years after the end of treatment, there have been no signs of recurrence. CONCLUSIONS: A patient after ACC treatment requires regular check-ups and long-term observation. Constant supervision enables early diagnosis of disease recurrence, and the use of treatment improves the prognosis.

Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone.

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97-100%) and 100% (95% CI: 96.15-100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24-98.13%) and 100% (95% CI: 93.94-100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.

Radical surgical treatment of neuroendocrine tumors of the appendix in children - a Polish multicenter study.

INTRODUCTION: The aim of the study was to examine management of pediatric appendiceal neuroendocrine tumors (ANETs) in Poland. METHODS: Records of 27 patients with ANET diagnosed incidentally after appendectomy in the last decade. RESULTS: Well-differentiated NET G1/G2 was diagnosed in 25 and well-differentiated neuroendocrine carcinoma G3 in 2 patients. Extended surgery was performed primarily in one instance and secondarily in 10 patients (right hemicolectomy in 9, ileocecal resection in 1) without adjuvant chemotherapy. Follow-up range was 1-121 months. Recurrence after secondary surgery was observed in 1 (3.7%) patient. CONCLUSIONS: Applying ENETS guidelines resulted in 100% overall survival of patients with NET.

Frequency assessment of BRAF mutation, KRas mutation, and RASSF1A methylation in nodular goitre based on fine-needle aspiration cytology specimens Ocena czestosci wystepowania mutacji genów BRAF, KRas oraz.

INTRODUCTION: Standard pre-operative diagnosis of nodular goitre is not always conclusive. The decision about nodular goitre surgery is increasingly based on molecular methods. The aim of the study was to determine BRAF T1799A mutation and KRas proto-oncogene mutation, and the analysis of RASSF1A promoter methylation level in cytological material obtained from FNAB specimens of thyroid nodules. MATERIAL AND METHODS: The study population consisted of 85 women and 12 men. The study material was genomic DNA isolated from peripheral blood and thyroid bioptates. Pyrosequencing was used for the evaluation of RASSF1 methylation level. KRas mutation was investigated with Sanger sequencing. BRAF mutation was analysed by standard methods of real-time amplification detection (real-time PCR) with the use of specific starters surrounding the mutated site. RESULTS: A significant positive correlation was demonstrated between mean methylation of four CpG islands of RASSF1A gene and thyroid tumour volume and its largest diameter (p < 0.05). KRas mutation was not detected in any of the 97 patients. In 7/85 subjects (8.2%) BRAF mutation was observed. In 6/7 patients with BRAF mutation, FNAB of thyroid nodules confirmed a benign nature of the lesions; the material was non-diagnostic in one patient, and papillary thyroid cancer was diagnosed on the basis of postoperative histopathology assessment. CONCLUSIONS: The results of genetic tests reported in our study indicate that the presence of BRAF mutation or higher RASSF1A methylation levels in FNAB cytology specimens of benign lesions may be useful in the assessment of oncological risk, while the evaluation of KRas proto-oncogene mutation is not a valuable test in pre-operative diagnosis of nodular goitre.

Two histologically different tumours in a neonate born from an assisted reproductive technology pregnancy.

The first case of a female neonate born from an in vitro fertilization with embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI) (IVF-ET (ICSI) with two histologically different tumours (craniopharyngioma and hepatoblastoma) is described. Anti-neoplasmatic therapy was abandoned due to the significant extent of the disease (craniopharyngioma, 15 x 12 cm in diameter with active internal hydrocephalus; and right liver lobe hepatoblastoma, 5 cm in diameter) and the severely impaired general condition of the neonate. The neonate died on the 30th day of life due to cerebellar and brainstem herniation, followed by circulatory and respiratory failure.

Effect of interleukin 6 deficiency on the expression of Bcl-2 and Bax in the murine heart.

Interleukin 6 (IL-6) is a pleiotropic cytokine that is highly expressed in response to ischemia and reperfusion. It has dichotomous roles in the heart, functioning both as an inflammatory mediator as well as a protective agent. The aim of this study was to evaluate the effect of IL-6 deficiency on the expression of apoptotic regulatory proteins under both baseline conditions and following induction of ischemia and reperfusion in the mouse heart. C57BL/6J IL-6-/-(TMKopf) (IL6KO) and C57BL/6J mice (WT) were subjected to 30 minutes of local reversible myocardial ischemia in vivo or a sham operation. The expression of Bcl-2, Bax and STAT3 in the heart was assessed by western blotting. Under both baseline conditions and following the sham operation, IL-6 deficiency was associated with reduced expression of Bcl-2 and Bax. The TUNEL-FITC, Evans blue and tetrazolium chloride staining of the hearts following ischemia and reperfusion revealed similar injury in operated IL6KO and WT animals. There was increased STAT3 phosphorylation in operated mice regardless of the genotype. Bcl-2 and Bax expression was also comparable between the mouse strains following ischemia and reperfusion. In summary, these results indicated that IL-6 deficiency affected the basal expression of apoptotic regulators, but this did not profoundly alter the extent of reperfusion injury or apoptosis in the mouse heart following ischemia and reperfusion.