Rare within Rare: A Girl with Severe Haemophilia A and Turner Syndrome.

A coincidental occurrence of severe haemophilia A and Turner syndrome in a female person is extremely rare (less than 10 cases published). In such challenging cases, a multidisciplinary approach based on medicine of precision with full access to genetic and bio-molecular exploration is indispensable. The article presents an eight-year-old girl, with a family history of haemophilia, without significant disease signs (only post-dental extraction bleeding and a shorter stature). Discordantly, however, the investigations revealed a challenging condition: a genotype of 46,X,i(Xq), with an Isochromosome Xq responsible for the Turner syndrome and simultaneously, for the detrimental transformation, interfering with X chromosome inactivation, of an obligate hemophilia carrier into a severe hemophilia case-two distinct and provocative diseases.

Challenges in the Diagnosis and Management of Non-Severe Hemophilia.

(1) Background: Mild and moderate hemophilia, synonymous with non-severe hemophilia (NSH), are of constant interest for the clinicians. Bleeding occurs usually after trauma, injury, surgery, or inhibitor development, sometimes leading to a shift of the clinical phenotype from mild to severe, even with life-threatening and unexpected outcomes. (2) Methods: We performed a retrospective observational study conducted on 112 persons with congenital coagulopathies, 26 of them with NSH, admitted to our clinic in the period 2000 to 2022. For the diagnosis, we used laboratory studies (complete blood cell count, coagulation assays, biochemistry, thromboelastography, genetic tests) and imaging investigations (X-ray, ultrasound, CT, MRI). We selected four cases confronted with pitfalls of diagnosis and evolution in order to illustrate the sometimes provocative field of NSH. (3) Results: Confronted with challenging cases with under-, missed or delayed diagnosis and severe consequences, we aimed at presenting four such selected cases with mild or moderate hemophilia, real pitfalls in our clinical activity. (4) Conclusions: In the field of NSH, if not timely recognized, tending sometimes to remain ignored by caregivers and patients themselves, we can be confronted with challenging diagnostic situations and life-threatening bleeds.

Role of imagistic techniques in diagnosing soft-tissue vascular anomalies in pediatric population - a 5-year experience.

Soft-tissue vascular anomalies have a worldwide estimated prevalence of 4.5% in the pediatric population. From January 1, 2014 until December 31, 2018, imagistic and histological evaluations were performed in 214 patients aged between one day and 18 years old, who were diagnosed with different soft-tissue vascular anomalies in our Center. From the 214 patients included in the study, 36.45% (n=78) were males, 63.55% (n=136) were females and 37.38% (n=80) of the patients were less than one year of age at time of admission. Infantile hemangioma was the most frequent type of soft-tissue vascular anomaly (35.51%) and the face was the most frequent affected region (25.7%). Ultrasound (US) examination is the most used imaging technique due to its wide accessibility and for providing valuable information about the anatomical localization of the lesions, the type of vessels involved, distribution and density of vascularization. Magnetic resonance imaging (MRI) can be used for assessing the extent of deep or large lesions, but it usually requires anesthesia. Computed tomography (CT) is useful when patients present contraindications to anesthesia and it has the advantage of a shorter image acquisition time. Histological studies have an important role in establishing the diagnosis even for the atypical cases of soft-tissue vascular anomalies. Furthermore, the prognosis depends on the histological type. In conclusion, there is a need for collaboration between the clinician, radiologist, pathologist and surgeon in order to establish a precise diagnosis and therapeutic strategy for each patient.

Type II pleuropulmonary blastoma in a 2-year-old girl: a case report.

Pleuropulmonary blastoma (PPB) is a very rare, malignant aggressive primary lung tumor, which occurs mainly in children less than 5 years old. Due to its poor prognosis, it is aggressively treated with multimodal therapy including surgery and chemotherapy. We present a case of PPB in a 2-year-old girl who was brought to the pediatric clinic for fever, cough and respiratory distress. Imaging studies showed a heterogeneous solid-cystic mass (12∕9∕11 cm) in the upper right pulmonary lobe. Through right thoracotomy, a specimen was obtained, the histopathological and immunohistochemical features of the specimen being suggestive for type II PPB. Aggressive chemotherapy and right pneumonectomy resulted in control of disease, the patient being currently in complete remission four years after the diagnosis.

Expression and significance of Ki-67 in lung cancer.

Ki-67 parameter is a proliferation marker in malignant tumors. The increased proliferation activity and the decreased prognosis in lung cancer determined us to investigate different parameters connected to the tumor's aggression, such as cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen (PCNA). We evaluated the proliferative activity in 62 primary lung tumors by determining the cell's percentage of Ki-67 and immunoreactive PCNA (using MIB-1 and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into three score groups. The results obtained emphasized a linkage between Ki-67 score with the histological tumor subtype, tumor cellularity and degree of differentiation and with other proliferation immunohistochemistry (IHC) markers, such as p53 cellular tumor antigen. The tumor's cellularity, the Ki-67 positivity rate and PCNA, together with the clinical stage and the histological differentiation bring extra pieces of useful information in order to anticipate the evolution and the prognosis of lung cancer.

Expression of E-cadherin in lung carcinoma, other than those with small cells (NSCLC).

It was suggested that the decrease and/or loss of E-cadherin expression in non-small cell lung cancer (NSCLC) is responsible for the development of the malignant phenotype. Moreover, clinical studies showed that the reduced expression of E-cadherin is associated with tumoral differentiation, with the presence of lymph node metastasis and with unfavorable diagnosis of patients with NSCLC. In order to evaluate if E-cadherin expression is involved in the NSCLC pathogenesis and significantly associated with clinicopathological parameters, we investigated the immunohistochemical (IHC) expression of E-cadherin in 47 lung carcinomas with tumoral resection pieces in the control peritumoral lung tissue, looking for possible correlations between the expression of this molecule and the clinicomorphological features and the evolutive prognosis of the patients. E-cadherin expression was preserved in 10 (21.28%) of the 47 NSCLCs immunostained with anti-E-cadherin antibody and reduced÷absent in 37 of the 47 (78.72%) NSCLCs studied. E-cadherin plays a major role in the intercellular adhesion. The reduced expression of E-cadherin indicates an unfavorable prognosis and can be a useful prognosis factor in NSCLC - for patients with reduced expression of the E-cadherin÷α-catenin complex, needing chemotherapy or radiotherapy.