Multiple oral and cerebral relapses of a Granular cell tumor (Abrikossoff Tumor) in a young girl affected by congenital dyserythropoietic anemia type II.

CASE REPORT: A 14-year-old girl presented with 1 cm large whitened lesion on the ventral surface of the tongue, appeared from 1 month. Past history showed congenital dyserythropoietic anemia type II. The lesion was excised and microscopic and immunohistochemical analyses were compatible with benign Abrikossoff tumor. Total body MRI was negative. After six months the patient presented a second tongue lesion and four months later another large painful lesion in the soft palate, with the same istological diagnosis. In addition, she had other multiple lesions: two apperead at pharyngeal level (not biopsied) that remain stable over time, and one at the pituitary gland. CONCLUSION: Granular cell tumors, with or without multiple lesions, are rare in children. About 50% of cases involve the head and neck region, with the tongue being the most affected site. Therapy is based on the surgical excision of the lesions; however some tumor forms, although their histological aspect of benignity, often have an important infiltrative power, making the therapeutic approach difficult, as in our case.

Extramedullary hematopoiesis in the facial sinus in a patient homozygous for Hemoglobin Lepore: the first case in literature.

Extramedullary hematopoiesis (EMH) is a proliferation of hematopoietic tissue outside the bone marrow. The most affected areas are paravertebral ones. We report the case of a patient with homozygous Hb Lepore, not regularly transfused since the age of four years until the age of 29 years, when paravertebral heterotopic masses were first observed. After about 10 years she started reporting clinical signs suggestive of sinusitis. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) showed heterotopic masses in the ethmoid and in the frontal sinuses. Involvement of the sinuses of the large facial area represents a rare localization of EMH. Various cases have been reported in patients with thalassemia intermedia, but no case has been reported with HbLepore. The diagnostic gold standard is MRI, which provides highly accurate and clear images. The treatment is based on hydroxyurea and/or an intensive transfusional regime and sometimes on surgery.

Retinal vein occlusion in child with rare mutations in genes for thrombophilia.

INTRODUCTION: Retinal vein occlusions (RVOs) are rare in the younger population. Hematological pro-thrombotic factors are thought to be important in a minority, amplifying an atherosclerotic anatomical predisposition. CASE REPORT: Anotherwise healthy 13-year-old girl presented two episodes of sudden decreased vision in few months.Ophthalmological exams pointed out post-thrombotic intra-retinal hemorrhage. All investigations were normal, thrombophilia screen showed factor XII deficiency and genetic mutations of methylenetetrahydrofolate reductase (MTHFR), angiotesin convertin enzyme (ACE) and angiotensinogen (AGT). Two intravitreal injection of bevacizumab was administered with improving visual acuity; subsequently the patient did not report further episodes. DISCUSSION: In addition to traditional factors with procoagulant activity, factor XII deficiency plays an important role in thrombosis's mechanism. Its deficiency causes a marked prolongation of the activated partial thromboplastin time in the laboratory examination. Moreover also MTHFR, ACE and AGT could have been involved in this case, so it is important to evaluate these parameters in the differential diagnosis of RVOs.

Do you remember scurvy?

Scurvy, a disease caused by a deficiency of ascorbic acid (vitamin C), is not very common disease especially in pediatric age. In the late nineteenth century, instead, we assisted to increase incidence of this problem for the use of heated milk and convenience foods. We report two cases of scurvy: a child of 3 years old came to our observation for an important gums' stomatitis, fever, widespread petechiae and ecchymosis on the skin of the lower limbs; in the second moment he had pain in upper and lower limbs with difficulty in walking; a second child of 4 years came to our observation for pain lower limbs and maintained the posture of the legs down, inability to walking, with reduced muscle tone and trophism in all limbs; at the instrumental examination he had an alveolar hemorrhage. The two boys had a history of a diet completely lacking in fruits and vegetables; they were drinking almost only milk. They carried various laboratory and instrumental tests, in particular X-ray of lower limbs that showed "a thick sclerotic metaphyseal line with beak-like excrescences of tibiae and femur". The characteristic radiological appearance, the particular clinical aspects, the dietary history and the dosage of vitamin C, have led us to the diagnosis of scurvy. They started therapy with vitamin C and they had a progressive improvement in general condition.

A case of spontaneous gastric rupture in a 5 years girl.

We describe a case of spontaneous gastric rupture in a child of 5 years old. The patient reached us in a serious condition; the anamnesis was negative for traumatic events or gastrointestinal disorders. An abdominal X-ray and CT scan revealed free air and fluid in the abdominal cavity, leading to the diagnosis of gastro-intestinal perforation. Submitted to urgent surgery, a rupture of the posterior wall of the stomach was found that was treated with gastrectomy "à la demande". The surgery follow-up was regular. Morphological and immunohistochemical study showed some muscular abnormalities of the muscular gastric wall.

Growth hormone deficiency in adults with thalassemia: an overview and the I-CET recommendations.

This review paper provides a summary of the current state of knowledge regarding GHD provides recommendations for the diagnosis and treatment of GHD in adult patients with thalassaemia major (TM). The reported prevalence of adult GHD and /or IGF-I deficiency in TM patients varies from 8% to 44 % in different centers. Because GH treatment requires analysis of many factors, including the effect of treatment on cardiac functions, metabolic parameters and psychosocial functioning, along with safety, ethical considerations, financial cost and other burdens of therapy, stringent diagnostic criteria are needed. The authors report the diagnostic recommendations of the International Study Group of Endocrine Complications in Thalassemia (I-CET) for adult TM patients.The pros and cons of GH treatment must be discussed with each patient, after which GH doses should be individualized and titrated to maximum efficacy with minimal side effects. Prospective studies to monitor potential benefits versus possible side-effects will enable endocrinologists to define recommendations on dosage and the long term effects, particularly on cardiovascular and bone status of GH therapy in adult TM patients.

International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow.

Most of the endocrine complications in thalassaemia are attributable to iron overload which may be the result of economic circumstances (expense of the chelation therapy), late onset of chelation therapy or poor compliance with the iron chelation therapy. The major difficulties reported by hematologists or pediatric endocrinologists experienced in thalassaemias or thalassaemia syndromes in following growth disorders and endocrine complications were: lack of familiarity with medical treatment of endocrine complications (40%), interpretation of endocrine tests (30%), costs (65%), absence of paediatric endocrinologist for consultation on growth disorders and endocrine complications (27%), facilities (27%), other (e.g. lack of collaboration and on-time consultation between thalassaemic Centers supervised by hematologists and endocrinologists) (17%). Because any progress we make in research into growth disorders and endocrine complications in thalassaemia should be passed on to all those suffering from it, guaranteeing them the same therapeutic benefits and the same quality of life, on the 8th of May, 2009 in Ferrara (Italy), the International Network on Endocrine Complications in Thalassemia (I-CET) was founded. The I-CET group is planning to conduct, in Ferrara in May 2012, a workshop, "MRI and Endocrine Complications in Thalassaemia", and in Doha (Qatar) in September 2012, a 3-day intensive course entitled, "Growth disorders and Endocrine Complications in Thalassaemia", to provide interested pediatricians, physicians and hematologists from all over the world with an in-depth approach to the diagnosis and management of growth and endocrine disorders in thalassaemic patients.

Assessment of traumatic brain injury and anterior pituitary dysfunction in adolescents.

Data from the Italian Ministry of Health show that approximately 300-500 per 100.000 Italians are admitted to hospital each year for either TBI or subarachnoid haemorrhage with an annual mortality of 20 per 100.000; 90% of these TBI are of medium severity. Traumatic brain injury-induced hypopituitarism in adults are more common than previously thought. The paucity of clinical reports relating to adolescents with past-TBI induced hypothalamic-pituitary-dysfunction suggests that this phenomenon might be less common that that observed in adults. In the last 25 years, in our Unit a pituitary dysfunction was established during childhood and adolescence in 3 patients (one patient had a precocious puberty, one patient had a gonadal dysfunction and one patient had a partial growth hormone deficiency). In all patients the TBI was severe (unpublished data, 2008). The physiopathological basis of hypopituitarism is lacking. Nevertheless, necrotic, hypoxic, ischemic and shearing lesions are at the hypothalamus and/or the pituitary are likely important factors. The subjects at highest risk appear to be those who have suffered a moderate or severe trauma. Clinical signs of anterior hypopituitarism are often subtle and may be masked by sequalae of TBI. Therefore, post-traumatic anterior pituitary dysfunction may remain undiagnosed and, possibly, aggravate symptoms of brain injury. Moreover it may, if undiagnosed, lead to potentially fatal endocrine crisis. Therefore, adolescents with moderate-severe traumatic brain injury should be screened for such endocrine deficiencies so that replacement therapy can be initiated to optimized the rehabilitation and outcome.

Growth and puberty in thalassemia major.

Present transfusional regimen protocols increase the life expectancy of patients with beta-thalassemia major, but cause a progressive iron overload that can be prevented or limited only by appropriate iron chelation. Siderosis is responsible for the clinical complications of the disease. Short stature and hypogonadism are extremely frequent in patients with thalassemia. Many factors are responsible for short stature in patients with thalassemia, the most important of which are dysfunction of the GH-IGF-I axis and desferoxamine (DFX)-induced bone dysplasia. Hypogonadism is the most frequent endocrine complication, mostly due to gonadotrophins deficiency secondary to iron overload. Sex steroid treatment for induction of puberty and/or maintenance of sexual characteristics is necessary. Both short stature and hypogonadism are present in a significant percentage of bone marrow transplanted patients with thalassemia. Factors responsible for short stature are previous iron overload, liver impairment, DFX treatment, and toxicity of chemotherapeutic agents. In some patients absence of pubertal development is due to gonadotropin insufficiency, probably secondary to previous iron overload; other patients exhibit hypergonadotrophic hypogonadism due to the toxic effect of chemotherapeutic agents on the gonads. Both groups need hormonal replacement therapy. These data support the need for vigilant follow-up of patients with thalassemia before and after transplantation, in order to treat endocrine dysfunctions at the appropriate age.

[Thoracic imaging in adolescence: news and perspectives]. / L'imaging toracico in età pediatrica adolescenziale: attualità e prospettive.

Technological advances modified actual trends in pediatric imaging. Up 25 years ago thoracic X-ray was the only resource in pediatric radiology. The introduction of CT, digital radiography, sonography and magnetic resonance and then of psitron emission tomography, led to a new dimension in thoracic pediatric imaging. In the future, new technological perspectives will make the functional study of the lung ventilation possible with techniques such as the 3-He hyperpolarized.

[Chest pain in adolescents]. / Il dolore toracico nell'adolescente.

In children and in adolescents, chest pain is relatively common and self-limiting. The close association between chest pain, cardiopathies and sudden death is the cause of intense anxiety in boys and their parents and even doctors. The most frequent causes of chest pain, the diagnosis and the eventual treatment are examined. Finally, the causes of chest pain due to drug abuse (in particular cocaine) and to CO poisoning are also examined. Good knowledge of the problem, an accurate anamnesis and a careful objective exam are useful to choose the most suitable treatment.

[Asthenia in adolescents]. / L'adolescente astenico.

Fatigue is defined as a subjective sensation of tiredness or weariness that occurs at rest. The perception of fatigue among 12-15 years-old Italian adolescents in a school survey was about 70%. Generally the symptoms are reported after a viral illness or an infection. In adolescents with persistent or severe fatigue a selected screening evaluation to look for an underlying organic disorder is warranted. A practical diagnostic approach is given and a brief description of chronic fatigue syndrome is reported according to CDC revised diagnostic criteria published in 1997.

Management of puberty for optimal auxological results in beta-thalassaemia major.

Short stature is present in a significant percentage of patients affected by beta-thalassaemia major. Growth failure of patients with thalassaemia is multifactorial. The most important contribution is attributed to the toxic effect of desferrioxamine and to endocrine disorders, due to iron overload. The commonest endocrine complication is hypogonadism. The growth pattern of patients with thalassaemia is characterized by normal growth during childhood, a deceleration of growth velocity around age 9-10 years, and a reduced pubertal growth spurt. In addition, reduced growth of the trunk is often present. Short stature and short trunk are more evident at pubertal age. Hypogonadism is usually considered responsible for the pubertal growth failure, as well as the aggravation of body disproportion at pubertal age. However, data suggest that pubertal height gain and final height are reduced in both patients with spontaneous puberty and patients with induced puberty. It is concluded that several aspects of peripubertal growth in patients with thalassaemia remain to be clarified.

Optimal therapy of pubertal disorders in precocious/early puberty.

GnRHa have been used in the treatment of central precocious puberty (CPP) for a decade and some final results of this therapy are now available. Treatment preserves height potential in younger patients and a complete recovery of the hypothalamic-pituitary-gonadal axis occurs at the end of treatment. However, some aspects of the management of CPP are still debated. Probably the age limits between normal and precocious puberty have to be lowered, and new diagnostic tools will modify and simplify diagnostic criteria. The possibility of progression of premature thelarche into precocious puberty, the pathogenesis of organic and idiopathic precocious puberty, the criteria for decision to treat and to stop treatment and the utility of an association with GH treatment will be better understood in the future. Follow-up of patients after stopping therapy includes frequency and characteristics of menses, the possible higher incidence of polycystic ovary-like syndrome and the correct achievement of a normal peak bone mass and body composition. In this review we discuss some of these points, with particular attention to precocious puberty in girls.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.