A case report of desmoplastic infantile astrocytoma/ganglioglioma in an infant: the gentle giant

Brain tumours are the most frequent solid tumours and the first cause of cancer-related death in childhood. Their diagnosis has been increasing due to the improvement of diagnostic tools. Low-grade gliomas and embryonal tumours are the most frequent (50% and 20%, respectively). A 10-month-old male presented with hyporeactivity, drowsiness, right arm hypomobility and inappetence. Hospitalised, his Fundus Oculi which showed papilla with regular margins, lightly congested and raised. EEG revealed slow track and specific activity in the back left temporal region. Gadolinium-MRI of the brain revealed a cystic tumour of 7 × 9×12 cm, with intense and heterogeneous enhancement that involved the left cerebral hemisphere. The mass compressed the left and third ventricle and the brainstem was shifted beyond the median line. The right ventricle was expanded and there was sweating of cerebrospinal fluid for the Monro’s foramen obstruction. The patient underwent complete exeresis of tumour. Histology confirmed diagnosis of Desmoplastic Infantile Astrocytoma/Ganglioglioma (DIA/DIG), grade I WHO. Immunophenotype: astrocytic (GFAP, Vimentin), neuronal (synaptophysin). MIB-1: 5%. After hospitalisation, the patient started rehabilitation with a gradual recovery of motor functions. Actually at 30 months of follow up the patient is free of disease and healthy. DIA/DIG is a rare paediatric brain tumour (1.25% of brain tumours), characterised by divergent glioneuronal differentiation and intense desmoplasia. Superficial in location and affecting mainly the frontotemporal region, it presents as a large, cystic, often dura-attached mass in patients younger than 2 years of age. On MRI, they are large hypodense cystic masses with a solid isodense or slightly hyperdense superficial portion. The histologic diagnosis is characterised by the presence of astrocytic, neuronal, and primitive neuroectodermal markers. The treatment of choice is radical surgical excision, which does not require additional treatment. Post-operative clinical and MRI controls should be used when only partial tumour removal can be performed; indeed, long-term stability or complete disappearance of the tumour residual may follow even an incomplete surgical tumour removal. Chemotherapy is used in partial exeresis and progressive disease; radiotherapy is a last resource. DIA/DIG diagnosis is crucial as they share some neuroradiological and histological findings of malignant brain tumours

Autoimmune lymphoproliferative syndrome (ALPS) in a child: a new disorder to ‘climb’

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the Fas apoptotic pathway. It can present with a wide range of clinical manifestations, including noninfectious nonmalignant lymphoadenopathy, splenomegaly and autoimmune pathology (frequently autoimmune citopenias). Revised diagnostic criteria allowed an improvement in its management. A 3-year-old boy was hospitalised for severe isolated thrombocytopenia (PLT 8000/mcl) and hemorragic syndrome. On physical examination, he had inguinal limphoadenopathy. His blood exams showed positivity for autoimmunity and normal lymphocyte population. Bone marrow aspirate revealed an immune throbocytopenia, so he started treatment with Immunoglobulins (Ig), with a good response. We performed an exeresis of his inguinal lymph node, increasing in dimensions, and found reactive follicular hyperplasia with dermatopathic aspects in absence of neoplasy. After one month, thrombocytopenia associated with neutropenia (N 800/mcl), positivity of direct and indirect Coombs test, anti-neutrophils antibodies negatives and splenomegaly on sonography. He assumed steroids for 2 weeks, with a good response. After 4 months, he presented again with thrombocytopenia, associated with emolitic autoimmune anaemia (Hb 5,2 g/dl) so he began therapy with Ig and steroids, with initial good response. Two months after stop therapy, new episode of thrombocytopenia, hemorragic syndrome and an increase of his splenomegaly. Therefore, we performed FAS-induced apoptosis test (negative) and researched double negative lymphocites that were positive (CD3+TCRαβ+CD4-CD8-:3,5%; CD19+CD27+:4,8%; CD3+CD25+/CD3+HLADR+ ratio:0,1%). He started therapy with mycophenolate mofetil and with Ig on demand. As we obteined a poor response, we shifted it to syrolimus, with progressive reduction of splenomegaly and increase of PLT. ALPS is a rare pathology that should be investigated in children with autoimmune citopenias and nonmalignant limphoproliferation. Its various clinical manifestations complicate diagnosis and treatment. First line treatment includes prednisone and Ig; for unresponsive patients mycophenolate mofetil and syrolimus are effective, the latter in children with refractory multilineage autoimmune cytopenias. Research over the past decades have increased our knowledge on its pathophysiology resulting in an improvement of its management. Its diagnosis is indeed crucial as ALPS may progress to lymphoma

Un esordio insidioso di epatite autoimmune

Bambina di 9 anni veniva ricoverata presso la Pediatria di altro Ospedale per tosse persistente. Anamnesi personale e familiare muta. All’esame obiettivo importante splenomegalia ed epatomegalia. Gli esami ematici evidenziavano pancitopenia (GB 3830/mcl, Hb 9,5 g/dl, PLT 81000/mcl), coagulazione alterata (PT INR 1,62), transaminasi aumentate (GPT/GOT 372/1274 UI/l), indici di flogosi e Rx torace negativi. Nel sospetto di malattia ematologia, veniva trasferita presso l’Oncoematologia pediatrica del nostro Ospedale. Veniva eseguita un’ecografia addominale con ecocolordoppler con riscontro di epatomegalia con ecostruttura disomogenea e splenomegalia (dl 19 cm) con asse splenoportale di calibro aumentato, epatopeto come da ipertensione portale. Aspirato midollare, ceruloplasmina, alfa1antitripsina, esami infettivologici per virus epatotropi negativi; mentre riscontro di ipergammaglobulinemia, iperIgG, segni di deficit di sintesi epatica con modesta coagulopatia ed iperbilirubinemia diretta, positivita di ASMA, ANA ed ANCA. Un esame obiettivo mirato mostrava cute subitterica, eritema palmare e spider nevi al volto ed agli arti superiori. Nel sospetto di epatite autoimmune (EA), la piccola veniva trasferita nella nostra UOC di Pediatria e sottoposta a biopsia epatica con esame istologico compatibile col sospetto diagnostico. A completamento si eseguivano Colangio-RM, ileo-colonscopia ed EGDS che escludevano, rispettivamente, alterazioni a carico dei dotti biliari, MICI e segni endoscopici di ipertensione portale. Si avviava terapia con prednisone, vitamina K ed acido ursodesossicolico. L’iniziale follow-up ha documentato una rapida e brillante risposta alla terapia. L’EA e una patologia infiammatoria progressiva del fegato ad eziologia sconosciuta, caratterizzata da incremento di transaminasi, gammaglobuline ed autoanticorpi e, istologicamente, da epatite da interfaccia. In base al tipo di autoanticorpi si distinguono due tipi di EA: tipo 1 (ANA e/o SMA); tipo 2 (LKM1 e/o LC1). Devono essere escluse altre cause di epatopatia con quadro sovrapponibile (epatiti virali, malattia di Wilson, NAFLD, deficit di alfa1antitripsina, epatiti da farmaci)1,2. Nel 40% dei casi l’esordio puo essere insidioso con astenia, malessere, prurito, artralgie, addominalgia ed ittero incostante. Inoltre, puo essere caratterizzato dal riscontro accidentale di aumento delle transaminasi in assenza di sintomi specifici, in corso di indagini per altra patologia. In una minoranza di casi l’EA si puo presentare con splenomegalia e pancitopenia, che possono orientare per malignita oncoematologiche2. L’EA risponde bene alla terapia immunosoppressiva se iniziata tempestivamente. Una rapida e completa remissione indotta con appropriata terapia migliora la prognosi, controllando l’evoluzione della fibrosi. Pertanto, e fondamentale considerare l’EA anche nei quadri piu sfumati dal momento che una diagnosi ritardata comporta un trattamento tardivo con maggiore probabilita di evoluzione verso il trapianto di fegato

TICK WITH TREAT

Ticks can determine various local reactions, among which scarring and nonscarring inflammatory alopecia. We describe a case of nonscarring alopecia in a two-year-old girl of Romanian origin who reported a recent history of tick bite. She referred to our pediatric department with diffuse alopecia of the scalp, in which there was an erythematous nodule, presumed site of the tick bite accursed two months prior. She did not develop fever, arthralgias or other systemic symptoms. In order to exclude autoimmune diseases and infectious etiologies, we performed laboratory exams, such as anti-thyroid, antinuclear, anti-transglutaminase, TORCH and anti-Borrelia antibodies, resulted negative. A punch biopsy specimen from the scalp (0.4×0.3×0.2 cm) revealed fibrosis of the derma and the peripheric areas of pili-sebaceous annexes. The following month, we observed a rapid centrifugal progression to total alopecia. Thus, we decided to attempt therapy with topic corticosteroids followed by a progressive hair regrowth during the following four months. Tick bite alopecia was first described in 1921. Since then, a few other cases have been reported in the international literature. The characteristic manifestation is a single zone of alopecia, often with a centrifugal spread, that appears 1–2 weeks after the tick removal. Sometimes, it can be associated with a central eschar, representing the site of tick bite. The nonscarring forms of alopecia manifest as ‘moth-eaten’ patches or, in alternative, as nodular or blood-crusted lesions. Clinically, patients may present with pain, pruritus or swelling. The precise mechanism for hair loss is not well understood but it is assumed to be caused by the host inflammatory response to tick saliva antigens. The result is the destruction of hair follicles or the alteration of the catagen/telogen phase. Histologic findings may show a heterogeneous inflammatory infiltrate and areas of fibrosis. The international literature does not report effective therapy for tick bite alopecia, while treatment with topic corticosteroids for alopecia areata is recognized. Prognosis is favourable with a complete hair regrowth usually within 3 months, although in some cases alopecia is reported to persist for 5 year

Benign neonatal pustolosis (BNP) / TO WORRY OR NOT TO WORRY

Benign neonatal pustolosis (BNP) comprehend a group of clinical diseases characterized by transient pustules or vescico-pustular lesions on newborn skin. These are asymptomatic and self-limiting conditions including benign cephalic pustolosis (BCP). A 40 days old girl was conducted to our Pediatric Unit for the appearance of multiple vescico-pustular lesions with serous sterile content on her forehead. She was born at term, had a regular perinatal period and never reported cutaneous problems. No lotions or creams for and after her baths were used and no direct contact to sunlight was described. At the time of consultation, she was in excellent health conditions. On suspicion of BCP, we did not prescribe exams or local and/or systemic treatments but indicated a strict follow-up with clinical revaluation after 3 days. At follow-up, the infant did not have clinical problems and her pustular lesions had begun to disappear. After 7 days, all pustules had completely disappeared without leaving any scar. Dermatosis that occur during the neonatal period can be infectious or sterile, such as BNP. Frequently, BNP are secondary to a physiological skin response or to environmental factors. They are benign, self-limited, asymptomatic cutaneous conditions that present during the first days of life. Their diagnosis is clinical but, sometimes, can require some investigations, principally non-invasive, to exclude more severe diseases. BNP include erythema toxicum neonatorum, transient neonatal pustular melanosis and BCP. BCP was first described by Aractingi in 1991. There is no consensus about its prevalence, which is estimated between 10% and 60%. Its presentation is asymptomatic and self-limiting and is characterized by numerous papules and pustules located on the face and scalp with onset between 5 days and approximately 3 weeks of age of the newborn. Numerous studies evaluated the possible role of Malassezia in the etiopathogenesis of BCP. Nevertheless, this correlation has not been demonstrated so far. In conclusion, the presence of pustules in newborns is always a reason of concern for parents and doctors, since neonatal skin is more vulnerable to bacterial, viral and fungal infections. These lesions can be a real challenge for clinicians who have to recognize serious diseases requiring hospitalisation from benign transient conditions, avoiding superfluous exams, treatments and worrie

A case of unsuspected pulmonary emboli in child with lymphoma

Background Pulmonary embolism (PE) is a potentially lethal condition. Although it’s usually manifested with severe symptoms causing right ventricular dysfunction or haemodynamic instability, in case of partial arterial obstruction it can be asymptomatic. Cancer patients are at high risk of thromboembolic complications. The use of contrast-enhanced computerised tomography for cancer staging has documented a high incidence of asymptomatic PE. Case presentation We present a case of unsuspected PE in paediatric oncology patient. A 10-year-old boy presented with cervical and axillary lymph node swellings. No response to antibiotic therapy. Infectivological tests (mononucleosis, tuberculosis, toxoplasmosis…) were negative. Staging imaging revealed a positron emission tomography/computed tomography (PET-CT) avid anterior mediastinal lymph node. There weren’t liver, spleen and lung injury. Excisional biopsy of the lymph node was consistent with an anaplastic large cell lymphoma ALK+, t(2;5). After positioning of central venous catheter (CVC), the patient began treatment with chemotherapy with reduction of the lymphadenopathy. Subsequently, repositioning of CVC due to malfunction and displacement. After three months, he performed restaging; CT showed bilateral thromboembolism of the pulmonary arteries with partial obstruction. Echocardiogram showed a blood pressure’s increase in pulmonary artery (PAP 38 mmHg) but the child didn’t present respiratory and cardiac symptoms. Echo-color-doppler didn’t report venous thrombosis of the legs. Laboratory tests showed high platelet count. d-dimer levels and activated partial thromboplastin time value were increased. Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) were normal. The patient discontinued chemotherapy and started standard anticoagulant treatment. Two weeks later, CT and ultrasound controls displayed substantial reduction of the obstruction of the pulmonary arteries and decrease of PAP. Conclusions Thromboembolic complications are frequent in children with lymphoma. Often, routine thoracic MDCT examinations of paediatric oncology patients reveal cases of unsuspected PE. It is necessary to identify children at an increased risk for the development of PE to define an appropriate management. However, recent studies have showed that the lack of diagnosis and treatment do not have a negative influence on patient outcome

UN CASO PRESSANTE DI LEISHMANIOSI

P.A., 7 anni 9 mesi, da 5 giorni astenia, febbre e addominalgie successive a trauma accidentale. Condotta in PS, vengono eseguiti esami ematici e TAC addome con riscontro di epatomegalia e splenomegalia (dl circa 30 cm). La piccola viene trasferita presso la U.O.C. di Chirurgia Pediatrica nel sospetto di rottura splenica. In tale sede, esclusa l’ipotesi chirurgica, per il riscontro di pancitopenia (GB 1570/ mcl, Hb 6 gr/dl, PLT 50.000/mcl) si inviava la paziente presso la nostra U.O.C. di Oncoematologia Pediatrica. All’ingresso in reparto la piccola presentava febbre (TC 38,8°C) e astenia. L’emocromo confermava la pancitopenia, l’ETG addome la splenomegalia (dl 25 cm). Si eseguiva aspirato midollare con evidenza di numerosi parassiti negli istiociti. L’esame sierologico è risultato positivo per leishmaniosi viscerale, (L. infantum, sierologia positiva:1/2560 (IFI)). Ha quindi iniziato trattamento con Ambisome (AmB, 3mg/kg per 5 gg) con miglioramento generale e riduzione della splenomegalia. Al gg+7 dalla terapia, comparsa di stato di incoscienza, areflessia, sguardo lateralizzato con pupille normoreagenti. All’EEG: “crisi subentranti con clonie oculari a dx>sn, talora suppresion burst”. Esegue RMN encefalo: “aree di alterato segnale che coinvolgono le regioni cerebrali parieto-occipitali ed il ponte: quadro suggestivo di Posterior Reversible Syndrome (PRES).” Trasferita in Rianimazione, ha iniziato terapia con IgHD e desametasone con miglioramento progressivo fino alla risoluzione dei segni clinici e dell’imaging. Nonostante la mancata somministrazione della 6° dose di AmB prevista al gg+10, si è assistito alla guarigione completa della parassitosi. La PRES è stata attribuita a tossicità farmacologica da Ambisome, antimicotico a veicolo liposomico, Nelle regioni del Mediterraneo, è il farmaco di scelta per il trattamento della Leishmaniosi viscerale, con efficace risposta e capacità di impedire recidive parassitarie. Tuttavia, l’Ambisome può causare disfunzioni renali, ipokaliemia, febbre e raramente una leucoencefalopatia, talora progressiva e fatale. Tale neurotossicità, dose correlata, è secondaria al legame del farmaco con la mielina, che provoca un aumento della permeabilità di membrana e dispersione delle componenti intracellulari. In conclusione, questo caso evidenzia l’importanza di tre elementi fondamentali nel percorso diagnostico- terapeutico della leishmaniosi viscerale in soggetti di età evolutiva: 1) la diagnosi differenziale con condizioni associate ad importante splenomegalia e simile presentazione clinica (ie: leucemie, linfomi, anemia emolitica, malaria, febbre tifoide, tubercolosi miliare, endocardite batterica, brucellosi, ipertensione portale); 2) un attento monitoraggio nella gestione terapeutica, tenendo presente i costi-benefici di un adeguato trattamento, anche se potenzialmente tossico; 3) l’accurata identificazione dell’agente eziologico, di grande importanza nel trattamento farmacologico perché specie diverse che infettano lo stesso tessuto possono presentare differente suscettibilità ad un determinato farmaco. Bibliografia 1. Sato M, Hirayanagi K, Makioka K, Ikeda Y. Reversal of leukoencephalopathy induced by liposomal amphotericin B in a patient with cryptococcal meningitis. J Neurol Sci. 2015 Mar 15;350(1-2):118-9. 2. di Martino L, Davidson RN, Giacchino R, Scotti S, Raimondi F, Castagnola E, Tasso L, Cascio A, Gradoni L, Gramiccia M, Pettoello-Mantovani M, Bryceson AD. Treatment of visceral leishmaniasis in children with liposomal amphotericin B. J Pediatr. 1997 Aug;131(2):271-7. 3. Antonini G, Morino S, Fiorelli M, Fazi P, Ceschin V, Petti C. Reversal of encephalopathy during treatment with amphotericin-B. J Neurol Sci. 1996 Dec;144(1-2):212-3

UN CASO DI CISTINURIA

La cistinuria è una malattia autosomica recessiva, basata su un difetto di trasporto degli aminoacidi cistina, lisina, ornitina e arginina a livello del tubulo renale, con aumentata escrezione urinaria e formazione ricorrente di calcoli di cistina. La frequenza stimata è di un caso per 15.000-20.000 nati. È conseguente a mutazioni dei geni SLC3A1 (2p21) e/o SLC7A9 (19q13.11), che codificano per le subunità dei trasportatori transepiteliali degli aminoacidi bibasici, responsabili della cistinuria tipo A e di tipo B rispettivamente. La terapia della cistinuria è finalizzata a prevenire la formazione e la crescita dei calcoli, e si basa essenzialmente sull’idratazione, alcalinizzazione delle urine e su farmaci chelanti la cistina. Quando il trattamento medico risulta inefficace va considerata la terapia chirurgica. CASISTICA E METODI. Si ricoverava C.D., di sesso femminile e anni 8, per recente IVU e dolori in sede lombare bilateralmente. Una ecografia renale evidenziava calcolosi renale bilaterale (a sin. a stampo) e idronefrosi di II grado a dx. Riscontro di alcalosi metabolica ed ipocitraturia; si eseguiva dosaggio degli aminoacidi urinari: aumento di cistina (418 mmol/mol creat U), lisina ,arginina e ornitina. Iniziava terapia con citrato di potassio,antibiotico ed iperidratazione. Si eseguiva test genetico molecolare: mutazioni in eterozigosi composta nel gene SLC3A1. Nei genitori: mutazioni in eterozigosi a carico dello stesso gene. RISULTATI. Controlli successivi mostravano miglioramento clinico, con scomparsa della sintomatologia dolorosa; esami seriati evidenziavano alcalinizzazione delle urine, ma persistenza di elevati valori di cistina nelle urine, per cui iniziava terapia con Tiopronina. CONCLUSIONI. La malattia richiede uno stretto monitoraggio clinico, ecografico e laboratoristico; in caso di mancato miglioramento va valutata terapia con chelanti della cistina, non scevri da importanti effetti collaterali, o il ricorso alla terapia chirurgica se la gestione conservativa della malattia dovesse risultare inefficace

HUMAN METAPNEUMOVIRUS RESPONSIBLE FOR A SEVERE ERYTHEMA MULTIFORME: AN UNUSUAL ASSOCIATION

Erythema Multiforme (EM) is an acute immune-mediated condition characterized by the appearance of typical target-like lesions on the skin. They most commonly appear in a symmetrical distribution on the extensor surfaces of the acral extremities and subsequently spread in a centripetal way. EM ‘major’ involves oral, genital and ocular mucosae with erosions or bullae. Although cutaneous lesions are usually asymptomatic, EM can be caused by drugs, autoimmune disease, malignancy, irradiation, sarcoidosis and in 90 percent of cases by infections (viral, bacterial, fungal). Herpes Simplex virus is the most frequent etiologic agent. Mycoplasma Pneumoniae infection is another important cause of EM, particularly in children. Laboratory findings are not specific and clinical finding are necessary for diagnosis. A skin biopsy should be performed when the diagnosis is unclear. CASE REPORT: 14 year old male came to our attention for the appearance of cutaneous lesions, accompanied by high fever. The skin appeared almost entirely affected by roundish, sharp, erythematous lesions, some of these with evident ‘coccard’ sign, other ecchymotic with hemorrhagic nuance, confluent to the trunk in large patches. No recent history of infections or drugs. Laboratory findings showed a neutrophilia (N 8810/mcl) and eosinophilia (E 980/mcl) and high inflammatory indices (PCR 4.75 mg/dl, ferritin 517 kg/ml). Peripheral smear, autoimmunity, virological and bacterial screening and instrumental examinations were negative. On the third day of admission, he performed a nasal swab (Multiplex) due to the appearance of rhinorrhea and cough. It was positive for Human Metapenumovirus (HM). On the seventh day, there was a new poussé of erythematous, itchy, coccard element on the whole body surface. He was treated with antihistaminic, steroid and antibiotic therapy with gradual rash regression, desquamation of skin lesions and defervescence. In literature it is known that HM is a common cause of upper respiratory tract infection in children. However, no further cases are reported regarding the possible relationship between skin lesions and HM. In our case the only laboratory finding associate to the EM was a positive RT-PCR for HM. This observation could lead to further scientific evaluations

WHEN A VIRUS HAS DIFFERENT FACES

Measles is a highly contagious viral illness, characterized by fever, malaise, cough, coryza and conjunctivitis, followed by maculopapular exanthema, which spreads cephalocaudally and centrifugally. Measles, mumps, rubella (MMR) vaccination has led to the interruption of measles virus transmission and gives protection to unvaccinated individuals via herd immunity. The morbilliform exanthema can be found in various conditions, including infectious mononucleosis. It is characterized by fever, pharyngitis, lymphadenopathy and a generalized maculopapular, urtical or petechial rash occasionally can be present, especially after administration of beta-lactams. CASE REPORT: 17 months old male was admitted in our pediatric department for the appearance, 4 days earlier, of rash and fever (T 38,8°C). The exanthema consisted of an erythematous, maculopapular, blanching rash, which began on the face and progressed to the truck and extremities involving the palms and soles. In some areas it showed confluent and hemorrhagic features. The physical examination showed the presence of laterocervical lymphadenopathy, nonpurulent conjunctivitis and pharyngitis. About 10 days earlier it was administered antibiotic therapy with Amoxicillin for a fever associated with malaise, cough and coryza. The child had no history of allergies and the MMR vaccine was repeatedly delayed and eventually not carried out for multiple episodes of respiratory infections. The laboratory tests showed leucocitosis with a normal differential count, mild elevation of transaminases, elevation of inflammatory markers and LDH; the morphological evaluation of the peripheral smear showed some activated lymphomonocitoid cells. Given the rash characteristics and the strong suspicion of measles, the patient was located in isolation and infectivological tests were performed (TORCH, Monotest, Respiratory Multiplex PCR panel and a serology for measles). They all came back negative except for the anti VCA IgM for EBV infection. The patient was treated with IV fluids and antipyretics. Antibiotic therapy was administered in order to prevent bacterial superinfections. After 72 hours the rash started to darken and then to gradually fade. The patient was dismissed with the diagnosis of maculopapular exanthema in mononucleosis infection. Clinical manifestations of infectious mononucleosis can be similar to those of measles and, especially in unvaccinated patients, can sometimes be confused with it. Maculopapular exanthema can be found in various conditions, such as common viral or bacterial infections, IgA vasculitis, Kawasaki disease or drug eruption. For this reason, it is important to consider mononucleosis in the differential diagnosis of measles, especially in case of hemorrhagic and infiltrated rash, not much described in the literatur