Neonato con tumore miofibroblastico infiammatorio associato a trombocitopenia

Neonato di sesso maschile, nato a termine da parto eutocico. Gravidanza insorta da ICSI omologa, normodecorsa. IgG materne per CMV positive, IgM negative. Sierologia materna per toxoplasma, treponema, HIV e HCV, HBsAg, tamponi vagino-rettali negativi. Apgar 9-10, riscontro di tumefazione ovalare dell’avambraccio sinistro, dura, disomogenea, calda, con cute sovrastante integra. Contemporaneo riscontro di piastrinopenia (PLT 9000). PCR per CMV, EBV, ADV su sangue, indici infiammatori ed emocoltura negativi. Principali anticorpi anti-piastrine assenti. Eco-encefalo, eco-addome e radiografia del torace nella norma. Un’ecodoppler della tumefazione evidenziava una formazione espansiva di 35x21x25 mm, con margini lineari, ecostruttura disomogenea e accentuati segnali vascolari, in sede sovrafasciale. Una RM confermava un quadro suggestivo per anomalia vascolare. Veniva formulata l’ipotesi che si trattasse di emangioendotelioma kaposiforme e si attribuiva la trombocitopenia ad una verosimile sindrome di Kasabach-Merritt. Dopo l’asportazione della lesione all’analisi istologica veniva posta diagnosi di tumore miofibroblastico infiammatorio infantile. Normalmente la sindrome di Kasabach-Merritt si associa all’emangioendotelioma kaposiforme, mentre il tumore miofibroblastico infiammatorio si presenta spesso associato a trombocitosi, veniva quindi meno l’ipotesi diagnostica posta per l’eziologia della piastrinopenia. Per il persistere della piastrinopenia si approfondiva con: antigeni/anticorpi HIV, sottopopolazioni linfocitarie ed immunità umorale, dosaggio di LDH, creatinina, tutti risultati nella norma. L’aspirato midollare metteva in evidenza midollo a cellularità discreta, non elementi indifferenziati, rari megacariociti, numerosi aggregati piastrinici (recente terapia trasfusionale con concentrati piastrinici), esami genetici in corso. All’esame istologico della biopsia midollare si riscontrava midollo emopoietico con normale rappresentazione delle popolazioni cellulari. PCR per CMV, EBV, Parvovirus B19 e HHV6 su midollo osseo negative. All’immunofenotipo su aspirato midollare non rilevate popolazioni anomale. Venivano quindi escluse altre cause più rare di piastrinopenia quali la trombocitopenia amegacariocitica congenita (TAMC). Considerata l’origine periferica, venivano somministrate immunoglobuline endovena per due giorni consecutivi, con risoluzione della piastrinopenia. Discussione: Nel nostro caso i principali anticorpi antipiastrine risultavano assenti e si era ipotizzato che la piastrinopenia fosse dovuta alla sindrome di Kasabach-Merritt. La diagnosi istologica della lesione è risultata però essere di tumore miofibroblastico infiammatorio, normalmente non associato a trombocitopenia; quest’ultima tra l’altro persisteva nonostante l’escissione della lesione. Esami di secondo livello hanno permesso di identificare la condizione come periferica. Nonostante l’assenza dei principali anticorpi antipiastrine, si è deciso di somministrare immunoglobuline. Tale strategia ha portato alla immediata e persistente risalita dei valori delle piastrine, confermando quindi la diagnosi di trombocitopenia causata da anticorpi antipiastrine. Si ribadisce quindi la possibilità di interpretare la piastrinopenia come alloimmune anche se gli autoanticorpi principali dovessero risultare negativi. Nei laboratori generalmente vengono valutati i principali e non tutti i possibili anticorpi antipiastrine, tale esame rappresenta quindi un primo screening e per quanto la sua normalità ci possa far protendere verso altre diagnosi non dovrebbe far escludere a priori dalle possibili diagnosi differenziali la trombocitopenia causata da anticorpi contro le piastrine. Nel nostro specifico caso vista l’età del paziente si trattava verosimilmente di una NATP (Neonatal Alloimmune Thrombocytopenic Purpura), considerando anche il fatto che l’anamnesi patologica materna negativa per trombocitopenia permetteva teoricamente di escludere una ITP (Idiopathic Thrombocytopenic Purpura) materna

Histopathology of intestinal villi in neonatal and paediatric age: main features with clinical correlation - Part II

: In this paper, we will continue the description of histological findings of infantile and paediatric small bowel alterations with the main clinical pictures and differential diagnosis. We emphasise once again the need to evaluate the biopsies in an adequate clinical contest and with a systematic approach, including epithelial alterations, lamina propria changes, mucosal architecture, and the distribution of inflammation, together with other morphological signs more specific of certain diseases. We describe the histological findings of coeliac and Crohn's disease, gastrointestinal food allergic diseases, Langerhans cell histiocytosis, nutritional deficiencies and infections. Finally, we suggest the principal issues in the drafting the pathological report for appropriate interpretation and usefulness in clinical practice

Histopathology of intestinal villi in neonatal and paediatric age: main features with clinical correlation - Part I

none8: The neonatal and paediatric spectrum of small bowel disorders encompass a wide variety of conditions, ranging from food allergies to life-threatening surgical emergencies or lifelong medical conditions and, as such, it comes with a whole set of diagnostic challenges for the non-paediatric pathologist. Histologic examination is a cornerstone of diagnosis in a large number of diseases and may still provide important diagnostic clues in the appropriate clinical context. In this review, divided in two sections, we aim to provide a comprehensive histopathological summary of paediatric small bowel alteration and their differential diagnoses with a reference to the main clinical aspects required for appropriate interpretation. Specifically, in this first part, we describe congenital and metabolic disorders, intestinal lymphangiectasia, immunodeficiencies, GVHD, and necrotising enterocolitis.noneRossi, Chiara; Simoncelli, Gloria; Arpa, Giovanni; Stracuzzi, Alessandra; Parente, Paola; Fassan, Matteo; Vanoli, Alessandro; Villanacci, VincenzoRossi, Chiara; Simoncelli, Gloria; Arpa, Giovanni; Stracuzzi, Alessandra; Parente, Paola; Fassan, Matteo; Vanoli, Alessandro; Villanacci, Vincenz

Inflammatory Myofibroblastic Tumor of the Upper Airways Harboring a New TRAF3-ALK Fusion Transcript

Inflammatory myofibroblastic tumor (IMT) is a rare disease that mainly involves the lung and the abdomen with an intermediate clinical course but a recurrence rate between 15–30%. Radical surgery represents the gold standard of treatment, while chemotherapy and radiotherapy are considered for unresectable lesions. The identification of ALK translocations in IMT opened the option for the use of target therapies. Indeed, the ALK inhibitors have changed the treatment approach for aggressive lesions, improving the prognosis. Intraluminal upper-way IMT is extremely rare and represents a medical challenge. We reported an endotracheal IMT case presenting a previously unknown TRAF3-ALK fusion transcript

The Pitfall of Ganglioneuroblastoma-Nodular Diagnosis: Clinical and Imaging Considerations over a Rare Bifocal Sporadic Case

Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN can coexist in the same mass, leading to incorrect risk staging when only biopsy is performed. Herein, we describe a case of multifocal NT (thoracic and abdominal localization) occurring in a 4-year-old male. Different histological subtypes, namely GNBI and GNBN, were revealed in the two lesions. We focus on the difficulties of proper diagnosis and risk stratification, underlining the usefulness of several diagnostic tools for appropriate management and therapeutic choices

Image_1_Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.tif

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.</p

Table_1_Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.docx

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.</p

Table_4_Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.docx

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.</p

Table_2_Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.xlsx

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.</p

Table_3_Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.docx

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.</p