The term “Mastocytosis” is collectively used to designate a heterogeneous group of hematopoietic disorders characterized by pathological expansion and accumulation of clonal neoplastic Mast cells (MCs) in the skin or in other organ systems, including bone marrow, spleen, liver, lymph nodes and gastrointestinal tract. Nowadays, the 2022 WHO 5th Edition and 2022 ICC classifications differentiate the disease into a cutaneous form (CM), a systemic form (SM) and Mast cell sarcoma. Mastocytosis can occur both in pediatric patients and in the adults, but the characteristics of the disease in these two categories are different. Cutaneous Mastocytosis is usually confined to skin involvement, more commonly seen in children, and has a good prognosis. On the contrary, the systemic form of the disorder manifests generally in adulthood and could be correlated to end-organ damage and worse outcome. A common diagnostic criterion associated to CM as well as to SM is the presence of the c-KIT proto-oncogene mutation, which encodes for the Stem Cell Factor Receptor (SCFR). The spectrum of clinical presentations of Mastocytosis is huge and varies also according to the symptomatology severity: this ranges from asymptomatic manifestations, mild or moderate symptoms to very aggressive, life-threatening multisystemic involvement. The main clinical findings are the result of degranulation of Mast cells and activation of Mast cells mediators. Mastocytosis in pediatric age is typically associated only to cutaneous involvement and, in the majority of the cases, the onset of skin lesions is seen before two years of age, but the disease could also be congenital. In literature, case report of pediatric mastocytosis with systemic manifestations are very rare. The evolution of pediatric Mastocytosis is still unpredictable: up to now there are no laboratory or genetic tests that could help distinguishing patients that will have a remission before the adolescence and the one in which the disease will progress and persist also in adulthood. In light of the renewed interest in the study of Mast cell disorders, new pathophysiological inside, novel clinical and immunogenetic knowledge, we have proposed an observational, retrospective long-term follow- up study whose data have been collected after consulting the medical records of 131 pediatric patients being treated or who have been treated at the Dermatology clinic of University of Pavia, Fondazione IRCCS Policlinico San Matteo, at the “Ambulatorio Multidisciplinare e Integrato delle Mastocitosi” from the year 2010 until November 2023. For the realization of this project epidemiological, clinical, genetic, laboratory and prognostic data have been analyzed. Additionally, when possible, the clinical course of these young patients was studied. Data gatering has been also possible thanks to the collaboration between the specialists of the Dermatology department, of the Pediatric clinic, of the Pathological Anatomy department and of the Immuno-Allergology Laboratory. Data analysis has been performed with the help of the Biometry and Statistics Unit, Fondazione IRCCS Policlinico San Matteo. The objective of this study is to increase knowledge on this infrequent disease and to define some prognostic features useful for defining personalized care and therapeutic approaches for the pediatric patients. In addition, this retrospective study has the objective of starting the recently approved registry on Mastocytosis of the adulthood and of the pediatric age and being prodromal for future prospective studies on this rare pathology. To our knowledge, this is one of the studies with the largest case series about pediatric Mastocytosis.
Il termine “Mastocitosi” è utilizzato per designare un gruppo eterogeneo di disordini ematopoietici caratterizzati da un’espansione patologica ed accumulo di mastociti neoplastici clonali (MC) nella pelle o in altri organi ed apparati. Al giorno d'oggi, la quinta edizione della classificazione dell'OMS (2022) e quella dell' ICC (2022) differenziano la malattia in una forma cutanea (MC), una forma sistemica (MS) e il sarcoma mastocitario. La mastocitosi può verificarsi sia nei pazienti pediatrici che negli adulti, ma le caratteristiche della malattia in queste due categorie differiscono. La mastocitosi cutanea è limitata all'interessamento della pelle, è più frequente nei bambini, generalmente associata a prognosi favorevole. La controparte sistemica si manifesta più frequentemente in età adulta e potrebbe essere correlata al danno degli organi periferici ed a una prognosi più infausta. Un criterio diagnostico comune è la presenza della mutazione del proto-oncogene c-KIT, che codifica per il recettore del fattore delle cellule staminali (SCFR). Lo spettro delle presentazioni cliniche della mastocitosi è vasto e varia anche a seconda della gravità della sintomatologia. I principali sintomi sono il risultato della degranulazione dei mastociti e dell'attivazione dei loro mediatori. La mastocitosi in età pediatrica è tipicamente associata solo ad interessamento cutaneo e, nella maggior parte dei casi, l'esordio delle lesioni cutanee si osserva prima dei due anni di età, ma la malattia potrebbe anche essere congenita. In letteratura sono riportati molto raramente casi di mastocitosi pediatrica con manifestazioni sistemiche. L'evoluzione della Mastocitosi in età infantile è ancora imprevedibile: non esistono ad oggi test di laboratorio o genetici che possano aiutare a distinguere i pazienti che andranno in remissione prima dell'adolescenza e quelli in cui la malattia progredirà e persisterà anche in età adulta. Alla luce del rinnovato interesse per lo studio delle malattie mastocitarie, delle nuove conoscenze fisiopatologiche e immunogenetiche, abbiamo proposto uno studio osservazionale, retrospettivo, i cui dati sono stati raccolti dopo aver consultato le cartelle cliniche di 131 pazienti pediatrici attualmente in cura o che sono stati presi in carico presso la Clinica Dermatologica dell'Università di Pavia, Fondazione IRCCS Policlinico San Matteo, presso l'“Ambulatorio Multidisciplinare e Integrato delle Mastocitosi”, dall'anno 2010 fino a novembre 2023. Per la realizzazione di questo progetto sono stati analizzati dati epidemiologici, clinici, genetici, di laboratorio e prognostici. Ove possibile, è stato studiato il decorso clinico di questi piccoli pazienti. La raccolta dei dati è stata effettuata grazie alla collaborazione tra gli specialisti del reparto di Dermatologia, Clinica Pediatrica, reparto di Anatomia Patologica e del Laboratorio di Immunoallergologia. L'analisi dei risultati è stata ottenuta con il supporto dell'Unità di Biometria e Statistica del Policlinico San Matteo. L'obiettivo di questo studio è quello di aumentare le conoscenze su questa malattia poco frequente e di proporre alcune caratteristiche prognostiche utili per definire cure personalizzate e approcci terapeutici appropriati per i pazienti pediatrici. Inoltre, questo studio retrospettivo si pone l'obiettivo di avviare il registro locale, recentemente approvato, sulla mastocitosi dell'età adulta e dell'età pediatrica e di essere prodromico per future analisi prospettiche su questa rara patologia.
MASTOCYTOSIS IN THE PEDIATRIC AGE: A SINGLE-CENTER LONG-TERM FOLLOW-UP STUDY OF 131 PATIENTS.
BONELLI, ALICE
2023/2024
Abstract
The term “Mastocytosis” is collectively used to designate a heterogeneous group of hematopoietic disorders characterized by pathological expansion and accumulation of clonal neoplastic Mast cells (MCs) in the skin or in other organ systems, including bone marrow, spleen, liver, lymph nodes and gastrointestinal tract. Nowadays, the 2022 WHO 5th Edition and 2022 ICC classifications differentiate the disease into a cutaneous form (CM), a systemic form (SM) and Mast cell sarcoma. Mastocytosis can occur both in pediatric patients and in the adults, but the characteristics of the disease in these two categories are different. Cutaneous Mastocytosis is usually confined to skin involvement, more commonly seen in children, and has a good prognosis. On the contrary, the systemic form of the disorder manifests generally in adulthood and could be correlated to end-organ damage and worse outcome. A common diagnostic criterion associated to CM as well as to SM is the presence of the c-KIT proto-oncogene mutation, which encodes for the Stem Cell Factor Receptor (SCFR). The spectrum of clinical presentations of Mastocytosis is huge and varies also according to the symptomatology severity: this ranges from asymptomatic manifestations, mild or moderate symptoms to very aggressive, life-threatening multisystemic involvement. The main clinical findings are the result of degranulation of Mast cells and activation of Mast cells mediators. Mastocytosis in pediatric age is typically associated only to cutaneous involvement and, in the majority of the cases, the onset of skin lesions is seen before two years of age, but the disease could also be congenital. In literature, case report of pediatric mastocytosis with systemic manifestations are very rare. The evolution of pediatric Mastocytosis is still unpredictable: up to now there are no laboratory or genetic tests that could help distinguishing patients that will have a remission before the adolescence and the one in which the disease will progress and persist also in adulthood. In light of the renewed interest in the study of Mast cell disorders, new pathophysiological inside, novel clinical and immunogenetic knowledge, we have proposed an observational, retrospective long-term follow- up study whose data have been collected after consulting the medical records of 131 pediatric patients being treated or who have been treated at the Dermatology clinic of University of Pavia, Fondazione IRCCS Policlinico San Matteo, at the “Ambulatorio Multidisciplinare e Integrato delle Mastocitosi” from the year 2010 until November 2023. For the realization of this project epidemiological, clinical, genetic, laboratory and prognostic data have been analyzed. Additionally, when possible, the clinical course of these young patients was studied. Data gatering has been also possible thanks to the collaboration between the specialists of the Dermatology department, of the Pediatric clinic, of the Pathological Anatomy department and of the Immuno-Allergology Laboratory. Data analysis has been performed with the help of the Biometry and Statistics Unit, Fondazione IRCCS Policlinico San Matteo. The objective of this study is to increase knowledge on this infrequent disease and to define some prognostic features useful for defining personalized care and therapeutic approaches for the pediatric patients. In addition, this retrospective study has the objective of starting the recently approved registry on Mastocytosis of the adulthood and of the pediatric age and being prodromal for future prospective studies on this rare pathology. To our knowledge, this is one of the studies with the largest case series about pediatric Mastocytosis.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
Per maggiori informazioni e per verifiche sull'eventuale disponibilità del file scrivere a: unitesi@unipv.it.
https://hdl.handle.net/20.500.14239/17577