Clinical spectrum of Li-Fraumeni syndrome/Li-Fraumeni-like syndrome in Brazilian individuals with the TP53 p.R337H mutation.

BACKGROUND: The TP53 p.R337H germline mutation is highly prevalent among children with adrenocortical tumors (ACTs) from South and Southeast Brazil. However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated. PATIENTS AND METHODS: We investigated tumor profile data and outcomes of individuals and their close relatives with the TP53 p.R337H germline mutation. A questionnaire and the Toronto protocol were used for evaluation of asymptomatic carriers of this TP53 mutation. RESULTS: The cohort of this study comprised 51 patients from 46 different families; 67% were female. All but one harbored the TP53 p.R337H mutation in heterozygous state; only one child was homozygous for this variant. Maternal allele inheritance occurred in 72% of the cases (p= 0,002). In pediatric group, ACT was the most common primary tumor at the diagnosis (55%; median age= 2 years). No patient of the pediatric group who initially presented with ACT developed a second primary tumor and 11% (n= 3) died due to complications related to the primary tumor (median follow-up time of 81.5 months, range= 3-378 months). In adult group, the main tumors at diagnosis were: adrenocortical carcinoma (ACC) (23%; median age= 29.5 years), breast cancer (12%; median age= 38.5 years), soft tissue sarcoma (8%; median age= 50.3 years) and choroid plexus carcinoma (CPC) (2%; median age= 18 years). Among adult patients who were diagnosed with ACC as the first primary tumor, all presented with aggressive disease as per histologic and clinical criteria at diagnosis, and 75% of patients died (median follow-up time of 19 months, range= 1-69 months). Five adult patients (22%) had a second primary tumor, including bronchoalveolar lung cancer (2 cases), ACC, uterine cervical carcinoma and fibrosarcoma. The diagnosis of these tumors was established from 8 to 36 months after the first primary tumor. Three families presented more than one case of ACT. Nine malignant neoplasms were diagnosed in asymptomatic carriers using Toronto protocol. CONCLUSIONS: This study confirms a high frequency of TP53 p.R337H mutation in pediatric group with ACT. In addition, we observed the occurrence of other tumors of LFS/LFL spectrum and a difference in the aggressiveness of ACTs depending on the age group in which they were diagnosed. The predominance of maternal mutated allele inheritance was first demonstrated in the affected Brazilian's families.

Linfoma adrenal primário apresentando-se como incidentaloma adrenal: relatode caso e revisão da literatura / Primary adrenal lymphoma presenting as an adrenal incidentaloma: case report and review of the literature

Introdução: O linfoma primário de glândulas adrenaisé um evento raro. Devido à agressividade dessetumor, a forma mais comum de apresentação é a insuficiênciaadrenal primária, sendo muito infrequente aapresentação na forma de um incidentaloma adrenal.Incidentalomas adrenais correspondem a tumores sóidentificados após a realização de exames de imagempara esclarecimento de alguma anormalidade semorigem, a princípio, nas glândulas adrenais. Objetivo:Descrever o caso de um paciente de 61 anos portadorde linfoma difuso de grandes células B com acometimentoprimário bilateral de glândulas adrenais, este seapresentando na forma de um incidentaloma adrenal.Material e Métodos: Relato do caso, revisão de examese discussão baseada na literatura. Os artigos selecionadospara a discussão foram buscados no PubMed edatam dos últimos 12 anos. Resultados: Paciente masculino,61 anos, previamente hígido, apresentou-se emconsulta ambulatorial com queixa de dor abdominaldifusa, perda de peso e astenia associados. Exames deimagem evidenciaram aumento volumétrico de ambasas adrenais. Não havia sintomas ou sinais clínicos sugestivosde hipofunção ou hiperfunção adrenal e osexames laboratoriais iniciais descartaram a presençade insuficiência adrenal, feocromocitoma, hiperaldosteronismoprimário e síndrome de Cushing. O pacienteevoluiu com queda do estado geral, vômitos e confusãomental, sendo diagnosticada crise adrenal, confirmadaapós laboratorialmente. O estudo histológico evidenciouneoplasia maligna indiferenciada, sendo definidaa presença de linfoma difuso de grandes células B naavaliação imunohistoquímica. Conclusões: Apesar deser uma condição rara, o linfoma primário de glândulasadrenais deve ser lembrado como um possível diagnósticono contexto de incidentaloma adrenal.

Introduction: Primary adrenal lymphoma is a rare event,Due to the agressiveness of this tumor, the most commonform of presentation is primary adrenal insufficiency ?presentation as an adrenal incidentaloma is very unusual.Adrenal incidentalomas are turmors only indentified afterradiologic evaluation in order to clarify some abnormalitythat is not originated, at the first instance, in adrenalglands. Objective: To describe a case of a 61-year-old patientwith lymphoma diffuse large B-cell involving adrenalglands bilaterally and presenting as an adrenal incidentaloma.Methods: Case report, review of tests and discussionbased on the literature. The articles choosen to thediscussion were searched in PubMed and date from thelast twelve years. Results: A 61 year-old male patient, helathypreviously, presented in outpatient service with diffuseabdominal pain, wheight loss and astenia associated.Imaging studies revealed an increase in volume of bothadrenal glands. There were no clinical signs or symptonssuggestive of adrenal hipofunction or hyperfunction andinitial laboratorial tests ruled out the presence of adrenalinsufficiency, pheocromocytoma, primary aldosteronismand Cushing?s syndrome. The patient developed then adecline in general status, emesis and mental confusionand an adrenal crisis was confirmed. Histologic study ofthe adrenal mass demonstrated an undifferenciated malignantneoplasm and the immunohistochemical evaluationshowed a large B-cell diffuse lymphoma. Conclusions:Despite being a rare condition, primmary adrenal lymphomashould be considered as a possible diagnosis in theclinical context of an adrenal incidentaloma.