Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis. Information on TP53 germline pathogenic variant (PV) prevalence when using Chompret criteria in South America and especially in Brazil is scarce. Therefore, the aim of this study was to characterize patients that fulfilled these specific criteria in southern Brazil, a region known for its high population frequency of a founder TP53 variant c.1010G>A (p.Arg337His), as known as R337H. TP53 germline testing of 191 cancer-affected and independent probands with LFS phenotype identified a heterozygous pathogenic/likely pathogenic variant in 26 (13.6%) probands, both in the DNA binding domain (group A) and in the oligomerization domain (group B) of the gene. Of the 26 carriers, 18 (69.23%) were R337H heterozygotes. Median age at diagnosis of the first tumor in groups A and B differed significantly in this cohort: 22 and 2 years, respectively (P = 0.009). The present study shows the clinical heterogeneity of LFS, highlights particularities of the R337H variant and underscores the need for larger collaborative studies to better define LFS prevalence, clinical spectrum and penetrance of different germline TP53 pathogenic variants.

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BACKGROUND T-cell large granular lymphocyte (T-LGL) leukemia is a clonal proliferation of cytotoxic T cells, characterized by peripheral blood and marrow lymphocytic infiltration with LGL. Common clinical manifestations are splenomegaly, cytopenias (neutropenia) , anemia, and thrombocytopenia. This condition is often associated with autoimmune disorders and other lymphoproliferative disorders. T-LGL leukemia has been rarely reported in children. We report a child with T-LGL leukemia who presented with neutropenia and went on to develop juvenile systemic lupus erythematosus CASE REPORTFemale infant with five years old, was admitted to critical care unit with severe refractory septic shock and pancytopenia, important colitis in the cecum and ileo-cecal region, and anterior and posterior anal laceration .Colonoscopy showed edemaciated ileo-cecal valve, mucosa of the cecum presenting three deep ulcers, three lacerations in the anus. Cecal biopsy showed chronic colitis and cryptitis and mild cryptic microabscesses. Based on these results, lesions in cecum were tought to be the result of an infectious process not seen at the time of initial presentation, and now in remission. Due to 3 episodes of fever during hospitalization, complementary tests were ordered, reporting leucopenia with neutropenia in 2 occasions, which led to the investigation of cyclic neutropenia or autoimmune neutropenia. Bone marrow biopsy was performed, and the medulogram showed discrete hypocellularity, normomaturative, and with normal morphology. Immunophenotyping was unchanged. Infant also had positive rheumatologic markers (FAN and antilupus coagulant) but no signs of systemic autoimmune disease.She presented febrile neutropenia again, associated with diarrhea, and was readmitted for treatment and further investigations of etiology. Chest X-ray and urine tests showed no alterations and abdominal echo had signs of colitis as well as in the first hospitalization. Metronidazole and cefepime were started. Patient evolved with leukopenia improvement, but still with neutropenia. It was decided to repeat the bone marrow biopsy and to carry out a new immunophenotyping., which led to the diagnosis of LGL leukemia.Methotrexate, prednisolone, filgrastima and sulfamethoxazole-trimethoprim were the drugs of treatment. She presented improvement of the neutropenia, being discharged with outpatient follow-up. Since then, she did not have neutropenia or leukopenia. CONCLUSIONAlthough rare, T-LGL leukemia must be considered in children with pancytopenia and autoimmune disorders,