ABSTRACT
ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.
Subject(s)
Anaplastic Lymphoma Kinase/antagonists & inhibitors , Anaplastic Lymphoma Kinase/analysis , Histiocytic Disorders, Malignant/drug therapy , Histiocytic Disorders, Malignant/pathology , Protein Kinase Inhibitors/therapeutic use , Adolescent , Adult , Anaplastic Lymphoma Kinase/genetics , Child , Child, Preschool , Female , Histiocytic Disorders, Malignant/complications , Histiocytic Disorders, Malignant/genetics , Humans , Infant , Male , Nervous System Diseases/etiology , Nervous System Diseases/genetics , Nervous System Diseases/pathology , Oncogene Proteins, Fusion/analysis , Oncogene Proteins, Fusion/antagonists & inhibitors , Oncogene Proteins, Fusion/genetics , Retrospective Studies , Young AdultABSTRACT
Primary hemophagocytic lymphohistiocytosis (pHLH) is a severe, life-threatening hyperinflammatory syndrome caused by defects in genes of the granule-dependent cytotoxic pathway. Here we investigated the clinical presentation and outcome in a large cohort of 143 patients with pHLH diagnosed in the last 15 years and enrolled in the Italian registry. The median age at diagnosis was 12 months (interquartile range, 2-81), and 92 patients (64%) fulfilled the HLH-2004 criteria. Of 111 patients who received first-line combined therapy (HLH-94, HLH-2004, Euro-HIT protocols), 65 (59%) achieved complete response and 21 (19%) partial response. Thereafter, 33 patients (30%) reactivated, and 92 (64%) received hematopoietic stem cell transplantation, 78 of whom (85%) survived and were alive at a median follow-up from diagnosis of 67 months. Thirty-six patients (25%) died before hematopoietic stem cell transplantation and 14 (10%) after. Overall, 93 patients (65%) were alive after a median follow-up of 30 months. Unadjusted predictors of non-response were age <6 months and high ferritin and bilirubin levels, while predictors of pre-transplant and overall mortality were high ferritin and bilirubin levels. At multivariable analysis, high levels of ferritin predicted non-response, while high levels of bilirubin predicted pre-transplant and overall mortality. Despite recent advances in therapeutic management, pHLH remains a life-threatening condition with significant early mortality. Liver dysfunction is the main predictor of poor prognosis.
Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphohistiocytosis, Hemophagocytic , Registries , Humans , Lymphohistiocytosis, Hemophagocytic/mortality , Lymphohistiocytosis, Hemophagocytic/therapy , Lymphohistiocytosis, Hemophagocytic/diagnosis , Italy/epidemiology , Male , Female , Infant , Child, Preschool , Child , Treatment Outcome , Adolescent , Prognosis , Combined Modality Therapy , Follow-Up StudiesABSTRACT
Hematopoietic stem cell transplantation (HSCT)-based approaches are increasingly investigated strategies to induce tolerance in recipients of solid allografts. However, in the majority of cases, these approaches rely on the infusion of hematopoietic stem cells recovered from the same solid organ donor. In this report, we describe the case of a boy who received liver transplantation from a deceased donor, who had successfully underwent allogeneic HSCT from an unrelated donor for hepatitis-associated aplastic anemia. In this patient, it was possible to permanently withdraw post-HSCT immune suppression without causing any sign of liver graft dysfunction. To the best of our knowledge, this is the first case of operational tolerance documented in a patient who received combined liver transplantation and HSCT from different donors.
Subject(s)
Anemia, Aplastic , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Liver Transplantation , Male , Humans , Child , Liver Transplantation/adverse effects , Tissue Donors , Hematopoietic Stem Cell Transplantation/adverse effects , Immune Tolerance , Transplantation, Homologous/adverse effects , Anemia, Aplastic/etiology , Graft vs Host Disease/etiologyABSTRACT
High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9-10/10 HLA-matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, using the locus median to stratify patients with 'high' or 'low' HED. Patients with high HED-B and -DRB1 showed significantly improved disease-free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED-B + -DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non-relapse-mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED-B + -DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA-DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Neoplasms , Humans , Child , Young Adult , Unrelated Donors , Retrospective Studies , Histocompatibility Testing , Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/etiologyABSTRACT
B-cell acute lymphoblastic leukaemia (B-ALL) reprograms the surrounding bone marrow (BM) stroma to create a leukaemia-supportive niche. To elucidate the contribution of immune cells to the leukaemic microenvironment, we investigated the involvement of monocyte/macrophage compartments, as well as several recruitment pathways in B-ALL development. Immunohistochemistry analyses showed that CD68-expressing macrophages were increased in leukaemic BM biopsies, compared to controls and predominantly expressed the M2-like markers CD163 and CD206. Furthermore, the "non-classical" CD14+ CD16++ monocyte subset, expressing high CX3CR1 levels, was significantly increased in B-ALL patients' peripheral blood. CX3CL1 was shown to be significantly upregulated in leukaemic BM plasma, thus providing an altered migratory pathway possibly guiding NC monocyte recruitment into the BM. Additionally, the monocyte/macrophage chemoattractant chemokine ligand 2 (CCL2) strongly increased in leukaemic BM plasma, possibly because of the interaction of leukaemic cells with mesenchymal stromal cells and vascular cells and due to a stimulatory effect of leukaemia-related inflammatory mediators. C5a, a macrophage chemoattractant and M2-polarizing factor, further appeared to be upregulated in the leukaemic BM, possibly as an effect of PTX3 decrease, that could unleash complement cascade activation. Overall, deregulated monocyte/macrophage compartments are part of the extensive BM microenvironment remodelling at B-ALL diagnosis and could represent valuable targets for novel treatments to be coupled with classical chemotherapy.
Subject(s)
Antigens, CD/metabolism , Macrophages/metabolism , Monocytes/metabolism , Neoplasm Proteins/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Tumor Microenvironment , Adolescent , Adult , Aged , Coculture Techniques , Female , Human Umbilical Vein Endothelial Cells , Humans , Macrophages/pathology , Male , Middle Aged , Monocytes/pathology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathologyABSTRACT
AIMS: Histiocytoses are a heterogeneous group of localized or disseminated diseases. Clinical presentation and patients' outcome vary greatly, ranging from mild to life-threatening disorders. Rare cases of systemic or localized histiocytosis harboring ALK rearrangement have been reported. METHODS: Two cases of CNS histiocytosis were thoroughly investigated by implementing multiple molecular tests, i.e. FISH, RT-qPCR, NGS analysis. RESULTS: In a 10-month old girl (patient #1), MRI showed two left hemispheric lesions and a right fronto-mesial lesion histologically consisting of a moderately cellular infiltrative proliferation, composed by CD68(PGM1)+/CD163+ spindle cells. ALK 5'/3'-imbalance and a KIF5B(exon 24)-ALK(exon 20) fusion were documented by RT-qPCR and NGS analysis, respectively. A subsequent CT scan showed multiple hepatic and pulmonary lesions. The patient was started on chemotherapy (vinblastine) associated to an ALK-inhibitor (Alectinib) with remarkable response. In a 11-year-old girl (patient #2), MRI showed a right frontal 1.5 cm lesion. Neuropathological examination revealed a histiocytic proliferation composed by medium sized CD68(PGM1)+/HLA-DR+ cells, showing moderate ALK1 positivity. ALK rearrangement and a KIF5B(exon 24)-ALK(exon 20) fusion were demonstrated also in this case. Subsequent CT, 18F-FDG-PET and MRI scans showed the presence of a single right femoral lesion, proved to be a fibrous cortical defect. CONCLUSIONS: In ALK-histiocytoses, CNS involvement may occur as part of a systemic disease or, rarely, as its only primary disease localization, which could remain otherwise asymptomatic. The diagnosis often relies on neuropathological examination of brain biopsy, which may pose a diagnostic challenge due to the variable histopathological features. An integrated histological and molecular approach in such cases is recommended.
Subject(s)
Anaplastic Lymphoma Kinase/metabolism , Central Nervous System/pathology , Histiocytosis/drug therapy , Protein Kinase Inhibitors/therapeutic use , Biopsy/methods , Central Nervous System/drug effects , Child , Female , Histiocytosis/diagnosis , Histiocytosis/pathology , Humans , Infant , Receptor Protein-Tyrosine Kinases/drug effects , Receptor Protein-Tyrosine Kinases/metabolismABSTRACT
Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that enters cells via the ACE2 receptor. SARS-CoV-2 infection causes a reduction in ACE2 levels, leading to an imbalance in the renin-angiotensin system (RAS), and consequently, in blood pressure and systemic vascular resistance. ERAP1 and ERAP2 are two RAS regulators and key components of MHC class I antigen processing. Their polymorphisms have been associated with autoimmune and inflammatory conditions, hypertension, and cancer. Based on their involvement in the RAS, we believe that the dysfunctional status of ERAP1 and ERAP2 enzymes may exacerbate the effect of SARS-CoV-2 infection, aggravating the symptomatology and clinical outcome of the disease. In this review, we discuss this hypothesis.
Subject(s)
Aminopeptidases/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Hypertension/enzymology , Minor Histocompatibility Antigens/metabolism , Renin-Angiotensin System , SARS-CoV-2/metabolism , Age Factors , Aminopeptidases/genetics , Antigen Presentation/genetics , COVID-19/virology , Female , Humans , Hypertension/genetics , Male , Minor Histocompatibility Antigens/genetics , Polymorphism, Single Nucleotide , Sex Factors , Virus InternalizationABSTRACT
Phylogeographic inference has provided extensive insight into the relative roles of geographical isolation and ecological processes during evolutionary radiations. However, the importance of cross-lineage admixture in facilitating adaptive radiations is increasingly being recognised, and suggested as a main cause of phylogenetic uncertainty. In this study, we used a double digest RADseq protocol to provide a high resolution (~4 Million bp) nuclear phylogeny of the Delphininae. Phylogenetic resolution of this group has been especially intractable, likely because it has experienced a recent species radiation. We carried out cross-lineage reticulation analyses, and tested for several sources of potential bias in determining phylogenies from genome sampling data. We assessed the divergence time and historical demography of T. truncatus and T. aduncus by sequencing the T. aduncus genome and comparing it with the T. truncatus reference genome. Our results suggest monophyly for the genus Tursiops, with the recently proposed T. australis species falling within the T. aduncus lineage. We also show the presence of extensive cross-lineage gene flow between pelagic and European coastal ecotypes of T. truncatus, as well as in the early stages of diversification between spotted (Stenella frontalis; Stenella attenuata), spinner (Stenella longirostris), striped (Stenella coeruleoalba), common (Delphinus delphis), and Fraser's (Lagenodelphis hosei) dolphins. Our study suggests that cross-lineage gene flow in this group has been more extensive and complex than previously thought. In the context of biogeography and local habitat dependence, these results improve our understanding of the evolutionary processes determining the history of this lineage.
Subject(s)
Dolphins/classification , Animals , Biological Evolution , Cell Nucleus/genetics , Dolphins/genetics , Ecosystem , Gene Flow , Genomics , Phylogeny , Phylogeography , Stenella/classificationABSTRACT
Pitt-Hopkins syndrome (PTHS, MIM #610954) is a rare neurodevelopmental disease characterized by the association of intellectual disability, characteristic facial gestalt and episodes of abnormal and irregular breathing. PTHS is due to heterozygous loss-of-function variants in the TCF4 gene (transcription factor 4, MIM #602272) encoding for a basic helix-loop-helix transcription factor. TCF4 is highly expressed during early development of the nervous system, and it is involved in cellular differentiation and proliferation. Since the first clinical description in 1978, less than 200 PTHS patients have been described. A comprehensive phenotype, especially regarding cancer predisposition, is not yet well defined. We report the case of a 7-year-old boy affected by PTHS with a 4-week history of progressive swelling of the frontal bones diagnosed with Langerhans cell histiocytosis.
Subject(s)
Histiocytosis, Langerhans-Cell/pathology , Hyperventilation/complications , Intellectual Disability/complications , Mutation , Transcription Factor 4/genetics , Child , Facies , Histiocytosis, Langerhans-Cell/etiology , Histiocytosis, Langerhans-Cell/metabolism , Humans , Male , PhenotypeABSTRACT
Since the beginning of life, every multicellular organism appeared to have a complex innate immune system although the adaptive immune system, centred on lymphocytes bearing antigen receptors generated by somatic recombination, arose in jawed fish approximately 500 million years ago. The major histocompatibility complex MHC, named the Human leucocyte antigen (HLA) system in humans, represents a vital function structure in the organism by presenting pathogen-derived peptides to T cells as the main initial step of the adaptive immune response. The huge level of polymorphism observed in HLA genes definitely reflects selection, favouring heterozygosity at the individual or population level, in a pathogen-rich environment, although many are located in introns or in exons that do not code for the antigen-biding site of the HLA. Over the past three decades, the extent of allelic diversity at HLA loci has been well characterized using high-resolution HLA-DNA typing and the number of new HLA alleles, produced through next-generation sequencing methods, is even more rapidly increasing. The level of the HLA system polymorphism represents an obstacle to the search of potential compatible donors for patients affected by haematological disease proposed for a hematopoietic stem cell transplant (HSCT). Data reported in literature clearly show that antigenic and/or allelic mismatches between related or unrelated donors and patients influences the successful HSCT outcome. However, the recent development of the new transplant strategy based on the choice of haploidentical donors for HSCT is questioning the role of HLA compatibility, since the great HLA disparities present do not worsen the overall clinical outcome. Nowadays, NGS has contributed to define at allelic levels the HLA polymorphism and solve potential ambiguities. However, HLA functions and tissue typing probably need to be further investigated in the next future, to understand the reasons why in haploidentical transplants the presence of a whole mismatch haplotype between donors and recipients, both the survival rate and the incidence of acute GvHD or graft rejection are similar to those reported for unrelated HSCTs.
Subject(s)
Graft Rejection/immunology , HLA Antigens/genetics , Haplotypes/immunology , Hematopoietic Stem Cell Transplantation/adverse effects , Alleles , Graft vs Host Disease/genetics , HLA Antigens/immunology , Haplotypes/genetics , Humans , Polymorphism, Genetic , Tissue Donors , Transplantation, Haploidentical/adverse effectsABSTRACT
B-cell precursor-acute lymphoblastic leukemia modulates the bone marrow (BM) niche to become leukemia-supporting and chemo-protective by reprogramming the stromal microenvironment. New therapies targeting the interplay between leukemia and stroma can help improve disease outcome. We identified ActivinA, a TGF-ß family member with a well-described role in promoting several solid malignancies, as a factor favoring leukemia that could represent a new potential target for therapy. ActivinA resulted over-expressed in the leukemic BM and its production was strongly induced in mesenchymal stromal cells after culture with leukemic cells. Moreover, MSCs isolated from BM of leukemic patients showed an intrinsic ability to secrete higher amounts of ActivinA compared to their normal counterparts. The pro-inflammatory leukemic BM microenvironment synergized with leukemic cells to induce stromal-derived ActivinA. Gene expression analysis of ActivinA-treated leukemic cells showed that this protein was able to significantly influence motility-associated pathways. Interestingly, ActivinA promoted random motility and CXCL12-driven migration of leukemic cells, even at suboptimal chemokine concentrations, characterizing the leukemic niche. Conversely, ActivinA severely impaired CXCL12-induced migration of healthy CD34+ cells. This opposite effect can be explained by the ability of ActivinA to increase intracellular calcium only in leukemic cells, boosting cytoskeleton dynamics through a higher rate of actin polymerization. Moreover, by stimulating the invasiveness of the leukemic cells, ActivinA was found to be a leukemia-promoting factor. Importantly, the ability of ActivinA to enhance BM engraftment and the metastatic potential of leukemic cells was confirmed in a xenograft mouse model of the disease. Overall, ActivinA was seen to be a key factor in conferring a migratory advantage to leukemic cells over healthy hematopoiesis within the leukemic niche.
Subject(s)
Activins/genetics , Biomarkers, Tumor , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/etiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Activins/metabolism , Animals , Bone Marrow/pathology , Bone Marrow Cells/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cytokines/metabolism , Disease Models, Animal , Gene Expression Regulation, Leukemic , Humans , Inflammation Mediators/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Stromal Cells/metabolismABSTRACT
Langherans' cell histiocytosis (LCH) is a rare disease mostly affecting children in the first decade of life. As clinical presentation is extremely heterogenous, a prompt diagnosis may be challenging, sometimes leading to a diagnostic delay, especially when the disease involves a single site. Herein, we report a case of a child with an unusual presentation of (LCH) mimicking a Pott puffy tumor with extracranial and epidural abscesses, surgically treated. Through this unique case we summarize possible manifestations of LCH with bone involvement and we underline the importance of considering possible complications due to bone erosions such as infection, to avoid a misdiagnosis.
Subject(s)
Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/pathology , Pott Puffy Tumor/diagnosis , Child , Diagnosis, Differential , Humans , Male , Pott Puffy Tumor/pathologyABSTRACT
Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively. Bortezomib (1·3 mg/m2 /dose) was administered intravenously on days 1, 4, 8, and 11. Chemotherapy agents were the same as those used in the TACL trial, consisting of dexamethasone, doxorubicin, vincristine and pegylated asparaginase. Three patients (8·1%) died due to infections. Twenty-seven patients (72·9%) achieved CR or CR with incomplete platelet recovery (CRp). Fourteen had minimal residual disease (MRD) lower than 0·1%. Twenty-two of 30 BCP-ALL patients (73·3%) and 5/7 patients (71%) with T-cell ALL achieved CR/CRp. The 2-year overall survival (OS) is 31·3%; CR/CRp patients with an MRD response had a remarkable 2-year OS of 68·4%. These data confirm that the combination of bortezomib with chemotherapy is a suitable/effective option for childhood relapsed/refractory ALL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bortezomib/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Asparaginase , Child , Child, Preschool , Dexamethasone , Doxorubicin , Female , Humans , Infant , Male , Neoplasm, Residual , Polyethylene Glycols , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Proteasome Inhibitors , Remission Induction , Salvage Therapy/methods , Survival Analysis , Vincristine , Young AdultABSTRACT
BACKGROUND: Low back pain is a common symptom in the pediatric population; approximately half of all children present with at least one episode of low back pain. The majority of cases are due to nonspecific causes such as musculoskeletal trauma with spontaneous regression. On some occasions, however, life-threatening diseases have to be considered. CASE REPORT: A 15-year-old girl presented to the Pediatric Emergency Department for a history of continuous 2-day duration of low back pain and transient paresthesia of the right gluteal area. Low back pain was diagnosed and nonsteroidal anti-inflammatory treatment combined with rest were prescribed. After 7 days, worsening of the clinical conditions was observed with bilateral gluteus paresthesia. A corset was recommended, and magnetic resonance imaging (MRI) and rheumatological evaluation were prescribed on an outpatient basis. After 5 days she was hospitalized due to urinary incontinence and persistence of pain. Blood tests revealed neutrophil leukocytosis associated with mild anemia, thrombocytopenia, hyperuricemia, and increased lactate dehydrogenase. MRI examination of the spine demonstrated a mass involving the sacral canal and the presacral region, extending through the sacral foramina, along the nerve roots. Similar tissue was found at multiple levels in the spine and in the right orbit. Bone marrow aspiration and biopsy highlighted the presence of myeloid blasts and myeloid dysplasia, consequently, myeloid sarcoma was diagnosed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case demonstrates the importance of prompt identification of diagnostic "red flags" in childhood low back pain, indicating the need for diagnostic investigations such as MRI and blood tests.