Posterior reversible encephalopathy syndrome in immunocompromised children - A single-center study from South India.

This study describes the profile of children diagnosed with posterior reversible encephalopathy syndrome (PRES) in the pediatric hematology oncology unit and highlights the clinical features of PRES in immunosuppressed children. This retrospective study included 10 children diagnosed with PRES with a mean age of 6.8 years. Acute lymphoblastic leukemia was the most common primary diagnosis followed by post-hematopoietic stem cell transplant patients. Most cases of PRES occurred within one month of treatment initiation. Hypertension was noted in all at the time of diagnosis. Neuroimaging revealed bilateral lesions with parietal and occipital lobe involvement being the most common. All patients received corticosteroids as part of treatment for primary diagnosis. Controlling blood pressure was critical in managing PRES. Consideration of PRES as a clinical possibility in pediatric hematology oncology unit in children presenting with symptoms such as headache, seizures, and visual disturbances will aid in early diagnosis after ruling out other causes of these symptoms.

Isolated Prothrombin Deficiency: A Case Report of a Rare Coagulation Disorder and Review of Literature.

Congenital prothrombin deficiency is a rare hemorrhagic disorder, frequent in areas with high degrees of consanguinity as it is autosomal recessive in nature. Clinical manifestations are highly variable, ranging from mild episodes of bleeding to severe hemorrhages. Here, we report a child with isolated prothrombin deficiency who presented with a history of pain and soreness in the prepuce associated with bleeding. Laboratory evaluation showed an altered coagulation profile with a prothrombin activity level of 29.8%, indicative of factor-II deficiency. This case highlights the importance of coagulation screening in all patients before even minor invasive procedures and the role of a detailed coagulation profile in confirming a diagnosis in the case of abnormal screening tests.

Preoperative three-dimensional modelling and virtual reality planning aids nephron sparing surgery in a child with bilateral Wilms tumour.

Bilateral Wilms tumour (BWT) is a surgically challenging condition. Virtual reality (VR) reconstruction aids surgeons to foresee the anatomy ahead of Nephron Sparing Surgery (NSS). Three-dimensional (3D) visualisation improves the anatomical orientation of surgeons performing NSS. We herewith report a case of BWT where VR planning and 3D printing were used to aid NSS. Conventional imaging is often found to be inadequate while assessing the tumour-organ-vascular anatomy. Advances like VR and 3D printing help surgeons plan better for complex surgeries like bilateral NSS. Next-generation extended reality tools will likely aid robotic-assisted precision NSS and improve patient outcomes.

Malignancy-Associated Secondary Hemophagocytic Lymphohistiocytosis Mimicking an Infection: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder of immune dysregulation associated with significant challenges in diagnosis and management. Described as primary HLH secondary to genetic defects or more commonly secondary to infections, it can also occur secondary to malignancy, i.e., malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH). A five-year-old male child presented with left cervical adenopathy and a high-spiking fever for two weeks. He had pallor, anasarca, multiple enlarged and matted cervical lymph nodes, respiratory distress, and hepatomegaly. He had continuous high-grade fever spikes (maximum 105 °F), not touching baseline despite broad-spectrum antibiotics. The CBC revealed anemia with thrombocytopenia. Liver function tests showed mild transaminitis and hypoalbuminemia. The HLH workup showed elevated ferritin, low fibrinogen, and elevated triglycerides. Lymph node biopsy showed intermediate to large atypical monomorphic lymphocyte cells with ALK, CD30, CD5, CD3, CD45, and BCL-2 (weak positive) positivity and Ki-67-95%, suggestive of anaplastic large cell lymphoma (ALCL). The bone marrow aspiration showed reactive marrow with hemophagocytosis. The patient was started on dexamethasone and chemotherapy per the Children's Oncology Group's (COG) ALCL protocol. He showed remarkable clinical improvement and went into remission after the induction phase. Malignancy associated with HLH can mimic infection, as in our patient with high-spiking fever, consolidation, and mediastinal adenopathy. A high index of suspicion is necessary to arrive at an appropriate, early diagnosis, and workup for malignancy is to be considered when an infectious etiology is not identified after thorough evaluation.

Evaluation of Pathway to Diagnosis of Pediatric Brain Tumors in Tamil Nadu, India.

PURPOSE: Delayed diagnosis and poor awareness are significant barriers to the early intervention of pediatric brain tumors. This multicenter observational study aimed to evaluate the baseline routes and time to diagnosis for pediatric brain tumors in Tamil Nadu (TN), with the goal of promoting early diagnosis and timely referrals in the future. METHODS: A standard proforma was used to retrospectively collect information on demographics, diagnosis, referral pathways, and symptoms of incident pediatric brain tumor cases between January 2018 and October 2020 across eight tertiary hospitals in TN. Dates of symptom onset, first presentation of health care, and diagnosis were used to calculate total diagnostic interval (TDI), patient interval (PI), and diagnostic interval (DI). RESULTS: A total of 144 cases (mean age, 6.64 years; range, 0-15.1 years) were included in the analysis. Among those, 94% (135/144) were from city/district areas, 40% (55/144) were self-referred, and 90% (129/144) had one to three health care professional visits before diagnosis. Median TDI, PI, and DI were 3.5 (IQR, 1-9.3), 0.6 (IQR, 0.1-4.6), and 0.6 (IQR, 0-3.3) weeks, respectively. Low-grade gliomas had the longest median TDI (6.6 weeks), followed by medulloblastomas (4.6 weeks) and high-grade gliomas (3.3 weeks). Average number of symptoms recorded was 1.7 at symptom onset and 1.9 at diagnosis. CONCLUSION: Although there are some similarities with data from the United Kingdom, many low-grade and optic pathway tumors were unaccounted for in our study. DIs were relatively short, which suggests that infrastructure may not be a problem in this cohort. Increased training and establishment of proper cancer registries, combined with proper referral pathways, could enhance early diagnosis for these children.

Experience with Generic Pegylated L-asparaginase in Children with Acute Lymphoblastic Leukemia from a Tertiary Care Oncology Center in South India.

Dhaarani JayaramanBackground Acute lymphoblastic leukemia (ALL) is a common type of leukemia in children. The innovator pegylated L-asparaginase has several advantages over native L-asparaginase; however, its use in India is limited due to availability and cost. Therefore, a generic pegylated L-asparaginase can be considered as an alternative to the innovator molecule. Methods A retrospective study was conducted to assess the outcome (minimal residual disease [MRD]) and toxicity of a generic pegylated L-asparaginase (Hamsyl) at the end of induction therapy. Results Eighty-eight (80.7%) and 21 (19.3%) patients had received generic pegylated L-asparaginase and conventional asparaginase, respectively, as a part of their treatment protocol. Nearly 82% of patients had B-type ALL. Eight-one percent of children had a white blood cell count of fewer than 50,000/mm 3 . At the end of induction, 80.7% (88) of children were minimal residual disease (MRD)-negative, and at the end of augmented consolidation therapy, 20.2% were MRD-negative. Ten percent of patients exhibited allergic reactions. Two children had pancreatitis, and one child had central venous thrombosis. Conclusion The generic pegylated L-asparaginase (Hamsyl) was effective and safe for use in pediatric ALL.

Role of Polymerase Chain Reaction-Based Diagnosis of Respiratory Viruses in Febrile Neutropenic Patients.

Background Neutropenic patients are commonly affected by respiratory infections, whereas respiratory viral infections causing high morbidity and mortality are routinely diagnosed in developing countries like India. Our study aimed to investigate the prevalence of respiratory viral infections in pediatric cancer patients with febrile neutropenia.  Methods This prospective study was performed on 45 neutropenia patients with hematological malignancies. Nasal swabs were collected and analyzed by real-time multiplex polymerase chain reaction (PCR), covering the following viruses: influenza A virus, influenza B virus, human parainfluenza virus (subtypes 1-4), human respiratory syncytial virus A and B, enterovirus, human-coronavirus (HCoV: HKU1, NL63, 229E, and OC43), human bocavirus, adenovirus, human rhinovirus, human-metapneumovirus A and B, human paraechovirus, and a bacterium Mycoplasma pneumoniae. Patients enrolled in the study since the COVID-19 pandemic was also detected for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Of the 45 cases included in our study, 26 cases showed the presence of at least one positivity by PCR (57.7%): 23 patients had monoinfection with only one virus, two patients were found positive for coinfection with two viruses, and one patient was found positive for three viruses. The most detected viruses were human rhinovirus (26.9%, n=7) and coronavirus 19 (19.2%, n=5). A total of 11.5% of the patients had multiple viral infections. About 19 (42.2%) of the patients enrolled in our study had no viral pathogen detected. Conclusion We found that respiratory viruses contribute significantly to the development of neutropenic fever, as evidenced by the results of our prospective study. Individualizing infection treatment can reduce antibiotic use in immunocompromised patients. Thus, routine screening for viremia may be warranted in this clinical setting.

Mercaptopurine induced myelosuppression in a child with a NUDT15 rs116855232 homozygous variant.

INTRODUCTION: Mercaptopurine (6-MP) is the backbone of the consolidation and maintenance therapy for paediatric acute lymphoblastic leukaemia (ALL). Nevertheless, it can cause critical myelosuppression. Predicting adverse reactions to 6-MP often involves the investigation of pharmacogenetic variants; in particular thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15). Lately, NUDT15 variants have been shown to play a significant pharmacogenetic role in predicting 6-MP intolerance in children of Asian descent. CASE REPORT: We present a six-year-old male child of Indian origin with persistent cytopenia after treatment. This prompted targeted sequencing of the genes TPMT and NUD15. The results revealed two copies of the variant of NUD15 rs116855232, that is, NUDT15*2 genotype. MANAGEMENT AND OUTCOME: Since the NUDT15*2 allele classified the patient as a poor metabolizer, he was restarted on a low dose of 6-MP, which he tolerated. DISCUSSION: Individuals with the NUDT15*2allele (*2/*2 genotype) are poor metabolizers of thiopurines which results in an adverse reaction to 6-MP. About 3.5% of Indians show variations in the TPMT gene as compared to 19.4% variations observed in NUDT15, which makes the latter a more reliable disease marker.

Nephrotic Syndrome and Hodgkins Lymphoma - an Unusual Association.

Background: An association between nephrotic syndrome and extrarenal neoplasia was described for the first time in 1922. The reported incidence of nephrotic syndrome in Hodgkin lymphoma is less than 1%. Clinical description: We present a 13 year old boy who was admitted with complaints of abdominal pain, vomiting and loose stools for 2 months. He had a history of significant weight loss of 5kg in a couple of months.On examination, he had bilateral pedal oedema and right cervical lymphadenopathy. Cervical lymph node biopsy revealed nodular sclerosis type of Hodgkin lymphoma. He also had hypoalbuminemia, massive proteinuria and hypercholesterolemia.Secondary nephrotic syndrome due to Hodgkin's lymphoma was made as a clinical diagnosis. Management and outcome: He had been started on chemotherapy (with Prednisolone, Vincristine, Doxorubicin, Etoposide) for stage 3B Hodgkin lymphoma. He tolerated the chemotherapy well. Though he had symptomatic edema, managed conservatively as the urine output was adequate. On follow up, he attained spontaneous remission of nephrotic syndrome. Conclusion: Overt proteinuria might be the manifestation of paraneoplastic syndrome in children with Hodgkin lymphoma and with the management of the primary disease, proteinuria resolves spontaneously.

Severe diabetic ketoacidosis and autoimmune pancreatitis with SIRS in an adolescent with LRBA deficiency - A rare complication of a common primary immunodeficiency disease.

Common variable immunodeficiency is the most common primary immunodeficiency disorder. Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency is categorized as a common variable immunodeficiency associated with autoimmune manifestations and inflammatory bowel diseases. We report a rare case, an adolescent presenting with severe diabetic ketoacidosis (DKA) and acute pancreatitis with multiorgan dysfunction with common variable immunodeficiency (CVID) with homozygous LRBA mutation.

CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature.

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

Renal Primitive Neuroectodermal Tumor Mimicking Wilms' Tumor in a Young Boy: A Case Report of a Rare Entity with Review of the Literature.

Primary renal primitive neuroectodermal tumors (PNET) are an extremely rare entity. The tumor is very aggressive presenting with metastasis and carries a dismal prognosis. We describe the case of renal PNET in an 11-year-old boy with a solid cystic lesion in the right kidney with a thrombus in the inferior vena cava and lung nodules, mimicking Wilms' tumor.

Successful Outcome of Metastatic Pancreatoblastoma in an Adolescent: A Case Report and Review of the Literature.

Pancreatoblastoma, an orphan disease, is the most common malignant epithelial neoplasm of the pancreas in children. With vague clinical features, diagnosis is made by radiological suggestions and histopathology. The presence of metastatic disease and inoperable/incomplete excision remains the poor prognostic markers. We present a rare instance of an adolescent who has survived metastatic pancreatoblastoma after neoadjuvant chemoreduction/complete surgical excision.

Disseminated Cytomegalovirus Infection in a Child with Langerhans Cell Histiocytosis.

Cytomegalovirus (CMV) reactivation is well known in post-transplant immunocompromised children. However, the incidence in non-transplant patients is significantly less, and only scarce case reports are available in the literature regarding CMV disease in children with solid tumors. We present a 3-year-old male child with multisystem refractory Langerhans cell histiocytosis, who had very high CMV viremia and disseminated CMV infection with secondary hemophagocytic lymphohistiocytosis and was successfully treated without organ damage and sequelae. Although routine screening is not recommended, CMV viremia/disease needs to be considered in non-transplant immunocompromised children with multisystem involvement with unexplained cytopenia.

A Journey Across Oceans With a Heavy Heart: Rare Presentation of a Pediatric Malignancy.

Myeloid sarcoma, due to extramedullary deposition of myeloblasts, is one of the rare presentations in acute myeloid leukemia. We present an extremely rare case of a 5-year-old boy with cardiac myeloid sarcoma. Noninvasive mode of diagnosis, timely initiation of chemotherapy and meticulous supportive care are the keys to successful outcome. (Level of Difficulty: Intermediate.).