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.

Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

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.

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.).