Aron Flagg

Synchronous occurrence of nasopharyngeal carcinoma and Hodgkin lymphoma

Latent Epstein-Barr virus infection is associated with several lymphoid and epithelial malignancies. This is the first reported case of a patient presenting with synchronous nasopharyngeal carcinoma and Hodgkin lymphoma associated with Epstein-Barr virus. A 17-year-old previously healthy African-American male presented with anterior mediastinal mass and a nasopharyngeal mass. Histology from biopsy of both lesions revealed evidence of Epstein-Barr virus. The patient successfully completed sequential therapies with chemo radiation with no evidence of active disease. Simultaneous occurrence of the two malignancies is undoubtedly a rare event, and their coexistence raises the question of a common etiologic factor.

Transient abnormal myelopoiesis of a newborn not associated with chromosome 21 abnormalities or GATA1 mutations

Transient abnormal myelopoiesis (TAM) is a disorder of Down syndrome newborns characterized by megakaryocytic blasts indistinguishable from acute myeloid leukemia (AML), which undergoes spontaneous remission. Acquired GATA1 mutations are present in blasts of both TAM and the subsequent AML which sometimes develops. We present a unique case of a newborn with leukemic megakaryoblasts indistinguishable from those of TAM who had neither extra material from chromosome 21 in the germline or blasts, nor evidence of GATA1 mutations. These findings suggest there are other genetic abnormalities that can lead to TAM besides GATA1 mutation in the setting of trisomy 21. Pediatr Blood Cancer 2015;62:353–355.

Gimap5-dependent inactivation of GSK3β is required for CD4 + T cell homeostasis and prevention of immune pathology

GTPase of immunity-associated protein 5 (Gimap5) is linked with lymphocyte survival, autoimmunity, and colitis, but its mechanisms of action are unclear. Here, we show that Gimap5 is essential for the inactivation of glycogen synthase kinase-3β (GSK3β) following T cell activation. In the absence of Gimap5, constitutive GSK3β activity constrains c-Myc induction and NFATc1 nuclear import, thereby limiting productive CD4+ T cell proliferation. Additionally, Gimap5 facilitates Ser389 phosphorylation and nuclear translocation of GSK3β, thereby limiting DNA damage in CD4+ T cells. Importantly, pharmacological inhibition and genetic targeting of GSK3β can override Gimap5 deficiency in CD4+ T cells and ameliorates immunopathology in mice. Finally, we show that a human patient with a GIMAP5 loss-of-function mutation has lymphopenia and impaired T cell proliferation in vitro that can be rescued with GSK3 inhibitors. Given that the expression of Gimap5 is lymphocyte-restricted, we propose that its control of GSK3β is an important checkpoint in lymphocyte proliferation.Loss of function GIMAP5 mutation is associated with lymphopenia, but how it mediates T cell homeostasis is unclear. Here the authors study Gimap5−/− mice and a patient with GIMAP5 deficiency to show how this GTPAse negatively regulates GSK3β activity to prevent DNA damage and cell death.

Extranodal marginal zone B cell lymphoma: An unexpected complication in children with Sjögren's syndrome

Sjögrens syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes into exocrine glands, resulting in the typical sicca symptoms. Unlike adults, primary SS is a very rare condition in childhood, and the risk of malignancy in juvenile SS (JSS) has not been defined. We report the detection of extranodal marginal zone B-cell lymphoma (EMZL) occurring in two children with SS. Fine needle aspiration of the salivary glands (SG) showed nonspecific findings that led to delayed diagnosis of SS. The diagnosis of B-cell lymphoma associated with JSS was based on morphologic and immunohistochemical staining done during the biopsy. To highlight awareness of EMZL as a timely and appropriate update of an unusual complication in children with SS.

Characteristics of Bacteremia in Pediatric Oncology Patients Based on Pathogen Classification as Associated with the Gastrointestinal Mucosa or Skin

Factors favoring blood stream infections associated with gastrointestinal mucosa versus skin organisms were explored. An observed difference was attributable to bacteremia from oral flora in patients with acute myelogenous leukemia or mucositis. Our data do not support the conclusion that isolation of enteric Gram-negatives is unrelated to the central catheter.

Testicular Myeloid Sarcoma: A Rare Manifestation of Acute Myeloid Leukemia in an Infant

Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experience with a 6-month-old boy who presented with painless scrotal swelling and was found to have bilateral testicular masses on ultrasonography. The patient underwent unilateral radical inguinal orchiectomy. Surgical pathology revealed myeloid sarcoma of the testicle. He developed peripheral blood involvement 1 week postoperatively. Bone marrow biopsy showed acute myeloid leukemia. He is in remission after 2 cycles of induction chemotherapy, local radiation therapy, and allogeneic bone marrow transplantation.