ABSTRACT
Malignant peripheral nerve sheath tumor (MPNST) is a rare soft-tissue sarcoma with an unfavorable prognosis and limited therapeutic options. MPNSTs can be sporadic, but are often associated with neurofibromatosis (NF) 1 and usually arise from preexisting neurofibromas. MPNSTs in patients with NF2 have been reported in only exceedingly rare cases, and the mechanisms underlying transformation into an MPNST have not been fully elucidated. Here, we describe the clinicopathological and genomic features of a peripheral nerve sheath tumor (PNST), with a primary diagnosis of a neurofibroma, as it transforms into a high-grade MPNST in the context of NF2.
Subject(s)
Nerve Sheath Neoplasms/pathology , Neurofibromatosis 2/pathology , Sarcoma/pathology , Cell Transformation, Neoplastic/pathology , Child , Humans , Male , Nerve Sheath Neoplasms/genetics , Neurofibromatosis 2/genetics , Sarcoma/geneticsSubject(s)
Antifungal Agents/therapeutic use , Common Variable Immunodeficiency/pathology , Fever/pathology , Histoplasmosis/pathology , Itraconazole/therapeutic use , Lymphoma, B-Cell, Marginal Zone/pathology , Common Variable Immunodeficiency/diagnostic imaging , Common Variable Immunodeficiency/drug therapy , Common Variable Immunodeficiency/immunology , Fever/diagnostic imaging , Fever/drug therapy , Fever/immunology , Histoplasma/drug effects , Histoplasma/growth & development , Histoplasma/pathogenicity , Histoplasmosis/diagnostic imaging , Histoplasmosis/drug therapy , Histoplasmosis/immunology , Humans , Immunoglobulins, Intravenous/therapeutic use , Lymphoma, B-Cell, Marginal Zone/diagnostic imaging , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, B-Cell, Marginal Zone/immunology , Male , Young AdultSubject(s)
Autoimmune Diseases/genetics , CTLA-4 Antigen/genetics , Lymphoproliferative Disorders/genetics , Adolescent , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Female , Haploinsufficiency , Humans , Lymphoproliferative Disorders/immunology , Lymphoproliferative Disorders/pathology , Submandibular Gland/pathology , T-Lymphocytes/immunologyABSTRACT
Rearrangements of the mixed lineage leukemia (MLL) gene occur frequently in infants with both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Conversions of leukemia cell lineage are rare, but occur most commonly in the setting of MLL-rearrangement. Blinatumomab is a bidirectional antibody targeting CD19 with significant activity in relapsed B-precursor ALL. We report an infant with ALL with t(4;11)(q21;q23) refractory to cytotoxic chemotherapy who was treated with blinatumomab. Following rapid initial clearance of peripheral lymphoblasts, bone marrow evaluation demonstrated a leukemic lineage switch to CD19-negative monoblastic AML. Complete remission was achieved with myeloid-directed chemotherapy.
Subject(s)
Antibodies, Bispecific/therapeutic use , Cell Lineage/drug effects , Leukemia, Myeloid, Acute/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Antigens, CD19 , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gene Rearrangement , Humans , Infant , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Male , Myeloid-Lymphoid Leukemia Protein/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
Monosomy 7 is a well-documented cytogenetic aberration in pediatric acute myeloid leukemia (AML) and may occur in combinations with molecular abnormalities including PTPN11 mutation. PTPN11 mutations contribute to leukemogenesis through upregulation of Ras pathway signaling. We present the case of a 3-year-old female with AML with monosomy 7 and somatic PTPN11 mutation who was refractory to conventional AML chemotherapy but responded to a novel regimen of azacitidine and sorafenib followed by stem cell transplantation. Combination therapy with azacitidine and sorafenib may be an effective therapeutic strategy for patients with AML with Ras pathway abnormalities.
Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Azacitidine/administration & dosage , Chromosome Deletion , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Niacinamide/analogs & derivatives , Phenylurea Compounds/administration & dosage , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Child, Preschool , Chromosomes, Human, Pair 7 , Drug Therapy, Combination , Female , Humans , Mutation , Niacinamide/administration & dosage , Sorafenib , Stem Cell TransplantationSubject(s)
Fever/etiology , Liver Diseases/etiology , Macrophage Activation Syndrome/complications , Mevalonate Kinase Deficiency/complications , Perforin/genetics , Polymorphism, Genetic , Female , Humans , Infant, Newborn , Macrophage Activation Syndrome/genetics , Mevalonate Kinase Deficiency/genetics , RecurrenceABSTRACT
Low-dose decitabine has encouraging activity and tolerability in adults with acute myeloid leukaemia (AML), but paediatric experience is lacking. We report our retrospective experience with decitabine in eight children and young adults (median age 4 years) with refractory/relapsed AML, who had failed multiple regimens or were not candidates for standard retrieval regimens due to prior toxicities. Three of eight patients (38%) had complete response (CR; 1 each of CR, CR with incomplete platelet recovery and CR with incomplete count recovery). Best responses were observed after a median of 2.5 cycles (range 1-4 cycles). Four patients received subsequent allogeneic stem cell transplant, and two remain in long-term CR.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/analogs & derivatives , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Adult , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/administration & dosage , Azacitidine/adverse effects , Azacitidine/therapeutic use , Bone Marrow/chemistry , Child , Child, Preschool , Combined Modality Therapy , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/analysis , Decitabine , Drug Evaluation , Female , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/surgery , Male , MicroRNAs/analysis , Neoplasm Proteins/analysis , Neutropenia/chemically induced , RNA, Neoplasm/analysis , Remission Induction , Salvage Therapy , Stem Cell Transplantation , Transplantation, Homologous , Treatment OutcomeABSTRACT
N-methyl-D-aspartate receptor (NMDAR) encephalitis is a life-threatening paraneoplastic neuropsychiatric encephalitis that predominantly affects young women and has a strong association with ovarian teratomas. Removal of the ovarian teratomas improves the prognosis and decreases the risk of recurrence. We present an 11-year-old girl with NMDAR encephalitis with small bilateral teratomas not initially appreciated on abdominal CT or pelvic MRI. A 12-mm teratoma was identified in the right ovary and a 7-mm teratoma was identified in the left ovary on US follow-up at 5 months. Intraoperative sonography was used to localize the teratomas for excision. In NMDAR encephalitis, the ovarian teratomas can be very small, particularly in children, and easily missed on cross-sectional imaging. Awareness of the association of NMDAR encephalitis and ovarian teratomas will improve the diagnostic accuracy and imaging interpretation. Periodic sonography and MRI might be warranted in children if the initial study is negative.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/complications , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Teratoma/diagnosis , Teratoma/surgery , Child , Female , Humans , Magnetic Resonance Imaging , Ovarian Neoplasms/complications , Teratoma/complications , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Fanconi anemia (FA) is characterized by progressive marrow failure, congenital anomalies, and predisposition to malignancy. Biallelic FANCD1/BRCA2 mutations are the genetic basis of disease in a small proportion of children with FA with earlier onset and increased incidence of leukemia and solid tumors. Patients with FA have increased sensitivity to chemotherapy and radiation, and upon development of a solid tumor, require modification of these therapies. We report clinical and molecular features of three patients with FA associated with FANCD1/BRCA2 mutations, including two novel mutations, and discuss treatment of malignancy and associated side effects in this particularly vulnerable group.
